2023 Impact Factor: 1.3
2023 CiteScore: 2.2
pISSN: 2251-6085
eISSN: 2251-6093
Chairman & Editor-in-Chief:
Dariush D. Farhud, MD, Ph.D., MG.
This journal is a member of, and subscribes to the principles of, the Committee on Publication Ethics (COPE). 
Vol 34 No Supple 1 (2005)
Articles
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Introduction: Asthmatic children are more at risk to environmental tobacco smoke exposure (ETS) due to impaired lower airway function. Objective: To investigate the association of low socio-economic status and ETS exposure in asthmatic children. Design: A cross-sectional study on 425 primary school children (aged 5-11years) in Merseyside, using a parent completed questionnaire and childrens’ saliva samples. Results: 25.9 % of children had doctor diagnosed asthma and 12 % had a history of hospital admission for respiratory illnesses. The symptom triad of cough, wheeze and breathlessness were reported for 8.5% of children. Mean cotinine level was 2.1 ng/ml (±0.6 SD). 45.6% of children were ETS exposed (cotinine levels >1.0 ng/ml). Asthmatic children and those from disadvantaged households were more likely to be ETS exposed, compared to non-asthmatic and those from advantaged households [OR=1.7 (95%CI=1.1-2.4)] and [OR=2.1(1.8-3.2) respectively]. A synergic effect of parental asthma, deprivation and high cotinine levels on childhood asthma was observed in multivariate analysis. Conclusions: A high cotinine level was significantly associated with an increased risk of asthma in children particularly amongst disadvantaged households. Interventions aimed at limiting ETS exposure particularly among disadvantaged groups with asthmatic children are needed.
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More than 20 years after the AIDS epidemic first emerged, almost 38 millions people (range 34.6–42.3 millions) were living with HIV till the end of 2004. International figures are indicated that AIDS has become the leading cause of death in some developing countries so that about 2.3 millions deaths were happened in Sub- Saharan Africa to the end of 2003. A lot of HIV-infected people do not know that they are carriers and millions of people have no knowledge how to protect themselves against HIV infection. High-risk behaviors are common among people who are incarcerated. To evaluate the knowledge of Iranian prisoners regarding HIV and AIDS, a cross-sectional study was conducted in Kerman prison. In a sample of 350 prisoners, data were collected by using a questionnaire including three sections, the overall knowledge of HIV/AIDS, transmission ways and prevention. The mean score was calculated to assess the knowledge. Furthermore, the differences between the levels of prisoners’ knowledge according to the personal characteristics were tested by Analysis of Variance and Kruskal-Wallis test. Results indicated that the prisoners had relatively high knowledge about HIV/AIDS and its modes of transmission. However, they had a lower level of knowledge about HIV/AIDS prevention. The overall knowledge of men about AIDS was significantly lower than women. Persons aged 46 years and older and illiterate inmates had the least knowledge about modes of transmission. In addition, the knowledge of illiterate prisoners about HIV/AIDS prevention was significantly lower than others. Further evaluation of attitudes and practices of Iranian prisoners and implementation of educational programs, regarding HIV/AIDS, is required.
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In the last decade, main health financing reforms in Iran’s integrated health care delivery system, have provided some degree of financial incentive both to the providers of secondary and tertiary care in supply side, and the consumers of these services in demand side, leaving the primary health facilities at lower level of system with fixed financing method in macro and micro levels. But in recent years, alternative set of primary health care delivery has been introduced to primary health care delivery system in Iran that provides financial incentive to the provider of services in new initiative, both at micro and macro levels. Regardless of the impact of financial incentive on the performance of secondary and tertiary facilities, we compared the performance of different primary health care providers each with different method of financing. In this comparative study, secondary and primary data were gathered cross-sectionally. In this article, the impact of financial incentive on the financial performance of alternative sets of primary health centers in a region of Iran will be reported.
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The National Health Service (NHS) was established in 1948 to provide equitable healthcare for all citizens. Over the years the NHS has gone under different reforms and changes. In 2002 the NHS launched one of its biggest changes in structure since its commencement in 1948. The scale of these changes are greater than those established following the white paper “Working for Patients” in 1989 (Conservative Government) that indicated the introduction of the internal market (focus on efficiency). This review therefore proposes to give a brief summarize of the structural changes and current structure of the NHS in the England. The NHS plan was published in July 2000 (Labour Government) and outlined a 10 year plan of investment in the NHS. This delineates a vision for a service planned around the patients and more responsive to patients’ needs. The Government emphasizes on the empowering of staff at all levels as a way to achieve this vision. "Shifting the Balance of Power" is part of the Government’s plans for implementation of the NHS Plan and has directed to the establishment of new structures. The main feature of change has been giving locally based Primary Care Trusts the role of running the NHS and, with the local authorities, improving health in their areas. The PCTs are receiving 75% of the NHS budget to act as primary services provider, commissioner (service purchaser), network developer and controller. In addition, all former Health Authorities have been abolished and new Strategic Health Authorities (SHA) have been created to serve larger areas and with a more strategic role. The SHAs are responsible for developing strategic frameworks for the local health service; performance of the local health service; and building capacity in the local health service. The Department of Health is also refocusing to reflect these changes, including the abolition of its Regional Offices and relegating some of its operational responsibilities to SHAs and other organizations. While NHS Trusts (the organizations responsible for running most NHS hospitals, mental health and learning disability services, ambulance services and patient transport) continue to have the similar functions as before, they will have to create new working relationships with PCTs and SHAs. In addition Foundation Trust, which often referred ‘Foundation Hospitals’, were set up in April 2004 and are freestanding hospitals with greater autonomy within the NHS. New structures signify new relationships and partnerships both between NHS organisations and with other stakeholders. All NHS organisations locally - PCTs, Care Trusts and NHS Trusts - are now part of a single structure in which they are supposed accountable to SHAs, which are in turn accountable to Department of Health and ultimately to Secretary of State for Health. Relationships with other collaborators such as Local Authorities and voluntary organisations are also crucial, particularly for PCTs as they work towards improving health and integrating health and social care.
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Conceptual framework: The political, technological and economic changes that have occurred over the past twenty years are increasingly difficult to manage within the conventional framework of health-care, and the organisation of health-care is seen to need transformation to respond to increasing uncertainty, instability and complexity. In this context, leadership has been emphasized as a key factor in driving organizations forward. Over the past two decades, there has been an increasing interest in a school of leadership theory referred as “New Leadership” Paradigm. It describes and categorizes a number of approaches to leadership to exhibit common or at least similar themes, although there are few differences between them. These theories are charismatic leadership, transformational leadership, and visionary leadership. The common thread of these theories is that these leaders are able to develop and implement a vision, communicate this vision, and motivate subordinates to commit resources and energy toward vision- oriented goals. The evidence shows that transformational leadership behavior is related to a wide variety of positive individual and organizational outcomes. Taking into account the importance of the new leadership paradigm, measurement of the transformational leadership behaviour could be used in better understanding of leadership process and leaders development. Objective: The review’s objective is to appraise the quantitative instruments available to health services researchers who want to measure “new leadership” paradigm. Data sources: A broad literature search was conducted using Medline, CINAHL, Embase, HMIC (including Helmis, DoHdata, king’s Fund database), PsychInfo, Social science citation Index for articles published up to January 2005. All citations were checked. The experts over the world were contacted in order to find instruments that are not in the published literature. The search concentrated on instruments used to quantify measure new leadership paradigm with a track record, or potential for use, in health care settings. Data extraction: For each instrument, these items were considered: conceptual or theoretical framework that the tool is derived from; the scientific properties of the instrument (methodological description of development and testing, reliability and validity); the number of items for each questionnaire; the measurement scales selected; and its strengths and limitations. Principal finding: six instruments were found that satisfied the inclusion criteria: Multifactor Leadership Questionnaire (MLQ); Leadership Practice Inventory (LPI); The Leadership Profile (TLP); Transformational Leadership Questionnaire (TLQ); Transformational Leadership Behaviour Inventory (TLI); and Conger- Kanungo Questionnaire (C-K 20 questionnaire). Four of them have been used in health care organizations (MLQ; LPI; TLP; and TLQ). The TLI has strong potential to be used in health care settings and the C-K 20 questionnaire has some potential for use in such setting. Conclusion: A range of instruments with different characteristics is available to researchers, all of which have limitations in terms of their scope, scientific properties, and ease of use. The choice of instrument should be considered in terms of the purpose of the investigation and availability of resources. Although the quantitatively based surveys have been the favoured approach to the study of leadership, it should be kept in mind that they may fail to capture the richness of leadership phenomena and its dynamic process. Therefore, quantitative approach could be supplemented by different qualitative methods to develop a more detailed understanding of the leadership phenomenon.
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Introduction: PMMA has been the most popular denture base material because of its advantages including good aesthetics, accurate fit, stability in the oral environment, easy laboratory and clinical manipulation and inexpensive equipments since the 1930’s. However, its fracture resistance is not satisfactory. Aim: The aim of this study is to improve the fracture resistance of denture bases made of PMMA by assessing the effect of resin type, packing and processing variables on biaxial flexural strength (BFS). Materials & methods: 930 discs, 12 mm diameter and 2 mm thick were prepared with the following variables: a. Veined (V) and Plain (P) PMMA. b. 5 different powder/liquid ratios by volume (1.5:1, 2:1, 2.5:1, 3:1, 3.5:1). c. Conventional (C) and Injection packing methods (I). d. Dry heat (D) Water bath (W); and e. different curing times. The discs were trimmed and stored in 37°C tap water for 50 hours before carrying out BFS test, according to BS EN ISO 1567: 2001. BFS test was carried out using a tensile-testing machine (Lloyd LRX, Lloyd instruments Ltd) (Figure.1 b), with a x-head speed of 1mm/min. ONE-WAY ANOVA analysis and TUKEY’S comparison were carried out (MINITAB). The temperature within the curing baths and inside of curing resin was evaluated by using a thermocouple. Results: BFS of Powder/liquid ratio of 1.5:1 is significantly lower than the other four ratios. Among the last four ratios, 2.5:1 was the strongest one although the difference was not significant. BFS of the plain type of PMMA is significantly higher than the veined type.• BFS of conventionally packed PMMA discs was greater than the injectional packed ones and the difference is significant. Water bath cured resin showed a significant higher BFS compared with dry heat curing. • Changing the curing time in the dry heat bath from 7h @ 75º C and 2hrs @ 95º C to 5hrs @ 75º C and 3hrs @ 95º C and then 2hrs @ 95º C improves BFS of PMMA. In the water bath the trend is identical although the difference is not significant. Analysis of the temperature climb and hold within the curing bathes showed a consistent performance with the water bath irrespective the number of the flasks being cured. Meanwhile, the dry heat bath showed very inconsistent results. Conclusion: 1. Type of resin, packing procedure and processing variables can have major effect on BFS of PMMA. 2. Using plain resin, conventional packing, water bath curing with two hours at 95 ºC are recommended conditions.
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Introduction: South Asian people in the United Kingdom have a higher risk of having coronary heart disease (CHD) and stroke than the general population. Haemoglobin A1c (HbA1c) is a specific type of glycosylated haemoglobin that strongly correlates with the level of ambient glycaemia during a 2-3 month period. It is not clear whether differences in traditional CHD risk factors alone fully explain the increased risk in South Asians. We aimed to compare HbA1c level in UK South Asians and Caucasians. Methods: Data from Health Survey for England 1999 were employed to study ethnic differences in fasting blood glucose and HbA1c. 535 South Asian 425 Caucasian aged 35-69 years with no history of cardiovascular diseases, taking lipid lowering medication, or diabetes, and with fasting blood glucose < 7.8 mmol/l (140 mg/100) were included in the analysis. Results: The HbA1c levels ranged from 4.3-7.7% in south Asians and 4.5-6.7% in Caucasians. Its level correlated with fasting blood glucose in both South Asians and Caucasians, r = 0.36 (P< 0.001) and r = 0.28 (P< 0.001) respectively. The distribution of HbA1c in South Asians was shifted to the right as compared with that of Caucasians. Caucasians had proportionately more HbA1c values in quartiles I and II of the total population, whilst 50.3% of South Asians were in the third and fourth quartiles compared to 29.9% of Caucasian participants. Conclusions: The difference in risk of CHD between non-diabetic South Asian and Caucasians is not explained by differences in the impact of the traditional risk factors. Part may be due to higher blood sugar concentrations in non-diabetic South Asians.
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Introduction: Obesity is an increasing medical and social problem, which affects all ages, both genders and all socio-economic groups in both developing and developed countries. It leads to adverse metabolic changes, raises the risk of coronary heart disease, stroke, diabetes mellitus and many forms of cancer. Aim: Aim of study was demonstrating a descriptive epidemiological feature of obesity in Grampian, Scotland. Method: A two percent stratified random sample was chosen from populations aged 16- 74 years, living in Grampian. The self-completion postal questionnaires were sent to 8,088 people and 3,758 of them were returned. In total 3,754 cases have been used for analysis. A statistical analysis has been conducted on the data sets using Chi squared and regression analysis. Results: The highest percentage of obesity was found in the age group 35-44 and the lowest percentage to the over 75- year-old category for both men and women. The percentage of overweight is higher in males (41.6%) than females (29.5%). However, the percentage of obese people is higher in females (13.1%) than in males (12.0%). In total 53.6% of men and 42.6% of women in this survey are overweight and/or obese. The chi-square test shows significant differences in BMI categories by gender (P< 0.001). The chi-square test shows that there is a significant relationship between age and BMI. (P< 0.001). The linear chi-square test shows that older people tend to be in higher BMI categories (P< 0.001). The percentage of overweight and obese men and women decreases as education level increases. The percentage of overweight and obese is higher in retired people (52.5% and 13.1% in men and 40.2% and 15.8% in women) and in people who are in paid work or self-employed fulltime groups than other groups. Permanently sick or disabled people percentages are more likely to be overweight or obese. The percentage of overweight people is higher in people who own their homes or rented from a private landlord. The percentage of obese people is highest in people who rented from councils or housing associations. The Chi-square test does not show any association between BMI and deprivation in this survey. The number of non-white people in the survey is very small and does not allow for further analysis. Conclusion and recommendations: This study revealed all age groups should be considered as a population target for prevention of obesity. Social factors such as level of education and housing tenure are associated with obesity as reported by other studies. Permanently ill or disabled people are more likely to be overweight and obese. The percentages of obesity are highest in people who rented homes from councils or housing associations which may be associated with ageing or medical conditions leading to less activity and a sedentary lifestyle. Prevention of obesity should be a priority of health policy. The increasing rate of overweight and obesity in all groups suggest that the whole community should be the focus including all age groups. Health promotion interventions should focus on both healthy eating interventions and increase physical activity.
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Parsons (1995) states that ‘Policy analysis is an approach to public policy that aims to integrate and contextualize models and research from those disciplines which have a problem and policy orientation’. Theories about policy making are concerned with process as well as outcomes and numerous groups are concerned about the policy process, including policy-makers, donors and international organizations as well as policy analysts. In health, research needs to be broadened to examine not only policy content, but also the process by which policy is formulated and implemented. The purpose of this research is to clarify the policy process, particularly policy formulation for organizational change in Iranian health institutions and to review the role of stakeholders, including health sector unions and professional organizations over the period 1980 to 2000.. This research analyzes the political mechanisms for making and controlling health institutional policy in Iran and illustrates how Iran’s power centre, affiliated with its public culture, was able to endorse a health policy or exercise a veto over health policy in both government and private contexts, and then how it gradually lost its hegemony as the politically reformed state became more firmly established. The research is also intended to provide an overview of existing theory of public policy formulation and to adapt and develop such theory in order to provide the means by which the impacts of policies for institutional change of Iranian health sector can be understood. This research is planned as a qualitative study, employing both documentary analysis and in–depth interviews.
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The UK National Health Service (NHS) came into existence on 5 July 1948 with the aim of providing a comprehensive range of health services to all in need. After 50 years, it is still a unique example of social engineering. It is the only social service in Britain, which is comprehensive in scope in the sense of looking after the entire population. It is, furthermore, the only service that is organized around an ethical imperative. Finally, it is remarkable for its sheer size, complexity and heterogeneity: with one million employees, drawn from a variety of professions and representing a wide range of skills, it is the largest employer in the country. By international comparison too, the NHS is unique, centrally financed and directed, yet operating in the pluralistic political environment. Yet the NHS has undergone many structural changes since its inception in 1948, and forces for change in the NHS are increasing at an exponential rate. This paper addresses the relationship of health sector reform and large-scale organisational change in England since the election of the Conservative government of 1979. The paper will argue that the degree of change achieved to the organisation and management of NHS is high. It will also be argued that there is a clear similarity and conformity between the policies of the Conservative government and of the New Labour government (elected in 1997) in respect of health organizational reform. I will conclude that New Labour’s ‘third way’ in health reform is a hybrid of the Conservative’s managerial approach in 1979-1997 and Labour’s traditional philosophy of centralisation.
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PBDE levels in 26 different indoor microenvironments including 13 homes, 12 offices and a private car were investigated. A mean indoor air concentration of 143.8 pg/m3 was determined with the offices being more contaminated than residential homes. The most abundant congener was identified to be BDE 47 followed by #s 99, 100, and 28, respectively. ΣPBDE concentrations in indoor air were on average ~ 7 times higher than HiVol derived outdoor air levels providing a significant source of these compounds to outdoor ambient air. The average daily human inhalation exposure to PBDEs was estimated to be 4.3 ng/person with a maximum intake value of 21.8 ng/person.
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In order to employ PUF disk passive air sampler (140 mm diameter, 12 mm thickness) as a quantitative sampling device a set of calibration experiments were carried out. Time integrated indoor air concentrations of PCBs and PBDEs were obtained from a low volume air sampler. The low volume active sampler was run alongside the passive samplers throughout the calibration period in an office microenvironment. Sampling rates of routinely employed passive sampler design were determined for 51 PCB and 6 PBDE congeners detected in all calibration samples. PUF disk R-values varied from 0.63 to 1.54 m3 day-1 for individual PCBs and from 1.1 to 1.9 m3 day-1 for PBDE congeners. The theory of passive sampling is also discussed and mass transfer coefficients (kA) of PCB and PBDE congeners provided.
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Objectives: To assess health-related quality of life (HRQL) in patients with suspected heart failure (HF) and to explore discriminate properties of the tools, two generic questionnaires, Short Form 36 (SF-36) and EuroQol 5D (EQ-5D) and one specific, the Minnesota Living with Heart Failure questionnaire (MLHF-Q) HRQL were employed and compared with New York Heart Association (NYHA) functional class. Method: All patients with symptoms suggestive of heart failure referred to University Hospital, Nottingham, between June 2002 and March 2003. Confirmation of left ventricular systolic dysfunction carried out by echocardiography. Main Results: 223 patients (median age=74) were referred. HF was confirmed in 81. Lower HRQL scores were found in older patients (SF-36 and EQ-5D: P< 0.001; MLHF-Q: P= ns), women (P<0.001; P< 0.05; P< 0.05 respectively) and BMI>30 (P= ns; P<0.05; P= ns respectively). Among those with confirmed heart failure, lower mean scores were found in both subscales of SF-36, four of six subscales in EQ-5D and all MLHF-Q subscales, but these were not statistically significant. SF-36 Mental Component Score (MCS) and the emotional subscale of MLHF-Q were more sensitive to depressive disorders than EQ-5D ((P< 0.001; p<0.001; and P< 0.05 respectively). Regression analysis indicated that only SF-36 Physical Component Score (PCS) was able to differentiate significantly between NYHA functional classes (P< 0.01). The validity of MLHF-Q was confirmed by correlation with various subclasses in other HRQL measures (P< 0.001) and known group analysis with NYHA functional class (P< 0.001 in both physical and emotional subscales). Conclusion: The specific HRQL measure, MLHF-Q, was more sensitive to functional status in heart failure but emotional abnormalities and general affections were more readily identified by generic tools. Employing both generic and specific HRQL instruments seems necessary in suspected and confirmed heart failure. MLHF-Q showed appropriate construct validity in this sample.
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Aim and Method: There is an urgent need to develop surrogate markers to aid in the diagnosis and assessment of treatment efficacy in human diabetic neuropathy. 22 diabetic patients underwent detailed assessment of Neuropathy Impairment Score in the lower limbs (NIS-LL), electrophysiology (EMG), quantitative sensory testing (QST), corneal confocal microscopy (CCFM) and skin biopsy. On the basis of NIS-LL, EMG and QST assessment 11 patients were classed to have no neuropathy (age= 5010 years, NIS-LL= 4+/-4, Peroneal Nerve Conduction Velocity (PNCV) 50+/- 10 m/s, Sural Nerve Amplitude Potential (SNAP) 11 +/- 7 mA, Tibial Nerve Onset Latency (TNOL) 15+/-2 ms, Vibration Perception Threshold (VPT) 7+/- 4 V, Cooling Detection Threshold (CDT) 57 +/- 28 pc, Deep Breathing Heart Rate Variability (DBHRV) 67+/-28 pc, and 11 had neuropathy (age 5311 years, NIS-LL=17+/-12, PNCV 39+/- 8 m/s, SNAP 5+/- 3 mA, TNOL 18+/-2 ms, VPT 30+/- 13 Volts, CDT 97+/- 2 pc, DBHRV 13+/-29 pc. CCFM was performed to quantify corneal nerve morphology: nerve fibre density (NFD), tortuosity (NFT), and branch density (NFBD) were compared with normative values from healthy volunteers (n=23, age 5215). 3 mm punch skin biopsies were performed from the dorsum of the foot and immunohistochemical staining was performed with PGP 9.5 to quantify dermal nerve fibre density (DNFD) and compared with normative values from 22 volunteers (age and sex matched). Results: 1) CCFM demonstrated differences between non neuropathic diabetic, neuropathic diabetic and control groups. Respective results are given as mean +/- SD: NFD 29+/-10, 35+/-13, and 46+/-16 nerves/mm2 (ANOVA P= 0.02), NFT 8+/-8, 19+/-14, 24+/-10 (tortuosity index, ANOVA P=0.002), NFBD 6+/-2, 6+/-3, 33+/-26 branches/mm2 (ANOVA P< 0.001). Post-hoc analysis showed a significant difference between both diabetic groups and controls for NFBD (P< 0.01), but only for non neuropathic diabetic groups compared to controls for NFD (P< 0.05), NFT (P< 0.01). 2) DNFD was reduced in all diabetic patients, non neuropathic and neuropathic, compared to controls (respectively 203+/-114, 190+/-58, and 414+/-196 fibres/mm2: mean + SD, ANOVA P< 0.001). No differences between the two patient groups were showed by post-hoc analysis. 3) Positive correlations were found between NFBD and SNAP (Pearson r= 0.55, P= 0.01), NFT and SNAP (r= 0.55, P= 0.004), and DNFD and SNAP (r=0.53, P= 0.01). NFD and NFBD inversely correlated with Peroneal F waves Latencies at (r=-0.63, P= 0.002) and r=-0.64, P= 0.001, respectively. Conclusions: Whilst both CCFM and DNFD were more reduced in diabetic patients with compared to those without neuropathy this did not reach significance. Corneal nerve morphology and skin DNFD correlated with electrophysiological parameters. However, they did not correlate to each other. This preliminary study demonstrates significant associations between corneal nerve morphology, ENFD and conventional measures of neuropathic severity suggesting that they may be reliable surrogate measures of human diabetic neuropathy. The correlation between some of the CCFM parameters and F waves suggests that CCFM may be particularly important in the very early stages of diabetic neuropathy.
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Aim: ‘Painful neuropathy’ is presumed to be secondary to small fibre damage from a variety of causes. Methods to detect, characterize and quantify small fibre damage are time consuming and highly variable (QST’s), or invasive (skin or nerve biopsy). We have recently shown that corneal nerve damage assessed using corneal confocal microscopy is an accurate surrogate marker for somatic nerve damage in patients with diabetic neuropathy. We have now assessed corneal nerve morphology in patients with painful neuropathy who had been labelled as having ‘small fibre neuropathy’. Methods: 30 patients aged 60 + 13 with ‘small fibre neuropathy’ and 12 age-matched control subjects underwent assessment of the Neuropathy Deficit Score in the lower limb (NDS), Neuropathy Symptom Profile (NSP), Electrophysiology, QST for thermal perception and corneal confocal microscopy (CCM). CCM quantified corneal nerve morphology: nerve fibre density (NFD), nerve branch density (NBD), nerve fibre length (NFL), nerve fibre tortuosity (NFT). Results: According to the results obtained for “neuropathy severity assessment” including NDS, NSP, electrophysiology and QST data , a significance reduction in corneal nerve NFD (P< 0.0001), NBD (P< 0.0001), NFL (P< 0.0001) and no statistical significant changes in tortuosity was shown. Discussion: Corneal confocal microscopy offers a rapid, non-invasive, and reiterative technique to accurately detect, and quantify nerve damage in patients with ‘small fibre neuropathy’.
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Background: Evaluation and accreditation of Health Care organizations has an important role in increasing the effectiveness and efficiency of these organizations and developing the quality of services provided. The current system of evaluation and accreditation of hospitals in Iran is based on structure only with out considering the context, process and output and this cause many problems for both health care providers and customers. Therefore, there is a pressing need for developing a model for health care systems’ evaluation and accreditation, which help these organizations to improve the quality of services. Method: The aim of this article is therefore: “To identify the strengths and weakness of the current system of evaluation and accreditation of hospitals in Iran, determining the ideal system of evaluation and accreditation to develop a model so that health care organizations aiming at achieving effectiveness and efficiency”. A descriptive study using a cross-sectional survey for data collection performed. All of hospital managers and hospital evaluators in Isfahan province were studied via a self administrated questionnaire (53 managers and 30 evaluators). This questionnaire specifies the respondents’ opinions about the current and ideal system of evaluation and accreditation of hospitals. Data was analyzed via SPSS11 software. Findings: The mean score of current system of evaluation and accreditation of hospitals was 3.12 0.83 and 4.41 0.34 (in a 5 scale).The mean score of structure, process and outcome were 3.10.73, 3.120.91and 3.091 in the current system of hospital evaluation respectively. From the view points of hospital managers and evaluators the differences between values of current and ideal scores of evaluation and accreditation system were statistically significant (P< 0.05). Therefore, there is a need for developing a model for hospital evaluation and accreditation. Based on these results an empirical model for Evaluation and Accreditation of Hospitals is developed. In this model, the context, structure (input), process and results (out put) were considered comprehensively. In this model items such as customer participation in treatment process, hospital information system, equity of services, employees’ participation in evaluation process, increasing employees and managers knowledge and capabilities level, risk and safety management and so on are considered. Discussion: The evaluation and accreditation system of Hospitals should be a comprehensive system in order to evaluate the whole dimensions of these organizations.
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Background: Total quality management (TQM) is a managerial practice to improve the effectiveness, efficiency, flexibility, and competitiveness of a business as a whole. However, in practice, these TQM benefits are not easy to achieve. Despite its theoretical promise and the enthusiastic response to TQM, recent evidence suggests that attempts to implement it are often unsuccessful. Many of these TQM programmes have been cancelled, or are in the process of being cancelled, as a result of the negative impact on profits. Therefore, there is a pressing need for a clinical approach to establishing TQM. Method: The aim of this article is therefore: “To identify the strengths and weakness of TQM, the logical steps towards TQM, and to develop a model so that health care organizations aiming at using TQM to achieve excellence can follow through easily”. Based on the research questions proposed in this study, the research strategies of a literature review, a questionnaire survey, semi-structured interviews, and a participatory action research were adopted in this study. For determining the success and barriers of TQM in health care organizations, a questionnaire survey has done in 90 health acre organizations in Isfahan Province, which implement TQM. The results of this survey were used for introducing a new model of TQM. This model will be developed via a semi-structured interview with at minimum 10 health care and quality managers. Then, through a participatory action research, this model will be implemented in 3 sites. At this time, the questionnaire survey has done and the model is introduced. Therefore, developing the model and its implementation will be done later. Results: In this survey, the mean score of TQM success was 3.48±0.68 (medium) from 5 credits. Implementation of TQM was very low, low, medium, high and very high successful respectively in 3.6, 10.9, 21.8, 56.4 and 7.3 percent of health care organizations. TQM had the most effect on process management and focus on employees and the less effect on focus on material resources, customers, and suppliers. The mean score of TQM implementation problems was 3.01±0.83 (medium) on a 5 scale. TQM Barriers in health care organizations were strategic problems, performance appraisal problems, human resource problems, structural problems, process problems respectively. Based on these results a Model with 10 enablers and 3 results’ indicators is introduced. Enablers are factors that enable organization to reach excellent and results are the out comes of organization, which can be achieved through implementation of enablers. This model will be developed through semi structure interviews and implemented in 3 health care organizations for determining the efficacy and efficiency ( this two phases has not done). Discussion: Total quality management is a good strategy for improving the productivity of organizations. However, if some important principles are not considered in TQM models before its implementation, the overall strategy of a TQM initiative may fail.
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This paper examines the relationship of learning organization variables with job satisfaction, organizational commitment and customer satisfaction among employees of health insurance organizations in the context of Iran. This study was conducted in three health insurance organizations. Two hundred sixty five employees and 1220 customers were randomly and proportionally selected, with a response rate of 80% for employees and 70 % for customers. The Job Satisfaction and organizational commitment instrument used all Items of G.H.Shwepker [2001] questionnaires for JS&OC (job satisfaction and organizational commitment) .The dimensions of learning organization questionnaire (DLOQ) of Watkins and Marsik [1997,2001,2003] was used to measure the state of development of three health insurance organizations in terms of learning organization dimensions. A third questionnaire was used with an eleven elements (developed by the researcher) to assess customer satisfaction. In terms of reliability analysis for all the three questionnaires, a Test-R-Test was used to test external reliability and Alpha Cronbach for internal consistency. In addition to content and face validity, construct validity was confirmed through confirmatory factor analysis, correlation statistics, and inferential statistics ANOVA (Kruskal Wallis Test) and t-test, were used to asses the relationships among the factors. Job satisfaction was found to be moderately and positively correlated to organizational commitment and positively and moderately to learning organization dimensions. Organizational commitment is positively and weekly correlated to learning organization dimensions. The result of Kruskal Wallis Test shows that the organization with higher mean ranks scores in most of it’s Learning organizations factors has higher result and significantly different result in terms of customer satisfaction in all CS (customer satisfaction) scales and subscales.
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Polychlorinated biphenyls (PCBs) are organochlorine chemicals that found widespread use in a diverse range of applications, with around 1.2 million tones produced worldwide. Although, the production of PCBs was banned in western nations in order to health concerns in the late 1970s, concentrations in the environment remain elevated, particularly in urban areas. There are two principal sources for atmospheric PCBs; primary source (ventilation of indoor air contaminated via leakage from old electrical equipment, building materials) and secondary source (volatilisation from soil contaminated as a result of past releases). Recent literature suggests that while PCB volatilisation from soil is likely to constitute a significant source of atmospheric PCB, new sources (primary) such as the ventilation of contaminated indoor air may constitute the most important contributions in urban areas. Aim: to evaluate the relative significance of primary and secondary sources of PCBs to the atmosphere at a number of locations in the West Midlands. Chiral analysis was employed to monitor enantiomeric fractions of selected chiral PCBs in topsoil and outdoor air over a one-year period. Overall 220 air and soil samples were collected from 10 different sites. Sampling locations were located on a southwest (upwind) to northeast (downwind) transect at intervals of between 3 and 15 km across the conurbation. In this way, a mix of rural, suburban, and urban sampling locations was studied. Samples were extracted, purified, and subjected to chiral GC/MS as previously described. Result: EFs in air for PCBs 136 and 149 are essentially racemic (EF= 0.5± 0.005) at all locations, while the EFs for PCB 95 in air are less obviously racemic, but display appreciable divergence from the EFs found in the corresponding soil samples. Volatilisation from soil appears to make a minimal contribution to atmospheric PCB concentrations at these locations. EFs of PCBs 95 and 136 are essentially racemic in all samples taken at the most urban location, which we tentatively hypothesised, was due to impaired microbial activity. The racemic EFs at Centenary Square may also reflect the fact that at this highly urbanised location, the supply of atmospheric PCB inputs (for which EFs are essentially racemic) may exceed the rate at which enantioselective degradation occurs. Further tentative support for this inverse relationship between degree of urbanisation and extent of enantioselective degradation comes from the fact that the greatest enantioselective degradation is observed at the most rural locations. An ANOVA test of chiral signatures in soil samples at each location in this study reveals no statistically significant seasonal or temporal (month - to - month) difference in edaphic chiral signatures. Furthermore, there are congener-specific variations in the extent of enantioselective degradation, with PCB 95 being degraded more than PCB 136 and 149. The direction of this enantioselective degradation is also broadly in line with our previous findings, although there appears to be less enantioselective degradation of 136 than previously observed. These results have potentially important implications for public health and environmental protection, as they imply that destruction of PCB stocks remaining in use in indoor environments are likely to result in a significant reduction in atmospheric concentrations. As the atmosphere is the principal point of entry of PCBs into the food chain, and is also the principal vector via which PCBs are transported from their – largely urban - source regions, such action is likely to reduce human exposure and limit the future spread of these compounds.
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Objectives: To determine the effectiveness of nutritional screening programmes in improving quality of care and patient outcomes compared with usual care. Methods: Searches were performed on MEDLINE, EMBASE, CINHAL, the Cochrane database, and Current Controlled Trials. Due to the assumed scarcity of high quality evidence, interventional studies in hospital or primary care settings with adequate reporting and comparisons were considered as eligible. Team members met after reviewing the papers. Decisions on inclusion or exclusion of papers were made when all agreed. Two reviewers independently extracted data from included studies. Results: 705 abstracts were considered and thirty full-text papers were ordered and reviewed. Following further review of the extracted data two papers met the inclusion criteria. One was a clustered randomized study of 26 general practices to evaluate the effectiveness of screening for elderly ailments including malnutrition. It concluded nutritional screening did not improve referral to dieticians, detection of nutritional problems, or patients’ quality of life. This study was underpowered for evaluating the effectiveness of nutritional screening. A non-randomized controlled before-after study of four hospital wards concluded that intervention improved weight recording, but not referral to dieticians or care at the mealtime of at risk patients. Discussion: Very few studies assess the effectiveness of nutritional screening with relevant outcomes and acceptable quality. The available evidence does not support systematic application of screening tools to hospital, or general practice patients. Given the current level of interest and political support for nutritional screening, further studies are urgently required.
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Introduction: Hearth disease is a major worldwide health problem with high incidence and prevalence in developed countries and rising incidence in developing countries. During last ten years, almost 20% of all acute hospital admissions are cardiac-related. More than 25,000 bypass procedures, about 40,000 angioplasty, and other coronary intervention procedures are carried out annually in the UK. CHD burdens the UK economy by £7.06 billion. Methods: Economic evaluation involves three basic steps of cost identification, cost valuation and cost measurement. The most accepted perspective is societal. Patient data are extracted from the patient file record or patients’ questionnaire or interview. Both quantitative and qualitative analyses are used. Discussion: Management is important clinically and from the economics viewpoint (e.g.; individuals and society) must be considered. CHD management is becoming increasingly costly. Direct and indirect costs divert scarce resources (patient’s or family and society) to medical care. Economic evaluation assesses the value of heart management in terms of their expected costs and expected benefits, if it includes an analysis of all direct and indirect cost and also all benefits forgone. Increasingly technical solutions are deployed and consideration must be given to which would better meet health sector objectives. Health care expectations: The basic principle is simple- comprehensive, high quality medical care should be available to all without financial barriers to access. However, in the face of increasing costs and ever more patients, this is under threat. In addition, sometimes, populations in greatest need are those least likely to receive it. It is expected economic evaluation aid to define choices on how best to use resources. The current distribution of resources leaves some high- priority demands unmet. The challenge of meeting the demand free public services is increasing. Demand for CHD treatment is undoubtedly rising. Rationing and allocation choice: Resource allocation strategies are designed to manage different areas of NHS effectively. There are several approaches to rationing however; there are moral considerations that ought to be recognised. Currently, rationing is according to a range of criteria that seem challenging. With scarce resources, it is important that services be provided efficiently. Efficiency within the NHS involved improving both productive efficiency and allocative efficiency. Equity in healthcare has become a priority. Willingness to pay (WTP): By evaluating WTP, patients’ preferences can be taken into account though there are difficulties in comparing user (patient) values with non-user (non-patient) values. There are also moral issues regarding the use of only economics data in decision-making. Moreover, there is need and preference conflict and requires to be managed appropriately. Conclusion: CHD growth in both developed and developing countries put health systems faced on greater demand to appropriate care. Thus, the notion of economic evaluation is to help health professional to divert resources to achieve the best health outcomes for individuals. There is an urgent need to develop preventive strategies in developing countries. Prevention and treatment strategies in developed countries should be modified for developing countries. These strategies should include approaches to prevent the development of risk factors in the population as a whole by changes in public policy as well as approaches that can be applied to high-risk individuals.
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Background: Patients with myocardial infarction (MI) and Heart failure (HF) have a poor prognosis. However, there is a paucity of data investigating the difference in the prognosis of patients who developed HF following either ST elevation (STEMI) or non-ST elevation MI (NSTEMI) as evidenced by electrocardiogram (ECG). Aim: To identify the prognosis of patients who develop HF following STEMI and NSTEMI. Method: Case notes of 204 patients who had an MI in 1998 were identified according to the hospital discharge summary by the Hull & East Yorkshire Hospitals Trust Information Department, were used to identify events between 1998 and 2005. Results: 40% had died by the end of 205. 68% of the sample were male (mean age 67 ±12 years). 71% of patients had STEMI and 29% had NSTEMI. The overall mortality was similar in STEMI and NSTEMI (41% vs 32%). However, there was a trend towards higher early mortality in STEMI during index admission (21% vs 11%). 81 patients developed HF following MI during the index admission. These patients had higher early (during first admission), late (during follow-up) and overall mortality rates when compared to those who did not develop heart failure Similar trends were observed in those with STEMI and NSTEMI. Patients with STEMI were at higher risk of developing HF during the first admission than those presenting with in NSTEMI. These patients had a similar overall mortality rate during the five-year follow-up. Patients with NSTEMI had higher late mortality compare to STEMI. Conclusion: Patients who develop heart failure following an MI have higher all cause mortality then those who do not develop heart failure. Patients presenting with STEMI and NSTEMI and develop HF have similar mortality over 5 years and hence require equally robust secondary prevention and heart failure management.
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Background: The predominant form of nursing education in Iran is university-based education. BSc, MSc, and PhD are the nursing programmes in Iran. The teaching method in Iran is very formal and nursing students obtain much theoretical information that they do not utilize it in practice settings. The system of nursing education in Iran involves a lot of exams and memorization, but students often forget the information after the exam. Thus, nursing students are not very satisfied with this kind of education. In contrast, there is not any professional relationship between practical settings and academic centers, and no major changes in the structure of nursing education were made in response to acceleration of university-based programme. In addition, it is worth mentioning that the dominant form of nursing care in the practical settings is the traditional form, and the practice experience is not integrated with the theoretical content presented in the school blocks of study. In fact, in the four years program of nursing education for getting BSc, there is need to study input, process, context, and output of educational process in order to reach a suitable model according to realities of Iran society health needs. Method: Using Grounded theory, this study is doing. The aim of this study is exploring the processes of theory-practice gap in nursing education in Iran at baccalaureate degree in order to reach a tentative theory about this gap. The phrase "grounded theory" refers to theory that is developed inductively from a corpus of data. If done well, this means that the resulting theory at least fits one dataset perfectly. Questions are included: Where is the gap between theory and practice, and which attempts should be made to bridge it? Samples are: nurse educators, nursing students, clinical nurses, and nurse administrators. The basic idea of the grounded theory approach is to read (and re-read) a textual database (such as a corpus of field notes) and "discover" or label variables (called categories, concepts and properties) and their interrelationships. The ability to perceive variables and relationships is termed "theoretical sensitivity" and is affected by a number of things including one’s reading of the literature and one’s use of techniques designed to enhance sensitivity. For covering this aims, constant comparison method throughout the open, axial, and selective coding of study has been applied. Strauss and Corbin method of coding is applying in this study. Finding: This study is in the early of its stage, and accordingly, the researcher is studying the nursing education context in UK (at Sheffield University). The early findings in UK are indicating that working based on local needs is the most important agent in nursing education. Conclusion: Getting to an appropriate educational model in nursing education needs a dynamic approach for realizing the realities, and practicing the attained model or theory based on local requirements. Accordingly, doing equivalent study for receiving a fitting model is an obvious need.
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Objective: A number of studies recently reported a positive association between the Glu298Asp polymorphism in endothelial nitric oxide synthase gene and coronary artery diseases (CAD), however, others were unable to replicate these finding. To re-evaluate the association between the Glu298Asp polymorphism and CAD in Caucasian population by performing a meta-analysis of all published case-control studies. Methods and Results: We searched Medline and Embase for articles about the Glu298Asp polymorphism and CAD, until March 2003. We found 20 studies and included 13 cases-control series from 8 studies in Caucasian, contained 7998 patients with CAD and 5471 healthy controls. The overall frequencies for TT, GT, and GG genotype were 12.6%, 43.0% 44.4% in cases, and 10.2%, 44.7%, and 45.1% in controls, respectively. The overall distribution of T allele in the case and control subjects was 34.1% and 32.5%. The pooled estimate odds ratio of CAD by use of Dersimonian and Laird’s random effects model was 1.11 (95% CI: 0.94, 1.30) for TT versus GG, and 1.12 (0.98, 1.28) for TT versus GT and GG combined. Conclusions: Our finding in a meta-analysis of 13 independent case-control studies, argued against the hypothesis that the eNOS Glu298Asp polymorphism is a major risk factor for coronary artery disease in the Caucasian population.
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Complexity science is about complex adaptive systems (CAS) and provides important concepts and tools for responding to challenge of health care in 21st century and as Holland describes, it is the science of 21st century. In this presentation, I will discuss some of the potential advantages of applying complexity science in my research in school health promotion. Complexity science originates from systems thinking and has been applied in biology, behaviour science, management, business, computer science and mathematics, physics and more recently, in health care. There are few reports about application of this theory in health but they look promising or at least challenging. A CAS is a collection of autonomous, interactive, and adaptive agents that act freely in diverse ways, which are unpredictable and, non-linear but interconnected. It is an ever-changing system, typically with fuzzy boundaries, built of multi-layer nested systems. The evolution of one system influences and influenced by that of other systems. Organisms such as human beings and organizations like health care organizations are good examples of these systems having Variation and non-linear pattern of cause and effect, interactions and change as concepts of CAS. One of the key benefits of the complex adaptive system approach is that it helps you see yourself in the context of a population of agents and helps you see your actions in the context of a population of strategies. In designing my research, I am able to choose from among a range of strategies, otherwise called research methods. I selected semi-structured interviews, participant observation and document analysis. I am interviewing, I meet and interact with teachers who are autonomous agents who make choices what strategies in a context of departmental and school policies described in documents.
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Comprehensive geriatric assessment (CGA) has become associated with a set of approaches to service provision in the care of older people. The models can be used in a variety of settings, including hospital inpatients, ambulatory care and nursing home care. In CGA programmes the multidisciplinary, multidimensional nature of the assessment of health, rehabilitation and social care needs is formalised, often using standardised assessment instruments. The results of these formal assessments are then either used to inform or prompt treatment and management recommendations which may be carried out in dedicated inpatient units (Geriatric Evaluation and Management Units- GEMU), provided as recommendations to the referring physician or team (Geriatric Consultation Service), or delivered in the patient’s home or other ambulatory care setting such as the day hospital or outpatient clinic. During the past 5 years or so, a key issue in the delivery of comprehensive assessment processes is the notion that they should be targeted to frail older people. In this context, frailty is now a well-defined and measurable concept, which has been shown to associate with key clinical syndromes in disease presentation. Measures of frailty can therefore be used to identify “need” for multidimensional assessment. Further, measures of frailty have been shown in some populations to be more effective predictors of outcome (principally mortality) than conventional clinical measures (such as diagnosis, specific disease severity or age). Being able to relate measures of frailty and comprehensive assessment to outcomes in the UK will help us to develop and target appropriate health care technologies more effectively and efficiently to the benefit of older people in need of inpatient hospital care. So; this study is to examine Interaction between CGA, Frailty and Clinical Syndrome and their Effects on Outcomes in Elderly hospitalized patients in Barnsley Hospital. Sheffield, UK.
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All health systems across the world have faced new challenges, which is primarily referable to increasing the cost of health care services as well as growing demands for new and expensive health technologies. The aim of this study is to analyse the main challenges facing the Iranian health system. A review of available governmental and relevant publications about Iranian health care system was undertaken to assess the direction of future healthcare policy. Electronic news agencies, newspapers, and parliament’s electronic news also reviewed to realise policy-makers points of view about the health system. Healthcare services in Iran have had a great success in primary healthcare services in last 25 years, which is mainly attributable to National Health Networks policy. Between 1979 and 2003, average life expectancy at birth increased from 57 to 70 and infant mortality rate fell from 104 to 26 per thousand live births. Active vaccination system, very good distribution and coverage, free end point services, family planning, maternal teaching, and primary referral system are of strong advantages of health networks in Iran. However, the healthcare system is now subject to a range of new pressures that must be addressed. Many of these pressures are common to all health services (rising consumer demands and expectations for expensive new technologies, changing disease patterns, and resources shortage), but some are largely specific to Iran. Financial fairness contribution of the population to health system, responsiveness of health system, overusing new technologies, inadequate integration of health services, and inequitable distribution of the resources are of the main challenges of health system in Iran. In addition, considering demographic changes of the Iranian population in recent decades, which made Iranian population young, potential pressures due to an aging population will reveal in coming years. Many of these pressures relate to policies and the management of the system. Therefore, the role of macro planning in health and health policy is considerable to manage the pressures. Realistic targeting, well planning, and well organising could make the current system more cost-effective, equitable, and accessible to all of the population. Health Technology Assessment, as an aid in decision-making, could be a valuable part of decision-making process in Iran in improving effectiveness and efficacy of the health system.
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Background: Iran has been a very disaster-prone country throughout its history. Wars, earthquakes, floods, droughts, inversion effects of air pollution in metropolitan have occurred many times, affected millions of people, and have claimed hundred thousands of lives during past century. Recently the fatal earthquake of Bam claimed more than 30000 lives and many casualties and economic lost, while in USA, a similar earthquake just killed 2 people and damaged much less. This may raise a fundamental question in our mind: why do disasters in developed countries cause the least amount of damages while in developing countries such Iran in the same situation the most indemnity? Methodology: This research aimed at studying existing Disaster Management System (DMS) in Iran and illuminating weaknesses during a crisis using a survey and reviewing the literature on DMS in developed and developing countries. Results and Discussion: In Iran, disaster management is managed by National Committee for Natural Disaster Management, which is located in Ministry of Interior. When the National Disaster Management Organization (NDMO) is located in a line ministry, it may not be able to guarantee the representation and participation of the other line ministries. Considering our culture and annually billions $ damages of natural and manmade disasters and claiming much life (which we cannot account their worth by money), psychological and economical problems as aftermath of disasters, Creating NDMO in president’s office has many advantages. Disaster management is a cycle started from mitigation, preparedness, response and ended with recovery. In Iran, in mitigation and preparedness phases we have not done much. There is no stiff rule in building code, planning for response, drill and etc. We have had many disasters and we have many experiences in response, so DMS, response to disasters rationally well. Preparedness for response increase effectiveness and efficiency of response. Recovery after major incidents includes psychology, jobs, homes, and treatment matters. There is a need for planning in this period. Finally, every phase of DM should comprise a cycle of comprehensive planning, execution and feedback. Any type of crisis planning needs sufficient information from databases. Lack of Access to great databases like spatial database information and Geographic Database Information and communication among organizations to interchange information are major problems for disaster managers before and after disasters. Another problem is fiscal affaires after disasters. In developed countries, insurance plays a main role in risk transfer and Funds for rebuilding. Finally, Experiences recognized education as a major part of reducing vulnerability. People need appropriate public education in self-protecting behaviors, relief aids, mitigation etc. Except some maneuvers and limited educations, we have not done much education to improve effectiveness of DM. Conclusion: there are some challenges In DMS: firstly, creation of an independent NDMO in President’s Office is a necessity. Secondly, in disaster management, all aspects must be considered in the same importance and as a whole not separately. Thirdly, disaster databases such as SDI or GDI should be created and finally insurance and education of people should consume great deal of efforts.
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Objective: This abstract focuses on theoretical background for the notion of “equity in health care” and on the implications of applying these theories to the health care of developed and developing countries. Equity Principals and the Implications: There are different theories about the principle of Equity or Justice such as Altruism, Utilitarians, Marxists, Rawls’ theory and Nazick’s entitlement. Among these theories, some of them are applicable to health care such as Libertarianism and Egalitarianism. The focus of the Libertarians is on the extent to which people are free to purchase the health care that they want. The Libertarians’ principle is the main equity base for private health systems. In contrast, Egalitarians suggest that finance of the health care should be according to the ability to pay and distribution of health care should be according to the need (ill health). It seems that policy makers in most developed countries such as European countries accept the Egalitarians’ principle and application of this equity principle by their health systems has significantly reduced health inequities and inequalities in these countries. There are a limited number of studies to look at equity in the health care of developing countries. A common equity principle for these countries is “equal access for everyone” and different mechanisms are applied to attain this target. Despite the overall improvements in health care in recent years, evidence indicates that many of developing countries have failed to provide equal access to health care for all in need. The financial limitations of the governments, spending about 70% of the health care resources on hospital-based care, unequal access to hospital services in favour of urban population, income inequalities among population, and lack of consistent and up-to-date information of inequalities, make developing countries unable to monitor and prevent inequities and inequalities of health care. Conclusion: The main equity principle in the health care of developed countries is Egalitarians’ principle in which, health care should be financed according to ability to pay and should be delivered according to the need. Applying the equity principals to the health care of developed countries has deeply promoted equitable health care in these countries. There are a limited number of studies about this issue in developing countries. A common equity target in these countries is “equal access for everyone in need” which is close to the Egalitarians’ point of view. However, some factors have hampered these countries’ attempts to achieve their equity goals. To be able to attain their equity targets, these countries need to reduce income and economic inequalities, to provide consistent and up-to-date information of the existing health inequities and to consider reallocation of limited health resources from hospital services to the basic preventive and curative care. Further evidence is needed to assess the issue of equity in the health care of developing countries.
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Introduction: An adverse event is defined as an unexpected event such as a patient fall, a drug reaction or an infection, which leads to patient injury and is caused by healthcare management rather than patient own diseases. There is evidence to suggest that adverse events frequently occur in modern health systems. However, there is a lack of knowledge about the nature of adverse events and the performance of different methods to explore them. This survey is part of a PhD project, which aims to investigate the scale and nature of adverse events and compare different methods to identify them. The project has not been completed yet. The aim of this abstract is to explain the design and methodology of the project. Objectives: To explore the relative performance of two promising methods of medical record review (18 item and 8 item-screening criteria) for detecting adverse events and to compare this method with the routine hospital incident reporting system for detecting adverse events. Methods: A proportionate stratified random sample of 1000 patient records from Surgery, Medicine, Elderly, Orthopaedics and Urology specialties of a large UK hospital were selected and reviewed by nurses using a list of explicit criteria. Identification of one or more positive criteria was considered as an indicator of a potential adverse event. Doctors then reviewed these records in more depth and decided if there was an adverse event. If the doctor was fairly convinced that there was an adverse event, a structured review form was completed to explore the nature and likely causes of adverse event. We also check the hospital incident reporting systems to see if any adverse events were reported to the system about any of the patients in our sample. The data collection and analysis has not been completed yet. A preliminary analysis of the data showed that in 407(40.7% of) cases at least one criterion was recorded positive by the nurses. Positive criteria do not necessarily mean an adverse event; however, these cases are considered as potential for adverse events and are forwarded for further review by the doctors to check if there is any adverse event. This study has the potential to contribute to methods of research in this field, which will inform future quality improvement initiatives and contribute to future research.
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Background: Dental caries is a process that may take place on any tooth surface in the oral cavity where a microbial biofilm (dental plaque) is allowed to develop over a period. From the public health perspective, the prevention of caries is still a major challenge. The development of dental caries within the mouth follows a fixed hierarchy indicating that tooth surfaces vary in caries susceptibility. The most susceptible surfaces are the buccal pits and occlusal-fissured surfaces of the first molar teeth. Since the 1960`s many trials have investigated the effectiveness of using sealants on pit and fissure surfaces. However, the cost effectiveness of sealants is an important issue considered by many studies noted that cost-effectiveness of sealants would be enhanced by using trained auxiliaries to apply them. The changes in dentistry and oral health reveal a need to review the roles of dental auxiliaries in order to deliver quality care cost-effectively. There were number of studies conducted on the effectiveness of dental auxiliaries around the world. According to the purpose of this project, studies evaluated the effectiveness of Professional complementary to dentistry (PCDs) and different type of dental auxiliaries in carrying out complete restorations and in the preventive therapies, fissure sealants, traumatic restorative treatment were evaluated in literature review. The aim of the present study is to review the literature and assess whether PCDs can perform pit and fissure sealants as effectively as dentist through investigation of the caries preventive effect of sealant placed by dentist relative to sealant placed by PCDs. Method: Electronic databases were searched till January 2005. The databases which were used are: Medline via Ovid, Cochrane databases of systematic review , DARE (Database of Abstracts of Reviews of Effectiveness), CCTR (Clinical Controlled Trials Register) Cochrane Library, Dissertation Abstracts International database, NHS EED, CENTRAL, NHS CRD (National Health System Centre for Review and Dissemination). In addition, a hand search of references has been done after searching relating articles in mentioned databases. Results: The conclusion of the Galloway review (2003) shows that the studies available were not only poor, but also old. They searched from the 1960s, with more coming from the 1970s than from other decades and few of these studies come from the UK. It also recommended that there is a need for rigorous British studies to improve the evidence about effectiveness and cost-effectiveness of PCDs. In updated search for effectiveness of work by PCDs in carrying out fissure sealants, only one of the studies compare the caries preventive effect of fissure sealant placed by PCDs but in the USA and in a single private practice. Folke et al concluded that assistants showed increased risk of failure in occlusal sealants compared with the Hygienists, whereas dentists did not differ significantly from the dental hygienists in one private practice. Conclusion: It can be seen from present review that, some new research has been published after Galloway review, which could answer some of the questions regarding quality of work by PCDs. In this regard further researches need to demonstrate the preventive effectiveness of fissure sealant placed by PCDs in the community services in the UK and compare them with the dentists’ work.
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Background: This paper is a review of current oral health in Iran Aim. The main aim of the review was to look at the current oral health profile of Iran from the dental public health point of view and to make comparison other countries. Methods: The review tried to consider all published papers and electronic information regarding the subject. Dental caries and periodontal disease rates, and dental health delivery services in Iran were explored. Some information was collected personally by e-mail or telephone contact with related people or organization. Results: About 15000 dentists (1/5000 population) are delivering oral health in private and community dental services. More than fifty percent of children age 12- year-old has some caries experience. Conclusion: There is not much difference between dental caries rate in Iran and other countries. However, the relevant studies in Iran are neither reliable nor carried out on a national basis. There is need for a nationwide survey of all aspects of oral health in Iran. Improving oral health should be considered as an important part of the public health programme in Iran.
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Objectives: The study examined the hypothesis that severe dental caries may affect growth and development in preschool children. Methods: The study examined 218 children with severe caries using standard diagnostic criteria. All children were weighed and measured and a food frequency questionnaire was completed for each. Six months subsequent to tooth extraction, 131 of the children were followed up and underwent repeat measurement of height, weight, dental health and food intake. For each child, body mass index (BMI) was calculated, and all measurements were converted into standard deviation scores and compared to the UK 1990 growth reference. Results: In the six months period after having their decayed teeth extracted the children’s BMIs had increased by 0.654. Two-sided t-tests for paired data showed this difference to be significant (P< 0.01). Conclusion: Treatment of gross dental disease appears to promote "catch-up" growth and normalisation of body mass index.
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Aim the main aim of this study was to examine the usability of a new dietary measure among a high caries population and examine whether reported food intake, when weighted by frequency and cariogenicity, was associated with increased caries rates within a high caries population. Key method Two hundred and eighteen children with caries were examined using standard caries diagnostic criteria. The examinations were carried out by a single calibrated dental examiner. A food frequency table was completed by the parents of each participant and this was analysed by weighting foods’ cariogenic potential by the frequency of consumption, and summing the product. The total cariogenicity score for each child was then plotted against its dmft and dt and correlation coefficients were calculated. Result the mean cariogenicity score using this new measure was 71.02, with a range of 31.96 to 135.24. The standard deviation was 16.72. Total cariogenicity scores using the new measure and dmft were weakly correlated, with the Pearson correlation co-efficient being 0.130 and for dt 0.131. These correlations did not reach significance. Conclusion The study has demonstrated that in children with caries, reported food intake (when weighted by frequency and cariogenicity) and caries are only weakly and non-significantly associated. Dietary intake, when measured in a way, which takes account of all food groups, was therefore not strongly associated with caries when measured on an individual level.
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Objectives: The aims of the study were to assess current practice in oral health care among residential homes for the elderly in Manchester, Salford and Stockport and to evaluate the effectiveness of a programme to increase carers’ knowledge in key areas. Methods: The study was part of a randomised control trial, conducted in 56 residential homes, allocated randomly to test and control groups matched using the minimisation method. Managers of participating homes were interviewed to gather baseline data on the homes and oral care provided. A training session in oral health care for the elderly was provided for care staff in the homes. Carers` knowledge was assessed before and after the training session and their perceptions of the training were sought. Results: The survey of mangers revealed common inadequacies: the lack of any training for care staff in oral care; the lack of protocols for oral care (at 68% of homes); the lack of initial oral assessment. After the training session, the oral health knowledge of carers (467 carers) showed a significant improvement (McNemar Test, P< 0.005). Conclusion: Current practice in most homes is inadequate. The training sessions improved the carers’ knowledge in key areas but improvements in the organisation and delivery of care are clearly also required.
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Objectives: To determine the prevalence of Knee Pain among Iranian industrial workers and how it varies with demographic factors, job title, and gender. To determine work exposure differences between occupational groups, and to explore associations between Knee pain and physical and psychosocial factors at work, as well as lifestyle factors. Summary of background data. Most knee Pain epidemiological data is related to developed and industrialized countries with high income and there is very little information about Knee Pain in the general population in developing and low-income countries. There are even fewer studies in working populations. Methods: All 18031 employees from the largest Industrial group in Iran were included and 77.7% responded. The prevalence of Knee Pain, work exposures and lifestyle factors were recorded according to the standardised Nordic Questionnaire for analysis of musculoskeletal symptoms. Demographic data and lifestyle factors (age, sex, education, weight, work experience, smoking, fitness training) were also collected. Multiple logistic regression model analyses were applied to determine the risk indicators. Results: The majority of this study population are young males (under 30) and a small proportion of the work force is female (4%). The one-year prevalence of self-reported Knee Pain in the Iranian industrial population was 22.9 % (Males=22.7, Females= 25.9). The one-week prevalence was 9.2 % and prevalence rate of absence due to low back pain was 4.5%. In the multiple logistic regression models, heavy lifting, repetitive work, no encouraging organizational culture and monotonous work were significant risk factors for Knee Pain in the previous 12 months. Conclusions: Knee Pain is common among industrial workers in Iran, but in comparison to western countries, there is a considerable difference in prevalence. Work-related physical and psychosocial factors influenced the prevalence of Knee Pain. In order to better understand the natural course of Knee Pain in a working population in developing countries further longitudinal studies for measuring, prevalence, incidence and recurrence simultaneously are recommended.
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Introduction: Globalisation increases the need for suitable “quality of life” (QOL) measures suitable for cross-national comparison or aggregation of data across cultures. QOL as a construct is noted to be influenced by many factors such as, socio-demographical and cultural variables. It is important, therefore, to ensure that an instrument developed in one culture is valid in another. In measuring SWB, some researchers prefer using a horizontal format of Visual Analogue Scale (VAS), while others opt for a vertical presentation of the VAS. However, some investigators suggested that the scales’ orientation and the type of VAS may affect the respondent’s response. Aims: The current study, including two experiments, was designed to compare the sensitivity ACSA (1) to cultural differences, (2) to some socioeconomic and demographic variables and (3) to variations in response format. Experiment 1: A sample of 424 volunteers, Iranians= 83, (teachers, 29 % females), and Belgians= 341, (students, 72 % females), rated their current SWB on the Anamnestic Comparative Self Assessment scale (ACSA), a rating scale for global SWB. Besides some socio demographic data were collected. The results of independent t-test comparing the mean and Levene’s test to compare variances of SWB of the two surveyed samples (Iranians and Belgians) revealed no significant difference between score means (MIran= 70.48, MBelgium=70.75) (t (422) = .11, P< .91) of SWB rating and also variances of scores of SWB ratings of two samples (SDIran= 19.81, SDBelgium=19.91) (F= .26, P= .61). Meanwhile, using Univariate Analysis of Variance (ANCOVA) a significant main effect of (1) gender (F (1, 45) = 5.57, P= .023) was found in Iranian sample (not Belgian sample). Experiment 2: A sample of 24 male and 124 female undergraduate students (M age= 19.10) who assigned randomly to three groups, were asked to rate their current overall SWB on the (ACSA). The ACSA presented in three formats: two equivalent vertical and horizontal bipolar scales and a numerical rating scale. Two sets of anchor points were evaluated: (-5 to +5) and (0-10). The results of the ANOVA to compare the score means and Levene’s test to compare variances of SWB rating on different formats of ACSA indicated that the SWB rating was not influenced by the direction of the scale (Vertical Vs Horizontal) nor by the kind of anchor points ((-5 to +5) or (0-10)). A negative skew for SWB rating displayed on all scales but a higher percentage of scores distributed on the upper part (center point to top) of the scale with anchor-points (-5 to +5) than scales with anchor-points (0-10). Conclusion: In cross-notational and cross-cultural comparison studies, depending on one’s study objectives, ACSA should be considered as a complement or an alternative to conventional SWB instruments.
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Diffusion MRI has become one of the most powerful tools for the detection of acute stroke. The signal attenuation caused by the diffusion process is normally assumed to be exponential .The decay constant which is often called the “apparent diffusion coefficient”(ADC) is measured by 2 or 3 points in clinical applications yielding mono-exponential decay curves. The diffusion signal attenuation of water molecules on human brain was measured with a certain pulse sequence. The sequence was modified to work over a range of diffusion times and high gradients. The decay was measured precisely for 96 b-values up to the maximum possible gradient amplitude of 28.8 mT/m. A significant deviation from mono-exponential behavior was observed consistent to the multi-exponential model. The NNLS-diff computational code, using a non-negative least squares (NNLS) algorithm was developed for the data analysis. The diffusion time dependence of human brain tissue was studied for diffusion times between 20 to 53 ms using 16 b-values ranged from b=0 to the maximum possible b-value in each case. At all diffusion times, there was a diffusion coefficient at approximately 1x10-3 mm2/s and another at about 6x10–5 mm2/s. For some diffusion times a small contribution at about 1x10 -2 mm2/s was also detected. Our results were consistent with work of others. However, we observe small diffusion time dependence for the smallest diffusion coefficient, which has not previously been reported. More work is required to identify the source of the new observation.
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Even though each the focal liver lesions image has, it special pattern but in most of case differentiation between them is not easy task for radiologist. It seems computer aided differentiation can be useful in this step of diagnostic. Two independent radiologist assessed slice of MR liver images and twenty-three patients with focal liver lesions (3 Cyst, 6 Haemangioma and 14 Metastasis) and 10 normal livers were chosen for study. A texture analysis software and mathematical software were utilized to differentiate region of interest (ROI) among and in between ill and healthy liver slice images based on their differences in texture parameters. Linear discrimination analysis (LDA), Principle Component Analysis (PCA), combinations, and fusions of LDA and PCA were used as classification methods. Multiple ROIs were defined on control images to find out their best features data and linear discrimination functions for differentiation with high rate confidence. Sample images examined using the control set examination findings. The results then compared with radiologist reports. All classification methods allowed discrimination among and between healthy and focal lesion regions on the images. Automated texture analysis concurred with radiological diagnosis in all Cyst patients and all but one metastasis report. However, Haemangioma reports were classified as metastasis lesions. All samples of normal livers and normal parts of metastasis liver were correctly differentiated from metastasis. But more than 50% of patients reported as a metastasis diagnosed as normal. Comparison with visual diagnostic reports of MR liver images suggest that automated texture analysis has the potential to improve classification rates in the radiological diagnosis.
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Ulcerative colitis (UC) is an idiopathic inflammatory bowel disease that affects the colonic mucosa. UC results from loss of tolerance towards the normal gut microbiota, leading to chronic mucosal inflammation. UC is incurable, and current therapies involve the use of immunosuppressant and anti-inflammatory drugs, steroids, and in extreme cases, surgery. UC treatments have a number of limitations, and can induce non-specific suppression of the host immune response, resulting in undesirable side effects, while having little effect on mucosal bacterial populations that are involved in disease aetiology. Manipulation of the composition of the microbiota to change mucosal cytokine profiles, by probiotics, may provide an alternative therapy. In vitro modeling was used to investigate the induction of immuno-modulatory cytokines in two human epithelial intestinal cell lines, Caco2 and HT-29. The cells were co-cultured for 3 and 8 hours with a range of mucosal bacteria: Clostridium clostridiiforme, Enterococcus faecalis, Escherichia coli, Lactobacillus paracasei, Peptostreptococcus anaerobius, and Bifidobacterium bifidum, Bif. longum, Bacteroides fragilis, Bact. thetaiotamicron and Bact. vulgatus. Quantitative real-time PCR assays for the cytokines interleukin-4 (IL-4), -10, -18 and transforming growth factor beta-1 (TGFb-1), -2, -3 were developed, and used to assess cytokine gene expression. Results were normalised for cell number against b-actin and GAPDH. High basal levels of IL-18 mRNA were detected in both cell lines. Caco2 expressed higher levels of TGFb_isoforms than HT-29 cells. Peptostreptococcus anaerobius, Bact. vulgatus and Bif. longum up-regulated IL18 in HT-29, whereas Bact. fragilis and Bact. thetaiotamicron down-regulated this cytokine. All bacterial isolates down-regulated IL-18 mRNA levels in Caco2, and all bacterial isolates except Bact. fragilis and Bact. thetaiotamicron significantly up-regulated TGFb-1. There was little change in expression of IL-4, IL-10, TGFb-2 and TGFb-3. Caco2 had higher baseline levels of cytokine mRNA, compared to HT-29. Mucosal bacteria induced a higher level of immune response in HT-29 than Caco2. This could be because the phenotype of HT-29 cells is that of crypt epithelial cells, which in healthy mucosa, do not normally encounter live bacteria. In a situation of chronic inflammation, these nascent epithelial cells respond to bacterial challenge by producing immuno-modulatory cytokines. In contrast, the more mature Caco2 cells are in constant contact with commensal bacteria and their products and have evolved to tolerate antigenic challenges, and maintain homeostasis. Accurate and reliable assays for the use of quantative rtPCR to investigate gene expression levels of human immuno-modulatory cytokines have been developed. Experimental evidence provided a working hypothesis regarding the abilities of different commensal organisms to trigger the immune system, and re-establish healthy immune status. Further studies to tailor potential immune modulating probiotic species for the treatment of individual UC patients, based on this hypothesis, are currently in progress.
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Studies of interaction between viruses and mitochondria have shown that they can affect the mitochondria and induce mitochondrial alterations. Sometimes this interaction leads to induction or inhibition of apoptosis in infected cells. Interaction between adenoviruses and mitochondria showed the first evidence that a viral infection could affect the cell and induces apoptotic process. In addition, linkage between human diseases and mitochondrial dysfunction has been revealed. A Previously work showed that poliovirus infection led to decrease in total cellular respiration induced by inhibition of mitochondrial electron transport chain. We have screened different human viruses to observe their effect on mitochondrial respiration using Oxygen Electrode (OE). Here we report the effect of influenza A virus (IAV) on mitochondrial cell respiration. The addition of antimycin A (AA) to respiring cells completely blocked cellular respiration that indicates nearly all of the cellular consumption of oxygen is attributed to the mitochondria. Our result showed human influenza A virus (IAV) decreases total cell respiration in infected MDCK cells.
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Body Mycobacterial diseases are an important group of animal infections, which have tremendous economic and public health ramifications. Bovine tuberculosis and paratuberculosis, both identified years ago, have no effective vaccine or treatment controls in farm animals. In Asia, there are only seven countries where test-and-slaughter schemes are currently ongoing to control bovine tuberculosis. On the other hand, among five mycobacteriology reference laboratories, licensed by OIE, in the world, none is located in Asia. Iran has proved to have an efficient control program against tuberculosis in cattle since the 1960s. While the locally made PPD tuberculins required for the testing of cattle are apparently useful in the Iranian scheme, there is no organised establishment in Iran to support the control programme with bacteriological services. This presentation considers the needs and potentials of a reference laboratory facility in Iran.
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Background: Resistance to antibiotic agents is a world- wide problem, based on some reports from different hospitals. Susceptibility and resistant pattern of microorganisms in hospitals is important for manage and treatment of hospital acquired infections. This study was designed to determined susceptibility and resistant pattern of isolated microorganisms in Loghman Hakim hospital. Methods: The research method was descriptive and its technique was observational in three month of spring of 2002 over the 268 patients that have been refer to loghman hakim hospital and for different reasons need to have specimen culture (blood, urine, sputum, ulcer, abscess, CSF, etc). Blood agar and Macconkey agar for blood culture, Chocolate and Blood agar and Macconkey agar for CSF and other specimen cultures have been used. Results: The most common culture- positive was from Poisoning ward and endotracheal tube samples. The most common microorganism was Escherichia coli (E.coli) (60, 19%) and klebesilla (54, 17%) respectively. Maximum resistance of E.coli observed to Co-trimoxazol (71.6%), Ampicillin (84.3%), Cephazolin (83.7%) and Maximum resistance of klebesiella reported to Co-trimoxazol (72.6%), Ampicillin (96.1%), Cefazolin (76.7%). High resistance rate of microorganisms such as E.coli, klebsiella and Pseudomonas to antimicrobials such as Co-trimaoxazol, Aminoglicosides and first generation cephalosprins and increasing of Oxacillin-Resistance Staphylococci coagulase negative may be resulted from over use of these antibiotic agents. Conclusion: Early beginning and inappropriate dosage of antibiotic agents may be associated with an increased likelihood of the development of multiresistant bacteria,. So it is highly recommended to prohibit unnecessary prescription of antibiotics.
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Background: Gemistocytic astrocytomas behave more aggressively than other diffusely growing astrocytic tumours. They are characterised by a high mutation rate of the p53 gene and cytological as well as immunological abnormalities including frequent perivascular mononuclear infiltrates. Microglia are resident brain macrophage precursor cells that form a network of immune competent cells within the normal central nervous system. They are of increasing interest in the context of glioma growth. Material and Methods: We selected 23 tumour samples from among 201 samples obtained from patients with gemistocytic astrocytomas operated on at the Mayo Clinic between 1985 and 1998. These tumours have been previously analysed for p53 mutations, p53 protein and proliferative activity (Neurosurgery 48:187-194, 2001). Immunolabelling for three established microglial markers, CR3/43, Ki-M1P and iba1 was carried out on adjacent tissue sections. In addition radioactive in-situ hybridization was carried out. Results: A high number of microglial cells were detected in gemistocytic astrocytomas. More microglia were present when the fraction of gemistocytes was high (correlation coefficient= 0.740, P< .0000542). Varying numbers of gemistocytic tumour cells expressed MHC class II molecules. Importantly, the more class II immunoreactive gemistocytes were present, the fewer class II positive microglial cells could be detected (correlation coefficient= -0.623, P<0.00148). Conclusions: Our findings support the view that gemistocytic astrocytomas contain unusually high numbers of microglial cells. The finding of aberrant MHC class II expression by gemistocytic tumour cells correlating with a loss of immune competent, MHC class II expressing microglia sheds new light on the immunology of these tumours. We suggest that the findings reported here may be related to the especially poor prognosis of gemistocytic astrocytomas. It is well known that the proliferative potential of neoplastic gemistocytes is very low and it has remained an intriguing question as to why these tumours are so “successful” biologically. The fact that aberrant expression of MHC class II molecules by non-professional antigen presenters may induce T cell anergy could provide one explanation.
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Human papillomavirus type 16 E5 protein (HPV16 E5) is expressed early in papillomavirus infection in the deep layers of the infected epithelium, and is localised primarily in the cell Golgi apparatus (GA) and endoplasmic reticulum (ER). We have shown that E5 prevents transport of the major histocompatibility class I (MHC I) to the cell surface and retains the complex in the GA. Here we show that these effects are due, at least in part, to the interaction between E5 and many types of MHC I heavy chain (Hc). In addition, we have further investigated the domain necessary to down-regulate surface MHC I and to interact with Hc, by using deletion mutants of E5, including either helical domain 1, 2 or 3. We show that the down-regulation of surface MHC I (HLA I in humans), and interaction with Hc are mediated by the first helical domain of E5. Although E5 down-regulates classical HLA selectively as it does not down-regulate non-classical HLA (ref. 4), the interaction with the Hc of classical HLA I is not specific for a particular type of HLA I, suggesting that E5 can interfere with antigen presentation by most, if not all, of classical HLA I types. The down-regulation of HLA I can potentially have serious consequences for the host immune response to viral infection, as the ability of infected cells to present antigenic peptides to effector T cells would be compromised.
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Visceral leishmaniosis as a zoonotic disease is one of the important infectious disease due to severe side effects and mortality in children and because of at least two endemic foci in Iran (Firooz Abad and Djahrom in Fars State, Meshkin Shar and Moghan in Ardabil State). Despite all preventive procedures, the incidence of the disease has commonly increased which indicates the possible existence of other vertebrate’s reservoirs in addition to carnivoirs (main reservoirs of the Mediterranean visceral Leishmaniasis); therefore, rodents were examined during this research (1995-1997) in the endemic region of Meshkin Shahr. Comprehensive parasitological studies were conducted. Serological tests (Direct Agglutination Test) and cultivation protozoa were done in 120 sample rodents, which were captured alive. The prepared blood smears were undergone microscopic studies. Rodents that showed positive titers in DAT were also undergone necropsy .The prepared impression smears from Reticulo endothelial tissues (Liver and Spleen) were cultivated in NNN media. The observed livers and spleens of many rodents showed very low titers in many cases but showed significant pathological signs (Hepatomegally and splenomegally) even compared to higher titer rodents. The research procedure was changed by just considering the pathological signs of livers and spleens of sample rodents and ignoring the results of DAT .All the suspicious organs were cultivated in NNN. The captured rodents were Meriones persicus (116), Mus musculus (3) Cricetulus migratorius (1) and for the first time in Iran Leishmania donovani was isolated from M.persicus. In isoenzyme studies, zymodeme of isolated L.donvani , LON 50, was identified. Among 116 M.persicus 10.3% showed positive parasitological results and 52.6% had sero titers between 1:10 to 1:200 in DAT.
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In the last few decades, parasitic infections have created a major human health problem across the world. In developing countries the problem is beyond control and the number of new cases is on a continuous rise. Leishmaniasis is a tropical disease affecting large number of population. Development of an effective and inexpensive vaccine represents a practical way to control this disease, as available chemotherapy is always accompanied by sever side effects. The major surface glycoproteins of the Leishmania parasites, gp63 and HASP-B1 have been postulated to be good candidates for vaccine development. In this study Leishmania parasite gp63 and HASP-B1 antigens were screened for potential immunogenic CTL epitopes (peptides) in HLA-A2 (HHD) transgenic mice. Three peptides given the code names of C1, C2 and B8 derived from gp63 were tested in HHDII mice for their immunogenicity. Two peptides (C2 and B8) were shown to be highly immunogenic following one in vivo immunisation however, 2 immunizations were needed to improve the immunogenicity of the C1 peptide. These results were also confirmed by INF-γ and IL-4 profiles in cultured spenocytes. In contrast to IL-4, the amount of INF-γ in splenocytes cultured with relevant immunogenic peptides was significantly higher than those in controls.
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Tumours may either fail to stimulate an immune response a process known as immune ignorance or they may elicit innate and/or adaptive immunity in a process known as immune editing. Major histocompatibility complex (MHC) may play a pivotal role in immune editing as they present peptides that are recognised by cytolytic T cells. In contrast if MHC antigens are down regulated to avoid T cell attack they become susceptible to NK killing. In this study a large set of samples from patients with primary operable invasive breast cancer was evaluated for the expression of MHC class I heavy and light by immunohistochemical staining of 439 breast carcinomas in a tissue microarray. Forty seven percent (206 / 439) of breast carcinomas were considered negative for HLA class I heavy chain, whereas lack of anti-β2 m-antibody staining was observed in 39% (167/424) of tumours, with only 3% of the β2 m -negative tumours expressing detectable HLA heavy chain. A correlation with patient outcome showed a direct relationship between patient survival and HLA-negative phenotype (Log rank= 0.004). A positive relationship was found between the intensity of expression of MHC class I light and heavy chains expression and histological grade of invasive tumour (P< 0.001) and Nottingham Prognostic Index (P<0.001). To investigate whether HLA expression had independent prognostic significance, Cox multivariate regression analysis, including the parameters of tumour size, lymph node stage, grade and intensity of HC10 and anti-β2 m staining, was performed. In this analysis, lymph node stage (P< 0.001), tumour grade (P= 0.005) and intensity of MHC class I light and heavy chains expression were shown to be independent prognostic factors predictive of overall survival (P-values for HC10 = 0.047 and β2m = 0.018).
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Introduction: STAT-1 is the main signal transducer of γIFN signalling through the IFGNR1. STAT-1 can act as a tumour suppressor by induction of the cycle inhibitors p27 and p21 and proapoptotic signals such as casapse 1. Both γIFN knockout mice and STAT-1 knockout mice show enhanced susceptibility to both carcinogen induced and spontaneous tumour formation implying that immune surveillance by this pathways is an important extrinsic tumour suppressor factor. Tumours that become resistant to this pathway by a process of “immune editing” may have a worse prognosis. Methods: In the present study, we have determined the immunohistochemical expression of IFNGR1, STAT1, p27 and p21 in a 730-specimen breast tissue array. These specimens comprise a well characterized series of patients (70 years of age or less, mean: 54) with primary operable breast cancer, diagnosed between 1987 and 1992. Results: All tumours expressed IFNGR1. Cytoplasmic and nuclear expression of STAT1 was detected in 312/730 (42.7%) and 148/730 (20.3%) of breast tumours respectively. Survival analysis demonstrated that patients with tumours with low STAT1 expression (either nuclear or cytoplasmic) had an improved survival compared with those with higher expression (log rank test, P= 0.03). In accordance, multivariate analysis using Cox regression in lymph node positive patients revealed that low expression of STAT1 was independently associated with a good prognosis (HR 0.425, 95% CI 0.225-0.802, P= 0.008). As STAT-1 has a very short half-life its expression is undetectable in normal tissues. In contrast, hyperactivation or mutation may result in an increased half-life but abnormal signal transduction. To assess if STAT-1 was active co-expression of p21 and p27 were also measured. Tumours expressing STAT-1 but not expressing either p27 or p21 had a significantly worse survival than STAT-1+ p21/p27+ tumours or STAT-1 – p21/p21+ or STAT-1- p21/p27- tumours. Conclusion: This study expression of STAT-1 is an independent prognostic marker predicting poor survival in lymph node positive beast cancer. As STAT-1 cannot be detected by immunohistochemistry in normal tissues due to its short half-life, expression in tumours implies abnormal expression. Perhaps breast tumours respond to immunosurveillance within lymph nodes by selection of variants with abnormal STAT-1 regulation which allows them to escape immune recognition.
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Chronic immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by antiplatelet autoantibodis. The major target of the anti platelet antibodies is platelet membrane glycoprotein IIb/IIIa. In order to characterize the immunodominant epitopes in the structure of GPIIIa, the extracellular portions of GPIIIa will be expressed and purified. These antigens will be tested for antigenicity in further investigation. The first segment of GPIIIa which was considered for expression as a recombinant glutathion S-transferase (GST) fusion proteins included IIIa22-262 which encompass amino acid residue 22-262 of the 762 amino acids of GPIIIa. A segment of GPIIIa complementary DNA (cDNA) was subcloned into the 39 end of the Schistosoma japonicum GST gene in the bacterial expression plasmid vector, pGEX 6P-1 (Amersham Pharmacia Biotech). In summary, the expression plasmid vector, pGEX 6P-1 containing segment IIIa22-262 was introduced to E.coli. Saturated overnight culture was used and the bacterial cells were grown to log-phase. IPTG was added to the culture to induce overexpression of fusion protein and the cells were grown for an additional 1-3 hours. Bacterial lysate containing recombinant protein was prepared by sonication. The fusion protein was purified from total cell extract using glutathione-agarose beads. Specificity of the GST-fusion proteins was confirmed on Immunoblot probed with rabbit anti-GST polyclonal antibodies. PreScission Protease was used to remove the GST tag. Protein extract and purified products were analyzed by SDS gel electrophoresis. The recombinant GST-fusion protein IIIa22-262 was successfully expressed and purified in large quantities but the yield of the IIIa22-262 peptide after enzyme treatment was low. When a good yield is fully obtained, the purified protein segment will be used for T-cell stimulation in culture.
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Colorectal cancer is the third leading cause of cancer death with an estimated 430,000 death per year worldwide. This cancer is a common disease that about 95% is sporadic. Accumulation of somatic mutations in a cell is the basis of sporadic colon cancer. Mutations of different classes of genes have been described in colon cancer etiology such as oncogenes and suppressor genes. Primary screening using single strand conformation polymorphism (SSCP) has been carried out for 132 colorectal cancer samples. Samples showing altered mobility on SSCP gels were sequenced. PCR-SSCP and Sequencing of the CHEK2 exons in DNA tumours revealed a polymorphism at nucleotide 252 in codon 84 and CHEK2 alteration in exon 11. These included missense mutations that altered amino acids Tyrosine to Histidine and Glutanic acid to Lysine in kinase domain of the CHEK2 protein. In addition, to find relationship between expression of CHEK2 protein and changes in CHEK2 gene in colorectal cancer, immunohistochemistry analysis was performed. Tumour samples, which contain the CHEK2 gene alterations, showed negative to very low levels of CHEK2 protein. We used methylation specific PCR techniques (MSP) to determine the methylation status of the CHEK2 promoter in colorectal cancer. We found that CpG rich regions of the CHEK2 gene promoter is methylated in random cases with negative to low level protein expression. CHEK2 alterations are not common in sporadic colorectal cancer but can be detected in about 6% of cases and methylation of CHEK2 promoter sequences was also detected approximately in 10% of the cases. EMAST (Elevated Microsatellite Alterations at Selected Tetranucleotides) that is a distinct subtype of microsatellite instability and can be a useful marker for the early detection of cancer. DNAs from tumours and normal mucosae were polymerase chain reaction (PCR) amplified at six tetranucleotide repeat microsatellite (EMAST) loci. EMAST was observed at least in one of six markers in 69.7% of colorectal tumours. All EMAST positive tumours were of advanced stage. Also 11.4% of cases demonstrated a loss of heterozygosity (LOH) with at least 1 of 6 microsatellite markers.
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Campylobacter enteritis is a common form of acute gastroenteritis. Among children, especially in developing countries, Campylobacter infections can cause sever life-threatening diarrheal disease. The incidence of Campylobacter infection among children is age related with a higher incidence among younger children in the developing world whereas in industrialized countries the incidence is highest in older children. In a study of American children, Campylobacter was isolated in 4.8% of diarrheal stools in aged 1-4 years. In 1985 the prevalence of Campylobacter diarrheal was 4.4%, whereas in current report 6% of stool samples from children aged<5 years with diarrhea grew Campylobacter jejuni. There were no significant differences between age groups of patients. All thirteen isolated strains of Campylobacter were resistance to Bactrim, Colistin and Polymyxin B and were sensitive to Neomycin, Erythromycin, Gentamicin and Nalidixic acid. The incidence of human campylobacteriosis is increasing worldwide. Thus, public health awareness about the problem is necessary, with a view towards setting up national surveillance programs.
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Cap-independent internal initiation of protein synthesis has been shown to occur on a number of viral and cellular mRNAs. Initiation of protein synthesis is directed by an internal ribosome entry site (IRES) element within the 5’ untranslated region (UTR) of the mRNA. Avian encephalomyelitis virus (AEV) belongs to the picornavirus family and shares protein sequence similarity with hepatitis A virus (HAV). Because of this, it was assigned to the hepatovirus genus. We have demonstrated that the 494 nucleotide 5’ UTR of this virus genome contains an internal ribosome entry site (IRES) element. However, in contrast to the HAV IRES, the AEV IRES functions efficiently in the presence of cleaved eIF4G, suggesting functional differences exist. Furthermore, comparison of the AEV IRES sequence with that of the hepatitis C virus (HCV) IRES revealed areas of striking similarity, especially in the region of the ribosome binding site. The AEV IRES is thus very similar to the recently described IRES from the picornavirus porcine teschovirus; this IRES also shows similarity to the HCV IRES. These results suggest that these viruses may have exchanged sequences during evolution.
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Chemokines are low molecular weight proteins (8-17 kDa). They are classified in four distinct groups as CXC, CC, CX3C and C. Depending on the presence or absence of a motif called ELR (Arg-Leu-Glu) before the first cysteine residue in their structure, CXC chemokines are also subdivided into ELR+ and ELR-. Increasing evidence has indicated the existence of a chemokine network in the liver which is involved in both physiological responses and, under certain circumstances, pathological and repair processes following hepatic injury. The CXC chemokines play a major role in both these processes, and much attention has been focused on their therapeutic applications to liver disease. However, whilst non-parenchymal cells represent a major source of chemokines, the secretion and role of hepatocyte-derived CXC chemokines in these processes is largely unknown. The responses of hepatocytes to the stress imposed during isolation by collagenase perfusion are thought to mimic those that the liver experiences after injury in vivo, such as during stress, trauma or after insults, and therefore provides a useful model to study the regulation of expression of these chemokines in vitro. The present study shows that the ELR- CXC chemokine, SDF-1, and the ELR+ chemokine, Gro/KC, are secreted from isolated rat hepatocytes immediately after isolation and early during culture. Two other chemokines IP-10/Mob-1 and IL-8/MIP-2 exhibited inducible expression, with IP-10/Mob-1 reaching maximal expression within 3h of cell isolation with a slightly delayed maximal expression (5h) for IL-8/MIP-2. The pro-inflammatory cytokines, TNF- and IFN-, selectively stimulated expression of IP-10/Mob-1 but were without effect on Gro/KC. IP-10/Mob-1, SDF-1 and Gro/KC expression by hepatocytes was stimulated in response to heat shock but only IP-10/Mob-1 expression increased in response to FCS, medium additives or maintenance of cells in suspension culture. The expression of the CXC chemokines IP-10/Mob-1 and Gro/KC was inhibited in the presence of inhibitors of specific protein kinases and signal pathways- SB203580, MG132, KN62 and Staurosporine. Expression of chemokines from isolated hepatocytes not only provides a useful model to study the induction of specific genes under stressful situations, but may also be beneficial in the development of therapeutic drugs that may regulate the pathological and regenerative processes that occur during, and following, liver disease.
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Desmoid tumors (aggressive fibromatosis) are locally invasive soft tissue tumors in which beta-catenin/TCF3 mediated Wnt signaling is activated. More than 80% of desmoid tumors contain activating mutations in ß-Catenin which leads to up-regulation of ß-Catenin. The functional consequences of up-regulation of ß-Catenin as an oncogene are complex in different tumors and tissues. TOP/FOP constructs are using to identify the activation of ß-Catenin-TCF4-mediated transcription. We have already shown constitutive ß-Catenin /TCF transcriptional activity in desmoids tumors. cDNA microarray analysis showed that differentially expressed genes in desmoid tumors were different than known Wnt target genes in colorectal cancer. (except for MMP7). Also we have shown that IGFBP6 is a direct target of ß-Catenin -TCF4-mediated repression in desmoid. Different ß-Catenin mutant can increase significantly TOP/FOP ratio in HEK293T cell line 32-52 folds while they cannot significantly modulate TOP/FOP ratio in CHO cell line. On the other hand, IGFBP6 as a direct target of ß-Catenin -TCF4-mediated transcription is down-regulated by S33 mutant ß-Catenin but not responsive to other mutant or deleted forms of ß-Catenin in CHO cell line. In Hek293T cell line, this promoter is slightly activated but no significant change. Here we show that induction of constitutive ß-Catenin /TCF transcriptional activity is dependent to cell context and TGF-Beta signaling pathway may regulate it in desmoid tumors. Our preliminary results suggest an additional role for TGF-Beta signaling pathway in modulating downstream targets in desmoids. TGF-Beta is activated in desmoid and their phenotype resembles mostly that of TGF-Beta activated myofibroblasts. In conclusion, we show that activation of constitutive ß-Catenin /TCF transcriptional activity depends to cell context and different mutant form of ß-Catenin can play different role in modulation of target genes. TGF-Beta signaling pathway may be the main regulator in this response in our tumor samples.
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The original sequence of an overexpressed clone from the Differential Display experiment (previously done in the lab) was analysed in NCBI database and comprises the 3’ terminus of a novel gene containing two hypothetical ubiquitin conjugating enzyme domain. To identify this novel gene some experiments were performed in vivo. Phenotypical analysis: RT PCR analysis of RNA samples from head & neck tumors showed that the transcript is over-expressed in 11 out of 14 samples (almost 78%). Immunocytochemistry experiments showed that the protein is localized in both the cytoplasm and the nucleus. This data were confirmed by confocal microscopy. Immunohistochemistry on HNSCC samples showed specific signal in tumor versus normal and control. The same expression pattern was observed by in situ hibridization. Functional analysis: 22 Different head and neck cell lines were checked for the expression of this gene at the RNA level and high/ low expressing cell line were selected to use in transfection experiments, in order to begin to understand which pathway(s) are disrupted in the HNSCC tumor, and the basis for the requirement for upregulation and downregulation of this protein. Initial results showed that overexpression inhibits clonogenicity and the rate of growth. FACS analysis of RPMI cells showed a G1 arrest in the cells transiently transfected with a plasmid that expresses the protein compared to control. These cells also were used to establish Stable transfectants. Mass spectrometry analysis of the purified flagged- protein showed some extra bands which could be considered as interacting partner and/or potential substrate for this putative E2 protein. Perspective: functional analysis of this gene including the study of the interactions such as ubiquitination between endogenous protein and its potential partner will be continued to explore the function and the potential role of this gene in cancer.
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The T-box gene mab-9 was originally identified in a screen for worms with mating defects; it is now known that correct mab-9 expression is required for the specification of cell fate in the posterior of the worm and for correct nervous system development. Ectopic, or mis-expression of mab-9 is deleterious, hence this gene must be tightly regulated, in both a temporal and a spatial manner. In order to identify upstream regulators of mab-9 expression, we have adopted two strategies that we hope will reveal both cis- and trans-acting factors. In order to identify trans-acting regulators of mab-9 expression, we have adopted a genome-wide RNAi screen of all transcription factors in C. elegans. Using the Ahringer RNAi feeding library, we have established a high-throughput screen to search for genes which, when silenced, lead to an alteration of GFP expression in a strain of worms carrying an integrated mab-9:: GFP reporter. In an initial screen, silencing of 27% of the transcription factors represented in the library resulted in detectable phenotypes, including embryonic lethality, larval arrest and morphological defects. From observation of the progeny of worms exposed to RNAi, we have identified 14 genes which have an altered mab-9::GFP expression pattern. These candidate genes are being screened further to confirm which, if any, play a direct role in mab-9 regulation. A comparison of the C. elegans mab-9 promoter sequence with that of the closest homologue in C. briggsae was used to highlight several regions of close DNA sequence homology (termed Homology Regions 0-5) that may be important in the regulation of mab-9 expression. These sequences have each been deleted from a mab-9::GFP rescuing construct with the aim of ascertaining whether GFP expression and/or rescue of the mutant phenotype is altered. To date, one of the sequences has been assigned a role, being both necessary and sufficient for expression in posterior hypodermal cells. This has enabled a functional role for mab-9 expression to be associated with tail hypodermal cells, distinct from the fate-determining role previously described for mab-9 in male specific blast cells. The upstream factor binding to this sequence is being sought in a candidate-led RNAi screen, based on transcription factor binding site sequences within the Homology Region.
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The ATP Binding Cassette Transporter (ABCA1) is a protein involved in lipid metabolism. Common polymorphisms in this gene could affect High Density Lipoprotein Cholesterol (HDL-C), triglyceride and Apolipoprotein A1 (apoA1) levels and thus the risk of atherosclerotic diseases. To assess the effects of different ABCA1 genotypes on lipid profile, a cohort of 181 healthy Scottish individuals with complete lipid profile data (adjusted for age, sex, BMI and smoking, drinking habits) along with another cohort of 194 healthy control subjects from Aberdeen with main lipid profile data were recruited. We studied four common polymorphisms in ABCA1 gene at different positions, G158A (Leu/Leu), G219A (Arg/Lys), G316A (Gly/Gly) and A1587G (Lys/Arg). Genotyping assays were based on Dynamic Allele Specific Hybridisation (DASH). Results: No significant differences were found in VLDL/TG, VLDL/Cholesterol, LDL, HDL2 and HDL3 concentrations in females or males between different genotypes in the Scottish and Aberdeen cohorts. However, in females with different A1587G genotypes in Scottish cohort, IDL was higher in “AA” genotype (table1). It was also higher in females with G219A “GG” genotype (table2). Males with G316A “GA” genotype also had a higher level of HDL (Mean HDL: “GG”, 53.27; “GA”, 63: P= 0.032). In conclusion, only A1587G “AA” and G219A “GG” genotypes may influence IDL in females. Females with G219A “GG” and those with “AA” genotypes might also have a higher total cholesterol (P=0.036) and a lower total HDL (P= 0.049) respectively.
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Human APOE gene is located in 19ql3.2 region of the human genome. The gene codes for a protein called apolipoprotein E. The protein involved in lipid metabolism, regulation of blood cholesterol level and some other important cell functions. Allele’s e2, e3, and e4 are the most spread in humans. Level of cholesterol is the highest in e4 allele carriers, medium for e3 and the lowest for e2 carriers. The high cholesterol level associated with e4 allele is a risk factor for cardiovascular diseases and Alzheimer disease in westernized societies but not in African hunter-gatherers. We have established APOE allele frequencies in Iranians and Pamir population as well as in some populations of Russia (Russians, Ukrainians and Byelorussians). E3 allele and e3/e3 genotype were found the most spread in all of the populations with frequencies 0.74-0.80 and 0.60-0.64 correspondingly. We also screened for available information on APOE allele frequencies and found the data for 144 populations from different parts of the world. We have found that АРОЕ *е4 allele frequencies have a latitudinal distribution in all parts of the world. Minimum e4 frequency (3-5%) as well as maximum e3 frequency (>90%) was found in populations inhabiting areas at the latitude that corresponds to the Northern tropic. The e4 allele frequencies are growing rather symmetrically both to the north and to the south from the latitude. Spearman`s correlation coefficient between the e4 allele frequency and the latitude is high and valid both for populations to the north from the tropic (rho=0.67, P< 0.001) and for populations to the south from the tropic (rho =0.46, p0.001). For each 200 of latitude the frequency is going 10% up for the northern populations and 20% up for the southern populations. The latitudinal distribution of e3 allele frequencies is a mirror distribution for e4 frequency. Spearman`s correlation coefficient is both high and valid for the northern populations (rho=0.66, P< 0.001) and for the southern populations (rho= 0.45, P< 0.00I). The latitudinal distribution is absent for e2 allele frequencies. The e4 frequencies are closer to each other for populations inhabiting the same latitude. The same is true for e3 allele frequencies. The phenomenon can be seen even for populations of the same latitude inhabiting different continents. That means that the distribution does not reflect a trace of human migrations. We believe that both APOE* e4 and e3 alleles, but not el allele, may be associated with adaptation of humans to climate conditions.
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Around the world, Coronary Artery Disease (CAD) is quickly becoming the most common cause of morbidity and mortality. Percutaneous coronary interventions- angioplasty and stent insertion- have proved effective and reliable treatments for CAD but their long-term efficacy is limited by the high rate of restenosis. This occurs in 30 – 50% of patients undergoing angioplasty and results in symptoms requiring repeat intervention in up to 75% of them. Stent insertion has been shown to reduce this rate but in-stent restenosis still occurs in 20-40% of cases. The high incidence of restenosis represents a large economic burden on health resources. As a consequence of the resistance of restenosis to traditional therapeutic approaches, gene therapy has emerged an attractive potential therapy for this problem. Excessive extracellular matrix (ECM) deposition in the neointima is the main mechanism leading to luminal loss after coronary stenting. Transforming growth factor-β (TGF-β) is a major regulator of ECM deposition and there is substantial evidence to suggest its role in restenosis. TGF-β1 is the predominant isoform in vascular tissues and its production is observed to be upregulated in human restenotic lesions and in the intima of injured animal vessels. The aim of this study is to develop, investigate and compare the effects of two potentially therapeutic recombinant, replication-deficient adenoviruses, which will give rise to the expression of transgenic proteins which antagonise the fibrogenic effects of TGF-β1 in coronary arteries post stent insertion. The cDNA for these proteins have each been inserted into replication deficient adenovirus vectors under the control of the Major Immediate/Early Murine Cytomegalovirus (MIEmCMV) promoter. Virus identity and the presence of transgenes have been confirmed by restriction analysis and Southern blotting respectively. Efficient transgene expression has been confirmed in cultured porcine coronary vascular smooth muscle cells (VSMC) by a series of immunocytochemistry. The work is currently underway to evaluate biological activity of transgenes in cultured VSMC and the transgenes expression and their effects on luminal loss in stented porcine coronary artery model in vivo.
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Duchenne Muscular Dystrophy (DMD) is one of a group of genetically heterogeneous muscular dystrophies that are characterized by progressive weakness and wasting of skeletal muscle. Loss of myofibres occurs in response to a deficiency of dystrophin, a protein which is believed to be responsible for myofibre maintenance and integrity. Dystrophin forms a link between the cytoskeleton and the membrane-spanning dystrophin-associated glycoprotein complex (DAPC), indicative of a structural role for dystrophin. The application of gene therapy protocols for DMD still presents many daunting challenges due partly to intrinsic features of the dystrophin gene. Hence, improvement in the understanding of the underlying primary molecular events leading to a dystrophic pathology might pave the way for the discovery of new starting points. Here we present a strategy to use RNAi technology to study the events occurring in muscle cell development due to dystrophin deficiency. RNAi has been proven to be a powerful technology to study molecular effects due to knockdown of single genes. We have used a series of siRNAs to target and knock down the expression of dystrophin in primary cultures of mouse muscle, and subsequently used transcriptomic array analysis to identify genes whose expression were affected in response to dystrophin deficiency. The data obtained from this experiment, which include some very interesting potential new targets, are currently being analysed. We have also developed a recombinant adeno-associated virus (rAAV) vector expressing an shRNA targeting dystrophin. The use of such rAAV-shDNA vectors enables us to target dystrophin in vivo to obtain a better and potentially curative insight into the pathophysiology of DMD.
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Oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the world and accounts for approximately 4% of all cancers and 2% of all cancer death.The single most important factor in the prevention of the disease is early detection although, due to increased risk of secondary malignancy, survival remains poor with only a 25% 5 years survival. Both hereditary and environmental factors have been shown to have a productive role in this disease. For example, although chronic exposure of oral epithelium to tobacco smoke and alcohol are amongst the most important aetiological factors, it is now becoming realized that infection with high risk types of human papilloma virus (HPV) are also involved as causative agent in a subset of this disease. All of these OSCC associated factors are known to promote genetic instability in the target oral epithelial cells. Work in our laboratories has indicated that the Tax interacting protein 1 (Tip-1) is also a target for the HPV 16 E6 protein may play an important role in controlling genetic instability during the oncogenic process (Hampson L., et al unpublished). So far 14 oral cancer cell lines have been grown in cell culture and RNA extracted from these. Tip-1 transcript levels were analyzed in this material by Northern blotting and competitive template quantitative PCR, which showed that Tip-1 levels were higher in some, cell lines than others (4 high, 6 moderate, 4 low level). Cell ploidy was determined by FACS analysis of propidium iodide stained cells, which showed that out of all the OSCC cell lines tested the cell line (BICR 68) had the greatest numbers of polyploid cells and also had the highest expression of Tip-1 RNA.
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Mitochondria, the powerhouses of the cell, possess their own translational system seemingly inherited from their proteo-bacterial ancestor. Termination of translation in bacteria is mediated by Release Factors 1, 2 and 3 (RF1, 2 & 3), the first two of which recognise stop codons UAA, UAG and UGA, while RF3 just enhances the efficiency of termination. In human mitochondria where translation termination is triggered by four stop codons (UAA, UAG, AGG and AGA), only one candidate gene (MTRF1) is purported in silico to encode a functional mitochondrial release factor. Having searched the human genome database, we have found another candidate (NP_061914) potentially capable of acting as mitochondrial release factor based upon its high similarity to bacterial RF1 and MTRF1. To determine whether these two candidates are located in the mitochondrion, they have been cloned into a GFP expression vector (pGFP3) and transfected into HeLa cells for 48 hours followed by staining with Mitotracker Red CMXRos. Analysis of the cells with Fluorescence Microscopy equipped with Metamorphosis software showed localization of the two GFP chimaeras to mitochondria, implying mitochondrial localization of MTRF1 and “NP_061914”. To determine whether “NP_061914” is actually imported into mitochondria, a radiolabelled product was generated in vitro and incubated with isolated rat liver mitochondria. N-terminal cleavage was demonstrated and the matured protein became insensitive to added proteinase, consistent with “NP_061914” accessing the mitochondrial matrix. This protein has now been renamed “MTRF2”.
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The induction of IFN-β expression is the first stage in the innate anti-viral response. In order to investigate the possible effects of HCV proteins on IFN-β signalling, a baculovirus delivery system was developed to introduce the whole genome of HCV genotype 1b into hepatoma cells. The construct used in this study lacks the 3’UTR which is required for HCV replication, thus enabling us to look at the effects of HCV proteins on the IFN-β signalling pathway without inducing IFN-β expression by virtue of the presence of replicating (double-stranded) viral RNA. To facilitate this analysis the expression of the HCV polyprotein was under the control of a tetracycline–responsive promoter coupled to the HCV 5’UTR. As a comparison, we have also generated a recombinant baculovirus containing the culture adapted sub-genomic replicon (FK5.1) also derived from HCV genotype 1b, and a mutant form thereof containing an inactivating mutation within the NS5B (RdRp) coding sequence (termed GND). We first confirmed that HepG2 cells were able to mount an effective IFN-β response. As expected, the baculovirus carrying the FK5.1 replicon induced the production of IFN-β as judged by the use of an IFN-β-promoter luciferase reporter construct, whereas the GND baculovirus and the full-length 3’UTR deletant failed to induce luciferase expression. We then proceeded to analyse the effect of the HCV polyprotein on exogenous induction of the IFN-β promoter (by transfecting cells with poly I/C). These studies demonstrated that neither the HCV polyprotein nor the non-structural proteins of HCV (expressed from the replicon) had any effect on the dsRNA-mediated induction of IFN-β promoter. Secondly we analysed potential effects on the inhibition of the IFN-β response, using an ISRE-luciferase construct. Again we observed no effect of either the complete polyprotein or the sub-genomic replicon. Lastly, we examined the activation of both IRF-3 and NFκB, two transcription factors induced by dsRNA signalling that are key to the activation of transcription from the IFN-β promoter. Intriguingly, both the wild type or GND-mutant replicon blocked the dsRNA-induced activation of IRF-3 and NFκB. In contrast the full-length 3’UTR deletant had no significant effect on either transcription factor. These results suggest a complex interplay between HCV and the IFN-β system that is dependent both on the context of polyprotein expression (full length compared with sub-genomic replicon) and the primary amino acid sequence (culture adapted compared with infectious clone).
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Introduction: Inflammatory bowel disease (IBD) has two major groups: Ulcerative Colitis (UC) and Crohn’s Disease (CD), diagnosed by routine invasive methods. In recent years, diagnostic value of immunologic tests including perinuclear Antineutrophil Cytoplasmic Antibody (pANCA) and Anti-Saccharomyces Cerevisiae Antibody (ASCA) has been mentioned. These tests are supposed to be used as a diagnostic tool and also have some relationship with clinical characteristics of IBD.In this study; we investigated the diagnostic value of above tests and their relationship with IBD manifestations. Methods: Sera from 144 patients with IBD (113 with UC and 31 with CD) as cases and 176 patients with non-IBD rectorrhagia, flatulence, dyspepsia, GI cancers, IBS as controls were analyzed. Patients’ serum was assayed for ASCA by Enzyme-Linked Immunosorbent Assay (ELISA) & for pANCA by indirect immunofluorescence assay (IFA). Results: Sensitivity, specificity, positive and negative predictive value of pANCA in UC were: 39%, 82%, 70%, and 56%. In patients with CD the above parameters were: 58%, 70%, 31%, and 87%, respectively. Using both tests increased the specificity and positive predictive value in UC patients to 89% and 84% and in patients with CD to 80% and 46%. There was a significant difference between CD and UC groups in ASCA results (P= 0.002).UC patients with Sclerosing Cholangitis (P=0.003) and severe bleeding (P=0.004) were significantly positive for pANCA more than other UC patients, respectively. Conclusion: We recommend pANCA & ASCA for differentiation of CD & UC, although it is not useful for screening. Using both tests together improves the specificity and positive predictive value. Positive pANCA results might be seen together with some complications like: Sclerosing Cholangitis & severe bleeding.
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Introduction: Physical activity may play a central role in the obesity epidemic. However, most epidemiological research is based on subjective measures of physical activity. The purpose of this study was to validate a wrist worn accelerometer to quantify physical activity of children, by comparison to direct observation. Methods: Data were analysed from 42 children, aged between 3-5 years (22 boys) observed each minute for 2 hours using the Children’s Activity Rating Scale (CARS) while wearing the Actiwatch accelerometer. Results: There were significant positive correlation between the mean CARS levels and the mean Actiwatch counts over simultaneous 1-10 minute periods ranging from r= 0.412 to r= 0.631(P< 0.001). Using a cross validation method the data were split in half at random and a predictive equation associating actiwatch scores and CARS scores generated. CARS prediction scores were then compared against actual CARS data in the other half of the sample. There was no significant difference between the predicted and the observed CARS. CARS score could be calculated with a 95% confidence level of plus or minus 0.74 CARS units. Discussion: These data suggest that wrist worn accelerometers are a valid tool for objectively assessing levels of physical activity in young children.
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Children Energy Expenditure by Doubly Labeled Water: Comparison of Multi-Point and Two-Point MethodsObjective: This study was designed to compare the multi-sample and two-sample methods in measuring children energy expenditure using doubly labeled water (DLW). Methods: Twenty-six healthy children (11 boys, 15girls; age 2-6 years) were recruited. The subjects in this study were from a subset of 90 children aged 2–6 years who were part of a larger study (RASCAL). After collection of a baseline urinary sample, every child was orally dosed with DLW based on body weight. Three urinary samples were taken at approximately 2, 4 and 6 hours after the isotope administration to determine the isotope dilution space and initial isotope enrichment. Further samples were collected, thereafter daily, preferably in the evening, for the next 14 days. Total energy expenditure (TEE) was measured over 7 and 14 days using the multi-point and two-point methods under free-living conditions by doubly labeled water. Results: There was no significant difference (T-test=0.79, P=0.439) between Total Energy Expenditure analyzed by the multipoint and two-point methods. There was also no significant difference between 7 and 14 days measurement of TEE using DLW. Conclusion: These data indicated that using 7 days measurement and two points method for measuring TEE in children is valid and cost-effective.
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Childhood overweight and obesity are already on the rise in developed and developing countries. Childhood obesity is becoming a serious health problem. The cause of this problem is poorly understood. Despite a variety of factors such as genetic and environmental, a sedentary lifestyle is a known major contributor to obesity in children. The purpose of this study was to investigate the association between physical activity, sedentary behaviour and body composition in children. Methods: The study group consisted of 89 children (42 boys, 47 girls), aged 4.06+/-1.33 years. Physical activity patterns were determined using Actiwatch during 7 days. The times spend on television and computer were estimated from the lifestyle questionnaire. Body composition was assessed by dual energy x-ray absorptiometry (DEXA). Results: Percentage of body fat was higher in girls (30.35+/-7.23) than boys (25.90+/-6.82). There was no significant difference in activity level and TV viewing between boys and girls. No association was found between physical activity pattern and body composition. Television viewing was negatively associated with body fat (r=0.324, P<0.05). Conclusion: This study supports the previous finding that inactivity is a major risk factor for childhood obesity
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Breakfast consumption appears to have declined in the last decades and eating breakfast, especially cereal, is associated with a lower risk of obesity. Serum cholesterol concentration is reported to be lower in adults eating breakfast (EB) and higher among those not. No study, to our knowledge, has investigated the effect of skipping breakfast (SB) on various aspect of energy metabolism. Thus, this study evaluated the effect of EB or SB on adult energy, carbohydrate and lipid metabolism. 10 healthy women (BMI: 23.2, SD: 1.4) were recruited after giving informed consent. Each subject participated in a randomised crossover trial which encompassed two 14-day intervention periods; EB in one of them and SB in the other with a 2-wk wash out period between. In EB, subjects were asked to consume a pack of whole grain cereal (Kellogg’s, UK, 45 g) with 200 ml semi-skimmed milk between 07:00-08:00 and eat a chocolate bar (Nestle, 48g.) at 10.30-11.00. Then, they consumed 4 further meals of similar content to usual in the rest of the day at predetermined times every day for 2 wk. In SB, subjects consumed the chocolate at 10.30-11.00, and then had the cereal and semi-skimmed milk at 12.00-12.30. Then, they consumed 4 further meals of similar content to usual as for EB. Subjects consumed their normal diet for a 2-wk washout period between the two intervention periods. Subjects recorded their food intake on 3 days during each intervention, and came to the laboratory after an overnight fast at the start and end of each intervention period and their weight and anthropometric variables were measured. Blood samples were taken for glucose, lipids and insulin before and for 3 hr after a test meal (milk shake containing 30 kJ/kg, 50% CHO). Resting metabolic rate (RMR) was measured by indirect calorimetry before and after the test meal. Repeated-measures ANOVA, and paired t.test were used for the statistical comparisons. SB was associated with higher fasting total (3.4±0.4 compared with 3.1±0.4 mmol/l after EB, P<0.02) and LDL (1.8±0.3 compared with 1.6±0.3 mmol/l after EB, P< 0.04) cholesterol. Fasting glucose and insulin were not affected by breakfast but AUC of insulin responses to the test meal was higher after SB compared to after EB (mean ± SD (mIU/l over 3h.) was 82.6±44.0 and 73.6±42.0 respectively, P< 0.01). Mean recorded energy intake was lower during EB (0.38 MJ/day lower than the mean energy intake of SB, P< 0.002) while fasting RMR and postprandial thermogenesis were not different between the two periods. In conclusion, skipping breakfast appears to produce higher total and LDL cholesterol and lower insulin sensitivity, which are known cardiovascular risk factors. SB may also produce positive energy balance if the observed higher energy intake continued in the long term.
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Glassy materials are not thermodynamically stable and during storage below the glass transition temperature (Tg), they are subjected to the time dependent changes towards the equilibrium. These changes are known as physical ageing, which is the basic feature of glassy materials below Tg. During ageing process, physical properties such as enthalpy and volume decrease and these changes are accompanied by important changes in mechanical properties such as change to modulus, compliance and mechanical relaxation, which are of great technological importance. The aim of this study is to investigate the occurrence of the mechanical relaxation in the glassy gelatin and compare it to the enthalpy relaxation phenomenon and try to correlate the rate of mechanical relaxation to the rate of enthalpy relaxation, which is the more reliable and frequent way for studying physical ageing. The extent of enthalpy relaxation of gelatin films with different water contents of 8%, 12 and 17%, measured by differential scanning calorimetry (DSC), was found to increase with increasing the ageing time. The mechanical behaviour of the gelatin films was measured, using dynamic mechanical thermal analysis (DMTA). The mechanical behaviour of gelatin showed time and frequency-dependent changes. Storage modulus increased during isothermal ageing and gelatin became harder and stiffer at higher frequency than that at low frequency. In order to assess the rate of mechanical relaxation, the classical time-ageing time superposition was applied to the results. The rate and extent of mechanical ageing were increased at higher water contents. A good agreement was found between the rate of the enthalpy relaxation and the changes to the mechanical properties at different water contents, suggesting that DSC measurements of enthalpy relaxation, which can be more easily implemented, can be used as indicator of mechanical changes.
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Static headspace measurements were performed using Atmospheric Pressure Chemical Ionisation- Mass Spectrometer (APCI-MS) to determine volatile partitioning from a series of milk-based emulsions. The 20 aroma compounds studied exhibited a broad range of hydrophobicity/ hydrophilicity in model emulsions. Experimental method was done using 6 samples with different lipid contents (0.002-0.102 g/mL). The results showed that there were three groups of volatile compounds due to their lipophilicities; the least, intermediate and most lipophilic volatile compounds. Overall, the release of lipophilic molecules was so dependent of the fat content of the matrix which opposed to the release of the very hydrophilic compounds.
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The nutritional status in patients in ITU appears to decline not only during their stay in ITU but long after discharge from ITU. The deterioration in nutritional status during and after ITU management is not fully understood. Re-establishing normal spontaneous feeding after critical illness is a vital component in the recuperative process. Gut released peptides, such as ghrelin and peptide YY (PYY) that regulate the initiation and termination of meals (Cummings et al. 2002, Batterham et al. 2002), could play a role in the altered eating behaviour patients. The aim of this study was to assess the pattern of ghrelin and PYY during the stay of ITU patients in hospital. 16 patients aged 60± 4.7yrs, BMI 28.1± 1.7kg/m2 (mean± SEM) admitted to ITU underwent fasting blood sample collections every second day throughout the first week on ITU and once a week thereafter until day 28 or discharge home. Changes in appetite, biochemical and anthropometric markers of nutritional status were recorded. Three fasting blood samples at least three days apart were collected from the 36 matched age and BMI healthy volunteers 54.3±2.9yrs, p=0.3 BMI 25.8±0.8kg/m2 P=0.2. As compared with healthy subjects, ITU patients exhibited a significantly lower level of ghrelin (day one 297±76.3 v. 919.8±88.3 pmol/l P<0.001) during their stay in ITU and afterwards with a trend to rise to the normal level during the last three weeks of stay. Conversely ITU patients showed a significantly higher level of PYY (day one 31.5±9.6 v. 11.2±1.6 pmol/l P<0.05) throught their stay in ITU with a downward trend to the normal level during the last three weeks of their stay however it did not reach the healthy subjects’ level. There was a negative correlation between percentage increase in ghrelin and percentage decrease in PYY (r=0.4 P>0.05). Column chromatography showed the ghrelin and PYY in the right place as standard and confirmed endogenous ghrelin/PYY like immumoreactivity. Our observations suggest that Ghrelin may be one mechanism involved in appetite regulation and PYY might be one mechanism involved in inhibiting appetite in these sick patients.
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Healthy lifestyle behaviors are associated with lower risk of having cardiovascular disease (CVD). There is a cluster of risk factors that predisposes people to CVD. Overweight/obesity, unhealthy diet, inactivity, and smoking are major lifestyle risk factors for CVD, which are also associated with other potent clinical risk factors including raised plasma lipids, coagulation factors and measures of inflammation. This study aimed to evaluate the association between lifestyle factors and some established clinical cardiovascular risk factors: C-reactive protein (CRP), total cholesterol, HDL-C, non-HDL-C and fibrinogen in Scottish adults with a high prevalence of CVD. Cross-sectional data from 5460 participants aged 16-74 years whom had valid biochemical measurements in the Scottish Health Survey (SHS) 1998 were analysed. Trained staff obtained anthropometric measures. Levels of physical activity, cigarette smoking, alcohol intake and dietary habits were measured by questionnaires. Non-HDL-C was calculated by subtracting HDL-C from total cholesterol. Data analysis was carried out using SPSS with different statistical tests. After adjusting for age, body mass index (BMI) was significantly associated with all risk factors in both sexes as obese subjects had the highest concentrations of CRP, total and non-HDL-C and fibrinogen, and the lowest concentrations of HDL-C (P< 0.01) compared to BMI< 25 kg/m². Cigarette smoking was positively associated with CRP, fibrinogen (P< 0.0001) and negatively with HDL-c in all subjects, and positively with total cholesterol and non-HDL-C in women (P< 0.01). Men and women who were inactive had the highest concentrations of CRP and fibrinogen and lowest concentration of HDL-C compared with active subjects (P< 0.001). Those subjects who consumed ≥ 400 grams fruits and vegetables per day had lowest CRP and fibrinogen (P< 0.001). Total fruit and vegetable consumption had a positive association with HDL-C concentration and negative association with non-HDL-C concentration only in women (P< 0.01). Men who consumed 1-21 units of alcohol per week and women who consumed 7-14 had lower CRP concentrations (P< 0.01). Alcohol consumption showed a positive association with HDL-C (P< 0.0001). Multivariate analysis produced slightly different results when analyzed with GLM, logistic and linear regression methods. However, all three methods confirmed that when all independent variables have been entered simultaneously in the models, BMI and smoking were the most important variables for the risk factors (P< 0.01). The odds ratios of having CRP ≥ 3mg/l, fibrinogen ≥ 3g/l, non-HDL-C > 4 mmol/l and HDL-c ≤ 1 mmol/l for obese subjects compared with BMI<25 kg/m² were 4.8, 2.2, 4.8, 3.6 respectively. These figures for current smokers compared with non-smokers were 2.0, 2.1 2, and 1.5 respectively (P< 0.01). After BMI and smoking, physical activity was most important factor that showed significant association with CRP, fibrinogen and HDL-C. Total fruit and vegetable consumption had a significant association with CRP, and alcohol intake with HDL-C. Overweight/obesity, cigarette smoking and physical inactivity were the main independent variables associated with the clinical CVD risk factors. They increase serum concentrations of CRP, fibrinogen, and plasma non-HDL-C and decrease HDL-C. These results suggest that lifestyle factors are important for modifying CVD risk and adopting healthy behaviors are beneficial.
