Immunophenotypic and functional analysis of lymphocyte subsets in common variable immunodeficiency patients without monogenic defects.

Common variable immunodeficiency (CVID) is accompanied by various lymphocyte abnormalities believed to be mostly responsible for disease features in patients with no diagnosed monogenic defects. Here, we evaluated the association of B and T lymphocyte abnormalities with the incidence of CVID. Twenty-six genetically unsolved CVID patients were examined for B and T lymphocyte subsets by flow cytometry and CD4+ T-cell proliferation by carboxyfluorescein succinimidyl ester (CFSE) test. We detected a reduction in total, naive, memory B cells and plasmablasts, and also total, naive, central memory and regulatory CD4+ T cells, besides naive CD8+ T cells. There was an increase in CD21low and transitional B cells, effector memory (EM) and terminally differentiated effector memory (TEMRA ) CD4+ T-cell subsets as well as total, EM, TEMRA , activated and cytotoxic CD8+ T cells among non-monogenic CVID patients. CD4+ T-cell proliferation response was reduced regarding both division index and percent divided. In conclusion, regarding the similarity of lymphocyte abnormalities between patients without genetic defects and those with monogenic defects, genetic mutations are not responsible for these specific lymphocyte changes. However, the novel correlations observed between lymphocyte alterations among genetically unsolved CVID patients may serve as a guide to predict the potential of future CVID development for hypogammaglobulinemia children.

Prospective Epidemiological Research Studies in Iran (the PERSIAN Cohort Study): Rationale, Objectives, and Design.

Noncommunicable diseases (NCDs) account for 76% of deaths in Iran, and this number is on the rise, in parallel with global rates. Many risk factors associated with NCDs are preventable; however, it is first necessary to conduct observational studies to identify relevant risk factors and the most appropriate approach to controlling them. Iran is a multiethnic country; therefore, in 2014 the Ministry of Health and Medical Education launched a nationwide cohort study-Prospective Epidemiological Research Studies in Iran (PERSIAN)-in order to identify the most prevalent NCDs among Iran's ethnic groups and to investigate effective methods of prevention. The PERSIAN study consists of 4 population-based cohorts; the adult component (the PERSIAN Cohort Study), described in this article, is a prospective cohort study including 180,000 persons aged 35-70 years from 18 distinct areas of Iran. Upon joining the cohort, participants respond to interviewer-administered questionnaires. Blood, urine, hair, and nail samples are collected and stored. To ensure consistency, centrally purchased equipment is sent to all sites, and the same team trains all personnel. Routine visits and quality assurance/control measures are taken to ensure protocol adherence. Participants are followed for 15 years postenrollment. The PERSIAN study is currently in the enrollment phase; cohort profiles will soon emerge.

Physical activity equivalent labeling vs. calorie labeling: a systematic review and meta-analysis.

BACKGROUND: Many countries are trying to identify strategies to control obesity. Nutrition labeling is a policy that could lead to healthy food choices by providing information to consumers. Calorie labeling, for example, could lead to consumers choosing lower calorie foods. However, its effectiveness has been limited. Recently, physical activity equivalent labeling (i.e., displaying calories in terms of estimated amount of physical activity to burn calories) has been proposed as an alternative to the calorie-only label. The aim of this review was to identify and evaluate the published literature comparing effects on health behavior between physical activity equivalent labeling and calorie-only labeling. METHOD: We searched the following databases: Pubmed/medline, Scopus, Web of science, Agris, Cochrane library, Google Scholar. We also searched along with reference lists of included articles. Articles that were published between 1 January 2000 and 31 October 2016 were eligible for inclusion provided they reported on studies that examined the effects of both types of labeling and included at least one outcome of interest. Mean and standard deviations of the included results were combined using a fixed-effect model. The difference in calories purchased between people exposed to physical activity labeling and calorie-only labeling was calculated as weighted mean difference by using a fixed-effect model. RESULT: The difference of calories ordered between physical activity label and calorie label groups was not statistically significant (SMD: -0.03; 95% CI: -0.13, 0.07). The difference of calories ordered between physical activity label and calorie label according to real vs unreal (e.g. web-based) condition was 65 Kcal fewer in real-world settings. CONCLUSION: Physical activity calorie equivalent labeling in minutes does not significantly reduce calories ordered compared to calorie-only labeling.

Association between low bone mass and the serum RANKL and OPG in patients with nephrolithiasis.

BACKGROUND: Nephrolithiasis is a risk factor for Osteopenia and osteoporosis. Receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) regulate bone remodeling and osteoclastogenesis. This study aimed to evaluate the relation between serum OPG, RANKL concentration, and bone mineral density (BMD) in patients with kidney stone disease. METHODS: Forty-four nephrolithiasis patients with either low bone mass or normal BMD (considered control group) were enrolled in this study. BMD was measured at lumbar spine (L1-L4) and femoral neck by dual-energy X-ray absorptiometry (DEXA). The serum OPG and RANKL were determined using the ELISA method. RESULTS: The median levels of serum OPG were significantly higher in nephrolithiasis patients with low bone mass compared to the nephrolithiasis patients with normal BMD (3.9 pmol/l versus 3.1 pmol/l; P = 0.03), respectively. Negative correlation was detected between bone densities of femoral neck and OPG in patients with nephrolithiasis (r = -.0344, P = 0.02). CONCLUSION: The present study showed that high serum fasting OPG levels may be indicative of femoral neck BMD in patients with nephrolithiasis.

Association of the CTLA-4 1722TC polymorphism and systemic lupus erythematosus: a systematic review and meta analysis.

BACKGROUND: Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an important negative regulator of Tcell responses. The -1722TC polymorphism of the CTLA-4 gene may be associated with systemic lupus erythematosus (SLE) risk, but related results from previous studies have been inconsistent. We carried out a metaanalysis to assess this association more precisely. METHODS: A systematic search through PubMed, Science Direct, and OVID, Iran doc, Iranmedex and SID (Scientific Information Database) databases was performed with the last search updated on December 30, 2011. The odds of ratio (OR) and its 95% confidence interval (95%CI) were used to assess the strength of the association. We evaluated both fixed and random effect models, depending on the presence of between-study heterogeneity. The analyses were conducted using STATA software, version 11.0. RESULTS: A total of 9 independent studies on the CTLA-4 gene -1722TC polymorphism and SLE, including 1422 cases and 1417 controls were used in this meta-analysis. In the present meta-analysis, we found a significant association between -1722TC polymorphism and SLE risk in the overall analysis (TT versus TC/CC: OR=1.18, 95%CI 0.84-1.66, p= 0.32; TT/TC versus CC: OR = 2.06, 95%CI 1.07-3.99, p= 0.03; TT versus CC: OR = 2.32, 95%CI 1.62-3.32, p< 0.001; TC versus CC: OR = 1.99, 95%CI 1.42-2.78, p<0.001; TT versus TC: OR = 1.2, 95%CI 0.86-1.66,p= 0.28; T versus C: OR = 1.22, 95%CI 0.91-1.64,p= 0.16). In the subgroup analysis by ethnicity, -1722TC polymorphism was significantly associated with SLE risk in Asian population. CONCLUSION: This meta-analysis suggests a significant association between -1722TC polymorphism and SLE susceptibility. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.

A methodological quality review of citations of randomized controlled trials of diabetes type2 in leading clinical practice guidelines and systematic reviews.

Objective: Evaluate methodological quality of type 2 diabetes RCTs conducted in Iran and cited in clinical practice guidelines and systematic reviews and meta-analyses. Methods: We conducted a descriptive methodological quality review, analyzing 286 Randomized Controlled Trials (RCTs) on diabetes mellitus published in Iran from July 2004 to 2021. We searched six databases systematically and evaluated eligible articles using the CONSORT 2010 checklist for abstracts. Two investigators assessed the data using a 17-item checklist derived from CONSORT. Additionally, we examined the citations of each RCT in 260 clinical practice guidelines, with a specific focus on the adequate reporting of outcomes. Results: Out of 6667 articles, 286 analyzed. Poor reporting and failure to meet criteria observed. Only 3.8% cited in guidelines. Reporting rates: primary outcomes (41.9%), randomization (61.8%), trial recruitment (12.6%), blinding (50.8%). 27.9% cited in systematic reviews, 50.34% in systematic reviews and meta-analyses, 26.57% in meta-analyses. 67.8% of papers cited in systematic reviews. Adherence highest for participants, objective, randomization, intervention, outcome; lowest for recruitment, trial design, funding source, harms, and reporting primary outcomes. Conclusions: Poor methodological reporting and adherence to CONSORT checklist in evaluated RCTs, especially in methodological sections. Improvements needed for reliable and applicable results in guidelines, reviews, and meta-analyses. Inadequate outcome reporting challenges researchers, clinicians, and policymakers, impacting evidence-based decision-making. Urgent improvements in RCT registration necessary.

Alterations in the Course of Inflammatory Bowel Disease Following Liver Transplantation: A Systematic Review and Meta-analysis.

BACKGROUND: This study aimed to systematically review and pool data regarding the alterations in the clinical course of inflammatory bowel disease (IBD) following liver transplantation (LT). METHODS: Relevant prospective and retrospective observational studies were identified by searching databases and gray literature through December 2020. Random-effects models were used to calculate the pooled frequency of IBD patients with disease course alterations ("improved," "unchanged," or "aggravated") after LT and the corresponding 95% confidence intervals (CIs). RESULTS: Twenty-five studies met our inclusion criteria, reporting the outcomes in 2 or 3 categories. In the analysis of studies with 3-category outcomes (n = 13), the pooled frequencies of patients with improved, unchanged, or aggravated IBD course after LT were 29.4% (95% CI, 16.9% to 41.9%), 51.4% (95% CI, 45.5% to 57.3%), and 25.2% (95% CI, 15.6% to 34.8%), respectively. Subgroup analyses revealed that patients with ulcerative colitis (UC), younger age at LT, or shorter duration of follow-up were more likely to have an improved disease course. Moreover, higher IBD exacerbation estimates were observed in studies with a low risk of bias. In the analysis of studies with 2-category outcomes (n = 12), the pooled frequencies of patients with improved/unchanged or aggravated IBD course were 73.6% (95% CI, 62.2% to 85.0%) and 24.1% (95% CI, 15.1% to 33.2%), respectively. The cumulative incidence of an exacerbated IBD course following LT was 0.22 (95% CI, 0.16-0.29; P < .001). CONCLUSION: We conclude that IBD activity remains unchanged (or improved/unchanged) in most IBD patients following LT. Furthermore, IBD type, age, and follow-up length can influence the IBD course after LT.

Our meta-analysis revealed that inflammatory bowel disease (IBD) activity remained "unchanged" (or "improved/unchanged") in most IBD patients following liver transplantation. IBD type, age, and follow-up length could influence the IBD course after liver transplantation.

QUS characteristics in Normal Population: a Mini Review and our experience.

Objectives: Quantitative ultrasound (QUS) is a bone densitometry method that is less expensive and more portable than DXA. It is also noninvasive. QUS parameters include speed of sound (SOS), broad band ultrasound attenuation (BUA), and stiffness index (SI). This study defined normal values of QUS parameters in Iranian men and women. Methods: QUS of heels measured in 258 Iranian men and women, aged 20-76 y/o. They were participants of Iranian Multicenter Osteoporosis study (IMOS), selected by randomized sampling. QUS device was an Achilles+ (GE-Lunar) device. Results: Percentiles of SI (2.5%, 50%, and 97.5%) determined. We found a good agreement between the Iranian reference values and western reference (used by device) value in defining normal and osteoporotic people (κ = 0.875). Conclusion: Results from this study suggest that QUS of the heel may be a good method for diagnosis of low bone mass in different regions.

Lymphocytes subsets in correlation with clinical profile in CVID patients without monogenic defects.

Objectives: Common variable immunodeficiency (CVID) patients experience clinical manifestations rather than recurrent respiratory infections including autoimmunity, enteropathy, and lymphoproliferation. We evaluated the correlation of lymphocyte subpopulations with such manifestations.Methods: Twenty-six genetically unsolved CVID patients were subdivided into four phenotypes: infection only (IO), autoimmunity (AI), chronic enteropathy (CE), and lymphoproliferative disorders (LP) and examined for lymphocyte subsets by flow cytometry and TCD4+ proliferation by Carboxyfluorescein succinimidyl ester (CFSE) test.Results: We detected reduced memory B and increased total, effector memory (EM), cytotoxic, and activated TCD8+ in IO, AI and CE, decreased plasmablasts, total and naive TCD4+, Regulatory TCD4+ (Treg) and naive TCD8+ in IO and CE, elevated CD21low B and terminally differentiated effector memory (TEMRA) TCD8+ in IO and AI, increased helper T (Th2) and Th17 in IO, decreased Th1 in AI and defective total and naive B and central memory (CM) TCD4+ in CE. IO showed reduced TCD4+ proliferation response.Conclusions: In genetically unsolved CVID patients, increased Th2 and Th17 and reduced Treg is associated with IO, increased CD21low B and TEMRA TCD8+ and reduced Th1 is contributed to AI and reduced total and naive B, CM TCD4+ and naive TCD8+ and expanded total TCD8+ is correlated with CE.

Association of vitamin D receptor gene polymorphism with the occurrence of low bone density, osteopenia, and osteoporosis in patients with type 2 diabetes.

PURPOSE: This study aims to analyze the association between VDR gene polymorphism and the occurrence of "low bone density (LBD)/osteopenia/osteoporosis" or LBDOO in type 2 diabetes (T2D) patients among a clustered population in northwest of Iran. The studied VDR gene polymorphism included ApaI (rs7975232), BsmI (rs1544410), FokI (rs2228570), EcoRV (rs4516035) and, TaqI (rs731236). METHODS: In this population-based cross-sectional study, patients with T2D were identified within a group of 1266 participants based on self-report of diabetes, history of diabetes medication, and recorded laboratory data. Separately for each polymorphism and gender, crude and adjusted (age, BMI) odds ratios (ORs) were calculated for participants with T2D through logistic regression analysis. RESULTS: The prevalence of T2D was 16.41% in people residing in the city of Sanandaj in 2011. Of the participants with T2D, 13.92% and 81.29% had osteoporosis and vitamin D deficiency, respectively. In women, the tt genotype of the TaqI gene significantly decreased the risk of LBDOO versus the Tt genotype, after adjusting for BMI and age (adjusted OR:0.18, CI95%: 0.03-0.97). Conversely, the EE genotype of the EcoRV gene enhanced the risk of LBDOO versus the Ee genotype (adjusted OR:7.64, CI95%: 2.03-28.72). CONCLUSION: The polymorphism of both TaqI and EcoRV genes was associated with the risk of LBDOO in women with T2D. This is the first time a study has highlighted this effect for the polymorphism of the EcoRV gene; we believe that this study would serve as a basis for future studies.

Prognostic value of endoscopic ultrasound in acute pancreatitis.

BACKGROUND/AIMS: Endoscopic ultrasonography (EUS) is a useful modality to diagnose causes of pancreatitis. The role of EUS for prediction of pancreatitis severity has not been studied. The aim of this study was to identify the utility of EUS in determining the severity of acute pancreatitis (AP). METHODS: All patients diagnosed with pancreatitis consecutively underwent EUS on the 2nd day of their admission. Atlanta criteria were used as the severity index of pancreatitis. RESULTS: During the study period, 114 patients (74 females, 40 males; mean age of 53.03 ± 17.7 years) were enrolled in the study. The most common cause of AP was gallstone (78.9%). According to the Atlanta criteria, pancreatitis was mild in 72 (63.2%) and severe in 42 (36.8%) patients. In univariate analysis, the presence of peripancreatic edema, pancreas inhomogeneity, common bile duct dilation and ascites were associated with severe pancreatitis. In multivariate analysis, only the presence of peripancreatic edema in EUS correlated with the severity of AP according to the Atlanta criteria (sensitivity, specificity and accuracy: 65.8, 75.7 and 72.2%, respectively). CONCLUSION: EUS may be a new useful imaging modality for prediction of severity of AP and may have prognostic significance in the early phase of AP. and IAP.

Transitional immature regulatory B cells and regulatory cytokines can discriminate chronic antibody-mediated rejection from stable graft function.

BACKGROUND: The balance between inflammatory and anti-inflammatory responses of the immune system has been demonstrated to determine the fate of transplanted allografts. Here we analyzed CD19+CD24hiCD38hi immature transitional regulatory B (TRB) cells, as well as the gene and protein levels of interleukin (IL)-10 and transforming growth factor (TGF)-ß in the three separate groups, include of stable transplanted subjects, chronic antibody-mediated rejection (cAMR) patients, and healthy individuals. METHOD: Peripheral blood mononuclear cells (PBMCs) from stable subjects (n = 36), cAMR patients (n = 36) and healthy controls (n = 18) were isolated. Flowcytometry was performed for CD19, CD24, and CD38 surface markers. ELISA and quantitative real-time PCR were performed for IL-10 and TGF-ß cytokines. RESULT: The percentages of immature TRB cells were significantly decrease in cAMR patients (0.98%) versus stable recipients (2.81%) and healthy subjects (4.03%) (P = 0.001 and P < 0.001, respectively). Total lymphocytes, circulating B cells, memory and mature subsets of B cells did not show any significant difference between the groups. TGF-ß mRNA was 3-fold upregulated in the cAMR group compared to stable patients (P < 0.001.), but without significant alteration at the protein level. Also, long-term survival renal transplant recipients had a higher protein but not mRNA levels of IL-10 than short-term survival renal transplant recipients. CONCLUSION: It seems that immature TRB cell subpopulation might be a crucial regulator of immune system response and plays an important role in determining the transplantation outcome. Furthermore, immunosuppressive IL-10 and TGF-ß cytokines might act as a double sword and can exhibit either pathogenic or protective effects against allograft.

Prediction of postnatal abnormal coiling of the umbilical cord in gestational diabetes mellitus: a diagnostic accuracy study.

Objective: To investigate whether evaluations of antenatal umbilical coiling index (aUCI) could predict postnatal umbilical coiling index (UCI) (pUCI) in people with gestational diabetes mellitus (GDM) compared with normal pregnancy independent of maternal demographic and reproductive characteristics.Method: In this prospective study, 105 women with normal pregnancy, and 117 women with pregnancy complicated by GDM were recruited. Ultrasound scan of umbilical cord was performed at 18-23 and 37-41 weeks of gestation (WG). Evaluation of pUCI, as the reference standard, was performed within 24 hours after delivery.Findings: There was no significant relationship between aUCI and maternal demographic and reproductive characteristics. The mean for pUCI was 0.21 ± 0.12 in the GDM group, and 0.21 ± 0.09 in the normal pregnancy (p = .61). In the GDM group, a significant association was found between aUCI and pUCI categories (p = .004). The area under curve (AUC) was less than 0.5 for hypocoiling in both groups. For hypercoiling it was 0.84 ± 0.04 in the GDM group and 0.75 ± 0.06 in the normal pregnancy group (18-23 WG). In the GDM group the cutoff points that predict hypercoiling were 0.28 (18-23WG), and 0.21 (37-41WG). These were 0.35 (18-23WG), and 0.33 (37-41WG) in the normal pregnancy group. Diagnostic accuracy analysis revealed that in the GDM group, the sensitivity and specificity of hypercoiling for prediction of pUCI were 0.94 and 0.70 respectively at 18-23 WG.Conclusions: Antenatal hypercoiling at the second trimester of pregnancy strongly predict postnatal hypercoiling in pregnancies complicated by GDM.

Evaluation of Golestan Province's Early Warning System for flash floods, Iran, 2006-7.

Golestan province located in NE Iran is well known for deadly flash floods. This study aimed to evaluate the region's Early Warning System (EWS) for flash floods. We used an adapted version of the questionnaire developed by the United Nations International Strategy for Disaster Reduction. We reviewed documents on the EWS of Golestan, and conducted a qualitative study comprising interviews with experts and affected people in Kalaleh and Minoodasht. Results were discussed by an expert panel. Regarding risk knowledge, there was a hazard map at Provincial Disaster Taskforce (PDT) drawn by the provincial Office for Water Resource Management, but no risk analysis was available. Local people were aware of their exposure to flooding, but not aware of the existence of a hazard map and their vulnerability situation. In terms of monitoring and warning, PDT faced serious limitations in issuing Early Warnings, including (1) an inability to make point predictions of rainfall, and (2) the absence of a warning threshold. Dissemination and communication issued by the Meteorological Office followed a top-to-bottom direction. The contents were neither clearly understood by other institutions nor reached the potential recipients within an appropriate time frame. There was a need for a comprehensive response plan with adequate exercises, and no evaluation framework existed. Golestan EWS is in dire need of improvement. To fill in the gaps ensuring local people receive timely warning, we propose a community-based model called "Village Disaster Taskforce" (VDT) in which individual villages act as operational units, but interlinked with other villages and PDT.

Prevalence of Malnutrition Among Elderly People in Iran: Protocol for a Systematic Review and Meta-Analysis.

BACKGROUND: Malnutrition occurs following a decrease or an imbalance in the absorption of energy, protein, vitamins, and minerals because of numerous factors. Thus, it has serious and life-threatening consequences. To plan for this issue, we need information on the burden of this problem. OBJECTIVE: The aim of this study is to determine the prevalence of malnutrition among elderly people in Iran. METHODS: For the purpose of this study, papers, including original articles, theses, and conference proceedings on the prevalence of malnutrition among people aged 60 years and above, and have been published in national and international journals until September 2018 will be included without any language limitation. The following keywords along with their synonyms in Persian will be used in the literature search: malnutrition, elderly, and Iran. At first, the screening process will be conducted based on our inclusion and exclusion criteria. Then, the full text of the remaining articles will be read carefully, and eligible articles will be selected according to the objectives of the study. Next, the methodological quality of the selected papers will be reviewed, and the required information will be extracted from those with acceptable quality. Finally, a meta-analysis will be performed using the Stata software (version 14) when optimum criteria are met. It should be noted that all stages of screening, selection, quality assessment of primary studies, and data extraction will be performed by two reviewers independently. RESULTS: This review is ongoing and will be completed at the end of 2019. CONCLUSIONS: This review aims to provide comprehensive evidence about the prevalence of malnutrition among elderly people in Iran. This can help Iranian health managers and policy makers make informed decisions for preventing malnutrition and promoting the health status of elderly people. TRIAL REGISTRATION: PROSPERO CRD42018115358; https://tinyurl.com/y28su47m. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15334.

The Effect of Vitamin D Supplements on Clinical and Para-Clinical Outcomes in Patients With Multiple Sclerosis: Protocol for a Systematic Review.

BACKGROUND: Multiple sclerosis (MS) is an inflammatory disease, which has a wide range of effects on patients. There are controversies regarding the role of vitamin D in clinical and laboratory improvements in MS patients. OBJECTIVE: The aim of this systematic review protocol is to evaluate the efficacy of vitamin D supplements on relapse rate, gadolinium-enhancing lesions of magnetic resonance imaging (MRI), and cytokine profiles. METHODS: We will search PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, ProQuest, American College of Physicians Journal Club database, Health Technology Assessment Database (The Cochrane Collaboration), and National Health System Economic Evaluation Database (The Cochrane Collaboration) and gray literature including reference of included studies and conference abstracts. Clinical trials reporting the effect of any doses of vitamin D on relapse rate, gadolinium-enhancing lesions of MRI, and cytokine profiles will be included. In total, 2 independent researchers will independently assess the studies, extract data, and evaluate the quality of primary studies. RESULTS: This systematic review was started in September 2017 and the process is continuing. The included articles are evaluated and researchers are going to extract the data. CONCLUSIONS: To our knowledge, this will be the first comprehensive systematic review aiming to assess the effect of vitamin D supplements on clinical and para-clinical outcomes in patients with multiple sclerosis. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12045.

Quadriceps architecture in individuals with patellofemoral pain: a systematic review protocol.

OBJECTIVE: The objective of this review is to identify differences in quadriceps architectural parameters between healthy individuals and those with patellofemoral pain (PFP). INTRODUCTION: Patellofemoral pain is one of the most common causes of knee pain among physically active populations. Muscular imbalance may play an important role in patellar malalignment or patellar maltracking. A systematic review will clarify the possible architectural changes of quadriceps muscles in persons with PFP. INCLUSION CRITERIA: Eligible observational studies will include individuals younger than 50 years who have been diagnosed with unilateral or bilateral PFP. The comparator will be the contralateral, asymptomatic limb of the individual with PFP or a healthy matched subject. Studies that include measurement of quadriceps muscle size as the primary outcome will be considered. Studies in which participants had coexisting pathology, a history of lower limb surgery or injury, or pain originating from other joints will be excluded. METHODS: PubMed/MEDLINE (NLM), Scopus, Embase, Physiotherapy Evidence Database, Web of Science and CINAHL databases and multiple gray literature sources will be searched. Studies published since 1 January 1990 will be considered; there will be no language restriction. Retrieval of full-text studies, assessment of methodological quality and data extraction will be performed independently by two reviewers. If possible, meta-analyses will be performed, and a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Summary of Findings presented.

Defining loneliness in older adults: protocol for a systematic review.

BACKGROUND: Socialization is an important part of the healthy aging process, but natural changes in the lifestyle and health of older people increased risk of loneliness. However, loneliness is not well defined and might differ in different cultures and settings. The main objective of this systematic review is to summarize literature on the topic and propose a definition that might help aging research and practice in the future. METHODS: Eight databases including PubMed, Scopus, CINAHL, Web of Science, EMBASE, PsycINFO, Proquest, and Age Line bibliographic will be run individually to retrieve relevant literature on loneliness among elderly population using subject headings and appropriate MeSH terms. Inclusion and exclusion criteria will be developed and refined by the research team. Two reviewers will participate in each search stage including abstract/title and full text screening, data extraction, and appraisal. We will restrict our search to articles published in the English language biomedical journal between 2000 and 2017. The protocol adheres to the standards recommended by the PRISMA-P. DISCUSSION: The results of this systematic review can present a more accurate definition of loneliness for researchers who aim at conducting new primary and secondary studies on this subject. SYSTEMATIC REVIEW REGISTRATION: CRD42017058729.

Prevalence of hepatitis D virus infection in hepatitis B surface antigen-positive subjects in Golestan province, northeast Iran.

BACKGROUND AND PURPOSE: Hepatitis D virus (HDV) is a defective RNA virus dependent on hepatitis B virus (HBV) infection for its replication and expression. It is known that coexistent infection with HDV tends to aggravate the course of HBV-associated liver disease. This study was carried out to determine the seroprevalence of HDV among hepatitis B surface antigen (HBsAg)-positive individuals in the northeast part of Iran. METHODS: 139 HBsAg-positive subjects detected from a population-based single stage cluster sampling in Golestan province of Iran were enrolled. All cases were evaluated for the presence of anti-HDV antibodies using commercially available enzyme-linked immunoabsorbent assay kits. Logistic regression was used to determine the relationship between independent variables and HDV seropositivity. RESULTS: Of 139 cases, 68 were males (48.9%) and 71 were females (51.1%). The mean age was 41.9 +/- 11.3 years (range, 25-64 years). Anti-HDV antibody was positive in 8 subjects (5.8%), with a female predominance (9.9% vs 1.5%, p=0.06; odds ratio, 7.32; 95% confidence interval, 0.87-61.23). No significant relationship was seen between anti-HDV seropositivity and demographic factors such as age, place of residence and marital status. CONCLUSIONS: These findings show that HDV infection is endemic in Golestan province (northeast) of Iran. Seroprevalence of anti-HDV in the present study was higher than in some previous studies from other parts of Iran. Our results suggest that the prevalence of HBV/HDV coinfection in Golestan province of Iran has increased during the last decade. Therefore, practitioners and health care managers should be made aware of the risk of dual infection with HBV and HDV.

Safety and efficacy of hematopoietic and mesanchymal stem cell therapy for treatment of T1DM: a systematic review and meta-analysis protocol.

INTRODUCTION: Insulin standard treatment of T1DM cannot cure the patients as different chronic complications occurred subsequently. Investigations on a curative treatment in T1DM propose cell replacement or maintenance instead of exogenous insulin therapy, but different dimensions of this novel treatment are not clarified. METHODS AND ANALYSIS: We will include all clinical trials which have evaluated the efficacy MSC or HSC transplantation in T1DM treatment; electronically search bibliographic databases, country registration data banks, and gray literatures; and hand-search two key journals, two experts' article, and references of the included articles with no language restriction. Primary outcome is the extent of reduction in insulin requirement and secondary outcomes are safety of MSC and HSC therapy, effect of this therapy on diabetic parameters, effect of the rout of transplantation and origin of the MSC or HSC on efficacy of treatment, studies heterogeneity and potential reasons of it. Heterogeneity and its severity will be calculated with Q Cochrane test, P value, and I2 index. STATA software version 12 will be used for meta-analysis. PROSPERO Registration number: CRD42016047176. ETHICS AND DISSEMINATION: We will publish the systematic review in a peer review journal; as it presents an analysis of published literature, the study does not require ethical approval. STRENGTHS AND LIMITATIONS OF THIS STUDY: This systematic review and meta-analysis will investigate the efficacy of MSC and HSC transplantation in T1DM treatment with no language restriction. Also we will evaluate gray literatures after hand searching. This protocol is prepared according to Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Two reviewers will evaluate screened full texts, extract data, and asses risk of bias of eligible primary studies independently. As there is the possibility that we miss some unpublished primary studies due to negative results, we will use funnel plot to detect this and correct it with fill and trim method.