IL-27 attenuates IL-23 mediated inflammatory arthritis.

Interleukin 27 has both pro-inflammatory and anti-inflammatory properties in autoimmunity. The anti-inflammatory effects of IL-27 are linked with inhibition of Th17 differentiation but the IL-27 effect on myeloid cells is less studied. Herein we demonstrate that IL-27 inhibits IL-23-induced inflammation associated not only with Th17 cells but also with myeloid cell infiltration in the joints and splenic myeloid populations of CD11b+ GR1+ and CD3-CD11b+CD11c-GR1- cells. The IL-27 anti-inflammatory response was associated with reduced levels of myeloid cells in the spleen and bone marrow. Overall, our data demonstrate that IL-27 has an immunosuppressive role that affects IL-23-dependent myelopoiesis in the bone marrow and its progression to inflammatory arthritis and plays a crucial role in controlling IL-23 driven joint inflammation by negatively regulating the expansion of myeloid cell subsets.

Cross-sectional analysis of potential risk factors of the pineal gland calcification.

The Pineal gland (PG) is the site of production of melatonin as an important central hormone in the body. It is not known yet whether PG calcification (PGC) is an age-associated physiological process or a pathologic condition caused by lifestyle-factors and metabolic-dysregulations.Here, we performed a cross-sectional analysis on 586 patients referred to have Computed Tomographic (CT) scans (above 15 years old), in the Ali Ebne Abi Taleb hospital radiology center in 2017-2018. Based on the CT-scans of the brain, the presence of PGC was recorded and a score of scale 0 to 6 (PGC_score) was calculated for its intensity based on the volume and the Hounsfield units of the calcified pineal. Logistic and ordered logistic regression tests were employed to determine potential risk factor of PGC and higher PGC_score, respectively, testing the factors age, sex, history of cardiovascular and metabolic diseases, smoking and opioid use. We found male sex (OR: 2.30 (95% CI:1.39-3.82) and smoking cigarettes (OR: 4.47 (95% CI:1.01-19.78)) as the main potential risk factors for the pineal gland calcification. For PGC_score, we found age to be dose-dependently associated with PGC_score only in patients aged below 63 (p-trend < 0.001). Stratifying for age, in patients < 63 years old, we found age, male sex (positive association) and dyslipidemia (negative association) as the main significantly associated factors of PGC_score. On the contrary, in patients aged > = 63, cigarette smoking was the only significantly associated factor of higher PGC_score.In conclusion, our results indicate that at ages below 63, age, male sex and blood lipid are the main associated factors of higher PGC, but at ages above that, the lifestyle factor smoking is significantly associated with higher pineal gland calcification.

The prevalence and associated factors of overweight/obesity and abdominal obesity in South-eastern of Iran: a cross-sectional study based on Rafsanjan cohort study.

BACKGROUND: Obesity has become a major health issue in both high and middle-income countries, increasing the risk of cardiovascular diseases and all-cause mortality. Risk of obesity is related to both unchangeable factors such as genetics and gender, and modifiable lifestyle factors. Most importantly, finding the major modifiable lifestyle factors which contribute to obesity may provide valuable benefits to every society. This study aimed to determine the association of demographic and lifestyle parameters with overweight/obesity and abdominal obesity in a population of Iranian adults. METHODS: In this cross-sectional study, adult participants of Rafsanjan Cohort Study (RCS) (as one of the district areas of the PERSIAN cohort (Prospective Epidemiological Research Studies in IrAN) included the study population. RCS is a population-based prospective cohort of men and women aged 35-70 years, launched in August 2015. Individuals were recruited from four urban and suburban areas of Rafsanjan, south-eastern of Iran. Trained experts interviewed each participant and completed the related questionnaires about his/her socioeconomic status, demography, anthropometric features, personal habits, physical activity and medical history. Multinomial logistic regression models were used to examine the relationships between overweight/obesity/abdominal obesity and associated factors. RESULTS: From 9980 participants, 1974 (42.42%) males and 2115 (39.70%) females were overweight, 784 (16.85%) males, 2223 (41.73%) females were obese and 1895 (40.73%) males and 989 (18.57%) females were normal weight. Also, 832 (17.9%) males and 4548 (85.4%) females had abdominal obesity and 3819 (82.1%) males and 778 (14.6%) females didn't have abdominal obesity. Based on the adjusted multiple logistic regression, overweight/obesity (BMI > 25) was associated with age > 45, female gender, education ≥ 13 years, heavy physical activity, wealth status index (WSI), alcohol consumption, current cigarette smoking and opium consumption compared to reference group. Also, odds of abdominal obesity displayed a significant association with age > 45, female gender, education > 5 years, physical activity, WSI, current cigarette smoking, alcohol and opium consumption compared to reference group. CONCLUSIONS: Our results recommend local public health strategies that promote training the society on the health benefits of avoiding alcohol, getting more physical exercise and gaining more personal education on the health-threatening lifestyle.

Cohort-based analysis of maternal age at menarche in relation to young adult offspring anthropometric and metabolic parameters.

OBJECTIVES: Age of menarche is a determinant factor of cardiometabolic risk, adiposity and stature at adulthood. However, little is known about the transgenerational effects of age of menarche, especially beyond childhood of any offspring, and the studies remain limited to anthropometric outcomes in children at birth or before adolescence. In the present study, we aim to investigate the relationship of maternal age at menarche (MAM) with anthropometric and metabolic parameters in the young adult offspring (aged 15-35 years) in a Persian population. DESIGN, PATIENTS AND MEASUREMENTS: In this cohort-based cross-sectional study, we recruited 1139 mother-young adult dyads enroled in Rafsanjan Cohort Study (RCS) at adult RCS (aged 35-70 years) and youth RCS (aged 15-35 years) as part of the comprehensive PERSIAN (Prospective Epidemiological Research Studies in IrAN). In this study, MAM was categorized to early (MAM < 12 years), normal (12 ≤ MAM ≤ 14) and late menarche (MAM > 14 years). For these analyses, bivariate and multiple logistic regression models were used to investigate the relationships between late or early MAM and offspring anthropometric and metabolic parameters. RESULTS: Early MAM displayed a significant association with an increased odds ratio (OR) of tall stature adjusting for sex, age, socioeconomic status index, maternal age at birth and maternal height (as genetically determined factor). Sensitivity analysis by sex indicated this relationship to be specific to male offspring only (adjusted OR: 1.84 95% CI: 1.13-3.00, p value: .014). In addition, late MAM displayed a significant association with reduced OR of overweight/obesity and abdominal obesity in daughters only (obesity adjusted OR: 0.49, 95% CI: 0.27-0.88, p value: .018, abdominal obesity adjusted OR: 0.44, 95% CI: 0.23-0.82, p value: .010). dose-response analysis by categorization of MAM, further supported our results. On the contrary, our analyses do not support a significant relationship between MAM and youth metabolic indices, that is, metabolic syndrome, fasting blood sugar (FBS), high-density lipoprotein (HDL) and triglyceride (TG). CONCLUSIONS: The results of the present study indicate an association of maternal age of menarche with anthropometric measures of offspring in young adulthood in a sex differential manner. The data does not support a significant relationship between the metabolic indices FBS, TG and HDL in offspring with MAM. Overall, this study provides evidence for the intergenerational effects of age at menarche in the development of anthropometric measures in offspring in young adulthood (15-35), which is the first study of this kind in this age range.

Association between nitrate concentration in drinking water and rate of colorectal cancer: a case study in northwestern Iran.

Nitrate, as a major pollutant of drinking water, is associated with colorectal cancer (CRC) and serves as an environmental health concern, especially in the districts with unregulated agriculture. In this case study in northwestern Iran, we used two databases of nitrate concentration (1999-2013) and age-standardized incidence rate (ASR) for CRC (2002-2012) from 19 counties of East Azerbaijan province. The trend and correlation between nitrate and ASR was investigated. Inverse distance weighted technique was used to spatially interpolate the maps. Expectedly, drinking water nitrate has increased throughout the province (8-20.5 mg/L) as well as the ASR for CRC of men (from 2.07 to 18.05 mg/L) and women (from 1.57 to 10.94 mg/L). While ASR for CRC of men was positively correlated to nitrate (Pearson's r = 0.624, p-value = 0.040), no statistically significant correlation was found between nitrate and ASR for women's CRC (Pearson's r = 0.289, p-value = 0.351). According to our findings, the incidence of CRC was not higher for those residing in the regions with higher nitrate, suggesting that risk factors such as genetic predisposition and diet that were not taken into account could be determinants of this pattern. However, even a small increase in CRC rate due to water nitrate could translate into a large public health concern. The incremental pattern observed in nitrate levels of different counties over the years gives the health policymakers a better perspective of the problem and how the control of water nitrate level as a CRC risk factor might contribute to the prevention of CRC.

The profile of Rafsanjan Cohort Study.

Owning the largest human-made jungle of pistachio, the second largest copper mine, and being located on the trade route of opium transit, distinguish Rafsanjan from many other cities in Iran. The environmental exposures and lifestyle factors associated with these characteristics of Rafsanjan, have raised concern about possible health outcomes for individuals living in and around this city. Thus, local health authorities initiated the Rafsanjan Cohort Study (RCS), as part of the prospective epidemiological research studies in IrAN (PERSIAN). RCS is a population-based prospective cohort of men and women aged 35-70 years, launched in August 2015. Individuals from diverse socioeconomic levels and lifestyles were recruited from four urban and suburban areas of Rafsanjan (participation rate 67.42%). Questionnaire-based interviews regarding demographics, dietary and environmental exposures, medical and occupational history, as well as anthropometric measurements were completed for all participants. Additionally, bio-specimens (blood, urine, hair, and nail) were collected, and dental and eye examinations were performed. The enrollment phase ended in December 2017, and a 15-year follow-up is planned. A total of 9990 individuals were enrolled in RCS (53.41% females). About 26% of men are pistachio farmers. The baseline prevalence of major non-communicable disease (NCD) risk factors such as cigarette smoking, alcohol consumption and opium use were 25.45%, 10.02%, and 23.81%, respectively. The mean ± SD of other common risk factors are as follows: body mass index (27.83 ± 4.89 mm Hg), systolic blood pressure (107.18 ± 17.56 mm Hg) diastolic blood pressure (71.13 ± 10.83), fasting blood sugar (113.27 ± 39.11 mg/dL) and plasma cholesterol (198.78 ± 41.89 mg/dL). These results indicate a concerning prevalence of NCD risk factors in Rafsanjan city, warranting further detailed investigations, particularly regarding the association of NDC with agricultural/industrial pollutants and drug abuse.

Smoking, alcohol and opioids effect on coronary microcirculation: an update overview.

Smoking, heavy alcohol drinking and drug abuse are detrimental lifestyle factors leading to loss of million years of healthy life annually. One of the major health complications caused by these substances is the development of cardiovascular diseases (CVD), which accounts for a significant proportion of substance-induced death. Smoking and excessive alcohol consumption are related to the higher risk of acute myocardial infarction. Similarly, opioid addiction, as one of the most commonly used substances worldwide, is associated with cardiac events such as ischemia and myocardial infarction (MI). As supported by many studies, coronary artery disease (CAD) is considered as a major cause for substance-induced cardiac events. Nonetheless, over the last three decades, a growing body of evidence indicates that a significant proportion of substance-induced cardiac ischemia or MI cases, do not manifest any signs of CAD. In the absence of CAD, the coronary microvascular dysfunction is believed to be the main underlying reason for CVD. To date, comprehensive literature reviews have been published on the clinicopathology of CAD caused by smoking and opioids, as well as macrovascular pathological features of the alcoholic cardiomyopathy. However, to the best of our knowledge there is no review article about the impact of these substances on the coronary microvascular network. Therefore, the present review will focus on the current understanding of the pathophysiological alterations in the coronary microcirculation triggered by smoking, alcohol and opioids.

Body image, internalized stigma and enacted stigma predict psychological distress in women with breast cancer: A serial mediation model.

AIMS: To investigate the roles of total stigma, enacted stigma, and internalized stigma in the prediction of psychological distress among breast cancer patients, and to evaluate the mediating effect of body image in this process. DESIGN: Cross-sectional. METHODS: Between Oct-2014 to May-2015, a cross-sectional study was conducted with participation of 223 patients from three cancer centres located in Tehran, Iran. The study variables were assessed using the stigma scale for chronic illnesses 8-item version (SSCI-8), body image scale (BIS), and depression anxiety stress scale (DASS-21). Structural equation modelling using MLR estimator was employed based on the two-step procedure to validate both the full measurement models and the structural models. Five models were tested to determine predictability of all stigma constructs for psychological distress, including stress, anxiety, and depression, through the mediation of body image. Three equivalent models were further examined to re-evaluate the direction of the relationships. RESULTS: Psychological distress and body image were largely predicted by total stigma, enacted stigma, and internalized stigma. The effect of stigma on psychological distress was mediated through body image. In a serial mediation model, the significance of the pathway of enacted stigma > internalized stigma > body image > psychological distress was confirmed. The serial model in which internalized stigma precedes body image was also supported by the equivalent models. CONCLUSION: Stigma has been identified as a major source of psychological distress among women with breast cancer. Enacted stigma not only psychologically disturbs the patients but also triggers a chain of other identity transformations (i.e. internalization of stigma and distortion of body image), their ultimate result being a full-blown psychological distress. IMPACT: Both enacted and internalized stigma distorts breast cancer patients' perception of their body image, which in turn renders them psychologically distressed. The serial process of enacted stigma, internalized stigma, and body image plays an important role in perpetuating distress in these patients. To break this chain of psychological consequences and for interventions to have a greater impact on overall well-being of patients, the effect of enacted stigma on distress via the sequence of two mediators needs to be specifically targeted at each stage.

Diagnostic and prognostic role of ascitic fluid calprotectin level: six-month outcome findings in cirrhotic patients.

AIM: To assess the role of ascites calprotectin in early detection of SBP in patients with cirrhosis and to investigate its prognostic value in determination of the 6-month outcome. Methods and material: In this cross-sectional study, patients with liver cirrhosis who were consecutively referred to Imam Reza hospital, tertiary referral center in the northwest of Iran, underwent abdominal paracentesis. The samples were collected for measurement of calprotectin, albumin, total protein, WBCs, and PMNs. RESULTS: The mean age of a total of 87 included patients was 56.86 (SD 16.05) years old with over half of the subjects (55.2%) being female. About 28.7% of performed paracenteses tested positive for SBP. Ascitic calprotectin was positively correlated to the PMN counts. Patients with SBP were found to have higher levels of ascites albumin, total protein, and calprotectin. Only 51 individuals survived the 6-month follow-up period and mortality outcomes were significantly related to the levels of aforementioned biochemical markers (p-value <.05). CONCLUSION: Alongside with standard PMN counts, calprotectin measurement in the ascitic fluid could be used as an available test for early diagnosis of SBP. Calprotectin can also serve as a valuable prognostic marker in the evaluation of cirrhotic patients.

Folliculin regulates ampk-dependent autophagy and metabolic stress survival.

Dysregulation of AMPK signaling has been implicated in many human diseases, which emphasizes the importance of characterizing AMPK regulators. The tumor suppressor FLCN, responsible for the Birt-Hogg Dubé renal neoplasia syndrome (BHD), is an AMPK-binding partner but the genetic and functional links between FLCN and AMPK have not been established. Strikingly, the majority of naturally occurring FLCN mutations predisposing to BHD are predicted to produce truncated proteins unable to bind AMPK, pointing to the critical role of this interaction in the tumor suppression mechanism. Here, we demonstrate that FLCN is an evolutionarily conserved negative regulator of AMPK. Using Caenorhabditis elegans and mammalian cells, we show that loss of FLCN results in constitutive activation of AMPK which induces autophagy, inhibits apoptosis, improves cellular bioenergetics, and confers resistance to energy-depleting stresses including oxidative stress, heat, anoxia, and serum deprivation. We further show that AMPK activation conferred by FLCN loss is independent of the cellular energy state suggesting that FLCN controls the AMPK energy sensing ability. Together, our data suggest that FLCN is an evolutionarily conserved regulator of AMPK signaling that may act as a tumor suppressor by negatively regulating AMPK function.

Metabolic syndrome: a population-based study of prevalence and risk factors.

The association between personal habits and metabolic syndrome (MetS) remains controversial. This study aimed to assess the prevalence of MetS among youths and its association with cigarette, tobacco, opium, and alcohol consumption in the Rafsanjan Youth Cohort Study (RYCS). The current cross-sectional study was based on data from RYCS, as part of the Rafsanjan Cohort Study (RCS). RCS is a branch of the prospective epidemiological research studies in Iran (PERSIAN). In the present study, 2843 youths aged 15-35 were included. MetS was diagnosed using the international diabetes federation (International IDF), National Cholesterol Education Panel- Adult Treatment Panel III (NCEP-ATPIII), and Iranian criteria (IDF Iranian). Binary logistic regression models were performed to estimate odds ratios (ORs) and confidence intervals (CIs). The prevalence of MetS was 7.67%, 7.14%, and 10.13% based on NCEP-ATPIII, IDF Iranian, and International IDF criteria respectively. The odds of MetS according to international IDF and Iranian IDF in the alcohol-drinking group in the last 12 months (OR: 1.51, 95%CI 1.02-2.21, OR: 1.66, 95%CI 1.11-2.48 respectively) were greater compared with the non-drinking group. The odds of having high TG in the alcohol-drinking group in the last 12 months was 1.53 times higher than the control group (OR = 1.53, 95% CI: 1.20-1.94). Furthermore, the odds of having high waist circumference (WC) according to IDF International was significantly higher in the tobacco-smoking group in the last 12 months and in the tobacco-smoking group in the last 12 months daily (OR: 1.23, 95%CI 1.01-1.49 and OR: 1.41, 95%CI 1.01-1.98 respectively) compared to the control groups. The prevalence of MetS was 7.67%, 7.14%, and 10.13% based on NCEP-ATPIII, IDF Iranian, and International IDF criteria respectively. The odds of MetS and high TG were greater in the alcohol-drinking group in the last 12 months compared with the non-drinking group. The odds of high WC in the last 12 months, were greater in the tobacco-smoking group compared with the non-smoking group. However, more longitudinal studies are needed to verify the associations observed in the current study.

Umbilical cord blood thyroid hormones are inversely related to telomere length and mitochondrial DNA copy number.

Hypothyroidism has been linked to reduced mortality rate and increased lifespan and health span. Telomere shortening, enhanced oxidative stress, and reduced cellular mitochondrial content are important hallmarks of aging shown to be related to age-associated diseases. It was proposed that the status of these markers in early life can be predictive of lifespan and the predisposition to certain age-associated disease in adulthood. Animal studies indicated that prenatal injection of thyroid hormones affects postnatal telomere length. Here, we sought to determine whether thyroid hormones TSH and fT4 are related to the telomere length, mitochondrial DNA copy number (mtDNAcn), and oxidative stress resistance marker GPX in the cord blood of newborns. In this study, we analyzed 70 mothers (18-42 years) and neonate dyads born in 2022 at the Nik Nafs maternity Hospital in Rafsanjan. The relative telomere length (RTL) and mtDNAcn were measured in the genomic DNA of cord blood leukocytes using real-time PCR. GPX enzyme activity was measured in the serum using colorimetric assays. In this study the correlation between these markers and the cord blood TSH and fT4 hormones were assessed using regression models. We found a reverse relationship between TSH levels and RTL in the cord blood of neonates. Additionally, our results displayed increased TSH levels associated with enhanced GPX activity. Regarding the mitochondrial DNA copy number, we found an indirect relationship between fT4 level and mtDNAcn only in male newborns. Future analyses of various oxidative stress markers, mitochondrial biogenesis status, telomerase activity, and the level of DNA damage are warranted to demonstrate the underlying mechanism of our observations.

Characterizing the tumor suppressor activity of FLCN in Birt-Hogg-Dubé syndrome through transcriptiomic and proteomic analysis.

Birt-Hogg-Dubé (BHD) syndrome patients are uniquely susceptible to all renal tumour subtypes. The underlying mechanism of carcinogenesis is unclear. To study cancer development in BHD, we used human proximal kidney (HK2) cells and found that long-term folliculin (FLCN) knockdown was required to increase their tumorigenic potential, forming larger spheroids in non-adherent conditions. Transcriptomic and proteomic analysis uncovered links between FLCN, cell cycle control and the DNA damage response (DDR) machinery. HK2 cells lacking FLCN had an altered transcriptome profile with cell cycle control gene enrichment. G1/S cell cycle checkpoint signaling was compromised with heightened protein levels of cyclin D1 (CCND1) and hyperphosphorylation of retinoblastoma 1 (RB1). A FLCN interactome screen uncovered FLCN binding to DNA-dependent protein kinase (DNA-PK). This novel interaction was reversed in an irradiation-responsive manner. Knockdown of FLCN in HK2 cells caused a marked elevation of γH2AX and RB1 phosphorylation. Both CCND1 and RB1 phosphorylation remained raised during DNA damage, showing an association with defective cell cycle control with FLCN knockdown. Furthermore, Flcn-knockdown C. elegans were defective in cell cycle arrest by DNA damage. This work implicates that long-term FLCN loss and associated cell cycle defects in BHD patients could contribute to their increased risk of cancer.

Sleep duration, hypnotic drug use, and risk factors: cross- sectional study.

Both short sleep duration (SSD) and long sleep duration (LSD) are associated with an increased risk of morbidity and mortality. Here, we aimed to assess the prevalence of sleep duration disturbances among adults in association with demographic, medication use, personal habits, and chronic diseases, while also considering the impact of hypnotic drug use. We performed a cross-sectional study of 9991 adult participants of the Rafsanjan Cohort Study (RCS), as part of the Prospective epidemiological research studies in Iran (PERSIAN). Multivariate logistic regression analyses were conducted to assess the association between short (< 6 h) and long (> 9 h) sleep duration with demographic and lifestyle parameters and common non-communicable diseases. Additionally, we performed stratified analysis to investigate the association of sleep duration with the abovementioned factors and diseases, in groups with and without hypnotic drug use. We found higher odds of SSD significantly associated with age (P < 0.001), BMI (P < 0.001), physical activity (P < 0.001), and depression (P = 0.023). LSD displayed a positive association with the female sex (P < 0.001), opium consumption (P < 0.001), and history of MI (P = 0.045), and a reverse connection with education (P = 0.007), physical activity (P < 0.001) and alcohol consumption (P = 0.027). Stratifying for the hypnotic drug use, our sensitivity analyses indicated that in hypnotic drug users, education (P = 0.034) and physical activity (P < 0.001) were associated with LSD, in this group, significantly increased odds ratio of LSD were associated with opium consumption (P = 0.046) and thyroid dysfunction (P = 0.037). Our findings demonstrated the demographic and lifestyle factors and diseases associated with long and short sleep duration in the population of the RCS. Additionally, after stratifying for hypnotic drug use, our results indicated that some diseases are only associated with abnormal sleep duration upon using hypnotic drugs.

Evaluation of H19, Mest, Meg3, and Peg3 genes affecting growth and metabolism in umbilical cord blood cells of infants born to mothers with gestational diabetes and healthy mothers in Rafsanjan City, Iran.

Hyperglycemia during the first trimester leads to an increased risk of innate malformations as well as death at times close to delivery dates. The methylated genes include those from paternal H19 and PEG3 and those from maternal MEST and MEG3 that are necessary for the growth and regulation of the human fetus and its placenta. The aim of this study was to evaluate and compare the expression of these genes in the cord blood of healthy infants born to mothers with gestational diabetes mellitus (GDM) and healthy mothers.This case-control study was conducted on the cord blood of 40 infants born to mothers with GDM and 35 infants born to healthy mothers. Mothers were identified by measuring oral glucose tolerance in the 24th-26th week of pregnancy. Cord blood was obtained post-delivery, and cord blood mononuclear cells were immediately extracted, using Ficoll solution. Then, RNA extraction and cDNA synthesis were performed, and gene expression of MEG3, PEG3, H19, and MEST was assessed through quantitative real-time PCR.Findings show that the expression levels of MEG3, PEG3, H19, and MEST genes were significantly decreased in mononuclear cord blood cells of infants born to mothers with GDM when compared to those of the healthy control group.These findings reveal that the reduction of imprinted genes in mothers with GDM is most likely due to changes in their methylation by an epigenetic process. Considering the importance of GDM due to its high prevalence and its side effects both for mother and fetus, recognizing their exact mechanisms is of high importance. This has to be studied more widely.

Distinct signatures on d-galactose-induced aging and preventive/protective potency of two low-dose vitamin D supplementation regimens on working memory, muscular damage, cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation.

Chronic administration of d-galactose (d-gal) in rodents reproduces the overproduction of reactive oxygen species of physiological aging. The present research shows for the first time distinct signatures on d-gal-induced aging (500 mg/kg, 6 weeks) and the preventive and protective potential of two vitamin D (50 IU) supplementation regimens (pre-induction and simultaneous, respectively) in two vital organs (heart and brain). d-gal-induced notorious alterations in working memory, a strong increase in brain malondialdehyde (MDA) oxidative levels, and strong downregulation of sirtuin 1 (SIRT1) in the heart and hippocampus and of calstabin2 in the heart. Cardiac and brain superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic antioxidant capacities were damaged, brain calstabin2 was downregulated, and neuropathology was observed. Heart damage also included a moderate increase in MDA levels, serologic lactate dehydrogenase (LDH), total creatine kinase (CK) activities, and histopathological alterations. The used dose of vitamin D was enough to prevent cognitive impairment, avoid muscular damage, hamper cardiac and cerebral oxidative stress, and SIRT1 and calstabin2 downregulation. Most importantly, the potencies of the two preventive schedules depended on the tissue and level of study. The pre-induction schedule prevented d-gal-induced aging by 1 order of magnitude higher than simultaneous administration in all the variables studied except for SIRT1, whose strong downregulation induced by d-gal was equally prevented by both schedules. The benefits of vitamin D for oxidative stress were stronger in the brain than in the heart. Brain MDA levels were more sensitive to damage, while SOD and GPx antioxidant enzymatic activities were in the heart. In this order, the magnitude of SOD, MDA, and GPx oxidative stress markers was sensitive to prevention. In summary, the results unveiled distinct aging induction, preventive signatures, and sensitivity of markers depending on different levels of study and tissues, which are relevant from a mechanistic view and in the design of targeted interventions.

The profile of Oral Health Branch of Rafsanjan Cohort Study (OHBRCS) in Rafsanjan City, southeast of Iran.

Oral health status can be affected by some factors including drug abuse, systemic conditions and environmental pollutants. The present study was designed to investigate the most important and prevalent dental and oral conditions in adult population of Rafsanjan with the age of 35-70 years. Dental and oral health cohort center as part of the Rafsanjan Cohort Study (RCS) included in the prospective epidemiological research studies in IrAN was established in 2015. Of 9991 subjects enrolled in the RCS, 8682 people participated in the Oral Health Branch of Rafsanjan Cohort Study (OHBRCS). The OHBRCS included 4021 men and 4661 women with the mean age of 49.94 ± 9.51. The most prevalent of oral lesion in total population was candidiasis and the least was aphthous lesion. The prevalence of candidiasis, white and red lesions, periodontal pocket, dental calculus, CAL and the mean of DMFT were higher in the male group than that of female group (p < 0.05). Candidiasis, herpes, oral cancer, white and red lesions were more prevalent in the older age groups (p < 0.05). The mean of DMFT index in total population was 21.30 and was higher among opium users, men and older age (p < 0.05). Also, the opium users had a higher rate of CAL, periodontal pocket, red and white lesions, and candidiasis but a lower rate of BOP (p < 0.05). Younger people had more decayed and filling teeth compared to other age groups, whereas older people had more missing teeth and a higher DMFT index (p < 0.001).

Efficacy of Oral Zinc Sulfate Supplementation on Clearance of Cervical Human Papillomavirus (HPV); A Randomized Controlled Clinical Trial.

AIM: Human Papillomavirus is one of the most crucial infectious disease in gynecology disease. To assess the efficacy of supplemental zinc treatment in clearance of HPV infection. METHODS: Eighty zinc-sufficient women between 21-55 years, with positive HPV DNA testing, and abnormal cervical cytology in Pap test (ASCUS or LISL) were randomly divided to case (n=40) and control group (n=40). Case group received oral tablets of zinc sulfate twice a day for 3 months while control group received no placebo. During follow-up patients underwent repeat HPV DNA test and PAP test and were evaluated for clearance/persistence of HPV infection and regression/progression in the lesion grading. RESULTS: As far as demographics, serum zinc levels and the relevant risk factors for persistence of HPV were concerned, there was no significant difference between two groups, except for the frequency distribution of HR-HPV which was significantly higher in case  group. Zinc treatment for 3 months reduced the risk of persistence of HPV infection and progression from baseline cytology (OR = 0.130) (CI 95% 0.04-0.381; p <0.001) and 0.301 (95% CI 0.777-0.116; p = 0.012), respectively. Age, initial cytology, HPV type, and contraceptive method were not related to persistence of HPV. Serum zinc levels increased in the casr group as a result of oral zinc consumption for 3-month period, though without any statistical significance (p = 0.407). CONCLUSION: The results of the following study suggested that oral intake of zinc sulfate supplement for 3 months increases the rates of HPV clearance and resolution of pre-existing cervical lesion.

Comparison between Single Versus Twice Application of Topical 85% Trichloroacetic Acid in the Treatment of Cervical Intraepithelial Neoplasia; A Randomized Clinical Trial on Efficacy and Tolerability.

PURPOSE: To compare the efficacy and safety of up to two-time administration of 85% TCA, as a promising alternative therapy to conservative and surgical management of grade one to three CINs. METHODS: In this two-armed randomized clinical trial, a total of 53 patients with biopsy-proven CIN lesions were allocated to two groups of TCA treatment. The first group (n=26) received a single dose of local therapy with 85% TCA while the second group (n=27) was treated on two separate occasions with a two-week interval. Two participants (one in each group) were lost to follow-up. At the two-month follow-up after TCA application, a colposcopy-guided biopsy was performed for all patients and the pathological specimens were studied by a single experienced pathologist to determine the post-intervention grading of CIN. RESULTS: Two groups were comparable in terms of age and base-line lesion grading, as CIN 1 lesions comprised the majority of cases (54%), followed by CIN 2(37%). While our sample was a poor representative of CIN3 lesions (7%), no significant difference was noticed between the single and twice TCA treated groups with a response rate of 52% and 54% respectively (either complete remission to normal histology or regression to any low-grade lesion). Either separate analysis (with respect to the base-line grading within each treatment group) or combined analysis (regardless of CIN sub-group) could not generate any statistical significance. The second dose of TCA did not increase the frequency of reported adverse events. CONCLUSION: The second dose of topical 85% TCA does not seem to increase the CIN response rate more so than its single dose. However, further controlled clinical trials with larger samples are warranted to verify current findings. The use of TCA was not limited by any major side effect, therefore, the potential to achieve an increased efficacy with more frequent TCA applications is appealing.

Cross-sectional study of passive opiate smoking in relation to stroke and some of stroke attributable risk factors in women.

Opiate use is related to neuropathological disorders, stroke and stroke attributable risk factors. However, secondary exposure to opiate in relation to the above-mentioned complications is studied only in animal models and remains to be evaluated in human populations. We tested whether passive exposure to opiate is associated with stroke and the known stroke predictive factors. We carried out a cross-sectional study of 1541 never smoker women who participated in the Rafsanjan Cohort Study (RCS) with their husbands (2015-2017 recruitment phase). RCS is one of the 19 geographic districts of the Prospective Epidemiological Research Studies in Iran (PERSIAN cohort study). Unadjusted and adjusted multiple logistic regression analyses were performed to evaluate the relationship between second-hand opiate exposure (husband opiate smoking after marriage) and the odds ratio of stroke and the following stroke risk factors and predictive parameters: overweight/obesity (BMI > 25), cholesterol (chol) > 200 mg/dl, fasting blood sugar (FBS) > 125 mg/dl, low density lipoprotein (LDL) > 100 mg/dl, triglyceride (TG) > = 150 mg/dl, hypertension, diabetes, and chronic headache. We observed a significant increased adjusted odds ratio (OR) of stroke (OR = 3.43, 95% CI:1.33-8.82) and its risk factors LDL > 100 mg/dl (OR = 1.37, 95% CI:1.01-1.87) and FBS > 125 mg/dl (OR = 1.58, 95% CI:1.08-2.30) in women associated with husbands' opiate smoking. This relationship was observed after adjusting for the confounding parameters including age, education years, and first-degree family history of the relevant diseases. The increased odds ratio for stroke and high LDL displayed a dose-sensitive trend with years of husband's opiate smoking after marriage (respective p-trends: 0.02 & 0.01). We did not observe a significant association between passive opiate smoking and high TG, high Chol or the diseases diabetes, hypertension and chronic headache. However, 89% increased odds ratio of chronic headache was observed to be associated with passive opiate smoking for more than 10 years (OR = 1.89, 95% CI:1.02-3.50). We found an increased risk of stroke and high LDL and FBS in women associated with passive opiate smoking. Furthermore, a dose-sensitive connection was found between the risks of stroke, high LDL and chronic headache with the years of passive opiate exposure. Our results point to the necessity of the future analyses, which further assess whether passive opiate exposure could be considered as an independent risk factor for stroke and metabolic diseases.