Polymorphisms of plasminogen activator inhibitor-1, angiotensin converting enzyme and coagulation factor XIII genes in patients with recurrent spontaneous abortion

We investigated polymorphisms of plasminogen activator inhibitor-1 (PAI-1), angiotensin converting enzyme (ACE ) and coagulation factor XIII (FXIII) genes and their association with recurrent spontaneous abortion (RSA) in Iranian patients and normal healthy controls. Ten (18.5%) patients were homozygote (4G/4G) for PAI-1 polymorphism, in contrast with two (2%) controls (p = 0.001). Patients with homozygote 4G mutation were significantly more prone to RSA in contrast to others (odds ratio: 11.0, 95% CI: 2.3-52.4). Nineteen (30.2%) patients and 25 (26.6%) controls were homozygote (DD) for ACE polymorphism. We observed only two patients and one control with homozygosity (34leu) for FXIII polymorphism. 4G/4G polymorphism for PAI-1 gene could be a thrombophilic mutation leading to abortion in Iranian population

Maternal haemoglobin concentrations before and during pregnancy and stillbirth risk: A population-based case-control study

Background: Results of previous studies on the association between maternal haemoglobin concentration during pregnancy and stillbirth risk are inconclusive. It is not clear if haemoglobin concentration before pregnancy has a role. Using prospectively collected information from pre-pregnancy and antenatal visits, we investigated associations of maternal haemoglobin concentrations before and during pregnancy and haemoglobin dilution with stillbirth risk. Methods: In a population-based case-control study from rural Golestan, a province in northern Iran, we identified 495 stillbirths (cases) and randomly selected 2,888 control live births among antenatal health-care visits between 2007 and 2009. Using logistic regression, we estimated associations of maternal haemoglobin concentrations, haemoglobin dilution at different stages of pregnancy, with stillbirth risk. Results: Compared with normal maternal haemoglobin concentration (110-120g/l) at the end of the second trimester, high maternal haemoglobin concentration (≥140g/l) was associated with a more than two-fold increased stillbirth risk (OR = 2.31, 95% CI [1.30-4.10]), while low maternal haemoglobin concentration (<110g/l) was associated with a 37% reduction in stillbirth risk. Haemoglobin concentration before pregnancy was not associated with stillbirth risk. Decreased haemoglobin concentration, as measured during pregnancy (OR = 0.61, 95% CI [0.46, 0.80]), or only during the second trimester (OR = 0.75, 95% CI [0.62, 0.90]), were associated with reduced stillbirth risk. The associations were essentially similar for preterm and term stillbirths. Conclusions: Haemoglobin concentration before pregnancy is not associated with stillbirth risk. High haemoglobin level and absence of haemoglobin dilution during pregnancy could be considered as indicators of a high-risk pregnancy. © 2016 The Author(s)

Consanguineous marriage, prepregnancy maternal characteristics and stillbirth risk: A population-based case-control study

Introduction. Consanguineous marriage is associated with increased risks for congenital anomalies, low birthweight, and other adverse perinatal outcomes. In this population-based, case-control study we investigated the association between consanguineous marriage (first-cousin marriage) and stillbirth risk, using prospectively collected information from prepregnancy visits. Material and methods. From 2007 to 2009, we identified 283 stillbirths (cases) and 2088 randomly selected live control births through prepregnancy visits in rural Golestan, Iran. The associations between consanguinity and prepregnancy maternal characteristics and stillbirth risk were examined using multivariate logistic regression. Results. The rate of consanguineous marriage was 19.4% among cases and 13.6% among controls. Consanguinity was associated with increased stillbirth risk [odds ratio (OR) 1.53; 95% CI 1.10-2.14]. The association was significantly increased for preterm stillbirth (< 37 gestational weeks) (OR 2.43; 95% CI 1.46-4.04) but not for term stillbirth (≥ 37 weeks) (OR 1.14; 95% CI 0.75-1.74). Low and high maternal age, underweight, obesity, nulliparity, a history of infertility or miscarriage, previous obstetric complications (preeclampsia, preterm delivery, and stillbirth in previous pregnancies) were also associated with increased stillbirth risks. Conclusions. Consanguineous marriage is associated with increased risk of stillbirth, particularly preterm stillbirth. Findings for other maternal risk factors for stillbirth in rural Iran are consistent with previously reported findings from high-income countries. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology

Lymphomas in Golestan province of Iran: Results of a population-based cancer registry

Introduction: Malignancies of lymphoid cells can be divided into Hodgkin and non-Hodgkin lymphomas (NHL) on the basis of pathologic features, clinical manifestations and treatment. In this paper we present data on lymphomas in Golestan province, in the northeast of Iran, during 2004-2006, using three years results of the Golestan population-based cancer registry (GPCR), a voting member of the International Association of Cancer Registries (IACR). Methods: GPCR started collecting data on all cancers from all public and private diagnostic and therapeutic centers (hospitals, specialist physicians' offices, pathology, laboratory, and imaging centers) of Golestan province in 2004. Here, we used the Iranian national census data to identify the population characteristics of this geographical area. The last census was done in 2006 and the next one will be done in 2011. The population data for years between the national census intervals are retrieved from provincial census done annually by health deputy of Golestan University of Medical Sciences (GOUMS). Results: A total of 5,076 cancer cases were diagnosed in the GPCR between 2004 and 2006. Of these, 237 (4.67 %) were lymphomas, among the ten top cancers of this area, the patients having a mean (±SD) age of 45.2 (±20.9) years. The number of cases, frequency, age specific rates, crude rates and age standardized incidence rates (ASR) (per 100,000 personyears) for lymphomas in males and females are presented. Conclusion: It could be concluded that according to available therapies for HL and NHL, the outcome of the patients could be improved in this area, due to the better diagnostic and therapeutic methods now available

Cancer incidence in Golestan province: Report of an ongoing population-based cancer registry in Iran between 2004 and 2008

Background: Golestan Province, at the western end of the Asian esophageal cancer (EC) belt in northeastern Iran, was reported to have one of the highest worldwide rates of EC in the 1970s. We have previously shown a declining incidence of EC in Golestan during the last decades. This study reports additional new results from the Golestan Population-based Cancer Registry (GPCR). Methods: The GPCR collected data from newly diagnosed (incident) cancer cases from all 68 public and private diagnostic and therapeutic centers in Golestan Province. CanReg-4 software was used for data entry and analysis based on the guidelines of the International Agency for Research on Cancer (IARC). Age-standardized incidence rates (ASR) of cancers were calculated using the 2000 world standard population. Results: From 2004 through 2008, 9007 new cancer cases were reported to the GPCR. The mean (SD) age was 55.5 (18.6) years, and 54 were diagnosed in men. The ASRs of all cancers were 175.3 and 141.1 per 100,000 person-years for males and females, respectively. Cancers of the stomach (ASR:30.7), esophagus (24.3), and lung (15.4) were the most common cancers in males. In females, breast cancer (ASR:26.9) was followed by malignancies of the esophagus (19.1) and stomach (12.4). The diagnosis of cancer was based on histopatho- logical reports in 71 and on death certificate only in 9 ofcases. Conclusions: The EC incidence rate continues to decline in Golestan, while the incidence rates of stomach, colorectal, and breast cancers continue to increase

Retinal photoisomerization versus counterion protonation in light and dark-adapted bacteriorhodopsin and its primary photoproduct

Discovered over 50 years ago, bacteriorhodopsin is the first recognized and most widely studied microbial retinal protein. Serving as a light-activated proton pump, it represents the archetypal ion-pumping system. Here we compare the photochemical dynamics of bacteriorhodopsin light and dark-adapted forms with that of the first metastable photocycle intermediate known as “K”. We observe that following thermal double isomerization of retinal in the dark from bio-active all-trans 15-anti to 13-cis, 15-syn, photochemistry proceeds even faster than the ~0.5 ps decay of the former, exhibiting ballistic wave packet curve crossing to the ground state. In contrast, photoexcitation of K containing a 13-cis, 15-anti chromophore leads to markedly multi-exponential excited state decay including much slower stages. QM/MM calculations, aimed to interpret these results, highlight the crucial role of protonation, showing that the classic quadrupole counterion model poorly reproduces spectral data and dynamics. Single protonation of ASP212 rectifies discrepancies and predicts triple ground state structural heterogeneity aligning with experimental observations. These findings prompt a reevaluation of counter ion protonation in bacteriorhodopsin and contribute to the broader understanding of its photochemical dynamics

Aflatoxin contamination of wheat flour and the risk of esophageal cancer in a high risk area in Iran

Background: Golestan province in northeastern Iran has been known as a high-risk area for esophageal cancer (EC). This study was conducted to assess aflatoxin (AF) contamination of wheat flour (WF) samples in high and low EC-risk areas of Golestan province. Methods: Four WF samples were collected randomly from each of 25 active silos throughout the province in 2009. The levels of AFs were measured using the High-performance liquid chromatography method. Using the data of EC rates obtained from Golestan population-based cancer registry, the province was divided into high and low risk areas for EC. Student t-test and multivariate regression analysis were used to compare the levels of aflatoxins as well as the condition of silos between the two areas. Results: One hundred WF samples were collected. The mean levels of total aflatoxin and aflatoxin B1 was 1.99 and 0.53ngg-1, respectively. The levels of total AF (p=0.03), AFG2 (p=0.02) and AFB1 (p=0.003) were significantly higher in samples obtained from high risk area. Multivariate regression analysis showed that humidity of silo was the most important source of difference between silos of the two areas (p=0.04). Conclusion: We found a positive relationship between AF level of WF samples and the risk of EC. So, AF contamination may be a possible risk factor for EC in our region. We also found that humidity of silos was the most important determinant of AF contamination of WF. Intensive control of silos conditions including humidity and temperature are needed especially in high EC-risk areas. © 2013 Elsevier Ltd

Recovery priorities in degenerative cervical myelopathy: a cross-sectional survey of an international, online community of patients.

OBJECTIVES: To establish the recovery priorities of individuals suffering with degenerative cervical myelopathy (DCM). DESIGN: A cross-sectional, observational study. SETTING: Patients from across the world with a diagnosis of DCM accessed the survey over an 18-month period on Myelopathy.org, an international myelopathy charity. PARTICIPANTS: 481 individuals suffering from DCM completed the online survey fully. MAIN OUTCOME MEASURES: Functional recovery domains were established through qualitative interviews and a consensus process. Individuals were asked about their disease characteristics, including limb pain (Visual Analogue Scale) and functional disability (patient-derived version of the modified Japanese Orthopaedic Association score). Individuals ranked recovery domains (arm and hand function, walking, upper body/trunk function, sexual function, elimination of pain, sensation and bladder/bowel function) in order of priority. Priorities were analysed as the modal first priority and mean ranking. The influence of demographics on selection was analysed, with significance p<0.05. RESULTS: Of 659 survey responses obtained, 481 were complete. Overall, pain was the most popular recovery priority (39.9%) of respondents, followed by walking (20.2%), sensation (11.9%) and arm and hand function (11.5%). Sexual function (5.7%), bladder and bowel (3.7%) and trunk function (3.5%) were chosen less frequently. When considering the average ranking of symptoms, while pain remained the priority (2.6±2.0), this was closely followed by walking (2.9±1.7) and arm/hand function (3.0±1.4). Sensation ranked lower (4.3±2.1). With respect to disease characteristics, overall pain remained the recovery priority, with the exception of patients with greater walking impairment (p<0.005) who prioritised walking, even among patients with lower pain scores. CONCLUSIONS: This is the first study investigating patient priorities in DCM. The patient priorities reported provide an important framework for future research and will help to ensure that it is aligned with patient needs.NIHR Welcome Trus

Rivaroxaban for the treatment of cerebral venous thrombosis

Background: New Oral Anticoagulants (NOACs) such as Rivaroxaban are introduced as alternatives to conventional vitamin-K antagonists in the long-term treatment of thrombotic events due to their lower bleeding risk. There is a lack of evidence on the effectiveness and safety of Rivaroxaban in Cerebral venous thrombosis (CVT). This study aims to assess the effectiveness and bleeding risk of Rivaroxaban in comparison with Warfarin for the treatment of CVT. Materials and methods: 36 patients with diagnosis of CVT were included. Clinical and background information was assessed on admission and patients were followed for at least 12 months. Measured outcomes were modified Rankin Scale (mRS), evidence of recanalization on contrast-enhanced Brain MR venography (MRV) and major or minor bleeding. Patients were divided into two groups according to the type of oral anticoagulant (Rivaroxaban vs Warfarin). Groups were compared in terms of final outcomes and side effects. Result: Overall, 13 (36.11) patients received Warfarin and 23 (63.89) received Rivaroxaban. Optimal mRS score (0�1) was attained in 9 of 10 (90) of patients treated with Rivaroxaban and 19 of 22 (86.36) of patients received Warfarin. MRV showed complete or partial recanalization in 12 of 14 (85.71) patients treated with Rivaroxaban and all patients in the Warfarin group. There was no significant difference between the two groups in terms of major and minor hemorrhage. Conclusion: Rivaroxaban holds promise for the treatment of CVT. © 2021, The Author(s)

The Testicular and Epididymal Expression Profile of PLCζ in Mouse and Human Does Not Support Its Role as a Sperm-Borne Oocyte Activating Factor

Phospholipase C zeta (PLCζ) is a candidate sperm-borne oocyte activating factor (SOAF) which has recently received attention as a potential biomarker of human male infertility. However, important SOAF attributes of PLCζ, including its developmental expression in mammalian spermiogenesis, its compartmentalization in sperm head perinuclear theca (PT) and its release into the ooplasm during fertilization have not been established and are addressed in this investigation. Different detergent extractions of sperm and head/tail fractions were compared for the presence of PLCζ by immunoblotting. In both human and mouse, the active isoform of PLCζ was detected in sperm fractions other than PT, where SOAF is expected to reside. Developmentally, PLCζ was incorporated as part of the acrosome during the Golgi phase of human and mouse spermiogenesis while diminishing gradually in the acrosome of elongated spermatids. Immunofluorescence localized PLCζ over the surface of the postacrosomal region of mouse and bull and head region of human spermatozoa leading us to examine its secretion in the epididymis. While previously thought to have strictly a testicular expression, PLCζ was found to be expressed and secreted by the epididymal epithelial cells explaining its presence on the sperm head surface. In vitro fertilization (IVF) revealed that PLCζ is no longer detectable after the acrosome reaction occurs on the surface of the zona pellucida and thus is not incorporated into the oocyte cytoplasm for activation. In summary, we show for the first time that PLCζ is compartmentalized as part of the acrosome early in human and mouse spermiogenesis and is secreted during sperm maturation in the epididymis. Most importantly, no evidence was found that PLCζ is incorporated into the detergent-resistant perinuclear theca fraction where SOAF resides