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Abstract Background Lysophospholipid acyltransferase (LPCAT) is crucial for surfactant biosynthesis. It is encoded by LPCAT genes. We investigated the LPCAT1-rs9728 genotypes in neonatal respiratory distress syndrome (NRDS) cases and their possible association with the cord arterial serum interleukin-10 (IL-10), macrophage migration inhibitory factor (MIF), and vascular endothelial growth factor (VEGF) levels. Methods The study included 160 neonates grouped into G1: 60 healthy neonates and G2: 100 NRDS cases. IL-10, MIF, and VEGF levels were measured by their corresponding kits. The Gene JETTM Whole Blood Genomic DNA Purification Mini Kit was used to extract the DNA from the newborn venous blood. The quantitative real-time polymerase chain reaction was carried out for LPCAT1-rs9728 genotyping. Results The IL-10 and MIF levels were significantly higher, while VEGF levels were significantly lower in G2 than in G1. The percentages of LPCAT1-rs9728 AA and LPCAT1-rs9728 AG genotypes were significantly higher in G2 than in G1. The IL-10 and MIF levels were significantly higher, while the VEGF levels, birth weight, and APGAR score at 1 and 5 min were significantly lower in neonates with LPCAT1-rs9728 AA genotype than in neonates with LPCAT1-rs9728 AG and LPCAT1-rs9728 GG genotypes and in neonates with LPCAT1-rs9728 AG genotype than in neonates with LPCAT1-rs9728 GG genotype. Conclusion There is an association between the LPCAT1-rs9728 AA genotype and its A allele and the NRDS development and severity. Further research may provide a better understanding of this association to help future management.

الأهداف: هدفت الدراسة التعرف إلى مستوى معوقات تطبيق اللغة الإنجليزية في تعلم المساقات العلمية بكليات التربية الرياضية في الجامعات الأردنية من وجهة نظر الطلبة، كذلك الفروق في مستوى تلك المعوقات تبعًا للمتغيرات (النوع الاجتماعي، العمر، المرحلة الدراسية، نوع المدرسة التي تخرج منها الطالب، المناطق الأقل حظًا وتخصص الثانوية العامة). المنهجية: اتبع البحث المنهج الوصفي على عينة مكونة من (240) طالبا وطالبة (108 ذكور، 132 إناث). وتم استخدام طريقة (دلفي) في بناء أداة الدراسة بواسطة Google Form))، والتي تكونت بصورتها النهائية من أربعة مجالات و(25) فقرة. ولمعالجة بيانات الدراسة اُستخدمت التكرارات، النسب المئوية، المتوسطات الحسابية والانحرافات المعيارية، ومعامل ألفا كرونباخ، اختبار "t" للعينات المستقلة وتحليل التباين الأحادي. النتائج: أظهرت نتائج الدراسة أن مستوى معوقات تطبيق اللغة الإنجليزية في تعلم المساقات العلمية بكليات التربية الرياضية في الجامعات الأردنية من وجهة نظر الطلبة كان متوسطًا (3.55)، كذلك حصل مجال التحديات المرتبطة بالطالب في المرحلة الدراسية التي تسبق مرحلة الدراسة الجامعية على أعلى متوسط حسابي (3.79) وبدرجة مرتفعة، بينما حصل المجال المرتبط بعضو الهيئة التدريسية على أقل متوسط حسابي (3.38). كذلك أظهرت الدراسة عدم وجود فروق ذات دلالة إحصائية في مستوى تلك المعوقات تبعًا لمتغيرات الدراسة. الخلاصة: يواجه الطلبة العديد من المعوقات عند استخدام اللغة الإنجليزية في تعلم المساقات العلمية بكليات التربية الرياضية، حيث تعتبر المعوقات المرتبطة بالطلبة في المراحل الدراسية التي تسبق مرحلة الدراسة الجامعية من أكثر تلك المعوقات. كذلك هناك معوقات واضحة ومرتبطة بالمؤسسات التعليمية الجامعية.

The American College of Radiology has implemented the Liver Imaging Reporting and Data System (LI-RADS) to help detect, interpret, and guide the management of suspected lesions on surveillance imaging for hepatocellular carcinoma (HCC) in patients with cirrhosis. The classification of indeterminate nodules with a grading algorithm can be used for multiple imaging modalities (US, CT, and MRI) and incorporates multiple imaging features to appropriately classify observations with different likelihood of being HCC. Contrast-enhanced ultrasound (CEUS) LI-RADS has been fully implemented since 2017. The aim of this pictorial article is to provide a comprehensive review of CEUS LI-RADS utilization, discuss its advantages, and highlight areas for potential improvement.

Background: As the impacts of diabetes-induced reproductive damage are now evident in young people, we are now in urgent need to devise new ways to protect and enhance the reproductive health of diabetic people. The present study aimed to evaluate the protective effects of enalapril (an ACE inhibitor) and paricalcitol (a vitamin D analog), individually or in combination, on streptozotocin (STZ)-diabetes-induced testicular dysfunction in rats and to identify the possible mechanisms for this protection. Material and methods: This study was carried out on 50 male Sprague-Dawley rats; 10 normal rats were allocated as a non-diabetic control group. A total of 40 rats developed diabetes after receiving a single dose of STZ; then, the diabetic rats were divided into four groups of equivalent numbers assigned as diabetic control, enalapril-treated, paricalcitol-treated, and combined enalapril-and-paricalcitol-treated groups. The effects of mono and combined therapy with paricalcitol and enalapril on testicular functions, sperm activity, glycemic state oxidative stress, and inflammatory parameters, as well as histopathological examinations, were assessed in comparison with the normal and diabetic control rats. Results: As a result of diabetes induction, epididymal sperm count, sperm motility, serum levels of testosterone, follicle-stimulating hormone (FSH) as well as luteinizing hormone (LH), and the antioxidant enzyme activities, were significantly decreased, while abnormal sperm (%), insulin resistance, nitric oxide (NO), malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were significantly increased, along with severe distortion of the testicular structure. Interestingly, treatment with paricalcitol and enalapril, either alone or in combination, significantly improved the sperm parameters, increased antioxidant enzyme activities in addition to serum levels of testosterone, FSH, and LH, reduced insulin resistance, IL-6, and TNF-α levels, and finally ameliorated the diabetes-induced testicular oxidative stress and histopathological damage, with somewhat superior effect for paricalcitol monotherapy and combined therapy with both drugs compared to monotherapy with enalapril alone. Conclusions: Monotherapy with paricalcitol and its combination therapy with enalapril has a somewhat superior effect in improving diabetes-induced testicular dysfunction (most probably as a result of their hypoglycemic, antioxidant, anti-inflammatory, and anti-apoptotic properties) compared with monotherapy with enalapril alone in male rats, recommending a synergistic impact of both drugs.

Background: Patients with chronic renal disease, particularly those on frequent hemodialysis, exhibit distinct mineral and endocrine changes. Extra-osseous bone formation promoters and inhibitors are out of balance, which results in vascular calcification, a dynamic process controlled by bone kidney disease.Aim of the work: To determine if hemodialysis patients' fetuin-A levels correlate with their risk of abdominal aortic calcification.Patients and Methods: Sixty Hemodialysis patients [30 cases and 30 controls] from Ain shams University Hospitals were enrolled in this comparative cross-sectional study. All the patients have signed an informed consent and underwent laboratory and radiological investigations, including a pelviabdominal x-ray examination. Multislice CT abdomen was done for the cases only.Results: In the group with aortic calcification, the mean serum fetuin-A concentration was 302.51±68.46 ng/ml [range: 201.3 – 414.6 ng/ml], while in the group without aortic calcification, it was 564.53±135.55 ng/ml [range: 284.3 – 793.2 ng/ml]. Regarding the relation between fetuin-A and aortic calcium score, there was a non-significant negative correlation [p-value = 0.376] [r = - 0.168] in the studied population.Conclusion: We found a statistically significant difference between the two groups in terms of serum fetuin-A levels. However, there was no significant association between fetuin-A and aortic calcium score. The duration of dialysis and Ca x P Product were the most critical two parameters affecting the fetuin-A level.

Abstract Background This case–control study aimed to compare lead (Pb), cadmium (Cd), and arsenic (As) levels in neonates with respiratory distress syndrome (NRDS) with those levels in normal neonates and tested their associations with the severity of NRDS indicated by the levels of serum surfactant protein D (SP-D) and cord blood cardiac troponin I (CTnI), and high-sensitive C-reactive protein (hs-CRP). Methods The study included two groups: G1 (60 healthy neonates) and G2 (100 cases with NRDS). Cord blood Pb, erythrocytic Cd (E-Cd), neonatal scalp hair As (N-As), maternal urinary Cd (U-Cd), and arsenic (U-As) were measured by a Thermo Scientific iCAP 6200, while CTnI, hs-CRP, and SP-D by their corresponding ELISA kits. Results The levels of cord blood Pb, E-Cd, N-As, U-Cd, U-As, SP-D, CTnI, and hs-CRP were significantly higher in G2 than G1 (p = 0.019, 0.040, 0.003, 0.010, 0.011,

Purpose – This study is not intended to be a prescriptive blueprint for any nation or region to fight terrorism, but rather it aims to analyze the development of policies supporting terrorism and their impact on regional as well as international relations. It is an examination of relevant facts, which might hopefully benefit policy makers and practitioners who diligently work on reducing or eliminating terrorist activities. Design/methodology/approach – In order to achieve the objectives of the paper and in light of the pool of the available literature and data, the study adopts the system-analysis method in analyzing the impact of policies supporting terrorism and the countermeasures to apply based on the inputs, outputs and conversions associated with the phenomenon of terrorism. Findings – Policies supporting terrorism differ from a state to another starting from providing safe haven to terrorist groups to providing direct finance and armaments to directly intervening militarily in a targeting country. Or deter such policies. This raised the concerns of many States in the region regarding the domination tendency of Turkey and called for a firm and pragmatic international, regional and Arab stand beyond verbal condemnation to deter Turkey from pursuing such policies. Originality/value – The importance of the academic study stems from the importance of addressing one of the central issues in the field of regional and international relations, which is the policies some states adopt to support terrorism, not only by financing terrorism but also by incubating terrorism. Most studies on terrorism focus on the concept and situations and not on policies that support terrorism and their impact on regional and international relations and the means of encountering terrorism.

Genetic associations can be biased by conditioning on a phenotype. This study presents ‘Slope-Hunter’, a method which uses model-based clustering to correct this bias, even in the presence of genetic correlation, assuming the class of SNPs affecting only the collider explains more variation in the collider than any other class of SNPs.

Introduction: Secondary hyperparathyroidism (SHPT) is one of the components of chronic kidney disease–mineral bone disorder (CKD-MBD) with significant contribution to the morbidity and mortality among prevalent hemodialysis (HD) patients. Objectives: This multi-centric experience study aims to compare the effectiveness of intravenous (IV) paricalcitol versus oral cinacalcet and oral cinacalcet plus oral alfacalcidol as treatment regimens of SHPT among chronic HD patients. Patients and Methods: This is a retrospective observational cohort study, in which 130 prevalent HD patients with SHPT was recruited from three main HD centres of Aljouf region in Saudi Arabia. Patients were divided into three groups; group I (50) HD patients were treated by IV paricalcitol, group II (50) HD patients who received oral cinacalcet plus oral alfacalcidol, group III (30) HD patients were on oral cinacalcet. Serum intact parathyroid hormone (iPTH), calcium (Ca), phosphorus (Po4) and alkaline phosphatase (ALP) tests were assessed at 0, 3, 6, and 9 months. Results: A total of 130 (61 (47%) females, (53%) 69 males) HD patients with mean age 56.30 ± 19.1 years, and with mean HD duration of 4.86±4.15 years were enrolled in the study. The mean of iPTH is significantly reduced in all studied groups (P0.05) with statistical non-significant differences. Increase of Ca×Po4 with paricalcitol group as mean ΔChange in (Ca×PO4) was in the groups I, II, III (15.39±9.46, 1.97±11.74, -2.89±9.37) respectively (P

Due to rapid urbanization around the world, high concentrations of vehicular pollutants have deteriorated the outdoor air quality, which can affect the physical and psychological well-being of humans. Numerous strategies have been proposed to overcome these harmful impacts by improving the dispersion of air pollutants. Consequently, a question arises regarding the potential effects of building morphology on the dispersion of pollutants. Subsequently, transient three-dimensional Computational Fluid Dynamics (CFD) simulations are performed to examine the effect of building morphology on PM10 dispersion. Eleven cases with various prototypes and morphological methods are compared with a simple building form to identify the patterns of PM10 dispersion within a given time sequence under a prevailing inflow condition. The results indicate that the different designs of building morphology with varying Relative compactness (RC) indicator highlight the importance of considering morphological factors to improve outdoor air quality. In addition, the proposed prototypes can reduce PM10 concentrations by approximately 30%–90% at specific points in the studied time sequence. In particular, the vertical, horizontal, and grid folded prototypes can be considered more effective as an approximate decrease between 70% and 90% in PM10 concentrations is observed, which reflects the influence of building morphology on improving outdoor air quality.

Introduction: Hepatitis C virus (HCV) infection is strongly associated with chronic kidney disease (CKD). It is an independent risk factor for developing CKD and significantly increases morbidity and mortality in CKD patients. Treatment with newer direct-acting antiviral (DAA) regimens in patients with CKD is showing conflicting results as regards safety and efficacy. Objectives: To evaluate the safety and efficacy of DAAs and their impact on kidney function in CKD patients. Patients and Methods: We conducted a prospective observational study on 100 CKD patients stages 3-4, receiving treatment for HCV at MASRI (Faculty of Medicine Ain Shams University Research Institute), with two different DAAs regimens (sofosbuvir/daclatasvir with or without ribavirin and ombitasvir/paritaprevir/ritonavir [OMV/PTV/RTV] with ribavirin), completed over six months follow up. Serum creatinine, estimated glomerular filtration rate (eGFR), and proteinuria were followed during and after treatment. Results: Sustained virological response (SVR) was achieved in all patients. Improvement of eGFR (8-15 mL/min/1.73 m2) and proteinuria was found in both study groups. Acute kidney injury (AKI) was uncommon; it occurred in three (3%) patients, out of them, two patients showed complete recovery. Adverse events were common (43%), but serious adverse events were uncommon (2%). Conclusion: DAA regimens were effective and well-tolerated for HCV infected patients with stage 3-4 CKD, where viral clearance caused improvement in eGFR and proteinuria.

Background: The ideal high-sensitivity troponin (hsTn) cutoff for identifying those at low risk of 30 days events is debated; however, the 99th percentile overall or gender-specific upper reference limit (URL) is most commonly used. The magnitude of risk and the best management strategy for those with low-level hsTn elevation hasn’t been extensively studied. Methods: We conducted a retrospective cohort analysis including 4396 chest pain patients (542 with low-level hsTn elevation) who ruled out for myocardial infarction (MI), had a stable high-sensitivity troponin T (hsTnT) levels (defined as

Background: Residing in greener areas is increasingly linked to beneficial health outcomes, but little is known about its effect on respiratory health. Objective: We examined associations between residential greenness and nearby green spaces with lung function up to 24 years in the UK Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Methods: Lung function was measured by spirometry at eight, 15 and 24 years of age. Greenness levels within circular buffers (100–1000 m) around the birth, eight-, 15- and 24-year home addresses were calculated using the satellite-derived Normalized Difference Vegetation Index and averaged (lifetime greenness). The presence and proportion of green spaces (urban green spaces, forests and agricultural land) within a 300 m buffer was determined. First, associations between repeated greenness and green space variables and repeated lung function parameters were assessed using generalized estimation equations (N = 7094, 47.9% male). Second, associations between lifetime average greenness and lifetime average proportion of green spaces with lung function at 24-years were assessed using linear regression models (N = 1763, 39.6% male). All models were adjusted for individual and environmental covariates. Results: Using repeated greenspace and lung function data at eight, 15 and 24 years, greenness in a 100 m buffer was associated with higher FEV1 and FVC (11.4 ml [2.6, 20.3] and 12.2 ml [1.8, 22.7], respectively, per interquartile range increase), as was the presence of urban green spaces in a 300 m buffer (20.3 ml [−0.1, 40.7] and 23.1 ml [-0.3, 46.5] for FEV1 and FVC, respectively). These associations were independent of air pollution, urbanicity and socio-economic status. Lifetime average greenness within a 100 m buffer and proportion of agricultural land within a 300 m buffer were associated with better lung function at 24 years but adjusting for asthma attenuated these associations. Discussion: This study provides suggestive evidence that children whose homes are in more vegetated places or are in close proximity of green spaces have better lung function up to 24 years of age.

This study aims to identify the values ​​of some kinematic variables for the starting stage in two different ways (the normal method, the track method) among Jordanian national team swimmers. It also aims to identify the differences in these values ​​according to the starting method, in addition to the relationship between the swimmer's speed and the kinematic variables under study. To achieve this goal, the researchers used a descriptive approach on a sample consisting of (6) swimmers in the Jordanian swimming team (age 18.75 ± 0.6 years, length 1.81 ± 3 cm, mass 70.50 ± 0.60 kg, years of experience 6 ± 0.60 years). The study dealt with some kinematic variables for the starting phase, including starting phase time, starting angle, water entry angle and swimmer's speed. The results of the study showed that the technique of the study sample in the initiation stage was tainted by some errors, but the study sample achieved better results in (7) variables by the track method. There are also statistically significant differences between the two methods in the variables of reaction time, start time and average swimmer speed. In addition, the results of the study showed a statistically significant inverse correlation between swimmer speed, start time and swimmer time under water.

Abstract Background Aedes-borne diseases as dengue, zika, chikungunya and yellow fever are an emerging problem worldwide, being transmitted by Aedes aegypti and Aedes albopictus. Lack of up to date information about the distribution of Aedes species hampers surveillance and control. Global databases have been compiled but these did not capture data in the WHO Eastern Mediterranean Region (EMR), and any models built using these datasets fail to identify highly suitable areas where one or both species may occur. The first objective of this study was therefore to update the existing Ae. aegypti (Linnaeus, 1762) and Ae. albopictus (Skuse, 1895) compendia and the second objective was to generate species distribution models targeted to the EMR. A final objective was to engage the WHO points of contacts within the region to provide feedback and hence validate all model outputs. Methods The Ae. aegypti and Ae. albopictus compendia provided by Kraemer et al. (Sci Data 2:150035, 2015; Dryad Digit Repos, 2015) were used as starting points. These datasets were extended with more recent species and disease data. In the next step, these sets were filtered using the Köppen–Geiger classification and the Mahalanobis distance. The occurrence data were supplemented with pseudo-absence data as input to Random Forests. The resulting suitability and maximum risk of establishment maps were combined into hard-classified maps per country for expert validation. Results The EMR datasets consisted of 1995 presence locations for Ae. aegypti and 2868 presence locations for Ae. albopictus. The resulting suitability maps indicated that there exist areas with high suitability and/or maximum risk of establishment for these disease vectors in contrast with previous model output. Precipitation and host availability, expressed as population density and night-time lights, were the most important variables for Ae. aegypti. Host availability was the most important predictor in case of Ae. albopictus. Internal validation was assessed geographically. External validation showed high agreement between the predicted maps and the experts’ extensive knowledge of the terrain. Conclusion Maps of distribution and maximum risk of establishment were created for Ae. aegypti and Ae. albopictus for the WHO EMR. These region-specific maps highlighted data gaps and these gaps will be filled using targeted monitoring and surveillance. This will increase the awareness and preparedness of the different countries for Aedes borne diseases.

Abstract Background Recently, transcatheter aortic valve replacement (TAVR) has become the procedure of choice in high surgical risk patients with aortic stenosis (AS). However, its value is still debated in operable AS cases. We performed this meta-analysis to compare the safety and efficacy of TAVR to surgical aortic valve replacement (SAVR) in low-to-moderate surgical risk patients with AS. Methods A systematic search of five authentic databases retrieved 11 eligible studies (20,056 patients). Relevant Data were pooled as risk ratios (RRs) or standardized mean differences (SMD), with their 95% confidence interval, using Comprehensive Meta-Analysis and RevMan software for windows. Results At one-year of follow-up, the pooled effect-estimates showed no significant difference between TAVR and SAVR groups in terms of all-cause mortality (RR 1.02, 95% CI [0.83, 1.26], stroke (RR 0.83, 95%CI [0.56, 1.21]), myocardial infarction (RR 0.82, 95% CI [0.57, 1.19]), and length of hospital stay (SMD -0.04, 95% CI [−0.34, 0.26]). The incidence of major bleeding (RR 0.45, 95% CI [0.24, 0.86]) and acute kidney injury (RR 0.52, 95% CI [0.30, 0.88]) was significantly lower in the TAVR group, compared to the SAVR group. However, TAVR was associated with a higher risk of permanent pacemaker implantation (RR 2.57, 95% CI [1.36, 4.86]), vascular-access complications at 1 year (RR 1.99, 95%CI [1.04, 3.80]), and paravalvular aortic regurgitation at 30 days (RR 3.90, 95% CI [1.25, 12.12]), compared to SAVR. Conclusions Due to the comparable mortality rates in SAVR and TAVR groups and the lower risk of life-threatening complications in the TAVR group, TAVR can be an acceptable alternative to SAVR in low-to-moderate risk patients with AS. However, larger trials with longer follow-up periods are required to compare the long-term outcomes of both techniques.

Abstract Background Fluid overload is associated with increased morbidity and mortality in critically ill patients. An accurate assessment of fluid status in neonatal cardiac pediatric patients is required for assessment of fluid overload. Estimation of fluid status using different Doppler parameters may be helpful in determination of fluid status. Purpose To evaluate difference in fluid status in neonates with and without congenital heart diseases. To detect sensitivity of Doppler Ultrasound in early determination of fluid status. To compare between different parameters (IVC diameter, IVCCI, and IVC/AO ratio) between cardiac and healthy neonates. Methods Transabdominal Doppler parameters of 25 full-term newborns with congenital heart diseases and congestive heart failure were compared to 25 post-natal age and sex-matched normal healthy neonates serving as controls. Aortic as well as inspiratory and expiratory inferior vena cava diameters were measured. Subsequently, inferior vena cava collapsibility index (IVCCI) and inferior vena cava-to-aortic ratio (IVC/AO) were calculated. Results Fluid overload detected by increased IVC diameter (decreased IVCCI and increased IVC/AO ratio) was observed in the cardiac compared to the control group. There was positive correlation between the fluid volume and the IVC diameter and IVC/AO ratio and negative correlation with the IVC collapsibility indices. Conclusions Fluid overload with increased IVC diameter and lack of IVC collapsibility were observed in neonates with congenital heart diseases and congestive heart failure compared with those hemodynamically stable controls. We recommend the use of IVC diameter, IVCCI, and IVC/AO ratio as rapid, easy and sensitive parameters in assessing volume status.

A previous study of the effect of a 2-chloro substituent on the rates and the mechanisms of the solvolysis of ethyl chloroformate is extended to the effect of a 3-chloro substituent on the previously studied solvolysis of propyl chloroformate and to the effect of a 4-chloro substituent on the here reported rates of solvolysis of butyl chloroformate. In each comparison, the influence of the chloro substituent is shown to be nicely consistent with the proposal, largely based on the application of the extended Grunwald–Winstein equation, of an addition-elimination mechanism for solvolysis in the solvents of only modest solvent ionizing power, which changes over to an ionization mechanism for solvents of relatively high ionizing power and low nucleophilicity, such as aqueous fluoroalcohols with an appreciable fluoroalcohol content.

BackgroundObservational studies on pubertal timing and asthma, mainly performed in females, have provided conflicting results about a possible association of early puberty with higher risk of adult asthma, possibly due to residual confounding. To overcome issues of confounding, we used Mendelian randomisation (MR), i.e., genetic variants were used as instrumental variables to estimate causal effects of early puberty on post-pubertal asthma in both females and males.Methods and findingsMR analyses were performed in UK Biobank on 243,316 women using 254 genetic variants for age at menarche, and on 192,067 men using 46 variants for age at voice breaking. Age at menarche, recorded in years, was categorised as early (14); age at voice breaking was recorded and analysed as early (younger than average), normal (about average age), or late (older than average). In females, we found evidence for a causal effect of pubertal timing on asthma, with an 8% increase in asthma risk for early menarche (odds ratio [OR] 1.08; 95% CI 1.04 to 1.12; p = 8.7 × 10(-5)) and an 8% decrease for late menarche (OR 0.92; 95% CI 0.89 to 0.97; p = 3.4 × 10(-4)), suggesting a continuous protective effect of increasing age at puberty. In males, we found very similar estimates of causal effects, although with wider confidence intervals (early voice breaking: OR 1.07; 95% CI 1.00 to 1.16; p = 0.06; late voice breaking: OR 0.93; 95% CI 0.87 to 0.99; p = 0.03). We detected only modest pleiotropy, and our findings showed robustness when different methods to account for pleiotropy were applied. BMI may either introduce pleiotropy or lie on the causal pathway; secondary analyses excluding variants associated with BMI yielded similar results to those of the main analyses. Our study relies on self-reported exposures and outcomes, which may have particularly affected the power of the analyses on age at voice breaking.ConclusionsThis large MR study provides evidence for a causal detrimental effect of early puberty on asthma, and does not support previous observational findings of a U-shaped relationship between pubertal timing and asthma. Common biological or psychological mechanisms associated with early puberty might explain the similarity of our results in females and males, but further research is needed to investigate this. Taken together with evidence for other detrimental effects of early puberty on health, our study emphasises the need to further investigate and address the causes of the secular shift towards earlier puberty observed worldwide.

ABSTRACT Purpose To evaluate the surgical outcome and predictors of failure of substitution urethroplasty using either dorsal onlay buccal mucosal (BM) graft or ventral onlay penile skin flap (PS) for anterior urethral stricture ≥ 8cm. Patients and methods Between March 2010 and January 2016, 50 patients with anterior urethral stricture ≥ 8 cm were treated at our hospital. The surgical outcome and success rate were assessed. The predictors of failure were analyzed using multivariate analysis. Failure was considered when subsequent urethrotomy or urethroplasty were needed. Results Dorsal onlay BM graft was carried out in 24 patients, while PS urethroplasty in 26 patients. There was no significant difference between both groups regarding patients demographics, stricture characteristics or follow-up period. One case in the BM group was lost during follow-up. Stricture recurrence was detected in 7 (30.4%) patients out of BM group while in 6 (23.1%) patients out of PS group (p value= 0.5). No significant differences between both groups regarding overall early and late complications were observed. Occurrence of early complications and the stricture length were the only predictors of failure in univariate analysis, while in multivariate analysis the occurrence of early complications was only significant. Conclusion On short-term follow-up, both dorsal onlay BM graft and ventral onlay PS flap urethroplasty have similar success rates. However, BM graft has a potential advantage to reduce operative time and is also technically easier. The surgeon should avoid early local complications as they represent a higher risk for failure.