Central body fat changes in men affected by post-surgical hypogonadotropic hypogonadism undergoing testosterone replacement therapy are modulated by androgen receptor CAG polymorphism

Background and aimsLittle is known about the effect of androgen receptor (AR) gene CAG repeat polymorphism in conditioning body composition changes after testosterone replacement therapy (TRT). In this study, we aimed to clarify this aspect by focussing our attention on male post-surgical hypogonadotropic hypogonadism, a condition often associated with partial or total hypopituitarism.Methods and resultsFourteen men affected by post-surgical hypogonadotropic hypogonadism and undergoing several replacement hormone therapies were evaluated before and after TRT. Dual-energy X-ray absorptiometry (DEXA)-derived body composition measurements, pituitary-dependent hormones and AR gene CAG repeat polymorphism were considered. While testosterone and insulin-like growth factor-1 (IGF-1) levels increased after TRT, cortisol concentration decreased. No anthropometric or body composition parameters varied significantly, except for abdominal fat decrease. The number of CAG triplets was positively and significantly correlated with this abdominal fat decrease, while the opposite occurred between the latter and Δ-testosterone. No correlation of IGF-1 or cortisol variation (Δ-) with Δ-abdominal fat was found. At multiple linear regression, after correction for Δ-testosterone, the positive association between CAG triplet number and abdominal fat change was confirmed.ConclusionsIn male post-surgical hypogonadotropic hypogonadism, shorter length of AR CAG repeat tract is independently associated with a more marked decrease of abdominal fat after TRT.     

The weight of MMRV-related febrile convulsions among other clinical factors contributing to febrile convulsions in children

Background

It was previously demonstrated that MMRV vaccine causes a higher rate of febrile convulsions (FC) compared to the MMR vaccine. Additional risk factors for FC include age, familial tendency, day care attendance, viral diseases, complications at birth and developmental delay.

Objective

We evaluated the relative and attributable risk of FC for vaccinees’ age, ethnicity, low birth weight, preterm birth and MMRV vaccination in 10–24 months old children.

Methods

Data on medical history and vaccination were extracted from data warehouses of Clalit Health Services and Israel's Ministry of Health and linked on an individual record level for 90,294 MMR- and 8344 MMRV-vaccinees. A retrospective study design was used to reveal the risk factors associated with FC in study participants.

Results

During the second week after immunization, an elevated relative risk of FC was demonstrated in MMRV-recipients (adjusted RR = 2.16 (95%CI: 1.01; 4.64)). However, the cumulative incidence of FC during the entire 40-day observation period did not differ between the MMR and MMRV vaccinees. The MMRV-specific attributable risk of FC was not statistically significant at any point of observation period and was exceedingly low compared to other risk factors, equaling 5.3 FC cases per 10,000 vaccinees (95%CI: −1.4; 12.2).

Discussion

Our findings demonstrate that MMRV-associated FC in 10–24 months old contributes very marginally to the overall rate of FC in this population.

Conclusion

Given the low number of MMRV-specific FC cases, their transient nature and the benefit of vaccination, the overall benefit-risk of the vaccine can be considered favourable. Nonetheless, the option of separate immunization with MMR + V should be offered to parents, in order to maintain sufficient vaccine uptake in the population.     

Association between sensitized to food allergens and childhood allergic respiratory diseases in Taiwan

BackgroundSensitization to allergen has long been known to be relate to childhood allergic diseases. Polysensitised children have more severe atopic diseases, whereas allergic rhinitis or asthma children with cosensitized to food and inhalant allergens were under-researched.ObjectiveTo realize the association between sensitization to food allergens and pediatric allergic rhinitis and asthma in Taiwan.MethodsWe included 138 participants with sensitized to allergen as assessed by serum-specific IgE. 87 of 138 participants had allergic rhinitis and 51 participants had asthma. All participants underwent a physical examination and measurement of serum total and specific IgE values. Besides, nasal peak expiratory flow rate (nPEFR) that was performed by the participants with allergic rhinitis and were requested to complete the Pediatric Rhinoconjunctivitis Quality of Life Questionnaires (PRQLQ). Lung function test and asthma control test (ACT)/child asthma control test (C-ACT) were performed by the participants with asthma.Results39 of 87 allergic rhinitis participants with sensitized to food and inhalant allergens (AR food group), 48 of 87 allergic rhinitis participants with sensitized to inhalant allergen alone (AR inhalant group). The AR food group had significantly lower nPEFR values and higher total IgE values (p < 0.05) compared with the AR inhalant group. The AR food group had higher PRQLQ scores than the AR inhalant group. 24 of 51 asthma participants with sensitized to food and inhalant allergens (Asthma food group), 27 of 51 asthma participants with sensitized to inhalant allergen alone (Asthma inhalant group). The Asthma food group had significantly higher total IgE values (p < 0.05) compared with the Asthma inhalant group. The Asthma food group had lower lung function test values and asthma control test (ACT) scores than the other group.ConclusionsChildren with cosensitized to food and inhalant allergens have more severe clinical symptoms and abnormal laboratory findings. Sensitization to food allergen was more related to pediatric allergic rhinitis than asthma. We may need larger, longer and extended studies to confirm these findings.     

Should IFN-γ, IL-17 and IL-2 be considered predictive biomarkers of acute rejection in liver and kidney transplant? Results of a multicentric study

Acute rejection (AR) remains a major challenge in organ transplantation, and there is a need for predictive biomarkers. In the present multicenter study, we prospectively examined a series of biomarkers in liver and kidney recipients. Intracellular expression of IFN-γ, IL-17 and IL-2 and IL-17 soluble production were evaluated both pre-transplantation and post-transplantation (1st and 2nd week, 1st, 2nd and 3rd month). 142 transplant patients (63 liver/79 kidney) were included in the study. Twenty-eight recipients (14 liver/14 kidney) developed AR. Pre- and post-transplantation intracellular expression of %IFN-γ⁺ in CD4⁺CD69⁺ and in CD8⁺CD69⁺ and soluble IL17 identified liver and kidney transplant patients at high risk of AR. Pre-transplantation, %IL-2⁺ in CD8⁺CD69⁺ also identified kidney patients at high risk. We constructed pre- and post-transplantation risk prediction models, based on a composite panel of biomarkers, which could provide the basis for future studies and will be a useful tool for the selection and adjustment of immunosuppressive treatments.     

基于肌电信号层级分类的手部动作识别方法

目的 利用肌电信号对手部动作进行识别,是控制现代康复假手的关键,其中使用少量电极识别出较多手势又是一难点。为更加充分利用所获得的肌电信息,本文提出一种层级分类方法。方法 首先提出一种基于层级分类的手部肌电信号动作识别方法,该方法首先根据被分类对象的多侧面属性,利用肌电积分值作为特征值,并通过线性判别函数实施预分类;其次建立肌电信号的自回归模型,将模型系数作为特征值,将人工神经网络作为分类器进行细分类;最后进行了对比实验论证。结果 实验结果表明,可以利用2个表面肌电电极以较高的识别率识别出8个常用手部动作。结论 该方法能够以较少的肌电电极识别出较多的动作,比未采用分层方法具有更好的分类效果。     

Discovery of Pyridone-Substituted Triazolopyrimidine Dual A2A/A1 AR Antagonists for the Treatment of Ischemic Stroke

Ischemic stroke is a complex systemic disease characterized by high morbidity, disability, and mortality. The activation of the presynaptic adenosine A_2A and A₁ receptors modifies a variety of brain insults from excitotoxicity to stroke. Therefore, the discovery of dual A_2A/A₁ adenosine receptor (AR)-targeting therapeutic compounds could be a strategy for the treatment of ischemic stroke. Inspired by two clinical phase III drugs, ASP-5854 (dual A_2A/A₁ AR antagonist) and preladenant (selective A_2A AR antagonist), and using the hybrid medicinal strategy, we characterized novel pyridone-substituted triazolopyrimidine scaffolds as dual A_2A/A₁ AR antagonists. Among them, compound 1a exerted excellent A_2A/A₁ AR binding affinity (K_i = 5.58/24.2 nM), an antagonistic effect (IC₅₀ = 5.72/25.9 nM), and good metabolic stability in human liver microsomes, rat liver microsomes, and dog liver microsomes. Importantly, compound 1a demonstrated a dose–effect relationship in the oxygen-glucose deprivation/reperfusion (OGD/R)-treated HT22 cell model. These findings support the development of dual A_2A/A₁ AR antagonists as a potential treatment for ischemic stroke.     

A Novel Angiographic Quantification of Aortic Regurgitation After TAVR Provides an Accurate Estimation of Regurgitation Fraction Derived From Cardiac Magnetic Resonance Imaging

Objectives

This study sought to compare a new quantitative angiographic technique to cardiac magnetic resonance-derived regurgitation fraction (CMR-RF) for the quantification of prosthetic valve regurgitation (PVR) after transcatheter aortic valve replacement (TAVR).

人精子顶体反应检测临床应用价值探讨

[目的]检测Ca2 载体A23187诱导精子顶体反应(AR)率,探讨其临床应用价值。[方法]对51例患者检测A23187诱导精子AR率,分析其与精液常规分析、宫腔内人工授精(IUI)、体外受精(IVF)、单精子卵泡浆内注射(ICSI)结果的关系。[结果]①精液常规分析对诱导AR率的相关性不显著;②诱导AR率低于18.1%理论值时,IVF受精率理论值为0;③3次IUI失败者AR率较受精正常者降低(P<0.05)。④不明原因不育者精子AR率与IVF受精率、卵裂率关系呈正相关(r=0.89,P<0.05),与ICSI受精率、卵裂率无显著关系;用ICSI治疗,其受精率、妊娠率高于IVF治疗组。⑤IVF受精不良病例AR率低,用ICSI治疗后受精率、优质胚胎率升高(P<0.05)。[结论]Ca2 载体A23187诱导顶体反应能预测精子的受精能力,有助于男性不育的临床诊断与治疗。