Cryopreservation of single human spermatozoa

A procedure is described that allows cryopreservation and efficient post-thaw recovery of either a single or a small group of human spermatozoa. This is achieved by injecting them into cell-free human, mouse or hamster zonae pellucidae before the addition of cryoprotectant. The method involves a combination of physical micromanipulation procedures and glycerol-mediated cryoprotection. Zonae were tracked by positioning them in straws between two small air bubbles prior to freezing. Spermatozoa from poor specimens were cryopreserved and their fertilizing ability after thawing was compared with that of fresh spermatozoa from fertile men. Human eggs used for fertilization testing were either 1 day old or in-vitro matured. Only 2% of the frozen zonae were lost and >75% of spermatozoa cryopreserved in this manner were recovered and prepared for intracytoplasmic sperm injection. The feasibility of cryopreserving a single spermatozoon was assessed. Fifteen motile spermatozoa were frozen in 15 zonae, of which 14 were recovered after thawing. Ten were injected into spare eggs, of which eight became fertilized. Spermatozoa recovered mechanically from human zonae fertilized the same proportion of oocytes as fresh fertile control spermatozoa. The recovery and fertilization rates with spermatozoa frozen in animal zonae were 87 and 78% respectively. The fertilization rate was marginally higher (P < 0.05) than that for spermatozoa frozen in human zonae, perhaps because the latter may have acrosome reacted more frequently. The zona pellucida appears to be an ideally suited sterile vehicle for storage of single spermatozoa.      

Steady‐state amprenavir and tenofovir pharmacokinetics after coadministration of unboosted or ritonavir‐boosted fosamprenavir with tenofovir disoproxil fumarate in healthy volunteers

Objective

An open‐label, three‐period pharmacokinetic study was conducted to investigate the drug interaction potential between fosamprenavir (FPV) and tenofovir disoproxil fumarate (TDF).

Methods

Thirty‐six healthy subjects received TDF 300 mg once daily (qd) for 7 days (period 1), and then were randomized to 14 days of either FPV 1400 mg twice daily (bid) or FPV/ritonavir (RTV) 700/100 mg bid alone or with TDF (period 2). Subjects continued their randomized dose of FPV for 14 more days, adding or removing TDF based upon its receipt in period 2 (period 3). Twenty‐four‐hour pharmacokinetic sampling was carried out on day 7 of period 1 and on day 14 of periods 2 and 3. Steady‐state plasma amprenavir (APV) and tenofovir (TFV) pharmacokinetics were assessed by noncompartmental analysis and parameter values observed with each regimen were compared using geometric mean ratios with 90% confidence intervals.

Results

After TDF coadministration, APV geometric mean minimum concentration (C_min), maximum concentration (C_max), and area under the plasma concentration–time curve (AUC) increased by 31, 3 and 7% above values observed with unboosted FPV alone; they also increased by 31, 4 and 16% above values observed with FPV/RTV alone. TFV C_min, C_max and AUC decreased by 12, 25 and 15% after FPV coadministration and by 9, 18 and 7% after FPV/RTV coadministration. No significant changes in RTV pharmacokinetics were observed. No differences were noted in adverse events among dosing periods.

Conclusions

In this evaluation of the interaction between FPV and TDF, increases in APV exposures and modest decreases in TFV exposures were observed. These were unlikely to be clinically significant.

     

西藏某VCT门诊自愿咨询检测者HIV感染状况分析

目的分析艾滋病自愿咨询检测（VCT）门诊,自愿咨询检测者的艾滋病病毒（HIV）感染状况,为西藏预防HIV传播提供科学依据。方法收集整理2003-2012年西藏某VCT门诊自愿咨询者的人口学信息及HIV抗体检测结果,用描述性方法进行统计分析。结果1929名自愿咨询检测者中,检出HIV抗体阳性188例,阳性率9．75％;女性阳性率（12．94％）高于男性（8．40％）;15～44岁年龄组阳性率达9．92％,其阳性人数占所有阳性者中的94．15％（177／188）。小学及以下文化程度HIV阳性率较高,为17．92％,无业者高于其他职业;静脉注射吸毒阳性率高达62．50％。性传播占总数的89．89％。结论青壮年、小学及以下文化程度者及无业者是感染HIV的高危人群,性接触是主要的传播方式,应针对高危人群的特点,加强艾滋病的宣传教育以及行为干预工作,阻断HIV传播。     

Craniofacial and dental development in cardio‐facio‐cutaneous syndrome: the importance of Ras signaling homeostasis

Cardio‐facio‐cutaneous syndrome (CFC) is a RASopathy that is characterized by craniofacial, dermatologic, gastrointestinal, ocular, cardiac, and neurologic anomalies. CFC is caused by activating mutations in the Ras/mitogen‐activated protein kinase (MAPK) signaling pathway that is downstream of receptor tyrosine kinase (RTK) signaling. RTK signaling is known to play a central role in craniofacial and dental development, but to date, no studies have systematically examined individuals with CFC to define key craniofacial and dental features. To fill this critical gap in our knowledge, we evaluated the craniofacial and dental phenotype of a large cohort (n = 32) of CFC individuals who attended the 2009 and 2011 CFC International Family Conferences. We quantified common craniofacial features in CFC which include macrocephaly, bitemporal narrowing, convex facial profile, and hypoplastic supraorbital ridges. In addition, there is a characteristic dental phenotype in CFC syndrome that includes malocclusion with open bite, posterior crossbite, and a high‐arched palate. This thorough evaluation of the craniofacial and dental phenotype in CFC individuals provides a step forward in our understanding of the role of RTK/MAPK signaling in human craniofacial development and will aid clinicians who treat patients with CFC.     

白芍总苷治疗干燥综合征的研究进展

干燥综合征（SS）是一种慢性自身免疫性疾病,常侵犯泪腺、唾液腺等外分泌腺,同时还会造成肺、肾、消化和神经系统损害甚至累及全身器官。其病因复杂,发病机制目前尚未完全阐明。本病临床治疗为对症治疗,常用药物为免疫抑制剂,糖皮质激素等。白芍总苷辅助治疗本病可改善患者的外分泌腺功能,具有较好的临床疗效和安全性。本文从白芍总苷治疗SS的相关机制进行综述,以期为相关实验研究及临床提供更多的理论依据。     

医学物理学实验教学模式改革实践

为了使各种类型学生在物理学实验课程中得到有关动手能力培养、物理知识增加、思维模式转换等,本文设计了两个与医学专业有联系的新型物理学实验.通过语音和脉搏这两个与人体信息相关的物理学实验,增加学生的研究兴趣,引导学生主动思考.调查结果显示,这种类型的物理学实验得到不同专业学生的普遍认可和欢迎.     

The erroneous perception of a clinical sign: Cholestasis preceding sepsis mimicking hepatitis in an adolescent patient

Jaundice should be considered as a first clinical sign preceding severe invasive bacterial infection or sepsis in patients of all ages including childhood and adolescence. Early laboratory investigations and MR imaging studies for osteomyelitis or myositis are paramount to avoid progression to life‐threatening sepsis and significant morbidity and mortality.