Safety of long-term interruption of successful antiretroviral therapy: the ATHENA cohort study

We studied the dynamics of CD4 cell counts after the interruption of virologically successful highly active antiretroviral therapy (HAART) in 139 patients. Changes in CD4 cell counts during HAART interruption followed a biphasic pattern: an initial rapid decline during the first month followed by a slow decrease. During 48 weeks of follow-up mean CD4 cell counts remained just above the mean pre-HAART level. This limits the feasibility of structured treatment interruptions for patients with low nadir CD4 cell counts.     

Genetic characterization of HA gene of low pathogenic H9N2 influenza viruses isolated in Israel during 2006–2012 periods

H9N2 influenza viruses are isolated in Israel since 2000 and became endemic. From November 2006 to the beginning of 2012, many H9N2 viruses were identified, all belonged to the Asian G1-like lineage represented by A/qu/Hong Kong/G1/97 (H9N2). In the present study, 66 isolates were selected for their hemagglutinin gene characterization. Most H9N2 isolates were distributed between two main groups, identified as the 4th and 5th introductions. The 5th introduction, was represented by a compact cluster containing viruses isolated in 2011–2012; the 4th introduction was subdivided into two subgroups, A and B, each containing at least two clusters, which can be identified as A-1, A-2, B-1, and B2, respectively. Genetic analysis of the deduced HA proteins of viruses, belonging to the 4th and 5th introductions, revealed amino acid variations in 79 out of 542 positions. All isolates had typical low pathogenicity motifs at the hemagglutinin (HA) cleavage site. Most viruses had leucine at position 216 in a receptor binding pocket that enables the virus to bind successfully with the cellular receptors intrinsic to mammals, including humans. It was shown that the differences between the HA proteins of viruses used for vaccine production and local field isolates increased in parallel with the duration and intensity of vaccine use, illustrating the genetic diversity of the H9N2 viruses in Israel.     

Teaching Geriatrics Using an Innovative,Individual‐Centered Educational Game: Students and Educators Win. A Proof‐of‐Concept Study

Given the increasingly aging population, nearly every doctor will encounter elderly adults who present with multiple complex comorbidities that can challenge even experienced physicians. This may explain why many medical students do not have a positive attitude toward elderly adults and find the complexity of their problems overwhelming. It was hypothesized that a recently developed medical school geriatrics course, based on the game GeriatriX and designed specifically to address the complexities associated with decision‐making in geriatrics, can have a positive effect on attitudes toward geriatrics and on perceived knowledge of geriatrics. The effects of this game‐based course were evaluated as a proof of concept. The assessment was based on the Aging Semantic Differential (ASD) and a validated self‐perceived knowledge scale of geriatric topics. The usability of (and satisfaction with) GeriatriX was also assessed using a 5‐point Likert scale. After completion of the course, the ASD changed significantly in the geriatrics course group (n = 29; P = .02) but not in a control group that took a neuroscience course (n = 24; P = .30). Moreover, the geriatrics course group had a significant increase in self‐perceived knowledge for 12 of the 18 topics (P = .002), whereas in the control group self‐perceived knowledge increased significantly for one topic only (sensory impairment) (P = .04). Finally, the geriatrics students reported enjoying GeriatriX. This proof‐of‐concept study clearly supports the hypothesis that a 4‐week course using a modern educational approach such as GeriatriX can improve students' self‐perceived knowledge of geriatrics and their attitudes toward elderly adults.     

Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome

Alterations in intestinal microbiota are associated with obesity and insulin resistance. We studied the effects of infusing intestinal microbiota from lean donors to male recipients with metabolic syndrome on the recipients' microbiota composition and glucose metabolism. Subjects were assigned randomly to groups that were given small intestinal infusions of allogenic or autologous microbiota. Six weeks after infusion of microbiota from lean donors, insulin sensitivity of recipients increased (median rate of glucose disappearance changed from 26.2 to 45.3 μmol/kg/min; P < .05) along with levels of butyrate-producing intestinal microbiota. Intestinal microbiota might be developed as therapeutic agents to increase insulin sensitivity in humans; www.trialregister.nl; registered at the Dutch Trial Register (NTR1776).     

Advances in genetics show the need for extending screening strategies for autosomal dominant hypercholesterolaemia

Aims Autosomal dominant hypercholesterolaemia (ADH) is a major risk factor for coronary artery disease. This disorder is caused by mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9). However, in 41% of the cases, we cannot find mutations in these genes. In this study, new genetic approaches were used for the identification and validation of new variants that cause ADH. Methods and results Using exome sequencing, we unexpectedly identified a novel APOB mutation, p.R3059C, in a small-sized ADH family. Since this mutation was located outside the regularly screened APOB region, we extended our routine sequencing strategy and identified another novel APOB mutation (p.K3394N) in a second family. In vitro analyses show that both mutations attenuate binding to the LDLR significantly. Despite this, both mutations were not always associated with ADH in both families, which prompted us to validate causality through using a novel genetic approach. Conclusion This study shows that advances in genetics help increasing our understanding of the causes of ADH. We identified two novel functional APOB mutations located outside the routinely analysed APOB region, suggesting that screening for mutations causing ADH should encompass the entire APOB coding sequence involved in LDL binding to help identifying and treating patients at increased cardiovascular risk.