Laparoscopic Watson Fundoplication Is Effective and Durable in Children with Gastrooesophageal Reflux

Gastroesophageal reflux (GOR) affects 2–8% of children over 3 years of age and is associated with significant morbidity. The disorder is particularly critical in neurologically impaired children, who have a high risk of aspiration. Traditionally, the surgical antireflux procedure of choice has been Nissen’s operation. However, this technique has a significant incidence of mechanical complications and has a reoperation rate of approximately 7%, leading to the development of alternative approaches. Watson’s technique of partial anterior fundoplication has been shown to achieve long-lasting reflux control in adults with few mechanical complications, but there is limited data in the paediatric population. We present here short- and long-term outcomes of laparoscopic Watson fundoplication in a series of 76 children and infants, 34% of whom had a degree of neurological impairment including severe cerebral palsy and hypoxic brain injury. The overall complication rate was 27.6%, of which only 1 was classified as major. To date, we have not recorded any incidences of perforation and no revisions. In our experience, Watson’s laparoscopic partial fundoplication can be performed with minimal complications and with durable results, not least in neurologically compromised children, making it a viable alternative to the Nissen procedure in paediatric surgery

National sentinel surveillance of transmitted drug resistance in antiretroviral-naive chronically HIV-infected patients in France over a decade: 2001-2011.

Objectives As recommended by the French ANRS programme for the surveillance of HIV-1 resistance, we estimated the prevalence of transmitted drug resistance-associated mutations (RAMs) in antiretroviral-naive, chronically HIV-1-infected patients. Methods RAMs were sought in samples from 661 newly diagnosed HIV-1-infected patients in 2010/11 at 36 HIV clinical care centres. Weighted analyses were used to derive representative estimates of the percentage of patients with RAMs. Results At patient inclusion, the prevalence of virus with protease (PR) or reverse transcriptase (RT) RAMs was 9.0% (95% CI 6.8%–11.2%). No integrase RAMs were observed. The prevalences of protease inhibitor, nucleoside RT inhibitor and non-nucleoside RT inhibitor RAMs were 1.8%, 6.2% and 2.4%, respectively. Resistance to one, two and three classes of antiretroviral agent was observed in 7.9%, 0.9% and 0.2% of patients, respectively. The frequency of RAMs was higher in patients infected with B compared with non-B subtype virus (11.9% versus 5.1%, P = 0.003). Baseline characteristics (gender, age, country of transmission, CD4 cell count and viral load) were not associated with the prevalence of transmitted RAMs. However, men having sex with men (MSM) were more frequently infected with resistant virus than were other transmission groups (12.5% versus 5.8%, P = 0.003). Compared with the 2006/07 survey, the overall prevalence of resistance remained stable. However, a significant decrease in the frequency of virus with PR RAMs was observed in 2010/11 compared with the 2006/07 survey (1.8% versus 5.0%, P = 0.003. Conclusions In France in 2010/11, the global prevalence of transmitted drug-resistant variants was 9.0%, and the prevalence was stable compared with the 2006/07 survey. MSM and B subtype-infected patients are the groups with a higher prevalence of drug resistance

A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging

Many genes that affect replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae also affect aging in other organisms such as C. elegans and M. musculus. We performed a systematic analysis of yeast RLS in a set of 4,698 viable single-gene deletion strains. Multiple functional gene clusters were identified, and full genome-to-genome comparison demonstrated a significant conservation in longevity pathways between yeast and C. elegans. Among the mechanisms of aging identified, deletion of tRNA exporter LOS1 robustly extended lifespan. Dietary restriction (DR) and inhibition of mechanistic Target of Rapamycin (mTOR) exclude Los1 from the nucleus in a Rad53-dependent manner. Moreover, lifespan extension from deletion of LOS1 is nonadditive with DR or mTOR inhibition, and results in Gcn4 transcription factor activation. Thus, the DNA damage response and mTOR converge on Los1-mediated nuclear tRNA export to regulate Gcn4 activity and aging