Balancing Selection of a Frame-Shift Mutation in the MRC2 Gene Accounts for the Outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle

We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Endoscopic laser therapy for small villous adenomas of the duodenum

Six patients with seven small, nonampullary duodenal villous or tubulovillous adenomas, two of which showed mild dysplasia, were treated by laser photocoagulation. The mean size of the tumors was 19 +/- 16 mm. Both argon and Nd-YAG lasers were used. All tumors were destroyed in one to five sessions. Recurrences of the lesion in two cases were successfully retreated, and both patients remained free of recurrence after 33 and 48 months, respectively. After a median follow-up of 59 months, all patients remained in remission, and five of them are still alive. One died after six months from a bronchogenic carcinoma. After a total of 18 laser sessions, no serious side-effects were observed, two patients exhibiting a transient melena possibly related to the procedure. We conclude that laser therapy is a good alternative to surgery for nonampullary duodenal villous tumors, especially in high-risk patients. Endoscopic follow-up is mandatory to detect and treat recurrence

A practical endoscopic procedure for jejunal intubation in presence of gastroparesia or (pseudo)-obstruction.

Patients with gastroparesia or intestinal pseudo-obstruction frequently have a motility disorder of the antro-pyloric region that makes the passage of tubes through the pylorus impossible or a very long procedure. We describe a rapid endoscopic method, inspired by the one used for nasobiliary drainage, that simplifies this procedure. In our manometric studies, we observed that spontaneous positioning needed a mean of 57 min (SD 34) in nondyspeptic subjects and a mean of 147 min (SD 68) in non-organic highly dyspeptic patients. Our method allowed us to shorten to a mean of 22 min (SD 5) the time needed to position the manometric tube and to start the recording of gastro-intestinal contractions in highly dyspeptic patients

Part 13: Synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 or pure antiretroviral activity

HIV-1 infection of the brain and PAF neurotoxicity are implicated in AIDS dementia complex. We previously reported that a trisubstituted piperazine derivative is able to diminish both HIV-1 replication in monocyte-derived macrophages and PAF-induced platelet aggregation. We report in this work new compounds obtained by modifying its piperazine substituents. The structure-activity relationship study shows that a better dual activity or even pure antiretroviral compounds can be obtained in this series. (c) 2006 Elsevier Ltd. All rights reserved