A new congenital multicore titinopathy associated with fast myosin heavy chain deficiency.

Congenital titinopathies are myopathies with variable phenotypes and inheritance modes. Here, we fully characterized, using an integrated approach (deep phenotyping, muscle morphology, mRNA and protein evaluation in muscle biopsies), two siblings with congenital multicore myopathy harboring three TTN variants predicted to affect titin stability and titin-myosin interactions. Muscle biopsies showed multicores, type 1 fiber uniformity and sarcomeric structure disruption with some thick filament loss.

Imidazopyridine-fused [1,3]diazepinones: modulations of positions 2 to 4 and their impacts on the anti-melanoma activity.

A series of 19 novel pyrido-imidazodiazepinones, with modulations of positions 2, 3 and 4 of the diazepine ring were synthesised and screened for their cytotoxic activities against two melanoma cell lines (A375 and MDA-MB-435) and for their potential toxicity against NIH-3T3 non-cancerous cells. Selected compounds were also evaluated on the NCI-60 cell line panel. The SAR study revealed that the molecular volume and the LogP of compounds modified at position 2 were significantly correlated with the activity of these compounds on melanoma cell lines.

Early Neolithic (ca. 5850-4500 cal BC) agricultural diffusion in the Western Mediterranean: An update of archaeobotanical data in SW France.

Farming economy was first introduced to the coastal areas of Southern France by Impressa groups (ca. 5850-5650 cal BC), originating from Italy, and subsequently spread to the hinterland by Cardial/Epicardial communities (ca. 5400-4500 cal BC).

Vibrio splendidus O-antigen structure: a trade-off between virulence to oysters and resistance to grazers.

A major debate in evolutionary biology is whether virulence is maintained as an adaptive trait and/or evolves to non-virulence. In the environment, virulence traits of non-obligatory parasites are subjected to diverse selective pressures and trade-offs. Here, we focus on a population of Vibrio splendidus that displays moderate virulence for oysters.

Deceleration of China's human water use and its key drivers.

Increased human water use combined with climate change have aggravated water scarcity from the regional to global scales. However, the lack of spatially detailed datasets limits our understanding of the historical water use trend and its key drivers. Here, we present a survey-based reconstruction of China's sectoral water use in 341 prefectures during 1965 to 2013.

Earliest African evidence of carcass processing and consumption in cave at 700 ka, Casablanca, Morocco.

To date, in Africa, evidence for animal processing and consumption in caves routinely used as living spaces is only documented in the late Middle Pleistocene of the North and South of the continent and postdates the Middle Pleistocene in East Africa. Here we report the earliest evidence in a North-African cave (Grotte des Rhinocéros at Casablanca, Morocco) of cut, percussion and human gnawing marks on faunal remains directly associated with lithic knapping activities in the same space and in a well-documented stratified context. Ages for this Acheulean site are provided by the dating of herbivorous teeth to 690-720 ka and 520-550 ka (lower and upper sets) by combined Electron Spin Resonance (ESR) and U-series techniques.

Impact of projected sea surface temperature biases on tropical cyclones projections in the South Pacific.

Climate model projections generally indicate fewer but more intense tropical cyclones (TCs) in response to increasing anthropogenic emissions. However these simulations suffer from long-standing biases in their Sea Surface Temperature (SST). While most studies investigating future changes in TC activity using high-resolution atmospheric models correct for the present-day SST bias, they do not consider the reliability of the projected SST changes from global climate models.

Reactivation of the Epicardium at the Origin of Myocardial Fibro-Fatty Infiltration During the Atrial Cardiomyopathy.

Rationale: Fibro-fatty infiltration of subepicardial layers of the atrial wall has been shown to contribute to the substrate of atrial fibrillation.

Objective: Here, we examined if the epicardium that contains multipotent cells is involved in this remodeling process.

Methods And Results: One hundred nine human surgical right atrial specimens were evaluated.

In Situ Fe and S isotope analyses in pyrite from the 3.2 Ga Mendon Formation (Barberton Greenstone Belt, South Africa): Evidence for early microbial iron reduction.

On the basis of phylogenetic studies and laboratory cultures, it has been proposed that the ability of microbes to metabolize iron has emerged prior to the Archaea/Bacteria split. However, no unambiguous geochemical data supporting this claim have been put forward in rocks older than 2.7-2.

Drug hypersensitivity reactions in Asia: regional issues and challenges.

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low.

Body mass index and weight change are associated with adult lung function trajectories: the prospective ECRHS study.

Background: Previous studies have reported an association between weight increase and excess lung function decline in young adults followed for short periods. We aimed to estimate lung function trajectories during adulthood from 20-year weight change profiles using data from the population-based European Community Respiratory Health Survey (ECRHS).

Methods: We included 3673 participants recruited at age 20-44 years with repeated measurements of weight and lung function (forced vital capacity (FVC), forced expiratory volume in 1 s (FEV)) in three study waves (1991-93, 1999-2003, 2010-14) until they were 39-67 years of age.

Kaposi sarcoma among people living with HIV in the French DAT'AIDS cohort between 2010 and 2015.

Background: Although antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS cases still occur in HIV-infected people.

Objective: To describe all KS cases observed between 2010 and 2015 in a country with high ART coverage.

Methods: Retrospective study using longitudinal data from 44 642 patients in the French Dat'AIDS multicenter cohort.

Imaging protocols for renal multiparametric MRI and MR urography: results of a consensus conference from the French Society of Genitourinary Imaging.

Objectives: To develop technical guidelines for magnetic resonance imaging aimed at characterising renal masses (multiparametric magnetic resonance imaging, mpMRI) and at imaging the bladder and upper urinary tract (magnetic resonance urography, MRU).

Methods: The French Society of Genitourinary Imaging organised a Delphi consensus conference with a two-round Delphi survey followed by a face-to-face meeting. Two separate questionnaires were issued for renal mpMRI and for MRU.

Epidemiology and prognosis of anti-infective therapy in the ICU setting during acute pancreatitis: a cohort study.

Background: Recent international guidelines for acute pancreatitis (AP) recommend limiting anti-infective therapy (AIT) to cases of suspected necrotizing AP or nosocomial extrapancreatic infection. Limited data are available concerning empirical and documented AIT prescribing practices in patients admitted to the intensive care unit (ICU) for the management of AP.

Methods: Using a multicentre, retrospective (2009-2014), observational database of ICU patients admitted for AP, our primary objective was to assess the incidence of AIT prescribing practices during the first 30 days following admission.

Brazilian montane rainforest expansion induced by Heinrich Stadial 1 event.

The origin of modern disjunct plant distributions in the Brazilian Highlands with strong floristic affinities to distant montane rainforests of isolated mountaintops in the northeast and northern Amazonia and the Guyana Shield remains unknown. We tested the hypothesis that these unexplained biogeographical patterns reflect former ecosystem rearrangements sustained by widespread plant migrations possibly due to climatic patterns that are very dissimilar from present-day conditions. To address this issue, we mapped the presence of the montane arboreal taxa Araucaria, Podocarpus, Drimys, Hedyosmum, Ilex, Myrsine, Symplocos, and Weinmannia, and cool-adapted plants in the families Myrtaceae, Ericaceae, and Arecaceae (palms) in 29 palynological records during Heinrich Stadial 1 Event, encompassing a latitudinal range of 30°S to 0°S.

Erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial.

Purpose: This Phase IIb (NCT02195180) open-label study evaluated erythrocyte-encapsulated asparaginase (eryaspase) in combination with chemotherapy in second-line advanced pancreatic adenocarcinoma.

Methods: Eligible patients were randomized 2:1 to either eryaspase in combination with gemcitabine or mFOLFOX6 (eryaspase arm), or to gemcitabine or mFOLFOX6 alone (control arm). Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients with low asparagine synthetase (ASNS) expression.

Respective contribution of intensive care unit-acquired limb muscle and severe diaphragm weakness on weaning outcome and mortality: a post hoc analysis of two cohorts.

Background: Intensive care unit (ICU)-acquired weakness (ICU-AW) and ICU-acquired diaphragm dysfunction (ICU-DD) occur frequently in mechanically ventilated (MV) patients. It is unknown whether they have different risk factors and different impacts on outcome. This study was designed to (1) describe the respective risk factors associated with ICU-AW and severe ICU-DD and (2) evaluate the respective impact of ICU-AW and severe ICU-DD on outcome.

Towards a more precise diagnosis of hypersensitivity to beta-lactams - an EAACI position paper.

A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta-lactam (BL) hypersensitivity demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost-effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation. The updated guidelines provide a risk stratification in BL hypersensitivity according to index reaction(s), as well as an algorithmic approach, based on cross-reactivity studies, in patients with a suspicion of BL hypersensitivity and an immediate need for antibiotic therapy, when referral to an allergist is not feasible.