Efficient Biochemical Method for Characterizing and Classifying Related Amyloidogenic Peptides.

Amyloidosis is a group of proteinopathies characterized by the systemic or organ-specific deposition of proteins in the form of amyloid fibers. Nearly 40 proteins play a role in these pathologies, and the structures of the associated fibers are beginning to be determined by Cryo-EM. However, the molecular events underlying the process, such as fiber nucleation and elongation, are poorly understood, which impairs developing efficient therapies.

AMETIS Preplanned Ancillary Study: Impact of Agitation During Mechanical Thrombectomy Under Sedation.

Background: Mechanical thrombectomy is the treatment of choice for ischemic strokes of the anterior circulation with proximal occlusion. Mechanical thrombectomy can be performed under sedation, which can lead to episodes of periprocedural agitation. The aim of this study is to describe the prevalence of agitation and determine the consequences during and after mechanical thrombectomy.

Late-Stage Pd(II)-Catalyzed C(sp3)-H Functionalization of Peptides Directed by a Removable, Backbone-Inserted Amidoxime Ether.

Palladium(II)-catalyzed C-H functionalization has attracted considerable attention as a pathway to late-stage modification of peptides. Herein, we report the Pd-catalyzed C(sp3)-H arylation of peptides directed by an amidoxime ether, which can be easily incorporated into peptides at any amide bond. Site- and stereoselective arylation of peptides has been achieved, including an unprecedented example of C-H arylation of an internal residue.

DNA methylation levels may contribute to severe hypertriglyceridemia in multifactorial chylomicronemia syndrome.

Background And Aims: Familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS) are the two main causes of severe hypertriglyceridemia (sHTG). FCS is a rare autosomal recessive form of sHTG, whereas MCS is mainly polygenic in nature with both common and rare variants accumulating and leading to sHTG. However, 30 to 50% of MCS patients have no identified genetic cause of sHTG.

Roles for Prlhr/GPR10 and Npffr2/GPR74 in Feeding Responses to PrRP.

Several groups of neurons in the NTS suppress food intake, including Prlh-expressing neurons (NTS cells). Not only does the artificial activation of NTS cells decrease feeding, but also the expression of Prlh (which encodes the neuropeptide PrRP) and neurotransmission by NTS neurons contributes to the restraint of food intake and body weight, especially in animals fed a high fat diet (HFD). We used animals lacking PrRP receptors GPR10 and/or GRP74 (encoded by Prlhr and Npffr2, respectively) to determine roles for each in the restraint of food intake and body weight by the increased expression of Prlh in NTS neurons (NTS mice) and in response to the anorectic PrRP analog, p52.

Development and validation of an LC-MS/MS method for quantifying total and unbound doravirine in human plasma.

A robust LC-MS/MS method was developed to quantify total and unbound doravirine in plasma samples from patients receiving daily doses of 100 mg doravirine, in combination with lamivudine and tenofovir disoproxil fumarate, in a phase 3 clinical trial. The trial is ongoing, and sample analysis is planned to commence once all samples have been collected. The method was validated to quantify both total and unbound doravirine using a single calibration curve.

The anthelmintic activity of the white wormwood (Artemisia herba Alba) against Haemonchus contortus in beef cattle.

The objective of the study was to determine the efficacy of white wormwood on helminthes in beef cattle production. Water extracts of white wormwood of different levels of phytotoxicity were used to treat female adult H. contortus over 8 h under controlled laboratory conditions.

Comparison of WatchPAT to polysomnography measurement of apnea-hypopnea index and obstructive sleep apnea severity in adolescents with overweight and obesity.

Study Objectives: The prevalence of obstructive sleep apnea (OSA) increases dramatically in adolescents with overweight or obesity. The gold standard for diagnosis of OSA is in-laboratory polysomnography (PSG). However, access to PSG can be challenging, necessitating development of alternative devices.

An α7 nicotinic and GABA receptor-mediated pathway controls acetylcholine release in the tripartite neuromuscular junction.

Terminal Schwann cells (TSCs) are capable of regulating acetylcholine (ACh) release at the neuromuscular junction (NMJ). We have identified GABA as a gliotransmitter at mouse NMJs. When ACh activates α7 nicotinic ACh receptor (nAChRs) on TSCs, GABA is released and activates GABA receptors on the nerve terminal that subsequently reduce ACh release.

Case Series of Infection-Related Glomerulonephritis in Quebec Indigenous Peoples.

Rationale: Infection-related glomerulonephritis (IRGN) is an immune-mediated glomerulonephritis caused by extra-renal infectious diseases. There has been an important shift in epidemiology in recent years, with a significant proportion of adults affected. The incidence of IRGN is higher amongst Indigenous populations and especially in those with multiple comorbidities.

Triple-Vessel Spontaneous Coronary Artery Dissection Managed Conservatively.

The management of spontaneous coronary artery dissection (SCAD) presents challenges and uncertainties. We present a case of a 54-year-old woman who developed SCAD in the three primary coronary artery territories including the distal left anterior descending artery (LAD), a diagonal branch, the first and second obtuse marginals (OMs), and the midright coronary artery (RCA). She was managed conservatively without procedural intervention, and follow-up coronary angiography demonstrated complete recovery.

A ganglioside-based immune checkpoint enables senescent cells to evade immunosurveillance during aging.

Although senescent cells can be eliminated by the immune system, they tend to accumulate with age in various tissues. Here we show that senescent cells can evade immune clearance by natural killer (NK) cells by upregulating the expression of the disialylated ganglioside GD3 at their surface. The increased level of GD3 expression on senescent cells that naturally occurs upon aging in liver, lung, kidney or bones leads to a strong suppression of NK-cell-mediated immunosurveillance.

The walnut tree as a source of progesterone for reproductive control in goats.

Intravaginal sponges impregnated with the progesterone (P4) analogue fluorogestone acetate (FGA) induce synchronous oestrous behaviour and normal ovulatory cycle in goats. To explore alternatives using natural P4 from plants, we developed a method of ethanolic extraction and a specific enzyme immunoassay (EIA) to measure P4 in the different parts of the walnut tree Juglans regia. We found a very high concentration of P4, specifically in the leaves of the three most common French varieties (∼100 mg/kg of DM) but not in flowers, fruits, septa, husk, oil or cake.

SMCHD1 genetic variants in type 2 facioscapulohumeral dystrophy and challenges in predicting pathogenicity and disease penetrance.

The molecular diagnosis of type 1 facioscapulohumeral muscular dystrophy (FSHD1) relies on the detection of a shortened D4Z4 array at the 4q35 locus. Until recently, the diagnosis of FSHD2 relied solely on the absence of a shortened D4Z4 allele in clinically affected patients. It is now established that most FSHD2 cases carry a heterozygous variant in the SMCHD1 gene.

Cyclosporine A Delays the Terminal Disease Stage in the Tfam KO Mitochondrial Myopathy Mouse Model Without Improving Mitochondrial Energy Production.

Introduction And Aims: Mitochondrial myopathies are rare genetic disorders for which no effective treatment exists. We previously showed that the pharmacological cyclophilin inhibitor cyclosporine A (CsA) extends the lifespan of fast-twitch skeletal muscle-specific mitochondrial transcription factor A knockout (Tfam KO) mice, lacking the ability to transcribe mitochondrial DNA and displaying lethal mitochondrial myopathy. Our present aim was to assess whether the positive effect of CsA was associated with improved in vivo mitochondrial energy production.

Framing resilience linked to parental ethnic-racial socialization as hidden: A hidden resilience conceptual framework.

Parental ethnic-racial socialization is a source of adolescents' resilience against ethnic-racial discrimination. Recent meta-analyses have documented the aspects of ethnic-racial socialization (i.e.

Muscle composition is not a prognostic factor for muscle strength recovery after anterior cruciate ligament surgery by hamstring tendon autograft.

Purpose: For the athlete, anterior Cruciate Ligament (ACL) rupture and its surgical management are often a turning point in their career. Success and time to return to sport are essential parameters for athletes and their support staff, so it is critical to understand the prognostic factors influencing return to sport after anterior cruciate ligament reconstruction (ACLR). The aim of this study was to determine the influence of hamstring muscle composition on muscle power following ACLR with autogenous hamstring grafts.

Exploratory study of erosion in cultivated organic soils using cesium-137 measurements.

Concerns about the sustainability of cultivated organic soils in Montérégie (Quebec, Canada), which can also be identified as histosols, led to this exploratory study aimed at quantifying erosion in these soils by using cesium-137 (Cs) measurements. Soil samples were taken from organic soils in twenty-two fields, and their Cs contents were measured by gamma spectrometry. The estimated mean annual erosion rates (±SD), adjusted with cropping history, ranged from 0.

Intracranial multimodal monitoring in neurocritical care (Neurocore-iMMM): an open, decentralized consensus.

Background: Intracranial multimodal monitoring (iMMM) is increasingly used in neurocritical care, but a lack of standardization hinders its evidence-based development. Here, we devised core outcome sets (COS) and reporting guidelines to harmonize iMMM practices and research.

Methods: An open, decentralized, three-round Delphi consensus study involved experts between December 2023 and June 2024.

Serial secretoneurin measurement and risk of ventricular arrhythmias and death in patients with left ventricular systolic dysfunction.

Background: Secretoneurin, a member of the granin protein family, is associated with the risk of mortality in patients with acute and chronic heart failure. Secretoneurin may play an important role in cardiomyocyte calcium handling, suggesting that it may influence cardiac arrhythmia risk. We hypothesized that baseline and serial measurements of circulating secretoneurin are associated with the risk of incident ventricular tachyarrhythmias (VA) and death, and that serial measurement would provide prognostic information beyond baseline values.

Broth microdilution protocol for determining antimicrobial susceptibility of Legionella pneumophila to clinically relevant antimicrobials.

Currently there is no detailed, internationally agreed protocol defined to evaluate antimicrobial susceptibility testing (AST) for Legionella pneumophila (required to establish epidemiological cut-off value or "ECOFF" boundaries); therefore, antimicrobial resistance in these isolates cannot be defined. AST methods utilising media containing activated charcoal as an ingredient, to enable Legionella growth, are unreliable as noted in an internationally authored opinion paper and a new gold standard is required. Here we define a detailed protocol for broth microdilution (BMD) using defined cell culture collection-deposited control reference strains (Philadelphia-1 and Knoxville-1) as well as two accessible reference strains with moderately (lpeAB-carrying) and markedly (23S rRNA mutation-carrying) elevated azithromycin minimum inhibitory concentration (MIC).