Evaluation of an oral small-molecule glucagon-like peptide-1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: A dose-ranging, phase 2, randomized, placebo-controlled study.

Aim: The aim was to investigate the effects of lotiglipron, a once-daily, oral small-molecule glucagon-like peptide-1 (GLP-1) receptor agonist, in participants with type 2 diabetes (T2D) or obesity.

Materials And Methods: A phase 2, randomized, double-blind, placebo-controlled, dose-ranging study investigated the efficacy and safety of lotiglipron. The study was terminated early for safety reasons after routine data and monitoring review.

CRYAB plays a role in terminating the presence of pro-inflammatory macrophages in the older, injured mouse peripheral nervous system.

Evidence indicates that dysfunction of older Schwann cells and macrophages contributes to poor regeneration of more mature peripheral nervous system (PNS) neurons after damage. Since the underlying molecular factors are largely unknown, we investigated if CRYAB, a small heat shock protein that is expressed by Schwann cells and axons and whose expression declines with age, impacts prominent deficits in the injured, older PNS including down-regulation of cholesterol biosynthesis enzyme genes, Schwann cell dysfunction, and macrophage persistence. Following sciatic nerve transection injury in 3- and 12-month-old wildtype and CRYAB knockout mice, we found by bulk RNA sequencing and RT-PCR, that while gene expression of cholesterol biosynthesis enzymes is markedly dysregulated in the aging, injured PNS, CRYAB is not involved.

What Do Scientists Mean When They Talk About Research Animals "Volunteering"?

This paper examines discourses around "volunteering" in animal research. Through a qualitative textual analysis of the scientific literature using animals in behavioral and psychological research, we demonstrate that "voluntary" and related terms are used by scientists in a variety of distinct ways, which carry a range of ethical and political connotations. While any reference to volunteering might be assumed to imply free, unconstrained, and unpaid participation in an activity, in the animal research literature the term is often used simply to signal a lack of physical restraint, even though other human-imposed constraints are at play.

Co-producing Human and Animal Experimental Subjects: Exploring the Views of UK COVID-19 Vaccine Trial Participants on Animal Testing.

Preclinical (animal) testing and human testing of drugs and vaccines are rarely considered by social scientists side by side. Where this is done, it is typically for theoretically exploring the ethics of the two situations to compare relative treatment. In contrast, we empirically explore how human clinical trial participants understand the role of animal test subjects in vaccine development.

COVID-19-Related Employment Disruptions and Increased Financial Burden Among Survivors of Adolescent and Young Adult Cancer.

Financial burden is a major concern for survivors of adolescent and young adult (AYA) cancers. We identified if employment disruptions during the COVID-19 pandemic affected AYA survivors' financial burden. AYAs who were enrolled in a cancer patient navigation program were e-mailed a survey in fall 2020.

Simultaneous sequencing of genetic and epigenetic bases in DNA.

DNA comprises molecular information stored in genetic and epigenetic bases, both of which are vital to our understanding of biology. Most DNA sequencing approaches address either genetics or epigenetics and thus capture incomplete information. Methods widely used to detect epigenetic DNA bases fail to capture common C-to-T mutations or distinguish 5-methylcytosine from 5-hydroxymethylcytosine.

Ixazomib With or Without Rituximab Following Maintenance Autologous Stem Cell Transplant in Mantle Cell Lymphoma: A Single-Center Phase I Trial.

Background: Induction chemotherapy followed by autologous stem cell transplantation (ASCT) is a standard first-line treatment for fit patients with mantle cell lymphoma (MCL). We conducted a single-center phase I trial investigating post-transplant maintenance with ixazomib, an oral proteasome inhibitor.

Methods: Patients enrolled between days +70 and +180 post ASCT.

Synergistic augmentation of rhythmic myogenic contractions of human stomach by arginine vasopressin and adrenaline: Implications for the induction of nausea.

Background And Purpose: Nausea is associated with the hormonal secretion of vasopressin and adrenaline, although their actions in inducing nausea is poorly understood. Here, we have investigated their actions on human stomach muscle.

Experimental Approach: Muscle strips were suspended in tissue baths and neuronal-/non-neuronally-mediated contractions were measured.

When research animals become pets and pets become research animals: care, death, and animal classification.

This paper explores what happens to care, and decisions about ending and extending life, when research animals become pets and pets become research animals. To do this, we draw on in-depth qualitative research on (i) rehoming of laboratory animals, (ii) veterinary clinical research, and (iii) the role of the Named Veterinary Surgeon (NVS) in UK animal research. We begin by exploring how (in theory and practice) the ethical, affective, and practical elements of care are split in the research laboratory.

A multi-parameter approach to measurement of spontaneous myogenic contractions in human stomach: Utilization to assess potential modulators of myogenic contractions.

Electrical slow waves, generated by interstitial cells of Cajal (ICC), cause spontaneous contractions of human stomach. Software was developed to measure muscle tone and eleven different parameters defining these contractions in human stomach, displaying data as radar plots. A pilot study assessed the effects of potential modulators, selected from among compounds known to influence ICC activity; n = 4-7 each concentration tested/compound.

Hybrid apes in the Anthropocene: Burden or asset for conservation?

Conservationists often view hybrid animals as problematic, at least if anthropogenic influence caused the intermixing to occur. However, critics propose that humans should respect non-human autonomy, reject and accept the creatures they have helped to create.Based on two case studies of our own ethological, genetic and ethnographic research about chimpanzee and orangutan subspecies hybrids, we assess what, if anything, should be done about such animals.

Expression of p16 Within Myenteric Neurons of the Aged Colon: A Potential Marker of Declining Function.

Human colonic neuromuscular functions decline among the elderly. The aim was to explore the involvement of senescence. A preliminary PCR study looked for age-dependent differences in expression of (encoding the senescence-related p21 protein) and (encoding p16 and p14) in human ascending and descending colon (without mucosa) from 39 (approximately 50: 50 male: female) adult (aged 27-60 years) and elderly donors (70-89 years).

Edge cases in animal research law: Constituting the regulatory borderlands of the UK's Animals (Scientific Procedures) Act.

This paper explores how the boundaries of the UK's Animals (Scientific Procedures) Act (A(SP)A) are constituted, as illustrative of the rising importance of legal procedures around animal research and how these are continuously being challenged and questioned. Drawing on empirical work in animal research communities, we consider how it is decided whether activities are undertaken for an "experimental or other scientific purpose". We do this by focusing on "edge cases", where debates occur about whether to include an activity within A(SP)A's remit.

Genetic interaction of Pax3 mutation and canonical Wnt signaling modulates neural tube defects and neural crest abnormalities.

Mouse models provide opportunities to investigate genetic interactions that cause or modify the frequency of neural tube defects (NTDs). Mutation of the PAX3 transcription factor prevents neural tube closure, leading to cranial and spinal NTDs whose frequency is responsive to folate status. Canonical Wnt signalling is implicated both in regulation of Pax3 expression and as a target of PAX3.

QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy.

A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted.

COVID-19 Vaccine Hesitancy Among Adolescent and Young Adult Cancer Survivors.

The study objective was to identify sociodemographic and coronavirus disease 2019 (COVID-19) factors that are associated with COVID-19 vaccine hesitancy among adolescent and young adult (AYA) cancer survivors. Eligible participants were 18 years or older and were diagnosed with cancer as an AYA (ages 15-39 years) and received services through an AYA cancer program. A total of 342 participants completed a cross-sectional survey.

Out of the laboratory, into the field: perspectives on social, ethical and regulatory challenges in UK wildlife research.

Drawing on insights from qualitative social science research, this paper aims to prompt reflection on social, ethical and regulatory challenges faced by scientists undertaking invasive animal research in the field and propose ways of addressing these challenges to promote good care for animals and environments. In particular, we explore challenges relating to the management of (i) relationships with publics and stakeholders, who may be present at field sites or crucial to research success; (ii) ethical considerations not present in the laboratory, such as the impacts of research on populations and ecosystems; (iii) working under an array of regulations, which may operate in accordance with competing ethical principles or objectives; and (iv) relationships with regulators (especially vets), which may involve disagreements over ethics and expertise, especially because regulators may be more accustomed to overseeing research in the laboratory than the field. We argue that flexibility-at a personal and policy level-and respect for others' expertise emerged as two key ways of negotiating ethical challenges, fostering positive working relationships and promoting good care for individual animals and broader ecosystems.

Efficacy and Safety of Ertugliflozin in Patients with Type 2 Diabetes Inadequately Controlled by Metformin and Sulfonylurea: A Sub-Study of VERTIS CV.

Introduction: VERTIS CV is the cardiovascular outcome trial for the sodium-glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin. A sub-study was conducted to assess the efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately glycemic-controlled on metformin and a sulfonylurea (SU).

Methods: Patients with T2DM, established atherosclerotic cardiovascular disease (ASCVD), and an HbA1c of 7.

Getting to grips with wildlife research by citizen scientists: What role for regulation?

Wildlife research by citizen scientists, involving the capture and handling of animals, provides clear scientific benefits, but also potential risks to animal welfare. We explore debates about how best to regulate such work to ensure that it is undertaken in an ethical manner.We focus on the UK as a case study, drawing on qualitative research and stakeholder engagement events.

Animal Research beyond the Laboratory: Report from a Workshop on Places Other than Licensed Establishments (POLEs) in the UK.

Research involving animals that occurs outside the laboratory raises an array of unique challenges. With regard to UK legislation, however, it receives only limited attention in terms of official guidelines, support, and statistics, which are unsurprisingly orientated towards the laboratory environment in which the majority of animal research takes place. In September 2019, four social scientists from the Animal Research Nexus program gathered together a group of 13 experts to discuss nonlaboratory research under the Animals (Scientific Procedures) Act (A(SP)A) of 1986 (mirroring European Union (EU) Directive 2010/63/EU), which is the primary mechanism for regulating animal research in the UK.

Cystatin C Plays a Sex-Dependent Detrimental Role in Experimental Autoimmune Encephalomyelitis.

The cysteine protease inhibitor Cystatin C (CST3) is highly expressed in the brains of multiple sclerosis (MS) patients and C57BL/6J mice with experimental autoimmune encephalomyelitis (EAE; a model of MS), but its roles in the diseases are unknown. Here, we show that CST3 plays a detrimental function in myelin oligodendrocyte glycoprotein 35-55 (MOG)-induced EAE but only in female animals. Female Cst3 null mice display significantly lower clinical signs of disease compared to wild-type (WT) littermates.

Management of Velopharyngeal Insufficiency in Cleft Patients With and Without Multidisciplinary Team Care.

Objective: To evaluate the effect of an American Cleft Palate-Craniofacial Association (ACPA)-approved multidisciplinary team on velopharyngeal insufficiency (VPI) diagnosis and treatment.

Design: Retrospective cohort setting; tertiary children's hospital patients; children with cleft palate repair identified through procedure codes.

Main Outcome Measures: Velopharyngeal insufficiency diagnosis was assigned based on surgeon or team assessment.

Normative database of spatiotemporal gait parameters using inertial sensors in typically developing children and young adults.

Background: Inertial sensors are increasingly useful to clinicians and researchers to detect gait deficits. Reference values are necessary for comparison to children with gait abnormalities.

Objective: To present a normative database of spatiotemporal gait and turning parameters in 164 typically developing children and young adults ages 5-30 utilizing the APDM Mobility Lab® system.

Inhibition of Neuromuscular Contractions of Human and Rat Colon by Bergamot Essential Oil and Linalool: Evidence to Support a Therapeutic Action.

Bergamot essential oil (BEO) added to food and drink promotes a citrus flavour. Folklore suggests benefits on gastrointestinal functions but with little supporting evidence. BEO and major constituents (linalool, limonene, linalyl acetate) were therefore examined for any ability to influence neuromuscular contractions of human and rat colon.