The Spectrum of Cutaneous Granulomatous Inflammation and Detection of Rubella Virus in Skin Biopsies of Patients With Common Variable Immune Deficiency.

Background: There is a known association between common variable immunodeficiency (CVID) and granulomas in multiple organ systems, including the skin, lung, liver, and spleen. Rubella virus has also been detected within cutaneous granulomas in both immunocompetent and immunocompromised hosts. We present a retrospective case series of patients with CVID and granulomatous skin disease and describe the spectrum of clinical and histopathologic features, including the status of rubella virus in the cutaneous granulomas.

Enhancing disciplinary diversity and inclusion in conservation science and practice based on a case study of the Society for Conservation Biology.

Effective conservation requires a variety of perspectives that center on different ways of knowing. Disciplinary diversity and inclusion (DDI) offers an important means of integrating different ways of knowing into pressing conservation challenges. However, DDI means more than multiple disciplinary approaches to conservation; cognitive diversity and epistemic justice are key.

Enterovirus A71 and coxsackievirus A6 circulation in England, UK, 2006-2017: A mathematical modelling study using cross-sectional seroprevalence data.

Enterovirus A71 (EV-A71) and coxsackievirus A6 (CVA6) primarily cause hand, foot and mouth disease and have emerged to cause potential fatal neurological and systemic manifestations. However, limited surveillance data collected through passive surveillance systems hampers characterization of their epidemiological dynamics. We fit a series of catalytic models to age-stratified seroprevalence data for EV-A71 and CVA6 collected in England at three time points (2006, 2011 and 2017) to estimate the force of infection (FOI) over time and assess possible changes in transmission.

CHK1 inhibitor SRA737 is active in PARP inhibitor resistant and amplified ovarian cancer.

High-grade serous ovarian cancers (HGSOCs) with homologous recombination deficiency (HRD) are initially responsive to poly (ADP-ribose) polymerase inhibitors (PARPi), but resistance ultimately emerges. HGSOC with amplification ( ) are associated with resistance to PARPi and platinum treatments. High replication stress in HRD and HGSOC leads to increased reliance on checkpoint kinase 1 (CHK1), a key regulator of cell cycle progression and the replication stress response.

Analytical Quality by Design as applied to the development of a SEC-HPLC platform procedure for the determination of monoclonal antibody purity without mobile phase additives.

This work presents the application of AQbD principles to the development of a size exclusion chromatography (SEC) HPLC procedure for the determination of monoclonal antibody (mAb) product purity using state-of-the-art column technology available via the Waters™ XBridge Premier Protein SEC column. Analytical Quality by Design (AQbD) emphasizes a systematic, risk-based lifecycle approach to analytical procedure development based on sound statistical methodologies. It has recently become increasingly recommended by regulatory agencies as a response to the need for greater efficiency, improved reliability, and increased robustness among modern analytical procedures in the pharmaceutical industry.

Epidemiology of heat-related illness in dogs under UK emergency veterinary care in 2022.

Background: Dogs are exposed to increasing environmental risk for developing heat-related illness (HRI), with 2022 recorded as the hottest year to date in the UK and most of Europe.

Methods: This study used VetCompass data to report the incidence risk, event fatality rate and canine risk factors for HRI in dogs presenting to Vets Now emergency care practices in the UK during 2022.

Results: From the clinical records of 167,751 dogs under care at Vets Now emergency clinics in 2022, 384 HRI events were identified.

Adaptation and Implementation of a Volunteer-Delivered, Telephone-Based, Social Support Program HOW-R-U? During the COVID-19 Pandemic: A Pragmatic Study.

Background And Objectives: Public health concerns surrounding social isolation and loneliness heightened during the coronavirus disease 2019 (COVID-19) pandemic, as infection prevention measures led to increased feelings of loneliness and depression. Our objective was to evaluate the implementation of the HOW-R-U? program, during the pandemic (March 2020-December 2021). HOW-R-U? is a weekly volunteer-delivered telephone program designed to facilitate social connection and ease feelings of social isolation, loneliness, and depression in older people.

Sequence- and Structure-Dependent Cytotoxicity of Phosphorothioate and 2'--Methyl Modified Single-Stranded Oligonucleotides.

Single-stranded oligonucleotides (SSOs) are a rapidly expanding class of therapeutics that comprises antisense oligonucleotides, microRNAs, and aptamers, with ten clinically approved molecules. Chemical modifications such as the phosphorothioate backbone and the 2'--methyl ribose can improve the stability and pharmacokinetic properties of therapeutic SSOs, but they can also lead to toxicity and through nonspecific interactions with cellular proteins, gene expression changes, disturbed RNA processing, and changes in nuclear structures and protein distribution. In this study, we screened a mini library of 277 phosphorothioate and 2'--methyl-modified SSOs, with or without mRNA complementarity, for cytotoxic properties in two cancer cell lines.

Targeting the hSSB1-INTS3 Interface: A Computational Screening Driven Approach to Identify Potential Modulators.

Human single-stranded DNA binding protein 1 (hSSB1) forms a heterotrimeric complex, known as a sensor of single-stranded DNA binding protein 1 (SOSS1), in conjunction with integrator complex subunit 3 (INTS3) and C9ORF80. This sensory protein plays an important role in homologous recombination repair of double-strand breaks in DNA to efficiently recruit other repair proteins at the damaged sites. Previous studies have identified elevated hSSB1-mediated DNA repair activities in various cancers, highlighting its potential as an anticancer target.

Membrane vesicles in class extreme acidophiles: influence on collective behaviors of ''.

Membrane vesicles (MVs) are envelope-derived extracellular sacs that perform a broad diversity of physiological functions in bacteria. While considerably studied in pathogenic microorganisms, the roles, relevance, and biotechnological potential of MVs from environmental bacteria are less well established. family bacteria are active players in the sulfur and iron biogeochemical cycles in extremely acidic environments and drivers of the leaching of mineral ores contributing to acid rock/mine drainage (ARD/AMD) and industrial bioleaching.

Racism as a public health issue in environmental health disparities and environmental justice: working toward solutions.

Background: Environmental health research in the US has shown that racial and ethnic minorities and members of low-socioeconomic groups, are disproportionately burdened by harmful environmental exposures, in their homes, workplace, and neighborhood environments that impact their overall health and well-being. Systemic racism is a fundamental cause of these disproportionate exposures and associated health effects. To invigorate and inform current efforts on environmental justice and to raise awareness of environmental racism, the National Institute of Environmental Health Sciences (NIEHS) hosted a workshop where community leaders, academic researchers, and NIEHS staff shared perspectives and discussed ways to inform future work to address health disparities.

Investigating ticagrelor in a preclinical pipeline as a novel therapeutic to prevent preterm birth.

In Brief: Preterm birth is the leading cause of perinatal morbidity and mortality, and new therapies that delay preterm birth and improve neonatal outcomes are urgently needed. This study investigates whether ticagrelor inhibits uterine contractility and inflammation in preclinical in vitro, ex vivo (human) and in vivo (mouse) studies, to explore the potential of repurposing ticagrelor for the prevention of preterm birth.

Abstract: Preterm birth remains a significant global health challenge, affecting approximately 10% of pregnancies and resulting in one million deaths globally every year.

An Exploration of Small Molecules That Bind Human Single-Stranded DNA Binding Protein 1.

Human single-stranded DNA binding protein 1 (hSSB1) is critical to preserving genome stability, interacting with single-stranded DNA (ssDNA) through an oligonucleotide/oligosaccharide binding-fold. The depletion of hSSB1 in cell-line models leads to aberrant DNA repair and increased sensitivity to irradiation. hSSB1 is over-expressed in several types of cancers, suggesting that hSSB1 could be a novel therapeutic target in malignant disease.

Using Community-Based Participatory Research to Develop Care Recommendations for People Aging With HIV.

Background And Objectives: Over 50% of New Yorkers living with human immunodeficiency virus (HIV) are 50 years old or older, and the emotional and physical consequences of being a long-term survivor are significant. This study aimed to identify the practical needs of long-term survivors and older people with HIV (consumers) in New York State and develop recommendations addressing those needs.

Research Design And Methods: The HIV + Aging/LTS/Perinatally Diagnosed Subcommittee of the Consumer Advisory and Quality Advisory committees in the New York State AIDS Institute used community-based participatory research (CBPR) methods to design a statewide survey about the care needs of consumers in New York State.

The Regulation of Endothelin-1 in Pregnancies Complicated by Gestational Diabetes: Uncovering the Vascular Effects of Insulin.

Gestational diabetes mellitus (GDM) is a condition of pregnancy defined by new-onset hyperglycemia. GDM is associated with impaired maternal endothelial and vascular reactivity. Endothelin-1 (ET-1) is a potent vasoconstrictor that contributes to endothelial dysfunction, however, its abundance and actions in GDM are unclear.

Pangenome-level analysis of nucleoid-associated proteins in the class: insights into their functional roles in mobile genetic elements biology.

Mobile genetic elements (MGEs) are relevant agents in bacterial adaptation and evolutionary diversification. Stable appropriation of these DNA elements depends on host factors, among which are the nucleoid-associated proteins (NAPs). NAPs are highly abundant proteins that bind and bend DNA, altering its topology and folding, thus affecting all known cellular DNA processes from replication to expression.

Increased reports of severe myocarditis associated with enterovirus infection in neonates, United Kingdom, 27 June 2022 to 26 April 2023.

Enteroviruses are a common cause of seasonal childhood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection.

Molecular hydrogen and water activation by transition metal frustrated Lewis pairs containing ruthenium or osmium components: catalytic hydrogenation assays.

The transition metal frustrated Lewis pair compounds [(Cym)M(κS,P,N-HL1)][SbF] (Cym = η--MeCHiPr; H2L1 = -(-tolyl)-'-(2-diphenylphosphanoethyl)thiourea; M = Ru (5), Os (6)) have been prepared from the corresponding dimer [{(Cym)MCl}(μ-Cl)] and H2L1 by successive chloride abstraction with NaSbF and AgSbF and NH deprotonation with NaHCO. Complexes 5 and 6 and the previously reported phosphano-guanidino compounds [(Cym)M(κP,N,N'-HL2)][SbF] [H2L2 = ,'-bis(-tolyl)-''-(2-diphenylphosphanoethyl) guanidine; M = Ru (7), Os (8)] and pyridinyl-guanidino compounds [(Cym)M(κN,N',N''-HL3)][SbF] [H2L3 = ,'-bis(-tolyl)-''-(2-pyridinylmethyl) guanidine; M = Ru (9), Os (10)] heterolytically activate H in a reversible manner affording the hydrido complexes [(Cym)MH(H2L)][SbF] (H2L = H2L1; M = Ru (11), Os (12); H2L = H2L2; M = Ru (13), Os (14); H2L = H2L3; M = Ru (15), Os (16)). DFT calculations carried out on the hydrogenation of complex 7 support an FLP mechanism for the process.

The effects of timing of high immune response phenotyping in relation to weaning on immune responses of crossbred beef calves.

Genetic selection for immune response has the potential to increase the sustainability of the beef industry by breeding cattle that are productive yet with an increased capacity to resist disease. Determining the optimal time to immunophenotype beef cattle is crucial for the accurate prediction of an animal's immune response. The objective of this study was to determine the effect of time of immunophenotyping in relation to weaning on immune responses of beef calves.

Cooling Methods Used to Manage Heat-Related Illness in Dogs Presented to Primary Care Veterinary Practices during 2016-2018 in the UK.

The management of heat-related illness (HRI) in dogs has received limited attention in the veterinary literature, especially regarding effective cooling methods. Guidelines published in 2016 for prehospital management of dogs with HRI advised "cool first, transport second", and recommended using cold-water immersion and evaporative cooling (water application with air movement) as the optimal approaches to reduce the patient's temperature. The current retrospective cross-sectional observation study analysed electronic patient records from the VetCompass programme to describe the cooling methods used in dogs with HRI presented to primary care veterinary practices during 2016-2018.