Living Dual Heat- and pH-Responsive Textiles.

Smart textiles that integrate multiple environmental sensing capabilities are an emerging frontier in wearable technology. In this study, we developed dual pH- and temperature-responsive textiles by combining engineered bacterial systems with bacterially derived proteins. For temperature sensing, we characterized the properties of a heat sensitive promoter, P, in () using enhanced green fluorescent protein as a reporter.

'Let's work together to pass medical school': a qualitative study of medical student attitudes to teamwork, competition and collaboration.

Teamwork is vital to all types of work, and graduates of higher education programmes must be prepared to contribute to a wide variety of professional teams. This is especially true in healthcare, where graduates will work in multidisciplinary teams (MDTs) under considerable pressure. This study is a follow-up to a previous study, where we described how competition between students is a barrier to constructive teamwork.

Assessment of right ventricular function in healthy Great Danes and in Great Danes with dilated cardiomyopathy.

Introduction: Right ventricular (RV) dysfunction is a significant negative prognostic indicator in human dilated cardiomyopathy (DCM). Many RV indices are weight-dependent, and there is a lack of reference values for the right heart in giant breed dogs (over 50 kg), including Great Danes (GDs). This study aimed to compare indices of RV function in echocardiographically normal GDs, those with preclinical DCM (PC-DCM), and those with DCM and congestive heart failure (DCM-CHF).

Discovery of SQSTM1/p62-dependent P-bodies that regulate the NLRP3 inflammasome.

Autophagy and ribonucleoprotein granules, such as P-bodies (PBs) and stress granules, represent vital stress responses to maintain cellular homeostasis. SQSTM1/p62 phase-separated droplets are known to play critical roles in selective autophagy; however, it is unknown whether p62 can exist as another form in addition to its autophagic droplets. Here, we found that, under stress conditions, including proteotoxicity, endotoxicity, and oxidation, autophagic p62 droplets are transformed to a type of enlarged PBs, termed p62-dependent P-bodies (pd-PBs).

Florbetapir PET-assessed demyelination is associated with faster tau accumulation in an APOE ε4-dependent manner.

Purpose: The main objectives were to test whether (1) a decrease in myelin is associated with enhanced rate of fibrillar tau accumulation and cognitive decline in Alzheimer's disease, and (2) whether apolipoprotein E (APOE) ε4 genotype is associated with worse myelin decrease and thus tau accumulation.

Methods: To address our objectives, we repurposed florbetapir-PET as a marker of myelin in the white matter (WM) based on previous validation studies showing that beta-amyloid (Aβ) PET tracers bind to WM myelin. We assessed 43 Aβ-biomarker negative (Aβ-) cognitively normal participants and 108 Aβ+ participants within the AD spectrum with florbetapir-PET at baseline and longitudinal flortaucipir-PET as a measure of fibrillar tau (tau-PET) over ~ 2 years.

Immunogenicity of COVID-19 vaccines and their effect on HIV reservoir in older people with HIV.

Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. Our study on 68 PWH and 23 HIV-negative participants aged 55 and older post-three vaccine doses showed equally strong anti-spike IgG responses in serum and saliva through week 48 from baseline, while PWH salivary IgA responses were low. PWH had diminished live-virus neutralization responses after two vaccine doses, which were 'rescued' post-booster.

Immunogenicity of COVID-19 vaccines and their effect on the HIV reservoir in older people with HIV.

Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. We followed 68 PWH aged 55 and older and 23 age-matched HIV-negative individuals for 48 weeks from the first vaccine dose, after the total of three doses. All PWH were on antiretroviral therapy (cART) and had different immune status, including immune responders (IR), immune non-responders (INR), and PWH with low-level viremia (LLV).

Long-term outcome and troponin I concentrations in Great Danes screened for dilated cardiomyopathy: an observational retrospective epidemiological study.

Introduction: Dilated cardiomyopathy (DCM) is common in Great Danes (GDs) but screening for this condition can be challenging. We hypothesised that cardiac troponin-I (cTnI) concentration is elevated in GDs with DCM and/or ventricular arrhythmias (VAs), and is associated with reduced survival time in GDs.

Animals: One hundred and twenty-four client-owned GDs assigned echocardiographically as normal (n = 53), equivocal (n = 37), preclinical DCM (n = 21), or clinical DCM (n = 13).

Discovery of STRO-002, a Novel Homogeneous ADC Targeting Folate Receptor Alpha, for the Treatment of Ovarian and Endometrial Cancers.

STRO-002 is a novel homogeneous folate receptor alpha (FolRα) targeting antibody-drug conjugate (ADC) currently being investigated in the clinic as a treatment for ovarian and endometrial cancers. Here, we describe the discovery, optimization, and antitumor properties of STRO-002. STRO-002 was generated by conjugation of a novel cleavable 3-aminophenyl hemiasterlin linker-warhead (SC239) to the nonnatural amino acid para-azidomethyl-L-phenylalanine incorporated at specific positions within a high affinity anti-FolRα antibody using Sutro's XpressCF+, which resulted in a homogeneous ADC with a drug-antibody ratio (DAR) of 4.

Uncovering undernutrition in chronic obstructive pulmonary disease: Beyond body mass index.

Background: Undernutrition, a common but treatable complication of chronic obstructive pulmonary disease (COPD), contributes to poor outcomes but is under-detected. Improved detection could prompt dietary intervention which may improve outcomes. We investigated whether adding a measure of muscle mass (fat-free mass index, FFMI) or a malnutrition screening tool (Mini Nutritional Assessment, MNA®) to the commonly used measure of body mass index (BMI), helps detect undernutrition in COPD.

Hemocytes are essential for Drosophila melanogaster post-embryonic development, independent of control of the microbiota.

Proven roles for hemocytes (blood cells) have expanded beyond the control of infections in Drosophila. Despite this, the crucial role of hemocytes in post-embryonic development has long thought to be limited to control of microorganisms during metamorphosis. This has previously been shown by rescue of adult development in hemocyte-ablation models under germ-free conditions.

HIV envelope antibodies and TLR7 agonist partially prevent viral rebound in chronically SHIV-infected monkeys.

A key challenge for the development of a cure to HIV-1 infection is the persistent viral reservoir established during early infection. Previous studies using Toll-like receptor 7 (TLR7) agonists and broadly neutralizing antibodies (bNAbs) have shown delay or prevention of viral rebound following antiretroviral therapy (ART) discontinuation in simian-human immunodeficiency virus (SHIV)-infected rhesus macaques. In these prior studies, ART was initiated early during acute infection, which limited the size and diversity of the viral reservoir.

Differential effects of modafinil on performance of low-performing and high-performing individuals during total sleep deprivation.

Background: Individual responses to the effects of inadequate sleep have been well documented; some people are more vulnerable to the effects of sleep loss than others. Fatigue-vulnerable individuals generally require access to effective fatigue countermeasures; however, the question arises as to whether these fatigue-vulnerable individuals receive the same benefits shown in group efficacy data. The present study administered modafinil to individuals to determine its differential effects on performance of best and worst performers during sleep deprivation.

The Witness-Aimed First Account (WAFA): A new technique for interviewing autistic witnesses and victims.

Autistic people may be more likely to be interviewed by police as a victim/witness, yet they experience social communication difficulties alongside specific memory difficulties that can impact their ability to recall information from memory. Police interviewing techniques do not take account of these differences, and so are often ineffective. We developed a new technique for interviewing autistic witnesses, referred to a Witness-Aimed First Account, which was designed to better support differences in the way that autistic witnesses process information in memory.

Gut and Whole-Body Microbiota of the Honey Bee Separate Thriving and Non-thriving Hives.

The recent worldwide decline of honey bee colonies is a major ecological problem which also threatens pollinated crop production. Several interacting stressors such as environmental pressures and pathogens are suspected. Recently, the gut microbiota has emerged as a critical factor affecting bee health and fitness.

Assessment of left ventricular function in healthy Great Danes and in Great Danes with dilated cardiomyopathy using speckle tracking echocardiography.

Objectives: Assess global circumferential and radial systolic and diastolic myocardial function with speckle tracking echocardiography (STE) in healthy Great Danes (GD) and in GD diagnosed with dilated cardiomyopathy (DCM).

Animals: Eighty-nine GD were included in the study: 39 healthy (normal group [NORMg]) and 50 diagnosed with DCM (DCMg).

Methods: This was a retrospective study.

RF1 attenuation enables efficient non-natural amino acid incorporation for production of homogeneous antibody drug conjugates.

Amber codon suppression for the insertion of non-natural amino acids (nnAAs) is limited by competition with release factor 1 (RF1). Here we describe the genome engineering of a RF1 mutant strain that enhances suppression efficiency during cell-free protein synthesis, without significantly impacting cell growth during biomass production. Specifically, an out membrane protease (OmpT) cleavage site was engineered into the switch loop of RF1, which enables its conditional inactivation during cell lysis.

Multivariate analysis of Scotch whisky by total reflection x-ray fluorescence and chemometric methods: A potential tool in the identification of counterfeits.

Most methods used in the identification of counterfeit whisky have focused on the profiling of volatile organic congeners determined by gas chromatography. We tested the use of total reflection x-ray fluorescence (TXRF) for trace element analysis of whisky and application of the data as a potential tool in the identification of counterfeit samples. Twenty five whiskies that were produced in different regions of Scotland or were blends, 5 counterfeit whiskies, 1 unmatured grain whisky, and 1 matured grain whisky were analysed for 11 elements (P, S, Cl, K, Ca, Mn, Fe, Cu, Zn, Br and Rb).

Cytological diagnosis of cardiac masses with ultrasound guided fine needle aspirates.

Background: Cardiac masses are uncommon in the canine population. When present, an attempt should be made to obtain a definitive diagnosis. Our goal with this case series was to report that as long as anatomic location permits, obtaining fine needle aspirates (FNAs) for cytological evaluation is practical, safe, and may provide a definitive diagnosis.

Beyond the grave: When is cell death critical for immunity to infection?

Immune cell death is often observed in response to infection. There are three potential beneficial outcomes after host cell death: (1) the removal of an intracellular niche for microbes, (2) direct microbicidal activity of released components and (3) the propagation of an inflammatory response. Recent findings suggest that three forms of non-apoptotic regulated cell death, pyroptosis, necroptosis and NETosis, can impact on immunity to bacterial infection.

Pancreatic amylase is an environmental signal for regulation of biofilm formation and host interaction in Campylobacter jejuni.

Campylobacter jejuni is a commensal bacterium in the intestines of animals and birds and a major cause of food-borne gastroenteritis in humans worldwide. Here we show that exposure to pancreatic amylase leads to secretion of an α-dextran by C. jejuni and that a secreted protease, Cj0511, is required.

A pedigree-based genetic appraisal of Boxer ARVC and the role of the Striatin mutation.

The objective of this paper was to investigate by pedigree-based genetic means the origins and inheritance of arrhythmogenic right ventricular cardiomyopathy (ARVC) in UK Boxers and assess the role of the proposed causal mutation in the gene, Striatin (STRN). All ARVC cases traced back to a small number of imported American dogs deriving from the group of Boxers studied by Harpster (1983) to define the disease, strongly suggesting that the disease is the same in the two countries. Dogs with and without the STRN mutation were found in both ARVC affected and normal Boxers showing that the mutation is not responsible for the disease.

Echocardiographic predictors of survival in dogs with myxomatous mitral valve disease.

Objectives: To evaluate vena contracta and other echocardiographic measures of myxomatous mitral valve disease (MMVD) severity in a multivariable analysis of survival in dogs.

Animals: 70 dogs diagnosed with MMVD from stored echocardiographic images that met study inclusion criteria.

Methods: Left heart dimensions were measured as well as mitral regurgitant jet area/left atrial area (JAR), early mitral filling velocity (Evel), extent of mitral valve prolapse in right and left views (ProlR, ProlL), Prol indexed to aortic diameter (ProlR:Ao, ProlL:Ao), presence of a flail leaflet (FlailR, FlailL), and mitral regurgitation vena contracta diameter (VCR, VCL) indexed to aortic diameter (VCR:Ao, VCL:Ao).

Pseudaminic acid on Campylobacter jejuni flagella modulates dendritic cell IL-10 expression via Siglec-10 receptor: a novel flagellin-host interaction.

Introduction: Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide. At present the identity of host-pathogen interactions that promote successful bacterial colonisation remain ill defined. Herein, we aimed to investigate C.