Ronald

No abstract text is available yet for this article.

Not all young children attend nurseries, childminders or other group settings before they start school, but many do. It is common for countries to set out a framework to guide practice for early years providers (such as nurseries) to follow. The conundrum regarding these frameworks for young children is that proving evidence of a causal link between early environments and later outcomes is very challenging scientifically. So how do governments choose what learning and development practices and goals to make mandatory for childcare providers? And is it realistic to expect early years providers to meet the legal requirements that these frameworks impose? We do not know which learning and development practices impact positively on later outcomes, and we certainly do not know if there is a one-size-fits-all approach for an early years framework that is guaranteed to work...

Former United States President Ronald Reagan's use of media and his charismatic connection with viewers earned him the moniker "the great communicator". One aspect of his charisma, the influence of elicited laughter, during a highly critical 5-minute news story by CBS reporter Leslie Stahl during the 1984 US presidential election is examined here. Two experiments examining the effects of audience laughter on perceptions of charismatic leadership are reported. In the first experiment the effects of audience laughter in response to Reagan's comments were investigated...

BACKGROUND: Hyperglycaemia influences the development of glomerular endothelial cell damage and nowhere is this more evident than in the progression of diabetic kidney disease (DKD). While the Set7 lysine methyltransferase is a known hyperglycaemic sensor, its role in endothelial cell function in the context of DKD remains poorly understood. METHODS: Single-cell transcriptomics was used to investigate Set7 regulation in a mouse model of DKD, followed by validation of findings using pharmacological and shRNA inhibition of Set7...

Small molecule photoswitches capable of toggling between two distinct molecular states in response to light are versatile tools to monitor biological processes, control photochemistry, and design smart materials. In this work, six novel dicyanorhodanine-based pyrrole-containing photoswitches are reported. The molecular design avails both the Z and E isomers from synthesis, where each can be isolated using chromatographic techniques. Inter- and intramolecular hydrogen bonding (H-bonding) interactions available to the E and Z isomers, respectively, uniquely impart thermal stability to each isomer over long time periods...

Electrophilic small molecules with novel reactivity are powerful tools that enable activity-based protein profiling and covalent inhibitor discovery. Here, we report a reactive heterocyclic scaffold, 4-chloro-pyrazolopyridine (CPzP) for selective modification of proteins via a nucleophilic aromatic substitution (SN Ar) mechanism. Chemoproteomic profiling reveals that CPzPs engage cysteines within functionally diverse protein sites including ribosomal protein S5 (RPS5), inosine monophosphate dehydrogenase 2 (IMPDH2), and heat shock protein 60 (HSP60)...

Plants use light as a resource and signal. Photons within the 400-700 nm waveband are considered photosynthetically active. Far-red photons (FR, 700-800 nm) are used by plants to detect nearby vegetation and elicit the shade avoidance syndrome. In addition, FR photons have also been shown to contribute to photosynthesis, but knowledge about these dual effects remains scarce. Here, we study shoot-architectural and photosynthetic responses to supplemental FR light during the photoperiod in several rice varieties...

Human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorder (HAND) affects up to half of people living with HIV-1 and causes long term neurological consequences. The pathophysiology of HIV-1-induced glial and neuronal functional deficits in humans remains enigmatic. To bridge this gap, we established a model simulating HIV-1 infection in the central nervous system using human induced pluripotent stem cell (iPSC)-derived microglia combined with sliced neocortical organoids. Incubation of microglia with two replication-competent macrophage-tropic HIV-1 strains (JRFL and YU2) elicited productive infection and inflammatory activation...

DNA sequencing of tumour tissue has become the standard care for many solid cancers because of the option to detect somatic variants that have significant therapeutic, diagnostic and prognostic implications. Variants found within the tumour may be either somatic or germline in origin. Somatic cancer gene panels are developed to detect acquired (somatic) variants that are relevant for therapeutic or molecular characterisation of the tumour, expanding gene panels now include genes which may also inform patient management such as cancer predisposition syndromes (CPS) genes...

INTRODUCTION: The use of ChatGPT (Generative Pretrained Transformer), which is a natural language artificial intelligence model, has gained unparalleled attention with the accumulation of over 100 million users within months of launching. As such, we aimed to compare: 1) orthopaedic surgeons' evaluation of the appropriateness of the answers to the most frequently asked patient questions after total hip arthroplasty (THA); and 2) patients' evaluation of ChatGPT and arthroplasty-trained nurses responses to answer their postoperative questions...

Despite self-congratulatory rhetoric, Canada compromised COVID-19 vaccine equity with policies impeding a proposed global waiver of vaccine intellectual property (IP) rules. To learn from Canada's vaccine nationalism we explore the worldview - a coherent textual picture of the world - in a sample of Government of Canada communications regarding global COVID-19 vaccine sharing. Analysed documents portray risks and disparities as unrelated to the dynamics and power relations of the Canadian and international economies...

BACKGROUND AND PURPOSE: With the growing interest for physical therapists to incorporate musculoskeletal (MSK) ultrasound comes a need to understand how to organize training to promote the transfer of training to clinical practice. A common training strategy blends asynchronous learning through online modules and virtual simulations with synchronous practice on live simulated participants. However, few physical therapists who attend MSK ultrasound continuing education courses integrate ultrasound into clinical practice...

INTRODUCTION: Given the growing emphasis on patient outcomes, including postoperative complications, in total joint arthroplasty (TJA), investigating the rise of outpatient arthroplasty is warranted. Concerns exist over the safety of discharging patients home on the same day due to increased readmission and complication rates. However, psychological benefits and lower costs provide an incentive for outpatient arthroplasty. The influence of social determinants of health disparities on outpatient arthroplasty remains unexplored...

Despite the importance of sleep to overall health and well-being, there is a high prevalence of undiagnosed sleep disorders and adverse sleep health, particularly among vulnerable populations. Such vulnerable populations include people experiencing homelessness (PEH), refugees, and incarcerated individuals. In this narrative review, we provide an overview of the literature on sleep health and disorders among key and vulnerable populations (e.g., PEH, refugees, and incarcerated individuals). The limited research among these populations indicated a high prevalence of sleep disorders, mainly insomnia, short sleep duration, and fatigue...

No abstract text is available yet for this article.

Prasinezumab, a monoclonal antibody that binds aggregated α-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III)...

T4 polynucleotide kinase (T4 PNK) phosphorylates the 5'-terminus of DNA and RNA substrates. It is widely used in molecular biology. Single nucleotides can serve as substrates if a 3'-phosphate group is present. In this study, the T4 PNK-catalyzed conversion of adenosine 3'-monophosphate (3'-AMP) to adenosine-3',5'-bisphosphate was characterized using isothermal titration calorimetry (ITC). Although ITC is typically used to study ligand binding, in this case the instrument was used to evaluate enzyme kinetics by monitoring the heat production due to reaction enthalpy...

OBJECTIVES: The aim of the Early-Stage LUNG cancer (ESLUNG) study was to compare outcomes after minimally invasive lobectomy (MIL) and stereotactic ablative radiotherapy (SABR) in patients with stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: In this retrospective cohort study, patients with clinical stage I NSCLC (according to TNM7), treated in 2014-2016 with MIL or SABR, were included. 5-year overall survival (OS) and recurrence-free survival (RFS) were calculated and compared between patients treated with MIL and a propensity score (PS)-weighted SABR population with characteristics comparable to those of the MIL group...

IMPORTANCE: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement. OBJECTIVES: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy...

BACKGROUND: Primary aldosteronism (PA) is caused by autonomous aldosterone overproduction and characterised by uncontrolled hypertension. There are currently no treatments that target aldosterone synthesis. We evaluated the safety and efficacy of a novel aldosterone synthase inhibitor, dexfadrostat phosphate, in patients with PA. METHODS: This multi-centre, randomised, phase 2 trial was conducted between November 2019 and May 2022 (NCT04007406; EudraCT code 2019-000919-85)...