Alterations in cardiac function correlate with a disruption in fatty acid metabolism in a mouse model of SMA.

Spinal Muscular Atrophy is an autosomal dominant disease caused by mutations and deletions within the SMN1 gene, with predominantly childhood onset. Although primarily a motor neuron disease, defects in non-neuronal tissues are described in both patients and mouse models. Here, we have undertaken a detailed study of the heart in the Smn2B/- mouse models of SMA, and reveal a thinning of the ventriclar walls as previously described in more severe mouse models of SMA.

Effects of Altered Haptic Feedback Gain Upon Balance Are Explained by Sensory Conflict Estimation.

Lightly touching a solid object reduces postural sway. Here, we determine the effect of artificially modifying haptic feedback for balance. Participants stood with their eyes closed, lightly gripping a manipulandum that moved synchronously with body sway to systematically enhance or attenuate feedback gain between +2 and -2, corresponding to motion in the same or opposite direction to the body, respectively.

Contagious Crying Revisited: A Cross-Cultural Investigation Into Infant Emotion Contagion Using Infrared Thermal Imaging.

Contagious crying in infants has been considered an early marker of their sensitivity to others' emotions, a form of emotional contagion, and an early basis for empathy. However, it remains unclear whether infant distress in response to peer distress is due to the emotional content of crying or acoustically aversive properties of crying. Additionally, research remains severely biased towards samples from Europe and North America.

SenPred: a single-cell RNA sequencing-based machine learning pipeline to classify deeply senescent dermal fibroblast cells for the detection of an in vivo senescent cell burden.

Background: Senescence classification is an acknowledged challenge within the field, as markers are cell-type and context dependent. Currently, multiple morphological and immunofluorescence markers are required. However, emerging scRNA-seq datasets have enabled an increased understanding of senescent cell heterogeneity.

Eating disorders in minority ethnic populations in Australia, Canada, Aotearoa New Zealand and the UK: a scoping review.

Background: Historically, eating disorder (ED) research has largely focused on White girls and women, with minority ethnic populations underrepresented. Most research exploring EDs in minority ethnic populations has been conducted in the United States (US). The aim of this scoping review, the first of its kind, was to systematically examine research on disordered eating and EDs among minority ethnic populations in Australia, Canada, Aotearoa New Zealand and the United Kingdom (UK), four countries with shared sociocultural and healthcare characteristics.

Evaluation of a biomarker for amyotrophic lateral sclerosis derived from a hypomethylated DNA signature of human motor neurons.

Amyotrophic lateral sclerosis (ALS) lacks a specific biomarker, but is defined by relatively selective toxicity to motor neurons (MN). As others have highlighted, this offers an opportunity to develop a sensitive and specific biomarker based on detection of DNA released from dying MN within accessible biofluids. Here we have performed whole genome bisulfite sequencing (WGBS) of iPSC-derived MN from neurologically normal individuals.

The value-for-money assessment and funding arrangements for high-priced drugs in an era of uncertainty: a comparative analysis of national health technology assessment agencies in South Korea, England, Australia, and Canada.

Background: Innovative health technologies have increasingly emerged as a promising solution for patients with untreatable or challenging conditions. However, these technologies often come with expensive costs and limited evidence at the time of launch. This study assessed how these high-priced drugs with limited evidence were appraised and introduced in South Korea, England, Australia, and Canada, where cost-effectiveness analysis (CEA) generally plays a central role in pricing and reimbursement decisions.

Exploring the barriers to cervical screening and perspectives on new self-sampling methods amongst under-served groups.

Background: Cervical screening rates have fallen in recent years in the UK, representing a health inequity for some under-served groups. Self-sampling alternatives to cervical screening may be useful where certain barriers prohibit access to routine cervical screening. However, there is limited evidence on whether self-sampling methods address known barriers to cervical screening and subsequently increase uptake amongst under-screened groups.

Service delivery and the role of clinical pharmacists in UK primary care for older people, including people with dementia: a scoping review.

Objective: As populations age globally, there is increasing prevalence of multiple long-term conditions, such as dementia, leading to many challenges. The burden on health and care services, economic pressures, and the necessity for innovative policies to better support older people and people with dementia becomes paramount. This review explores how clinical pharmacists working in UK primary care support older people and people with dementia.

Don't assume, ask! A focus group study on end-of-life care planning with people with intellectual disabilities from minoritised ethnic groups.

Background: People with intellectual disabilities are less likely to have access to palliative care, and the evidence shows that their deaths are often unanticipated, unplanned for, and poorly managed. Within the general population, people from minoritised ethnic groups are under-represented within palliative care services. End-of-life care planning with people with intellectual disabilities from minoritised ethnic groups may be a way to address these issues.

Enantioselective OTUD7B fragment discovery through chemoproteomics screening and high-throughput optimisation.

Deubiquitinating enzymes (DUBs) are key regulators of cellular homoeostasis, and their dysregulation is associated with several human diseases. The ovarian tumour protease (OTU) family of DUBs are biochemically well-characterised and of therapeutic interest, yet only a few tool compounds exist to study their cellular function and therapeutic potential. Here we present a chemoproteomics fragment screening platform for identifying novel DUB-specific hit matter, that combines activity-based protein profiling with high-throughput chemistry direct-to-biology optimisation to enable rapid elaboration of initial fragment hits against OTU DUBs.

Multi-omics architecture of childhood obesity and metabolic dysfunction uncovers biological pathways and prenatal determinants.

Childhood obesity poses a significant public health challenge, yet the molecular intricacies underlying its pathobiology remain elusive. Leveraging extensive multi-omics profiling (methylome, miRNome, transcriptome, proteins and metabolites) and a rich phenotypic characterization across two parts of Europe within the population-based Human Early Life Exposome project, we unravel the molecular landscape of childhood obesity and associated metabolic dysfunction. Our integrative analysis uncovers three clusters of children defined by specific multi-omics profiles, one of which characterized not only by higher adiposity but also by a high degree of metabolic complications.

GGCX promotes Eurasian avian-like H1N1 swine influenza virus adaption to interspecies receptor binding.

The Eurasian avian-like (EA) H1N1 swine influenza virus (SIV) possesses the capacity to instigate the next influenza pandemic, owing to its heightened affinity for the human-type α-2,6 sialic acid (SA) receptor. Nevertheless, the molecular mechanisms underlying the switch in receptor binding preferences of EA H1N1 SIV remain elusive. In this study, we conduct a comprehensive genome-wide CRISPR/Cas9 knockout screen utilizing EA H1N1 SIV in porcine kidney cells.

'Obviously, because it's a tear it won't necessarily mend itself': a qualitative study of patient experiences and expectations of treatment for a meniscal tear.

Objectives: There is a paucity of qualitative research exploring the patient experience of living with a meniscal tear, vital to effective patient management. The aim of this study was to explore the experiences and expectations of treatment of patients aged 18-55 years with a meniscal tear of the knee.

Design: Qualitative study involving semistructured interviews.

RNA splicing: a split consensus reveals two major 5' splice site classes.

The established consensus sequence for human 5' splice sites masks the presence of two major splice site classes defined by preferential base-pairing potentials with either U5 snRNA loop 1 or the U6 snRNA ACAGA box. The two 5' splice site classes are separable in genome sequences, sensitized by specific genotypes and associated with splicing complexity. The two classes reflect the commitment to 5' splice site usage occurring primarily during 5' splice site transfer to U6 snRNA.

Awakening not associated with an increased rate of cortisol secretion.

Cortisol is released upon activation of the hypothalamic-pituitary-adrenal axis, varies across the day, possesses an underlying diurnal rhythm and is responsive to stressors. The endogenous circadian peak of cortisol occurs in the morning, and increases in cortisol observed post-awakening have been named the cortisol awakening response (CAR) based on the belief that the act of waking up stimulates cortisol secretion. However, objective evidence that awakening induces cortisol secretion is limited.

Effects of 24-Hour Diet- or Exercise-Induced Energy Availability Manipulations on Substrate Utilization and Performance.

Purpose: To examine sex-based differences in substrate oxidation, postprandial metabolism, and performance in response to 24-hour manipulations in energy availability (EA), induced by manipulations to energy intake (EI) or exercise energy expenditure (EEE).

Methods: In a Latin Square design, 20 endurance athletes (10 females using monophasic oral contraceptives and 10 males) undertook five trials, each comprising three consecutive days. Day one was a standardized period of high EA; EA was then manipulated on day two; post-intervention testing occurred on day three.

Predictors of inter-individual variation in nausea and vomiting in pregnancy in two samples of women attending a pregnancy clinic.

Problem: The aetiology of nausea and vomiting in pregnancy is still not well understood.

Background: Previous research suggests that its incidence and severity are influenced by many different factors, including demographic, lifestyle and psychosocial factors.

Aim: This study aimed to test the effect of multiple factors (use of combined oral contraception (COC) on meeting the father, sex of the foetus, age when pregnant, parity, education, life standard/income, smoking before pregnancy and BMI) on levels of nausea and vomiting in pregnancy.

The current clinical practice and experiences in buccal midazolam prescribing in community for status epilepticus termination in the United Kingdom: The Rescue Epilepsy Medication and Training (REMIT) study.

Background: Epilepsy is one of the commonest neurological conditions worldwide and confers a significant mortality risk, partly driven by status epilepticus (SE). Terminating SE is the goal of pharmaceutical rescue therapies. This survey evaluates UK-based healthcare professionals' clinical practice and experience in community-based rescue therapy prescribing.

Graded porous scaffold mediates internal fluidic environment for 3D in vitro mechanobiology.

Most cell types are mechanosensitive, their activities such as differentiation, proliferation and apoptosis, can be influenced by the mechanical environment through mechanical stimulation. In three dimensional (3D) mechanobiological in vitro studies, the porous structure of scaffold controls the local mechanical environment that applied to cells. Many previous studies have focused on the topological design of homogeneous scaffold struts.

Buried or exposed kirschner wires in paediatric upper extremity fracture fixation: A systematic review and meta-analysis of infection rates and complications.

Background: Paediatric upper limb fractures are commonly treated with Kirschner (K) wire fixation, which can be buried or left exposed. Although both techniques are widely used, controversy remains regarding infection risk, complications, and other clinical outcomes between buried and exposed K-wires. This systematic review and meta-analysis aimed to compare infection rates and secondary outcomes between buried and exposed K-wires in paediatric upper limb fractures located distal to and including the elbow, and proximal to the carpus.