WNT7A-positive dendritic cytonemes control synaptogenesis in cortical neurons.

Synaptogenesis involves the transformation of dendritic filopodial contacts into stable connections with the exact apposition of synaptic components. Signalling triggered by Wnt/β-catenin and calcium has been postulated to aid this process. However, it is unclear how such a signalling process orchestrates synapse formation to organise the spatial arrangement of synapses along dendrites.

Changepoint detection on daily home activity pattern: a sliced Poisson process method.

The problem of health and care of people is being revolutionized. An important component of that revolution is disease prevention and health improvement from home. A natural approach to the health problem is monitoring changes in people's behavior or activities.

Oral cavity squamous cell carcinomas in zoo-managed Goeldi's monkeys (Callimico goeldii).

Background: Oral cavity squamous cell carcinomas (OCSCCs) are relatively common in multiple non-human primate species but are poorly documented in Goeldi's monkeys.

Methods: Four Goeldi's monkeys with OCSCC, from three zoological collections, underwent necropsy with cytology, histopathology, immunohistochemistry, and pan-herpesvirus PCR analysis.

Results: All animals were euthanised and exhibited poor-to-emaciated body condition.

Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease.

Introduction: The goal of this study is to explore the pharmacological potential of the amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)-associated kinases (ROCK) inhibitor, in the P301S tau transgenic mouse model (Line PS19) of neurodegenerative tauopathy and Alzheimer's disease (AD).

Methods: We used LC-MS/MS, ELISA and bioinformatic approaches to investigate the effect of treatment with fasudil on the brain proteomic profile in PS19 tau transgenic mice. We also explored the efficacy of fasudil in reducing tau phosphorylation, and the potential beneficial and/or toxic effects of its administration in mice.

Reduction of Phosphorylated Tau in Alzheimer's Disease Induced Pluripotent Stem Cell-Derived Neuro-Spheroids by Rho-Associated Coiled-Coil Kinase Inhibitor Fasudil.

Background: Alzheimer's disease (AD) is the most predominant form of dementia. Rho-associated coiled coil kinase (ROCK) inhibitor, fasudil, is one of the candidate drugs against the AD progression.

Objective: We aimed to investigate possible changes of AD associated markers in three-dimensional neuro-spheroids (3D neuro-spheroids) generated from induced pluripotent stem cells derived from AD patients or healthy control subjects (HC) and to determine the impact of pharmacological intervention with the ROCK inhibitor fasudil.

Masking the transmembrane region of the amyloid β precursor protein as a safe means to lower amyloid β production.

Introduction: Reducing brain levels of both soluble and insoluble forms of amyloid beta (Aβ) remains the primary goal of most therapies that target Alzheimer's disease (AD). However, no treatment has so far resulted in patient benefit, and clinical trials of the most promising drug candidates have generally failed due to significant adverse effects. This highlights the need for safer and more selective ways to target and modulate Aβ biogenesis.

Sleep Deficiency and Cardiometabolic Disease.

Epidemiologic studies have demonstrated that short sleep duration is associated with an increased risk of cardio-metabolic health outcomes including cardiovascular disease mortality, coronary heart disease, type 2 diabetes mellitus, hypertension, and metabolic syndrome. Experimental sleep restriction studies have sought to explain these findings. This review describes the main evidence of these associations and possible mechanisms explaining them.

Neurodegenerative Disease Associated Pathways in the Brains of Triple Transgenic Alzheimer's Model Mice Are Reversed Following Two Weeks of Peripheral Administration of Fasudil.

The pan Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor fasudil acts as a vasodilator and has been used as a medication for post-cerebral stroke for the past 29 years in Japan and China. More recently, based on the involvement of ROCK inhibition in synaptic function, neuronal survival, and processes associated with neuroinflammation, it has been suggested that the drug may be repurposed for neurodegenerative diseases. Indeed, fasudil has demonstrated preclinical efficacy in many neurodegenerative disease models.

Delay in loop ileostomy reversal surgery does not impact upon post-operative clinical outcomes. Complications are associated with an increased loss of microflora in the defunctioned intestine.

Loop ileostomy is a common surgical procedure to allow downstream tissue healing, with the aim of re-joining the bowel approximately 12 months later. The reversal procedure is associated with a substantial morbidity up to 40%. Our previous research demonstrated that defunctioned ileum becomes atrophied, with extensive microbial dysbiosis.

The Health Effects of 72 Hours of Simulated Wind Turbine Infrasound: A Double-Blind Randomized Crossover Study in Noise-Sensitive, Healthy Adults.

Background: Large electricity-generating wind turbines emit both audible sound and inaudible infrasound at very low frequencies that are outside of the normal human range of hearing. Sufferers of wind turbine syndrome (WTS) have attributed their ill-health and particularly their sleep disturbance to the signature pattern of infrasound. Critics have argued that these symptoms are psychological in origin and are attributable to nocebo effects.

Comparing the Efficacy of a New Clinical Skills Model with a Traditional Method to Teach Tube Feeding of an Avian Patient.

Interactive clinical skills models have been demonstrated to be useful for teaching medical and veterinary clinical skills, yet to date, very few exist for teaching skills relevant to zoological companion animals and wildlife species including birds. This two-part study aimed to create, develop, and validate a model. Interviews and a survey were conducted using veterinary and wildlife professionals to select an avian clinical skill that is challenging and performed frequently.

NRF2: An emerging role in neural stem cell regulation and neurogenesis.

The birth of new neurons from neural stem cells (NSC)s during developmental and adult neurogenesis arises from a myriad of highly complex signalling cascades. Emerging as one of these is the nuclear factor erythroid 2-related factor (NRF2)-signaling pathway. Regulation by NRF2 is reported to span the neurogenic process from early neural lineage specification and NSC regulation to neuronal fate commitment and differentiation.

There is no dose-response relationship between the amount of exercise and improvement in HbA1c in interventions over 12 weeks in patients with type 2 diabetes: a meta-analysis and meta-regression.

Aims: Aerobic exercise is well recognised as an effective treatment for people with type 2 diabetes but the optimal amount of aerobic exercise to improve glycaemic control remains to be determined. Thus, the aim of this meta-analysis and meta-regression was to assess the impact of volume and intensity of aerobic exercise on glycaemic control.

Methods: Medline, Cochrane, Embase, and Web of Science databases were searched up until 15 December 2020 for the terms "aerobic exercise AND glycaemic control", "type 2 diabetes AND exercise", and "exercise AND glycaemic control AND Type 2 diabetes AND randomised control trial".

Modeling and forecasting of at home activity in older adults using passive sensor technology.

Life expectancy in the UK has increased since the 19th century. As of 2019, there are just under 12 million people in the UK aged 65 or over, with close to a quarter living by themselves. Thus, many families and carers are looking for new ways to improve the health and care of older people.

Sleep Deficiency and Cardiometabolic Disease.

Epidemiologic studies have demonstrated that short sleep duration is associated with an increased risk of cardio-metabolic health outcomes including cardiovascular disease mortality, coronary heart disease, type 2 diabetes mellitus, hypertension, and metabolic syndrome. Experimental sleep restriction studies have sought to explain these findings. This review describes the main evidence of these associations and possible mechanisms explaining them.

Development and validation of a model for diagnosis of obstructive sleep apnoea in primary care.

Background And Objective: Use of in-laboratory polysomnography (PSG) to diagnose obstructive sleep apnoea (OSA) is cost and resource intensive. Questionnaires, physical measurements and home monitors have been studied as potential simpler alternatives. This study aimed to develop a diagnostic model for OSA for use in primary care.

Infants Oscillatory Frequencies change during Free-Play.

Social interactions are known to be an essential component of infant development. For this reason, exploring functional neural activity while infants are engaged in social interactions will enable a better understanding of the infant social brain. This in turn, will enable the beginning of disentangling the neural basis of social and non-social interactions as well as the influence that maternal engagement has on infant brain function.

In vivo multi-parametric manganese-enhanced MRI for detecting amyloid plaques in rodent models of Alzheimer's disease.

Amyloid plaques are a hallmark of Alzheimer's disease (AD) that develop in its earliest stages. Thus, non-invasive detection of these plaques would be invaluable for diagnosis and the development and monitoring of treatments, but this remains a challenge due to their small size. Here, we investigated the utility of manganese-enhanced MRI (MEMRI) for visualizing plaques in transgenic rodent models of AD across two species: 5xFAD mice and TgF344-AD rats.

Is there seasonal variation in gallstone related admissions in England?

Background: Gallstone related pathology (GRP) accounts for a significant proportion of general surgery admissions. The aim of this study is to investigate if seasonal variation for GRP admissions exist in England allowing improved resource allocation and planning.

Methods: This multicentre retrospective cohort study included only emergency adult (≥18 years old) admissions to acute secondary care with ICD-10 codes associated with gallstones between 01/01/2010 to 31/12/2019 in England using Hospital Episode Statistics data.

The Impact of Device Modifications and Pressure Delivery on Adherence.

This article reviews the evidence to date examining whether adherence to positive airway pressure (PAP) therapy is affected by any device modifications to pressure delivery. To date there is no robust evidence from systematic reviews and meta-analyses indicating that any modification to standard fixed-pressure PAP makes a clinically significant difference to patient adherence to therapy. The main modifications are reviewed in this article and whether improving pressure could drive adherence, in turn improving patient outcomes, is discussed.

EARLY-ONSET LEUKOENCEPHALOMYELOPATHY AND POLYNEUROPATHY IN EASTERN QUOLLS () IN THE EUROPEAN CAPTIVE POPULATION.

Leukoencephalomyelopathy (LEM) is suggested to be an age-related degenerative condition in geriatric Eastern quolls (), manifesting in animals greater than 3.5 yr of age. This case series describes four LEM cases from two zoologic collections; three in nongeriatric animals, with one only 1 yr of age, and details advanced diagnostic investigation, including magnetic resonance imaging, cerebrospinal fluid analysis, and electrodiagnostic studies, not previously reported in Eastern quolls.

Transcription-based drug repurposing for COVID-19.

We have utilised the transcriptional response of lung epithelial cells following infection by the original Severe Acute Respiratory Syndrome coronavirus (SARS) to identify repurposable drugs for COVID-19. Drugs best able to recapitulate the infection profile are highly enriched for antiviral activity. Nine of these have been tested against SARS-2 and found to potently antagonise SARS-2 infection/replication, with a number now being considered for clinical trials.