Real-world clinical utility of Xpert MTB/RIF Ultra in the assessment of tuberculosis in a low-TB-incidence, high-resource setting.

Background: Tuberculosis (TB) diagnosis in the UK is impacted by delay and suboptimal culture-based microbiological confirmation rates due to the high prevalence of paucibacillary disease. We examine the real-world clinical utility of Xpert MTB/RIF Ultra (Xpert-Ultra) as a diagnostic test and biomarker of transmissible infection in a UK TB service.

Methods: Clinical specimens from suspected TB cases triple tested (smear microscopy, mycobacterial culture and Xpert-Ultra) at University Hospitals of Leicester NHS Trust (1 March 2018-28 February 2019) were retrospectively analysed.

Antiseizure properties of fenamate NSAIDs determined in mature human stem-cell derived neuroglial circuits.

Repeated and uncontrolled seizures in epilepsy result in brain cell loss and neural inflammation. Current anticonvulsants primarily target ion channels and receptors implicated in seizure activity. Identification of neurotherapeutics that can inhibit epileptiform activity and reduce inflammation in the brain may offer significant benefits in the long-term management of epilepsy.

Impact of a Neuropsychiatric Therapeutics Course and a Case-Based Course on Pharmacy Students' Mental Health Stigma.

Objective: Mental health education can reduce the stigma held by medical and nursing students; however, findings in this regard are limited in pharmacy academia. This study investigated the impact of a neuropsychiatric therapeutics course followed by a case-based course on the mental health stigma held by pharmacy students.

Methods: A survey was conducted of second-year pharmacy students (n = 202) on the first and last day of a neuropsychiatric therapeutics course and 4 months later, at the end of a case-based course.

Neuropharmacology of human TERA2.cl.SP12 stem cell-derived neurons in ultra-long-term culture for antiseizure drug discovery.

Modeling the complex and prolonged development of the mammalian central nervous system remains a profound challenge. Most studies of human stem cell derived neurons are conducted over days to weeks and may or may not include glia. Here we have utilized a single human pluripotent stem cell line, TERA2.

An Electrophysiological and Pharmacological Study of the Properties of Human iPSC-Derived Neurons for Drug Discovery.

Human stem cell-derived neurons are increasingly considered powerful models in drug discovery and disease modeling, despite limited characterization of their molecular properties. Here, we have conducted a detailed study of the properties of a commercial human induced Pluripotent Stem Cell (iPSC)-derived neuron line, iCell [GABA] neurons, maintained for up to 3 months in vitro. We confirmed that iCell neurons display neurite outgrowth within 24 h of plating and label for the pan-neuronal marker, βIII tubulin within the first week.

Clinical utility of a rapid 'on-demand' laboratory-based SARS-CoV-2 diagnostic testing service in an acute hospital setting admitting COVID-19 patients.

Background: With the onset of the COVID-19 pandemic in 2020, hospital clinical teams have realised that there is a need for a rapid, accurate testing facility that will allow them to move patients quickly into isolation rooms or specific COVID-19 cohort wards as soon as possible after admission.

Methods: Starting from July 2020, PCR-based test platforms, which could test 4-8 samples in parallel with turnaround (sample-to-result) times of 50-80 min, were placed in a satellite laboratory. This laboratory was on the same floor and within walking distance to the acute respiratory admissions ward.

Adolescent Substance Abuse, Transgenerational Consequences and Epigenetics.

Adolescence is the transitional period between childhood and adulthood and a critical period in brain development. Adolescence in humans is also associated with increased expression of risk-taking behaviors. Epidemiological and clinical studies, for example, show a surge of drug abuse and raise the hypothesis that the adolescent brain undergoes critical changes resulting in diminished control.

Immunopathogenesis of the feline atopic syndrome.

Background: Feline diseases of possible allergic origin with similar clinical phenotypes can have a varied underlying pathogenesis. Clinical phenotype, precise aetiology and underlying immunopathogenesis all need to be considered if advances in this neglected area of dermatology are to be made.

Objectives: To document the status of research into the immunopathogenesis of the diseases that fall within the spectrum of the feline atopic syndrome (FAS ), to summarize the conclusions, identify the limitations and recommend future research directions.

Feline allergic diseases: introduction and proposed nomenclature.

Background: Feline allergic diseases present as challenging problems for clinicians, not least because of the number of reaction patterns of the feline skin, none of which are specific for allergy. Furthermore, there is some controversy over the nomenclature that should be used in their description.

Objectives: To review the literature, assess the status of knowledge of the topic and the extent to which these diseases could be categorized as atopic in nature, and make recommendations concerning nomenclature.

Adolescent drug exposure: A review of evidence for the development of persistent changes in brain function.

Over the past decade, many studies have indicated that adolescence is a critical period of brain development and maturation. The refinement and maturation of the central nervous system over this prolonged period, however, makes the adolescent brain highly susceptible to perturbations from acute and chronic drug exposure. Here we review the preclinical literature addressing the long-term consequences of adolescent exposure to common recreational drugs and drugs-of-abuse.

Co-reactivity between related and unrelated environmental allergens in equine allergen-specific IgE serology testing in the UK.

Background: Identification of environmental allergens in horses with allergic disease facilitates allergen avoidance and targeted immunotherapy.

Hypothesis/objectives: To evaluate allergenic co-reactivity between 44 environmental allergens.

Animals: Horses with suspected allergic disease (n = 344) whose sera were submitted for environmental allergen testing.

Mechanisms Underlying Neuroprotection by the NSAID Mefenamic Acid in an Experimental Model of Stroke.

Stroke is a devastating neurological event with limited treatment opportunities. Recent advances in understanding the underlying pathogenesis of cerebral ischemia support the involvement of multiple biochemical pathways in the development of the ischemic damage. Fenamates are classical non-steroidal anti-inflammatory drugs but they are also highly subunit-selective modulators of GABA receptors, activators of I potassium channels and antagonists of non-selective cation channels and the NLRP3 inflammosome.

Implication of Major Adverse Postoperative Events and Myocardial Injury on Disability and Survival: A Planned Subanalysis of the ENIGMA-II Trial.

Background: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery.

Methods: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients.

Spray Drying as a Reliable Route to Produce Metastable Carbamazepine Form IV.

Carbamazepine (CBZ) is an active pharmaceutical ingredient used in the treatment of epilepsy that can form at least 5 polymorphic forms. Metastable form IV was originally discovered from crystallization with polymer additives; however, it has not been observed from subsequent solvent-only crystallization efforts. This work reports the reproducible formation of phase pure crystalline form IV by spray drying of methanolic CBZ solution.

Electrophysiological properties of neurons derived from human stem cells and iNeurons in vitro.

Functional studies of neurons have traditionally used nervous system tissues from a variety of non-human vertebrate and invertebrate species, even when the focus of much of this research has been directed at understanding human brain function. Over the last decade, the identification and isolation of human stem cells from embryonic, tissue (or adult) and induced pluripotent stem cells (iPSCs) has revolutionized the availability of human neurons for experimental studies in vitro. In addition, the direct conversion of terminally differentiated fibroblasts into Induced neurons (iN) has generated great excitement because of the likely value of such human stem cell derived neurons (hSCNs) and iN cells in drug discovery, neuropharmacology, neurotoxicology and regenerative medicine.

Co-sensitization and cross-reactivity between related and unrelated food allergens in dogs - a serological study.

Background: Knowledge of cross-reactivity between foods is useful so that potentially cross-reactive allergens can be avoided in diet trials.

Hypothesis/objectives: To evaluate allergenic cross-reactivity in related foods.

Animals: Sera from 469 dogs with suspected adverse food reactions.

Stress in new graduates: can the profession do more to help?

Richard Halliwell and colleagues believe that it can, on the basis of a survey they conducted to assess the incidence of poor mental health and wellbeing in recent veterinary graduates, and workplace factors that might be associated with this.

Cardiac assessment prior to non-cardiac surgery.

Background: Increasingly, patients undergoing non-cardiac surgery are older and have more comorbidities yet preoperative cardiac assessment appears haphazard and unsystematic. We hypothesised that patients at high cardiac risk were not receiving adequate cardiac assessment, and patients with low-cardiac risk were being over-investigated.

Aims: To compare in a representative sample of patients undergoing non-cardiac surgery the use of cardiac investigations in patients at high and low preoperative cardiac risk.

Acute pain management: scientific evidence, fourth edition, 2015.

This guideline summary describes the fourth edition of Acute pain management: scientific evidence, which was published by the Australian and New Zealand College of Anaesthetists (ANZCA) and its Faculty of Pain Medicine (FPMANZCA) in December 2015. The fourth edition summarises the best available evidence on acute pain management, following methods established over the preceding three editions. It provides additional information by scoring the quality of and reporting further details on randomised controlled trials and meta-analyses.