Quantifying prescribed high dose opioids in the community and risk of overdose.

Background: Opioid prescribing for a range of health issues is increasing globally. The risk of fatal and non-fatal overdose is increased among people prescribed strong opioids: in high doses in the context of polypharmacy (the use of multiple medications at the same time), especially with other sedatives; and among people with multiple morbidities including cardiorespiratory, hepatic and renal conditions. This study described and quantified the prescribing of strong opioids, comorbidities and other overdose risk factors among those prescribed strong opioids, and factors associated with high/very high opioid dosage in a regional health authority in Scotland as part of a wider service improvement exercise.

The Effect of Congenital and Acquired Bilateral Anophthalmia on Brain Structure.

The aim of this study was to compare the pattern of changes in brain structure resulting from congenital and acquired bilateral anophthalmia. Brain structure was investigated using 3T magnetic resonance imaging (MRI) in Oxford (congenital) or Manchester (acquired). T1-weighted structural and diffusion-weighted scans were acquired from people with anophthalmia and sighted control participants.

Treatment of infantile-onset spinal muscular atrophy with nusinersen: final report of a phase 2, open-label, multicentre, dose-escalation study.

Background: Nusinersen showed a favourable benefit-risk profile in participants with infantile-onset spinal muscular atrophy at the interim analysis of a phase 2 clinical study. We present the study's final analysis, assessing the efficacy and safety of nusinersen over 3 years.

Methods: This phase 2, open-label, multicentre, dose-escalation study was done in three university hospital sites in the USA and one in Canada.

Generic Health-Related Quality of Life in Patients Seeking Care for Pelvic Organ Prolapse.

Objective: Using the American Urogynecologic Society multicenter Pelvic Floor Disorder Registry for Research, we (1) compared generic quality of life (QOL) in women planning pelvic organ prolapse (POP) treatment (surgery vs pessary), (2) correlated generic and condition-specific QOL scores, and (3) identified associations between generic QOL and other factors.

Methods: This cross-sectional analysis assessed generic physical and mental QOL using the Patient-Reported Outcomes Measurement Information System Global Health Scale at baseline. Global Physical and Mental T-scores center on a representative US population sample (mean [SD], 50 [10]; higher scores, better health).

Examining stereotypy in naturalistic contexts: Differential reinforcement and context-specific redirection.

This study examined stereotypy in naturalistic classroom contexts (i.e., academic programming, leisure skill acquisition) with differential reinforcement of contextually appropriate behavior (DRA).

The combination of the NS5A and cyclophilin inhibitors results in an additive anti-HCV inhibition in humanized mice without development of resistance.

We and others previously reported that the direct-acting agents (DAA) NS5A inhibitors (NS5Ai) and the host-targeting agents cyclophilin inhibitors (CypIs) inhibit HCV replication in vitro. In this study, we investigated whether the combination of NS5Ai and CypI offers a potent anti-HCV effect in vivo. A single administration of NS5Ai or CypI alone to HCV-infected humanized-mice inhibits HCV replication.

Combining SIMS and mechanistic modelling to reveal nutrient kinetics in an algal-bacterial mutualism.

Microbial communities are of considerable significance for biogeochemical processes, for the health of both animals and plants, and for biotechnological purposes. A key feature of microbial interactions is the exchange of nutrients between cells. Isotope labelling followed by analysis with secondary ion mass spectrometry (SIMS) can identify nutrient fluxes and heterogeneity of substrate utilisation on a single cell level.

Circadian Biology and Stroke.

Circadian biology modulates almost all aspects of mammalian physiology, disease, and response to therapies. Emerging data suggest that circadian biology may significantly affect the mechanisms of susceptibility, injury, recovery, and the response to therapy in stroke. In this review/perspective, we survey the accumulating literature and attempt to connect molecular, cellular, and physiological pathways in circadian biology to clinical consequences in stroke.

ORAI1 Ca Channel as a Therapeutic Target in Pathological Vascular Remodelling.

In the adult, vascular smooth muscle cells (VSMC) are normally physiologically quiescent, arranged circumferentially in one or more layers within blood vessel walls. Remodelling of native VSMC to a proliferative state for vascular development, adaptation or repair is driven by platelet-derived growth factor (PDGF). A key effector downstream of PDGF receptors is store-operated calcium entry (SOCE) mediated through the plasma membrane calcium ion channel, ORAI1, which is activated by the endoplasmic reticulum (ER) calcium store sensor, stromal interaction molecule-1 (STIM1).

Clinical characteristics of full thickness macular holes that closed without surgery.

Purpose: To ascertain the anatomic factors that help achieve non-surgical sealing in full thickness macular hole (FTMH).

Methods: Retrospective collaborative study of FTMH that closed without surgical intervention.

Results: A total of 78 patients (mean age 57.

Do environmental risk factors for the development of psychosis distribute differently across dimensionally assessed psychotic experiences?

Psychotic experiences (PE) are associated with poorer functioning, higher distress and the onset of serious mental illness. Environmental exposures (e.g.

Pulmonary Embolism as the Initial Presentation of Coronavirus Disease 2019 in Adolescents.

The current coronavirus disease 2019 pandemic has been particularly challenging for the clinician because of the unclear nature of the underlying disease mechanisms. One of the hallmarks of the disease involves an increased risk of thrombosis and hypercoagulable state. Here, we describe 2 cases of patients admitted with submassive pulmonary embolism in the setting of positive tests for severe acute respiratory syndrome coronavirus 2.

The relationship between fasting-induced torpor, sleep, and wakefulness in laboratory mice.

Study Objectives: Torpor is a regulated and reversible state of metabolic suppression used by many mammalian species to conserve energy. Whereas the relationship between torpor and sleep has been well-studied in seasonal hibernators, less is known about the effects of fasting-induced torpor on states of vigilance and brain activity in laboratory mice.

Methods: Continuous monitoring of electroencephalogram (EEG), electromyogram (EMG), and surface body temperature was undertaken in adult, male C57BL/6 mice over consecutive days of scheduled restricted feeding.

Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice.

The accumulation of adenosine is strongly correlated with the need for sleep and the detection of sleep pressure is antagonised by caffeine. Caffeine also affects the circadian timing system directly and independently of sleep physiology, but how caffeine mediates these effects upon the circadian clock is unclear. Here we identify an adenosine-based regulatory mechanism that allows sleep and circadian processes to interact for the optimisation of sleep/wake timing in mice.

Enhanced x-ray emission coinciding with giant radio pulses from the Crab Pulsar.

Giant radio pulses (GRPs) are sporadic bursts emitted by some pulsars that last a few microseconds and are hundreds to thousands of times brighter than regular pulses from these sources. The only GRP-associated emission outside of radio wavelengths is from the Crab Pulsar, where optical emission is enhanced by a few percentage points during GRPs. We observed the Crab Pulsar simultaneously at x-ray and radio wavelengths, finding enhancement of the x-ray emission by 3.

A Cluster Randomized Trial to Reduce Missed Abusive Head Trauma in Pediatric Intensive Care Settings.

Objective: To estimate the impact of the PediBIRN (Pediatric Brain Injury Research Network) 4-variable clinical decision rule (CDR) on abuse evaluations and missed abusive head trauma in pediatric intensive care settings.

Study Design: This was a cluster randomized trial. Participants included 8 pediatric intensive care units (PICUs) in US academic medical centers; PICU and child abuse physicians; and consecutive patients with acute head injures <3 years (n = 183 and n = 237, intervention vs control).

Adverse impact of polyphasic sleep patterns in humans: Report of the National Sleep Foundation sleep timing and variability consensus panel.

Polyphasic sleep is the practice of distributing multiple short sleep episodes across the 24-hour day rather than having one major and possibly a minor ("nap") sleep episode each day. While the prevalence of polyphasic sleep is unknown, anecdotal reports suggest attempts to follow this practice are common, particularly among young adults. Polyphasic-sleep advocates claim to thrive on as little as 2 hours of total sleep per day.

Outcome of Off-Label AREDS 2 Supplementation for the Treatment of Macular Degeneration in Non-Proliferative Idiopathic Type 2 Macular Telangiectasia.

Purpose: To evaluate if off-label Age-Related Eye Disease Study 2 (AREDS2) supplementation prevents visual and anatomical deterioration in non-proliferative Idiopathic Macular Telangiectasia Type 2 (IMT2).

Patients And Methods: This is a single-center retrospective, comparative study of 82 IMT2 eyes treated with AREDS2 from January 1st, 2013 to January 1st, 2018. The study analysis consisted of a non-comparative arm, which included all AREDS2 eyes, and a comparative arm (27 AREDS2 and 42 untreated eyes) that only included eyes with complete follow-up data.

The G Protein Biased Small Molecule Apelin Agonist CMF-019 is Disease Modifying in Endothelial Cell Apoptosis and Induces Vasodilatation Without Desensitisation .

Signaling through the apelin receptor is beneficial for a number of diseases including pulmonary arterial hypertension. The endogenous small peptides, apelin and elabela/toddler, are downregulated in pulmonary arterial hypertension but are not suitable for exogenous administration owing to a lack of bioavailability, proteolytic instability and susceptibility to renal clearance. CMF-019, a small molecule apelin agonist that displays strong bias towards G protein signaling over β-arrestin (∼400 fold), may be more suitable.

The next step in optimising the stair horizontal-vertical illusion: Does a perception-action link exist in older adults?

Introduction: Tripping on stairs results from insufficient foot to step edge clearance and can often lead to a fall in older adults. A stair horizontal-vertical illusion is suggested to increase the perceived riser height of a step and increase foot clearance when stepping up. However, this perception-action link has not been empirically determined in older adults.

Identification of transcription factors controlling cell wall invertase gene expression for reproductive development via bioinformatic and transgenic analyses.

Cell wall invertase (CWIN) hydrolyses sucrose into glucose and fructose in the extracellular matrix and plays crucial roles in assimilate partitioning and sugar signalling. However, the molecular regulators controlling CWIN gene transcription remain unknown. As the first step to address this issue, we performed bioinformatic and transgenic studies, which identified a cohort of transcription factors (TFs) modulating CWIN gene expression in Arabidopsis thaliana.