Thalamocortical mGlu8 Modulates Dorsal Thalamus Excitatory Transmission and Sensorimotor Activity.

Metabotropic glutamate receptor 8 (mGlu8) is a heterogeneously expressed and poorly understood glutamate receptor with potential pharmacological significance. The thalamic reticular nucleus (TRN) is a critical inhibitory modulator of the thalamocortical-corticothalamic (TC-CT) network and plays a crucial role in information processing throughout the brain, is implicated in a variety of psychiatric conditions, and is also a site of significant mGlu8 expression. Using both male and female mice, we determined via fluorescent in situ hybridization that parvalbumin-expressing cells in the TRN core and shell matrices (identified by spp1+ and ecel1+ expression, respectively) as well as the cortical layers involved in corticothalamic signaling, express grm8 mRNA. We then assayed the physiological and behavioral impacts of perturbing grm8 signaling in the TC circuit through conditional (AAV-CRE mediated) and cell type-specific constitutive deletion strategies. We show that constitutive parvalbumin grm8 knockout (PV grm8 KO) mice exhibited 1) increased spontaneous excitatory drive onto dorsal thalamus relay cells and 2) impaired sensorimotor gating, measured via paired-pulse inhibition, but observed no differences in locomotion and thigmotaxis in repeated bouts of open field testing. Conversely, we observed hyperlocomotive phenotypes and anxiolytic effects of AAV-mediated conditional knockdown of grm8 in the TRN (TRN grm8 KD) in repeated open field testing. Our findings underscore a role for mGlu8 in regulating excitatory neurotransmission as well as anxiety-related locomotor behavior and sensorimotor gating, revealing potential therapeutic applications for various neuropsychiatric disorders and guiding future research endeavors into mGlu8 signaling and TRN function.Significance statement Group III mGlu receptors and the Thalamic Reticular Nucleus (TRN) are critical modulators of reciprocal cortico-thalamic neurotransmission and are implicated in anxiety and locomotor behaviors. The present study demonstrates a specific enrichment of grm8 mRNA within the TRN and thalamus-projecting cortical layers and characterizes the role of mGlu8 receptors in controlling spontaneous excitatory neurotransmission onto cells located within the dorsal thalamus and regulating sensorimotor behaviors from open field and PPI testing. These findings add to growing bodies of literature regarding both TRN and grm8 regulation of thalamocortical activity and related behaviors implicated in neurological and neuropsychiatric disorders.

Forced Abstinence from Volitional Ethanol Intake Drives a Vulnerable Period of Hyperexcitability in BNST-Projecting Insular Cortex Neurons.

The insular cortex (IC) integrates sensory and interoceptive cues to inform downstream circuitry executing adaptive behavioral responses. The IC communicates with areas involved canonically in stress and motivation. IC projections govern stress and ethanol recruitment of bed nucleus of the stria terminalis (BNST) activity necessary for the emergence of negative affective behaviors during alcohol abstinence. Here, we assess the impact of the chronic drinking forced abstinence (CDFA) volitional home cage ethanol intake paradigm on synaptic and excitable properties of IC neurons that project to the BNST (IC→BNST). Using whole-cell patch-clamp electrophysiology, we investigated IC→BNST circuitry 24 h or 2 weeks following forced abstinence (FA) in female C57BL6/J mice. We find that IC→BNST cells are transiently more excitable following acute ethanol withdrawal. In contrast, in vivo ethanol exposure via intraperitoneal injection, ex vivo via ethanol wash, and acute FA from a natural reward (sucrose) all failed to alter excitability. In situ hybridization studies revealed that at 24 h post FA BK channel mRNA expression is reduced in IC. Further, pharmacological inhibition of BK channels mimicked the 24 h FA phenotype, while BK activation was able to decrease AP firing in control and 24 h FA subjects. All together these data suggest a novel mechanism of homeostatic plasticity that occurs in the IC→BNST circuitry following chronic drinking.

Genesis of a functional astrocyte syncytium in the developing mouse hippocampus.

Astrocytes are increasingly shown to operate as an isopotential syncytium in brain function. Protoplasmic astrocytes acquire this ability to functionally go beyond the single-cell level by evolving into a spongiform morphology, cytoplasmically connecting into a syncytium, and expressing a high density of K+ conductance. However, none of these cellular/functional features exist in neonatal newborn astrocytes, which imposes a basic question of when a functional syncytium evolves in the developing brain. Our results show that the spongiform morphology of individual astrocytes and their spatial organization all reach stationary levels by postnatal day (P) 15 in the hippocampal CA1 region. Functionally, astrocytes begin to uniformly express a mature level of passive K+ conductance by P11. We next used syncytial isopotentiality measurement to monitor the maturation of the astrocyte syncytium. In uncoupled P1 astrocytes, the substitution of endogenous K+ by a Na+ -electrode solution ([Na+ ]p ) resulted in the total elimination of the physiological membrane potential (VM ), and outward K+ conductance as predicted by the Goldman-Hodgkin-Katz (GHK) equation. As more astrocytes are coupled to each other through gap junctions during development, the [Na+ ]p -induced loss of physiological VM and the outward K+ conductance is progressively compensated by the neighboring astrocytes. By P15, a stably established syncytial isopotentiality (-73 mV), and a fully compensated outward K+ conductance appeared in all [Na+ ]p -recorded astrocytes. Thus, in view of the developmental timeframe wherein a singular syncytium is anatomically and functionally established for intra-syncytium K+ equilibration, an astrocyte syncytium becomes fully operational at P15 in the mouse hippocampus.

Acute Hemodynamics in the Fontan Circulation: Open-Label Study of Vasopressin.

OBJECTIVE: To describe the acute hemodynamic effect of vasopressin on the Fontan circulation, including systemic and pulmonary pressures and resistances, left atrial pressure, and cardiac index. DESIGN: Prospective, open-label, nonrandomized study (NCT04463394). SETTING: Cardiac catheterization laboratory at Lucile Packard Children's Hospital, Stanford. PATIENTS: Patients 3-50 years old with a Fontan circulation who were referred to the cardiac catheterization laboratory for hemodynamic assessment and/or intervention. INTERVENTIONS: A 0.03 U/kg IV (maximum dose 1 unit) bolus of vasopressin was administered over 5 minutes, followed by a maintenance infusion of 0.3 mU/kg/min (maximum dose 0.03 U/min). MEASUREMENTS AND MAIN RESULTS: Comprehensive cardiac catheterization measurements before and after vasopressin administration. Measurements included pulmonary artery, atrial, and systemic arterial pressures, oxygen saturations, and systemic and pulmonary flows and resistances. There were 28 patients studied. Median age was 13.5 (9.1, 17) years, and 16 (57%) patients had a single or dominant right ventricle. Following vasopressin administration, systolic blood pressure and systemic vascular resistance (SVR) increased by 17.5 (13.0, 22.8) mm Hg ( Z value -4.6, p < 0.001) and 3.8 (1.8, 7.5) Wood Units ( Z value -4.6, p < 0.001), respectively. The pulmonary vascular resistance (PVR) decreased by 0.4 ± 0.4 WU ( t statistic 6.2, p < 0.001), and the left atrial pressure increased by 1.0 (0.0, 2.0) mm Hg ( Z value -3.5, p < 0.001). The PVR:SVR decreased by 0.04 ± 0.03 ( t statistic 8.1, p < 0.001). Neither the pulmonary artery pressure (median difference 0.0 [-1.0, 1.0], Z value -0.4, p = 0.69) nor cardiac index (0.1 ± 0.3, t statistic -1.4, p = 0.18) changed significantly. There were no adverse events. CONCLUSIONS: In Fontan patients undergoing cardiac catheterization, vasopressin administration resulted in a significant increase in systolic blood pressure, SVR, and left atrial pressure, decrease in PVR, and no change in cardiac index or pulmonary artery pressure. These findings suggest that in Fontan patients vasopressin may be an option for treating systemic hypotension during sedation or general anesthesia.

Immune checkpoint inhibitors in kidney transplant recipients: a multicentre, single-arm, phase 1 study.

BACKGROUND: Most kidney transplant recipients with cancer stop or reduce immunosuppressive therapy before starting treatment with an immune checkpoint inhibitor, and approximately 40% of such patients will develop allograft rejection. Isolated immunosuppression reduction might be associated with organ rejection. Whether immunosuppression manipulation, immune checkpoint inhibition, or both, induce organ rejection is difficult to ascertain. The aim of this study was to examine the risk of allograft rejection with immune checkpoint inhibitor exposure when baseline immunosuppression was left unchanged. METHODS: We conducted a multicentre, single-arm, phase 1 study in three hospitals in Australia. Kidney transplant recipients aged 18 years or older with incurable, locally advanced cancer or defined metastatic solid tumours were eligible if they had a creatinine concentration of less than 180 mmol/L, no or low concentrations of donor-specific HLA antibodies, and an Eastern Cooperative Oncology Group status of 0-2. Patients received standard doses of nivolumab (3 mg/kg intravenously every 14 days for five cycles, then 480 mg every 28 days for up to 2 years). The primary endpoint was the proportion of patients with irretrievable allograft rejection and no evidence of tumour response. Primary outcome analyses and safety analyses were done in the modified intention-to-treat population. This trial is registered with the Australian and New Zealand Clinical Trials Register, ANZCTR12617000741381, and is completed. FINDINGS: Between May 31, 2017, and Aug 6, 2021, 22 kidney transplant recipients with various solid tumours were screened and enrolled, four of whom chose not to proceed in the study and one of whom had unexpected disease progression. 17 patients (six [35%] women and 11 [65%] men; median age 67 years [IQR 59-71]) were allocated treatment with nivolumab and were included in the analyses. The trial was then stopped due to ongoing difficulties with running clinical trials during COVID-19 health restrictions. Patients were treated with a median of three infusions (IQR 2-10) and median follow-up was 28 months (IQR 16-34). No patients had irretrievable allograft rejection without evidence of tumour response. There were no treatment-related deaths or treatment-related serious adverse events. The most common grade 3 or grade 4 adverse events were decreased lymphocyte count in four (24%) patients, fever or infection in four (24%) patients, decreased haemoglobin in three (18%) patients, and increased creatinine in three (18%) patients. INTERPRETATION: Maintaining baseline immunosuppression before treatment with an immune checkpoint inhibitor in kidney transplant recipients might not affect expected efficacy and might reduce the risk of allograft rejection mediated by immune checkpoint inhibitors. FUNDING: Bristol Myers Squibb.

Ventricular arrhythmias following transcatheter pulmonary valve replacement with the harmony TPV25 device.

BACKGROUND: Transcatheter pulmonary valve replacement (TPVR) with the Harmony valve (Medtronic, Inc.) was recently approved to treat postoperative native outflow tract pulmonary regurgitation. While the 22 mm Harmony valve Early Feasibility Study demonstrated ventricular tachycardia (VT) in only 5% of patients, little is known about ventricular arrhythmias after TPVR with the larger 25 mm valve (TPV25). METHODS: A single center review was performed of patients with TPV25 implant from 2020 to 2021. Demographic, cardiac, procedural, and postimplant cardiac telemetry data were collected and compared between patients who did and did not have peri-implant ventricular arrhythmia. RESULTS: Thirty patients underwent TPV25 at a median age of 30 years. On postimplant telemetry, VT events were documented in 12 patients (40%); 11 nonsustained VT (NSVT) (median 3 episodes per patient and 6 beats per episode, maximum 157 episodes) and 1 sustained VT (3%), with Torsades de Pointes secondary to a short coupled premature ventricular contraction (PVC). VT events were associated with annular valve positioning (p < 0.001) and increased postimplant PVC burden (p < 0.0001), but there was no association between VT and other demongraphic, historical, or procedural factors. The frequency of NSVT events fell from 3/h from 0 to 12 h postimplant to 0.5/hr from 12 to 24 h (p < 0.001). CONCLUSION: VT occurred commonly (40%) in the first 24 h after TPV25 implant, with self-limited NSVT in 11 of 12 patients and 1 patient with cardiac arrest secondary to Torsades de Pointes. VT only occurred with annular valve positioning. Larger, longer-term studies are needed to determine risk factors for and natural history of post-TPVR VT.

Sexual Shame as a Unique Distress Outcome of Morally Incongruent Pornography Use: Modifications and Methodological Considerations.

Researchers focused on the model of pornography problems due to moral incongruence (PPMI) have suggested that perceptions of addiction, stemming from a misalignment between one's moral values and online sexual behavior, may lead to heightened sexual shame. Even so, it has been suggested that the associations found in previous models of PPMI may have been inflated by the inclusion of the emotional distress subscale in the widely used Cyber Pornography Use Inventory (CPUI-9), leading many to use the abridged 4-item version (i.e., the CPUI-4), which excludes emotional distress. Prior models assessing sexual shame have yet to fully address this potential methodological limitation. Considering advances in the conceptualization of PPMI and recommendations concerning best practices, a sample of participants (N = 296) that reported using pornography in the last six months was utilized to compare findings from two moderated mediation models. The first model assessed the differential strength of effects when the subscales of the CPUI-9 were assessed as separate mediators of the associations between moral incongruence and sexual shame, while the second model examined whether such associations persisted when using the recommended CPUI-4. Model results provide further justification for previous findings, indicating that associations between constructs were not the sole result of emotional distress, which supports the utility of the CPUI-4 in models that include sexual shame. Findings provide added support for sexual shame as a unique outcome among those who, due to moral incongruence, perceive that they are addicted to Internet pornography.

Sensitivity of Freshwater Australian Bass (Macquaria novemaculeata) and Silver Perch (Bidyanus bidyanus) to Waterborne Antimony: Exposure-Dose-Response Characteristics and Ion Homeostasis.

We conducted acute toxicity studies using semi-static protocols to examine the lethal responses of Australian bass and silver perch exposed to antimony (Sb) oxidation states in Sb(III) (10.5-30.5 mg L-1) and Sb(V) (95.9-258.7 mg L-1). Bioavailability and the effects of Sb on body ion regulation (Na, Ca, Mg, and K) were also investigated. Antimony species-specific effects were observed with exposure to both Sb oxidation states. Median lethal concentrations (LC50s) for Sb(III) were 13.6 and 18 mg L-1 for Australian bass and silver perch, respectively, and the LC50 for Sb(V) in Australian bass was 165.3 mg L-1. The LC50 could not be calculated for silver perch exposed to Sb(V) as the maximum exposure concentrations produced 40% mortality but a larger-than value of > 258.7 mg L-1 was estimated. Relative median potency values derived from the LC50s were 0.1 Sb(III) and 12.2 and 16.6 Sb(V) for Australian bass and silver perch, respectively, demonstrating greater toxicity of Sb(III) to both fish species. Antimony uptake in fish was observed. Median critical body residue (CBR50) values of 77.7 and 26.6 mg kg-1 for Sb(III) were estimated for Australian bass and silver perch, respectively, and 628.1 mg kg-1 for Sb(V) in Australian bass. Bioconcentration factors (BCFs) for both Sb(III) and Sb(V) did not change with exposure but the greater BCFs for fish exposed to Sb(III) indicate that it is more bioavailable than Sb(V) in acute exposure. No effects on whole-body Na, Ca, Mg, or K ions were observed with fish exposure to either Sb species.

Design, development and implementation of the virtual, coordination, access, referral and escalation service in western New South Wales.

PROBLEM: People in rural and remote New South Wales experience avoidable admissions, limited access to skilled clinicians and commonly travel >400 km to access specialist services within the district and >700 km for tertiary services outside. DESIGN: Iterative use of New South Wales Health redesign methodology in the period 2015-2020. SETTING: Western New South Wales Local Health District is geographically the largest Health District within New South Wales and includes disadvantaged communities. Virtual Coordination Access Referral Escalation is an audio-visually enabled transport, patient flow and clinical advice unit established in 2006 to support patients and clinicians at 35 small, rural and remote hospitals. KEY MEASURES FOR IMPROVEMENT: Right care, right place and right time by the right team the first time. Care delivery close to home and 'on country'. Safe and cost-effective transport. Performance measures to support quality, safety and clinical outcomes. Improving the human experience. STRATEGIES FOR CHANGE: Cycles of strategic planning, innovation, productive partnerships, change management and human systems development. EFFECTS OF CHANGE: Virtual Coordination Access Referral Escalation critical care telehealth more effectively supports rural and remote health care across large distances. LESSONS LEARNT: Improvements include expanded/redefined management and nursing roles, integration of dedicated critical care emergency medicine specialists within the service, delegated authority to accept transfers, upgraded technology, 24-hour service provision and a central 'Virtual Support' proactive outreach model.

The preventable burden of breast cancers for premenopausal and postmenopausal women in Australia: A pooled cohort study.

Estimates of the future breast cancer burden preventable through modifications to current behaviours are lacking. We assessed the effect of individual and joint behaviour modifications on breast cancer burden for premenopausal and postmenopausal Australian women, and whether effects differed between population subgroups. We linked pooled data from six Australian cohort studies (n = 214,536) to national cancer and death registries, and estimated the strength of the associations between behaviours causally related to cancer incidence and death using adjusted proportional hazards models. We estimated exposure prevalence from representative health surveys. We combined these estimates to calculate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), and compared PAFs for population subgroups. During the first 10 years follow-up, there were 640 incident breast cancers for premenopausal women, 2,632 for postmenopausal women, and 8,761 deaths from any cause. Of future breast cancers for premenopausal women, any regular alcohol consumption explains 12.6% (CI = 4.3-20.2%), current use of oral contraceptives for ≥5 years 7.1% (CI = 0.3-13.5%), and these factors combined 18.8% (CI = 9.1-27.4%). Of future breast cancers for postmenopausal women, overweight or obesity (BMI ≥25 kg/m2 ) explains 12.8% (CI = 7.8-17.5%), current use of menopausal hormone therapy (MHT) 6.9% (CI = 4.8-8.9%), any regular alcohol consumption 6.6% (CI = 1.5-11.4%), and these factors combined 24.2% (CI = 17.6-30.3%). The MHT-related postmenopausal breast cancer burden varied by body fatness, alcohol consumption and socio-economic status, the body fatness-related postmenopausal breast cancer burden by alcohol consumption and educational attainment, and the alcohol-related postmenopausal breast cancer burden by breast feeding history. Our results provide evidence to support targeted and population-level cancer control activities.

Adrenergic Polymorphisms and Survival in African Americans With Heart Failure: Results From A-HeFT.

BACKGROUND: Polymorphisms in adrenergic signaling affect the molecular function of adrenergic receptors and related proteins. The ß1 adrenergic receptor (ADRB1) Arg389Gly, G-protein receptor kinase type 5 (GRK5) Gln41Leu, G-protein ß-3 subunit (GNB3) 825 C/T, and α2c deletion affect adrenergic tone, impact heart failure outcomes and differ in prevalence by ethnicity. Their combined effect within black cohorts remains unknown. METHODS AND RESULTS: We analyzed subjects from the African American Heart Failure Trial (A-HeFT) by assessing event-free survival, quality of life, and gene coinheritance. Significant coinheritance effects on survival included GRK5 Leu41 among subjects co-inheriting GNB3 825 C alleles (n = 166, 90.4% vs 69.0%, P < 0.001). By contrast, the impact of ADRB1 Arg389Arg genotype was magnified among subjects with GNB3 825 TT genotype (n = 181, 66.3% vs 85.7%, P = .002). The lack of the α2c deletion (ie, insertion) led to a greater impact of the ARG389Arg genotype (n = 289, 76.4% vs 86.1%, P = .007). CONCLUSIONS: Polymorphisms in adrenergic signaling affects outcomes in black subjects with heart failure. Coinheritance patterns in genetic variation may help determine heart failure survival.

Burden and trend of diet-related non-communicable diseases in Australia and comparison with 34 OECD countries, 1990-2015: findings from the Global Burden of Disease Study 2015.

BACKGROUND: Diet is a major determining factor for many non-communicable chronic diseases (NCDs). However, evidence on diet-related NCD burden remains limited. We assessed the trends in diet-related NCDs in Australia from 1990 to 2015 and compared the results with other countries of the Organization for Economic Co-operation and Development (OECD). METHODS: We used data and methods from the Global Burden of Disease (GBD) 2015 study to estimate the NCD mortality and disability-adjusted life years (DALYs) attributable to 14 dietary risk factors in Australia and 34 OECD nations. Countries were further ranked from the lowest (first) to highest (35th) burden using an age-standardized population attributable fraction (PAF). RESULTS: In 2015, the estimated number of deaths attributable to dietary risks was 29,414 deaths [95% uncertainty interval (UI) 24,697 - 34,058 or 19.7% of NCD deaths] and 443,385 DALYs (95% UI 377,680-511,388 or 9.5% of NCD DALYs) in Australia. Young (25-49 years) and middle-age (50-69 years) male adults had a higher PAF of diet-related NCD deaths and DALYs than their female counterparts. Diets low in fruits, vegetables, nuts and seeds and whole grains, but high in sodium, were the major contributors to both NCD deaths and DALYs. Overall, 42.3% of cardiovascular deaths were attributable to dietary risk factors. The age-standardized PAF of diet-related NCD mortality and DALYs decreased over the study period by 28.2% (from 27.0% in 1990 to 19.4% in 2015) and 41.0% (from 14.3% in 1990 to 8.4% in 2015), respectively. In 2015, Australia ranked 12th of 35 examined countries in diet-related mortality. A small improvement of rank was recorded compared to the previous 25 years. CONCLUSIONS: Despite a reduction in diet-related NCD burden over 25 years, dietary risks are still the major contributors to a high burden of NCDs in Australia. Interventions targeting NCDs should focus on dietary behaviours of individuals and population groups.

The burden of pancreatic cancer in Australia attributable to smoking.

OBJECTIVE: To estimate the burden of pancreatic cancer in Australia attributable to modifiable exposures, particularly smoking. DESIGN: Prospective pooled cohort study. SETTING, PARTICIPANTS: Seven prospective Australian study cohorts (total sample size, 365 084 adults); participant data linked to national registries to identify cases of pancreatic cancer and deaths. MAIN OUTCOME MEASURES: Associations between exposures and incidence of pancreatic cancer, estimated in a proportional hazards model, adjusted for age, sex, study, and other exposures; future burden of pancreatic cancer avoidable by changes in exposure estimated as population attributable fractions (PAFs) for whole population and for specific population subgroups with a method accounting for competing risk of death. RESULTS: There were 604 incident cases of pancreatic cancer during the first 10 years of follow-up. Current and recent smoking explained 21.7% (95% CI, 13.8-28.9%) and current smoking alone explained 15.3% (95% CI, 8.6-22.6%) of future pancreatic cancer burden. This proportion of the burden would be avoidable over 25 years were current smokers to quit and there were no new smokers. The burden attributable to current smoking is greater for men (23.9%; 95% CI, 13.3-33.3%) than for women (7.2%; 95% CI, -0.4% to 14.2%; P = 0.007) and for those under 65 (19.0%; 95% CI, 8.1-28.6%) than for older people (6.6%; 95% CI, 1.9-11.1%; P = 0.030). There were no independent relationships between body mass index or alcohol consumption and pancreatic cancer. CONCLUSIONS: Strategies that reduce the uptake of smoking and encourage current smokers to quit could substantially reduce the future incidence of pancreatic cancer in Australia, particularly among men.

Trends of mortality attributable to child and maternal undernutrition, overweight/obesity and dietary risk factors of non-communicable diseases in sub-Saharan Africa, 1990-2015: findings from the Global Burden of Disease Study 2015.

OBJECTIVE: To assess trends of mortality attributable to child and maternal undernutrition (CMU), overweight/obesity and dietary risks of non-communicable diseases (NCD) in sub-Saharan Africa (SSA) using data from the Global Burden of Disease (GBD) Study 2015. DESIGN: For each risk factor, a systematic review of data was used to compute the exposure level and the effect size. A Bayesian hierarchical meta-regression analysis was used to estimate the exposure level of the risk factors by age, sex, geography and year. The burden of all-cause mortality attributable to CMU, fourteen dietary risk factors (eight diets, five nutrients and fibre intake) and overweight/obesity was estimated. SETTING: Sub-Saharan Africa.ParticipantsAll age groups and both sexes. RESULTS: In 2015, CMU, overweight/obesity and dietary risks of NCD accounted for 826204 (95 % uncertainty interval (UI) 737346, 923789), 266768 (95 % UI 189051, 353096) and 558578 (95 % UI 453433, 680197) deaths, respectively, representing 10·3 % (95 % UI 9·1, 11·6 %), 3·3 % (95 % UI 2·4, 4·4 %) and 7·0 % (95 % UI 5·8, 8·3 %) of all-cause mortality. While the age-standardized proportion of all-cause mortality accounted for by CMU decreased by 55·2 % between 1990 and 2015 in SSA, it increased by 63·3 and 17·2 % for overweight/obesity and dietary risks of NCD, respectively. CONCLUSIONS: The increasing burden of diet- and obesity-related diseases and the reduction of mortality attributable to CMU indicate that SSA is undergoing a rapid nutritional transition. To tackle the impact in SSA, interventions and international development agendas should also target dietary risks associated with NCD and overweight/obesity.

Prevalence and healthcare usage of knee pain in South Australia: a population-based study.

BACKGROUND: It is known that South Australia (SA) has the highest rate of knee arthroscopy use of any state in Australia; however, Level 1 evidence demonstrates that knee arthroscopy in patients with uncomplicated knee osteoarthritis confers no benefit. In SA, which patients are presenting with knee pain and what treatments are they receiving? AIMS: To determine the prevalence, persistence and treatment modalities of knee pain in SA. METHODS: This study analysed data from the North-West Adelaide Health Study (1999-2015), a longitudinal, population-based cohort study of people aged 18 years and over (n = 4060), initially randomly selected from the north-west region of Adelaide, SA. It incorporated clinic assessments, self-completed questionnaires and telephone interviews to collect demographic, anthropometric and biochemical data over four main stages (1, 2, 3 and North-West 15 (NW15)). Data were linked to Medical Benefits Scheme data. RESULTS: In stages 3 and NW15 of the North-West Adelaide Health Study, 30-35% of participants reported knee pain (n = 803, 452). Demographic variables associated with knee pain included older age and lower educational level, while risk factors included obesity and high waist circumference. In the 12 months preceding NW15, 33% of participants with knee pain/stiffness consulted a general practitioner for their knee pain, 10.2% an orthopaedic surgeon, and 12.6% a physiotherapist. Between 2011 and 2015, 3.0% the cohort underwent a knee arthroscopy, and 3.1% underwent knee magnetic resonance imaging. CONCLUSIONS: Knee pain affects large proportions of the SA population. Knee pain was persistent with underuse of non-pharmacological treatments and high use of specialist referral. These data support the need for a national strategy to manage osteoarthritis effectively.

Increasing gaps in health inequalities related to non-communicable diseases in South Australia; implications towards behavioural risk factor surveillance systems to provide evidence for action.

BACKGROUND: Although Australia is a country cited as having generally low health inequalities among different socioeconomic groups, inequalities have persisted. The aim of this analysis was to highlight how inequalities have evolved over a 13 years period in South Australia (SA). METHODS: Since 2002, over 600 interviews per month have been undertaken with SA residents through a computer assisted telephone survey method (total 77,000+). Major risk factors and chronic diseases have been analyzed providing trends by two socio-economic variables: education and a proxy of income (ability to save). RESULTS: While income and educational gaps are reducing over time in SA, those that remain in the lower socio-economic groups have a generally higher prevalence of risk factors and chronic diseases. The health disparity gap is still relevant, although at a different extent, for all the variables considered in our study, with most appearing to be stable if not increasing over time. CONCLUSIONS: Surveillance can be a good source of information both to show the evolution of problems and to evaluate possible future interventions. Extensive effort is still required to "close the gap" of health inequalities in SA. More precisely targeted and properly implemented interventions are needed.

Analysis of the alcohol drinking behavior and influencing factors among emerging adults and young adults: a cross-sectional study in Wuhan, China.

BACKGROUND: The relationship between alcohol use in adolescents and young adults and outcomes has not been widely researched in China. The aim of the current study was to understand the current status of drinking behavior of Chinese youth transitioning into adulthood. METHODS: The cross-sectional study included 1634 participants between 18 and 34 years of age. The participants were randomly chosen from 13 administrative districts in Wuhan, and invited to complete a questionnaire. Univariate analysis was performed to describe the demographic distribution of alcohol consumption and the association with drinking status. Stepwise Logistic regression analysis was undertaken analyzing the factors influencing the drinking behaviors. The data were weighted to the population in Wuhan and analyzed using SAS version 9.3. RESULTS: For our sample of emerging and young Chinese adults the prevalence of drinking alcohol was 45.84%. The non-drinkers predominated, accounting for 54.16% and light drinkers accounted for 42.94%, while moderate and heavy drinkers were in the minority (2.90%). The earlier the age of first alcohol drinking or the age of first being intoxicated, the greater the likelihood of being a moderate or heavy drinker. People with high emerging adulthood were more likely to have moderate or heavy drinking behaviors. The logistic regression analysis indicated that heavy drinkers were more likely to not be married and to be classified as high emerging adulthood. CONCLUSIONS: Our findings suggested that the drinking pattern should be further evaluated over time to explore the ways in which social and cultural factors shape the drinking route of this age group. Effective drinking behavior prevention and interventions and appropriate guidance should be formulated to establish an appropriate attitude towards drinking alcohol and develop a drinking behavior which is conducive to physical and mental health between this particular demographic.

A qualitative exploration of the effect of visual field loss on daily life in home-dwelling stroke survivors.

OBJECTIVE: To explore the effect of visual field loss on the daily life of community-dwelling stroke survivors. DESIGN: A qualitative interview study. PARTICIPANTS: Adult stroke survivors with visual field loss of at least six months' duration. METHODS: Semi-structured interviews were conducted with a non-purposive sample of 12 stroke survivors in their own homes. These were recorded, transcribed verbatim and analyzed with the framework method, using an inductive approach. RESULTS: Two key analytical themes emerged. 'Perception, experience and knowledge' describes participant's conflicted experience of having knowledge of their impaired vision but lacking perception of that visual field loss and operating under the assumption that they were viewing an intact visual scene when engaged in activities. Inability to recognize and deal with visual difficulties, and experiencing the consequences, contributed to their fear and loss of self-confidence. 'Avoidance and adaptation' were two typologies of participant response to visual field loss. Initially, all participants consciously avoided activities. Some later adapted to vision loss using self-directed head and eye scanning techniques. CONCLUSIONS: Visual field loss has a marked impact on stroke survivors. Stroke survivors lack perception of their visual loss in everyday life, resulting in fear and loss of confidence. Activity avoidance is a common response, but in some, it is replaced by self-initiated adaptive techniques.

Syncytial isopotentiality: A system-wide electrical feature of astrocytic networks in the brain.

Syncytial isopotentiality, resulting from a strong electrical coupling, emerges as a physiological mechanism that coordinates individual astrocytes to function as a highly efficient system in brain homeostasis. However, whether syncytial isopotentiality occurs selectively to certain brain regions or is universal to astrocytic networks remains unknown. Here, we have explored the correlation of syncytial isopotentiality with different astrocyte subtypes in various brain regions. Using a nonphysiological K+ -free/Na+ electrode solution to depolarize a recorded astrocyte in situ, the existence of syncytial isopotentiality can be revealed: the recorded astrocyte's membrane potential remains at a quasi-physiological level due to strong electrical coupling with neighboring astrocytes. Syncytial isopotentiality appears in Layer I of the motor, sensory, and visual cortical regions, where astrocytes are organized with comparable cell densities, interastrocytic distances, and the quantity of directly coupled neighbors. Second, though astrocytes vary in their cytoarchitecture in association with neuronal circuits from Layers I-VI, the established syncytial isopotentiality remains comparable among different layers in the visual cortex. Third, neurons and astrocytes are uniquely organized as barrels in Layer IV somatosensory cortex; interestingly, astrocytes both inside and outside of the barrels do electrically communicate with each other and also share syncytial isopotentiality. Fourth, syncytial isopotentiality appears in radial-shaped Bergmann glia and velate astrocytes in the cerebellar cortex. Fifth, although fibrous astrocytes in white matter exhibit a distinct morphology, their network syncytial isopotentiality is comparable with protoplasmic astrocytes. Altogether, syncytial isopotentiality appears as a system-wide electrical feature of astrocytic networks in the brain.

Heart Failure With Recovered Ejection Fraction in African Americans: Results From the African-American Heart Failure Trial.

BACKGROUND: Recent studies have described the entity of heart failure with recovered ejection fraction (HFrecEF), but population-specific studies remain lacking. The aim of this study was to characterize patients enrolled in the African-American Heart Failure Trial (A-HeFT) who had significant improvement in their ejection fraction (EF) during the 1st 6 months of follow-up. METHODS AND RESULTS: Subjects with HFrecEF (improvement in EF from <35% to >40% in 6 months; n = 59) were compared with 259 subjects with heart failure and persistently reduced EF (HFrEF), defined as EF ≤40% at 6-month follow-up. The effects of improvement in EF on all-cause mortality and 1st and all hospitalizations were analyzed. Compared with HFrEF, subjects with HFrecEF had a nonsignificant trend toward lower mortality (hazard ratio [HR] 0.16, 95% confidence interval [CI] 0.02-1.15; P = .068), fewer 1st HF hospitalizations (HR 0.22, 95% CI 0.07-0.71; P = .011), fewer recurrent HF hospitalizations (HR 0.13, 95% CI 0.05-0.37; P <.001), similar 1st all-cause hospitalizations (HR 0.67, 95% CI 0.39-1.15; P = .150), and fewer recurrent all-cause hospitalizations (HR 0.41, 95% CI 0.24-0.68; P <.001). CONCLUSIONS: These data confirm that, as in other populations, a small subgroup of black patients receiving standard care improve their EF with favorable outcomes. Further studies are required to determine whether myocardial recovery is permanent and the best management strategies in such patients.