Building momentum through networks: Bioimaging across the Americas.

In September 2023, the two largest bioimaging networks in the Americas, Latin America Bioimaging (LABI) and BioImaging North America (BINA), came together during a 1-week meeting in Mexico. This meeting provided opportunities for participants to interact closely with decision-makers from imaging core facilities across the Americas. The meeting was held in a hybrid format and attended in-person by imaging scientists from across the Americas, including Canada, the United States, Mexico, Colombia, Peru, Argentina, Chile, Brazil and Uruguay. The aims of the meeting were to discuss progress achieved over the past year, to foster networking and collaborative efforts among members of both communities, to bring together key members of the international imaging community to promote the exchange of experience and expertise, to engage with industry partners, and to establish future directions within each individual network, as well as common goals. This meeting report summarises the discussions exchanged, the achievements shared, and the goals set during the LABIxBINA2023: Bioimaging across the Americas meeting.

Genomic factors shape carbon and nitrogen metabolic niche breadth across Saccharomycotina yeasts.

Organisms exhibit extensive variation in ecological niche breadth, from very narrow (specialists) to very broad (generalists). Two general paradigms have been proposed to explain this variation: (i) trade-offs between performance efficiency and breadth and (ii) the joint influence of extrinsic (environmental) and intrinsic (genomic) factors. We assembled genomic, metabolic, and ecological data from nearly all known species of the ancient fungal subphylum Saccharomycotina (1154 yeast strains from 1051 species), grown in 24 different environmental conditions, to examine niche breadth evolution. We found that large differences in the breadth of carbon utilization traits between yeasts stem from intrinsic differences in genes encoding specific metabolic pathways, but we found limited evidence for trade-offs. These comprehensive data argue that intrinsic factors shape niche breadth variation in microbes.

"They start on the zero-alcohol and they wanna try the real thing": Parents' views on zero-alcohol beverages and their use by adolescents.

OBJECTIVE: Zero-alcohol beverages containing 0.0-0.5% alcohol by volume may offer public health benefits if individuals use them to substitute for alcohol-containing products, thereby reducing alcohol use. There are, however, concerns that zero-alcohol beverages may encourage adolescents' earlier interest in alcohol and increase exposure to alcohol company branding. As this poses a challenge for parents, we studied parents' views on zero-alcohol beverages and their provision to adolescents. METHODS: We interviewed n=38 parents of 12-17-year-olds and used reflexive thematic analysis to interpret interview data. RESULTS: Parents considered zero-alcohol beverages to be 'adult beverages' that potentially supported reduced adult drinking but were unnecessary for adolescents. Parents were concerned that adolescent zero-alcohol beverage use could normalise alcohol consumption and be a precursor to alcohol initiation. There was a potential conflict between moderate provision in 'appropriate' contexts, and potential benefits, which were each supported by some parents. Uncertainty on health qualities was also reported. CONCLUSIONS: Parents reported conflicting and cautious views on zero-alcohol beverage provision to adolescents. IMPLICATIONS FOR PUBLIC HEALTH: As evidence on the impacts of zero-alcohol beverage availability develops, parent-targeted messages highlighting the potential risk of normalisation of alcohol use for young people could be developed, in conjunction with broader policy responses.

Pediatric suicide: Review of a preventable tragedy.

Concepts of suicide are explored in this issue with a focus on suicide in children and adolescents. The epidemiology of pediatric suicide in the United States is reviewed; also, risk and protective factors, as well as prevention strategies, are discussed. Suicide in the pediatric athlete and the potential protective effect of exercise are examined. In addition, this analysis addresses the beneficial role of psychological management as well as current research on pharmacologic treatment and brain stimulation procedures as part of comprehensive pediatric suicide prevention. Though death by suicide in pediatric persons has been and remains a tragic phenomenon, there is much that clinicians, other healthcare professionals, and society itself can accomplish in the prevention of pediatric suicide as well as the management of suicidality in our children and adolescents.

Evaluation of a novel augmented reality educational tool and its effects on patient experience: A randomized controlled trial.

Introduction: Patient education is an essential element of the treatment pathway. Augmented reality (AR), with disease simulations and three-dimensional visuals, offers a developing approach to patient education. We aim to determine whether this tool can increase patient understanding of their disease and post-visit satisfaction in comparison to current standard of care (SOC) educational practices in a randomized control study. Methods: Our single-site study consisted of 100 patients with initial diagnoses of kidney masses or stones randomly enrolled in the AR or SOC arm. In the AR arm, a physician used AR software on a tablet to educate the patient. SOC patients were educated through traditional discussion, imaging, and hand-drawn illustrations. Participants completed pre- and post-physician encounter surveys adapted from the Press Ganey® patient questionnaire to assess understanding and satisfaction. Their responses were evaluated in the Readability Studio® and analyzed to quantify rates of improvement in self-reported understanding and satisfaction scores. Results: There was no significant difference in participant education level (P = 0.828) or visit length (27.6 vs. 25.0 min, P = 0.065) between cohorts. Our data indicate that the rate of change in pre- to post-visit self-reported understanding was similar in each arm (P ≥ 0.106 for all responses). The AR arm, however, had significantly higher patient satisfaction scores concerning the educational effectiveness and understanding of images used during the consultation (P < 0.05). Conclusions: While AR did not significantly increase self-reported patient understanding of their disease compared to SOC, this study suggests AR as a potential avenue to increase patient satisfaction with educational tools used during consultations.

Prevention of internalizing difficulties in the middle years: Protocol for a noninferiority randomized trial of Mindfulness-Based Cognitive Therapy for Children and Cognitive Behavioural Therapy.

AIM: Mindfulness-based interventions have been tested as preventive programs for childhood internalizing difficulties, but most research has been at a 'universal' level with small to null effects. Mindfulness-Based Cognitive Therapy for Children (MBCT-C) has similar effects to Cognitive Behaviour Therapy (CBT) when used as a small-group, targeted preventive program. Knowledge gaps include the longer-term effectiveness of MBCT-C relative to CBT and the benefits of adding a parent module. This trial aims to compare MCBT-C to traditional CBT, including a parent module, to 15-months post-intervention and to test the feasibility and acceptability of adding a parent module. METHODS: Participants will be recruited from primary schools in areas of socio-economic disadvantage in South Australia (n = 194). Children (aged 9-12) years with signs of internalizing difficulties (e.g., shy, withdrawn, worried), and their parents, will be eligible for this two-armed randomized controlled non-inferiority trial (RCT). Children will participate in 10 group sessions of MBCT-C or CBT, facilitated by psychologists, and parents from both conditions will participate in two parent-only group sessions. Child self-report measures include depression and anxiety, as well as attention, mindfulness and self-compassion. Parent measures include symptoms of depression and anxiety, mindfulness, and parent-child relationship strength. The primary outcome will be child anxiety and depression (Revised Child Anxiety and Depression Scale-25). Measures will be collected pre and post intervention, and at 3, 6, 12 and 15-month follow up. RESULTS: Schools will be recruited from October 2022. Nomination of children will commence from February 2023. Program implementation will begin May 2023. CONCLUSIONS: This trial will have implications for the feasibility of involving parents in preventative programs, as well as whether mindfulness-based interventions prevent internalizing difficulties over time.

Rehabilitation Following a Triceps Branch to Axillary Motor Nerve Transfer-A Pragmatic Therapy Guide.

Peripheral motor nerve transfer surgery is a technique that may be used to restore motor function to paralyzed muscles. Motor nerve transfer involves harvesting an expendable motor nerve branch, and transfer to the motor branch of the denervated target muscle, using microsurgical coaptation. To date, a standardized rehabilitation protocol does not exist. The 6 stages of rehabilitation after motor nerve transfer surgery were outlined by colleagues in the Birmingham Peripheral Nerve Injury service in 2019. This article aims to provide a practical therapy perspective on the rehabilitation stages of motor nerve transfer surgery outlined in that paper, focusing on the radial to axillary nerve transfer. Timeframes for each stage along with exercise prescription and rationale are provided.

Clinical Implications of Microscopic Colitis Isolated to Polyps.

Microscopic colitis is generally identified on random colon biopsies performed for chronic diarrhea, but rarely incidental polyps have histologic features of microscopic colitis. We compared patients with polypoid microscopic colitis to control patients with conventional polyps to determine the implications of polypoid microscopic colitis.Medical records were searched for patients without prior or concurrent microscopic colitis who were found to have polypoid microscopic colitis. For each patient with polypoid microscopic colitis, one patient with conventional polyps was selected as a control. We reviewed the histologic features of each polypoid microscopic colitis specimen, and evaluated endoscopic and clinical findings for polypoid microscopic colitis patients and controls.Twenty-six patients with polypoid microscopic colitis were identified with histologic features of collagenous colitis in 8 patients (31%) and lymphocytic colitis in 18 patients (69%). Polypoid microscopic colitis was unifocal in 14 patients (54%) and multifocal in 12 patients (46%). Patients with polypoid microscopic colitis were older than control patients (median age = 60 years vs 66 years, P = .04). On follow-up 7 patients with polypoid microscopic colitis (33%) developed chronic diarrhea compared to 3 (12%) controls (P = .16). Of patients with follow-up biopsies, 1 patient with polypoid microscopic colitis (13%) and no control patients developed microscopic colitis (P = 1).Polypoid microscopic colitis may be identified in asymptomatic patients and most patients do not develop chronic diarrhea, but some patients with polypoid microscopic colitis develop diarrhea (33% vs 12% in controls) or conventional microscopic colitis on follow-up. Thus pathologists should distinguish polypoid microscopic colitis from conventional microscopic colitis but may inform clinicians of the uncertain association with chronic diarrhea to guide decisions regarding follow-up.

Which parents provide zero-alcohol beverages to adolescents? A survey of Australian parents' practices and intentions.

OBJECTIVE: Zero-alcohol beverages (<0.5% alcohol by volume) appear and taste similar to alcoholic beverages but are regulated similarly to soft drinks in many countries, blurring the distinction between alcoholic and non-alcoholic beverages. How parents view provision of zero-alcohol beverages to adolescents is likely a key determinant of adolescent consumption. We investigated factors associated with parents' provision of zero-alcohol beverages to adolescents, including attitudes toward zero-alcohol beverages and demographic, knowledge, and behavioural factors known to be associated with provision of alcoholic beverages. METHODS: We conducted an online cross-sectional survey of N = 1197 Australian parents of adolescents aged 12-17 years in April-May 2022. We examined associations with zero-alcohol beverage provision using binomial logistic regression, and with future provision intentions using multinomial logistic regression analyses. RESULTS: Factors significantly associated (p < .001) with parents' provision and future intentions to provide zero-alcohol beverages to their adolescent included beliefs that zero-alcohol beverages had benefits for adolescents (Adjusted Odds Ratio [AOR] 2.69 (provision); 3.72 (intentions)), provision of alcoholic beverages (AOR 2.67 (provision); 3.72 (intentions)), and an incorrect understanding of alcohol guidelines for adolescents (AOR 2.38 (provision); 1.95 (intentions)). CONCLUSIONS: Parents' provision and intentions to provide zero-alcohol beverages were associated with beliefs about zero-alcohol beverages as well as some factors associated with provision of alcoholic beverages. Precautionary advice to parents that the provision of zero-alcohol beverages may serve to normalise alcohol consumption may be warranted.

Excess mortality in residents of aged care facilities during COVID-19 in Australia, 2019-22.

BACKGROUND: To date, the excess mortality experienced by residential aged care facility (RACF) residents related to COVID-19 has not been estimated in Australia. This study examined (i) the historical mortality trends (2008-09 to 2021-22) and (ii) the excess mortality (2019-20 to 2021-22) of Australian RACF residents. METHODS: A retrospective population-based study was conducted using the Australian Institute of Health and Welfare's GEN website data (publicly available aged care services information). Non-Aboriginal, older (≥65 years old) RACF residents between 2008-09 and 2021-22 were evaluated. The observed mortality rate was estimated from RACF exits compared with the RACF cohort yearly. Direct standardization was employed to estimate age-standardized mortality rates and 95% CIs. Excess mortality and 95% prediction intervals (PIs) for 2019-20 to 2021-22 were estimated using four negative binomial (NB) and NB generalized additive models and compared. RESULTS: The age-standardized mortality rate in 2018-19 was 23 061/100 000 residents (95% CI, 22 711-23 412). This rate remained similar in 2019-20 (23 023/100 000; 95% CI, 22 674-23 372), decreased in 2020-21 (22 559/100 000; 95% CI, 22 210-22 909) and increased in 2021-22 (24 885/100 000; 95% CI, 24 543-25 227). The mortality rate increase between 2020-21 and 2021-22 was observed in all age and sex groups. All models yielded excess mortality in 2021-22. Using the best-performing model (NB), the excess mortality for 2019-20 was -160 (95% PI, -418 to 98), -958 (95% PI, -1279 to -637) for 2020-21 and 4896 (95% PI, 4503-5288) for 2021-22. CONCLUSIONS: In 2021-22, RACF residents, who represented <1% of the population, experienced 21% of the Australian national excess mortality (4896/22 886). As Australia adjusts to COVID-19, RACF residents remain a population vulnerable to COVID-19.

Versatility of the double fascicular transfer in reconstruction of elbow flexion paralysis: Intermediate term follow-up and patient-related outcome measures.

OBJECTIVES: The use of fascicle transfers in the reconstruction of traumatic brachial plexus injury is well established, but limited evidence is available regarding their use in atraumatic elbow flexion paralysis. This retrospective case review aimed to verify whether median and ulnar fascicle transfers are similarly effective in atraumatic versus traumatic elbow flexion paralysis when measured using the British Medical Research Council (MRC) scale, Brachial plexus Assessment Tool (BrAT) and Stanmore Percentage of Normal Elbow Assessment (SPONEA) scores at long-term follow-up. METHODS: All median and ulnar fascicle transfer cases performed at the Queen Elizabeth Hospital Birmingham between August 2007 and November 2018 were reviewed to compare the outcomes of transfers performed for traumatic and atraumatic indications. Data on patient demographics, mechanism and nature of injury, date of injury or symptom onset, date of operation, and other nerve transfers performed were collected. Outcome measures collected included the British MRC scale and two patient-reported outcome measures (PROMs), BrAT and SPONEA. RESULTS: In total, 34 patients with 45 median and ulnar fascicle transfers were identified. This included 27 traumatic and seven atraumatic brachial plexus insults. Thirty patients had sufficient follow-up to be included in MRC analysis and 17 patients had sufficient follow-up to be included in PROM analysis. No significant differences were found between traumatic and atraumatic subgroups for median MRC, BrAT, or SPONEA scores. CONCLUSIONS: This study suggests that nerve transfers might be considered effective reconstructive options in atraumatic pathology and provides validation for further research on the subject.

Development of a core outcome set for traumatic brachial plexus injury.

The aim of the present study was to reach international consensus on the minimum set of outcomes to measure and report in adult traumatic brachial plexus injury care and research. This would facilitate comparison of outcomes from different centres and meta-analysis in research. A list of outcomes was developed from a systematic review (n = 54) and patient interviews (n = 12). The outcomes were rated in a three-round online Delphi survey completed by international surgeons, patients and therapists. Two online consensus meetings with patients and clinicians ratified the final core outcome set. A total of 72 people (20 surgeons, 21 patients, 31 therapists) from 19 countries completed all survey rounds. Thirty-eight people from nine countries attended separate patient (n = 13) and clinician consensus (n = 25) meetings. Outcomes were included if recommended by more than 85% of contributors. Pain, voluntary movement and carrying out a daily routine are the core outcome domains that should be assessed and reported when treating and researching adults with a traumatic brachial plexus injury. LEVEL OF EVIDENCE: V.

Myocardial Elasticity Imaging Correlates with Histopathology in a Model of Anthracycline-Induced Cardiotoxicity.

Background: There is considerable focus on developing strategies for identifying subclinical cardiac decline prior to cardiac failure. Myocardial tissue elasticity changes may precede irreversible cardiac damage, providing promise for an early biomarker for cardiac decline. Biomarker strategies are of particular interest in cardio-oncology due to cardiotoxic effects of anti-neoplastic therapies, particularly anthracycline-based chemotherapeutics. Current clinical methods for diagnosing cardiotoxicity are too coarse to identify cardiac decline early enough for meaningful therapeutic intervention, or too cumbersome for clinical implementation. Methods: Utilizing changes in myocardial elasticity as a biomarker for subclinical cardiac decline, we developed a biomechanical model-based elasticity imaging methodology (BEIM) to estimate spatial maps of left ventricle (LV) myocardial elasticity. In this study, we employ this methodology to assess changes in LV elasticity in a non-human primate model of doxorubicin-induced cardiotoxicity. Cardiac magnetic resonance imaging of five African Green monkeys was acquired at baseline prior to doxorubicin administration, 6-weeks, and 15-weeks after final doxorubicin dose and histopathological samples of the LV were taken at 15-weeks after final doxorubicin dose. Spatial elasticity maps of the mid-short axis plane of the LV were estimated at each image acquisition. Global and regional LV elasticity were calculated and changes between imaging time points was assessed. LV elasticity at baseline and final time point were compared to cardiomyocyte size and collagen volume fraction measurements calculated from histopathological staining of archived tissue bank samples and study endpoint tissue samples utilizing Pearson's correlation coefficients. Results: We identify significant changes in LV elasticity between each imaging time point both globally and regionally. We also demonstrate strong correlation between LV elasticity and cardiomyocyte size and collagen volume fraction measurements. Results indicate that LV elasticity estimates calculated using BEIM correlate with histopathological changes that occur due to doxorubicin administration, validating LV elasticity solutions and providing significant promise for use of BEIM to non-invasively elucidate cardiac injury. Conclusions: This methodology can show progressive changes in LV elasticity and has potential to be a more sensitive indicator of elasticity changes than current clinical measures of cardiotoxicity. LV elasticity may provide a valuable biomarker for cardiotoxic effects of anthracycline-based chemotherapeutics and cardiac disease detection.

Is it time to increase the cost of tobacco licences after 10 years of stagnation?

OBJECTIVE: Reducing tobacco licences is one potential lever to reduce tobacco-related harms. A 15-fold increase in annual tobacco retailer licence fees in 2007 led to a 24% decline in the number of licences in 2009. This study investigates the changes in tobacco licences over a subsequent decade in the absence of real fee increases. METHODS: The South Australian (SA) government tobacco licencing system databases for 2009 and 2020 were audited, measuring changes in the number and distribution of tobacco and vending machine licences by outlet type, disadvantage, and remoteness. RESULTS: The number of tobacco licences declined by 33.1% overall. Large reductions were observed in food service venues (65.2%) and hotel/motels (37.2%). In 2020, most licences were in service stations (25.1%), hotel/motels (22.9%), and supermarkets (22.2%). Despite proportional reductions across all disadvantage quintiles, the most disadvantaged areas continued to have the largest number of tobacco licensees. Vending machines declined by 63.6% and remained concentrated in hotels/motels (91.4%). CONCLUSIONS: Since a 15-fold licence fee increase in 2007 effectively reduced tobacco retailers from 2007-2009, the decline since has been incremental. IMPLICATIONS FOR PUBLIC HEALTH: Increasing tobacco licence fees is a straightforward and effective measure to reduce tobacco availability and should be re-prioritised.

Prevalence of parental supply of alcohol to minors: a systematic review.

Parental supply of alcohol to minors (i.e. those under the legal drinking age) is often perceived by parents as protective against harms from drinking, despite evidence linking it with adverse alcohol-related outcomes. This systematic review describes the prevalence of parental supply of alcohol, as reported in the international literature. The review was registered with PROSPERO (CRD42020218754). We searched seven online databases (Medline, Embase, PsycINFO, CINAHL, Scopus, Web of Science and Public Health Database) and grey literature from January 2011 to December 2022 and assessed the risk of bias with the JBI Critical Appraisal Checklist. Among 58 articles included in narrative synthesis from 29 unique datasets, there was substantial variation in the definition and measurement of parental supply of alcohol. Overall prevalence rates ranged from 7.0 to 60.0% for minor-report samples, and from 24.0 to 48.0% for parent-report samples. Data indicate that parental supply prevalence is generally proportionately higher for older minors or later-stage students, for girls, and has increased over time among minors who report drinking. Literature on the prevalence of parental supply of alcohol is robust in quantity but inconsistent in quality and reported prevalence. Greater consistency in defining and measuring parental supply is needed to better inform health promotion initiatives aimed at increasing parents' awareness.

Reducing neuropathies between the 2020 and 2021 Covid-19 surges in a large UK intensive care unit: A quality improvement project.

BACKGROUND: Peripheral nerve injuries (PNIs) can be acquired by patients in intensive care unit (ICU) who are critically unwell with Covid pneumonitis. Prone position ventilation has been linked to this life-changing complication. AIM: To reduce the occurrence and severity of PNIs for patients with Covid pneumonitis requiring prone positioning whilst sedated and ventilated in ICU. STUDY DESIGN: This study is a quality improvement project that evolved over the course of the first two surges of Covid pneumonitis admissions within the ICU at the Queen Elizabeth Hospital Birmingham (Surge 1: March 2020-July 2020, 93 prone ventilation survivors; Surge 2: September 2020-May 2021, 309 prone ventilation survivors). Implementation of updated prone positioning guidelines that aimed to reduce the risk of PNI. This was supplemented by face-to-face teaching for ICU professionals. The number of patients who sustained PNI and the severity of such injuries were recorded. RESULTS: During the first surge 21 patients (22.6%) had at least one high grade PNI. During the second surge there were 12 patients (3.9%) sustaining an intermediate or high grade PNI. For PNI patients, there was an increase in the mean proning episodes (6-13) and duration (17.8-18.6 h). This represents an 82% reduction in PNI cases. High grade injuries reduced from 14/21 (66%) to 4/12 (33%). CONCLUSIONS: Optimizing the position of patients in the prone position in ICU with Covid pneumonitis may be key in reducing the development of PNI. Changes to pharmacological management may have influenced the results seen in this study. RELEVANCE TO CLINICAL PRACTICE: Clinicians working within ICU with acutely unwell patients with Covid pneumonitis should acknowledge the heightened risk of PNI and take relevant steps to reduce the risk of injury acquisition.

Genomic and ecological factors shaping specialism and generalism across an entire subphylum.

Organisms exhibit extensive variation in ecological niche breadth, from very narrow (specialists) to very broad (generalists). Paradigms proposed to explain this variation either invoke trade-offs between performance efficiency and breadth or underlying intrinsic or extrinsic factors. We assembled genomic (1,154 yeast strains from 1,049 species), metabolic (quantitative measures of growth of 843 species in 24 conditions), and ecological (environmental ontology of 1,088 species) data from nearly all known species of the ancient fungal subphylum Saccharomycotina to examine niche breadth evolution. We found large interspecific differences in carbon breadth stem from intrinsic differences in genes encoding specific metabolic pathways but no evidence of trade-offs and a limited role of extrinsic ecological factors. These comprehensive data argue that intrinsic factors driving microbial niche breadth variation.

Impact of diabetes and chronic kidney disease on active surveillance outcomes for small renal masses: A cohort study.

Introduction: The American Cancer Society estimates 79,000 individuals will be diagnosed with kidney cancer in 2022, most of which are initially found as small renal masses (SRMs). Proper management of SRM patients includes careful evaluation of risk factors such as medical comorbidities and renal function. To investigate the importance of these risk factors, we examined their effect on crossover to delayed intervention (DI) and overall survival (OS) in patients undergoing active surveillance (AS) for SRMs. Methods: This is an Institutional Review Board-approved retrospective analysis of AS patients presented at kidney tumor conferences with SRMs between 2007 and 2017. Univariable and multivariable logistic regression analyses were performed to determine how factors including estimated glomerular filtration rate (eGFR), diabetes, and chronic kidney disease are associated with DI and OS. Results: A total of 111 cases were reviewed. In general, AS patients were elderly and had significant comorbidities. On univariate analysis, intervention was more likely to occur in patients with a younger age (P = 0.01), better kidney function (P = 0.01), and higher tumor growth rates (GRs) (P = 0.02). Higher eGFR was associated with better survival (P = 0.03), while higher tumor GRs (P = 0.014), greater Charlson Comorbidity Index (P = 0.01), and larger tumors (P = 0.01) were associated with worse OS. Of the comorbidities, diabetes was found to be an independent predictor of worse OS (P = 0.01). Conclusions: Patient-level factors - such as diabetes and eGFR - are associated with the rate of DI and OS among SRM patients. Consideration of these factors may facilitate better AS protocols and improve patient outcomes for those with SRMs.

Muscle assessment in brachial plexus injury: A reliability study.

PURPOSE: Motor outcome following a brachial plexus injury is frequently measured to evaluate the success of surgical interventions. We aimed to identify whether the manual muscle testing using the Medical Research Council (MRC) method in adults with C5/6/7 motor weakness was reliable and whether its results correlated with functional recovery. METHODS: Two experienced clinicians examined 30 adults with C5/6/7 weakness following proximal nerve injury. The examination included using the modified MRC to assess motor outcome in the upper limb. Kappa statistics were calculated to evaluate inter-tester reliability. Correlation coefficients was calculated to explore the correlation between the MRC and the Disabilities of the Arm Shoulder and Hand (DASH) score and each EQ5D domain. RESULTS: We found that grades 3-5 of the modified and unmodified MRC motor rating scales have poor inter-rater reliability when assessing C5/6/7 innervated muscles in adults with a proximal nerve injury. The Deltoid Posterior and the Extensor Carpi Radialis Longus were the only muscles (using the modified MRC) to achieve a Kappa over 0.6 indicating substantial reliability. Higher combined MRC scores correlated significantly with a lower DASH and vice versa. Similarly, higher combined scores of MRC correlated significantly with a higher rating of overall health on the EQ5D VAS. CONCLUSIONS: This study demonstrates that the MRC motor rating scale has poor inter-rater reliability when assessing C5/C6/C7 innervated muscles in adults following proximal nerve injury. Other methods of assessing motor outcome following proximal nerve injury need to be considered.

Enhanced Ca2+-channeling complex formation at the ER-mitochondria interface underlies the pathogenesis of alcohol-associated liver disease.

Ca2+ overload-induced mitochondrial dysfunction is considered as a major contributing factor in the pathogenesis of alcohol-associated liver disease (ALD). However, the initiating factors that drive mitochondrial Ca2+ accumulation in ALD remain elusive. Here, we demonstrate that an aberrant increase in hepatic GRP75-mediated mitochondria-associated ER membrane (MAM) Ca2+-channeling (MCC) complex formation promotes mitochondrial dysfunction in vitro and in male mouse model of ALD. Unbiased transcriptomic analysis reveals PDK4 as a prominently inducible MAM kinase in ALD. Analysis of human ALD cohorts further corroborate these findings. Additional mass spectrometry analysis unveils GRP75 as a downstream phosphorylation target of PDK4. Conversely, non-phosphorylatable GRP75 mutation or genetic ablation of PDK4 prevents alcohol-induced MCC complex formation and subsequent mitochondrial Ca2+ accumulation and dysfunction. Finally, ectopic induction of MAM formation reverses the protective effect of PDK4 deficiency in alcohol-induced liver injury. Together, our study defines a mediatory role of PDK4 in promoting mitochondrial dysfunction in ALD.