Outcomes of Total Shoulder Arthroplasty With and Without Prior Rotator Cuff Repair: A Systematic Review.

Background: The effect of prior rotator cuff repair (RCR) on clinical outcomes after total shoulder arthroplasty (TSA) is unclear. Purpose: To systematically review the literature to compare the outcomes of TSA in patients with and without prior RCR. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines by searching the PubMed, Cochrane Library, and Embase databases to identify studies comparing outcomes of TSA with and without prior RCR. The inclusion criteria were full-text studies that directly compared outcomes between patients undergoing anatomic or reverse TSA with and without prior RCR. A quality assessment was performed using the Modified Coleman Methodology Score (MCMS), and risk of bias assessment was performed using the Risk Of Bias In Non-randomized Studies-of Interventions (ROBINS-I) tool. A total of 1542 articles were identified for review based on initial database queries. Weighted means of quantifiable demographics and patient-reported outcomes were calculated for all included studies and compiled, in addition to the MCMS and ROBINS-I tool. Results: Twelve studies (10 level 3, 2 level 4) met inclusion criteria, including a total of 885 patients who underwent RCR before TSA (mean age, 68.2 years) and 2275 patients with no prior RCR (mean age, 70.0 years). Of all outcomes evaluated, patients with reverse TSA showed superior results in the no prior RCR group. Three reverse TSA studies found the no prior RCR group to have significantly higher postoperative American Shoulder and Elbow Surgeons scores when compared with the prior RCR group (P < .05). Multiple reverse TSA studies found the no prior RCR group to have significantly higher postoperative Simple Shoulder Test scores (P < .05) and significantly improved forward elevation (P < .05) when compared with the prior RCR group. Of all outcomes in anatomic TSA studies, only complication rate was different between groups, with 1 study finding a significantly lower complication rate in the no prior RCR group (P = .01). Conclusion: Patients undergoing reverse TSA without prior RCR can be expected to experience statistically better outcomes when compared with patients with prior RCR, while patients undergoing anatomic TSA can be expected to have similar outcomes regardless of prior RCR status.

Evaluation of Mental Health First Aid training and simulated psychosis care role-plays for pharmacy education.

OBJECTIVE: This study explored the impact of Mental Health First Aid (MHFA) training and simulated psychosis care role-plays on pharmacy students' stigma, confidence and behaviors when supporting people experiencing mental health symptoms or crises. METHODS: MHFA training was delivered to final year pharmacy students. Post-MHFA training, students were invited to participate in simulated psychosis care role-plays (co-designed and content validated with mental health stakeholders) with trained actors. Role-plays were observed by peers, tutors and mental health consumer educators (MHCEs). Students immediately engaged in self-assessment, feedback and debrief discussions with peers, tutors and MHCEs. Quantitative analyses (ANOVA and chi-square tests) were conducted on scores awarded by each rater (self, tutor, MHCE) and for each scenario (n=3). Students completed a 15-item survey exploring mental health stigma and mental health confidence, at three timepoints (pre-MHFA training, post-MHFA training, post-role-plays). Survey scores were analyzed using paired t-tests. RESULTS: Of 209 MHFA-trained students, 86 participated in role-play. Self-assessment mean score was lowest and MHCEs' mean score highest. Post-MHFA training, 14 survey item scores significantly improved, implying reduced stigma and increased confidence in providing psychosis care. Post-role-play scores suggested improvements in 12 survey items. CONCLUSION: Psychosis care role-plays are associated with short-term improvements in pharmacy students' stigma and mental health confidence post-MHFA training; students' self-assessment scores are lower than tutors and MHCEs. It is recommended that future studies further integrate observed behaviors with self-reported data and use simulated patients in clinical practice to evaluate MHFA outcomes longitudinally.

Genotypic and phenotypic characterisation of three local chicken ecotypes of Ghana based on principal component analysis and body measurements.

This study aimed to characterise three Ghanaian local chicken ecotypes, namely, Interior Savannah, Forest, and Coastal Savannah, based on morphological data and single nucleotide polymorphism (SNP) genotypes. Morphological data including body weight, shank length, body girth, back length, thigh length, beak length, comb length, and wattle length were collected from 250 local chickens. DNA isolated from blood of 1,440 local chickens was used for SNP genotyping with the Affymetrix chicken 600k SNP chip. Principal component analysis showed that Forest and Coastal Savannah birds were closely related. Generally, all three ecotypes exhibited high genetic diversity, especially birds from the Interior Savannah zone. Morphological characterisation showed that ecotype (p = 0.016) and sex (p = 0.000) had significant effects on body weight. Birds of the Interior Savannah ecotype were the heaviest (p = 0.004), with mean weights of 1.23 kg for females and 1.40 kg for males. Sex also had a strong significant effect on most of the morphological measurements, but the sex * ecotype interaction effect was not significant. Very few of the feather phenotypes previously reported to be associated with heat resistance-frizzle (2%) and naked neck (1.6%)-were found in the studied populations. It is concluded that the three local ecotypes are genetically diverse but with similar morphological features and the information provided would be useful for future selection decisions.

Resolution of Persistent Chylothorax With a Ketogenic Diet: A Case Report.

This is the first case report of a very low-carbohydrate, high-fat ketogenic diet for the treatment of chylothorax. A 61-year-old female with recurrent chylothorax following thoracic surgery was refractory to a very low-fat diet managed by a hospital dietitian. She required repeated palliative thoracentesis to the point where she was scheduled for a thoracic duct embolization. Prior to the embolization, she was placed on a very low-carbohydrate (<20 total grams daily), high-fat, ketogenic diet. Metabolic markers and imaging were obtained regularly. The patient had improvements in her serum triglycerides, triglyceride/HDL ratio, and triglyceride-glucose index, as well as clinical and radiographic improvements in her chylothorax as assessed by a chest X-ray and CT scan. Within three months of starting her ketogenic diet, imaging revealed complete resolution of the chylous pleural effusion. This case suggests that metabolic optimization to decrease insulin resistance, improve chylomicron metabolism, decrease lymphatic permeability, and lower serum triglycerides, as occurs with a ketogenic diet, should be considered for conservative treatment of chylothorax and warrants further study.

Comparison of Medical Research Abstracts Written by Surgical Trainees and Senior Surgeons or Generated by Large Language Models.

Importance: Artificial intelligence (AI) has permeated academia, especially OpenAI Chat Generative Pretrained Transformer (ChatGPT), a large language model. However, little has been reported on its use in medical research. Objective: To assess a chatbot's capability to generate and grade medical research abstracts. Design, Setting, and Participants: In this cross-sectional study, ChatGPT versions 3.5 and 4.0 (referred to as chatbot 1 and chatbot 2) were coached to generate 10 abstracts by providing background literature, prompts, analyzed data for each topic, and 10 previously presented, unassociated abstracts to serve as models. The study was conducted between August 2023 and February 2024 (including data analysis). Exposure: Abstract versions utilizing the same topic and data were written by a surgical trainee or a senior physician or generated by chatbot 1 and chatbot 2 for comparison. The 10 training abstracts were written by 8 surgical residents or fellows, edited by the same senior surgeon, at a high-volume hospital in the Southeastern US with an emphasis on outcomes-based research. Abstract comparison was then based on 10 abstracts written by 5 surgical trainees within the first 6 months of their research year, edited by the same senior author. Main Outcomes and Measures: The primary outcome measurements were the abstract grades using 10- and 20-point scales and ranks (first to fourth). Abstract versions by chatbot 1, chatbot 2, junior residents, and the senior author were compared and judged by blinded surgeon-reviewers as well as both chatbot models. Five academic attending surgeons from Denmark, the UK, and the US, with extensive experience in surgical organizations, research, and abstract evaluation served as reviewers. Results: Surgeon-reviewers were unable to differentiate between abstract versions. Each reviewer ranked an AI-generated version first at least once. Abstracts demonstrated no difference in their median (IQR) 10-point scores (resident, 7.0 [6.0-8.0]; senior author, 7.0 [6.0-8.0]; chatbot 1, 7.0 [6.0-8.0]; chatbot 2, 7.0 [6.0-8.0]; P = .61), 20-point scores (resident, 14.0 [12.0-7.0]; senior author, 15.0 [13.0-17.0]; chatbot 1, 14.0 [12.0-16.0]; chatbot 2, 14.0 [13.0-16.0]; P = .50), or rank (resident, 3.0 [1.0-4.0]; senior author, 2.0 [1.0-4.0]; chatbot 1, 3.0 [2.0-4.0]; chatbot 2, 2.0 [1.0-3.0]; P = .14). The abstract grades given by chatbot 1 were comparable to the surgeon-reviewers' grades. However, chatbot 2 graded more favorably than the surgeon-reviewers and chatbot 1. Median (IQR) chatbot 2-reviewer grades were higher than surgeon-reviewer grades of all 4 abstract versions (resident, 14.0 [12.0-17.0] vs 16.9 [16.0-17.5]; P = .02; senior author, 15.0 [13.0-17.0] vs 17.0 [16.5-18.0]; P = .03; chatbot 1, 14.0 [12.0-16.0] vs 17.8 [17.5-18.5]; P = .002; chatbot 2, 14.0 [13.0-16.0] vs 16.8 [14.5-18.0]; P = .04). When comparing the grades of the 2 chatbots, chatbot 2 gave higher median (IQR) grades for abstracts than chatbot 1 (resident, 14.0 [13.0-15.0] vs 16.9 [16.0-17.5]; P = .003; senior author, 13.5 [13.0-15.5] vs 17.0 [16.5-18.0]; P = .004; chatbot 1, 14.5 [13.0-15.0] vs 17.8 [17.5-18.5]; P = .003; chatbot 2, 14.0 [13.0-15.0] vs 16.8 [14.5-18.0]; P = .01). Conclusions and Relevance: In this cross-sectional study, trained chatbots generated convincing medical abstracts, undifferentiable from resident or senior author drafts. Chatbot 1 graded abstracts similarly to surgeon-reviewers, while chatbot 2 was less stringent. These findings may assist surgeon-scientists in successfully implementing AI in medical research.

Trajectories of Inflammation in Youth and Risk of Mental and Cardiometabolic Disorders in Adulthood.

Importance: Research suggests that low-grade, nonresolving inflammation may predate adult mental and physical illness. However, evidence to date is largely cross-sectional or focuses on single disorder outcomes. Objectives: To examine trajectories of inflammation as measured by C-reactive protein (CRP) levels in a large sample of children and adolescents, and to explore associations between different identified trajectories and mental and related cardiometabolic health outcomes in early adulthood. Design, Setting, and Participants: In a longitudinal cohort study using data from the large UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), latent class growth analysis (LCGA) was used to explore different trajectories of inflammation, with logistic regression exploring association with mental and physical health outcomes. Participants with measurable CRP data and associated mental and cardiometabolic health outcomes recorded were included in the analysis. Data analysis was performed from May 1, 2023, to March 30, 2024. Exposures: Inflammation was assessed via CRP levels at ages 9, 15, and 17 years. LCGA was used to identify different trajectories of inflammation. Main Outcomes and Measures: Outcomes assessed at age 24 years included psychotic disorders, depressive disorders, anxiety disorders, hypomania, and, as a measure of insulin resistance, Homeostasis Model Assessment (HOMA2) score. Results: A total of 6556 participants (3303 [50.4%] female) were included. Three classes of inflammation were identified: persistently low CRP levels (reference class, n = 6109); persistently raised CRP levels, peaking at age 9 years (early peak, n = 197); and persistently raised CRP levels, peaking at age 17 years (late peak, n = 250). Participants in the early peak group were associated with a higher risk of psychotic disorder (odds ratio [OR], 4.60; 95% CI, 1.81-11.70; P = .008), a higher risk of severe depression (OR, 4.37; 95% CI, 1.64-11.63; P = .02), and higher HOMA2 scores (ß = 0.05; 95% CI, 0.01-0.62, P = .04) compared with participants with persistently low CRP. The late peak group was not associated with any outcomes at age 24 years. Conclusions and Relevance: Low-grade systemic inflammation peaking in midchildhood was associated with specific mental and cardiometabolic disorders in young adulthood. These findings suggest that low-grade persistent inflammation in early life may be an important shared common factor for mental-physical comorbidity and so could be relevant to future efforts of patient stratification and risk profiling.

Neuromorphic overparameterisation and few-shot learning in multilayer physical neural networks.

Physical neuromorphic computing, exploiting the complex dynamics of physical systems, has seen rapid advancements in sophistication and performance. Physical reservoir computing, a subset of neuromorphic computing, faces limitations due to its reliance on single systems. This constrains output dimensionality and dynamic range, limiting performance to a narrow range of tasks. Here, we engineer a suite of nanomagnetic array physical reservoirs and interconnect them in parallel and series to create a multilayer neural network architecture. The output of one reservoir is recorded, scaled and virtually fed as input to the next reservoir. This networked approach increases output dimensionality, internal dynamics and computational performance. We demonstrate that a physical neuromorphic system can achieve an overparameterised state, facilitating meta-learning on small training sets and yielding strong performance across a wide range of tasks. Our approach's efficacy is further demonstrated through few-shot learning, where the system rapidly adapts to new tasks.

Potential roles for pharmacists within youth mental health services: A qualitative exploration of staff views.

Background: The prevalence and burden of mental illness among young people is rising, globally. Youth mental health services, such as headspace, offer young people access to multidisciplinary mental healthcare, specifically designed to address their needs. Pharmacists are medicines experts and possess a skillset increasingly being utilised in expanded areas of practice. There is potential for pharmacists to perform roles within youth mental health services, however sparse literature exploring pharmacist-delivered mental healthcare for young people exists. Objective: To explore views of headspace staff on medication use among young people who use youth mental health services and pharmacists' potential roles within the headspace youth mental health service model. Methods: Individual semi-structured interviews were conducted with staff from one inner city headspace centre in Sydney, Australia. An interview guide was developed to capture participants' views on medication use among young people using youth mental health services and potential roles for pharmacists within this context. Reflexive thematic analysis was conducted to analyse the findings of this exploratory pilot study. Results: Twelve staff members were interviewed, allowing for a range of multidisciplinary perspectives. Four themes were identified from the data: (i) gaps in medication-related care, (ii) potential roles for pharmacists at headspace (iii) collaboration between pharmacists and general practitioners, and (iv) a "one-stop shop". Conclusions: There are opportunities for pharmacists to improve young peoples' experiences using psychotropic medications through the provision of medication information to clients and caregivers. Pharmacists have a potential role to play in contributing to multidisciplinary case reviews but clarifying their specific roles when working alongside general practitioners is necessary. Uncertainty regarding the feasibility of pharmacist-led services within the headspace youth mental health service model and a lack of awareness regarding pharmacists' full scope of practice are barriers to pharmacists' potential roles within the headspace model.

Development of Novel Bacterial Topoisomerase Inhibitors Assisted by Computational Screening.

Multidrug-resistant bacterial infections pose an ever-evolving threat to public health. Since the outset of the antibacterial age, bacteria have developed a multitude of diverse resistance mechanisms that suppress the effectiveness of current therapies. New drug entities, such as Novel Bacterial Topoisomerase Inhibitors (NBTIs), can circumvent this major issue. A computational docking model was employed to predict the binding to DNA gyrase of atypical NBTIs with novel pharmacophores. Synthesis of NBTIs based on computational docking and subsequent antibacterial evaluation against both Gram-positive and Gram-negative bacteria yielded congeners with outstanding anti-staphylococcal activity and varying activity against select Gram-negative pathogens.

A simplified protocol for deriving sterile, infectious murine Heligmosomoides polygyrus bakeri larvae.

Gastrointestinal helminth infection occurs within a diverse microbiome, complicating the interpretation of whether effects are caused by the parasite versus the microbial community. Here, we present a protocol for deriving sterile larvae of the murine helminth, Heligmosomoides polygyrus bakeri (H. polygyrus), providing experimental control of the microbiome. We describe steps for sterilizing with a bleach solution and developing into infectious larvae using E. coli. We then detail procedures for removing bacterial contaminants before harvesting to ensure the generation of germ-free larvae.

Evaluation of industrial and consumer 3-D resin printer fabrication of microdevices for quality management of genetic resources in aquatic species.

Aquatic germplasm repositories can play a pivotal role in securing the genetic diversity of natural populations and agriculturally important aquatic species. However, existing technologies for repository development and operation face challenges in terms of accuracy, precision, efficiency, and cost-effectiveness, especially for microdevices used in gamete quality evaluation. Quality management is critical throughout genetic resource protection processes from sample collection to final usage. In this study, we examined the potential of using three-dimensional (3-D) stereolithography resin printing to address these challenges and evaluated the overall capabilities and limitations of a representative industrial 3-D resin printer with a price of US$18,000, a consumer-level printer with a price

Antegrade vs Retrograde Intra-Medullary Nailing in Femoral Shaft Fractures: A Systematic Review and Meta-Analysis.

Objectives: Femoral shaft fractures are one of the most prevalent fractures found in clinical practice. Numerous operative and non-operative options are readily available for the treatment of such fractures with intra-medullary nailing being the gold standard. To date, no consensus has been reached favoring one approach over the other. Thus, this meta-analysis aims to compare the outcomes between an antegrade and retrograde intra-medullary nailing for the treatment of femoral shaft fractures. Methods: PubMed, Cochrane, Google Scholar (page 1-20), and Embase were searched till January 2024. The clinical outcomes evaluated were the incidence of adverse events, reoperations, hip and knee pain, and surgery-related parameters. Results: Higher rates of hip pain, and heterotopic ossification (p=0.0003, and p=0.0002 respectively) was observed with antegrade nailing. However, a higher rate of knee pain (p=0.02) was appreciated in retrograde nailing. There was no statistically significant difference in the remaining analyzed outcomes such as operative time, reoperation rate or other complications. Conclusion: Despite a higher rate of heterotopic ossification using the antegrade nailing technique, both the antegrade and retrograde nailing techniques yield overall similar outcomes. Therefore, the decision to choose one or the other should be based on patient-related factors, and the surgeon's experience and preference.

ChatGPT: A concise Google alternative for people seeking accurate and comprehensive carpal tunnel syndrome information.

Popular artificial intelligence systems, like ChatGPT, may be used by anyone to generate humanlike answers to questions. This study assessed whether ChatGPT version 3.5 (ChatGPTv3.5) or the first five results from a Google search provide more accurate, complete, and concise answers to the most common questions patients have about carpal tunnel syndrome. Three orthopedic hand surgeons blindly graded the answers using Likert scales to assess accuracy, completeness, and conciseness. ChatGPTv3.5 and the first five Google results provide answers to carpal tunnel syndrome questions that are similar in accuracy and completeness, but ChatGPTv3.5 answers are more concise. ChatGPTv3.5, being freely accessible to the public, is therefore a good resource for patients seeking concise, Google-equivalent answers to specific medical questions regarding carpal tunnel syndrome. ChatGPTv3.5, given its lack of updated sourcing and risk of presenting false information, should not replace frequently updated academic websites as the primary online medical resource for patients.

The impact of mental health on shoulder arthroplasty and rotator cuff repair: a meta-analysis.

BACKGROUND: The aim of this study was to evaluate the impact of mental health attributes, such as the presence of psychiatric comorbidities or psychological comorbidities (low resilience), on outcomes after rotator cuff repair (RCR) and total shoulder arthroplasty (TSA). METHODS: PubMed, Cochrane, and Google Scholar (results pages 1-20) were searched up to November 2023. Mental health problems of interest included the presence of psychiatric comorbidities (depression, anxiety) or indicators of poor psychological functioning, such as low resilience or the presence of distress. Patients were assigned to poor or good mental health groups in this study based on their grouping in the original study. RESULTS: Fourteen studies were included in the meta-analysis. Patients with good mental health had greater improvements in postoperative American Shoulder and Elbow Surgeons and Simple Shoulder Test scores in the TSA cohort (P=0.003 and P=0.01), RCR cohort (P<0.001), and the combined TSA and RCR cohort (P<0.001). No difference was found in visual analog scale score, satisfaction, external rotation, or flexion between the two mental health groups. Patients with poor mental health undergoing RCR experienced higher rates of adverse events and transfusions (P<0.001). Patients with poor mental health also had greater rates of revision and emergency department visits in the TSA cohort (P<0.001), RCR cohort (P=0.05 and P=0.03), and combined cohort (P<0.001). Patients with poor mental health undergoing TSA had a higher rate of re-admission (P<0.001). CONCLUSIONS: Patients with poor preoperative mental health showed inferior patient-reported outcome scores and increased rates of adverse events, revisions, and re-admissions. Level of evidence: III.

Enhancing simulation feasibility for multi-layer 2D MoS2 RRAM devices: reliability performance learnings from a passive network model.

While two-dimensional (2D) MoS2 has recently shown promise as a material for resistive random-access memory (RRAM) devices due to its demonstrated resistive switching (RS) characteristics, its practical application faces a significant challenge in industry regarding its limited yield and endurance. Our earlier work introduced an effective switching layer model to understand RS behavior in both mono- and multi-layered MoS2. However, functioning as a phenomenological percolation modeling tool, it lacks the capability to accurately simulate the intricate current-voltage (I-V) characteristics of the device, thereby hindering its practical applicability in 2D RRAM research. In contrast to the established conductive filament model for oxide-based RRAM, the RS mechanism in 2D RRAM remains elusive. This paper presents a novel simulator aimed at providing an intuitive, visual representation of the stochastic behaviors involved in the RS process of multi-layer 2D MoS2 RRAM devices. Building upon the previously proposed phenomenological simulator for 2D RRAM, users can now simulate both the I-V characteristics and the resistive switching behaviors of the RRAM devices. Through comparison with experimental data, it was observed that yield and endurance characteristics are linked to defect distributions in MoS2.

Minibeam Radiation Therapy Treatment (MBRT): Commissioning and First Clinical Implementation.

PURPOSE: Minibeam radiation therapy (MBRT) is characterized by the delivery of submillimeter-wide regions of high "peak" and low "valley" doses throughout a tumor. Preclinical studies have long shown the promise of this technique, and we report here the first clinical implementation of MBRT. METHODS AND MATERIALS: A clinical orthovoltage unit was commissioned for MBRT patient treatments using 3-, 4-, 5-, 8-, and 10-cm diameter cones. The 180 kVp output was spatially separated into minibeams using a tungsten collimator with 0.5 mm wide slits spaced 1.1 mm on center. Percentage depth dose (PDD) measurements were obtained using film dosimetry and plastic water for both peak and valley doses. PDDs were measured on the central axis for offsets of 0, 0.5, and 1 cm. The peak-to-valley ratio was calculated at each depth for all cones and offsets. To mitigate the effects of patient motion on delivered dose, patient-specific 3-dimensional-printed collimator holders were created. These conformed to the unique anatomy of each patient and affixed the tungsten collimator directly to the body. Two patients were treated with MBRT; both received 2 fractions. RESULTS: Peak PDDs decreased gradually with depth. Valley PDDs initially increased slightly with depth, then decreased gradually beyond 2 cm. The peak-to-valley ratios were highest at the surface for smaller cone sizes and offsets. In vivo film dosimetry confirmed a distinct delineation of peak and valley doses in both patients treated with MBRT with no dose blurring. Both patients experienced prompt improvement in symptoms and tumor response. CONCLUSIONS: We report commissioning results, treatment processes, and the first 2 patients treated with MBRT using a clinical orthovoltage unit. While demonstrating the feasibility of this approach is a crucial first step toward wider translation, clinical trials are needed to further establish safety and efficacy.

Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease.

BACKGROUND: Increased white matter hyperintensity (WMH) volume visible on MRI is a common finding in Alzheimer's disease (AD). We hypothesized that WMH in preclinical AD is associated with the presence of advanced vessel amyloidosis manifested as microhemorrhages (MCH). OBJECTIVES: 1) To assess the relationship between baseline WMH volume and baseline MCH. 2) To assess the relationship between longitudinal WMH accumulation and last MRI MCH during the double-blind phase of the A4 trial. DESIGN: A multicenter, randomized, double-blind, placebo-controlled, Phase 3 study comparing solanezumab with placebo given as infusions once every 4 weeks over 4.5 years in subjects with preclinical AD, defined as having evidence of elevated brain amyloid before the stage of clinically evident cognitive impairment, with an optional open-label extension period. SETTING: Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) study. PARTICIPANTS: A sample of 1157 cognitively unimpaired older adults (mean age = 71.9 years [SD = 4.8 years], 59% women, 59% APOE ε4 carriers). MEASUREMENTS: A linear regression model was used to assess the impact of baseline MCH amount (0, 1, 2+) on WMH volume. A linear mixed-effects model was used to assess the impact of last MRI MCH on longitudinal WMH. All models were corrected for age, sex, grey matter volume, cortical amyloid PET, APOE ε4 status, and treatment group. RESULTS: Baseline WMH volume was greater in individuals with more than one MCH compared to those with no MCH (t=4.8, p<0.001). The longitudinal increase in WMH amongst individuals with one (t=2.3, p=0.025) and more than one MCH (t=6.7, p<0.001) at the last MRI was greater than those with no MCH. CONCLUSION: These results indicate a strong association between WMH and MCH, a common manifestation of cerebral amyloid angiopathy and ARIA-H. These results suggest that increased WMH volume may represent an early sign of vessel amyloidosis, likely prior to the emergence of MCH.

Long-term outcomes following the Ross procedure in neonates and infants: A multi-institutional analysis.

OBJECTIVES: For neonates and infants with aortic valve pathology, the Ross procedure historically has been associated with high rates of morbidity and mortality. Data regarding long-term durability are lacking. METHODS: The international, multi-institutional Ross Collaborative included 6 tertiary care centers. Infants who underwent a Ross operation between 1996 and 2016 (allowing a minimum 5 years of follow-up) were retrospectively identified. Serial echocardiograms were examined to study evolution in neoaortic size and function. RESULTS: Primary diagnoses for the 133 patients (n = 30 neonates) included isolated aortic stenosis (14%, n = 19), Shone complex (14%, n = 19), and aortic stenosis plus other (excluding Shone complex; n = 95, 71%), including arch obstruction (n = 55), left ventricular hypoplasia (n = 9), and mitral disease (moderate or greater stenosis or regurgitation, n = 31). At the time of the Ross procedure, median age was 96 days (interquartile range, 36-186), and median weight was 4.4 kg (3.6-6.5). In-hospital mortality occurred in 13 of 133 patients (10%) (4/30 [13%] neonates). Postdischarge mortality occurred in 10 of 120 patients (8%) at a median of 298 days post-Ross. Post-Ross neoaortic dilatation occurred, peaking at 4 to 5 SDs above normal at 2 to 3 years before returning to near-baseline z-score at a median follow-up of 11.5 [6.4-17.4] years. Autograft/left ventricular outflow tract reintervention was required in 5 of 120 patients (4%) at a median of 10.3 [4.1-12.8] years. Freedom from moderate or greater neoaortic regurgitation was 86% at 15 years. CONCLUSIONS: Neonates and infants experience excellent postdischarge survival and long-term freedom from autograft reintervention and aortic regurgitation after the Ross. Neoaortic dilatation normalizes in this population in the long-term. Increased consideration should be given to Ross in neonates and infants with aortic valve disease.

Huntingtin contains an ubiquitin-binding domain and regulates lysosomal targeting of mitochondrial and RNA-binding proteins.

Understanding the normal function of the Huntingtin (HTT) protein is of significance in the design and implementation of therapeutic strategies for Huntington's disease (HD). Expansion of the CAG repeat in the HTT gene, encoding an expanded polyglutamine (polyQ) repeat within the HTT protein, causes HD and may compromise HTT's normal activity contributing to HD pathology. Here, we investigated the previously defined role of HTT in autophagy specifically through studying HTT's association with ubiquitin. We find that HTT interacts directly with ubiquitin in vitro. Tandem affinity purification was used to identify ubiquitinated and ubiquitin-associated proteins that copurify with a HTT N-terminal fragment under basal conditions. Copurification is enhanced by HTT polyQ expansion and reduced by mimicking HTT serine 421 phosphorylation. The identified HTT-interacting proteins include RNA-binding proteins (RBPs) involved in mRNA translation, proteins enriched in stress granules, the nuclear proteome, the defective ribosomal products (DRiPs) proteome and the brain-derived autophagosomal proteome. To determine whether the proteins interacting with HTT are autophagic targets, HTT knockout (KO) cells and immunoprecipitation of lysosomes were used to investigate autophagy in the absence of HTT. HTT KO was associated with reduced abundance of mitochondrial proteins in the lysosome, indicating a potential compromise in basal mitophagy, and increased lysosomal abundance of RBPs which may result from compensatory up-regulation of starvation-induced macroautophagy. We suggest HTT is critical for appropriate basal clearance of mitochondrial proteins and RBPs, hence reduced HTT proteostatic function with mutation may contribute to the neuropathology of HD.