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Abstract Background In this case series, results from daily visual exposure to intense polychromatic light of 2000 to 4000 LUX is presented. Bright light treatment is a standard procedure for treating seasonal affective disorder and prodromal Parkinson’s disease with high success. With the post-encephalitic symptoms of long-COVID closely approximating those of prodromal Parkinson’s disease, we treated insomnia and sleep-related parameters in these patients, including total sleep, number of awakenings, tendency to fall back to sleep, and fatigue, to determine whether mending sleep could improve quality of life. Case presentation We present three female and two male Caucasian patients aged 42–70 years with long-COVID that persisted from 12 weeks to 139 weeks after contracting coronavirus disease. Conclusion A light presentation protocol was adapted for long-COVID that not only restored sleep in all patients, but also unexpectedly repaired the depression, anxiety, and cognitive changes (brain fog) as well. A robust pattern of recovery commencing 4–5 days after treatment and was maintained for weeks to months without relapse. These preliminary findings represent a novel, minimally invasive approach for managing the most debilitating symptoms of long-COVID, making it an ideal candidate for the drug hypersensitive, post-encephalitic brain. That a compromised circadian mechanism seen in Parkinson’s disease may also underlie post-encephalitic long-COVID implicates a compromised role of the circadian system in these disorders.

Background: The real-world safety of robotic resections after neoadjuvant chemoimmunotherapy remains poorly defined in patients with non-small cell lung cancer. Due to reported increased operative challenges after neoadjuvant immunotherapy, we aim to describe our early institutional experience and outcomes after robotic resection in this clinical context. Methods: We performed a retrospective chart review of patients with non-small cell lung cancer who underwent a robotic lobectomy, comparing patients from June 1, 2022, through October 31, 2023, who were treated with neoadjuvant chemoimmunotherapy consistent with the Checkmate-816 protocol and a control group with upfront resection. Results: A total of 21 patients underwent neoadjuvant chemoimmunotherapy and robotic lobectomy in our cohort, and 64 patients were in the control group. Compared with control, the median tumor size was 3.2 cm vs 2.0 cm (P = .001). The most common clinical stage was IIIA (11 patients, 52%) in the neoadjuvant chemoimmunotherapy group and IA2 in the control group (26 patients, 45%) (P < .001). Operative time was greater in the neoadjuvant chemoimmunotherapy group (224 vs 177 minutes, P = .011). The median quantity of lymph nodes resected in the neoadjuvant chemoimmunotherapy group was greater (21 vs 16.5, P = .042). A R0 resection was achieved in all cases and no conversions to an open lobectomy occurred. Postoperative length of stay was 2 days in both groups (P = .92), and there were similar rates of postoperative air leak (33% vs 48%, P = .23) and acute post-hemorrhagic anemia (19% vs 14%, P = .58). Conclusions: In our cohort, robotic-assisted lobectomy was safe and of comparable quality in the setting of neoadjuvant chemoimmunotherapy.

Background: Pectus excavatum (PE) is the most common congenital chest wall defect and is characterized by the inward displacement of the sternum and costal cartilages. To date, there are limited data on adult patients undergoing the Nuss procedure for PE. This study aimed to assess the complication rate between the pediatric and adult populations and assess the trends in demographics. Methods: Retrospective analysis was conducted using a global health care database, TriNetX. Current Procedural Terminology codes (21742, 21743) were used to identify all patients who underwent Nuss procedures in the years 2004 to 2023. The cohort was then subdivided on the basis of age and sex. These patients were assessed for 30-day and 90-day major and minor postoperative complications, as well as acute pain and chronic postoperative pain. Results: A total of 2843 patients who underwent Nuss repair were identified. Patients aged >18 years had increased hemorrhagic complications (3% vs 0.86% in patients aged 18 years vs 39.1% in patients aged

Although perception of stigma (PS) has been dubbed as a key barrier to the optimal uptake of PrEP, research on PS is sparse. More specifically, no scholarly work has explored factors associated with the expression of PS toward PrEP use. This study addresses the literature gap by investigating factors associated with PS toward PrEP use. Data were drawn from the baseline survey (2017–2019) of the “Keeping It LITE Study”, involving a large cohort (n = 3330) of young sexual minority men, transgender men and women, and non-binary individuals in the US. Participants’ ages ranged from 13 to 34 years, with the majority (87%) assigned male at birth. The racial composition of the sample was diverse, with 53.9% identifying as white, 19.8% as Latinx, 10.7% as Black or African American, and smaller proportions as Asian, American Indian or Alaska Native, Native Hawaiian or other Pacific Islander, and another race/ethnicity. Logistic regression models were utilized to examine two common measures of PS in PrEP use: (1) the perception that PrEP users are seen as promiscuous and (2) the perception that PrEP users are assumed to be HIV-positive. Two sets of models were developed to account for the correlation between gender identity and sex assigned at birth. The results suggest strong PS among current PrEP users, which can explain the weak PrEP adherence reported among this group. The findings underscore the need for targeted interventions to mitigate PS and enhance PrEP uptake and adherence in vulnerable populations. Social and practical implications of the results and directions for future research are discussed.

Abstract Cenobamate has demonstrated efficacy in patients with treatment-resistant epilepsy, including patients who continued to have seizures after epilepsy surgery. This article provides recommendations for cenobamate use in patients referred for epilepsy surgery evaluation. A panel of six senior epileptologists from the United States and Europe with experience in presurgical evaluation of patients with epilepsy and in the use of antiseizure medications (ASMs) was convened to provide consensus recommendations for the use of cenobamate in patients referred for epilepsy surgery evaluation. Many patients referred for surgical evaluation may benefit from ASM optimization; both ASM and surgical treatment should be individualized. Based on previous clinical studies and the authors’ clinical experience with cenobamate, a substantial proportion of patients with treatment-resistant epilepsy can become seizure-free with cenobamate. We recommend a cenobamate trial and ASM optimization in parallel with presurgical evaluations. Cenobamate can be started before phase two monitoring, especially in patients who are found to be suboptimal surgery candidates. As neurostimulation therapies are generally palliative, we recommend trying cenobamate before vagus nerve stimulation (VNS), deep brain stimulation, or responsive neurostimulation (RNS). In surgically remediable cases (mesial temporal sclerosis, benign discrete lesion in non-eloquent cortex, cavernous angioma, etc.), cenobamate use should not delay imminent surgery; however, a patient may decide to defer or even cancel surgery should they achieve sustained seizure freedom with cenobamate. This decision should be made on an individual, case-by-case basis based on seizure etiology, patient preferences, potential surgical risks (mortality and morbidity), and likely surgical outcome. The addition of cenobamate after unsuccessful surgery or palliative neuromodulation may also be associated with better outcomes.

Interacting with target-language speakers online has become an important way for many second language students around the world to improve their skills in their target language. These types of learning interactions can take place on a wide range of online platforms, whether paid or unpaid, one-on-one or in small groups. Although research on these types of activities, often called virtual exchanges (VE), has increased, relatively little research has compared students’ experiences across different platforms. The present study compared the experiences of first and second-year university students with native speakers in in-person interactions as well as through several online services that connect language learners. Results indicate that students claimed to learn more in the in-person interactions than in the online settings. They also claimed to feel less anxiety in the in-person interactions. However, they also felt that certain online services improved their language learning in ways that were similar to the in-person interactions. In addition, each online or in-person setting offered unique advantages and disadvantages in terms of practicality and learning.

Introduction: Non-bacterial thrombotic endocarditis is well documented in the literature to occur in patients with known malignancies. It is, however, much less common for patients to be diagnosed with marantic endocarditis as the presenting sign of an unknown primary malignancy. Case Presentation: We discuss a case in which a patient was undergoing routine surveillance for his known heart failure with a transthoracic echocardiogram when an aortic valve vegetation was discovered. After further investigation, he was found to have metastatic adenocarcinoma of the lung. Next-generation sequencing was utilized to identify an EGFR mutation, which led to the patient being treated with osimertinib. Conclusion: Adequate treatment of his primary malignancy, along with anticoagulation, led to overall clinical improvement of the patient.

A healthy body mass contributes to a positive quality of life, and for overweight/obese individuals, weight loss of even modest proportions improves health-related outcomes. A novel approach to promoting body mass regulation is to pair exercise with high altitude, thereby upregulating metabolic processes and increasing caloric expenditure. As an added measure of body mass regulation, data suggest that high altitude stimulates the production of the appetite-suppressing hormone leptin. Issues arise, however, given that high altitude compromises aerobic exercise capacity. Whereas exercising at high altitude may compromise exercise intensity and duration, recovering at high altitude retains the integrity of exercise while still potentially conferring the benefits of the low oxygen environment on energy expenditure and energy intake. The purpose of this study was to perform a proof-of-concept pilot test on whether post-exercise exposure to a simulated high altitude influenced acute energy balance. Twelve healthy men and women ran for 30 min at a moderate intensity on two separate occasions. Following exercise, participants recovered for 30 min while breathing either sea level air or low oxygen air simulating high altitude (equivalent to 4500 m elevation). Blood samples and hunger ratings were collected pre-exercise and post-recovery. Heart rate was recorded throughout exercise and recovery and used to calculate caloric expenditure. Post-exercise energy expenditure was significantly higher (p = 0.03) following high altitude recovery (139 ± 15 kcal) compared to sea-level recovery (98 ± 11 kcal). Participants reported a lower desire to eat when they recovered in the high altitude environment (p = 0.01), though post-recovery leptin concentrations were similar between the two conditions. Post-exercise exposure to a simulated high altitude environment represents a promising method for increasing daily caloric expenditure and lowering appetite. Given the pilot nature of this study, future research is needed to address the question of high altitude recovery on a larger sample over a longer time period and with robust measures of caloric expenditure.

Introduction Tacrolimus is an immunosuppressant commonly administered in transplant recipients. Given its narrow therapeutic range and susceptibility to various influencing variables, determining its optimal dosage is challenging. This systematic review seeks to identify effective analytical modelling techniques and methods for optimal tacrolimus dose prediction in solid transplant recipients.Methods and analysis This review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The study will review the literature published from database inception to 11 March 2024, that assesses predictive models of tacrolimus dosing through analytical modelling techniques. We will include both randomised and non-randomised, as well as cross-sectional, qualitative and before-and-after studies and will perform our searches in four main databases—Ovid/MEDLINE, PubMed/MEDLINE, Scopus, Embase and Web of Science, and search engines including Centers for Disease Control (CDC) and Google Scholar. Papers that are not published in English or French are excluded from this study. A narrative synthesis and meta-analysis will be done if the extracted information permits such analysis. Conference abstracts will be ignored unless they are recent (published within 2 years of the search date).Ethics and dissemination Ethics clearance is not required for this study as no primary data will be collected. The completed manuscript will be published, and the results of the study will be presented at conferences.Study registration International Prospective Register of Systematic Reviews (PROSPERO), CRD42024537212.

Summary: The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Alpha variant in 2020 demonstrated the need for reanalysis of diagnostic tests to ensure detection of emerging variants. Here, we present a protocol for creating and characterizing SARS-CoV-2 variant testing panels using remnant clinical samples for diagnostic assay testing. We describe steps for characterizing SARS-CoV-2 remnant clinical samples and preparing them into pools and their use in preparing varying quantities of virus. We then detail procedures for verifying variant detection using the resulting sample panel.For complete details on the use and execution of this protocol, please refer to Rao et al.1,2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background It is well established that traumatic brain injury (TBI) causes acute and chronic alterations in systemic immune function and that systemic immune changes contribute to posttraumatic neuroinflammation and neurodegeneration. However, how TBI affects bone marrow (BM) hematopoietic stem/progenitor cells chronically and to what extent such changes may negatively impact innate immunity and neurological function has not been examined. Methods To further understand the role of BM cell derivatives on TBI outcome, we generated BM chimeric mice by transplanting BM from chronically injured or sham (i.e., 90 days post-surgery) congenic donor mice into otherwise healthy, age-matched, irradiated CD45.2 C57BL/6 (WT) hosts. Immune changes were evaluated by flow cytometry, multiplex ELISA, and NanoString technology. Moderate-to-severe TBI was induced by controlled cortical impact injury and neurological function was measured using a battery of behavioral tests. Results TBI induced chronic alterations in the transcriptome of BM lineage−c-Kit+Sca1+ (LSK+) cells in C57BL/6 mice, including modified epigenetic and senescence pathways. After 8 weeks of reconstitution, peripheral myeloid cells from TBI→WT mice showed significantly higher oxidative stress levels and reduced phagocytic activity. At eight months after reconstitution, TBI→WT chimeric mice were leukopenic, with continued alterations in phagocytosis and oxidative stress responses, as well as persistent neurological deficits. Gene expression analysis revealed BM-driven changes in neuroinflammation and neuropathology after 8 weeks and 8 months of reconstitution, respectively. Chimeric mice subjected to TBI at 8 weeks and 8 months post-reconstitution showed that longer reconstitution periods (i.e., time post-injury) were associated with increased microgliosis and leukocyte infiltration. Pre-treatment with a senolytic agent, ABT-263, significantly improved behavioral performance of aged C57BL/6 mice at baseline, although it did not attenuate neuroinflammation in the acutely injured brain. Conclusions TBI causes chronic activation and progressive dysfunction of the BM stem/progenitor cell pool, which drives long-term deficits in hematopoiesis, innate immunity, and neurological function, as well as altered sensitivity to subsequent brain injury.

Summary: Background: Genetic variants and gene expression predict risk of chronic obstructive pulmonary disease (COPD), but their effect on COPD heterogeneity is unclear. We aimed to define high-risk COPD subtypes using genetics (polygenic risk score, PRS) and blood gene expression (transcriptional risk score, TRS) and assess differences in clinical and molecular characteristics. Methods: We defined high-risk groups based on PRS and TRS quantiles by maximising differences in protein biomarkers in a COPDGene training set and identified these groups in COPDGene and ECLIPSE test sets. We tested multivariable associations of subgroups with clinical outcomes and compared protein–protein interaction networks and drug repurposing analyses between high-risk groups. Findings: We examined two high-risk omics-defined groups in non-overlapping test sets (n = 1133 NHW COPDGene, n = 299 African American (AA) COPDGene, n = 468 ECLIPSE). We defined “high activity” (low PRS, high TRS) and “severe risk” (high PRS, high TRS) subgroups. Participants in both subgroups had lower body-mass index (BMI), lower lung function, and alterations in metabolic, growth, and immune signalling processes compared to a low-risk (low PRS, low TRS) subgroup. “High activity” but not “severe risk” participants had greater prospective FEV1 decline (COPDGene: −51 mL/year; ECLIPSE: −40 mL/year) and proteomic profiles were enriched in gene sets perturbed by treatment with 5-lipoxygenase inhibitors and angiotensin-converting enzyme (ACE) inhibitors. Interpretation: Concomitant use of polygenic and transcriptional risk scores identified clinical and molecular heterogeneity amongst high-risk individuals. Proteomic and drug repurposing analysis identified subtype-specific enrichment for therapies and suggest prior drug repurposing failures may be explained by patient selection. Funding: National Institutes of Health.

BackgroundSurvey-driven research is a reliable method for large-scale data collection. Investigators incorporating mixed-mode survey designs report benefits for survey research including greater engagement, improved survey access, and higher response rate. Mix-mode survey designs combine 2 or more modes for data collection including web, phone, face-to-face, and mail. Types of mixed-mode survey designs include simultaneous (ie, concurrent), sequential, delayed concurrent, and adaptive. This paper describes a research protocol using mixed-mode survey designs to explore health IT (HIT) maturity and care environments reported by administrators and nurse practitioners (NPs), respectively, in US nursing homes (NHs). ObjectiveThe aim of this study is to describe a research protocol using mixed-mode survey designs in research using 2 survey tools to explore HIT maturity and NP care environments in US NHs. MethodsWe are conducting a national survey of 1400 NH administrators and NPs. Two data sets (ie, Care Compare and IQVIA) were used to identify eligible facilities at random. The protocol incorporates 2 surveys to explore how HIT maturity (survey 1 collected by administrators) impacts care environments where NPs work (survey 2 collected by NPs). Higher HIT maturity collected by administrators indicates greater IT capabilities, use, and integration in resident care, clinical support, and administrative activities. The NP care environment survey measures relationships, independent practice, resource availability, and visibility. The research team conducted 3 iterative focus groups, including 14 clinicians (NP and NH experts) and recruiters from 2 national survey teams experienced with these populations to achieve consensus on which mixed-mode designs to use. During focus groups we identified the pros and cons of using mixed-mode designs in these settings. We determined that 2 mixed-mode designs with regular follow-up calls (Delayed Concurrent Mode and Sequential Mode) is effective for recruiting NH administrators while a concurrent mixed-mode design is best to recruit NPs. ResultsParticipant recruitment for the project began in June 2023. As of April 22, 2024, a total of 98 HIT maturity surveys and 81 NP surveys have been returned. Recruitment of NH administrators and NPs is anticipated through July 2025. About 71% of the HIT maturity surveys have been submitted using the electronic link and 23% were submitted after a QR code was sent to the administrator. Approximately 95% of the NP surveys were returned with electronic survey links. ConclusionsPros of mixed-mode designs for NH research identified by the team were that delayed concurrent, concurrent, and sequential mixed-mode methods of delivering surveys to potential participants save on recruitment time compared to single mode delivery methods. One disadvantage of single-mode strategies is decreased versatility and adaptability to different organizational capabilities (eg, access to email and firewalls), which could reduce response rates. International Registered Report Identifier (IRRID)DERR1-10.2196/56170

Abstract Current eddy‐permitting and eddy‐resolving ocean models require dissipation to prevent a spurious accumulation of enstrophy at the grid scale. We introduce a new numerical scheme for momentum advection in large‐scale ocean models that involves upwinding through a weighted essentially non‐oscillatory (WENO) reconstruction. The new scheme provides implicit dissipation and thereby avoids the need for an additional explicit dissipation that may require calibration of unknown parameters. This approach uses the rotational, “vector invariant” formulation of the momentum advection operator that is widely employed by global general circulation models. A novel formulation of the WENO “smoothness indicators” is key for avoiding excessive numerical dissipation of kinetic energy and enstrophy at grid‐resolved scales. We test the new advection scheme against a standard approach that combines explicit dissipation with a dispersive discretization of the rotational advection operator in two scenarios: (a) two‐dimensional turbulence and (b) three‐dimensional baroclinic equilibration. In both cases, the solutions are stable, free from dispersive artifacts, and achieve increased “effective” resolution compared to other approaches commonly used in ocean models.

Background Aging‐associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)–magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model. Methods and Results Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6‐month‐old senescence‐accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET‐MRI at 4.7 T. Collagen‐targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium‐ or lung‐to‐muscle ratio. Percent signal intensity increase and Δ lung‐to‐muscle ratio were computed from the pre‐/postinjection magnetic resonance images. Elevated allysine in the heart (P=0.02) and lungs (P=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (P

Background Cardiovascular disease (CVD) is the most important comorbidity in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations not only contribute to COPD progression but may also elevate the risk of CVD. This study aimed to determine whether COPD exacerbations increase the risk of subsequent CVD events using up to 15 years of prospective longitudinal follow‐up data from the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study. Methods and Results The COPDGene study is a large, multicenter, longitudinal investigation of COPD, including subjects at enrollment aged 45 to 80 years with a minimum of 10 pack‐years of smoking history. Cox proportional hazards models and Kaplan‐Meier survival curves were used to assess the risk of a composite end point of CVD based on the COPD exacerbation rate. Frequent exacerbators exhibited a higher cumulative incidence of composite CVD end points than infrequent exacerbators, irrespective of the presence of CVD at baseline. After adjusting for covariates, frequent exacerbators still maintained higher hazard ratios (HRs) than the infrequent exacerbator group (without CVD: HR, 1.81 [95% CI, 1.47–2.22]; with CVD: HR, 1.92 [95% CI, 1.51–2.44]). This observation remained consistently significant in moderate to severe COPD subjects and the preserved ratio impaired spirometry population. In the mild COPD population, frequent exacerbators showed a trend toward more CVD events. Conclusions COPD exacerbations are associated with an increased risk of subsequent cardiovascular events in subjects with and without preexisting CVD. Patients with COPD experiencing frequent exacerbations may necessitate careful monitoring and additional management for subsequent potential CVD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00608764.

Abstract Lymph node metastases are a major prognostic factor in survival of patients with oesophageal cancer. The number of lymph nodes removed during oesophagectomy has been previously proven to be associated with improved survival. The aim of this study was to examine the effect of lymph node harvest on survival specifically in pathologically node negative (pN0) patients with oesophageal cancer. Data were extracted from a prospectively populated single-surgeon database of oesophageal resections for cancer. All consecutive patients with pN0 were included. Patient-specific risk adjusted analysis of overall and disease-free survival was performed to identify the number of lymph nodes associated with improved survival. Inclusion criteria were met by 137 patients (49 squamous cell carcinoma and 88 adenocarcinoma). Adjusted for cancer stage, tumour (histological type, degree of differentiation, lympho-vascular invasion, neo-adjuvant therapy) and patient related factors (age, sex), increased lymph node number was associated with significant improvement in overall (P = 0.045) and disease free (P = 0.030) survival. Lymph node count ≥ 17 was associated with improved overall and disease-free survival. In this cohort of patients with pathologically node-negative oesophageal cancer, lymph node count of 17 or above was associated with significantly improved survival.

Abstract Widespread adoption of mirror-image biological systems presents difficulties in accessing the requisite D-protein substrates. In particular, mirror-image phage display has the potential for high-throughput generation of biologically stable macrocyclic D-peptide binders with potentially unique recognition modes but is hindered by the individualized optimization required for D-protein chemical synthesis. We demonstrate a general mirror-image phage display pipeline that utilizes automated flow peptide synthesis to prepare D-proteins in a single run. With this approach, we prepare and characterize 12 D-proteins – almost one third of all reported D-proteins to date. With access to mirror-image protein targets, we describe the successful discovery of six macrocyclic D-peptide binders: three to the oncoprotein MDM2, and three to the E3 ubiquitin ligase CHIP. Reliable production of mirror-image proteins can unlock the full potential of D-peptide drug discovery and streamline the study of mirror-image biology more broadly.

Abstract Background This study estimated the prevalence of evidence-based care received by a population-based sample of Australian residents in long-term care (LTC) aged ≥ 65 years in 2021, measured by adherence to clinical practice guideline (CPG) recommendations. Methods Sixteen conditions/processes of care amendable to estimating evidence-based care at a population level were identified from prevalence data and CPGs. Candidate recommendations (n = 5609) were extracted from 139 CPGs which were converted to indicators. National experts in each condition rated the indicators via the RAND-UCLA Delphi process. For the 16 conditions, 236 evidence-based care indicators were ratified. A multi-stage sampling of LTC facilities and residents was undertaken. Trained aged-care nurses then undertook manual structured record reviews of care delivered between 1 March and 31 May 2021 (our record review period) to assess adherence with the indicators. Results Care received by 294 residents with 27,585 care encounters in 25 LTC facilities was evaluated. Residents received care for one to thirteen separate clinical conditions/processes of care (median = 10, mean = 9.7). Adherence to evidence-based care indicators was estimated at 53.2% (95% CI: 48.6, 57.7) ranging from a high of 81.3% (95% CI: 75.6, 86.3) for Bladder and Bowel to a low of 12.2% (95% CI: 1.6, 36.8) for Depression. Six conditions (skin integrity, end-of-life care, infection, sleep, medication, and depression) had less than 50% adherence with indicators. Conclusions This is the first study of adherence to evidence-based care for people in LTC using multiple conditions and a standardised method. Vulnerable older people are not receiving evidence-based care for many physical problems, nor care to support their mental health nor for end-of-life care. The six conditions in which adherence with indicators was less than 50% could be the focus of improvement efforts.

Abstract Understanding the thermal decomposition behavior of TATB (1,3,5-triamino-2,4,6-trinitrobenzene) is a major focus in energetic materials research because of safety issues. Previous research and modelling efforts have suggested benzo-monofurazan condensation producing H2O is the initiating decomposition step. However, early evolving CO2 (m/z 44) along with H2O (m/z 18) evolution have been observed by mass spectrometric monitoring of head-space gases in both constant heating rate and isothermal decomposition studies. The source of the CO2 has not been explained, until now. With the recent successful synthesis of 13C6-TATB (13C incorporated into the benzene ring), the same experiments have been used to show the source of the CO2 is the early breakdown of the TATB ring, not adventitious C from impurities and/or adsorbed CO2. A shift in mass m/z 44 (CO2) to m/z 45 is observed throughout the decomposition process indicating the isotopically labeled 13C ring breakdown occurs at the onset of thermal decomposition along with furazan formation. Partially labeled (N18O2)3-TATB confirms at least some of the oxygen comes from the nitro-groups. This finding has a significant bearing on decomposition computational models for prediction of energy release and deflagration to detonation transitions, with respect to conditions which currently do not recognize this oxidation step.

Abstract Cannabis is the most prevalently used psychoactive substance in the United States. Cannabis has conflicting federal and state legal status in the US, however medical and recreational cannabis use are increasing. When assessing health outcomes, cannabis use classification has been modeled largely as current use status (never/former/current) or cumulative use (joint-years). These methods do not describe longitudinal patterns of use which may have unique relationships with health outcomes. We used cannabis use data spanning 30 years from the Coronary Artery Risk Development in Young Adults Cohort (CARDIA) to create trajectories of current cannabis use during young and middle adulthood. We identified 5 unique patterns of the probability of cannabis use during young and middle adulthood in the CARDIA Cohort. To support the cannabis probability trajectories, we qualitatively examined cumulative cannabis use as joint-years for each trajectory group. Trajectory group 5 had high probability of consistent cannabis use (0.8–0.9% probability of use) and had the highest number of joint-years (0.6 +/− 0.4). Trajectory group 1 who had a lower probability of cannabis use (0.05–0% probability of use) with the lowest number of joint-years (0.1 +/− 0.1).

Good visibility of lane markings is important for all road users, particularly autonomous vehicles. In general, nighttime retroreflectivity is one of the most challenging marking visibility characteristics for agencies to monitor and maintain, particularly in cold weather climates where agency snowplows remove retroreflective material during winter operations. Traditional surface-applied paint and glass beads typically only last one season in cold weather climates with routine snowplow activity. Recently, transportation agencies in cold weather climates have begun deploying improved recessed, durable pavement markings that can last several years and have very high retroreflective properties. Several dozen installations may occur in a state in any calendar year, presenting a challenge for states that need to program annual repainting of traditional waterborne paint lines, but not paint over the much more costly durable markings. This study reports on the utilization of mobile mapping LiDAR systems to classify and evaluate pavement markings along a 73-mile section of westbound I-74 in Indiana. LiDAR intensity data can be used to classify pavement markings as either tape or non-tape and then identify areas of tape markings that need maintenance. RGB images collected during LiDAR intensity data collection were used to validate the LiDAR classification. These techniques can be used by agencies to develop accurate pavement marking inventories to ensure that only painted lines (or segments with missing tape) are repainted during annual maintenance. Repeated tests can also track the marking intensity over time, allowing agencies to better understand material lifecycles.

In the original publication (Cowart et al [...]

Objective To compare longitudinal changes in spirometric measures between patients with rheumatoid arthritis (RA) and non-RA comparators.Methods We analysed longitudinal data from two prospective cohorts: the UK Biobank and COPDGene. Spirometry was conducted at baseline and a second visit after 5–7 years. RA was identified based on self-report and disease-modifying antirheumatic drug use; non-RA comparators reported neither. The primary outcomes were annual changes in the per cent-predicted forced expiratory volume in 1 s (FEV1%) and per cent predicted forced vital capacity (FVC%). Statistical comparisons were performed using multivariable linear regression. The analysis was stratified based on baseline smoking status and the presence of obstructive pattern (FEV1/FVC

Summary:. Calcinosis cutis is a disease process characterized by calcified lesions in the skin. Although there are five subtypes of calcinosis, idiopathic calcinosis cutis is a rare disease process with no clear etiology. It has been described in many parts of the body; however, there are only five reported cases specifically involving the hands. We describe the presentation and successful treatment of a case of idiopathic calcinosis cutis in a 65-year-old man with lesions on his bilateral hands. We believe that surgical excision of symptomatic lesions is a safe and effective treatment for idiopathic calcinosis cutis of the hands.

Background Equity, diversity and inclusion (EDI) in the healthcare field are crucial in meeting the healthcare needs of a progressively diverse society. In fact, a diverse healthcare workforce enables culturally sensitive care, promotes health equity and enhances the understanding of various needs and patients’ viewpoints, potentially resulting in more effective patient treatment and improved patient outcomes. Despite this, information on the effectiveness of policies or programmes promoting EDI in health institutions is scarce. The objective of this systematic review is to assess the effects and outcomes of EDI programmes in healthcare institutions.Methods We will conduct Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of studies on EDI programmes and describe their effects and outcomes in healthcare institutions. We will search PubMed, Scopus, Web of Science, CINAHL and PsycINFO databases. Selected studies will include randomised control trials (RCTs), non-RCTs and cross-sectional studies published either in English or French. Quality appraisal of studies and a narrative synthesis of extracted data will be conducted as well as a meta-analysis if possible. The quality of evidence in this review will be assessed by the Grades of Recommendation, Assessment, Development and Evaluation.Anticipated results We anticipate that this systematic review will reveal information on the effect of EDI programmes and their outcomes in healthcare institutions. We expect this information will provide insights that will lead to improvements in designing EDI policies and programmes in healthcare institutions.Ethics and dissemination No ethical clearance is required for this study as no primary data will be collected. The final manuscript will be submitted to a journal for publication. In addition to this, the results of the study will also be disseminated through conference presentations to inform the research and clinical practice.Review registration This protocol has been registered with the International Prospective Register of Systematic Reviews; registration number CRD42024502781.

Abstract Distributed sensors and electronics can be used in agriculture to optimize crop management and improve environmental outcomes. Electronic devices in these outdoor spaces require medium to long range (>1m) wireless communication of data over several weeks or months, which in turn requires high conductivity (1 × 105 Sm−1) antennas. Printed bioinert or ecoresorbable conductors, comprising carbon, magnesium, or zinc fillers, typically exhibit conductivity on the order of 10–1000 Sm−1 and lifetimes from a few hours to a few days. A print‐based fabrication process for chemically treated zinc traces, which achieves conductivity of up to 6 × 105 Sm−1 is reported here. The ink formulation uses a non‐water‐soluble soil biodegradable polycaprolactone binder. The ink and printing processes reported here led to stable conductive traces that are used in ultra high frequency radio frequency identification (UHF‐RFID) folded dipole antennas operating at 915 MHz. The conductivity of the printed traces is maintained for over 70 days in ambient environments when traces are protected by a biodegradable beeswax encapsulation layer.

Limited data highlight the need to understand differences in SARS-CoV-2 omicron (B.1.1.529) variant viral load between the gold standard nasopharyngeal (NP) swab, mid-turbinate (MT)/anterior nasal swabs, oropharyngeal (OP) swabs, and saliva. MT, OP, and saliva samples from symptomatic individuals in Atlanta, GA, in January 2022 and longitudinal samples from a small familial cohort were tested by both RT-PCR and ultrasensitive antigen assays. Higher concentrations in the nares were observed in the familial cohort, but a dominant sample type was not found among 39 cases in the cross-sectional cohort. The composite of positive MT or OP assay for both RT-PCR and antigen assay trended toward higher diagnostic yield but did not achieve significant difference. Our data did not identify a singular preferred sample type for SARS-CoV-2 testing, but higher levels of saliva nucleocapsid, a trend toward higher yield of composite OP/MT result, and association of apparent MT or OP predominance with symptoms warrant further study.

Abstract Molecules that induce novel interactions between proteins hold great promise for the study of biological systems and the development of therapeutics, but their discovery has been limited by the complexities of rationally designing interactions between three components, and because known binders to each protein are typically required to inform initial designs. Here, we report a general and rapid method for discovering α-helically constrained (Helicon) polypeptides that cooperatively induce the interaction between two target proteins without relying on previously known binders or an intrinsic affinity between the proteins. We show that Helicons are capable of binding every major class of E3 ubiquitin ligases, which are of great biological and therapeutic interest but remain largely intractable to targeting by small molecules. We then describe a phage-based screening method for discovering “trimerizer” Helicons, and apply it to reprogram E3s to cooperatively bind an enzyme (PPIA), a transcription factor (TEAD4), and a transcriptional coactivator (β-catenin).

Abstract A key challenge in bioelectronics is to establish and improve the interface between electronic devices and living tissues, enabling a direct assessment of biological systems. Sensors integrated with plant tissue can provide valuable information about the plant itself as well as the surrounding environment, including air and soil quality. An obstacle in developing interfaces to plant tissue is mitigating the formation of fibrotic tissues, which can hinder continuous and accurate sensor operation over extended timeframes. Electronic systems that utilize suitable biocompatible materials alongside appropriate fabrication techniques to establish plant-electronic interfaces could provide for enhanced environmental understanding and ecosystem management capabilities. To meet these demands, this study introduces an approach for integrating printed electronic materials with biocompatible cryogels, resulting in stable implantable hydrogel-based bioelectronic devices capable of long-term operation within plant tissue. These inkjet-printed cryogels can be customized to provide various electronic functionalities, including electrodes and organic electrochemical transistors (OECTs), that exhibit high electrical conductivity for embedded conducting polymer traces (up to 350 S/cm), transconductance for OECTs in the mS range, a capacitance of up to 4.2 mF g−1 in suitable structures, high stretchability (up to 330% strain), and self-healing properties. The biocompatible functionalized cryogel-based electrodes and transistors were successfully implanted in plant tissue, and ionic activity in tomato plant stems was collected for over two months with minimal scar tissue formation, making these cryogel-based printed electronic devices excellent candidates for continuous, in-situ monitoring of plant and environmental status and health.

Abstract Background Disease from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) remains the seventh leading cause of death in the United States. Many patients infected with this virus develop later cardiovascular complications including myocardial infarctions, stroke, arrhythmia, heart failure, and sudden cardiac death (20–28%). The purpose of this study is to understand the primary mechanism of myocardial injury in patients infected with SARS-CoV-2. Methods We investigated a consecutive cohort of 48 medical examiner cases who died with PCR-positive SARS-CoV-2 (COVpos) infection in 2020. We compared them to a consecutive cohort of 46 age- and sex-matched controls who were PCR-negative for SARS-CoV-2 (COVneg). Clinical information available at postmortem examination was reviewed on each patient. Formalin-fixed sections were examined using antibodies directed against CD42 (platelets), CD15 (myeloid cells), CD68 (monocytes), C4d, fibrin, CD34 (stem cell antigen), CD56 (natural killer cells), and myeloperoxidase (MPO) (neutrophils and neutrophil extracellular traps(NETs)). We used a Welch 2-sample T-test to determine significance. A cluster analysis of marker distribution was also done. Results We found a significant difference between COVpos and COVneg samples for CD42, CD15, CD68, C4d, fibrin, and MPO, all of which were significant at p

Abstract Background Type B lactic acidosis is a rare but serious side effect of metformin use. The risk of metformin-associated lactic acidosis is elevated in renal or liver impairment, heart failure and in metformin overdose. Metformin-associated lactic acidosis is treated with renal replacement therapy although this can be limited by metformin’s large volume of distribution and a patient’s hemodynamic instability. Tris-hydroxymethyl aminomethane is a buffer that rapidly equilibrates in liver cells and increases the intracellular pH of hepatocytes. Intracellular alkalosis increases lactate uptake by the liver and can promote gluconeogenesis which results in increased lactate metabolism and decreased lactate production. Unlike intravenous bicarbonate which can worsen acidosis due to carbon dioxide retention and hypocalcemia, tris-hydroxymethyl aminomethane does not generate large amounts of carbon dioxide and can improve cardiac contractility in experimental models. Case presentation We present a case of a 43-year-old African American male who intentionally ingested 480,000 g of metformin. He developed severe metformin-associated lactic acidosis that was refractory to 21 hours of high flux hemodialysis. This was followed by an additional 12 hours of high flux hemodialysis augmented by continuous intravenous infusion of tris-hydroxymethyl aminomethane. After initiating tris-hydroxymethyl aminomethane, the patient had rapid reversal of lactic acidosis and was weaned off vasopressors and mechanical ventilation. Conclusions While metformin-associated lactic acidosis can be treated with renal replacement therapy, severe cases of lactic acidosis may not be amenable to renal replacement therapy alone. Through its unique buffer mechanisms, tris-hydroxymethyl aminomethane can be used in conjunction with dialysis to rapidly improve acidosis associated with metformin.

Abstract Although macrophages contribute to cancer cell dissemination, immune evasion, and metastatic outgrowth, they have also been reported to coordinate tumor-specific immune responses. We therefore hypothesized that macrophage polarization could be modulated therapeutically to prevent metastasis. Here, we show that macrophages respond to β-glucan (odetiglucan) treatment by inhibiting liver metastasis. β-glucan activated liver-resident macrophages (Kupffer cells), suppressed cancer cell proliferation, and invoked productive T cell-mediated responses against liver metastasis in pancreatic cancer mouse models. Although excluded from metastatic lesions, Kupffer cells were critical for the anti-metastatic activity of β-glucan, which also required T cells. Furthermore, β-glucan drove T cell activation and macrophage re-polarization in liver metastases in mice and humans and sensitized metastatic lesions to anti-PD1 therapy. These findings demonstrate the significance of macrophage function in metastasis and identify Kupffer cells as a potential therapeutic target against pancreatic cancer metastasis to the liver.

Abstract Recent literature has shown, theoretically as well as experimentally, that while a beam splitter does not split a single photon, it nonetheless divides the electromagnetic wave into transmitted and reflected, with both containing energies. This implies the existence of a spacetime of pure electromagnetic waves of energies but without particles; also, it prompts the question on how much energy a photon loses after coming out of a beam splitter, which impacts on interferometry and hence quantum communication. This paper shows that, by Gauss divergence theorem, the gravitational force inside an electromagnetic wave ball results in a point energy that is three times as the wave energy; thus, a 50/50 beam splitter is to cause a photon to lose half of a quarter, or 1/8, of its initial wave energy.

Objectives: Although sublobar resections have gained traction, wedge resections vary widely in quality. We seek to characterize the demographic and facility-level variables associated with high-quality wedge resections. Methods: The National Cancer Database was queried from 2010 to 2018. Patients with T1/T2 N0 M0 non–small cell lung cancer 2 cm or less who underwent wedge resection without neoadjuvant therapy were included. A wedge resection with no nodes sampled or with positive margins was categorized as a low-quality wedge. A wedge resection with 4 or more nodes sampled and negative margins was categorized as a high-quality wedge. Facility-specific variables were investigated via quartile analysis based on the overall volume and proportion of high-quality wedge or low-quality wedge resections performed. Results: A total of 21,742 patients met inclusion criteria, 6390 (29.4%) of whom received a high-quality wedge resection. Factors associated with high-quality wedge resection included treatment at an academic center (3005 [47.0%] vs low-quality wedge 6279 [40.9%]; P

Duchenne muscular dystrophy is an X-linked disorder typically caused by out-of-frame mutations in the DMD gene. Most of these are deletions of one or more exons, which can theoretically be corrected through CRISPR-Cas9-mediated knockin. Homology-independent targeted integration is a mechanism for achieving such a knockin without reliance on homology-directed repair pathways, which are inactive in muscle. We designed a system based on insertion into intron 19 of a DNA fragment containing a pre-spliced mega-exon encoding DMD exons 1–19, along with the MHCK7 promoter, and delivered it via a pair of AAV9 vectors in mice carrying a Dmd exon 2 duplication. Maximal efficiency was achieved using a Cas9:donor adeno-associated virus (AAV) ratio of 1:5, with Cas9 under the control of the SPc5-12 promoter. This approach achieved editing of 1.4% of genomes in the heart, leading to 30% correction at the transcript level and restoration of 11% of normal dystrophin levels. Treatment efficacy was lower in skeletal muscles. Sequencing additionally revealed integration of fragmentary and recombined AAV genomes at the target site. These data provide proof of concept for a gene editing system that could restore full-length dystrophin in individuals carrying mutations upstream of intron 19, accounting for approximately 25% of Duchenne muscular dystrophy patients.

Dinoflagellate species that form some of the most frequent toxic blooms are also bioluminescent, yet the two traits are rarely linked when studying bloom development and persistence. P. bahamense is a toxic, bioluminescent dinoflagellate that previously bloomed in Florida with no known record of saxitoxin (STX) production. Over the past 20 years, STX was identified in P. bahamense populations. The goal of this study was to examine toxin dynamics and associated molecular mechanisms in spatially and temporally distinct P. bahamense populations from the Indian River Lagoon, FL. SxtA4 is a key gene required for toxin biosynthesis. SxtA4 genotype analysis was performed on individual cells from multiple sites. Cell abundance, toxin quota cell−1, and sxtA4 and RubisCo (rbcL) transcript abundance were also measured. There was a significant negative correlation between cell abundance and toxin quota cell−1. While the sxtA4+ genotype was dominant at all sites, its frequency varied, but it occurred at 90–100% in many samples. The underlying mechanism for toxin decrease with increased cell abundance remains unknown. However, a strong, statistically significant negative correlation was found between stxA4 transcripts and the sxtA4/rbcL ratio, suggesting cells make fewer sxtA4 transcripts as a bloom progresses. However, the influence of sxtA4− cells must also be considered. Future plans include bioluminescence measurements, normalized to a per cell basis, at sites when toxicity is measured along with concomitant quantification of sxtA4 gene and transcript copy numbers as a means to elucidate whether changes in bloom toxicity are driven more at the genetic (emergence of sxtA4− cells) or transcriptional (repression of sxtA4 in sxtA4+ cells) level. Based on the results of this study, a model is proposed that links the combined traits of toxicity and bioluminescence in P. bahamense bloom development.

G protein-coupled receptor (GPCR) transmembrane protein family members play essential roles in physiology. Numerous pharmaceuticals target GPCRs, and many drug discovery programs utilize virtual screening (VS) against GPCR targets. Improvements in the accuracy of predicting new molecules that bind to and either activate or inhibit GPCR function would accelerate such drug discovery programs. This work addresses two significant research questions. First, do ligand interaction fingerprints provide a substantial advantage over automated methods of binding site selection for classical docking? Second, can the functional status of prospective screening candidates be predicted from ligand interaction fingerprints using a random forest classifier? Ligand interaction fingerprints were found to offer modest advantages in sampling accurate poses, but no substantial advantage in the final set of top-ranked poses after scoring, and, thus, were not used in the generation of the ligand–receptor complexes used to train and test the random forest classifier. A binary classifier which treated agonists, antagonists, and inverse agonists as active and all other ligands as inactive proved highly effective in ligand function prediction in an external test set of GPR31 and TAAR2 candidate ligands with a hit rate of 82.6% actual actives within the set of predicted actives.

Abstract Using protein structure to predict function, interactions, and evolutionary history is still an open challenge, with existing approaches relying extensively on protein homology and families. Here, we present Machaon, a data-driven method combining orientation invariant metrics on phi-psi angles, inter-residue contacts and surface complexity. It can be readily applied on whole structures or segments—such as domains and binding sites. Machaon was applied on SARS-CoV-2 Spike monomers of native, Delta and Omicron variants and identified correlations with a wide range of viral proteins from close to distant taxonomy ranks, as well as host proteins, such as ACE2 receptor. Machaon’s meta-analysis of the results highlights structural, chemical and transcriptional similarities between the Spike monomer and human proteins, indicating a multi-level viral mimicry. This extended analysis also revealed relationships of the Spike protein with biological processes such as ubiquitination and angiogenesis and highlighted different patterns in virus attachment among the studied variants. Available at: https://machaonweb.com .

Abstract Background Older adults with frailty are at an increased risk of adverse outcomes after surgery. Exercise before surgery (exercise prehabilitation) may reduce adverse events and improve recovery after surgery. However, adherence with exercise therapy is often low, especially in older populations. The purpose of this study was to qualitatively assess the barriers and facilitators to participating in exercise prehabilitation from the perspective of older people with frailty participating in the intervention arm of a randomized trial. Methods This was a research ethics approved, nested descriptive qualitative study within a randomized controlled trial of home-based exercise prehabilitation vs. standard care with older patients (≥ 60 years) having elective cancer surgery, and who were living with frailty (Clinical Frailty Scale ≥ 4). The intervention was a home-based prehabilitation program for at least 3 weeks before surgery that involved aerobic activity, strength and stretching, and nutritional advice. After completing the prehabilitation program, participants were asked to partake in a semi-structured interview informed by the Theoretical Domains Framework (TDF). Qualitative analysis was guided by the TDF. Results Fifteen qualitative interviews were completed. Facilitators included: 1) the program being manageable and suitable to older adults with frailty, 2) adequate resources to support engagement, 3) support from others, 4) a sense of control, intrinsic value, noticing progress and improving health outcomes and 5) the program was enjoyable and facilitated by previous experience. Barriers included: 1) pre-existing conditions, fatigue and baseline fitness, 2) weather, and 3) guilt and frustration when unable to exercise. A need for individualization and variety was offered as a suggestion by participants and was therefore described as both a barrier and facilitator. Conclusions Home-based exercise prehabilitation is feasible and acceptable to older people with frailty preparing for cancer surgery. Participants identified that a home-based program was manageable, easy to follow with helpful resources, included valuable support from the research team, and they reported self-perceived health benefits and a sense of control over their health. Future studies and implementation should consider increased personalization based on health and fitness, psychosocial support and modifications to aerobic exercises in response to adverse weather conditions.

Abstract We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare “clumping-and-thresholding” (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals.

Angiogenesis is critical for tissue repair following myocardial infarction (MI), which is exacerbated under insulin resistance or diabetes. MicroRNAs are regulators of angiogenesis. We examined the metabolic regulation of miR-409-3p in post-infarct angiogenesis. miR-409-3p was increased in patients with acute coronary syndrome (ACS) and in a mouse model of acute MI. In endothelial cells (ECs), miR-409-3p was induced by palmitate, while vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) decreased its expression. Overexpression of miR-409-3p decreased EC proliferation and migration in the presence of palmitate, whereas inhibition had the opposite effects. RNA sequencing (RNA-seq) profiling in ECs identified DNAJ homolog subfamily B member 9 (DNAJB9) as a target of miR-409-3p. Overexpression of miR-409-3p decreased DNAJB9 mRNA and protein expression by 47% and 31% respectively, while enriching DNAJB9 mRNA by 1.9-fold after Argonaute2 microribonucleoprotein immunoprecipitation. These effects were mediated through p38 mitogen-activated protein kinase (MAPK). Ischemia-reperfusion (I/R) injury in EC-specific miR-409-3p knockout (KO) mice (miR-409ECKO) fed a high-fat, high-sucrose diet increased isolectin B4 (53.3%), CD31 (56%), and DNAJB9 (41.5%). The left ventricular ejection fraction (EF) was improved by 28%, and the infarct area was decreased by 33.8% in miR-409ECKO compared with control mice. These findings support an important role of miR-409-3p in the angiogenic EC response to myocardial ischemia.

The palatability of pediatric pharmaceutical products plays a crucial role of influencing medication compliance. Rejection of unpalatable medications can potentially lead to treatment failure which can have immediate and delayed consequences. With advances in both the food and pharmaceutical industries, the systematic assessment of palatability has gained importance. Various methods such as visual analogue scales, facial hedonic scales, and facial recognition software, have been employed to assess palatability. While proven to be useful, these methods have significant limitations and may not be workable for young children. Despite these advancements, a universally accepted “gold standard” for assessing pediatric mediation palatability, recognized by drug regulatory agencies, is yet to be established.

BackgroundElectrolytes (sodium, potassium, calcium, magnesium, chloride, phosphate) are required in specific amounts for proper functioning of the human body. Although the body has different organ systems, such as the kidneys, that regulate electrolyte levels in the blood, electrolyte abnormalities occur frequently in people with eating disorders. The objective of this review will be to examine the association between electrolyte imbalances and adverse outcomes in people with eating disorders.MethodsA systematic review of studies on eating and electrolyte disorders shall be conducted. Electronic searches shall be done in the Ovid MEDLINE, EMBASE, and PsycINFO databases. Selected studies shall include randomized control trials (RCTs), non-randomized controlled trials, and cross-sectional studies published in English or French. Quality appraisal of studies and a narrative synthesis of extracted data shall be conducted.DiscussionThis review will synthesize existing evidence on electrolyte abnormalities in people with eating disorders. It will identify the type of electrolyte imbalances, their impact, and outcomes in people with eating disorders. We anticipate that information that will be useful to policy makers and clinicians in designing better policies to prevent eating disorders and or manage people with eating disorders shall be elucidated in this study.DisseminationThe final manuscript will be submitted for publication in a journal.Review registrationThis protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number CRD42023477497.

Background: There are several approaches such as the Bankart repair, Latarjet, and Remplissage to treat recurrent glenohumeral instability. Indications: We chose to augment an arthroscopic Bankart repair with a Remplissage in this 26-year-old patient given the presence of a Hill-Sachs lesion, history of recurrent shoulder dislocations, and young age of the patient. Technique Description: We established four portals using previously well-documented techniques. The Hill-Sachs lesion was evaluated using the anterosuperior portal. Two anchors were placed, one on both the superior and inferior aspects of the Hill-Sachs lesion. The sutures were shuttled through the knotless anchor mechanism and tensioned after confirming the cannula was through the deltoid. Then, we completed the Remplissage by repairing the infraspinatus tendon and capsule into the posterior humeral head. Results: The Remplissage procedure is very successful at reducing recurrent instability in young, active patients. Previous studies have reported very low rates, even 0% recurrent instability, after surgery with 80% to 90% of patients returning to sports. Studies have also documented excellent patient-reported outcomes at short- to mid-term follow-up. Complication rates are historically lower when the Remplissage is done with an arthroscopic Bankart repair than the Bankart repair alone. Discussion/Conclusion: The Remplissage procedure is a safe, effective option at reducing future instances of shoulder dislocations in conjunction with Bankart repairs. Patients can expect to return to their active lifestyles, with many patients achieving the same level of activity as before the initial shoulder dislocation. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.