The correlation of neurosurgery motor examinations with ISNCSCI motor examinations in patients with spinal cord injury: a multicenter TRACK-SCI study.

OBJECTIVE: The International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) assessment is the gold standard for evaluation of neurological function after spinal cord injury (SCI). Although it is an invaluable tool for diagnostic and research purposes, it is time consuming and can be impractical in acute injury settings. Clinical neurosurgery motor examinations (NMEs) could serve as an expeditious surrogate for SCI research when ISNCSCI motor examinations are not feasible. The aim of this study was to evaluate the agreement between motor examinations performed by the neurosurgery clinical team and ISNCSCI examiners. METHODS: The multicenter prospective Transforming Research and Clinical Knowledge in Spinal Cord Injury (TRACK-SCI) registry was queried to identify patients with recorded neurosurgery and research motor examinations within 24 hours of each other. Pearson correlations and modified Bland-Altman analyses were performed using data from matching upper-extremity, lower-extremity, and combined examinations. Kappa analysis was used to test interrater reliability with respect to determination of American Spinal Injury Association Impairment Scale (AIS) grade. RESULTS: There were 72 pairs of matching clinical and research examinations in 63 patients. NME scores were strongly correlated with ISNCSCI motor scores (R = 0.962, p < 0.001). Both upper- and lower-extremity NME scores were strongly correlated with upper- and lower-extremity ISNCSCI motor scores, respectively (R = 0.939, p < 0.001; and R = 0.959, p < 0.001, respectively). In modified Bland-Altman analyses, total, upper-extremity, and lower-extremity NME scores and ISNCSCI motor scores showed low systematic bias and high agreeability (total: bias = 0.3, limit of agreement [LoA] = 36.6; upper extremity: bias = -0.5, LoA = 17.6; lower extremity: bias = 0.8, LoA = 24.0). There were 66 pairs of examinations that had thorough sensory and rectal examinations for AIS grade calculation. Using kappa analysis to test the interrater reliability of AIS grade calculation using NME versus ISNCSCI motor scores, the authors found a weighted kappa of 0.883 (SE 0.061, 95% CI 0.736-0.976), indicating strong agreement. CONCLUSIONS: Overall, this study suggests that ISNCSCI motor scores and NME scores are strongly correlated and highly agreeable. When conducting SCI research, a thorough clinical motor examination may be a useful surrogate when ISNCSCI examinations are missing.

Distribution and Characteristics of Blackwater Rivers and Streams of the Contiguous United States.

Blackwater rivers and streams have stained or tea-colored water from tannins released by decaying plant matter. Natural conditions in these waters often differ from non-blackwater systems. For example, the pH and oxygen levels in waters can be very low, but completely natural. We examined an existing USEPA data set and found that blackwaters existed across the contiguous United States but were most common in the east. Water chemistry showed differences between blackwater and non-blackwater sites, but differences were not consistent across ecoregions making national scale generalizations difficult. Physical habitat data analysis did not show dramatic differences between blackwater and non-blackwater sites. Blackwater typically arises from streams that drain tannin-rich bogs/muskeg and wetlands, so as expected blackwater sites had a shorter Euclidean distance to wetlands than non-blackwater sites and existed in watersheds with a higher percentage of wetland habitat. Blackwaters in Northern and Temperate Plains tended to have higher acid neutralizing capacity, conductivity, and lower True Color; a visual color scale used for water purity. We posit that differences were because Color and Dissolved Organic Carbon at these sites were from buried wetland deposits rather than contemporary wetland habitats. Research needs that may increase our understanding and management of blackwaters include development of an operational definition that includes a classification framework and reference conditions for different blackwater types, identification of stressors and their associated dynamics that negatively impact blackwater systems, and development of data-driven, consistent, and repeatable assessment methods, including development of targets, protective of unique conditions in blackwater rivers and streams.

Post ambulatory swollen hands (POTASH): a case report.

Background: Post ambulatory swollen hands (POTASH) is an acquired condition that presents as asymptomatic swelling of the hands and their digits during ambulatory activities such as walking, hiking, and running. Affected individuals cannot clench their fingers into their palm to make a fist and thereby have a positive fist sign. The benign condition typically resolves spontaneously within 2 hours with complete resolution of the swelling; the individual can make a tight fist and has a negative fist sign. Case Description: A 65-year-old man developed POTASH, when he was rapidly walking during a 13.1-mile half marathon race, that presented as asymptomatic swelling of his fingers and hands. His hands and their digits began to swell after the first hour of running and continued to progressively become larger during the remainder of the race. In addition, he had a positive fist sign demonstrated by being unable to clench his fingers to his palm and make a fist. Within 2 hours after he stopped ambulating, the swelling spontaneously resolved completely, and he had a negative fist sign by being able to make a tight fist by clenching his fingers into his palm. Conclusions: POTASH is an idiopathic recurrent condition whose pathogenesis remains to be determined. A report of occurrence in a brother and sister raises the possibility that in some individuals, genetic factors may have a contributory role in the etiology of the condition. There is a paucity of papers on POTASH in the medical literature which suggests a lack of awareness of this condition. It is important that healthcare providers are aware of this recurrent and benign condition and can appropriately counsel affected individuals.

Impacts of resident physician unionization on house staff compensation.

BACKGROUND: Physicians-in-training in the United States work long hours for relatively low wages. In response to increased economic burden, the popularity of unionization in residency training programs has increased dramatically. In this study, we conducted a cross-sectional investigation of the association between unionization status and Internal Medicine PGY-1 compensation and benefits. METHODS AND FINDINGS: We compiled residency salary and benefits data from all Internal Medicine residency training programs in the United States. Using a mixed effects modeling approach, we evaluated the differences in salary and total compensation while adjusting for regional factors and cost-of-living differences. In aggregate, PGY-1 salary was higher for unionized vs. non-unionized programs ($69648 vs. $62214; [95% CI 670.7-3563.7]). However, there was no difference after adjusting for cost-of-living ($62515 vs $62475; [95% CI. -1317.5, 1299.7]). Unionized programs do however offer greater monetary benefits in the form of stipend disbursements, and total compensation is higher in unionized vs. non-unionized residency programs ($65887 vs $63515; [95% CI 607.6, 3551.5]). CONCLUSIONS: Unionized residency programs offer higher total compensation packages than their non-unionized counterparts. This increase in compensation is driven in large part by an increased variety and amount of stipend disbursement.

Enhancing Conceptual Clarity regarding the Construct of Moral Injury.

BACKGROUND: The construct of "moral injury" is used widely in the research literature and media to broadly describe the impact of events involving perceived violations of one's sense of right and wrong (herein referred to as "potentially morally injurious events" [PMIEs]). SUMMARY: In this theoretical review, we provided a brief overview of the "moral injury" construct and its limitations including the lack of consensus-drawn boundaries and operational definitions to guide hypothesis-driven research. We discussed whether this construct can be reliably distinguished from established psychiatric diagnoses and psychological constructs and the inherent challenges in separating or classifying the impact of high-magnitude stressful life events that likely form the majority of PMIEs. Assessments that purportedly measure "moral injury" are reviewed and limitations are discussed such as shared measurement variance with established psychological instruments. KEY MESSAGES: We identified conceptual strategies for investigating behavioral and neurobiological features of PMIEs that could be used to inform the field of traumatic stress. We concluded that the construct of "moral injury" may provide an interpretive framework for positing why someone may be beset by guilt, shame, and/or rage whereas existing psychiatric diagnoses such as post-traumatic stress disorder and depression provide comprehensive descriptions regarding what someone might experience following extremely stressful events. We proposed directions to better clarify the boundaries of "moral injury" versus established psychiatric categories that could be used to enhance the conceptualization and assessment of this construct.

Lagrangian approach to origami vertex analysis: kinematics.

The use of origami in engineering has significantly expanded in recent years, spanning deployable structures across scales, folding robotics and mechanical metamaterials. However, finding foldable paths can be a formidable task as the kinematics are determined by a nonlinear system of equations, often with several degrees of freedom. In this article, we leverage a Lagrangian approach to derive reduced-order compatibility conditions for rigid-facet origami vertices with reflection and rotational symmetries. Then, using the reduced-order conditions, we derive exact, multi-degree of freedom solutions for degree 6 and degree 8 vertices with prescribed symmetries. The exact kinematic solutions allow us to efficiently investigate the topology of allowable kinematics, including the consideration of a self-contact constraint, and then visually interpret the role of geometric design parameters on these admissible fold paths by monitoring the change in the kinematic topology. We then introduce a procedure to construct lower-symmetry kinematic solutions by breaking symmetry of higher-order kinematic solutions in a systematic way that preserves compatibility. The multi-degree of freedom solutions discovered here should assist with building intuition of the kinematic feasibility of higher-degree origami vertices and also facilitate the development of new algorithmic procedures for origami-engineering design.This article is part of the theme issue 'Origami/Kirigami-inspired structures: from fundamentals to applications'.

An aza-Diels-Alder approach to nitrogen-containing tetrabenzoacene derivatives.

Acenes and N-heteroacenes have been synthesized and studied for over a century because of their fundamentally interesting materials properties and promise for device applications. Within this context, our laboratory has previously synthesized nitrogen-containing tetrabenzo[de,hi,op,st]pentacenes via an aza-Diels-Alder reaction-based approach, and herein, we expand our methodology to obtain substituted, expanded, functionalized, and dimeric tetrabenzoacenes. Overall, our study adds to the limited number of tetrabenzoacene derivatives reported to date and may open further opportunities for these materials in organic optoelectronics applications.

Toxicologic Pathology Forum*: mRNA Vaccine Safety-Separating Fact From Fiction.

SARS-CoV-2 spread rapidly across the globe, contributing to the death of millions of individuals from 2019 to 2023, and has continued to be a major cause of morbidity and mortality after the pandemic. At the start of the pandemic, no vaccines or anti-viral treatments were available to reduce the burden of disease associated with this virus, as it was a novel SARS coronavirus. Because of the tremendous need, the development of vaccines to protect against COVID-19 was critically important. The flexibility and ease of manufacture of nucleic acid-based vaccines, specifically mRNA-based products, allowed the accelerated development of COVID-19 vaccines. Although mRNA-based vaccines and therapeutics had been in clinical trials for over a decade, there were no licensed mRNA vaccines on the market at the start of the pandemic. The rapid development of mRNA-based COVID-19 vaccines reduced serious complications and death from the virus but also engendered significant public concerns, which continue now, years after emergency-use authorization and subsequent licensure of these vaccines. This article summarizes and addresses some of the safety concerns that continue to be expressed about these vaccines and their underlying technology.

Vitamin D deficiency and associated demographic risk factors in children at a tertiary hospital in Abu Dhabi.

BACKGROUND: Despite ample sunshine, vitamin D deficiency continues to be prevalent in the Middle East. This pilot study aimed to identify the rate of vitamin D deficiency at a tertiary hospital in Abu Dhabi and to identify the associated risk factors in children and adolescents. METHODOLOGY: A retrospective observational study was conducted using electronic medical records of paediatric patients who underwent 25-hydroxyvitamin D testing at Sheikh Shakhbout Medical City, Abu Dhabi between 1 January 2020 and 31 December 2021. Data on age, gender, ethnicity, weight, body mass index and other potential risk factors for vitamin D deficiency in children were recorded. Patients who were already receiving treatment for vitamin D deficiency were excluded. The collected data were analysed using standard statistical methods. RESULTS: Of 26,818 patients under 18 years of age who attended the outpatient clinic, 1519 underwent 25-hydroxyvitamin D testing; 51% were male (n = 755). After applying the exclusion criteria, 1311 participants were included, 755 (58%) of whom had vitamin D concentrations of ≤50 nmol/L. Vitamin D deficiency was more common in children aged ≥10 years (69%) than in those <10 years of age (53%) (p < 0.0001). The highest prevalence of vitamin D deficiency was in those older than 16 years (86%). More females (63%, n = 407) than males (52%, n = 348) were identified as vitamin D-deficient (p = 0.0001). Vitamin D deficiency was more commonly identified during summer and autumn (59%) than in winter and spring (44%, p < 0.00001). CONCLUSION: Vitamin D deficiency is prevalent in children seeking medical care in the UAE, especially in girls, older children and adolescents, and during the summer and autumn. Paediatricians should have a low screening threshold for hypovitaminosis D, or widespread supplementation should be considered.

HiMAL: Multimodal Hierarchical Multi-task Auxiliary Learning framework for predicting Alzheimer's disease progression.

Objective: We aimed to develop and validate a novel multimodal framework Hierarchical Multi-task Auxiliary Learning (HiMAL) framework, for predicting cognitive composite functions as auxiliary tasks that estimate the longitudinal risk of transition from Mild Cognitive Impairment (MCI) to Alzheimer's Disease (AD). Materials and Methods: HiMAL utilized multimodal longitudinal visit data including imaging features, cognitive assessment scores, and clinical variables from MCI patients in the Alzheimer's Disease Neuroimaging Initiative dataset, to predict at each visit if an MCI patient will progress to AD within the next 6 months. Performance of HiMAL was compared with state-of-the-art single-task and multitask baselines using area under the receiver operator curve (AUROC) and precision recall curve (AUPRC) metrics. An ablation study was performed to assess the impact of each input modality on model performance. Additionally, longitudinal explanations regarding risk of disease progression were provided to interpret the predicted cognitive decline. Results: Out of 634 MCI patients (mean [IQR] age: 72.8 [67-78], 60% male), 209 (32%) progressed to AD. HiMAL showed better prediction performance compared to all state-of-the-art longitudinal single-modality singe-task baselines (AUROC = 0.923 [0.915-0.937]; AUPRC = 0.623 [0.605-0.644]; all P < .05). Ablation analysis highlighted that imaging and cognition scores with maximum contribution towards prediction of disease progression. Discussion: Clinically informative model explanations anticipate cognitive decline 6 months in advance, aiding clinicians in future disease progression assessment. HiMAL relies on routinely collected electronic health records (EHR) variables for proximal (6 months) prediction of AD onset, indicating its translational potential for point-of-care monitoring and managing of high-risk patients.

[Genetic therapy by CRISPR-Cas: paving the way to clinical practice]. / Genetische therapie met CRISPR-Cas.

CRISPR-Cas technology is a revolutionary technology to modify DNA sequences. Owing to its effectiveness and accuracy, CRISPR-Cas holds important promises for 'genetic therapy' for various hereditary disorders. CRISPR-Cas enables researchers to modify specific parts of the genome with unprecedented precision, which, in specific cases, can be applied to correct disease-causing DNA variants. However, several important barriers are complicating the clinical implementation trajectory. There are for example concerns regarding the safety, effectiveness and ethical justification. Nevertheless, as CRISPR-Cas becomes more widely known, doctors and healthcare providers are expected to be well aware of the developments surrounding CRISPR-Cas therapy. Professional expertise and clear communication about the possibilities and limitations to patients with genetic disorders are essential, partly to avoid making promises that are unrealistic in the short term. Altogether, geneticists, medical centers and regulators are now facing the challenges to start translating CRISPR-Cas technology into clinical practice, in an effective and ethical manner.

An observational cohort of patients with colorectal peritoneal metastases or pseudomyxoma peritonei treated with CRS-HIPEC: Development and first results of the Dutch CRS-HIPEC quality registry.

INTRODUCTION: To improve care for patients with colorectal peritoneal metastases (CRC-PM) or pseudomyxoma peritonei (PMP), the Dutch CRS-HIPEC quality registry was initiated in 2019. The aims are to describe the development and content of this registry and to give insight into the data collected during the first years. MATERIALS AND METHODS: The registry is an observational cohort in the Netherlands. All patients with CRC-PM or PMP who intend to undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) from 6 hospitals are included. Clinical data and outcomes (including hospital variation) were analyzed. RESULTS: In 2019-2022, 889 patients were included in the CRS-HIPEC quality registry: 749 (84 %) with CRC-PM and 140 (16 %) with PMP. Peritoneal metastases were diagnosed synchronously in 51 % of CRC-PM patients and in 94 % of PMP patients. In patients undergoing complete CRS, the median peritoneal cancer index was 8 (IQR 4-13) for CRC-PM and 15 (IQR 6-26) for PMP. Complete cytoreduction was achieved in 639 CRC-PM patients (97 %) and 108 PMP patients (82 %). HIPEC was mainly performed with mitomycin C (CRC-PM: 94 %, PMP: 92 %). Major postoperative complications (Clavien-Dindo grade ≥3) occurred in 148 CRC-PM patients (22 %) and 30 PMP patients (23 %) with 90-day mortality rates of 2 %. In CRC-PM, differences between hospitals were observed regarding proportions of diagnostic laparoscopies/laparotomies, (neo)adjuvant treatment, ostomy formations and re-admissions. CONCLUSION: The CRS-HIPEC quality registry provides insight into the outcomes of CRS-HIPEC and enables clinical auditing and observational cohort studies aiming to improve treatment outcomes for patients with CRC-PM and PMP.

Metabolomic Fingerprints of Medical Therapy Versus Bariatric Surgery in Patients With Obesity and Type 2 Diabetes: The STAMPEDE Trial.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are effective procedures to treat and manage type 2 diabetes (T2D). However, the underlying metabolic adaptations that mediate improvements in glucose homeostasis remain largely elusive. The purpose of this study was to identify metabolic signatures associated with biochemical resolution of T2D after medical therapy (MT) or bariatric surgery. RESEARCH DESIGN AND METHODS: Plasma samples from 90 patients (age 49.9 ± 7.6 years; 57.7% female) randomly assigned to MT (n = 30), RYGB (n = 30), or SG (n = 30) were retrospectively subjected to untargeted metabolomic analysis using ultra performance liquid chromatography with tandem mass spectrometry at baseline and 24 months of treatment. Phenotypic importance was determined by supervised machine learning. Associations between change in glucose homeostasis and circulating metabolites were assessed using a linear mixed effects model. RESULTS: The circulating metabolome was dramatically remodeled after SG and RYGB, with largely overlapping signatures after MT. Compared with MT, SG and RYGB profoundly enhanced the concentration of metabolites associated with lipid and amino acid signaling, while limiting xenobiotic metabolites, a function of decreased medication use. Random forest analysis revealed 2-hydroxydecanoate as having selective importance to RYGB and as the most distinguishing feature between MT, SG, and RYGB. To this end, change in 2-hydroxydecanoate correlated with reductions in fasting glucose after RYGB but not SG or MT. CONCLUSIONS: We identified a novel metabolomic fingerprint characterizing the longer-term adaptations to MT, RYGB, and SG. Notably, the metabolomic profiles of RYGB and SG procedures were distinct, indicating equivalent weight loss may be achieved by divergent effects on metabolism.

The carbon footprint of a laparoscopic cholecystectomy.

BACKGROUND: Gallbladder removal is one of the most common surgical procedures worldwide. The keyhole operation treats patients with symptomatic gallstones. This procedure uses many single-use tools and results in a lot of waste. Before we can make this operation more sustainable, we need to assess the amount of waste and CO2 emissions. AIM: The aim of this study was to identify the types of waste and measure the CO2 emissions created by a gallbladder removal. METHOD: We collected waste from 15 gallbladder operations at three hospitals. We noted the medications used and measured the surgery duration to estimate electricity consumption. We also asked all the staff how they travelled to the hospital that day. FINDINGS AND CONCLUSION: The operation produces about 56.5 kg of CO2. The main sources of CO2 are single-use tools, packaging materials and disposable drapes and gowns. This study helps us understand where most CO2 is produced, so we can work on reducing it more effectively.^ieng

Evolving Characteristics of Decedents With Hepatitis A Listed as a Cause of Death, United States, 2011-2021.

Hepatitis A is a vaccine-preventable disease that typically causes mild illness. Hepatitis A outbreaks associated with person-to-person transmission have been widespread in the United States since 2016. We used public-use US Multiple Cause of Death data to compare characteristics and listed comorbidities among decedents with hepatitis A-listed deaths during non-outbreak (2011-2015) and outbreak (2017-2021) periods and assessed the median age at death among decedents with and without hepatitis A-listed deaths during the outbreak period. From the non-outbreak period to the outbreak period, hepatitis A-listed deaths more than doubled (from 369 to 801), while the hepatitis A-listed age-adjusted mortality rate increased 150% (p < 0.001). When compared with the non-outbreak period, hepatitis A-listed decedents during the outbreak period were more frequently male, aged 18-49 years, non-Hispanic White, died in an inpatient setting, and had hepatitis A listed as their underlying cause of death. The median age at death for hepatitis A-listed decedents was significantly younger during the outbreak period overall and among females (62 and 66 years, respectively) compared with the non-outbreak period (64 and 72 years, respectively, p < 0.001). During the outbreak period, median age at death for hepatitis A-listed decedents was 14 years younger than decedents without hepatitis A listed. Compared with the general US population, decedents with hepatitis A listed on the death certificate died at younger ages during 2017-2021. Efforts are needed to improve hepatitis A vaccination coverage among adults recommended for hepatitis A vaccination to prevent additional premature hepatitis A deaths.

Send in the Clowns: A Special Tribute to Medical Clowning and Clown Eponyms in Dermatology.

Clowns have long delighted circus crowds and are celebrated not only in popular culture but also in the dermatology literature as medical eponyms. This contribution discusses four such eponyms: 1) clown nose-like lesion, 2) clown eczema (perioral dermatitis) 3) clown alopecia pattern in frontal fibrosing alopecia and 4) clown's face of Brachman de Lange syndrome (Cornelia de Lange syndrome). This contribution also highlights the role of medical clowning in patient care by paying tribute to Cobo the Clown, also known as Barbara Joyce Cohen, who has served as a dedicated caring clown for over thirty years.

Identification of a Novel Subset of Human Airway Epithelial Basal Stem Cells.

The basal cell maintains the airway's respiratory epithelium as the putative resident stem cell. Basal cells are known to self-renew and differentiate into airway ciliated and secretory cells. However, it is not clear if every basal cell functions as a stem cell. To address functional heterogeneity amongst the basal cell population, we developed a novel monoclonal antibody, HLO1-6H5, that identifies a subset of KRT5+ (cytokeratin 5) basal cells. We used HLO1-6H5 and other known basal cell-reactive reagents to isolate viable airway subsets from primary human airway epithelium by Fluorescence Activated Cell Sorting. Isolated primary cell subsets were assessed for the stem cell capabilities of self-renewal and differentiation in the bronchosphere assay, which revealed that bipotent stem cells were, at minimum 3-fold enriched in the HLO1-6H5+ cell subset. Crosslinking-mass spectrometry identified the HLO1-6H5 target as a glycosylated TFRC/CD71 (transferrin receptor) proteoform. The HLO1-6H5 antibody provides a valuable new tool for identifying and isolating a subset of primary human airway basal cells that are substantially enriched for bipotent stem/progenitor cells and reveals TFRC as a defining surface marker for this novel cell subset.

Multi-modal risk factors differentiate suicide attempters from ideators in military veterans with major depressive disorder.

BACKGROUND: The suicide rate for United States military veterans is 1.5× higher than that of non-veterans. To meaningfully advance suicide prevention efforts, research is needed to delineate factors that differentiate veterans with suicide attempt/s, particularly in high-risk groups, e.g., major depressive disorder (MDD), from those with suicidal ideation (no history of attempt/s). The current study aimed to identify clinical, neurocognitive, and neuroimaging variables that differentiate suicide-severity groups in veterans with MDD. METHODS: Sixty-eight veterans with a DSM-5 diagnosis of MDD, including those with no ideation or suicide attempt (N = 21; MDD-SI/SA), ideation-only (N = 17; MDD + SI), and one-or-more suicide attempts (N = 30; MDD + SA; aborted, interrupted, actual attempts), participated in this study. Participants underwent a structured diagnostic interview, neurocognitive assessment, and 3 T-structural/diffusion tensor magnetic-resonance-imaging (MRI). Multinomial logistic regression models were conducted to identify variables that differentiated groups with respect to the severity of suicidal behavior. RESULTS: Relative to veterans with MDD-SI/SA, those with MDD + SA had significantly higher left cingulum fractional anisotropy, decreased attentional control on emotional-Stroop, and faster response time with intact accuracy on Go/No-Go. Relative to MDD + SI, MDD + SA had higher left cingulum fractional anisotropy and faster response time with intact accuracy on Go/No-Go. LIMITATIONS: Findings are based on retrospective, cross-sectional data and cannot identify causal relationships. Also, a healthy control group was not included given the study's focus on differentiating suicide profiles in MDD. CONCLUSIONS: This study suggests that MRI and neurocognition differentiate veterans with MDD along the suicide-risk spectrum and could inform suicide-risk stratification and prevention efforts in veterans and other vulnerable populations.