A historical syndemic? The impact of synergistic epidemics of measles and scarlet fever on life expectancy in Victoria, Australia (1860s-1870s).

OBJECTIVES: To explore whether synergistic epidemics of measles and scarlet fever in 1860s-1870s Victoria, Australia could be characterized as syndemics, we apply the methods of Sawchuk, Tripp, and Samakaroon (Social Science & Medicine 2022, 295, 112956) to quantify the impact of each of the two major co-occurring epidemic events (1867, 1875) in terms of life expectancy (LE) changes. Sawchuk et al. posit the presence of a harvesting effect, indicated by a statistically significant increase in LE in the immediate post-epidemic "fallow period", as a criterion for identification of a historical syndemic. We test an alternate hypothesis that the same methods can identify a short-term scarring effect. MATERIALS AND METHODS: Using annual age- and cause-specific death statistics and census population data, we constructed abridged period life tables for baseline period, potential syndemic year, and "fallow" year for each of the two periods (1860s and 1870s). We compared LE at birth using Z-tests. We decomposed age-cause-specific mortality according to Arriaga's method to identify age-and cause-specific contributions to LE change. RESULTS: LE was significantly lower than baseline (1864-1865) in 1867 but not in the "fallow" year (1869). LE in 1875 and the 1878 "fallow" year were both significantly below baseline (1871-1873). Age-cause-specific decomposition showed similar patterns for 1867 and 1875 for measles and scarlet fever combined effects. DISCUSSION: Evidence of a scarring effect following the 1875 measles/scarlet fever combined peak supports the interpretation of this event as a syndemic. We suggest the short-term scarring effect can be a useful additional criterion for identifying historical syndemics.

Feature-Agnostic Metabolomics for Determining Effective Sub-cytotoxic Doses of Common Pesticides in Human Cells.

While classical molecular biology assays can provide a measure of cellular response to chemical challenges, they rely on a single biological phenomenon to infer a broader measure of cellular metabolic response. These methods do not always afford the necessary sensitivity to answer questions of sub-cytotoxic effects, nor do they work for all cell types. Likewise, boutique assays such as cardiomyocyte beat rate may indirectly measure cellular metabolic response, but they too, are limited to measuring a specific biological phenomenon and are often limited to a single cell type. For these reasons, toxicological researchers need new approaches to determine metabolic changes across various doses in differing cell types, especially within the low-dose regime. The data collected herein demonstrate that LC-MS/MS-based untargeted metabolomics with a feature-agnostic view of the data, combined with a suite of statistical methods including an adapted environmental threshold analysis, provides a versatile, robust, and holistic approach to directly monitoring the overall cellular metabolomic response to pesticides. When employing this method in investigating two different cell types, human cardiomyocytes and neurons, this approach revealed separate sub-cytotoxic metabolomic responses at doses of 0.1 µM and 1 µM of chlorpyrifos and carbaryl. These findings suggest that this agnostic approach to untargeted metabolomics can provide a new tool for determining effective dose by metabolomics (EDm) of chemical challenges, such as pesticides, in a direct measurement of metabolomic response that is not cell type-specific or observable using traditional assays.

Racial Health Disparity Associated With Poor Pediatric Cardiac Surgery Outcomes: A Multicentered, Cross-Sectional Study.

Background: Health disparities are known to play a role in pediatric cardiac surgery outcomes. Objectives: Risk factors associated with poor clinical outcomes were assessed. Methods: Using Pediatric Health Information System Database, pediatric subjects undergoing cardiac surgery using International Classification of Diseases 10th Revision from October 2015 to December 2020 were evaluated. Subjects were categorized by case complexity using the newly validated Risk Adjustment for Congenital Heart Surgery-2 (RACHS-2). Multivariable regression analyses were conducted to ascertain risk factors. Results: A total of 59,856 subjects, median age 7.4 months (IQR: 1.5-61 months) were included; 38,917 (low), 9,833 (medium), and 11,106 (high) RACHS-2. Overall, hospital mortality was 3% and postoperative length of stay (LOS) was 7 days (IQR: 4-18 days), with significant increases in both mortality and postoperative LOS from low to high RACHS-2 scores by multivariable analysis, Kaplan-Meier, and Cox regression. Mechanical ventilation, extracorporeal membrane oxygenation, infection, and surgical complication were most significantly associated with increased mortality by 1.198 to 10.227 times (P < 0.008). After controlling for these significant variables as well as RACHS-2, age at surgery and emergency/urgent admission type, multivariable analysis revealed that non-White race was associated with increased mortality (relative risk: 1.2, 95% CI: 0.729-0.955, P = 0.008) and increased postoperative LOS by 1.04 days (95% CI: 0.95-0.97, P < 0.001). This significant increase in both clinical outcomes was concordant in non-White neonates (mortality relative risk: 1.3, 95% CI: 1.1-1.6, P = 0.003; and postoperative LOS by 2.05 weeks (95% CI: 1.36-3.10, P < 0.001). Conclusions: The influence of racial differences in neonates and children should be further evaluated to mitigate any disparity in those undergoing cardiac surgery.

Neoadjuvant Cisplatin, Gemcitabine, and Docetaxel in Sarcomatoid Bladder Cancer: Clinical Activity and Whole Transcriptome Analysis.

BACKGROUND: Sarcomatoid urothelial cancer of the bladder (SBC) is a rare, but aggressive histological subtype for which novel treatments are needed. OBJECTIVE: We evaluated the clinical activity and safety of neoadjuvant cisplatin plus gemcitabine plus docetaxel (CGD) in muscle-invasive patients with SBC and assessed SBC tumor biology by whole transcriptome RNA sequencing. METHODS: A single-institution, retrospective analysis of muscle-invasive SBC patients treated with neoadjuvant CGD with molecular analysis. Patients received cisplatin 35 mg/m2 + gemcitabine 800 mg/m2 + docetaxel 35 mg/m2 intravenously on days 1 and 8 + pegfilgrastim 6 mg subcutaneously on day 9 every 3 weeks for 4 cycles followed by cystectomy. The primary endpoint was pathologic complete response (ypCR) rate. RESULTS: Sixteen patients with SBC received neoadjuvant CGD with a ypCR rate of 38% and a < ypT2 rate of 50%. Grade 3 and 4 toxicity occurred in 80% and 40% of patients, but was manageable with 81% of patients completing > 3 CGD cycles. Whole transcriptome RNA sequencing demonstrates co-clustering of SBC with conventional urothelial tumors. SBC tumors are characterized by basal-squamous and stroma rich gene signatures with frequent increased expression of immune checkpoint (CD274 (PD-L1)), chemokine (CXCL9), and T-cell (CD8A) genes. CONCLUSIONS: SBC is a chemosensitive subtype, with ypCR rate similar to urothelial bladder cancer following CGD neoadjuvant therapy. Whole transcriptome tissue analyses demonstrate increased expression of immune checkpoint and T-cell genes with therapeutic implications.

VISTA Emerges as a Promising Target against Immune Evasion Mechanisms in Medulloblastoma.

BACKGROUND: Relapsed medulloblastoma (MB) poses a significant therapeutic challenge due to its highly immunosuppressive tumor microenvironment. Immune checkpoint inhibitors (ICIs) have struggled to mitigate this challenge, largely due to low T-cell infiltration and minimal PD-L1 expression. Identifying the mechanisms driving low T-cell infiltration is crucial for developing more effective immunotherapies. METHODS: We utilize a syngeneic mouse model to investigate the tumor immune microenvironment of MB and compare our findings to transcriptomic and proteomic data from human MB. RESULTS: Flow cytometry reveals a notable presence of CD45hi/CD11bhi macrophage-like and CD45int/CD11bint microglia-like tumor-associated macrophages (TAMs), alongside regulatory T-cells (Tregs), expressing high levels of the inhibitory checkpoint molecule VISTA. Compared to sham control mice, the CD45hi/CD11bhi compartment significantly expands in tumor-bearing mice and exhibits a myeloid-specific signature composed of VISTA, CD80, PD-L1, CTLA-4, MHCII, CD40, and CD68. These findings are corroborated by proteomic and transcriptomic analyses of human MB samples. Immunohistochemistry highlights an abundance of VISTA-expressing myeloid cells clustering at the tumor-cerebellar border, while T-cells are scarce and express FOXP3. Additionally, tumor cells exhibit immunosuppressive properties, inhibiting CD4 T-cell proliferation in vitro. Identification of VISTA's binding partner, VSIG8, on tumor cells, and its correlation with increased VISTA expression in human transcriptomic analyses suggests a potential therapeutic target. CONCLUSIONS: This study underscores the multifaceted mechanisms of immune evasion in MB and highlights the therapeutic potential of targeting the VISTA-VSIG axis to enhance anti-tumor responses.

Management of Femoral and Tibial Shaft Fractures in Chronic Spinal Cord Injury Patients.

OBJECTIVES: To compare outcomes and complications between non-operative and operative management of femur and tibia fractures in patients with paraplegia or quadriplegia from chronic spinal cord injury (SCI). METHODS: Design: Retrospective cohort study. SETTING: Three Level-1 Trauma centers. PATIENT SELECTION CRITERIA: All adult patients with paraplegia or quadriplegia due to a chronic SCI with operative or nonoperative treatment of a femoral or tibial shaft fracture from 01/01/2009 through 12/31/2019 were included. OUTCOME MEASURES AND COMPARISONS: Outcomes collected included range of motion, pain, return to baseline activity, extent of malunion and treatment complications (infection, pressure ulcers, nonunion, DVT/PE, stroke, amputation, death). Comparison between operative and nonoperative treatment were made for each outcome. RESULTS: Fifty-nine patients with acute lower extremity fracture in the setting of chronic SCI fulfilled inclusion criteria with a median age of 46 years in the operative group and 47 years in the non-operative group. Twelve patients (70.6%) in the nonoperative group were male with 32 (76.2%) male patients in the operative group. Forty-six patients (78%) presented as low energy trauma. Differences were seen between operative and non-operative management for pressure ulcers (19% vs 52.9%, p=0.009) and mean VAS pain score at first follow-up (1.19 vs 3.3, p=0.03). No difference was seen for rates of infection, nonunion, DVT/PE, stroke, amputation, death, return to baseline activity, and range of motion. CONCLUSIONS: Tibial and femoral shaft fractures commonly resulted from low energy mechanisms in patients with chronic SCI. Operative treatment seemed to decrease morbidity in these patients via lowered rates of pressure ulcers and decreased pain compared to non-operative management. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Correction: Development and initial validation of the Orthotic Patient-Reported Outcomes-Mobility (OPRO-M): An item bank for evaluating mobility of people who use lower-limb orthoses.

[This corrects the article DOI: 10.1371/journal.pone.0293848.].

Assessing the safety and efficacy of prescribing psychologists in New Mexico and Louisiana.

This study aimed to compare patient outcomes between prescribing psychologists, psychiatrists, and primary care physicians (PCPs). Private insurance claims (2005-2021; n = 307,478) were used to conduct an active comparator, new user longitudinal cohort study developed using target trial emulation. Inverse propensity for treatment weighting was used to adjust for baseline differences in a range of sociodemographic, clinical, and contextual patient factors. Differences in the 1-year rate of health care visits for adverse drug events (ADEs), psychiatric emergency department (ED) utilization, medication adherence, and psychotropic polypharmacy were identified between prescribing psychologists and the other provider types using doubly robust Cox proportional hazards models. Compared to patients of psychiatrists, patients of prescribing psychologists had a 24% lower rate of ADEs (95% CI [0.60, 0.96]), a 20% lower rate of psychotropic polypharmacy (95% CI [0.74, 0.86]), and similar rates of psychiatric ED utilization and medication nonadherence. Compared to patients of PCPs, patients of prescribing psychologists had 138% higher rates of psychiatric ED utilization (95% CI [1.67, 3.39]), 175% higher rates of psychotropic polypharmacy (95% CI [2.53, 2.99]), 28% lower rates of medication nonadherence (95% CI [0.66, 0.78]), and similar rates of ADEs. Using robust pharmacoepidemiological methods, we noted that among mental health specialists, prescribing psychologists appear to be as safe and efficacious as psychiatrists in a large sample of privately insured patients. Notable differences in safety and efficacy when compared to PCPs may be attributable to differences between specialty and primary care. Future research on prescribing psychologists should move toward studies of care quality. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Characterization of Caulimovirid-like Sequences from Upland Cotton (Gossypium hirsutum L.) Exhibiting Terminal Abortion in Georgia, USA.

In this study, we investigated the potential involvement of endogenous viral elements (EVEs) in the development of apical tissue necrosis, resulting in the terminal abortion of upland cotton (Gossypium hirsutum L.) in Georgia. The high-throughput sequence analysis of symptomatic and asymptomatic plant tissue samples revealed near-complete EVE-Georgia (EVE-GA) sequences closely related to caulimoviruses. The analysis of EVE-GA's putative open reading frames (ORFs) compared to cotton virus A and endogenous cotton pararetroviral elements (eCPRVE) revealed their similarity in putative ORFs 1-4. However, in the ORF 5 and ORF 6 encoding putative coat protein and reverse transcriptase, respectively, the sequences from EVE-GA have stop codons similar to eCPRVE sequences from Mississippi. In silico mining of the cotton genome database using EVE-GA as a query uncovered near-complete viral sequence insertions in the genomes of G. hirsutum species (~7 kb) but partial in G. tomentosum (~5.3 kb) and G. mustelinum (~5.1 kb) species. Furthermore, cotton EVEs' episomal forms and messenger RNA (mRNA) transcripts were detected in both symptomatic and asymptomatic plants collected from cotton fields. No significant yield difference was observed between symptomatic and asymptomatic plants of the two varieties evaluated in the experimental plot. Additionally, EVEs were also detected in cotton seeds and seedlings. This study emphasizes the need for future research on EVE sequences, their coding capacity, and any potential role in host immunity or pathogenicity.

Utilization of orthoses and assistive devices among a national sample of lower limb orthosis users.

Introduction: Lower limb orthoses (LLOs) and assistive devices (ADs) can be used together or separately to improve mobility when performing daily activities. The goal of this study was to examine utilization of LLOs and ADs in a national sample of adult LLO users. Methods: A survey was designed to ask participants whether they typically use their LLOs and/or ADs to perform 20 daily activities. LLO users from orthotic clinics across the United States were invited to complete the survey. Descriptive statistics were used to examine utilization trends. Results: Survey responses from 1036 LLO users were analyzed. Community-based activities were performed with LLOs by at least 80% of participants. Activities that involved walking short distances in the home were more often performed without LLOs or ADs. Among participants with the four most prevalent health conditions, LLO use in the community was greatest among participants with Charcot-Marie-Tooth disease. Conclusions: LLOs were frequently used for a wide range of community-based activities. Simultaneous use of ADs and LLOs may be most beneficial for LLO users when performing activities outside of the home. Clinicians can discuss LLO and AD use with patients to optimize their functional outcomes at home and in the community.

Functional and perceptive differences between conventional and advanced ankle foot orthoses in community ambulators post-limb trauma: the injuries managed with advanced bracing of the lower extremity (IM ABLE) study.

Introduction: Many military service members and civilians suffer from lower extremity trauma. Despite recent advancements in lower limb bracing technology, it remains unclear whether these newer advanced braces offer improved comfort and functionality compared to conventional options. The IDEO (Intrepid Dynamic Exoskeletal Orthosis), a type of "advanced" orthosis was developed to assist in maintaining high functional performance in patients who have experienced high-energy lower extremity trauma and underwent limb salvage surgeries. Methods: A cross-sector multi-site initiative was completed to study the efficacy of advanced ankle foot orthoses (AFO) for lower limb trauma and injury compared to a conventional AFO. Following fitting, training, and accommodation, the subjects were assessed in each AFO system for mobility, self-reported function, safety and pain, and preference. Results: They preferred the advanced over the conventional AFO and the mobility and exertion perception improved with the advanced AFO with no difference in pain or overall health status scores. Discussion: Thus, an advanced AFO is an option for trauma affecting the lower limb. Long-term studies are required to better understand the accommodation and learning process of using an advanced AFO.

Femoral Head Fractures: Evaluation, Management, and Outcomes.

Fractures of the femoral head typically occur after high-energy trauma. Radiographs and cross-sectional imaging are used to appropriately classify and identify associated injuries or morphologic characteristics that may influence management. Identification of the radiographic and clinical hallmarks of an irreducible variant is critical to optimizing the patient's outcome. Nonsurgical treatment can be used in the setting of small, infrafoveal femoral head fractures without hip instability. When surgical treatment is indicated, an anterior (Smith-Petersen), posterior (Kocher-Langenbeck), or surgical hip dislocation approach may be used depending on injury details and surgeon preference. The purpose of this review was to summarize current evidence on femoral head fractures regarding indications, variant patterns, surgical approaches, and outcomes.

Scope-of-Practice Expansions Associated with Reduced Racial Disparities in Pediatric Mental Health Care.

To examine the association between scope-of-practice (SoP) regulations and racial disparities in pediatric mental health services. We used the National Survey of Children's Health (2016-2020; n = 33,790) to examine racial disparities in unmet mental health care needs and receipt of mental health medication between states with and without SoP expansions for psychologists and nurse practitioners (NP). Our primary outcomes were (1) unmet mental health care needs and (2) receipt of mental health medication. We examined heterogeneous treatment effects of SoP expansion on the outcomes using logistic regression with interaction terms between SoP expansion and race/ethnicity. We estimated population-level racial disparities for both outcomes stratified by SoP expansion to identify differences in racial disparities. The psychologist SoP expansion-associated reduction in unmet need was 15.8 percentage-points (CI= -25.3, -6.2) larger for Other-race children than for White children. The psychologist SoP expansion-associated increase in medication was 5.1%-points (CI=. 0.8, 9.4) larger for Black children and 5.6%-points (CI = 0.5, 10.8) for Other-race children. No differences were found for NP SoP expansion. Racial disparities in both outcomes were lower in psychologist SoP expansion states but varied in NP SoP states. Expanded SoP was generally associated with lower racial disparities in pediatric mental health care access.

A mindful approach to complications: Brief review of the literature and practical guide for the surgeon.

Patient complications and adverse outcomes are inherent to surgical practice and training. In addition to the impact on patients, there are profound and well-documented impacts of complications on surgeons, surgical trainees, and surgical teams. This manuscript reviews the literature regarding mindfulness-based practices and the associated mitigation of the adverse impact of complications. These mindfulness-based practices prepare surgeons for complications by improving mental and cognitive resilience facilitating more effective management of complications that avoids undue psychological and emotional stress. Practical recommendations are provided for the practicing surgeon from providers experienced in mindfulness-based training and preparation.

Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study.

BACKGROUND: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. METHODS: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. FINDINGS: Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. INTERPRETATION: Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. FUNDING: US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

The Effect of Extracorporeal Membrane Oxygenation in Patients With Multiple Orthopaedic Injuries.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) plays a vital role in providing life support for patients with reversible cardiac or respiratory failure. Given the high rate of complications and difficulties associated with caring for ECMO patients, the goal of this study was to compare outcomes of orthopaedic surgery in polytrauma patients who received ECMO with similar patients who have not. This will help elucidate the timing and type of fixation that should be considered in patients on ECMO. METHODS: A retrospective cohort was collected from the electronic medical record of two level I trauma centers over an 8-year period (2015 to 2022) using Current Procedural Terminology codes. Patients were matched with a similar counterpart not requiring ECMO based on sex, age, American Society of Anesthesiologists score, body mass index, injury severity score, and fracture characteristics. Outcomes measured included length of stay, number of revisions, time to definitive fixation, infection, amputation, revision surgery to promote bone healing, implant failure, bleeding requiring return to the operating room, and mortality. RESULTS: Thirty-two patients comprised our ECMO cohort with a patient-matched control group. The ECMO cohort had an increased length of stay (40 versus 17.5 days, P = 0.001), number of amputations (7 versus 0, P = 0.011), and mortality rate (19% versus 0%, P = 0.024). When comparing patients placed on ECMO before definitive fixation and after definitive fixation, the group placed on ECMO before definitive fixation had significantly longer time to definitive fixation than the group placed on ECMO after fixation (14 versus 2.0 days, P < 0.001). CONCLUSION: ECMO is a lifesaving measure for trauma patients with cardiopulmonary issues but can complicate fracture care. Although it is not associated with an increase in revision surgery rates, ECMO was associated with prolonged hospital stay and delays in definitive fracture surgery when initiated before definitive fixation. LEVEL OF EVIDENCE: III.

Implementing automated Medicaid eligibility renewals was not associated with higher levels of program participation.

Increasing participation in Medicaid among eligible individuals is critical for improving access to care among low-income populations. The administrative burdens of enrolling and renewing eligibility are a major barrier to participation. To reduce these burdens, the Affordable Care Act required states to adopt automated renewal processes that use available databases to verify ongoing eligibility. By 2019, nearly all states adopted automated renewals, but little is known about how this policy affected Medicaid participation rates. Using the 2015-2019 American Community Survey, we found that participation rates among nondisabled, nonelderly adults and children varied widely by state, with an average of 70.8% and 90.7%, respectively. Among Medicaid-eligible adults, participation was lower among younger adults, males, unmarried individuals, childless households, and those living in non-expansion states compared with their counterparts. State adoption of automated renewals varied over time, but participation rates were not associated with adoption. This finding could reflect limitations to current automated renewal processes or barriers to participation outside of the eligibility renewal process, which will be important to address as additional states expand Medicaid and pandemic-era protections on enrollment expire.

Influences of sleep, cortisol reactivity, and risk/reward-based decision-making on suicide.

BACKGROUND AND OBJECTIVES: Poor sleep quality is a known contributor to suicidal thoughts and behaviors. This study examines whether sleep quality modulates the effect of an individual's stress response and risk/reward-based decision making on suicide risk. METHODS: Participants were 160 adults at a residential substance use treatment facility with lifetime exposure to trauma who completed a clinician-administered measure of suicide risk, the Iowa Gambling Task (IGT), and a self-report measure of sleep. Cortisol reactivity (i.e., changes in cortisol before and after a personalized trauma script) was used to measure stress response. We used quantile regression to examine the effects of sleep, cortisol, and risk/reward decision-making on suicide risk. RESULTS: We found poor sleep quality to be increasingly salient in individuals at greater risk for suicide than those at lower risk for suicide. Furthermore, individuals with moderate to moderate-high levels of suicide risk seem to have greater cortisol reactivity. In the low-moderate quantile, we found suicide risk to be associated with both high stress reactivity and low-risk, high-reward decision-making, as well as low stress reactivity and high-risk/low-reward decision-making. LIMITATIONS: These findings should be interpreted considering several methodological constraints, such as the use of a pre-determined sample and instruments not tailored for our hypotheses, the MINI 'Suicide' Module's limited differentiation between suicidal ideation and behavior, and variably timed cortisol sampling. CONCLUSIONS: Despite these limitations, the findings from this study support the use of evidence-based interventions focused on improving sleep quality and managing emotional reactivity to decrease suicide risk.

Neurosurgical Intervention for Nerve and Muscle Biopsies.

(1) Background: Neurologic and musculoskeletal diseases represent a considerable portion of the underlying etiologies responsible for the widely prevalent symptoms of pain, weakness, numbness, and paresthesia. Because of the subjective and often nonspecific nature of these symptoms, different diagnostic modalities have been explored and utilized. (2) Methods: Literature review. (3) Results: Nerve and muscle biopsy remains the gold standard for diagnosing many of the responsible neurological and musculoskeletal conditions. However, the need for invasive tissue sampling is diminishing as more investigations explore alternative diagnostic modalities. Because of this, it is important to explore the current role of neurosurgical intervention for nerve and muscle biopsies and its current relevance in the diagnostic landscape of neurological and musculoskeletal disorders. With consideration of the role of nerve and muscle biopsy, it is also important to explore innovations and emerging techniques for conducting these procedures. This review explores the indications and emerging techniques for neurological intervention for nerve and muscle biopsies. (4) Conclusions: The role of neurosurgical intervention for nerve and muscle biopsy remains relevant in diagnosing many neurological and musculoskeletal disorders. Biopsy is especially relevant as a supportive point of evidence for diagnosis in atypical cases. Additionally, emerging techniques have been explored to guide diagnostics and biopsy, conduct less invasive biopsies, and reduce risks of worsening neurologic function and other symptoms secondary to biopsy.

The AID2 system offers a potent tool for rapid, reversible, or sustained degradation of essential proteins in live mice.

Studying essential genes required for dynamic processes in live mice is challenging as genetic perturbations are irreversible and limited by slow protein depletion kinetics. The first-generation auxin-inducible-degron (AID) system is a powerful tool for analyzing inducible protein loss in cultured cells. However, auxin administration is toxic to mice, preventing its long-term use in animals. Here, we use an optimized second-generation AID system to achieve the conditional and reversible loss of the essential centrosomal protein CEP192 in live mice. We show that the auxin derivative 5-Ph-IAA is well tolerated over two weeks and drives near-complete CEP192-mAID degradation in less than one hour in vivo. Prolonged CEP192 loss led to cell division failure and cell death in proliferative tissues. Thus, the second-generation AID system is well suited for rapid and/or sustained protein depletion in live mice, offering a valuable new tool for interrogating protein function in vivo.