Therapeutic implications of the metabolic changes associated with BRAF inhibition in melanoma.

Melanoma metabolism can be reprogrammed by activating BRAF mutations. These mutations are present in up to 50% of cutaneous melanomas, with the most common being V600E. BRAF mutations augment glycolysis to promote macromolecular synthesis and proliferation. Prior to the development of targeted anti-BRAF therapies, these mutations were associated with accelerated clinical disease in the metastatic setting. Combination BRAF and MEK inhibition is a first line treatment option for locally advanced or metastatic melanoma harboring targetable BRAF mutations. This therapy shows excellent response rates but these responses are not durable, with almost all patients developing resistance. When BRAF mutated melanoma cells are inhibited with targeted therapies the metabolism of those cells also changes. These cells rely less on glycolysis for energy production, and instead shift to a mitochondrial phenotype with upregulated TCA cycle activity and oxidative phosphorylation. An increased dependence on glutamine utilization is exhibited to support TCA cycle substrates in this metabolic rewiring of BRAF mutated melanoma. Herein we describe the relevant core metabolic pathways modulated by BRAF inhibition. These adaptive pathways represent vulnerabilities that could be targeted to overcome resistance to BRAF inhibitors. This review evaluates current and future therapeutic strategies that target metabolic reprogramming in melanoma cells, particularly in response to BRAF inhibition.

Perceptions of incarcerated people: prison conditions, public health, and justice in the United States.

Carceral conditions in the United States may serve as a proxy for crises within justice and health systems. This study seeks to consider and measure prison climate from the perspective of incarcerated people. By examining within-facility differences in carceral experiences, results shed light on the complex nexus between the carceral context, health, and justice. We administered the Prison Climate Questionnaire (PCQ) to the complete population of incarcerated men in a correctional facility located in the Eastern United States. In this facility, housing units hold distinct populations, fulfill different functions, and can offer unique programming. We regress select items from the PCQ on a set of dummies corresponding to different residential units within the facility. Responses indicate low but relatively uniform perceptions of overall personal health, as well as access to, and satisfaction with, medical care. Between-unit differences emerge regarding staff relationships, experiences of discrimination, and levels of isolation. The perspectives of incarcerated people can, and should, play a role in understanding and conceptualizing the nature of the prison environment. Policy responses, especially those that impact the health and well-being of currently and formerly incarcerated people, can be informed by these perspectives.

HumanIslets: An integrated platform for human islet data access and analysis.

Comprehensive molecular and cellular phenotyping of human islets can enable deep mechanistic insights for diabetes research. We established the Human Islet Data Analysis and Sharing (HI-DAS) consortium to advance goals in accessibility, usability, and integration of data from human islets isolated from donors with and without diabetes at the Alberta Diabetes Institute (ADI) IsletCore. Here we introduce HumanIslets.com, an open resource for the research community. This platform, which presently includes data on 547 human islet donors, allows users to access linked datasets describing molecular profiles, islet function and donor phenotypes, and to perform various statistical and functional analyses at the donor, islet and single-cell levels. As an example of the analytic capacity of this resource we show a dissociation between cell culture effects on transcript and protein expression, and an approach to correct for exocrine contamination found in hand-picked islets. Finally, we provide an example workflow and visualization that highlights links between type 2 diabetes status, SERCA3b Ca2+-ATPase levels at the transcript and protein level, insulin secretion and islet cell phenotypes. HumanIslets.com provides a growing and adaptable set of resources and tools to support the metabolism and diabetes research community.

Minority Stress, Psychological Distress, Sexual Compulsivity, and Avoidance-Based Motivations Associated with Methamphetamine Use Among Sexual Minority Men Living with HIV: Examining Direct and Indirect Associations Using Cross-Sectional Structural Equation Modeling.

OBJECTIVE: Sexual minority men (SMM) living with HIV report significantly greater methamphetamine use compared with heterosexual and HIV-negative peers. Greater use may be related to stressors (e.g., HIV-related stigma) faced by SMM living with HIV and subsequent psychological and behavioral sequelae. We tested an integrated theoretical model comprised of pathways between stigma, discrimination, childhood sexual abuse, psychological distress, sexual compulsivity, and cognitive escape in predicting methamphetamine use among SMM living with HIV. METHODS: Among 423 SMM living with HIV, we tested a structural equation model examining factors hypothesized to be directly and indirectly associated with methamphetamine use. Analyses were adjusted for demographic covariates and sampling bias. RESULTS: The model showed good fit (CFI = 0.96, RMSEA = 0.01). Heterosexist discrimination was associated with psychological distress (ß = 0.39, p < 0.001) and psychological distress was associated with sexual compulsivity (ß = 0.33, p < 0.001). Sexual compulsivity was associated with cognitive escape (ß = 0.31, p < 0.001), which was associated with methamphetamine use (ß = 0.51, p < 0.001). Psychological distress was associated with methamphetamine use via serial indirect effects of sexual compulsivity and cognitive escape (ß = 0.05, p < 0.05). CONCLUSIONS: Heterosexist discrimination contributed to psychological distress among SMM living with HIV. Psychological distress is linked to methamphetamine use via sexual compulsivity and cognitive avoidance. Interventions seeking to reduce the likelihood that SMM living with HIV use methamphetamine should include coping strategies specific to heterosexism and related psychological distress.

Initial Perspectives From Rural-Residing Adults on a Digital Cognitive Health Coaching Intervention: Exploratory Qualitative Analysis.

BACKGROUND: A growing body of research has examined lifestyle-based interventions for dementia prevention. Specifically, health coaching interventions have been linked to decreased risk of Alzheimer disease (AD) comorbidities, such as diabetes. Despite the association, there is a lack of research examining the efficacy and perception of digital health coaching on reducing AD risk. Understanding the perceived benefits of participating in a digital health coach program is critical to ensure long-term use, including participant adherence and engagement. OBJECTIVE: The purpose of this study is to examine the initial attitudes toward a digital health coaching intervention aimed at preventing cognitive decline among at-risk, rural participants. METHODS: This exploratory qualitative study is part of the ongoing Digital Cognitive Multidomain Alzheimer Risk Velocity Study (DC-MARVel; ClinicalTrials.gov NCT04559789), a 2-year randomized control trial examining the effects of a digital health coaching intervention on dementia risk, cognitive decline, and general health outcomes. Participants were recruited from the northwest region of Arkansas via word of mouth, email, local radio, and social media. At the time of the analysis, 103 participants randomly assigned to the health coaching group completed an average of 4 coaching sessions over a 4-month period. The intervention included asynchronous messages 1-2 times per week from their health coach that contained health education articles based on the participant's goals (eg, increase physical activity), unlimited access to their coach for questions and recommendations, and monthly meetings with their coach via videoconference or phone to discuss their goals. Participants were asked 2 open-ended questions, "What were your top 1 or 2 takeaways from your recent Health Coaching session?" and "Is there anything you would change about our Health Coaching sessions?" A thematic analysis was conducted using feedback responses from 80 participants (mean age, SD 7.6 years). RESULTS: The following four themes emerged from participants' feedback: (1) healthy lifestyle and behavioral changes, (2) a sense of self-awareness through introspection, (3) value in coach support, and (4) a desire for a change in program format (eg, frequency). In total, 93% (n=74) of participants expressed that the intervention needed no changes. CONCLUSIONS: Initial participation in the digital cognitive health coaching intervention was well received, as evidenced by participants reporting value in goal setting and strategies for healthy lifestyle and behavioral changes as well as self-reflection on their personal lifestyle choices. Feedback about their assigned coach also offers insight into the importance of the coach-participant relationship and may serve as a significant factor in overall participant success. Given the exploratory nature of this study, more robust research is needed to elicit more information from participants about their experiences to fully understand the acceptability of the digital health coaching intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04559789; https://clinicaltrials.gov/show/NCT04559789. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/31841.

Association of Tumor-informed Circulating Tumor DNA Detectability Before and After Radical Cystectomy with Disease-free Survival in Patients with Bladder Cancer.

BACKGROUND AND OBJECTIVE: Despite curative-intent radical cystectomy (RC), patients with muscle-invasive bladder cancer (MIBC) are at high risk of recurrence. Biomarkers are urgently needed to refine prognostication and selection of appropriate perioperative systemic therapies. Our aim was to evaluate the prognostic and predictive value of tumor-informed circulating tumor DNA (ctDNA) results in a multicenter cohort of patients with bladder cancer who underwent RC. METHODS: We performed a retrospective analysis of real-world data for a commercial ctDNA test (Signatera; Natera, Austin, TX, USA) performed in 167 patients (852 plasma samples) before RC and during molecular residual disease (MRD; adjuvant decision) and surveillance windows. We assessed the correlation between recurrence and ctDNA status before and after RC using Cox regression analysis. RESULTS AND LIMITATIONS: During study-defined postoperative MRD and surveillance windows, detectable ctDNA was associated with shorter disease-free survival (DFS) when compared to undetectable ctDNA (MRD: hazard ratio 6.93; p < 0.001; surveillance: hazard ratio 23.02; p < 0.001). Of note, patients with undetectable ctDNA did not appear to benefit from adjuvant therapy (p = 0.34). Detectable ctDNA in the pre-RC (p = 0.045), MRD (p = 0.002), and surveillance (p < 0.001) windows was the only risk factor independently associated with shorter DFS. Limitations include the retrospective and nonrandomized nature of the study. CONCLUSIONS: ctDNA testing in patients with bladder cancer undergoing RC was prognostic and potentially predictive. Identification of patients at high risk of recurrence may aid in patient counseling and decision-making. PATIENT SUMMARY: We found that outcomes for patients with muscle-invasive bladder cancer are strongly linked to detection of tumor DNA in blood samples. The results show the value of tumor-informed testing for tumor DNA in blood for decisions on the best treatment for each individual patient.

Pipkin IV fracture dislocation of the hip in a football athlete - A case report.

Pipkin type IV fracture dislocation of the hip is a rare, high-energy injury, that is associated with poor functional outcomes and complications. We report a case of a 20-year old male quarterback who sustained a Pipkin type IV fracture dislocation during a football game. He underwent immediate closed reduction, transfer to a Level I trauma centre, surgical management, and progressive rehabilitation. Clinical and radiographic assessments were carried out periodically for 1 year. At 10 months post-injury, the athlete returned to full-time play as the starting quarterback of his University football team. He completed a pain-free season at 1-year post-injury. Clinical and radiographic evaluations demonstrated appropriate healing with no complications. Despite the high-energy and often devastating nature of Pipkin Type IV injuries, this case report demonstrates that prompt, appropriate management and rehabilitation of this injury in a University quarterback led to positive functional outcomes. Further studies on the treatment and outcomes of this rare sport injury are needed to optimize management.

Attitudes toward and preparedness for lung transplantation among individuals with cystic fibrosis in the era of highly effective modulators.

BACKGROUND: Outcomes for individuals with cystic fibrosis (CF) have improved due to highly effective modulator therapy (HEMT). However, lung transplant (LTx) remains an important treatment for people with advanced lung disease. This study assessed attitudes and knowledge about LTx in the HEMT era. METHODS: All patients from the University of Washington CF clinic were surveyed March 25-May 30, 2020. Questions addressed self-rated LTx preparedness and knowledge, as well as barriers and facilitators to discussing LTx. Demographic and clinical data were extracted from the electronic health record. RESULTS: There were 159/224 (71%) responses. Respondents had a median forced expiratory volume in one second (FEV1) of 70%, and 142 (89%) were on modulatory therapy. One hundred thirteen (71%) respondents felt that it was moderately or very important to be prepared to make decisions about LTx, though only 56 (35%) felt moderately or very prepared. Only 83 (30%) and 47 (52%) participants correctly answered questions about life expectancy and improved quality of life after LTx, respectively. Respondents with Medicaid insurance less frequently answered questions correctly. The most common barriers to discussing LTx were fear of being a burden on loved ones for 58 respondents (36%) and cost of LTx for 46 (29%). Most participants (94%) trusted their CF doctor, and 75% of participants selected trust as a facilitator for LTx discussions. CONCLUSIONS: Many individuals with CF, especially those with lower socioeconomic status, lacked knowledge and did not feel very prepared for decisions about LTx. Earlier education and discussions about LTx represent an area for improvement in CF care.

Impact of Obesity on Timing of Tracheotomy: A Multi-institutional Retrospective Study.

OBJECTIVE: To examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short-term surgical complications requiring a return to the operating room and 30-day mortality utilizing data from the Multi-Institutional Study on Tracheotomy (MIST). METHODS: A retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications. RESULTS: Among the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy (p = 0.001). Morbidly obese patients (BMI ≥35 kg/m2) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%-75%]: 11.0 days [7-17 days] versus 9.0 days [5-14 days]; p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days (p = 0.12) or mortality (p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%-75%]: 10.0 days [6-15 days] versus 10.0 days [6-15 days]; p = 0.36). CONCLUSION: BMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

Resident and Fellow Performance and Supervision in Surgical Oncology Procedures.

BACKGROUND: Previous research has highlighted concerns among trainees and attendings that general surgery training and fellowship are inadequately preparing trainees for practice. Providing trainees with supervision that matches their proficiency may help bridge this gap. We sought to benchmark operative performance and supervision levels among senior surgery residents (post-graduate year 4 or 5) and fellows performing general surgical oncology procedures. STUDY DESIGN: Observational data were obtained from the Society for Improving Medical Procedural Learning (SIMPL) OR application for core general surgical oncology procedures performed at 103 unique residency and fellowship programs. Procedures were divided into breast and soft tissue, endocrine, and hepatopancreatobiliary (HPB). Case evaluations completed by trainees and attendings were analyzed to benchmark trainee operative performance and level of supervision. RESULTS: There were 4,907 resident cases and 425 fellow cases. Practice-ready performance, as assessed by trainees and faculty, was achieved by relatively low proportions of residents and fellows for breast and soft tissue cases (residents: 38%, fellows: 48%), endocrine cases (residents: 22%, fellows: 41%), and HPB cases (residents: 10%, fellows: 40%). Among cases in which trainees did achieve practice-ready performance, supervision only was provided for low proportions of cases as rated by trainees (residents: 17%, fellows: 18%) and attendings (residents: 21%, fellows 25%). CONCLUSION: In a sample of 103 residency and fellowship programs, attending surgeons rarely provided senior residents and fellows with levels of supervision commensurate to performance for surgical oncology procedures, even for high performing trainees. These findings suggest a critical need for surgical training programs to prioritize providing greater levels of independence to trainees that have demonstrated excellent performance.

Understanding Vaccine Hesitancy in U.S. Prisons: Perspectives from a Statewide Survey of Incarcerated People.

Much of the American response to the COVID-19 pandemic was characterized by a divergence between general public opinion and public health policy. With little attention paid to individuals incarcerated during this time, there is limited direct evidence regarding how incarcerated people perceived efforts to mediate the harms of COVID-19. Prisons operate as a microcosm of society in many ways but they also face unique public health challenges. This study examines vaccine hesitancy-and acceptance-among a sample of individuals incarcerated within adult prisons in Pennsylvania. Using administrative records as well as rich attitudinal data from a survey of the incarcerated population, this study identifies a variety of social and historical factors that are-and are not-associated with an incarcerated person's willingness to receive the COVID-19 vaccine. Our findings highlight vaccination challenges unique to the carceral context and offer policy recommendations to improve trust in credible health messengers and health service provision for this often overlooked but vulnerable population.

Retrospective Evaluation of Clinical and Clinicopathologic Findings, Case Management, and Outcome for Dogs and Cats Exposed to Micrurus fulvius (Eastern Coral Snake): 92 Cases (2021-2022).

This retrospective, observational study describes the clinical findings, case management trends, and outcomes of 83 dogs and nine cats exposed to eastern coral snakes in a university teaching hospital setting. The medical records of dogs and cats that received antivenom following coral snake exposure were reviewed. Data collected included signalment, time to antivenom administration, physical and laboratory characteristics at presentation, clinical course during hospitalization, length of hospitalization, and survival to discharge. The mean time from presentation to coral snake antivenom administration was 2.26 ± 1.46 h. Excluding cases where the owner declined in-hospital care, the mean hospitalization time for dogs and cats was 50.8 h and 34 h, respectively. The mean number of antivenom vials was 1.29 (1-4). Gastrointestinal signs (vomiting and ptyalism) occurred in 42.2% (35/83) of dogs and 33.3% (3/9) of cats. Peripheral neurologic system deficits (ataxia, paresis to plegia, absent reflexes, and hypoventilation) were noted in 19.6% (18/92) of dogs and cats. Hemolysis was also common in 37.9% (25/66) of dogs but was not observed in cats. Mechanical ventilation (MV) was indicated in 12% (10/83) of dogs but no cats. Acute kidney injury (AKI), while rare, was a common cause of euthanasia at 20% (2/5) and was the most common complication during MV at 44.4% (4/9). Pigmenturia/hemolysis occurred in 88.9% (8/9) of MV cases and in all cases with AKI. Despite delays in antivenom administration by several hours, dogs and cats with coral snake exposure have low mortality rates (6% of dogs (5/83) and 0% of cats). Gastrointestinal signs were common but were not predictive of progression to neurological signs. Thus, differentiating between coral snake exposure and envenomation before the onset of neurological signs remains challenging.

COVID-19-Related Increases in Depressive and Anxious Symptoms Are Associated with Maladaptive Eating Among Patients up to 4 years Post-bariatric Surgery.

INTRODUCTION: Depressive and anxious symptoms and maladaptive eating behaviors fluctuate with stressful events for patients seeking bariatric surgery. These associations are less clear for patients postoperatively. Using the COVID-19 pandemic as a frame, we examined associations between changes in depressive and anxious symptoms and maladaptive eating behaviors between up to four years postoperatively. METHODS: Participants (N = 703) who underwent surgery between 2018 and 2021 completed web-based questionnaires between 2021 and 2022. Demographic and surgical data were obtained from electronic health records. Participants reported whether depressive and anxious symptoms increased or were stable/decreased during the COVID-19 pandemic, and completed eating behavior measures. RESULTS: Many participants reported increased depressive (27.5%) and anxious (33.7%) symptoms during the COVID-19 pandemic. Compared to those who reported stable or decreased symptoms, these participants were as follows: (1) more likely to endorse presence of binge, loss-of-control, graze, and night eating; (2) reported higher emotional eating in response to anger and frustration, depression, and anxiety; and (3) reported higher driven and compulsive eating behaviors. Frequency of binge, loss-of-control, graze, and night eating episodes did not differ between groups (e.g., increased vs. stable/decreased anxious symptoms) among participants who endorsed any episodes. CONCLUSION: A large portion of the sample reported increased depressive and anxious symptoms during the COVID-19 pandemic, and these increases were associated with maladaptive eating behaviors. Depressive and anxious symptoms and eating behaviors should be assessed postoperatively as significant stressors may be associated with increased distress and maladaptive eating behaviors that can affect postoperative outcomes. Postoperative interventions may be useful at simultaneously targeting these concerns.

Offering nurse care management for opioid use disorder in primary care: Impact on emergency and hospital utilization in a cluster-randomized implementation trial.

BACKGROUND: Patients with opioid use disorder (OUD) have increased emergency and hospital utilization. The PROUD trial showed that implementation of office-based addiction treatment (OBAT) increased OUD medication treatment compared to usual care, but did not decrease acute care utilization in patients with OUD documented pre-randomization (clinicaltrials.gov/study/NCT03407638). This paper reports secondary emergency and hospital utilization outcomes in patients with documented OUD in the PROUD trial. METHODS: This cluster-randomized implementation trial was conducted in 12 clinics from 6 diverse health systems (March 2015-February 2020). Patients who visited trial clinics and had an OUD diagnosis within 3 years pre-randomization were included in primary analyses; secondary analyses added patients with OUD who were new to the clinic or with newly-documented OUD post-randomization. Outcomes included days of emergency care and hospital utilization over 2 years post-randomization. Explanatory outcomes included measures of OUD treatment. Patient-level analyses used mixed-effect regression with clinic-specific random intercepts. RESULTS: Among 1988 patients with documented OUD seen pre-randomization (mean age 49, 53 % female), days of emergency care or hospitalization did not differ between intervention and usual care; OUD treatment also did not differ. In secondary analyses among 1347 patients with OUD post-randomization, there remained no difference in emergency or hospital utilization despite intervention patients receiving 32.2 (95 % CI 4.7, 59.7) more days of OUD treatment relative to usual care. CONCLUSIONS: Implementation of OBAT did not reduce emergency or hospital utilization among patients with OUD, even in the sample with OUD first documented post-randomization in whom the intervention increased treatment.

Diastereoselective Synthesis of the HIV Protease Inhibitor Darunavir and Related Derivatives via a Titanium Tetrachloride-Mediated Asymmetric Glycolate Aldol Addition Reaction.

Darunavir is a potent HIV protease inhibitor that has been established as an effective tool in the fight against the progression of HIV/AIDS in the global community. The successful application of this drug has spurred the development of derivatives wherein strategic regions (e.g., P1, P1', P2, and P2') of the darunavir framework have been structurally modified. An alternate route for the synthesis of darunavir and three related P1 and P1' derivatives has been developed. This synthetic pathway involves the use of a Crimmins titanium tetrachloride-mediated oxazolidine-2-thione-guided asymmetric glycolate aldol addition reaction. The resultant aldol adduct introduces the P1 fragment of darunavir via an aldehyde. Transamidation with a selected amine (isobutylamine or 2-ethyl-1-butylamine) to cleave the auxiliary yields an amide wherein the P1' component is introduced. From this stage, the amide is reduced to the corresponding ß-amino alcohol and the substrate is then bis-nosylated to introduce the requisite p-nitrobenzenesulfonamide component and activate the secondary alcohol for nucleophilic substitution. Treatment with sodium azide yielded the desired azides, and the deprotection of the p-methoxyphenoxy group is achieved with the use of ceric ammonium nitrate. Finally, hydrogenation to reduce both the aniline and azide functionalities with concurrent acylation yields darunavir and its derivatives.

Hospital Quality Indicators for Opioid-Exposed Infants: Results From an Expert Consensus Panel.

OBJECTIVE: To elicit expert consensus on quality indicators for the hospital-based care of opioid-exposed infants. METHODS: We used the ExpertLens online platform to conduct a 3-round modified Delphi panel. Expert panelists included health care providers, parents in recovery, quality experts, and public health experts. We identified 49 candidate quality indicators from a literature review and environmental scan. A total of 32 experts rated the importance and feasibility of the indicators using a 9-point Likert scale (Round 1), reviewed and discussed the initial ratings (round 2), and revised their original ratings (Round 3). Numeric scores corresponded with descriptive ratings of "low" (1-3), "uncertain" (4-6), or "high" (7-9). We measured consensus using the RAND/UCLA Appropriateness Method. RESULTS: Candidate quality indicators assessed structures, processes, and outcomes in multiple domains of clinical care. After the final round, 36 indicators were rated "high" on importance and feasibility. Experts had strong consensus on the importance of quality indicators to assess universal screening of pregnant people for substance use disorder, hospital staff training, standardized assessment for neonatal opioid withdrawal syndrome, nonpharmacologic interventions, and transitions of care. For indicators focused on processes and outcomes, experts saw feasibility as dependent on the information routinely documented in electronic medical records or billing records. To present a more complete picture of hospital quality, experts suggested development of composite measures that summarize quality across multiple indicators. CONCLUSIONS: A panel of experts reached consensus on a range of quality indicators for hospital-based care of opioid-exposed infants, with potential for use in national benchmarking, intervention studies, or hospital performance measurement.

Public Health Involvement in United States' Vision Zero Initiatives: A Mixed-Methods Study.

CONTEXT: Vision Zero (VZ) aims to reduce fatalities and serious injuries from road traffic crashes to zero through multidisciplinary coordination. While public health officials are often recognized as critical to VZ, their involvement in VZ across the United States has not been quantified. OBJECTIVE: To explore how United States public health officials were involved in VZ development and implementation. DESIGN: We used a mixed-method design including a quantitative assessment of VZ plans and in-depth interviewing with VZ coordinators. SETTING: United States. PARTICIPANTS: Twenty-two in-depth interviews with municipal (n = 12) and regional (n = 10) VZ coordinators and 43 VZ plans were reviewed. MAIN OUTCOME MEASURE: Public health involvement in VZ development and implementation. RESULTS: In the United States, 64 municipalities and 21 regional entities had first-time VZ plans published between 2014 and 2022. We abstracted a sample of municipal (n = 22) and all (n = 21) regional plans. Most plans described key groups involved in plan development (municipal 81.8%, regional 100%). About two-thirds (67.4%; 59.1% municipal, 76.2% regional) of the plans noted public health officials in the plan development. Most plans described the principles forming the foundation of their plan (83.7%), but few mentioned public health as part of the plan principles (22.7% municipal, 14.3% regional). Public health officials were involved in engaging the community (9.1% municipal, 33.3% regional) and providing data (22.7% municipal, 52.4% regional) for plan development, as documented in the plans. For proposed implementation, public health officials were identified as involved in: community engagement (31.8% municipal, 42.9% regional), sharing/analyzing data (40.9% municipal, 33.3% regional), and identifying/providing funding sources (13.6% municipal, 4.8% regional). The in-depth interviews provided further context and a more detailed understanding of public health involvement in VZ. CONCLUSIONS: Evidence from the VZ plans and interviews provided examples of how public health officials engaged in the development and implementation of VZ initiatives.

Brief Self-Compassion Intervention for Women of Higher Weight and Internalized Weight Bias: A Randomized Pilot Study.

BACKGROUND: Internalized weight bias (IWB) negatively impacts mental and physical health, and disproportionately affects women of higher weight. Although self-compassion training may be advantageous for reducing IWB and associated sequalae, further examination of its clinical significance and cultural acceptability is warranted. METHOD: A randomized pilot study was conducted to evaluate the feasibility, including cultural acceptability, and clinical significance of a 3-session self-compassion intervention (SCI) for women with IWB. Women with BMIs of > 25 and IWB (N = 34) were randomly assigned to the SCI or a waitlist control group. Participants completed pre, post, and 1-month follow-up surveys on IWB, self-compassion, body image, eating behaviors, physical activity, and affect. Analyses of covariance were employed and percentages of change were calculated to examine post-intervention between-group differences in outcomes. Cultural acceptability was evaluated through participants' ratings of the perceived inclusivity and relevancy of the SCI. RESULTS: There were 59% (n = 10) and 47% (n = 8) completion rates in the SCI and waitlist control groups, respectively. Compared to the waitlist control group, SCI participants reported greater pre-post improvements in self-compassion, IWB, body shame and surveillance, uncontrolled eating, and physical activity with medium to large effect sizes, and emotional eating with small effects. The SCI was perceived to be beneficial overall, and cultural acceptability ratings were mostly favorable despite individual differences. CONCLUSION: This brief SCI may be beneficial for women impacted by weight stigma and IWB. Attention to increased diversity and cultural acceptability is warranted in future trials.

Local Modeling by Adapting Source Calibration Models to Analyte Shifted Target Domain Samples Without Reference Values.

Spectral multivariate calibration aims to derive models characterizing mathematical relationships between sample analyte amounts and corresponding spectral responses. These models are effective at predicting target domain sample analyte amounts when target samples are within the analyte and spectral calibration source domain. Models fail when target samples shift (analyte amounts and/or spectra) from the original calibration domain model. A total recalibration solution requires acquisition of new sample reference values and spectra. However, obtaining enough reference values to distinguish the target domain may be challenging or expensive. A simpler approach adapts the original model to the target domain using target sample spectra without analyte reference values (unlabeled). Analytical chemists have developed several machine learning algorithms using unlabeled regression domain adaptation processes. Unfortunately, prediction accuracy declines for these methods depending on how much the target domain analyte distribution has shifted from the calibration distribution, and regression transfer learning methods are instead needed. Regression domain adaptation and transfer learning are often referred to as model updating in analytical chemistry, but regression domain adaptation only applies to spectral shifts. The regression transfer learning method presented in this paper named null augmentation regression constant analyte (NARCA) leverages unlabeled repeat spectra of a single target sample to update an original calibration model to the shifted target domain sample. With sample repeat spectra, the analyte amount can be assumed constant or nearly constant for NARCA and because models are formed for one sample, NARCA operates as a local modeling method. The performance of NARCA as a regression transfer learning method is evaluated using five near-infrared data sets.

Evaluating Changes in Pulsatile Flow With Endovascular Stents in an In Vitro Blood Vessel Model: Potential Implications for the Future Management of Neurovascular Compression Syndromes.

BACKGROUND: Neurovascular compression syndromes (NVCS), encompassing conditions such as trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia, significantly impair patient quality of life through abnormal vascular compression and micro-pulsation of vasculature on cranial nerves at the Obersteiner-Redlich zone. The modulation of pulsatile flow dynamics via endovascular stents presents a novel research frontier for alleviating these syndromes. AIM: The primary aim of this investigation was to delineate the impact of various endovascular stents on pulsatile flow within an in vitro model of a blood vessel, thereby elucidating their potential applicability in the therapeutic management of NVCS. MATERIALS AND METHODS: A simple in vitro analog of a posterior circulation artery was developed, employing an intravenous pump to replicate cardiac-induced blood flow. Within this model, alterations in pulsatile flow were quantitatively assessed following the introduction of three categorically distinct endovascular stents, varying in size. This assessment was facilitated through the employment of both micro-Doppler and Doppler ultrasound methodologies. RESULTS: The Pipeline 5x35 mm stent (Medtronic, Minneapolis, MN) demonstrated the most significant reductions in peak systolic velocity (Vmax) and pulsatility index (PI), PI especially over the stent, suggesting its potential for drastically altering blood flow dynamics. Similarly, Neuroform Atlas 4.5x30 mm and Neuroform Atlas 4x24 mm stents (Stryker, Kalamazoo, MI) also showed notable decreases in hemodynamic parameters, albeit to different extents. Statistical analysis confirmed that these changes were significantly different from the control (P < 0.0001 for PI and Vmax; P < 0.05 for inter-stent comparisons), except for proximal PI means, which did not significantly differ from the control (P = 0.2777). CONCLUSION: These findings affirm the potential of endovascular stents to substantially modulate arterial pulsatility. The observed decrease in pulsatile flow resultant from endovascular stent application has the potential to attenuate ectopic nerve excitation, a hallmark of NVCS. Consequently, this research highlights the prospective utility of endovascular stents in developing minimally invasive therapeutic approaches for NVCS.