An assessment of the psychometric properties of the Coping Strategies Questionnaire - Sickle Cell Disease (CSQ-SCD) among adults in the United States.

BACKGROUND: Previous studies have reported conflicting factor structures of the Coping Strategies Questionnaire - Sickle Cell Disease (CSQ-SCD). This study examined the psychometric properties of the CSQ-SCD among adults with SCD in the United States. METHODS: This study implemented a cross-sectional study design with web-based self-administered surveys. Individuals with SCD were recruited via an online panel. Psychometric properties, including factorial and construct validity, and internal consistency reliability, of the CSQ-SCD were assessed. RESULTS: A total of 196 adults with SCD completed the survey. Confirmatory factor analysis (CFA), using maximum likelihood estimation and the 13 subscale scores as factor indicators, supported a three-factor model for the CSQ-SCD compared to a two-factor model. Model fit statistics for the three-factor model were: Chi-square [df] = 227.084 [62]; CFI = 0.817; TLI = 0.770; RMSEA [90% CI] = 0.117 [0.101-0.133]; SRMR = 0.096. All standardized factor loadings (except for the subscales isolation, resting, taking fluids, and praying and hoping) were > 0.5 and statistically significant, indicating evidence of convergent validity. Correlations between all subscales (except praying and hoping) were lower than hypothesized; however, model testing revealed that the three latent factors, active coping, affective coping, and passive adherence coping were not perfectly correlated, suggesting discriminant validity. Internal consistency reliabilities for the active coping factor (α = 0.803) and affective coping factor (α = 0.787) were satisfactory, however, reliability was inadequate for the passive adherence coping factor (α = 0.531). Given this overall pattern of results, a follow-up exploratory factor analysis (EFA) was also conducted. The new factor structure extracted by EFA supported a three-factor structure (based on the results of a parallel analysis), wherein the subscale of praying and hoping loaded on the active coping factor. CONCLUSIONS: Overall, the CSQ-SCD was found to have less than adequate psychometric validity in our sample of adults with SCD. These results provide clarification around the conflicting factor structure results reported in the literature and demonstrate a need for the future development of a SCD specific coping instrument.

Superficial Acral Fibromyxoma on the Thumb-Nail Bed.

Superficial acral fibromyxoma, also known as digital fibromyxoma, is a benign soft tissue tumor. The acral regions, including the palms, soles, fingers, toes, and nail units, are the commonly affected locations. The subungual region of the great toe is the most common site reported in current literature. The tumor is slowly progressive and benign in nature. Histology commonly reveals a fibromyxoid neoplasm with immunoreactivity to CD34 and CD99 markers.1,2,3 We present the case of a 39-year-old female with a nine-year history of repetitive digital trauma presenting with superficial acral fibromyxoma of the thumb-nail bed. Our case is unique due to the tumor location and the patient's prior long history of trauma to the tumor site.

Affinity Purification of Membrane ß-Barrel Proteins via Biotin-Tagged Peptidiscs.

ß-barrel membrane proteins play a crucial role in bacterial pathogenesis and antibiotic resistance, making them a prime focus for the development of new antibiotics and therapeutics. However, their inherent hydrophobic nature and limited presence pose challenges for their high-throughput characterization using conventional methods. In this context, we present a simple but efficacious approach using peptidisc, a membrane mimetic, to overcome the low abundance and hydrophobicity of these proteins. Our methodology, illustrated here using Escherichia coli (E. coli) as a model organism, covers the entire process from outer membrane fraction preparation to data analysis. This detailed protocol outlines the purification of a diverse collection of ß-barrel membrane proteins, rendering them water-soluble and readily amenable to mass spectrometry and downstream drug screening strategies.

Proximity to the water surface markedly enhances the force production on underwater flapping wings.

The potential application of flapping wings in micro-aerial vehicles is gaining interest due to their ability to generate high lift even in confined spaces. Most studies in the past have investigated hovering wings as well as those flapping near solid surfaces. However, the presence of surface tension at the water-air interface and the ability of the water surface to move might differentiate its response to the proximity of wings, compared to that of solid surfaces. Motivated by underwater, amphibian robots and several underwater experimental studies on flapping wings, our study investigated the effects of the proximity of flapping wings to the water surface at low Reynolds numbers (Re = 3400). Experiments were performed on a rectangular wing in a water tank with prescribed flapping kinematics and the aerodynamic forces were measured. The effects of surface proximity on the wing in its both upright and inverted orientations were studied. Broadly, the mean lift and drag coefficients in both orientations decreased significantly (by up to 60%) as the distance from the water surface was increased. In the case of the upright orientation, the mean lift coefficient was slightly decreased very close to the water surface with its peak being observed at the normalized clearance of [Formula: see text]. Overall, the study revealed an enhancement in the aerodynamic forces closer to the water surface.

Perceptions of Justice in Clinical Learning Environments: Development and Validation of an Organizational Justice Measure for Medical Trainees.

PURPOSE: This study aimed to develop an instrument to measure medical trainees' perceptions of justice in clinical learning environments. METHOD: Between 2019 and 2023, the authors conducted a multiyear, multi-institutional, multiphase study to develop a 16-item justice measure with 4 dimensions: interpersonal, informational, procedural, and distributive. The authors gathered validity evidence based on test content, internal structure, and relationships with other variables across 3 phases. Phase 1 involved drafting items and gathering evidence that items measured intended dimensions. Phase 2 involved analyzing relevance of items for target groups, examining interitem correlations and factor loadings in a preliminary analysis, and obtaining reliability estimates. Phase 3 involved a confirmatory factor analysis and collecting convergent and discriminant validity evidence. RESULTS: In phase 1, 63 of 91 draft items were retained following a content validation exercise gauging how well items measured targeted dimensions (mean [SD] item ratings within dimensions, 4.16 [0.36] to 4.39 [0.34]) on a 5-point Likert scale (with 1 indicating not at all well and 5 indicating extremely well). In phase 2, 30 items were removed due to low factor loadings (i.e., < 0.40), and 4 items per dimension were selected (factor loadings, 0.42-0.89). In phase 3, a confirmatory factor analysis supported the 4-dimension model (χ2 = 610.14, P < .001; comparative fit index = 0.90, Tucker-Lewis Index = 0.87, root mean squared error of approximation = 0.11, standardized root mean squared residual = 0.06), with convergent and discriminant validity evidence showing hypothesized positive correlations with a justice measure (r = 0.93, P < .001), trait positive affect (r = 0.46, P < .001), and emotional stability (r = 0.33, P < .001) and negative correlations with trait negative affect (r = -0.39, P < .001). CONCLUSIONS: Results indicate the measure's potential utility in understanding justice perceptions and designing targeted interventions.

Thymic en-bloc resection with veins: case demonstrations and review of the literature.

Locally invasive thymic neoplasms are challenging clinical scenarios and typically require a multidisciplinary approach. The involvement of major mediastinal veins such as the superior vena cava (SVC) used to be a contraindication to surgery, but with improved surgical technique and outcomes, this paradigm has shifted. In some situations, complex resections and reconstructions may be indicated and required to improve the long-term outcome of these patients. We report two of our cases along with a current review of literature. We also describe the preoperative workup, operative techniques, postoperative management, complications, and outcomes of patients with invasive thymic neoplasms that involve the mediastinal veins. Our first case describes a patient who was diagnosed with a thymoma extending from the diaphragm to the base of the neck that was also encasing major vascular structures including the SVC and left innominate vein. Our second case describes a patient who was also diagnosed with a large anterior mediastinal mass encasing the great veins and invading the chest wall. We describe the management of these patients and then delve deeper into operative techniques including SVC resection and reconstruction. We describe the types of conduits that can be used and complications to be mindful of when clamping the great veins, such as the SVC. Improvements in conduit materials and neoadjuvant and adjuvant therapies over the years have made it more feasible for patients with invasive thymic neoplasms to undergo surgery.

Characterization of membrane protein interactions by peptidisc-mediated mass photometry.

Membrane proteins perform numerous critical functions in the cell, making many of them primary drug targets. However, their preference for a lipid environment makes them challenging to study using established solution-based methods. Here, we show that peptidiscs, a recently developed membrane mimetic, provide an ideal platform to study membrane proteins and their interactions with mass photometry (MP) in detergent-free conditions. The mass resolution for membrane protein complexes is similar to that achievable with soluble proteins owing to the low carrier heterogeneity. Using the ABC transporter BtuCD, we show that MP can quantify interactions between peptidisc-reconstituted membrane protein receptors and their soluble protein binding partners. Using the BAM complex, we further show that MP reveals interactions between a membrane protein receptor and a bactericidal antibody. Our results highlight the utility of peptidiscs for membrane protein characterization in detergent-free solution and provide a rapid and powerful platform for quantifying membrane protein interactions.

A novel antibiotic class targeting the lipopolysaccharide transporter.

Carbapenem-resistant Acinetobacter baumannii (CRAB) has emerged as a major global pathogen with limited treatment options1. No new antibiotic chemical class with activity against A. baumannii has reached patients in over 50 years1. Here we report the identification and optimization of tethered macrocyclic peptide (MCP) antibiotics with potent antibacterial activity against CRAB. The mechanism of action of this molecule class involves blocking the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane, through inhibition of the LptB2FGC complex. A clinical candidate derived from the MCP class, zosurabalpin (RG6006), effectively treats highly drug-resistant contemporary isolates of CRAB both in vitro and in mouse models of infection, overcoming existing antibiotic resistance mechanisms. This chemical class represents a promising treatment paradigm for patients with invasive infections due to CRAB, for whom current treatment options are inadequate, and additionally identifies LptB2FGC as a tractable target for antimicrobial drug development.

A network analysis of Hurricane Maria-related traumatic stress and substance use among Puerto Rican youth.

Youth exposed to natural disasters are at risk of developing trauma-related symptoms as well as engaging in substance use. Although previous research has established associations between disaster-related stressors and substance use in youth, less has focused on how symptoms of posttraumatic stress disorder (PTSD) may underpin this association. The current study used network analysis to identify specific PTSD symptoms associated with substance use following a natural disaster. Participants were 91,732 youths (Grades 3-12) from across Puerto Rico who completed a needs assessment 5-9 months after Hurricane Maria made landfall in September 2017. We examined associations between PTSD symptoms and substance use, identified clusters of symptoms and bridges between them, and explored age- and binary gender-related differences in associations between specific PTSD symptoms and substance use. Analyses identified two symptom communities: (a) arousal and reactivity, negative alterations in cognition and mood, and substance use, and (b) avoidance and intrusion. Broader findings suggested that substance use was most strongly associated with PTSD-related irritability and angry outbursts among youths. Surrounding nodes explained only 4.1% of the variance in substance use, but this was higher among youths who reported not having a supportive adult, R2 = 8.5; friend, R2 = 7.9; or teacher/counselor, R2 = 7.7, in their life. The bridge symptoms of sleep disruption and physiological reactivity were identified as potentially critical intervention targets for disrupting PTSD symptom networks after a natural disaster. Implications for triaged mental health care following natural disasters and directions for future research are discussed.

Antimicrobial Susceptibility of Francisella tularensis Isolates in the United States, 2009-2018.

Francisella tularensis is the causative agent of tularemia. We tested the susceptibility of 278 F. tularensis isolates from the United States received during 2009-2018 to 8 antimicrobial drugs (ciprofloxacin, levofloxacin, doxycycline, tetracycline, gentamicin, streptomycin, chloramphenicol, and erythromycin). All isolates were susceptible to all tested drugs.

The effects of sleep deprivation, acute hypoxia, and exercise on cognitive performance: A multi-experiment combined stressors study.

INTRODUCTION: Both sleep deprivation and hypoxia have been shown to impair executive function. Conversely, moderate intensity exercise is known to improve executive function. In a multi-experiment study, we tested the hypotheses that moderate intensity exercise would ameliorate any decline in executive function after i) three consecutive nights of partial sleep deprivation (PSD) (Experiment 1) and ii) the isolated and combined effects of a single night of total sleep deprivation (TSD) and acute hypoxia (Experiment 2). METHODS: Using a rigorous randomised controlled crossover design, 12 healthy participants volunteered in each experiment (24 total, 5 females). In both experiments seven executive function tasks (2-choice reaction time, logical relations, manikin, mathematical processing, 1-back, 2-back, 3-back) were completed at rest and during 20 min semi-recumbent, moderate intensity cycling. Tasks were completed in the following conditions: before and after three consecutive nights of PSD and habitual sleep (Experiment 1) and in normoxia and acute hypoxia (FIO2 = 0.12) following one night of habitual sleep and one night of TSD (Experiment 2). RESULTS: Although the effects of three nights of PSD on executive functions were inconsistent, one night of TSD (regardless of hypoxic status) reduced executive functions. Significantly, regardless of sleep or hypoxic status, executive functions are improved during an acute bout of moderate intensity exercise. CONCLUSION: These novel data indicate that moderate intensity exercise improves executive function performance after both PSD and TSD, regardless of hypoxic status. The key determinants and/or mechanism(s) responsible for this improvement still need to be elucidated. Future work should seek to identify these mechanisms and translate these significant findings into occupational and skilled performance settings.

Mandated checkups, knowledge of own health status, and chronic care utilization: The effect of HIV medical evaluation mandates on healthcare quality and expenditure in a US-single payer system.

In an effort to improve military readiness, in 2014 the US Air Force reduced the frequency of mandated HIV medical evaluation visits from every 6 months to every 12 months. We employ this natural experiment using data for 2676 active-duty Military Health System beneficiaries living with HIV with a difference-in-differences empirical strategy using the Army, Navy, and Marines as a control group to estimate the causal effect of reducing the frequency of mandated evaluation visits on the quality and cost of medical care for active-duty military members living with HIV. We find that reducing the frequency of mandated HIV medical evaluation visits reduced the likelihood of regular HIV visits by 23 percentage points but did not affect the likelihood of receiving other preventive care, adhering to HIV therapy, or maintaining viral testing and suppression. The study finds evidence that the recommended level of regular HIV visits may be higher than necessary. The reduction in regular HIV visits was not associated with a similar reduction in the studied quality of care measures, therefore, the effect of alleviating the mandate was overall positive in terms of reducing healthcare utilization without adversely affecting preventive care, HIV therapy, or viral testing and suppression.

Lifestyle interventions to delay senescence.

Senescence is a condition of cell cycle arrest that increases inflammation and contributes to the development of chronic diseases in the aging human body. While several compounds described as senolytics and senomorphics produce health benefits by reducing the burden of senescence, less attention has been devoted to lifestyle interventions that produce similar effects. We describe here the effects of exercise, nutrition, caloric restriction, intermittent fasting, phytochemicals from natural products, prebiotics and probiotics, and adequate sleep on senescence in model organisms and humans. These interventions can be integrated within a healthy lifestyle to reduce senescence and inflammation and delay the consequences of aging.

Limited Effect of Prevention Strategies on Incidence of Clinically Detectable Venous Thromboembolism After Lung Transplantation.

BACKGROUND: Thromboembolic complications are common post-lung transplant, leading to significant morbidity. We instituted multiple interventions because of an observed 36.8% incidence of venous thromboembolism (VTE) (Incidence rate (IR) 5.74/1000 pt days) in our recipients. METHODS: Our initiative commenced January 2015 with enoxaparin initiation within 6-8 hours of intensive care unit arrival and continuation for 4-6 weeks. We evaluated the IR of VTE in lung transplant recipients within 90 days of transplant. In 2017, the protocol was modified to extend the time to initiation of prophylaxis to within 72 hours of ICU arrival. In 2019, we further amended our intraoperative vascular access strategy. RESULTS: Eighteen of 26 lung transplant recipients (LTR) met inclusion criteria in the 2015 cohort. Six of 18 (33.3%) developed VTE, 50% of which were upper extremity (UE), line associated. Fifty two of 75 LTR were eligible for enoxaparin prophylaxis in the 2017 cohort. Fifteen of 52 subjects (28.8%) developed VTE, 77.8% of which were UE and line associated. Despite improved adherence in 2017, there was little change in VTE IR (3.90/1000 pt days compared with 3.85/1000 pt days). Twenty six of 43 LTR met protocol inclusion criteria in the 2019 cohort. Ten subjects (38.5%) developed VTE, 67% of which were UE and line associated (IR 5.18/1000 pt days). CONCLUSION: Our prospective study found that LTR remain at high risk for VTE despite aggressive prophylaxis with 4-6 weeks of enoxaparin and adjustment of vascular access approach. Alternative interventions should be investigated to minimize VTE development in this vulnerable population.

Disaster exposure and mental health among Puerto Rican teachers after Hurricane Maria.

The purpose of the study was to assess the prevalence rates of anxiety, depression, and posttraumatic stress disorder (PTSD) outcomes among teachers (N = 8,167) exposed to Hurricane Maria in Puerto Rico. The findings indicate that the rates of likely significant symptoms of anxiety, depression, and PTSD were 13.1%, 8.7%, and 5.4%, respectively. There were no significant disparities in psychopathological symptoms based on sex, except that female participants were more likely to exhibit anxiety symptoms than their male counterparts, odds ratio (OR) = 1.53. Key disaster-related factors, such as perceived threat, actual threat, and disruption of life were found to significantly influence all psychopathology outcomes, ORs = 1.20-3.57, whereas increased social support significantly buffered the manifestation of clinically significant psychopathology symptoms across all domains, ORs = 0.30-0.46. These outcomes, strongly linked to peritraumatic consequences, were not constrained by geographical or socioeconomic boundaries, highlighting the wide-ranging impact of the hurricane. Nevertheless, social support emerged as a significant counteracting force, reducing the likelihood of detrimental mental health symptoms. Consistent with prior studies, this study emphasizes the crucial role of social support in nurturing posttraumatic resilience and curbing the severity of posttraumatic stress outcomes, thus underscoring the need for incorporating robust social support systems within disaster response strategies.

Discovery of 4,5,6,7-Tetrahydropyrazolo[1.5-a]pyrizine Derivatives as Core Protein Allosteric Modulators (CpAMs) for the Inhibition of Hepatitis B Virus.

Hepatitis B Virus (HBV) core protein allosteric modulators (CpAMs) are an attractive class of potential anti-HBV therapeutic agents. Here we describe the efforts toward the discovery of a series of 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine (THPP) compounds as HBV CpAMs that effectively inhibit a broad range of nucleos(t)ide-resistant HBV variants. The lead compound 45 demonstrated inhibition of HBV DNA viral load in a HBV AAV mouse model by oral administration.

Recent advances in membrane mimetics for membrane protein research.

Membrane proteins are a highly relevant class of biological molecules and comprise ∼60% of current drug targets. Before being analyzed by structural, biochemical, and biophysical methods, membrane proteins must first be extracted from cellular membranes - often using detergents. Detergent-extracted membrane proteins are amenable to analysis by structural, biochemical, and biophysical techniques. In certain cases, however, detergents can disturb native protein conformations and/or biological activity. This has led to the development of membrane mimetics, which stabilize membrane proteins in a native membrane-like environment that is water-soluble and detergent-free. This review provides an overview of recent developments in the membrane mimetic field, with a focus on nanodiscs, Saposin lipid nanoparticles (SapNPs), peptidiscs, and SMA lipid particles (SMALPs) - and highlights their utility for supporting biophysical, biochemical, and structural characterization of membrane proteins and complexes.

A Peptidisc-Based Survey of the Plasma Membrane Proteome of a Mammalian Cell.

Membrane proteins play critical roles at the cell surface and their misfunction is a hallmark of many human diseases. A precise evaluation of the plasma membrane proteome is therefore essential for cell biology and for discovering novel biomarkers and therapeutic targets. However, the low abundance of this proteome relative to soluble proteins makes it difficult to characterize, even with the most advanced proteomics technologies. Here, we apply the peptidisc membrane mimetic to purify the cell membrane proteome. Using the HeLa cell line as a reference, we capture 500 different integral membrane proteins, with half annotated to the plasma membrane. Notably, the peptidisc library is enriched with several ABC, SLC, GPCR, CD, and cell adhesion molecules that generally exist at low to very low copy numbers in the cell. We extend the method to compare two pancreatic cell lines, Panc-1 and hPSC. Here we observe a striking difference in the relative abundance of the cell surface cancer markers L1CAM, ANPEP, ITGB4, and CD70. We also identify two novel SLC transporters, SLC30A1 and SLC12A7, that are highly present in the Panc-1 cell only. The peptidisc library thus emerges as an effective way to survey and compare the membrane proteome of mammalian cells. Furthermore, since the method stabilizes membrane proteins in a water-soluble state, members of the library, here SLC12A7, can be specifically isolated.