95038 research outputs found
Sort by
CD39 polymorphism enables lung thrombosis in sickle cell disease
Full text linkSickle cell disease (SCD) is the most common monogenic-hemolytic disorder affecting people of African ancestry. Adenosine diphosphate (ADP) released following intravascular hemolysis activates platelets by stimulating purinergic receptors to promote thrombosis. Despite brisk intravascular hemolysis, which releases high levels of ADP into plasma, and evidence of platelet and hemostatic activation, it remains elusive why only a subset of SCD patients develop lung thrombosis. Using real-time in vivo lung microscopy, we report a surprising finding that humanized SCD mice are protected from ADP-induced lung thrombosis, which is secondary to the degradation of ADP by CD39 present in circulating extracellular vesicles released by the lung endothelium. ADP-induced platelet aggregation is also impaired in the blood of SCD patients with elevated levels of CD39+ extracellular vesicles. CD39 polymorphism rs3176891A→G is associated with the incidence of lung thrombosis in SCD patients but not healthy humans of African ancestry. Remarkably, CD39+ extracellular vesicles are fewer and ADP-induced platelet aggregation is higher in the blood of SCD patients with rs3176891G allele. This study identifies a novel extracellular vesicle-dependent mechanism preventing lung thrombosis in SCD and reveals how CD39 polymorphisms may impair this protection to increase the risk for lung thrombosis in a subset of SCD patients
The Conceptualization and Operationalization of Shame: An Exhaustive Review of Variables, Methodologies, and Theoretical Frameworks
Full text linkThe scientific study of emotion has long grappled with the challenge of quantifying subjective experience, yet few constructs present as formidable a challenge to operationalization as shame. In the landscape of affective science, shame occupies a unique and paradoxical position: it is a ubiquitous, universal human experience central to social regulation and self-identity, yet its very phenomenological nature is one of concealment, withdrawal, and invisibility. Unlike "basic" emotions such as anger or fear, which often manifest in explosive, outwardly directed behavioral vectors, shame is an implosive force. It is the emotion of the self turning against the self, characterized by a desire to disappear, to hide, and to cover one’s face from the gaze of the "Other." Consequently, the researcher tasked with conceptualizing shame as a variable faces an immediate ontological hurdle: How does one recognize and measure a phenomenon whose primary functional imperative is to remain unrecognized
Genome-wide Gene by Sleepiness Interaction Analysis for Sleep Apnea
Full text linkSTUDY OBJECTIVES: Excessive daytime sleepiness (EDS), influenced by environmental and social-behavioral factors, is reported by a subset of patients with sleep apnea - a group that may be at elevated cardiovascular risk. However, it is unclear whether sleep apnea with and without EDS have distinct genetic underpinnings. In this study, we perform gene-by-EDS interaction analyses for apnea hypopnea index (AHI), a diagnostic marker of sleep apnea severity, to understand EDS's influence on its underlying genetic risk. METHODS: Discovery interaction analyses for common variants and gene-based rare variants were conducted respectively using multi-ethnic Trans-Omics for Precision Medicine (TOPMed) (N=11619) data, followed by replication and subsequent meta-analysis in additional TOPMed-imputed data (N=8904). The 1 degree-of-freedom (1df) GxE test and the 2df joint G, GxE tests were utilized. Sex-stratified analyses were additionally performed. RESULTS: Discovery analysis revealed two common intronic variants- rs13118183 (CCDC3) and rs281851 (MARCHF1) - and three rare variant gene sets mapped to SCUBE2, TMEM26, and CPS4FL - to exhibit interaction with EDS. Meta-analysis revealed EDS interaction with 11 rare variant gene sets mapped to UBLCP1, MED31, RAP1GAP, CPNE5, MYMX, YY1, ZNF773, YBEY, IQCB1, PI4K2B, and CORO1A. CONCLUSION: Genetic loci reveal connections to cardiovascular risk, insulin resistance, thiamine deficiency, and resveratrol mechanism. Discovered genetic signals may offer insight into pertinent biological pathways for sleep apnea patients with an excessively sleepy subtype
Effects of external hand force modeling on validity of inverse analysis of lifting
Full text linkManual lifting tasks pose the risk of musculoskeletal injury, including damage to lumbar intervertebral discs. To assess the risk, spinal joint reaction forces are often estimated using musculoskeletal simulations. However, such analyses require information of external hand force and moment (EHF&M), which has mostly been estimated using simplified models without sufficient validation. This study evaluates the validity of two common EHF&M models by comparing their analysis outcomes to those resulting from directly measured EHF&M. Simplified models yielded negligible errors during the middle phase of symmetric lifting and lowering, but caused substantial errors at the beginning and end of each task, leading to inaccurate estimation of peak spinal joint reaction forces. These findings highlight the limitations of simplified models in evaluating mechanical factors of injury risk. The measurement platform and analysis method developed in this study can also contribute to validating EHF&M modeling for other tasks and improving assessment accuracy
Real-Time Identification and Quantification of Per- and Polyfluoroalkyl Substances Using High-Resolution Time-of-Flight Chemical Ionization Mass Spectrometry with Positive Reagent Ions
Full text linkPer- and polyfluoroalkyl substances (PFAS) are emerging pollutants of concern, primarily due to their terminal degradation products, which exhibit environmental persistence and mobility. Several groups of PFAS, including hydrofluoroolefins (HFOs), perfluoro olefins (PFOs), perfluoro vinyl ethers (PVEs), and hydrofluoroalkanes (HF-alkanes), are volatile and reside predominantly in the gas phase. PFAS such as HFOs, PFOs, and PVEs are considered reactive and may generate short-chain degradation products that persist in the environment. Despite the importance of these gaseous PFAS, there is a lack of analytical techniques capable of providing high-resolution temporal measurements of potential precursors to terminal degradation products. This study presents the first real-time method for detecting and quantifying atmospheric HFOs, PFOs, PVEs, and HF-alkanes using a high-resolution chemical ionization mass spectrometer (HR-CIMS). Using NO+ mixed with O2+ (NO+/O2+), and O2+ as reagent ions, the CIMS was able to identify and quantify PFAS via fluoride abstraction (M - F)+, hydride abstraction (M - H)+, or charge transfer (M+) mechanisms. The method achieves 10-s limits of detection (LOD) ranging from 2 to 40 ppt, enabling online monitoring in ambient air, especially near emission sources or in indoor environments. The use of NO+/O2+ and O2+ reagent ions with HR-CIMS provides a novel and sensitive approach for real-time detection of PFAS via positive reagent ion modes, especially for emerging gas-phase PFAS that currently lack suitable online measurement techniques to better constrain their atmospheric emissions and concentrations
Prenatal Inflammation and Trauma Symptoms in Latina Mothers: The Role of Discrimination and Growing up in an Ethnic Minority Context
Full text linkBackground The race-based traumatic stress model proposes that discrimination elicits trauma-related symptoms. Cumulative discriminatory experiences and subsequent trauma symptoms may lead to prenatal inflammation, with far reaching consequences for the health of a mother and her child. Methods Latina mothers, primarily of Mexican and Central American heritage (n=150), completed the Everyday Discrimination Scale and the Traumatic Avoidance subscale of the Inventory of Depression and Anxiety Symptoms-II during pregnancy (24–32 weeks). Plasma levels of cytokines were measured with multiplex assays, which were aggregated into a pro-inflammatory cytokine profile (IL-1β, TNF-α, IFN-γ, and IL-8) after a Confirmatory Factor Analysis supported this approach. Results Latina mothers who grew up in the US reported more discrimination, more traumatic avoidance symptoms, and had a more elevated cytokine profile than those who immigrated after childhood. Based on a two-mediator sequential model, discrimination and traumatic avoidance symptoms sequentially provided mechanistic support for the higher levels of cytokines observed in mothers who grew up in the US. Additionally, mothers who experienced trauma symptoms in response to discrimination had an elevated cytokine profile, whereas those who did not had a suppressed cytokine profile. Conclusion This is among the first studies to examine the association between trauma symptoms, discrimination, and inflammation during pregnancy. In so doing, it elucidates critical pathways by which discrimination may be differentially biologically embedded across immigrant generations. Emotional responses to and chronicity of discrimination may be critical factors for understanding how experiences of discrimination may influence the maternal inflammatory milieu
Trends in parcel delivery driver injury: Evidence from NEISS-Work
Full text linkIntroduction: The rise of e-commerce has rapidly increased the proportion of goods delivered directly to customers’ homes. These increases have placed notable demands on delivery personnel, with potential health and safety consequences. In this paper, we examined trends in parcel delivery driver injury through analyses of injuries treated in emergency departments (ED) in the United States from 2015 through 2022. Methodology: We explored trends among Couriers and Messengers as well as Postal Service personnel as designated by Bureau of Census (BOC) industry codes. We estimated counts and rates of injuries per 10,000 full time worker equivalents and examined demographics (e.g., age, sex) and other characteristics (e.g., source of injury, injury diagnosis) associated with these injuries. Results: We found that: (1) ED-treated injury rates between 2015 and 2022, among both the Postal Service and Couriers and Messengers, have demonstrated an upward trajectory, contrasting with overall U.S. industry injury rates, which have trended downward; and (2) while ED-treated injury rates for these industries have taken different paths over time, both industries’ ED-treated injury rates have converged toward a position much higher than average. Moreover, we found that female personnel and young personnel disproportionately experienced ED injuries. Conclusions: In addition to calling attention to worrying injury trends among delivery drivers, we conclude that the current data landscape prevents the development of a nuanced picture of injury trends and hazards. These limits inhibit exploration of many specific hazards, and therefore preventive measures that would be designed based on such specific exploration. Practical Applications: Our results serve both as a foundation toward improved safety practices in an industry that continues to experience rapid changes and as a step toward motivating updated data collection and dissemination practices that could help understanding of the modern workplace injury landscape
Care Models to Improve Pain and Reduce Opioids Among Patients Prescribed Long-Term Opioid Therapy
Full text linkPatients prescribed long-term opioid therapy for chronic pain often experience unrelieved pain, poor quality of life, and serious adverse events. To compare the effects of integrated pain team (IPT) vs pharmacist collaborative management (PCM) on pain and opioid dosage. This study was a pragmatic multisite 12-month randomized comparative effectiveness trial with masked outcome assessment. Patients were recruited from October 2017 to March 2021; follow-up was completed June 2022. The study sites were Veterans Affairs primary care clinics. Eligible patients had moderate to severe chronic pain despite long-term opioid therapy (≥20 mg/d for at least 3 months). IPT involved interdisciplinary pain care planning, visits throughout 12 months with medical and mental health clinicians, and emphasis on nondrug therapies and motivational interviewing. PCM was a collaborative care intervention involving visits throughout 12 months with a clinical pharmacist care manager who conducted structured monitoring and medication optimization. Both interventions provided individualized pain care and opioid tapering recommendations to patients. The primary outcome was pain response (≥30% decrease in Brief Pain Inventory total score) at 12 months. The main secondary outcome was 50% or greater reduction in opioid daily dosage at 12 months. A total of 820 patients were randomized to IPT (n = 411) or PCM (n = 409). Participants’ mean (SD) age was 62.2 (10.6) years, and 709 (86.5%) were male. A pain response was achieved in 58/350 patients in the IPT group (16.4%) vs 54/362 patients in the PCM group (14.9%) (odds ratio, 1.11 [95% CI, 0.74-1.67]; P = .61). A 50% opioid dose reduction was achieved in 102/403 patients in the IPT group (25.3%) vs 98/399 patients in the PCM group (24.6%) (odds ratio, 1.03 [95% CI, 0.75-1.42]; P = .85). Over 12 months, the mean (SD) Brief Pain Inventory total score improved from 6.7 (1.5) points to 6.1 (1.8) points (P < .001) in IPT and from 6.6 (1.6) points to 6.0 (1.9) points (P < .001) in PCM (between-group P = .82). Over 12 months, mean (SD) opioid daily dosage decreased from 80.8 (74.2) mg/d to 54.2 (65.0) mg/d in IPT (P < .001) and from 74.5 (56.9) mg/d to 52.8 (51.9) mg/d (P < .001) in PCM (between-group P = .22). Outcomes in this randomized clinical trial did not differ between groups; both had small improvements in pain and substantial reductions in opioid dosage. ClinicalTrials.gov Identifier: NCT0302679
Concerns about the paper, “benefits of targeted vibration for bone strength and bone density in postmenopausal women with osteopenia: a randomized, sham-controlled trial.”
Full text linkWe write to raise serious concerns regarding the clinical significance and conclusions of a paper recently published in JBMR-Plus, “Benefits of Targeted Vibration for Bone Strength and Bone Density in Postmenopausal Women with Osteopenia: A Randomized, Sham-Controlled Trial”
Author Correction: Digital automation of transdermal drug delivery with high spatiotemporal resolution
Full text linkAuthor Correction to "Digital automation of transdermal drug delivery with high spatiotemporal resolution