Miracle-dz/UniFAR-FTUs huggingface dataset:
Patients’ recovery after severe TBI is associated with their close relatives’ interpersonal functioning: a 12-months prospective cohort study

ABSTRACT Objective The aim of this study was to investigate the association between relatives’ interpersonal functioning and patients’ recovery after severe traumatic brain injury (TBI) across one year in Switzerland. Design: This prospective, multi-center cohort study is comprised of 188 adult patients with severe TBI (Abbreviated Head Injury Score > 3) and their relatives. Patients and relatives were assessed 3, 6, and 12 months post-injury. Main outcome measures: Interpersonal functioning (Patient Competency Rating Scale for Neurorehabilitation, PCRS-NR), Physical and Mental Health related Quality of Life (HRQoL, SF-12), and overall functioning (Glasgow Outcome Comma Scale Extended, GOSE). Results: Multilevel analyses showed that relatives’ interpersonal functioning was positively associated with a) patients’ mental HRQoL (p =.002; slope = 2.95; β =.24) independently of age, b) a moderation time*patients’ physical HRQoL among patients > 50 years of age (p <.045; slope = 2.63; β =.2) and c) patients’ GOSE among younger individuals (p <.001; slope =.60; β =.23). Conclusion: These findings show that health and overall functioning are linked with interpersonal dimensions. Thus, the interplay between relatives and patients with TBI needs to be further investigated.
Ultra-processed foods drive to unhealthy diets: evidence from Chile

Abstract Objectives: To assess the consumption of ultra-processed foods and its association with the overall dietary content of nutrients related to non-communicable diseases (NCD) in the Chilean diet and to estimate the population attributable fraction of ultra-processed food consumption on the unhealthy nutrient content. Design: Cross-sectional analysis of dietary data collected through a national survey (2010). Setting: Chile. Participants: Chilean population aged ≥2 years (n 4920). Results: In Chile, ultra-processed foods represented 28·6 % of the total energy intake. A significant positive association was found between the dietary share of ultra-processed foods and NCD-promoting nutrients such as dietary energy density (standardised regression coefficient (β) = 0·22), content of free sugars (β = 0·45), total fats (β = 0·26), saturated fats (β = 0·19), trans fats (β = 0·09) and Na:K ratio (β = 0·04), while a significant negative association was found with the content of NCD-protective nutrients such as K (β = –0·19) and fibre (β = –0·31). The content of Na (β = 0·02) presented no significant association. Except for Na, the prevalence of inadequate intake of all nutrients (WHO recommendations) increased across quintiles of the dietary share of ultra-processed foods. With the reduction of ultra-processed foods consumption to the level seen among the 20 % lowest consumers (3·8 % (0–9·3 %) of the total energy from ultra-processed foods), the prevalence of nutrient inadequacy would be reduced in almost three-fourths for trans fats; in half for energy density (foods); in around one-third for saturated fats, energy density (beverages), free sugars and total fats; in near 20 % for fibre and Na:K ratio and in 13 % for K. Conclusions: In Chile, decreasing the consumption of ultra-processed foods is a potentially effective way to achieve the WHO nutrient goals for the prevention of diet-related NCD.
Association of six-minute walk distance with subsequent lower extremity events in peripheral artery disease

The prognostic significance of the six-minute walk distance for lower extremity events in people with peripheral artery disease (PAD) is unknown. This longitudinal study assessed whether a poorer six-minute walk distance at baseline was associated with higher rates of subsequent lower extremity atherosclerotic disease events in PAD. A total of 369 patients (mean age 69.4 ± 10.0 years; mean ankle–brachial index (ABI) 0.67 ± 0.17; 31% women; 30% black individuals) from Chicago-area medical centers with PAD were enrolled. Participants underwent baseline six-minute walk testing and returned for annual study visits. Lower extremity events consisted of one or more of the following: ABI decline greater than 15% or medical record adjudicated lower extremity revascularization, critical limb ischemia, or amputation. At a mean follow-up of 33.3 months, lower extremity events occurred in 66/123 (53.7%) people in the first (worst) tertile of six-minute walk performance, 55/124 (44.4%) in the second tertile, and 56/122 (45.9%) in the third (best) tertile. After adjusting for age, sex, race, ABI, comorbidities, and other confounders, participants in the first (worst) tertile of six-minute walk distance at baseline had higher rates of lower extremity events during follow-up, compared to those in the best tertile at baseline (HR = 1.74, 95% CI 1.17–2.60, p = 0.0067). Among people with PAD, a poorer six-minute walk distance was associated with higher rates of subsequent lower extremity PAD-related events after adjusting for confounders. Further study is needed to determine whether interventions that improve six-minute walk distance can reduce lower extremity adverse events in people with PAD.
Novel approaches and current challenges with targeting the endocannabinoid system

ABSTRACT Introduction The pathophysiological relevance of the endocannabinoid system has been widely demonstrated in a variety of diseases including cancer, neurological disorders, and metabolic issues. Therefore, targeting the receptors and the endogenous machinery involved in this system can provide a successful therapeutic outcome. Ligands targeting the canonical cannabinoid receptors, CB1 and CB2, along with inhibitors of the endocannabinoid enzymes have been thoroughly studied in diverse disease models. In fact, phytocannabinoids such as cannabidiol or Δ9-tetrahydrocannabinol are currently on the market for the management of neuropathic pain due to spasticity in multiple sclerosis or seizures in children epilepsy amongst others. Areas covered Challenges in the pharmacology of cannabinoids arise from its pharmacokinetics, off-target effects, and psychoactive effects. In this context, the current review outlines the novel molecular approaches emerging in the field discussing their clinical potential. Expert opinion Even if orthosteric CB1 and CB2 ligands are on the forefront in cannabinoid clinical research, emerging strategies such as allosteric or biased modulation of these receptors along with controlled off-targets effects may increase the therapeutic potential of cannabinoids.
The role of dietary antioxidant index and index of nutritional quality in MS onset: finding from an Iranian population-based incident case–control study

ABSTRACT Introduction: The role of nutritional factors in MS etiology is a matter of debate. Employing dietary antioxidant index (DAI) as well as index of nutritional quality (INQ) we aimed to investigate the possible link between diet and MS risk. Methods This was a large population-based case–control study recruiting 547 incident cases and 1057 population controls between August 2013 and February 2015. DAI and INQ were calculated based on the adolescence dietary intake of the participants. Logistic regression was employed for estimating adjusted odds ratios (OR) and their 95% confidence interval in 2018. Results Participants with less than median DAI values had two-fold increased risk of MS onset (adjusted OR 2.05, 95% CI: 1.64–2.58, P < 0.001). A significant dose–response pattern for DAI (adjusted OR 1.35, 95% CI: 1.18–1.55, P for trend <0.001) was also detected. In the case of INQ, the strongest decreased risk were detected for vitamin D (OR = 0.09) and Zinc (OR = 0.34), followed by vitamin A (OR = 0.49), Calcium (OR = 0.49) and vitamin B6 (OR = 0.51) (All P-values < 0.05). Conclusion Considering the inherent limitation of case–control designs, an appropriate intake of nutrient antioxidants may have a role in decreasing the likelihood of MS risk. Moreover, those with healthier diet assessed by index of nutritional quality were at decreased risk for MS.
Incentive sensitization for exercise reinforcement to increase exercise behaviors

Individuals can be sensitized to the reinforcing effects of exercise, although it is unknown if this process increases habitual exercise behavior. Sedentary men and women (body mass index: 25–35 kg/m2, N = 52) participated in a 12-week aerobic exercise intervention. Exercise reinforcement was determined by how much work was performed for exercise relative to a sedentary alternative in a progressive ratio schedule task. Habitual physical activity was assessed via accelerometry. Post-intervention increases in exercise reinforcement predicted increases in physical activity bouts among those who expended over 2000 kcal per week in exercise and who compensated for less than 50 percent of their exercise energy expenditure.
Plasma myeloperoxidase levels in acute brain ischaemia and high grade carotid stenosis

Myeloperoxidase (MPO) is an important oxidative enzyme participating in different stages of cardiovascular disease and predicts prognosis. Little is known about its role in acute cerebrovascular events and carotid plaque vulnerability. In this study, the aim was to assess plasma MPO levels in acute stroke patients and their correlation to stroke severity and stroke outcome.
Trichoplein binds PCM1 and controls endothelial cell function by regulating autophagy

Autophagy is an essential cellular quality control process that has emerged as a critical one for vascular homeostasis. Here, we show that trichoplein (TCHP) links autophagy with endothelial cell (EC) function. TCHP localizes to centriolar satellites, where it binds and stabilizes PCM1. Loss of TCHP leads to delocalization and proteasome‐dependent degradation of PCM1, further resulting in degradation of PCM1's binding partner GABARAP. Autophagic flux under basal conditions is impaired in THCP‐depleted ECs, and SQSTM1/p62 (p62) accumulates. We further show that TCHP promotes autophagosome maturation and efficient clearance of p62 within lysosomes, without affecting their degradative capacity. Reduced TCHP and high p62 levels are detected in primary ECs from patients with coronary artery disease. This phenotype correlates with impaired EC function and can be ameliorated by NF‐κB inhibition. Moreover, Tchp knock‐out mice accumulate of p62 in the heart and cardiac vessels correlating with reduced cardiac vascularization. Taken together, our data reveal that TCHP regulates endothelial cell function via an autophagy‐mediated mechanism.
Pathways From ADHD Symptoms to Suicidal Ideation During College Years: A Longitudinal Study on the i-Share Cohort

Objective: To estimate the association between ADHD symptoms and suicidal ideation in college students, and to test mediation by depressive symptoms or self-esteem. Method: Based on the i-Share cohort (prospective cohort of 2,331 college students in France). Self-reported measures included ADHD symptoms at baseline, self-esteem and depressive symptoms at 3 months, and suicidal ideation at 1-year follow-up. We conducted path analysis to estimate total, direct, and indirect effect. Results: Participants with high ADHD symptoms were more likely to report suicidal ideation 1 year later (p < .0001). Indirect effects through depressive symptoms (p < .0001) and self-esteem (p < .0001) explained 44% and 25% of this association, respectively. An indirect pathway via a combination of self-esteem, then depressive symptoms, was also identified (p < .0001), explaining 19% of the total effect. The direct effect was not significant (p = .524). Conclusion: ADHD symptoms seem to have no direct but indirect effect through both self-esteem and depressive symptoms on suicidal ideation.
Increased Arterial Stiffness Amplifies the Association Between Home Blood Pressure Variability and Cardiac Overload

Supplemental Digital Content is available in the text. Increased blood pressure (BP) variability, an index of hemodynamic stress, leads to cardiac overload and worse cardiovascular prognosis. The association between day-by-day home BP variability and NT-proBNP (N-terminal pro-B-type natriuretic peptide) as an index of cardiac overload may be amplified by increased arterial stiffness as assessed by brachial-ankle pulse wave velocity (baPWV). J-HOP (Japan Morning Surge-Home Blood Pressure) Study participants who were selected from a practitioner-based population with at least one cardiovascular risk factor underwent home BP monitoring, and their BP levels and SD, coefficient of variation, and average real variability as indexes of systolic BP variability were assessed. We analyzed 2115 individuals without prevalent heart failure and divided them into lower (<1800 cm/s, n=1464) and higher (≥1800 cm/s, n=651) baPWV groups. The higher baPWV group had significantly higher SDSBP, CVSBP, ARVSBP values, and NT-proBNP levels than the lower baPWV group (all P<0.001). In the higher baPWV group, a multiple linear regression analysis revealed that the SDSBP was associated with the NT-proBNP level after adjustment for traditional cardiovascular risk factors including the average home systolic BP (coefficient per 1 SD increase, 0.049 [95% CI, 0.018–0.081]; P=0.002). Similar trends were found for CVSBP (P=0.003) and ARVSBP (P=0.004). However, these associations were not found in the lower baPWV group. There was an interaction between all indexes of systolic BP variability and the NT-proBNP level according to lower or higher baPWV group (all P<0.05). Arterial stiffness amplified the association between home BP variability and cardiac overload.
Experiences and Insights from the Early US COVID-19 Epicenter: A Rapid Assessment Procedure Informed Clinical Ethnography Case Series

Objective The Coronavirus disease (COVID-19) outbreak has evolved into a pandemic crisis, with King County in Washington State emerging as the early US epicenter. A literature review revealed few reports providing front-line clinical and research teams guidance related to multilevel, rapidly evolving COVID-19 directives. Method The Rapid Assessment Procedure Informed Clinical Ethnography (RAPICE) method was used to develop a clinical case series and conduct participant observation during an ongoing comparative effectiveness trial of peer-integrated, patient-centered interventions after traumatic injury. Participants were patients enrolled in the intervention arm of the ongoing trial, as well as front-line clinicians, patient peer interventionists, and clinical research team members implementing the trial. All participants were exposed to the Washington State COVID-19 outbreak. Results Primary and secondary COVID-19 prevention strategies were feasibly integrated into ongoing care coordination and behavioral interventions for at-risk patients. Beyond the compilation of case studies, as an iterative method, RAPICE data collection naturalistically evolved to include observations of intervention team activity occurring within the larger pandemic epicenter context. A daily clinical research team huddle that flexibly accommodated virtual participation was also feasibly implemented. Conclusions Primary and secondary COVID-19 prevention strategies can be feasibly integrated into ongoing clinical interventions during the pandemic. Routine, proactive clinical and research team communication that transparently addresses ethical tensions and health-sustaining activities may promote well-being for providers grappling with rapidly evolving pandemic directives. Proactive assessments of individual provider vulnerabilities for severe COVID-19 related respiratory illness may also be a crucial element of the health care system pandemic responses.
We're in this together: Promoting health equity, diversity, and inclusion in tobacco research for sexual and gender minority populations.

Sexual and gender minority (SGM) individuals have higher tobacco use prevalence and consequently higher burden of tobacco-caused diseases including cancer and cardiovascular disease compared with their heterosexual or cisgender counterparts. Yet, there is a critical gap in research focused on measuring SGM tobacco-related health disparities and addressing unmet needs of SGM individuals in the context of nicotine and tobacco research. In this commentary, we summarize recommendations discussed during a preconference workshop focused on challenges and opportunities in conducting SGM tobacco control research at the 2019 Society for Research on Nicotine and Tobacco Annual Meeting. Specifically, we recommend defining and measuring SGM identity in all nicotine and tobacco research routinely, using novel methods to engage a demographically diverse sample of the SGM population, and eliciting SGM community voices in tobacco control research. Addressing these critical research gaps will enable the scientific community to generate the data to fully understand and support SGM individuals in tobacco use prevention and cessation.
Perspectives on Fentanyl Test Strip Use among People Who Inject Drugs in Rural Appalachia

Abstract Background: Fentanyl-associated overdose fatalities have increased dramatically throughout the United States. Fentanyl test strips (FTS) may be used by people who inject drugs (PWID) to lower overdose risks; however, virtually no research has been conducted to understand the perspectives of rural PWID in Appalachia on FTS utilization. Objectives: We aim to explore FTS awareness and potential use among PWID in two rural counties in West Virginia (WV). Methods: Semi-structured interviews with PWID (n = 48) in two rural counties in WV were conducted to explore FTS awareness, potential use, and possible behavioral changes following FTS utilization. Participants were recruited in areas where PWID congregate in each county. With participants’ permission, interviews were audio recorded and transcribed verbatim. Transcripts were analyzed using an iterative, constant comparative approach. Results: Very few participants had heard of FTS prior to the interview. Upon learning about FTS, PWID who reported frequently injecting heroin expressed high willingness to use FTS. Participants explained that learning their drugs contained fentanyl may make them more likely to engage in overdose risk reduction behaviors, such as: using less, doing tester shots, and not using the drugs entirely. Conclusion: Among our sample of rural PWID in Appalachia, most were unaware of FTS but expressed high willingness to utilize the technology. Participants described how receiving a positive FTS result may lead them to engage in overdose risk reduction behaviors. Augmenting existing overdose prevention initiatives in rural Appalachia such that rural PWID have access to FTS may result in reductions in overdose fatalities.
d-Alanine–d-alanine ligase as a model for the activation of ATP-grasp enzymes by monovalent cations

The ATP-grasp superfamily of enzymes shares an atypical nucleotide-binding site known as the ATP-grasp fold. These enzymes are involved in many biological pathways in all domains of life. One ATP-grasp enzyme, d-alanine–d-alanine ligase (Ddl), catalyzes ATP-dependent formation of the d-alanyl–d-alanine dipeptide essential for bacterial cell wall biosynthesis and is therefore an important antibiotic drug target. Ddl is activated by the monovalent cation (MVC) K+, but despite its clinical relevance and decades of research, how this activation occurs has not been elucidated. We demonstrate here that activating MVCs bind adjacent to the active site of Ddl from Thermus thermophilus and used a combined biochemical and structural approach to characterize MVC activation. We found that TtDdl is a type II MVC-activated enzyme, retaining activity in the absence of MVCs. However, the efficiency of TtDdl increased ∼20-fold in the presence of activating MVCs, and it was maximally activated by K+ and Rb+ ions. A strict dependence on ionic radius of the MVC was observed, with Li+ and Na+ providing little to no TtDdl activation. To understand the mechanism of MVC activation, we solved crystal structures of TtDdl representing distinct catalytic stages in complex with K+, Rb+, or Cs+. Comparison of these structures with apo TtDdl revealed no evident conformational change on MVC binding. Of note, the identified MVC binding site is structurally conserved within the ATP-grasp superfamily. We propose that MVCs activate Ddl by altering the charge distribution of its active site. These findings provide insight into the catalytic mechanism of ATP-grasp enzymes.
Detection of circulating anti-skin antibodies by indirect immunofluorescence and by ELISA: a comparative systematic review and meta-analysis

Abstract Background Both enzyme-linked immunosorbent assays (ELISAs) and indirect immunofluorescence (IIF) are available for the diagnosis of autoimmune bullous diseases (AIBD). Many studies have reported on the performance of ELISAs and concluded that ELISAs could replace IIF. This study compares the diagnostic accuracy of ELISA and IIF for the detection of autoantibodies to desmoglein 1 (DSG1), desmoglein 3 (DSG3), bullous pemphigoid antigen 2 (BP180) and bullous pemphigoid antigen 1 (BP230) to support the diagnosis of pemphigus vulgaris (PV), pemphigus foliaceus (PF) and bullous pemphigoid (BP). Methods A literature search was performed in the PubMed database. The meta-analysis was performed using summary values and a bivariate random effect model. Results The five included studies on PV did not demonstrate significant differences between IIF and DSG3-ELISA (sensitivity 82.3% vs. 81.6%, p = 0.9284; specificity 95.6% vs. 93.9%, p = 0.5318; diagnostic odds ratio [DOR] 101.60 vs. 67.760, p = 0.6206). The three included studies on PF did not demonstrate significant differences between IIF and DSG1-ELISA (sensitivity 80.6% vs. 83.1%, p = 0.8501; specificity 97.5% vs. 93.9%, p = 0.3614; DOR 160.72 vs. 75.615, p = 0.5381). The eight included studies on BP showed that BP230-ELISA differed significantly from both IIF on monkey esophagus (MO) and BP180-ELISA with regard to DOR (11.384 vs. 68.349, p = 0.0008; 11.384 vs. 41.699, p = 0.0125, respectively) Conclusions Our meta-analysis shows that ELISA performs as well as IIF for diagnosing PV, PF and BP.
Cloning and characterization of the rat Slo3 (KCa5.1) channel: From biophysics to pharmacology

The Slo3 potassium (KCa5.1) channel, which is specifically expressed in the testis and sperm, is essential for mammalian male fertilization. The sequence divergence of the bovine, mouse and human Slo3 α‐subunit revealed a rapid evolution rate across different species. The rat Slo3 (rSlo3) channel has not been cloned and characterized previously.
Thai trauma nurses' knowledge of neuro-protective nursing care of traumatic brain injury patients: A survey study.

Thai trauma nurses play a vital role in neuro-protective nursing care of patients with moderate or severe traumatic brain injury. Nurses' knowledge of the evidence underpinning initial neuro-protective nursing care vital to safe and high quality patient care. However, the current state of knowledge of Thai trauma nurses is poorly understood. In this study, we investigated Thai nurses' knowledge of neuro-protective nursing care of patients with moderate or severe traumatic brain injury. Data were collected by a survey, comprising a section on participant characteristics and series of multiple-choice questions. All registered nurses (n = 22) and nursing assistants (n = 13) from trauma ward of a regional Thai hospital were invited to participate: the response rate was 100%. Participants had limited knowledge of carbon dioxide monitoring; causes and implications of hypercapnia; mean arterial pressure and cerebral perfusion pressure targets; management of sedatives and analgesics; and management of hyperthermia. Improving their knowledge focusing on knowledge deficits through educational training and implementation of evidence-based practice is essential to improve the safety and quality of care for Thai patients with moderate or severe traumatic brain injury. This article is protected by copyright. All rights reserved.