Deletion of Sigmar1 leads to increased arterial stiffness and altered mitochondrial respiration resulting in vascular dysfunction.

Sigmar1 is a ubiquitously expressed, multifunctional protein known for its cardioprotective roles in cardiovascular diseases. While accumulating evidence indicate a critical role of Sigmar1 in cardiac biology, its physiological function in the vasculature remains unknown. In this study, we characterized the expression of Sigmar1 in the vascular wall and assessed its physiological function in the vascular system using global Sigmar1 knockout (Sigmar1-/-) mice. We determined the expression of Sigmar1 in the vascular tissue using immunostaining and biochemical experiments in both human and mouse blood vessels. Deletion of Sigmar1 globally in mice (Sigmar1-/-) led to blood vessel wall reorganizations characterized by nuclei disarray of vascular smooth muscle cells, altered organizations of elastic lamina, and higher collagen fibers deposition in and around the arteries compared to wildtype littermate controls (Wt). Vascular function was assessed in mice using non-invasive time-transit method of aortic stiffness measurement and flow-mediated dilation (FMD) of the left femoral artery. Sigmar1-/- mice showed a notable increase in arterial stiffness in the abdominal aorta and failed to increase the vessel diameter in response to reactive-hyperemia compared to Wt. This was consistent with reduced plasma and tissue nitric-oxide bioavailability (NOx) and decreased phosphorylation of endothelial nitric oxide synthase (eNOS) in the aorta of Sigmar1-/- mice. Ultrastructural analysis by transmission electron microscopy (TEM) of aorta sections showed accumulation of elongated shaped mitochondria in both vascular smooth muscle and endothelial cells of Sigmar1-/- mice. In accordance, decreased mitochondrial respirometry parameters were found in ex-vivo aortic rings from Sigmar1 deficient mice compared to Wt controls. These data indicate a potential role of Sigmar1 in maintaining vascular homeostasis.

Interactions between integrin α9ß1 and VCAM-1 promote neutrophil hyperactivation and mediate poststroke DVT.

ABSTRACT: Venous thromboembolic events are significant contributors to morbidity and mortality in patients with stroke. Neutrophils are among the first cells in the blood to respond to stroke and are known to promote deep vein thrombosis (DVT). Integrin α9 is a transmembrane glycoprotein highly expressed on neutrophils and stabilizes neutrophil adhesion to activated endothelium via vascular cell adhesion molecule 1 (VCAM-1). Nevertheless, the causative role of neutrophil integrin α9 in poststroke DVT remains unknown. Here, we found higher neutrophil integrin α9 and plasma VCAM-1 levels in humans and mice with stroke. Using mice with embolic stroke, we observed enhanced DVT severity in a novel model of poststroke DVT. Neutrophil-specific integrin α9-deficient mice (α9fl/flMrp8Cre+/-) exhibited a significant reduction in poststroke DVT severity along with decreased neutrophils and citrullinated histone H3 in thrombi. Unbiased transcriptomics indicated that α9/VCAM-1 interactions induced pathways related to neutrophil inflammation, exocytosis, NF-κB signaling, and chemotaxis. Mechanistic studies revealed that integrin α9/VCAM-1 interactions mediate neutrophil adhesion at the venous shear rate, promote neutrophil hyperactivation, increase phosphorylation of extracellular signal-regulated kinase, and induce endothelial cell apoptosis. Using pharmacogenomic profiling, virtual screening, and in vitro assays, we identified macitentan as a potent inhibitor of integrin α9/VCAM-1 interactions and neutrophil adhesion to activated endothelial cells. Macitentan reduced DVT severity in control mice with and without stroke, but not in α9fl/flMrp8Cre+/- mice, suggesting that macitentan improves DVT outcomes by inhibiting neutrophil integrin α9. Collectively, we uncovered a previously unrecognized and critical pathway involving the α9/VCAM-1 axis in neutrophil hyperactivation and DVT.

An enhanced Swin Transformer for soccer player reidentification.

The re-identification (ReID) of objects in images is a widely studied topic in computer vision, with significant relevance to various applications. The ReID of players in broadcast videos of team sports is the focus of this study. We specifically focus on identifying the same player in images taken at any given moment during a game from various camera angles. This work varies from other person ReID apps since the same team wears very similar clothes, there are few samples for each identification, and image resolutions are low. One of the hardest parts of object ReID is robust feature representation extraction. Despite the great success of current convolutional neural network-based (CNN) methods, most studies only consider learning representations from images, neglecting long-range dependency. Transformer-based model studies are increasing and yielding encouraging results. Transformers still have trouble extracting features from small objects and visual cues. To address these issues, we enhanced the Swin Transformer with the levering of CNNs. We created a regional feature extraction Swin Transformer (RFES) backbone to increase local feature extraction and small-scale object feature extraction. We also use three loss functions to handle imbalanced data and highlight challenging situations. Re-ranking with k-reciprocal encoding was used in this study's retrieval phase, and its assessment findings were provided. Finally, we conducted experiments on the Market-1501 and SoccerNet-v3 ReID datasets. Experimental results show that the proposed re-ID method reaches rank-1 accuracy of 96.2% with mAP: 89.1 and rank-1 accuracy of 84.1% with mAP: 86.7 on the Market-1501 and SoccerNet-v3 datasets, respectively, outperforming the state-of-the-art approaches.

Methamphetamine-associated pulmonary arterial hypertension: data from the national biological sample and data repository for pulmonary arterial hypertension (PAH Biobank).

OBJECTIVE: This study compares the clinical and haemodynamic severity of methamphetamine-associated pulmonary arterial hypertension (MA-PAH) with idiopathic pulmonary arterial hypertension (IPAH) and connective tissue-associated pulmonary arterial hypertension (CTD-PAH). It also examines sex differences in clinical and physiological parameters among those with MA-PAH. DESIGN: This is a cross-sectional study using clinically derived data from the National Biological Sample and Data Repository for Pulmonary Arterial Hypertension (PAH biobank), a US-based registry, to compare clinical and physiological characteristics between males and females with MA-PAH. POPULATION: The analysis included 1830 patients enrolled in the PAH biobank, with a diagnosis of MA-PAH (n=42), IPAH (n=1073), or CTD-PAH (n=715). MAIN OUTCOME MEASURES: The study assessed and compared the clinical and haemodynamic parameters of patients with MA-PAH, IPAH and CTD-PAH. RESULTS: Among the patients analysed, 42 had MA-PAH, with 69.1% being female. There were no statistically significant differences in functional class among patients with MA-PAH, IPAH and CTD-PAH. The per cent predicted 6-min walk distance (6MWD) was comparable between the three groups. Patients with MA-PAH had similar mean pulmonary artery pressure and pulmonary vascular resistance to patients with IPAH but higher compared with patients with CTD-PAH. Male patients with MA-PAH exhibited a worse functional class and lower per cent predicted 6MWD, but no significant differences in haemodynamic findings were observed between the sexes. CONCLUSION: There were no differences in haemodynamic between MA-PAH and IPAH but we found that MA-PAH differed from CTD-PAH. The study did not find evidence of sex differences in MA-PAH. Further research is necessary to identify risk factors and underlying mechanisms of MA-PAH, particularly considering the increasing prevalence of methamphetamine use. Such investigations will contribute to the development of effective prevention and treatment strategies for this condition.

Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation.

Hydropersulfide and hydropolysulfide metabolites are increasingly important reactive sulfur species (RSS) regulating numerous cellular redox dependent functions. Intracellular production of these species is known to occur through RSS interactions or through translational mechanisms involving cysteinyl t-RNA synthetases. However, regulation of these species under cell stress conditions, such as hypoxia, that are known to modulate RSS remain poorly understood. Here we define an important mechanism of increased persulfide and polysulfide production involving cystathionine gamma lyase (CSE) phosphorylation at serine 346 and threonine 355 in a substrate specific manner, under acute hypoxic conditions. Hypoxic phosphorylation of CSE occurs in an AMP kinase dependent manner increasing enzyme activity involving unique inter- and intramolecular interactions within the tetramer. Importantly, both cellular hypoxia and tissue ischemia result in AMP Kinase dependent CSE phosphorylation that regulates blood flow in ischemic tissues. Our findings reveal hypoxia molecular signaling pathways regulating CSE dependent persulfide and polysulfide production impacting tissue and cellular response to stress.

Social-geographic disparities in suicidal ideations among methamphetamine users in the USA.

IMPORTANCE: Methamphetamine use is a growing public health concern nationwide. Suicide is the second leading cause of death in 2019 for US citizens aged 10-14 years and 25-34 years and is also a significant public health concern. Understanding the intersection of methamphetamine use and suicidal ideation (SI) is necessary to develop public health and policy solutions that mitigate these ongoing severe public health issues. OBJECTIVE: Our objective was to examine SI in methamphetamine users to allow us to determine prevalence and trends by age, sex, race, and geographical region. DESIGN, SETTINGS, AND PARTICIPANTS: Using data collected between 2008 and 2019 from the National Inpatient Sample (NIS) database, we identified hospital admissions (HA) of patients ≥18 years of age with a primary or secondary diagnosis of SI who were also diagnosed as methamphetamine users. Those who used other substances with methamphetamine were excluded from the analysis. MAIN OUTCOME AND MEASURES: To determine the trend and prevalence of hospital admissions due to SI and SI among methamphetamine users, we used trend weights to calculate the national estimates and performed design-based analysis to account for complex survey design and sampling weights on data collected between 2008 and 2019 in the US. RESULTS: The prevalence ratio (PR) of hospitalizations with concurrent SI and methamphetamine use increased 16-fold from 2008 to 2019. The most significant increase occurred between 2015 and 2016; the PR doubled from 6.07 to 12.14. The PR of hospitalizations with concurrent SI and methamphetamine use was highest in patients aged 26-40 (49.08%) and 41-64 (28.49%). Patients aged 41-64 showed the most significant increase from 2008 to 2019 (15.8-fold). While non-Hispanic White patients comprised most of these hospitalizations (77.02%), non-Hispanic Black patients showed the highest proportional increase (39.1-fold). The Southern and Western regions in the US showed the highest PR for these hospitalizations (34.86% and 34.31%, respectively). CONCLUSION AND RELEVANCE: Our findings indicate that SI in methamphetamine users has been increasing for some time and is likely to grow. In addition, our results suggest that these patients are demographically different. Both conditions are associated with a lesser likelihood of seeking and receiving care. Therefore, when addressing increased SI or methamphetamine use, learning more about patients who share both conditions is necessary to ensure proper care.

Short-term Outcome of Peroral Endoscopic Myotomy Performed by the Same Endoscopist on Achalasia and Nonachalasia Esophageal Motility Disorders.

BACKGROUND: Peroral endoscopic myotomy (POEM) is a relatively new but increasingly therapeutic option for achalasia. In recent years, POEM has been used for nonachalasia esophageal motility disorders (NAEMDs), such as diffuse esophageal spasm, esophagogastric junction outlet obstruction, and hypercontractile disorder, with some clinical success. No studies thus far compare the outcomes of these two groups. We perform the first head-to-head comparison of outcomes after POEM in patients with achalasia and NAEMD. PATIENTS AND METHODS: A retrospective analysis of all patients undergoing POEM at one university hospital by a single expert endoscopist from July 2021 to December 2022 was performed. All patients were symptomatic, and the presence of esophageal motility disorders was confirmed using multiple diagnostic modalities. These patients were then divided into 2 groups, achalasia and NAEMD, based on the underlying diagnosis. Statistical analysis of different clinical outcomes, including effectiveness and safety, was performed. RESULTS: Thirty-seven patients (mean age: 59.55, females: 22) underwent POEM in the study period. Twenty patients had achalasia and 17 patients had NAEMD. The median myotomy length was 5.5 cm for the achalasia group and 10 cm for the NAEMD group. This excluded patients with esophagogastric junction outlet obstruction in which the median myotomy length was 3 cm. The procedure time, the duration of hospital stays, the rates of same-day discharge, and complications were similar between the two. Short-term outcomes of POEM for the two groups were similar with improvement in 94% of patients in the achalasia group and 93.75% in the NAEMD group. CONCLUSION: Contrary to prior observations, our study highlights that POEM is equally effective in achieving clinical improvement in patients with NAEMD as achalasia over 6 months of follow-up. In addition, POEM has a comparable safety profile in both patient groups making it a feasible therapeutic option for these debilitating and challenging disorders.

Therapeutic Plasma Exchange in Severe Rhabdomyolysis: A Case-Control Study.

INTRODUCTION:  Rhabdomyolysis is a serious condition that can cause acute kidney injury (AKI), compartment syndrome, severe metabolic and electrolyte derangement leading to arrhythmias, and even death. Total plasma exchange (TPE) has been used as a treatment modality to clear myoglobin, but the evidence is limited. In this study, we aim to investigate the use of TPE in critically ill rhabdomyolysis patients. METHODS:  We retrospectively chart reviewed adult patients admitted to the intensive care unit (ICU) with a diagnosis of rhabdomyolysis between 2012 and 2021. We dichotomized patients into two groups based on whether TPE was used or not in addition to standard care. PRISMA machines with TPE2000 filters and either 5% albumin or fresh frozen plasma were used in the TPE group. RESULTS:  The patients' age ranged from 23 years to 87 years (mean 49.4, SD 18.1), and 51% were male. Initial creatinine ranged from 0.6 to 16mg/dL (mean 3.4, SD 2.7), creatinine phosphokinase (CPK) from 403-93,232 U/L, and myoglobin from 934 to >20,000. The Sequential Organ Failure Assessment (SOFA)scores on admission ranged from 6 to 17 (mean 7.23, SD 3.40). Overall, 28.78% (N=19) of the patients received therapeutic plasma exchange. The overall mortality in our study was 31.9%, with the length of ICU stay ranging from 1-25 days (mean 7.10, SD 5.91) among survivors. Older age and the presence of shock were predictive of mortality in univariate and multivariate analyses. There was no statistically significant association in mortality between the TPE and non-TPE groups (36.84% in TPE vs. 36.17% in the non-TPE group, OR 0.7209, p=0.959). Only two patients in the non-TPE group developed CKD/ESRD on long-term follow-up. CONCLUSION: Our study showed that TPE administration in critically ill patients with rhabdomyolysis did not improve mortality or length of ICU stay. Further studies are required to elucidate its indication and effect on long-term renal outcomes.

Safety of catheter ablation for atrial fibrillation in patients with cancer: a nationwide cohort study.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in patients with cancer, especially breast, gastrointestinal, respiratory, urinary tract, and hematological malignancies. Catheter ablation (CA) is a well-established, safe treatment option in healthy patients; however, literature regarding safety of CA for AF in patients with cancer is limited and confined to single centers. OBJECTIVE: We aimed to assess the outcomes and peri-procedural safety of CA for AF in patients with certain types of cancer. METHODS: The NIS database was queried between 2016 and 2019 to identify primary hospitalizations with AF and CA. Hospitalizations with secondary diagnosis of atrial flutter and other arrhythmias were excluded. Propensity score matching was used to balance the covariates between cancer and non-cancer groups. Logistic regression was used to analyze the association. RESULTS: During this period, 47,765 CA procedures were identified, out of which 750 (1.6%) hospitalizations had a diagnosis of cancer. After propensity matching, hospitalizations with cancer diagnosis had higher in-hospital mortality (OR 3.0, 95% CI 1.5-6.2, p = 0.001), lower home discharge rates (OR 0.7, 95% CI 0.6-0.9, p < 0.001) as well as other complications such as major bleeding (OR 1.8, 95% CI 1.3-2.7, p = 0.001) and pulmonary embolism (OR 6.1, 95% CI 2.1-17.8, p < 0.001) but not associated with any major cardiac complications (OR 1.2, 95% CI 0.7-1.8, p = 0.53). CONCLUSION: Patients with cancer who underwent CA for AF had significantly higher odds of in-hospital mortality, major bleeding, and pulmonary embolism. Further larger prospective observational studies are needed to validate these findings.

Sigmar1 ablation leads to lung pathological changes associated with pulmonary fibrosis, inflammation, and altered surfactant proteins levels.

Sigma1 receptor protein (Sigmar1) is a small, multifunctional molecular chaperone protein ubiquitously expressed in almost all body tissues. This protein has previously shown its cardioprotective roles in rodent models of cardiac hypertrophy, heart failure, and ischemia-reperfusion injury. Extensive literature also suggested its protective functions in several central nervous system disorders. Sigmar1's molecular functions in the pulmonary system remained unknown. Therefore, we aimed to determine the expression of Sigmar1 in the lungs. We also examined whether Sigmar1 ablation results in histological, ultrastructural, and biochemical changes associated with lung pathology over aging in mice. In the current study, we first confirmed the presence of Sigmar1 protein in human and mouse lungs using immunohistochemistry and immunostaining. We used the Sigmar1 global knockout mouse (Sigmar1-/-) to determine the pathophysiological role of Sigmar1 in lungs over aging. The histological staining of lung sections showed altered alveolar structures, higher immune cells infiltration, and upregulation of inflammatory markers (such as pNFκB) in Sigmar1-/- mice compared to wildtype (Wt) littermate control mice (Wt). This indicates higher pulmonary inflammation resulting from Sigmar1 deficiency in mice, which was associated with increased pulmonary fibrosis. The protein levels of some fibrotic markers, fibronectin, and pSMAD2 Ser 245/250/255 and Ser 465/467, were also elevated in mice lungs in the absence of Sigmar1 compared to Wt. The ultrastructural analysis of lungs in Wt mice showed numerous multilamellar bodies of different sizes with densely packed lipid lamellae and mitochondria with a dark matrix and dense cristae. In contrast, the Sigmar1-/- mice lung tissues showed altered multilamellar body structures in alveolar epithelial type-II pneumocytes with partial loss of lipid lamellae structures in the lamellar bodies. This was further associated with higher protein levels of all four surfactant proteins, SFTP-A, SFTP-B, SFTP-C, and SFTP-D, in the Sigmar1-/- mice lungs. This is the first study showing Sigmar1's expression pattern in human and mouse lungs and its association with lung pathophysiology. Our findings suggest that Sigmar1 deficiency leads to increased pulmonary inflammation, higher pulmonary fibrosis, alterations of the multilamellar body stuructures, and elevated levels of lung surfactant proteins.

Topical cannabidiol is well tolerated in individuals with a history of elite physical performance and chronic lower extremity pain.

INTRODUCTION: Cannabidiol (CBD) is a potential therapeutic for pain management. Yet, there exists a dearth of studies of its tolerability and efficacy, especially in special populations. Former elite athletes are a special population both susceptible to chronic pain and also highly trained and attuned to assess medication tolerability concerns. The purpose of the present open-label pilot study was to assess the tolerability of CBD in this population. MATERIALS AND METHODS: Retrospective analysis was conducted in deidentified data from 20 individuals who were all previously professional athletes in US/American football, track and field, or basketball, with careers ranging from 4 to 10 years. Participants received topical CBD (10 mg twice daily by controlled dispenser) for chronic pain resulting from acute lower extremity injuries. Assessments of tolerability and secondary analyses of pain, pain-related disability, and activities of daily living were collected by self-report over the 6-week study period. Data were analyzed by descriptive statistics, pairwise t-test, and linear regression. RESULTS: Seventy percent of participants completed the study. Of the individuals who completed the study, 50% reported minor adverse effects, none of which required medical attention, and 50% did not report any adverse effects. The mostly commonly reported effects were skin dryness (43% of study completers) and skin rash (21% of study completers), which rapidly resolved. There was a significant improvement in self-reported pain levels (intake mean 3.5 ± 0.29; exit mean 1.7 ± 0.23; P < 0.001) and pain-related disability, including family and home responsibilities, life support activities, occupational activities, recreational activities, self-care, sexual function, and social activities (all P < 0.001). DISCUSSION: To the best of our knowledge, this is the first study to assess CBD treatment in elite athletes, who are disproportionally susceptible to disabling injuries. Topical administration of CBD was tolerated well by this population and resulted in only minor adverse effects. As elite athletes are trained and attuned to assess their own bodies due to their professional lives, this population is likely to detect tolerability concerns. However, this study was limited to a convenience sample and self-reported data. These pilot findings warrant further study of topical CBD in randomized and controlled studies of elite athletes.

Elevated plasma sulfides are associated with cognitive dysfunction and brain atrophy in human Alzheimer's disease and related dementias.

Emerging evidence indicates that vascular stress is an important contributor to the pathophysiology of Alzheimer's disease and related dementias (ADRD). Hydrogen sulfide (H2S) and its metabolites (acid-labile (e.g., iron-sulfur clusters) and bound (e.g., per-, poly-) sulfides) have been shown to modulate both vascular and neuronal homeostasis. We recently reported that elevated plasma sulfides were associated with cognitive dysfunction and measures of microvascular disease in ADRD. Here we extend our previous work to show associations between elevated sulfides and magnetic resonance-based metrics of brain atrophy and white matter integrity. Elevated bound sulfides were associated with decreased grey matter volume, while increased acid labile sulfides were associated with decreased white matter integrity and greater ventricular volume. These findings are consistent with alterations in sulfide metabolism in ADRD which may represent maladaptive responses to oxidative stress.

Using the social vulnerability index to assess COVID-19 vaccine uptake in Louisiana.

Using data from the Louisiana Department of Public Health, we explored the spatial relationships between the Social Vulnerability Index (SVI) and COVID-19-related vaccination and mortality rates. Publicly available COVID-19 vaccination and mortality data accrued from December 2020 to October 2021 was downloaded from the Louisiana Department of Health website and merged with the SVI data; geospatial analysis was then performed to identify the spatial association between the SVI and vaccine uptake and mortality rate. Bivariate Moran's I analysis revealed significant clustering of high SVI ranking with low COVID-19 vaccination rates (1.00, p < 0.001) and high smoothed mortality rates (0.61, p < 0.001). Regression revealed that for each 10% increase in SVI ranking, COVID-19 vaccination rates decreased by 3.02-fold (95% CI = 3.73-2.30), and mortality rates increased by a factor of 1.19 (95% CI = 0.99-1.43). SVI values are spatially linked and significantly associated with Louisiana's COVID-19-related vaccination and mortality rates. We also found that vaccination uptake was higher in whites than in blacks. These findings can help identify regions with low vaccination rates and high mortality, enabling the necessary steps to increase vaccination rates in disadvantaged neighborhoods.

Pathological Sequelae Associated with Skeletal Muscle Atrophy and Histopathology in G93A*SOD1 Mice.

Amyotrophic lateral sclerosis (ALS) is a complex systemic disease that primarily involves motor neuron dysfunction and skeletal muscle atrophy. One commonly used mouse model to study ALS was generated by transgenic expression of a mutant form of human superoxide dismutase 1 (SOD1) gene harboring a single amino acid substitution of glycine to alanine at codon 93 (G93A*SOD1). Although mutant-SOD1 is ubiquitously expressed in G93A*SOD1 mice, a detailed analysis of the skeletal muscle expression pattern of the mutant protein and the resultant muscle pathology were never performed. Using different skeletal muscles isolated from G93A*SOD1 mice, we extensively characterized the pathological sequelae of histological, molecular, ultrastructural, and biochemical alterations. Muscle atrophy in G93A*SOD1 mice was associated with increased and differential expression of mutant-SOD1 across myofibers and increased MuRF1 protein level. In addition, high collagen deposition and myopathic changes sections accompanied the reduced muscle strength in the G93A*SOD1 mice. Furthermore, all the muscles in G93A*SOD1 mice showed altered protein levels associated with different signaling pathways, including inflammation, mitochondrial membrane transport, mitochondrial lipid uptake, and antioxidant enzymes. In addition, the mutant-SOD1 protein was found in the mitochondrial fraction in the muscles from G93A*SOD1 mice, which was accompanied by vacuolized and abnormal mitochondria, altered OXPHOS and PDH complex protein levels, and defects in mitochondrial respiration. Overall, we reported the pathological sequelae observed in the skeletal muscles of G93A*SOD1 mice resulting from the whole-body mutant-SOD1 protein expression.

Social media use and body image issues among adolescents in a vulnerable Louisiana community.

Widespread concern has been expressed regarding unrealistic body image and adolescent eating disorder promoting content on social media (SM) platforms. Numerous research studies have examined the impact of SM on body image as well as social vulnerability on negative mental health outcomes. Despite this, few previous studies have examined the impact of SM on body image specifically in vulnerable, underserved, or predominantly minority communities. This study examines the impact of SM on body image issues (BII) in adolescents in a public school system where greater than 50% of the students live in impoverished households. In late 2019, high school student leaders in Northwest Louisiana developed a survey alongside Step Forward, a collective impact initiative. Questions investigated adolescent SM use and mental health in Caddo Parish, namely BII. Teachers within Caddo Parish Public School System administered the survey. Out of the 11,248 total high school students in the school system, nearly 50% were sampled for a sample size of 5,070. Hypotheses included: (1) females were more likely to use SM than males, (2) increasing time spent on SM would correlate with females reporting BII, with males remaining largely unaffected, and (3) highly visual social media (HVSM) platforms would be associated with greater reports of BII than non-HVSM platforms. Results showed females were more likely to use SM (p < 0.001) and report BII (p < 0.001) compared to males, while both sexes reported BII with increasing time spent on SM (p < 0.001). A diversity of platforms were associated with increased BII among SM users compared to non-users (p < 0.001): Pinterest, Reddit, Snapchat, TikTok, Twitter, and YouTube. This conclusion is tempered by the omission of race as a variable in the study design, the use of self-report, and the use of an unvalidated instrument. These findings suggest that the harmful association between SM use and BII may transcend culture and socioeconomic status for a broadly deleterious effect on adolescent mental wellbeing.

Mitochondrial dysfunction and autophagy activation are associated with cardiomyopathy developed by extended methamphetamine self-administration in rats.

The recent rise in illicit use of methamphetamine (METH), a highly addictive psychostimulant, is a huge health care burden due to its central and peripheral toxic effects. Mounting clinical studies have noted that METH use in humans is associated with the development of cardiomyopathy; however, preclinical studies and animal models to dissect detailed molecular mechanisms of METH-associated cardiomyopathy development are scarce. The present study utilized a unique very long-access binge and crash procedure of METH self-administration to characterize the sequelae of pathological alterations that occur with METH-associated cardiomyopathy. Rats were allowed to intravenously self-administer METH for 96 h continuous weekly sessions over 8 weeks. Cardiac function, histochemistry, ultrastructure, and biochemical experiments were performed 24 h after the cessation of drug administration. Voluntary METH self-administration induced pathological cardiac remodeling as indicated by cardiomyocyte hypertrophy, myocyte disarray, interstitial and perivascular fibrosis accompanied by compromised cardiac systolic function. Ultrastructural examination and native gel electrophoresis revealed altered mitochondrial morphology and reduced mitochondrial oxidative phosphorylation (OXPHOS) supercomplexes (SCs) stability and assembly in METH exposed hearts. Redox-sensitive assays revealed significantly attenuated mitochondrial respiratory complex activities with a compensatory increase in pyruvate dehydrogenase (PDH) activity reminiscent of metabolic remodeling. Increased autophagy flux and increased mitochondrial antioxidant protein level was observed in METH exposed heart. Treatment with mitoTEMPO reduced the autophagy level indicating the involvement of mitochondrial dysfunction in the adaptive activation of autophagy in METH exposed hearts. Altogether, we have reported a novel METH-associated cardiomyopathy model using voluntary drug seeking behavior. Our studies indicated that METH self-administration profoundly affects mitochondrial ultrastructure, OXPHOS SCs assembly and redox activity accompanied by increased PDH activity that may underlie observed cardiac dysfunction.

COVID-19 drive-through mass vaccination in Northwest Louisiana.

Background: Vaccinating susceptible populations quickly and safely is vital during a pandemic. Mass vaccination programs using a drive-through method have been shown to reach large numbers of people efficiently during vaccine campaigns. Methods: We performed a quantitative, cross-sectional study analyzing data collected by the COVID-19 mass vaccination program conducted by Louisiana State University Health Shreveport (LSUSH). Results: Between December 2020 and September 2021, the vaccination program administered 90,655 COVID-19 vaccines. Among those who received at least the first dose of the vaccine, there were 21,700 men and 28,269 women; 22,820 were ≥60 years of age; 28,031 identified as Caucasian, 19,249 as African American, 47,916 as non-Hispanic, and most of them reported that they had not tested positive for COVID-19 before vaccination. Discussion: The LSUHS vaccination center served people from different regions within Louisiana as well as those from outside Louisiana. Vaccination is a crucial public health measure in the fight against the COVID-19 pandemic. Conclusions: Our study showed that the mass vaccination program conducted by LSUHS had a considerable positive impact on communities in Northwest Louisiana. This drive-through method is an effective strategy with which to reach a significant number of people during a pandemic.

Low left atrial appendage emptying velocity is a predictor of atrial fibrillation recurrence after catheter ablation.

BACKGROUND: Recurrence of atrial fibrillation (AF) after catheter ablation (CA) remains common and studies have shown about 5%-9% annual recurrence rate after CA. We sought to assess the echocardiogram derived left atrial appendage (LAA) emptying velocity as a predictor of AF recurrence after CA. OBJECTIVE: To determine if LAA emptying is a marker of recurrence of AF post-CA METHODS: A total of 303 consecutive patients who underwent CA for AF between 2014 and 2020 were included. Baseline clinical characteristics and echocardiographic data of the patients were obtained by chart review. LAA emptying velocities were obtained from transesophageal echocardiogram (TEE). LA voltage was obtained during the mapping for CA. Chi-square test and nominal logistic regression were used for statistical analysis. An receiver operator characteristic curve was used to determine LAA velocity cut-off. RESULTS: Mean patient age was 61.7 ± 10.5; 32% were female. Mean LAA emptying velocity was 47.5 ± 20.2. A total of 103 (40%) patients had recurrence after CA. In the multivariable model, after adjusting for potential confounders, LAA emptying velocity of ≥52.3 was associated with decreased AF recurrence postablation (odds ratio [OR]: 0.55; 95% confidence interval  [CI]: 0.31-0.97; p = .03*). There were 190 (73%) patients in normal sinus rhythm during TEE and CA, and sensitivity analysis of these patients showed that LAA velocity ≥52.3 remained associated with decreased AF recurrence (OR: 0.35; 95% CI: 0.15-0.82; p = .01*). CONCLUSION: LAA emptying velocity measured during preprocedural TEE can serve as a predictor of AF recurrence in patients undergoing CA.

Molecular Characterization of Skeletal Muscle Dysfunction in Sigma 1 Receptor (Sigmar1) Knockout Mice.

Sigma 1 receptor (Sigmar1) is a widely expressed, multitasking molecular chaperone protein that plays functional roles in several cellular processes. Mutations in the Sigmar1 gene are associated with several distal neuropathies with strong manifestation in skeletal muscle dysfunction with phenotypes like muscle wasting and atrophy. However, the physiological function of Sigmar1 in skeletal muscle remains unknown. Herein, the physiological role of Sigmar1 in skeletal muscle structure and function in gastrocnemius, quadriceps, soleus, extensor digitorum longus, and tibialis anterior muscles was determined. Quantification of myofiber cross-sectional area showed altered myofiber size distribution and changes in myofiber type in the skeletal muscle of the Sigmar1-/- mice. Interestingly, ultrastructural analysis by transmission electron microscopy showed the presence of abnormal mitochondria, and immunostaining showed derangements in dystrophin localization in skeletal muscles from Sigmar1-/- mice. In addition, myopathy in Sigmar1-/- mice was associated with an increased number of central nuclei, increased collagen deposition, and fibrosis. Functional studies also showed reduced endurance and exercise capacity in the Sigmar1-/- mice without any changes in voluntary locomotion, markers for muscle denervation, and muscle atrophy. Overall, this study shows, for the first time, a potential physiological function of Sigmar1 in maintaining healthy skeletal muscle structure and function.