TFEB/3 Govern Repair Schwann Cell Generation and Function Following Peripheral Nerve Injury.

TFEB and TFE3 (TFEB/3), key regulators of lysosomal biogenesis and autophagy, play diverse roles depending on cell type. This study highlights a hitherto unrecognized role of TFEB/3 crucial for peripheral nerve repair. Specifically, they promote the generation of progenitor-like repair Schwann cells after axonal injury. In Schwann cell-specific TFEB/3 double knock-out mice of either sex, the TFEB/3 loss disrupts the transcriptomic reprogramming that is essential for the formation of repair Schwann cells. Consequently, mutant mice fail to populate the injured nerve with repair Schwann cells and exhibit defects in axon regrowth, target reinnervation, and functional recovery. TFEB/3 deficiency inhibits the expression of injury-responsive repair Schwann cell genes, despite the continued expression of c-jun, a previously identified regulator of repair Schwann cell function. TFEB/3 binding motifs are enriched in the enhancer regions of injury-responsive genes, suggesting their role in repair gene activation. Autophagy-dependent myelin breakdown is not impaired despite TFEB/3 deficiency. These findings underscore a unique role of TFEB/3 in adult Schwann cells that is required for proper peripheral nerve regeneration.

Analysis of gliomas DNA methylation: Assessment of pre-analytical variables.

Precision oncology is driven by biomarkers. For glioblastoma multiforme (GBM), the most common malignant adult primary brain tumor, O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation is an important prognostic and treatment clinical biomarker. Time consuming pre-analytical steps such as biospecimen storage, fixation, sampling, and processing are sources of data irreproducibility, and all these pre-analytical variables are confounded by intratumor heterogeneity of MGMT promoter methylation. To assess the effect of pre-analytical variables on GBM DNA methylation, tissue storage/sampling (CryoGrid), sample preparation multi-sonicator (PIXUL), and 5-methylcytosine (5mC) DNA immunoprecipitation (Matrix MeDIP-qPCR/seq) platforms were used. MGMT promoter methylation status assayed by MeDIP-qPCR was validated with methylation specific PCR (MS-PCR). MGMT promoter methylation levels in frozen and formalin fixed paraffin embedded (FFPE) sample pairs were not statistically different, confirming reliability of FFPEs for MGMT promoter methylation analysis. Warm ex-vivo ischemia (up to 4hrs at 37oC) and 3 cycles of repeated sample thawing and freezing did not statistically impact 5mC at MGMT promoter, exon, and enhancer regions, indicating the resistance of DNA methylation to common variations in sample processing conditions that might be encountered in research and clinical settings. 26-34% of specimens exhibited intratumor heterogeneity in the MGMT DNA promoter methylation. These data demonstrate that variations in sample fixation, ischemia duration and temperature, and DNA methylation assay technique do not have a statistically significant impact on MGMT promoter methylation assessment. However, intratumor methylation heterogeneity underscores the value of multiple biopsies at different GBM geographic tumor sites in the evaluation of MGMT promoter methylation status. Matrix-MeDIP-seq analysis revealed that MGMT promoter methylation status clustered with other differentially methylated genomic loci (e.g. HOXA and lncRNAs) that are resilient to variation in the above pre-analytical conditions. These observations offer new opportunities to develop more granular data-based epigenetic GBM biomarkers. In this regard, the high throughput CryoGrid-PIXUL-Matrix toolbox could be useful.

Longitudinal association of exclusive and dual use of cigarettes and cigars with asthma exacerbation among US adults: a cohort study.

BACKGROUND: Cigar use among adults in the United States has remained relatively stable in the past decade and occupies a growing part of the tobacco marketplace as cigarette use has declined. While studies have established the detrimental respiratory health effects of cigarette use, the effects of cigar use need further characterization. In this study, we evaluate the prospective association between cigar use, with or without cigarettes, and asthma exacerbation. METHODS: We used data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study to run generalized estimating equation models examining the association between time-varying, one-wave-lagged cigarette and cigar use and self-reported asthma exacerbation among US adults (18+). We defined our exposure as non-established (reference), former, exclusive cigarette, exclusive cigar, and dual use. We defined an asthma exacerbation event as a reported asthma attack in the past 12 months necessitating oral or injected steroid medication or asthma symptoms disrupting sleep at least once a week in the past 30 days. We adjusted for age, sex, race and ethnicity, household income, health insurance, established electronic nicotine delivery systems use, cigarette pack-years, secondhand smoke exposure, obesity, and baseline asthma exacerbation. RESULTS: Exclusive cigarette use (incidence rate ratio (IRR): 1.26, 95% confidence interval (CI): 1.03-1.54) and dual use (IRR: 1.41, 95% CI: 1.08-1.85) were associated with a higher rate of asthma exacerbation compared to non-established use, while former use (IRR: 1.01, 95% CI: 0.80-1.28) and exclusive cigar use (IRR: 0.70, 95% CI: 0.42-1.17) were not. CONCLUSION: We found no association between exclusive cigar use and self-reported asthma exacerbation. However, exclusive cigarette use and dual cigarette and cigar use were associated with higher incidence rates of self-reported asthma exacerbation compared to non-established use. Studies should evaluate strategies to improve cigarette and cigar smoking cessation among adults with asthma who continue to smoke.

Leveraging single-cell sequencing to classify and characterize tumor subgroups in bulk RNA-sequencing data.

PURPOSE: Accurate classification of cancer subgroups is essential for precision medicine, tailoring treatments to individual patients based on their cancer subtypes. In recent years, advances in high-throughput sequencing technologies have enabled the generation of large-scale transcriptomic data from cancer samples. These data have provided opportunities for developing computational methods that can improve cancer subtyping and enable better personalized treatment strategies. METHODS: Here in this study, we evaluated different feature selection schemes in the context of meningioma classification. To integrate interpretable features from the bulk (n = 77 samples) and single-cell profiling (∼ 10 K cells), we developed an algorithm named CLIPPR which combines the top-performing single-cell models, RNA-inferred copy number variation (CNV) signals, and the initial bulk model to create a meta-model. RESULTS: While the scheme relying solely on bulk transcriptomic data showed good classification accuracy, it exhibited confusion between malignant and benign molecular classes in approximately ∼ 8% of meningioma samples. In contrast, models trained on features learned from meningioma single-cell data accurately resolved the sub-groups confused by bulk-transcriptomic data but showed limited overall accuracy. CLIPPR showed superior overall accuracy and resolved benign-malignant confusion as validated on n = 789 bulk meningioma samples gathered from multiple institutions. Finally, we showed the generalizability of our algorithm using our in-house single-cell (∼ 200 K cells) and bulk TCGA glioma data (n = 711 samples). CONCLUSION: Overall, our algorithm CLIPPR synergizes the resolution of single-cell data with the depth of bulk sequencing and enables improved cancer sub-group diagnoses and insights into their biology.

Hospital Outcomes in Patients Who Developed Acute Respiratory Distress Syndrome After Community-Acquired Pneumonia.

Purpose: To identify risk factors for and outcomes in acute respiratory distress syndrome (ARDS) in patients hospitalized with community-acquired pneumonia (CAP). Methods: This is a retrospective study using the Premier Healthcare Database between 2016 and 2020. Patients diagnosed with pneumonia, requiring mechanical ventilation (MV), antimicrobial therapy, and hospital admission ≥2 days were included. Multivariable regression models were used for outcomes including in-hospital mortality, hospital length of stay (LOS), intensive care unit (ICU) LOS, and days on MV. Results: 1924 (2.7%) of 72 107 patients with CAP developed ARDS. ARDS was associated with higher mortality (33.7% vs 18.9%; adjusted odds ratio 2.4; 95% confidence interval [CI] 2.16-2.66), longer hospital LOS (13 vs 9 days; adjusted incidence risk ratio (aIRR) 1.24; 95% CI 1.20-1.27), ICU LOS (9 vs 5 days; aIRR 1.51; 95% CI 1.46-1.56), more MV days (8 vs 5; aIRR 1.54; 95% CI 1.48-1.59), and increased hospitalization cost ($46 459 vs $29 441; aIRR 1.50; 95% CI 1.45-1.55). Conclusion: In CAP, ARDS was associated with worse in-patient outcomes in terms of mortality, LOS, and hospitalization cost. Future studies are needed to explore outcomes in patients with CAP with ARDS and explore risk factors for development of ARDS after CAP.

Evidence-Based Update on Transcatheter Therapies for Pulmonary Embolism.

PURPOSE OF REVIEW: Pulmonary embolism (PE) remains a leading cause of cardiovascular morbidity and mortality. Multiple new therapies are in development and under study to improve our contemporary care of patients with PE. We review and compare here these novel therapeutics and technologies. RECENT FINDINGS: Multiple novel therapeutic devices have been developed and are under active study. This work has advanced the care of patients with intermediate and high-risk PE. Novel therapies are improving care of complex PE patients. These have inspired large multicenter international randomized controlled trials that are actively recruiting patients to advance the care of PE. These studies will work towards advancing guidelines for clinical care of patients with PE.

Implementing a 'Lead [Apron]-Free' Cardiac Catheterization: Current Status.

PURPOSE OF REVIEW: In this review, we discuss the status of novel radiation shielding and other methods to reduce radiation exposure and its associated health risks within the CCL. RECENT FINDINGS: There are many devices on the market each with its unique advantages and inherent flaws. Several are available for widespread use with promising data, while others still in development. The field of percutaneous transcatheter interventions includes complex procedures often involving significant radiation exposure. Increased radiation exposes the proceduralist and CCL staff to potential harm from both direct effects of radiation but also from the ergonomic consequences of daily use of heavy personal protective equipment. Here we discuss several innovative efforts to reduce both radiation exposure and orthopedic injury within the CCL that are available, leading to a safer daily routine in a "lead [apron]-free" environment.

Targeting GBM with an Oncolytic Picornavirus SVV-001 alone and in combination with fractionated Radiation in a Novel Panel of Orthotopic PDX models.

BACKGROUND: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM. MATERIALS AND METHODS: 23 patient tumor samples were implanted into the brains of NOD/SCID mice (1 × 105 cells/mouse). Tumor histology, gene expression (RNAseq), and growth rate of the developed patient-derived orthotopic xenograft (PDOX) models were compared with the originating patient tumors during serial subtransplantations. Anti-tumor activities of SVV-001 were examined in vivo; and therapeutic efficacy validated in vivo via single i.v. injection (1 × 1011 viral particle) with or without fractionated (2 Gy/day x 5 days) radiation followed by analysis of animal survival times, viral infection, and DNA damage. RESULTS: PDOX formation was confirmed in 17/23 (73.9%) GBMs while maintaining key histopathological features and diffuse invasion of the patient tumors. Using differentially expressed genes, we subclassified PDOX models into proneural, classic and mesenchymal groups. Animal survival times were inversely correlated with the implanted tumor cells. SVV-001 was active in vitro by killing primary monolayer culture (4/13 models), 3D neurospheres (7/13 models) and glioma stem cells. In 2/2 models, SVV-001 infected PDOX cells in vivo without harming normal brain cells and significantly prolonged survival times in 2/2 models. When combined with radiation, SVV-001 enhanced DNA damages and further prolonged animal survival times. CONCLUSION: A panel of 17 clinically relevant and molecularly annotated PDOX modes of GBM is developed, and SVV-001 exhibited strong anti-tumor activities in vitro and in vivo.

Detrimental Effects of Alcohol on the Heart: Hypertension and Cardiomyopathy.

Background: Epidemiological evidence suggests a J-shaped association between alcohol consumption and cardiovascular mortality, with higher cardiovascular event rates occurring among abstainers and heavy drinkers compared to moderate consumers. However, this hypothesis has been challenged by more recent studies. Furthermore, ethnicity, gender, type of alcoholic beverage, and pattern of alcohol intake, influence the relationship between alcohol and heart health. Methods: We undertook a review of the relavent literature utilizing PubMed. Results: Heavy alcohol consumption causes resistant hypertension, cardiomyopathy, arrhythmias, hemorrhagic strokes, as well as hepatic cirrhosis and pancreatitis. Excessive drinking is the third most preventable cause of death worldwide behind hypertension and smoking. Conclusions: In this review, we discuss the effects of alcohol abuse on hypertension (a major cause of myocardial infarction and stroke) and alcoholic cardiomyopathy. Another article in this Special Issue "Alcohol and Heart Health" discusses the problem with alcohol and arrhythmias sudden cardiac death.

Alcohol and Cardiovascular Disease: Helpful or Hurtful.

Alcohol has been considered throughout history as both a tonic and a poison. The answer as to which likely depends on one's current health, the amount one consumes, and with what regularity. In examining the relationship of alcohol and cardiovascular health, most, but not all, epidemiological studies suggest that light to moderate alcohol consumption can reduce the incidence of coronary artery disease (CAD), ischemic stroke, and peripheral arterial disease events. Conversely, abuse of alcohol can lead to cardiomyopathy, heart failure, sudden death, and hemorrhagic strokes. In this article, we review the literature studying the effects of alcohol on coronary artery disease and stroke. A recently published study concluded there was no amount of alcohol per day that was heart healthy. Yet more than one hundred previous studies have found that people who drink in moderation have a lower risk of cardiovascular disease events when compared to those who do not drink or drink heavily. Moderate drinking is defined as one to two drinks per day; where one drink is defined as 12 ounces of beer, 5 ounces of wine or 1.5 ounces of hard liquor. In this article we reviewed the data suggesting that consuming alcohol in moderation on a regular basis-as opposed to 7 drinks on Saturday night-could have cardiovascular protective effects.

Integrated clinical genomic analysis reveals xenobiotic metabolic genes are downregulated in meningiomas of current smokers.

INTRODUCTION: Meningiomas are the most common primary intracranial tumor. Recently, various genetic classification systems for meningioma have been described. We sought to identify clinical drivers of different molecular changes in meningioma. As such, clinical and genomic consequences of smoking in patients with meningiomas remain unexplored. METHODS: 88 tumor samples were analyzed in this study. Whole exome sequencing (WES) was used to assess somatic mutation burden. RNA sequencing data was used to identify differentially expressed genes (DEG) and genes sets (GSEA). RESULTS: Fifty-seven patients had no history of smoking, twenty-two were past smokers, and nine were current smokers. The clinical data showed no major differences in natural history across smoking status. WES revealed absence of AKT1 mutation rate in current or past smokers compared to non-smokers (p = 0.046). Current smokers had increased mutation rate in NOTCH2 compared to past and never smokers (p < 0.05). Mutational signature from current and past smokers showed disrupted DNA mismatch repair (cosine-similarity = 0.759 and 0.783). DEG analysis revealed the xenobiotic metabolic genes UGT2A1 and UGT2A2 were both significantly downregulated in current smokers compared to past (Log2FC = - 3.97, padj = 0.0347 and Log2FC = - 4.18, padj = 0.0304) and never smokers (Log2FC = - 3.86, padj = 0.0235 and Log2FC = - 4.20, padj = 0.0149). GSEA analysis of current smokers showed downregulation of xenobiotic metabolism and enrichment for G2M checkpoint, E2F targets, and mitotic spindle compared to past and never smokers (FDR < 25% each). CONCLUSION: In this study, we conducted a comparative analysis of meningioma patients based on their smoking history, examining both their clinical trajectories and molecular changes. Meningiomas from current smokers were more likely to harbor NOTCH2 mutations, and AKT1 mutations were absent in current or past smokers. Moreover, both current and past smokers exhibited a mutational signature associated with DNA mismatch repair. Meningiomas from current smokers demonstrate downregulation of xenobiotic metabolic enzymes UGT2A1 and UGT2A2, which are downregulated in other smoking related cancers. Furthermore, current smokers exhibited downregulation xenobiotic metabolic gene sets, as well as enrichment in gene sets related to mitotic spindle, E2F targets, and G2M checkpoint, which are hallmark pathways involved in cell division and DNA replication control. In aggregate, our results demonstrate novel alterations in meningioma molecular biology in response to systemic carcinogens.

Longitudinal associations between exclusive, dual, and polytobacco use and asthma among US youth.

Little is known about the respiratory health effects of dual (two products) and polytobacco (three or more products) use among youth in the United States. Thus, we followed a longitudinal cohort of youth into adulthood using data from Waves 1-5 (2013-2019) of the Population Assessment of Tobacco and Health Study, examining incident asthma at each follow-up (Waves 2-5). We classified past 30-day tobacco use as 1) no products (never/former use), 2) exclusive cigarettes, 3) exclusive electronic nicotine delivery systems (ENDS), 4) exclusive other combustible (OC) tobacco products (cigars, hookah, pipe), 5) dual cigarettes/OC and ENDS, 6) dual cigarettes and OCs, and 7) polytobacco use (cigarettes, OCs, and ENDS). Using discrete time survival models, we analyzed the incidence of asthma across Waves 2-5, predicted by time-varying tobacco use lagged by one wave, and adjusted for potential baseline confounders. Asthma was reported by 574 of the 9141 respondents, with an average annual incidence of 1.44% (range 0.35% to 2.02%, Waves 2-5). In adjusted models, exclusive cigarette use (HR: 1.71, 95% CI: 1.11-2.64) and dual cigarette and OC use (HR: 2.78, 95% CI: 1.65-4.70) were associated with incident asthma compared to never/former use, while exclusive ENDS use (HR: 1.50, 95% CI: 0.92-2.44) and polytobacco use (HR: 1.95, 95% CI: 0.86-4.44) were not. To conclude, youth who use cigarettes with or without OCs had higher risk of incident asthma. Further longitudinal studies on the respiratory health effects of ENDS and dual/polytobacco use are needed as products continue to evolve.

Longitudinal Associations Between Exclusive and Dual Use of Electronic Nicotine Delivery Systems and Cigarettes and Self-Reported Incident Diagnosed Cardiovascular Disease Among Adults.

INTRODUCTION: The cardiovascular health effects of electronic nicotine delivery systems (ENDS) use are not well characterized, making it difficult to assess ENDS as a potential harm reduction tool for adults who use cigarettes. AIMS AND METHODS: Using waves 1-5 of the Population Assessment of Tobacco and Health Study (2013-2019), we analyzed the risk of self-reported incident diagnosed myocardial infarction (MI; 280 incident cases) and stroke (186 incident cases) associated with ENDS and/or cigarette use among adults aged 40 + using discrete time survival models. We employed a time-varying exposure lagged by one wave, defined as exclusive or dual established use of ENDS and/or cigarettes every day or some days, and controlled for demographics, clinical factors, and past smoking history. RESULTS: The analytic samples (MI = 11 031; stroke = 11 076) were predominantly female and non-Hispanic White with a mean age of 58 years. At baseline, 14.2% of respondents exclusively smoked cigarettes, 0.6% exclusively used ENDS, and 1.0% used both products. Incident MI and stroke were rare during follow-up (< 1% at each wave). Compared to no cigarette or ENDS use, exclusive cigarette use increased the risk of MI (aHR 1.99, 95% CI = 1.40-2.84) and stroke (aHR 2.26, 95% CI = 1.51-3.39), while exclusive ENDS use (MI: aHR 0.61, 95% CI = 0.12-3.04; stroke: aHR 1.74, 95% CI = 0.55-5.49) and dual use (MI: aHR 1.84, 95% CI = 0.64-5.30; stroke: aHR 1.12, 95% CI = 0.33-3.79) were not significantly associated with the risk of either outcome. CONCLUSIONS: Compared to non-use, exclusive cigarette use was associated with an increased risk of self-reported incident diagnosed cardiovascular disease over a 5-year period, while ENDS use was not associated with a statistically significant increase in the outcomes. IMPLICATIONS: Existing literature on the health effects of ENDS use has important limitations, including potential reverse causation and improper control for cigarette smoking. We accounted for these issues by using a prospective design and adjusting for current and former smoking status and cigarette pack-years. In this context, we did not find that ENDS use was associated with a statistically significant increase in self-reported incident diagnosed myocardial infarction or stroke over a 5-year period. While more studies are needed, this analysis provides an important foundation and key methodological considerations for future research on the health effects of ENDS use.

Impact of Coronavirus Disease 2019 Pandemic on Cardiac Arrest and Emergency Care.

The incidence of both out-of-hospital and in-hospital cardiac arrest increased during the coronavirus disease 2019 (COVID-19) pandemic. Patient survival and neurologic outcome after both out-of-hospital and in-hospital cardiac arrest were reduced. Direct effects of the COVID-19 illness combined with indirect effects of the pandemic on patient's behavior and health care systems contributed to these changes. Understanding the potential factors offers the opportunity to improve future response and save lives.

The effects of sport, setting, and demographics on sunscreen use and education in young athletes.

Participation in outdoor sports increases exposure to ultraviolet radiation, necessitating mitigation through sunscreen use. This prospective study examined the effects of sport, setting (practice vs. competition), gender, age and geographic location on sunscreen use and education among youth athletes in various sports. Six hundred and twelve athletes ≤18 years old completed an online survey on sunscreen education and use during competitions and practices. Regardless of sport, reported sunscreen use was higher during practices than competition (p < 0.0001). Sunscreen was used most by swimmers/divers (odds ratio: OR ≥ 1.9, p < 0.001) and least by American football players (OR ≤ 0.57, p ≤ 0.001). Coaches mentioned sunscreen use the most in track and field (OR 1.84, p = 0.001) and the least in American football (OR 0.67, p = 0.03). Athletes used sunscreen more if they were female (OR ≥ 1.9 1.38, p ≤ 0.06) and younger (age OR ≤ 0.88, p < 0.001). In conclusion, youth athletes differ in sunscreen use by sport and setting, highlighting the need for continued photoprotective education.

Waste to energy: a decision-making process for technology selection through characterization of waste, considering energy and emission in the city of Ahmedabad, India.

Municipal solid waste (MSW) disposal has become major issue for the city of Ahmedabad, India. Development, concentrated population and economic growth have led to a substantial increase of MSW generation. Therefore, the objective of the study was to characterize MSW for selection of waste processing technology. To provide a solution for sustainable processing and for safe disposal of fresh MSW, Abellon Clean Energy Ltd joined forces with Ahmedabad Municipal Corporation (AMC) under Public-Private Partnership (PPP) to establish a 14.9MW advanced controlled combustion-based waste to energy (WTE) generation facility to process and dispose 1000 tons/day of fresh MSW. For waste characterization, samples (n=201) were collected from the Pirana waste dumping site using quadrate sampling method. A yearly weighted average Low Heating Value (LHV) of 9.85/kg and ash content 25.12% for unsegregated MSW makes controlled combustion with electricity generation an eligible technology. After combustion, the waste volume is reduced by 75%. The 14.9MW WTE facility replaces 417 t coal/day, reducing greenhouse gas (GHG) emissions of 300.38 tCO2eq/day through coal replacement, while avoiding 735.24 t CO2eq/day on account of landfill emissions from MSW dumping. Waste to energy is the fastest solution to reduce waste volume by generating electricity through reduction of GHG.

XCVATR: detection and characterization of variant impact on the Embeddings of single -cell and bulk RNA-sequencing samples.

BACKGROUND: RNA-sequencing has become a standard tool for analyzing gene activity in bulk samples and at the single-cell level. By increasing sample sizes and cell counts, this technique can uncover substantial information about cellular transcriptional states. Beyond quantification of gene expression, RNA-seq can be used for detecting variants, including single nucleotide polymorphisms, small insertions/deletions, and larger variants, such as copy number variants. Notably, joint analysis of variants with cellular transcriptional states may provide insights into the impact of mutations, especially for complex and heterogeneous samples. However, this analysis is often challenging due to a prohibitively high number of variants and cells, which are difficult to summarize and visualize. Further, there is a dearth of methods that assess and summarize the association between detected variants and cellular transcriptional states. RESULTS: Here, we introduce XCVATR (eXpressed Clusters of Variant Alleles in Transcriptome pRofiles), a method that identifies variants and detects local enrichment of expressed variants within embedding of samples and cells in single-cell and bulk RNA-seq datasets. XCVATR visualizes local "clumps" of small and large-scale variants and searches for patterns of association between each variant and cellular states, as described by the coordinates of cell embedding, which can be computed independently using any type of distance metrics, such as principal component analysis or t-distributed stochastic neighbor embedding. Through simulations and analysis of real datasets, we demonstrate that XCVATR can detect enrichment of expressed variants and provide insight into the transcriptional states of cells and samples. We next sequenced 2 new single cell RNA-seq tumor samples and applied XCVATR. XCVATR revealed subtle differences in CNV impact on tumors. CONCLUSIONS: XCVATR is publicly available to download from https://github.com/harmancilab/XCVATR .

A Scoping Review on the Concept of Physician Caring.

BACKGROUND: Physicians' interest in the health and well-being of their patients is a tenet of medical practice. Physicians' ability to act upon this interest by caring for and about their patients is central to high-quality clinical medicine and may affect burnout. To date, a strong theoretical and empirical understanding of physician caring does not exist. To establish a practical, evidence-based approach to improve health care delivery and potentially address physician burnout, we sought to identify and synthesize existing conceptual models, frameworks, and definitions of physician caring. METHODS: We performed a scoping review on physician caring. In November 2019 and September 2020, we searched PubMed MEDLINE, Embase, PsycINFO, CINAHL, and CENTRAL Register of Controlled Trials to identify conceptual models, frameworks, and definitions of physician caring. Eligible articles involved discussion or study of care or caring among medical practitioners. We created a content summary and performed thematic analysis of extracted data. RESULTS: Of 11,776 articles, we reviewed the full text of 297 articles; 61 articles met inclusion criteria. Commonly identified concepts referenced Peabody's "secret of care" and the ethics of care. In bioethics, caring is described as a virtue. Contradictions exist among concepts of caring, such as whether caring is an attitude, emotion, or behavior, and the role of relationship development. Thematic analysis of all concepts and definitions identified six aspects of physician caring: (1) relational aspects, (2) technical aspects, (3) physician attitudes and characteristics, (4) agency, (5) reciprocity, and (6) physician self-care. DISCUSSION: Caring is instrumental to clinical medicine. However, scientific understanding of what constitutes caring from physicians is limited by contradictions across concepts. A unifying concept of physician caring does not yet exist. This review proposes six aspects of physician caring which can be used to develop evidence-based approaches to improve health care delivery and potentially mitigate physician burnout.

A longitudinal study of menthol cigarette use and smoking cessation among adult smokers in the US: Assessing the roles of racial disparities and E-cigarette use.

Using nationally representative longitudinal data from Wave 1 to Wave 4 of the Population Assessment of Tobacco and Health Study in the United States, we examined whether the association between menthol cigarette use and smoking cessation was modified by race/ethnicity and e-cigarette use. Multivariable discrete-time survival models were fit to an unbalanced person-period data set (person n = 7423, risk period n = 18,897) for adult respondents (ages 25+) who were current established cigarette smokers at baseline. We found that adults who smoke menthol cigarettes had lower odds of smoking cessation, but the effect was modified by race/ethnicity as non-Hispanic (NH) Black menthol smokers had lower odds of quitting smoking than NH White or Hispanic menthol smokers. We also found that e-cigarette use was associated with higher odds of smoking cessation among both menthol and non-menthol smokers, but the association was stronger among menthol smokers. Our results suggest that a menthol smoking ban may have a favorable impact on smoking cessation for NH Black adults. In addition, our results also suggest that a menthol smoking ban may be more effective if menthol smokers have access to e-cigarettes as a way to quit cigarette use.

Low-voltage area substrate modification for atrial fibrillation ablation: a systematic review and meta-analysis of clinical trials.

AIMS: The value of additional ablation beyond pulmonary vein isolation for atrial fibrillation (AF) ablation is unclear, especially for persistent AF. The optimal target for substrate modification to improve outcomes is uncertain. We investigate the utility of low-voltage area (LVA) substrate modification in patients undergoing catheter ablation for AF. METHODS AND RESULTS: This meta-analysis was reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Medline, Scopus and Cochrane Central Register of Controlled Trials were systematically searched to identify relevant studies. Risk of bias was assessed using the Cochrane risk of bias tool. Only randomized studies were included. AF patients who underwent catheter ablation with voltage-guided substrate modification targeting LVA (LVA group) vs. conventional ablation approaches not targeting LVA (non-LVA group) were compared. Four studies comprising 539 patients were included (36% female). Freedom from arrhythmia (FFA) in patients with persistent AF was greater in the LVA group [risk ratio (RR) 1.30; 95% confidence interval (CI) 1.03-1.64]. There was no difference in FFA in patients with paroxysmal AF between groups (RR 1.30; 95% CI 0.89-1.91). There was no difference in total procedural time (mean difference -17.54 min; 95% CI -64.37 to 29.28 min) or total ablation time (mean difference -36.17 min; 95% CI -93.69 to 21.35 min) in all included patients regardless of AF type between groups. There was no difference in periprocedural complications between groups in all included patients regardless of AF type (RR 0.93; 95% CI 0.22-3.82). CONCLUSION: This meta-analysis demonstrates improved FFA in persistent AF patients who underwent voltage-guided substrate modification targeting LVA.