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To assess the predictive significance of blood neutrophil count and the ratio between neutrophil and lymphocyte count (neutrophil-to-lymphocyte ratio [NLR]) for disease severity and mortality in systemic sclerosis (SSc).Neutrophil and lymphocyte counts were prospectively measured in the Genetics versus Environment in Scleroderma Outcome Study (GENISOS) and the Scleroderma Lung Study II (SLS II). Forced vital capacity percent predicted (FVC%) and modified Rodnan skin thickness score (MRSS) were used as surrogate measures for disease severity. Longitudinal analyses were performed using generalized linear mixed models. Cox proportional hazards models evaluated the predictive significance of these cell counts for mortality.Of the 447 SSc patients in the GENISOS cohort at the time of analysis, 377 (84.3%) had available baseline blood neutrophil and lymphocyte counts. Higher baseline neutrophil count and NLR predicted lower serially obtained FVC% (b = -4.74, P = 0.009 and b = -2.68, P = 0.028, respectively) and higher serially obtained MRSS (b = 4.07, P 0.001 and b = 2.32, P 0.001, respectively). Longitudinal neutrophil and NLR measurements also significantly correlated with lower concurrently obtained FVC% measurements and higher concurrently obtained MRSS. Baseline neutrophil count and NLR predicted increased risk of long-term mortality, even after adjustment for baseline demographic and clinical factors (hazard ratio [HR] 1.42, P = 0.02 and HR 1.48, P 0.001, respectively). The predictive significance of higher baseline neutrophil count and NLR for declining FVC% and increased long-term mortality was confirmed in the SLS II.Higher blood neutrophil count and NLR are predictive of more severe disease course and increased mortality, indicating that these easily obtainable laboratory studies might be a reflection of pathologic immune processes in SSc.

Background: Symptom burden differences may contribute to racial disparities in breast cancer survival. We compared symptom changes from before to during chemotherapy among women with breast cancer. Methods: This observational study followed a cohort of Black and White women diagnosed with Stage I–III, hormone receptor–positive breast cancer from a large cancer center in 2007 to 2015, and reported symptoms before and during chemotherapy. We identified patients who experienced a one-standard deviation (SD) increase in symptom burden after starting chemotherapy using four validated composite scores (General Physical Symptoms, Treatment Side Effects, Acute Distress, and Despair). Kitagawa–Blinder–Oaxaca decomposition was used to quantify race differences in symptom changes explained by baseline characteristics (sociodemographic, baseline scores, cancer stage) and first-line chemotherapy regimens. Results: Among 1,273 patients, Black women (n = 405, 31.8%) were more likely to report one-SD increase in General Physical Symptoms (55.6% vs. 48.2%, P = 0.015), Treatment Side Effects (74.0% vs. 63.4%, P < 0.001), and Acute Distress (27.4% vs. 20.0%, P = 0.010) than White women. Baseline characteristics and first-line chemotherapy regimens explained a large and significant proportion of the difference in Acute Distress changes (93.7%, P = 0.001), but not General Physical Symptoms (25.7%, P = 0.25) or Treatment Side Effects (16.4%, P = 0.28). Conclusions: Black women with early-stage breast cancer were more likely to experience significant increases in physical and psychological symptom burden during chemotherapy. Most of the difference in physical symptom changes remained unexplained by baseline characteristics, which suggests inadequate symptom management among Black women. Impact: Future studies should identify strategies to improve symptom management among Black women and reduce differences in symptom burden. See related commentary by Rosenzweig and Mazanec, p. 157

Calcium transfer into the mitochondrial matrix during sarcoplasmic reticulum (SR) Ca2+ release is essential to boost energy production in ventricular cardiomyocytes (VCMs) and match increased metabolic demand. Mitochondria from female hearts exhibit lower mito-[Ca2+] and produce less reactive oxygen species (ROS) compared to males, without change in respiration capacity. We hypothesized that in female VCMs, more efficient electron transport chain (ETC) organization into supercomplexes offsets the deficit in mito-Ca2+ accumulation, thereby reducing ROS production and stress-induced intracellular Ca2+ mishandling. Experiments using mitochondria-targeted biosensors confirmed lower mito-ROS and mito-[Ca2+] in female rat VCMs challenged with β-adrenergic agonist isoproterenol compared to males. Biochemical studies revealed decreased mitochondria Ca2+ uniporter expression and increased supercomplex assembly in rat and human female ventricular tissues vs male. Importantly, western blot analysis showed higher expression levels of COX7RP, an estrogen-dependent supercomplex assembly factor in female heart tissues vs males. Furthermore, COX7RP was decreased in hearts from aged and ovariectomized female rats. COX7RP overexpression in male VCMs increased mitochondrial supercomplexes, reduced mito-ROS and spontaneous SR Ca2+ release in response to ISO. Conversely, shRNA-mediated knockdown of COX7RP in female VCMs reduced supercomplexes and increased mito-ROS, promoting intracellular Ca2+ mishandling. Compared to males, mitochondria in female VCMs exhibit higher ETC subunit incorporation into supercomplexes, supporting more efficient electron transport. Such organization coupled to lower levels of mito-[Ca2+] limits mito-ROS under stress conditions and lowers propensity to pro-arrhythmic spontaneous SR Ca2+ release. We conclude that sexual dimorphism in mito-Ca2+ handling and ETC organization may contribute to cardioprotection in healthy premenopausal females.

Coping in the context of racial-ethnic discrimination is often framed as an individualistic process, where the focus is on how the individual deals with the racialized stressor to mitigate its negative effects. However, individuals exist within social contexts including the family and coping processes may operate interdependently as well. Further, racialized stressors have the potential to disrupt the entire family system, regardless of whether the experience in that moment is shared among all its members. Despite these realities, few studies have considered how Latinx youth and their parents may cope together in the face of racial-ethnic discrimination. To address this gap, we analyzed focus group data from Mexican-origin adolescents (n = 17; Mage = 12.8; 71% girls) and their parents (n = 17; Mage = 42.8; 82% mothers) to explore the coping strategies used in response to racial-ethnic discrimination. An inductive thematic analysis identified a broad range of coping strategies representing both individualistic and interdependent approaches to deal with racial-ethnic discrimination. Strategies included (a) reframing (with pride) and ignoring an encounter, (b) standing up for oneself, (c) talking issues out, (d) problem-solving together, and (e) protection tactics. These findings provide evidence for the ways in which Mexican-origin families help adolescents cope with racial-ethnic discrimination and offer a glimpse as to how adolescents may help their families cope as well. Future research is needed to further explore the interdependent nature of coping as Latinx family members protect and support one another in the face of pervasive racialized stressors. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

This study aims to better understand how racially/ethnically minoritized youth exhibit adaptive psychological functioning (less anxiety) and health behaviors (better sleep and less binge drinking) in the context of discrimination, ethnic-racial identity and coping. Among 364 minoritized emerging adults (M

The objective of this study was to assess the predictive significance of anti-Scl-70 (anti-topoisomerase I) antibodies, as determined by three different methods, for decline in forced vital capacity (FVC) within the first year of follow-up in patients with systemic sclerosis (SSc)-related interstitial lung disease (ILD).Patients in the Genetics Versus Environment in Scleroderma Outcome Study cohort who had ILD (verified by imaging) and available FVC% at enrollment, plus 12 to 18 months thereafter, were examined. All patients had a disease duration of 5 years or less at enrollment. The annualized percentage change in FVC% at 1 year follow-up was the outcome variable. Anti-Scl-70 antibodies were determined by passive immunodiffusion (ID) against calf thymus extract, chemiluminescent immunoassay (CIA), and line blot immunoassay (LIA).Ninety-one patients with a mean disease duration of 2.36 years were included. Anti-Scl-70 antibodies by ID predicted a faster rate of FVC% decline (b = -0.06, P = 0.04). None of the other clinical or serological variables significantly predicted ILD progression. Interestingly, anti-Scl-70 antibodies as determined by CIA and LIA were not significant predictors of FVC decline (P = 0.26 and 0.64, respectively). The observed level of agreement between ID and LIA was moderate (κ = 0.568), whereas it was good between ID and CIA (κ = 0.66).Anti-Scl-70 antibodies determined by ID predicted faster FVC decline in patients with SSc-related ILD. Notably, both CIA and LIA for the same antibody did not predict rate of FVC decline at their current cutoffs of positivity. The discrepancy observed between anti-Scl-70 antibody assays can have relevant implications for clinical care and trial enrichment strategies in SSc-ILD.

Critical civic engagement (CCE) refers to interpersonal, community, and political actions to combat and cope with racial inequity. While discrimination and identity are well-known drivers of civic engagement, it is less well-known how parental preparation for bias socialization, which teaches Black youth how to cope with unequal social systems, works in concert with discrimination and identity to predict CCE. Furthermore, there are several ways individuals may be civically engaged, and these factors may be differentially associated with the various types of CCE. This study uses a sample of 186 Black college students (

BackgroundCOVID-19 was declared a global pandemic in March 2020. Early reports were primarily in adults, and sickle cell disease (SCD) was classified as a risk factor for severe COVID-19 disease. However, there are a limited number of primarily multi-center studies reporting on the clinical course of pediatric patients with SCD and COVID-19.MethodsWe conducted an observational study of all patients with SCD diagnosed with COVID-19 at our institution between March 31, 2020, and February 12, 2021. Demographic and clinical characteristics of this group were collected by retrospective chart review.ResultsA total of 55 patients were studied, including 38 children and 17 adolescents. Demographics, acute COVID-19 clinical presentation, respiratory support, laboratory findings, healthcare utilization, and SCD modifying therapies were comparable between the children and adolescents. Seventy-three percent (N = 40) of all patients required emergency department care or hospitalization. While 47% (N = 26) were hospitalized, only 5% (N = 3) of all patients required intensive care unit admission. Patients frequently had concurrent vaso-occlusive pain crisis (VOC) (N = 17, 43%) and acute chest syndrome (ACS) (N = 14, 35%). Those with ACS or an oxygen requirement had significantly higher white blood cell count, lower nadir hemoglobin, and higher D-dimers, supporting a pro-inflammatory and coagulopathic picture. Non-hospitalized patients were more likely to be on hydroxyurea than hospitalized patients (79 vs. 50%, p = 0.023).ConclusionChildren and adolescent patients with SCD and acute COVID-19 often present with ACS and VOC pain requiring hospital-level care. Hydroxyurea treatment appears to be protective. We observed no mortality despite variable morbidity.

Racial-ethnic inequity is deeply entrenched in U.S. social systems, yet adolescents’ voices and understanding around inequity are not often directly examined. The current qualitative study uses focus group data from African American ( n = 21), Chinese- ( n = 17), Indian- ( n = 13), and Mexican- ( n = 17) origin adolescents ( Mage = 12.93 years; SD = 1.23; 51% boys) to provide insight on how youth navigate their attitudes and beliefs about these issues. Using a racial-ethnic socialization lens, we explore proximal (e.g., parents, peers, teachers) and distal (e.g., media, society) ways in which adolescents come to understand racial-ethnic inequity. Three themes characterized adolescents’ discussions. School diversity, of peers and of thought, and messages around egalitarianism were two prominent influences on their perceptions. A third theme related to perceptions of social hierarchies, which appeared to be shaped by stereotypes, peer interactions, and ideas about inequity itself. Emergent themes suggest that the school context is a particularly salient social setting that encompasses multiple sources of socialization (e.g., teachers, classmates, academics, climate), and parents, peers, and the media also play prominent roles.

The objective of this study was to assess the feasibility, acceptability, and potential efficacy of ENABLE (Educate, Nurture, Advise, Before Life Ends) Cornerstone-a lay navigator-led, early palliative care telehealth intervention for African American/Black and/or rural-dwelling family caregivers of individuals with advanced cancer (ClinicalTrials.gov identifier NCT03464188).This was a pilot randomized trial (November 2019 to March 2021). Family caregivers of patients with newly diagnosed, stage III/IV, solid-tumor cancers were randomized to receive either an intervention or usual care. Intervention caregivers were paired with a specially trained lay navigator who delivered 6 weekly, 20-minute to 60-minute telehealth coaching sessions plus monthly follow-up for 24 weeks, reviewing skills in stress management, self-care, getting help, staying organized, and future planning. Feasibility was assessed according to the completion of sessions and questionnaires (predefined as a completion rate ≥80%). Acceptability was determined through intervention participants' ratings of their likelihood of recommending the intervention. Measures of caregiver distress and quality of life were collected at 8 and 24 weeks.Sixty-three family caregivers were randomized (usual care, n = 32; intervention, n = 31). Caregivers completed 65% of intervention sessions and 87% of questionnaires. Average ratings for recommending the program were 9.4, from 1 (not at all likely) to 10 (extremely likely). Over 24 weeks, the mean ± SE Hospital Anxiety and Depression Scale score improved by 0.30 ± 1.44 points in the intervention group and worsened by 1.99 ± 1.39 points in the usual care group (difference, -2.29; Cohen d, -0.32). The mean between-group difference scores in caregiver quality of life was -1.56 (usual care - intervention; d, -0.07). Similar outcome results were observed for patient participants.The authors piloted ENABLE Cornerstone, an intervention for African American and rural-dwelling advanced cancer family caregivers. The acceptability of the intervention and data collection rates were high, and the preliminary efficacy for caregiver distress was promising.To date, very few programs have been developed to support under-resourced cancer family caregivers. To address this need, the authors successfully pilot tested an early palliative care program, called Educate, Nurture, Advise, Before Life Ends (ENABLE) Cornerstone, for African American and rural family caregivers of individuals with advanced cancer. Cornerstone is led by specially trained lay people and involves a series of weekly phone sessions focused on coaching caregivers to manage stress and provide effective support to patients with cancer. The authors are now testing Cornerstone in a larger trial. If the program demonstrates benefit, it may yield a model of caregiver support that could be widely implemented.

ObjectiveThis scoping review of reviews aims to describe the current landscape of measures of emotional well-being (EWB).MethodsFollowing established practices for scoping reviews, we searched the PsycInfo, ERIC, Scopus and PubMed databases in June and July 2021 for reviews of measures of EWB that described their review methods and psychometric properties of included measures. From each eligible article, two coders independently extracted the authors’ (1) definition of EWB, (2) purpose for the review, (3) methods (eg, search terms, inclusion and exclusion criteria), (4) identified measures (including any noted adaptations) and (5) the scope of psychometric information presented. Descriptive and content analyses were used to examine data.ResultsForty-nine reviews were included in this scoping review. Reviews included anywhere between 1 and 34 measures of EWB and 135 unique EWB measures were captured across all reviews. We found that there was no consistent definition of EWB, identified measures varied widely and reviews were published in a range of disciplines. Psychometric evidence varied as did authors’ purposes for conducting the reviews.ConclusionsOverall, these reviews suggest that literature on EWB measurement is disjointed and diffuse. Conceptual integration and harmonisation of measures is needed to advance knowledge of EWB and its measurement.Trial registration numbers10.17605/OSF.IO/BQDS7 and 10.17605/OSF.IO/WV8PF.

Objectives Based on the conceptual overlap between shift-&-persist (S&P) and culturally based strategies (critical civic engagement [CCE] and spiritually based coping), this study tests whether associations between these three previously disparate strategies are attributable to the existence of a higher-order coping construct: culturally informed S&P. Methods Among 364 diverse minoritized youth (Mage = 18.79, 85.2% female), we tested for the existence of this higher-order factor through confirmatory factor analysis. Results We found theoretical and empirical support for the existence of a higher-order factor structure and for our higher-order factor-culturally informed S&P. Culturally informed S&P promotes fewer depressive symptoms as a main effect in addition to completely protecting against the negative impact of discrimination on depressive symptoms when culturally informed S&P is high. Conclusions The current study illustrates relations between three previously distinct coping strategies through their association with culturally informed S&P. Results highlight culturally informed S&P's promotive and protective effects in the face of ethnic-racial discrimination. Implications for subsequent study of culturally based coping are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19 pneumonia. We hypothesize that SARS-CoV-2 causes alveolar injury and hypoxemia by damaging mitochondria in airway epithelial cells (AEC) and pulmonary artery smooth muscle cells (PASMC), triggering apoptosis and bioenergetic impairment, and impairing hypoxic pulmonary vasoconstriction (HPV), respectively.We examined the effects of: A) human betacoronaviruses, SARS-CoV-2 and HCoV-OC43, and individual SARS-CoV-2 proteins on apoptosis, mitochondrial fission, and bioenergetics in AEC; and B) SARS-CoV-2 proteins and mouse hepatitis virus (MHV-1) infection on HPV.We used transcriptomic data to identify temporal changes in mitochondrial-relevant gene ontology (GO) pathways post-SARS-CoV-2 infection. We also transduced AECs with SARS-CoV-2 proteins (M, Nsp7 or Nsp9) and determined effects on mitochondrial permeability transition pore (mPTP) activity, relative membrane potential, apoptosis, mitochondrial fission, and oxygen consumption rates (OCR). In human PASMC, we assessed the effects of SARS-CoV-2 proteins on hypoxic increases in cytosolic calcium, an HPV proxy. In MHV-1 pneumonia, we assessed HPV via cardiac catheterization and apoptosis using the TUNEL assay.SARS-CoV-2 regulated mitochondrial apoptosis, mitochondrial membrane permeabilization and electron transport chain (ETC) GO pathways within 2 hours of infection. SARS-CoV-2 downregulated ETC Complex I and ATP synthase genes, and upregulated apoptosis-inducing genes. SARS-CoV-2 and HCoV-OC43 upregulated and activated dynamin-related protein 1 (Drp1) and increased mitochondrial fission. SARS-CoV-2 and transduced SARS-CoV-2 proteins increased apoptosis inducing factor (AIF) expression and activated caspase 7, resulting in apoptosis. Coronaviruses also reduced OCR, decreased ETC Complex I activity and lowered ATP levels in AEC. M protein transduction also increased mPTP opening. In human PASMC, M and Nsp9 proteins inhibited HPV. In MHV-1 pneumonia, infected AEC displayed apoptosis and HPV was suppressed. BAY K8644, a calcium channel agonist, increased HPV and improved SpOCoronaviruses, including SARS-CoV-2, cause AEC apoptosis, mitochondrial fission, and bioenergetic impairment. SARS-CoV-2 also suppresses HPV by targeting mitochondria. This mitochondriopathy is replicated by transduction with SARS-CoV-2 proteins, indicating a mechanistic role for viral-host mitochondrial protein interactions. Mitochondriopathy is a conserved feature of coronaviral pneumonia that may exacerbate hypoxemia and constitutes a therapeutic target.

Pneumoconiosis due to silicosis is still present due to modern industries such stone carving, garment industry, and road construction. We aim to discuss how to accurately diagnose silicosis, appropriately risk stratify patients with silicosis, and discuss potential new pharmacotherapies that may be of potential use in the future. Acute silicosis, chronic silicosis, and accelerated silicosis are 3 distinct clinical categories. Acute silicosis is the least common form and occurs with high exposures of silica dust in a short time frame. Patients with prolonged exposures at low concentrations have the highest risk of developing chronic silicosis. Chronic silicosis is the classic presentation of silicosis with a slow onset of symptoms. Accelerated silicosis has an earlier onset than chronic silicosis and presents within 5 to 10 years of exposure. Chronic silicosis and accelerated silicosis can lead to progressive massive fibrosis, which is silica nodules merging together with associated fibrosis. Based on cumulative dose, patients with silica exposure had an independent increased risk of developing lung cancer, with an additional cumulative risk among smokers. Lung transplant should be considered in patients with silicosis who develop severe lung disease. There is no current role for any pharmacological agents in silicosis; however, there is ongoing research to identify possible pharmacological agents. The diagnosis of silicosis is made based on occupational history, appropriate radiographic findings, and exclusion of other potential etiologies. Prevention of silica dust exposure remains crucial to reduce damage to the lungs.

Though lay navigation programs have proven beneficial for individuals during cancer treatment, little is known about the effects of lay navigation on health care utilization and Medicare spending among older adults during cancer survivorship. This retrospective cohort study used administrative claims data to evaluate a lay navigation program implemented from 2012 to 2015 at 12 academic and community cancer centers in the Southeast. Medicare beneficiaries age ≥65 years navigated during survivorship were compared to propensity score–matched, non-navigated cancer survivors. Quarterly trends in Medicare spending were estimated using repeated measures mixed models. Rate ratios (RRs) and 95% confidence intervals (CIs) were estimated using repeated measures generalized linear models for quarterly emergency room (ER) visits and hospitalizations. Medicare spending for navigated (n = 3255) versus non-navigated older cancer survivors (n = 3255) was initially higher but declined faster by $513 per patient per quarter (95% CI −$616, −$410). Per patient per quarter risk of ER visits decreased by 11% (RR 0.89, 95% CI 0.86, 0.92) and hospitalizations decreased by 16% (RR 0.84, 95% CI 0.81, 0.88) over time comparing navigated versus non-navigated patients. Similar results were seen for patients enrolled in navigation post-treatment (N = 1893). In older cancer survivors receiving care in the Deep South, patients receiving lay navigation compared to those non-navigated had significant reductions in Medicare spending, hospitalizations, and ER visits. Though much emphasis has been placed on lay navigation during initial cancer treatment, navigation is needed throughout survivorship due to the high costs and health care utilization that persist post-treatment.

Assess the feasibility, acceptability, and preliminary efficacy of a healthy lifestyle website, SurvivorSHINE ( www.survivorshine.org ), for cancer survivors using a mixed-methods approach. Formative research included a comprehensive literature review and four focus groups on website preferences with diagnosis-diverse cancer survivors (N = 17). Their feedback informed a web adaptation of a telephone counseling and mailed-print lifestyle intervention previously found effective for cancer survivors. The resulting web-based intervention was examined in a 3-week, single-arm trial among 41 cancer survivors. Assessments of physical activity, diet, body weight, and knowledge related to exercise and diet guidelines for cancer survivors occurred at baseline and 3 weeks later, along with exit interviews. Themes from focus groups indicated cancer survivors’ desire for easy-to-use, interactive web-based platforms to access credible diet and exercise information. The study sample was recruited within 12 months, and study retention was high (85.4%). Participants showed significant pre- to post-test improvements in diet and exercise knowledge (t = 5.31, p

Adjuvant endocrine therapy (AET) reduces breast cancer recurrence, but symptom burden is a key barrier to adherence. Black women have lower AET adherence and worse health outcomes than White women.To investigate the association between symptom burden and AET adherence differences by race.A retrospective cohort study using electronic health records with patient-reported data from a large cancer center in the US. Patients included Black and White women initiating AET therapy for early-stage breast cancer from August 2007 to December 2015 who were followed for 1 year from AET initiation. Sixty symptoms classified into 7 physical and 2 psychological symptom clusters were evaluated. For each cluster, the number of symptoms with moderate severity at baseline, and symptoms with 3-point or greater increases during AET were counted. Adherence was measured as the proportion of days covered by AET during the first-year follow-up. Multivariable regressions for patients' adherence adjusting for race, symptom measures, sociodemographic characteristics, and clinical characteristics were conducted. Kitagawa-Blinder-Oaxaca decomposition was used to quantify racial differences in adherence explained by symptoms and patient characteristics. Analyses were conducted from July 2021 to January 2022.Physical and psychological symptoms at baseline and changes during AET.Among 559 patients (168 [30.1%] Black and 391 [69.9%] White; mean [SD] age 65.5 [12.1] years), Black women received diagnoses younger (mean [SD] age at diagnosis, 58.7 [13.7] vs 68.5 [10.0] years old) than White women, with more advanced stages (30 Black participants [17.9%] vs 31 White participants [7.9%] had stage III disease at diagnosis), and lived in areas with fewer adults attaining high school education (mean [SD], 78.8% [7.8%] vs 84.0% [9.3%]). AET adherence in the first year was 78.8% for Black and 82.3% for White women. Black women reported higher severity in most symptom clusters than White women. Neuropsychological, vasomotor, musculoskeletal, cardiorespiratory, distress, and despair symptoms at baseline and increases during the follow-up were associated with 1.2 to 2.6 percentage points decreases in adherence, which corresponds to 4 to 9 missed days receiving AET in the first year. After adjusting for psychological symptoms, being Black was associated with 6.5 percentage points higher adherence than being White.In this cohort study, severe symptoms were associated with lower AET adherence. Black women had lower adherence rates that were explained by their higher symptom burden and baseline characteristics. These findings suggest that better symptom management with a focus on psychological symptoms could improve AET adherence and reduce racial disparities in cancer outcomes.

Rationale: Pulmonary arterial hypertension (PAH) often results in death from right ventricular failure (RVF). NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)-macrophage activation may promote RVF in PAH. Objectives: Evaluating the contribution of the NLRP3 inflammasome in RV macrophages to PAH RVF. Methods: Rats with decompensated RV hypertrophy (monocrotaline [MCT] and Sugen-5416 hypoxia [SuHx]) were compared with compensated RV hypertrophy rats (pulmonary artery banding). Echocardiography and right heart catheterization were performed. Macrophages, atrial natriuretic peptides, and fibrosis were evaluated by microscopy or flow cytometry. NLRP3 inflammasome activation and cardiotoxicity were confirmed by immunoblot and in vitro strategies. MCT rats were treated with SC-144 (a GP130 antagonist) or MCC950 (an NLRP3 inhibitor). Macrophage-NLRP3 activity was evaluated in patients with PAH RVF. Measurements and Main Results: Macrophages, fibrosis, and atrial natriuretic peptides were increased in MCT and SuHx RVs but not in left ventricles or pulmonary artery banding rats. Although MCT RV macrophages were inflammatory, lung macrophages were antiinflammatory. CCR2+ macrophages (monocyte-derived) were increased in MCT and SuHx RVs and highly expressed NLRP3. The macrophage-NLRP3 pathway was upregulated in patients with PAH with decompensated RVs. Cultured MCT monocytes showed NLRP3 activation, and in coculture experiments resulted in cardiomyocyte mitochondrial damage, which MCC950 prevented. In vivo, MCC950 reduced NLRP3 activation and regressed pulmonary vascular disease and RVF. SC-144 reduced RV macrophages and NLRP3 content, prevented STAT3 (signal transducer and activator of transcription 3) activation, and improved RV function without regressing pulmonary vascular disease. Conclusions: NLRP3-macrophage activation occurs in the decompensated RV in preclinical PAH models and patients with PAH. Inhibiting GP130 or NLRP3 signaling improves RV function. The concept that PAH RVF results from RV inflammation rather than solely from elevated RV afterload suggests a new therapeutic paradigm.

PURPOSE: In general, participation rates in cancer clinical trials are very low. However, participation rates are especially low among the socially disadvantaged and racial and ethnic minority groups. These groups have been historically under-represented in cancer clinical trials. Although many patient-related barriers have been studied, institutional factors that are essential for building clinical research infrastructure around the clinical trial enterprise in academic medical centers have been underexplored. MATERIALS AND METHODS: We assessed perspectives of cancer center professional stakeholders on the institutional factors that can potentially influence racial and ethnic minority recruitment for cancer clinical trials. Ninety-one qualitative interviews were conducted at five US cancer centers among four stakeholder groups: cancer center leaders, principal investigators, referring clinicians, and research staff. Qualitative analyses examined response data focused on institutional factors related to minority recruitment for cancer clinical trials. RESULTS: Four prominent themes emerged regarding institutional barriers among clinical and research professionals. (1) There are no existing programs currently being used to recruit or retain minorities to clinical trials. (2) Institutional efforts are needed to increase trial participation and are not specific to potential minority participants. (3) Access to cancer clinical trials and navigation within an Academic Medical Center need to be simplified to better facilitate recruitment of minority patients. (4) Community outreach by cancer centers will increase clinical research awareness in the community. CONCLUSION: Our research highlights the need to address institutional barriers to improve the success of minority recruitment. To increase participation among minority populations, medical centers must address mutable institutional barriers such as setting specific minority recruitment goals for cancer clinical trials, ensuring that cancer clinical trials are accessible, especially to minority patients, and supporting sustained community outreach programs to increase clinical research awareness.

Anorectal malformations (ARMs) have a wide spectrum of presentation ranging from mild defects with perineal fistulas to more severe defects requiring complex management. A primary repair of ARMs with perineal or rectovestibular fistulas has been shown to have good outcomes. However, the timing of the reconstruction is still debated. The aim of this study is to investigate the safety of early versus delayed repair.This study was performed using data from the National Surgical Quality Improvement Program-Pediatric (NSQIP-P) from 2012 to 2017. Patients who underwent repair of anorectal malformation with perineal or vestibular fistula were included in the study. Patients with associated diagnosis for Hirschsprung disease, cloaca, rectal prolapse or stenosis, bladder exstrophy, and tracheoesophageal fistula were excluded. 30-day postoperative outcomes included wound and nonwound complications, readmissions, and reoperations. Outcomes were compared by early (≤7 days of age) versus delayed repair (6 weeks to 8 months).A total of 291 patients were included, with 66 in the early and 231 in the delayed group. Patients in the early group were more likely to be male (68.2% vs 31.8%; p 0.01) and have cardiac risk factors (71.2% vs 49.4%, p 0.01). The mean operative time was significantly shorter in the early group (90.1 vs 129.6 min; p 0.01). 30-day complications were not statistically significant between the two groups (p = 0.76). After multivariate analysis, timing of repair did not affect 30-day complications (p = 0.15).Our study shows that early repair of low anorectal malformations with a perineal or vestibular fistula appears to be associated with no increase in risk of postoperative complications as compared to delayed repair. At present, the decision remains dependent on the surgeon's experience and judgment.Level III. Retrospective comparative study.

Lung cancer is one of the most common and deadliest cancers affecting millions of men and women worldwide. Historically, lung cancer predominantly affects men, but in recent years there have been significant changes in the epidemiology of lung cancer among women. Additionally, further understanding of lung cancer has changed our approach to the diagnosis and management of lung cancer. This article aims to discuss recent changes in lung cancer among women including incidence, mortality, risk factors, diagnosis, staging, treatment, and prognosis. The incidence of lung cancer among women is declining overall but at a significantly slower rate compared to men. The implementation of smoking prevention and cessation efforts has decreased the incidence of cigarette smoking of the past 50 years which has revealed other important risk factors for developing lung cancer. Additionally, new algorithms for diagnosis and staging have led to further changes in management strategies for lung cancer. Lung cancer among women is a growing concern with incidence rates decreasing significantly slower compared to men. Risk factors such as age, race, socioeconomic status, and geographic locations are becoming more apparent as important variables in the development of lung cancer among women. Lastly, new advancements in diagnosis, staging, and management are likely to result in improved short- and long-term prognosis in patients with lung cancer.

INTRODUCTION The safety of bronchoscopy in obese patients and those with obstructive sleep apnea (OSA) is unclear. Our objective was to evaluate the incidence of complications during bronchoscopy under moderate sedation in obese patients and to assess the impact of OSA, body mass index (BMI), and duration of the procedure. METHODS We performed a retrospective study in adult patients undergoing bronchoscopy from January 2010 to August 2019. All patients with BMI > 30 kg/m2 were included. Logistic regression analyses were used to identify the factors associated with all-complications and respiratory complications. RESULTS A total of 345 obese patients were identified. The average BMI in our cohort was 35.3 ± 5.1 kg/m2 . During the pre-procedure risk assessment, 165 (47.8%) patients were labelled as "suspected OSA." The most common doses of sedation given during the bronchoscopies were fentanyl 50 mcg (34.5%) and midazolam 3 mg (33.6%). The incidence of major complications was 0.6% and minor complications were 41.2%. Minor respiratory (22.9%) and cardiac (26.4%) complications were common. No deaths occurred due to bronchoscopy. Factors that were associated with increased respiratory complications were female gender, suspected OSA, and bronchoscopy duration 20-30 minutes and bronchoscopy duration greater than 1 hour. CONCLUSION Bronchoscopy under moderate sedation performed in obese patients is safe; however, increased risk may exist with females, increased procedure time, and suspected OSA.

Objetivo: verificar como o conhecimento sobre os bundles de prevenção de pneumonia associada à ventilação mecânica interfere na prática profissional e na incidência de casos. Método: estudo do tipo pesquisa-intervenção, com abordagem quantitativa, conduzido em um grande hospital público de emergência do Município de Rio de Janeiro-RJ. A coleta de dados foi realizada nas unidades de terapia intensiva da instituição, entre outubro e novembro de 2017. Resultados: Participaram do estudo 71 profissionais de saúde. Verificamos que 100% dos participantes classificaram a intervenção como relevante, 63,24% apontaram a estratégia utilizada como muito adequada e 95,65% relataram que a intervenção poderia mudar sua prática profissional. No mês seguinte à realização do estudo houve queda no número de casos de pneumonia geral e de pneumonia associada à ventilação mecânica. Conclusão: foi possível avaliar o impacto da intervenção na prática profissional dos participantes.

This study analyzed a new drying method using airborne ultrasound combined with microwave vacuum to study its effect on the quality characteristics and microstructure of dehydrated L. edodes. Ultrasonic treatment resulted in many micropores in the product, forming the sponge effect caused by ultrasonic waves, which can promote the rapid evaporation of water in the product. Samples of Lentinula edodes individuals were dried using four methods: hot air drying (HAD), microwave vacuum drying (MVD), microwave vacuum drying after ultrasonic pretreatment (US+MVD) and airborne ultrasonic treatment combined with microwave vacuum drying (USMVD). The results showed that USMVD can reduced the loss of total sugar, total phenol, and total antioxidants in L. edodes, and increased the relative content of ergosterol, sulfur compounds, and free amino acids (p < 0.05). Scanning electron microscope observation revealed that USMVD resulted in a uniform reticular porous structure, which could better maintain desirable levels of nutrients. Therefore, USMVD can produce high quality products. PRACTICAL APPLICATION: Airborne ultrasonic waves combined with MVD provides an innovative drying method for mushrooms, which has not been studied at present. The mixed drying method has great potential in maintaining product quality. It provides a theoretical basis for studying drying technology in the future.

PURPOSE: To qualitatively explore exercise barriers and facilitators experienced by rural female cancer survivors from the program interventionist and recipient perspective for the purpose of enhancing exercise program implementation and uptake in rural settings. METHODS: A descriptive qualitative study design was utilized. Focus groups were conducted prior to implementation of an evidence-based exercise program by a rural non-research cancer clinical site. Nineteen rural female cancer survivors (mean age = 61.7 ± 10.9 years) and 11 potential interventionists (mean age = 42.3 ± 15.3 years) completed focus groups (stratified by participant role). Focus groups were audio recorded, transcribed, coded, and analyzed using inductive thematic analysis with NVivo 11. RESULTS: Cancer survivors identified twelve barrier themes (cancer specific adverse effects, lack of support, lack of knowledge, perceived negative aspects of exercise, cost, lack of resources, motivation, inconvenience, lack of program flexibility, time, weather, safety) and eight facilitator themes (knowledge, ease of access, resources, awareness, cost, options, organized, fun) related to exercise. Interventionists identified seven barrier themes (cost, transportation, lack of cancer survivor and interventionist knowledge, fear, motivation, lack of support, lack of resources) and four facilitator themes (resources, support, knowledge, motivation). Narratives revealed differing role-specific perspectives on shared themes between survivors and interventionists as well as potential implementation strategies for enhancing exercise participation and exercise program uptake among rural female cancer survivors. CONCLUSION: Exploring multi-level stakeholder perspectives on cancer survivors’ exercise needs and related strategies yields important information for organizations to consider when implementing exercise programs in rural contexts.

Radiation treatment interruption associated with unplanned hospitalization remains understudied. The intent of this study was to benchmark the frequency of hospitalization-associated radiation therapy interruptions (HARTI), characterize disease processes causing hospitalization during radiation, identify factors predictive for HARTI, and localize neighborhood environments associated with HARTI at our academic referral center.This retrospective review of electronic health records provided descriptive statistics of HARTI event rates at our institutional practice. Uni- and multivariable logistic regression models were developed to identify significant factors predictive for HARTI. Causes of hospitalization were established from primary discharge diagnoses. HARTI rates were mapped according to patient residence addresses.Between January 1, 2015, and December 31, 2017, 197 HARTI events (5.3%) were captured across 3729 patients with 727 total missed treatments. The 3 most common causes of hospitalization were malnutrition/dehydration (n = 28; 17.7%), respiratory distress/infection (n = 24; 13.7%), and fever/sepsis (n = 17; 9.7%). Factors predictive for HARTI included African-American race (odds ratio [OR]: 1.48; 95% confidence interval [CI], 1.07-2.06;HARTI disproportionately affected socioeconomically disadvantaged urban patients facing a high treatment burden in our catchment population. A complementary geospatial analysis also captured the risk experienced by middle-income suburban patients independent of race or insurance status. Confirmatory studies are warranted to provide scale and context to guide intervention strategies to equitably reduce HARTI events.

Background Scalable, multiple behavior change interventions are needed to address poor diet, inactivity, and excess adiposity among the rising number of cancer survivors. Efficacy-tested diet (RENEW) and exercise (BEAT Cancer) programs were adapted for web delivery among middle-aged and older cancer survivors for the AMPLIFI study, a National Cancer Institute-funded, multi-site, program project. Methods Throughout the continental U.S., survivors of several obesity-related cancers are being recruited for three interconnected randomized controlled trials (RCTs). Projects 1 and 2 test 6-month diet or exercise interventions versus a wait-list control condition. Upon completion of the 6-month study period, the intervention participants receive the next behavior change sequence (i.e., diet receives exercise, exercise receives diet) and the wait-list control arm initiates a 12-month combined diet and exercise intervention. Project 3 tests the efficacy of the sequential versus simultaneous interventions. Assessments occur at baseline and semi-annually for up to 2-years and include: body mass index, health behaviors (diet quality, accelerometry-assessed physical activity/sleep), waist circumference, D3 creatine-assessed muscle mass, physical performance, potential mediators/moderators of treatment efficacy, biomarkers of inflammation and metabolic regulation, health care utilization, cost, and overall health. Four shared resources support AMPLIFI RCTs: 1) Administrative; 2) Adaptation, Dissemination and Implementation; 3) Recruitment and Retention; and 4) Assessment and Analysis. Discussion Representing a new generation of RCTs, AMPLIFI will exclusively use remote technologies to recruit, intervene and assess the efficacy of the newly-adapted, web-based diet and exercise interventions and determine whether sequential or combined delivery works best for at-risk (older, rural, racial minority) cancer survivors. Trial registration ClinicalTrials.gov, NCT04000880. Registered 27 June 2019.

Case Presentation A 35-year-old woman with no known medical history presented to the ED with complaints of progressive dyspnea for several months. The patient also reported episodic cough with yellow to green sputum production. She denied fever, chills, weight loss, or hemoptysis. She also denied any history of previous lung diseases in her family. She denied any history of tobacco or recreational drug use or any exposures. She was originally from El Salvador and immigrated to the United States approximately 3 years earlier. She was evaluated in El Salvador at age 15 for "lung issues" but had never received a formal diagnosis.

The 2016–2017 Inaugural Class of the Society of Behavioral Medicine Leadership Institute (SBM LI) debuted to an eager team of 36 mid-career fellows led by energetic mentors, professional coaches, and career development experts. Fellows were divided into learning communities of eight participants for deeper engagement. Our “Green Team” learning community bonded quickly and actively committed to our collective progress and projects. Upon returning home from the in-person sessions, our activities included monthly team conference calls and consultation with our mentors and selected coaches. The Green Team regularly communicated throughout the year, giving feedback to each other about our projects to be presented at the 2017 SBM Annual Meeting. We also discussed our mentoring and coaching experiences, leadership skills put to use at our institutions, and personal development. Contact continued via social media, email, teleconferencing, and collaborations at other professional meetings. The Green Team utilized the Tuckman and Jensen model of small group development to describe how we developed into a high-functioning group that maximized the resources afforded by the SBM LI to yield successful leadership outcomes. This commentary will offer an example of how a productive SBM LI team works collaboratively to utilize its mentors and resources for professional development.

This review article aims to highlight the common and uncommon imaging features of work-related and environmental lung disease to help the clinicians suspect diagnosis in patients with occult or known exposures to inhalational potent substances. Occupational and environmental lung disease are the most frequent work-related illness in the USA with a recent resurgence mainly due to inadequate exposure control, prolonged working hours, developing industries, and new antigens. Failure to accurately diagnose and promptly manage these lung disorders can lead to long-term and irreversible health conditions. Several case reports have documented misdiagnosis of these lung disorders which could be due to underestimation of their prevalence. It is critical for radiologist and clinicians to recognize the classic and uncommon imaging features of occupational and environmental lung diseases. Accurate elicitation of occupational history is a key point for differentiation in this patient population.

Indonesia dikenal sebagai Negara dengan sumber daya alam yang melimpah, termasuk dibagian industri perikanan dan kelautan, yang dimana di setiap tahunnya tingkat konsumsi ikan meningkat disetiap tahunnya. Dengan meningkatnya kebutuhan ikan disetiap tahunnya, dibutuhkan alat tangkap ikan yang lebih efisien demi memenuhi permintaan produktivitas tersebut, salah satunya yaitu alat bantu tangkap ikan, yaitu fishing deck machinery tipe hidrolik. Alat ini menggunakan roda gigi untuk dapat memutar tiang pengangkatnya. Berdasarkan fungsi tersebut, komponen roda gigi menjadi bagian yang penting dalam menopang beban tiang dan kompoenen lainnya yang bergerak memutar. Roda gigi yang dipakai adalah jenis roda gigi lurus. Untuk mendapatkan hasil analisis tegangan roda gigi menggunakan bantuan software Solidwork, sedangkan untuk desainnya digunakan software Inventor. Dengan mendapatkan hasil analisis tegangan roda gigi ini, dapat mengoptimalkan pemilihan dimensi serta material yang digunakan untuk aplikasinya.