Differences in outcomes by race/ethnicity after thoracic surgery in a large integrated health system.

Background: Disparities exist throughout surgery. We aimed to assess for racial/ethnic disparities among outcomes in a large thoracic surgery patient population. Methods: We reviewed all thoracic surgery patients treated at our integrated health system from January 1, 2016-December 31, 2020. Post-operative outcomes including length of stay (LOS), 30-day return to the emergency department (30d-ED), 30-day readmission, 30- and 90-day outpatient appointments, and 30- and 90-day mortality were compared by race/ethnicity. Bivariate analyses and multivariable logistic regression were performed. Our multivariable models adjusted for age, sex, body mass index, Charlson Comorbidity Index, surgery type, neighborhood deprivation index, insurance, and home region. Results: Of 2730 included patients, 59.4 % were non-Hispanic White, 15.0 % were Asian, 11.9 % were Hispanic, 9.6 % were Black, and 4.1 % were Other. Median (Q1-Q3) LOS (in hours) was shortest among non-Hispanic White (37.3 (29.2-76.1)) and Other (36.5 (29.3-75.4)) patients followed by Hispanic (46.8 (29.9-78.1)) patients with Asian (51.3 (30.7-81.9)) and Black (53.7 (30.6-101.6)) patients experiencing the longest LOS (p < 0.01). 30d-ED rates were highest among Hispanic patients (21.3 %), followed by Black (19.2 %), non-Hispanic White (18.1 %), Asian (13.4 %), and Other (8.0 %) patients (p < 0.01). On multivariable analysis, Hispanic ethnicity (Odds Ratio (OR) 1.43 (95 % CI 1.03-1.97)) and Medicaid insurance (OR 2.37 (95 % CI 1.48-3.81)) were associated with higher 30d-ED rates. No racial/ethnic disparities were found among other outcomes. Conclusions: Despite parity across multiple surgical outcomes, disparities remain related to patient encounters within our system. Health systems must track such disparities in addition to standard clinical outcomes. Key message: While our large integrated health system has been able to demonstrate parity across many major surgical outcomes among our thoracic surgery patients, race/ethnicity disparities persist including in the number of post-operative return trips to the emergency department. Tracking outcome disparities to a granular level such as return visits to the emergency department and number of follow up appointments is critical as health systems strive to achieve equitable care.

Association of Risk Factors and Comorbidities With Chronic Pain in the Elderly Population.

INTRODUCTION/OBJECTIVE: Chronic pain disorders affect about 20% of adults in the United States, and it disproportionately affects individuals living in the neighborhoods of extreme socioeconomic disadvantage. In many instances, chronic pain has been noted to arise from an aggregation of multiple risk factors and events. Therefore, it is of importance to recognize the modifiable risk factors. The aim of this study was to investigate the comorbid medical conditions and risk factors associated with chronic pain disorders in patients aged 65 years and older. METHODS: Our team retrospectively reviewed medical records of elderly patients (65 years and older) who were evaluated in our outpatient medicine office between July 1, 2020 and June 30, 2021 for acute problems, management of chronic medical problems, or well visits. We divided our patients into a group who suffered from chronic pain disorder, and another group who did not have chronic pain disorder. The association of variables were compared between those groups. RESULTS: Of the 2431 patients, 493 (20.3%) had a chronic pain disorder. A higher frequency of females in the group with chronic pain disorder was found compared to the group without a chronic pain disorder (60.6% vs 55.2%; P = .033). The mean ages between the two groups were similar in the group with a chronic pain disorder compared to the group without (76.35 ± 7.5 year vs 76.81 ± 7.59 year; P = .228). There were significant associations of certain comorbidities in the group with a chronic pain disorder compared to the group without a chronic pain disorder, such as depression (21.9% vs 15.2%; P < .001), anxiety (27.0% vs 17.1%; P < .001), chronic obstructive pulmonary disease (8.7% vs 6.1%; P = .036), obstructive sleep apnea (16.8% vs 11.6%; P = .002), gastroesophageal reflux disease (40.8% vs 29.0%; P < .001), osteoarthritis (49.3% vs 26.1%; P < .001), other rheumatologic diseases (24.9% vs 19.4%; P = .006), and peripheral neuropathy (14.4% vs 5.3%; P < .001). CONCLUSION: Female sex, depression, anxiety, chronic obstructive pulmonary disease, obstructive sleep apnea, gastroesophageal reflux disease, osteoarthritis, other rheumatologic diseases, and peripheral neuropathy were significantly associated with chronic pain disorder in elderly patients, while BMI was not associated with chronic pain disorder.

Severe CNS involvement in a subset of long-term treated children with infantile-onset Pompe disease.

INTRODUCTION: The standard of care for patients with infantile-onset Pompe disease (IOPD) is enzyme replacement therapy (ERT), which does not cross the blood brain barrier. While neuromuscular manifestations of IOPD are well-described, central nervous system (CNS) manifestations of this disorder are far less characterized. Here we describe severe CNS-related neurological manifestations including seizures and encephalopathy in six individuals with IOPD. METHOD: We identified six children with IOPD who developed CNS manifestations such as seizures and/or encephalopathy. We studied their brain magnetic resonance imaging scans (MRIs) and graded the severity of white matter hyperintensities (WMHI) using the Fazekas scale scoring system as previously published. Longitudinal cognitive measures were available from 4/6 children. RESULTS: All six IOPD patients (4 males/2 females) had been treated with ERT for 12-15 years. Seizures and/or encephalopathy were noted at a median age at onset of 11.9 years (range 9-15 years). All were noted to have extensive WMHI in the brain MRIs and very high Fazekas scores which preceded the onset of neurological symptoms. Longitudinal IQ scores from four of these children suggested developmental plateauing. DISCUSSION: Among a subset of IOPD patients on long-term ERT, CNS manifestations including hyperreflexia, encephalopathy and seizures may become prominent, and there is likely an association between these symptoms and significant WMHI on MRI. Further study is needed to identify risk factors for CNS deterioration among children with IOPD and develop interventions to prevent neurological decline.

Institutionalizing Community-engaged Translational Science in an Academic Institution: A Community Stakeholder-Driven Process.

BACKGROUND: Although studies have described the power imbalance in academic-community partnerships, little has been published describing how community-based participatory research-informed practitioners can change academic institutions to promote more effective community-engaged research. OBJECTIVES: This paper describes a university-funded community-based participatory project in which academic researchers and their community partners worked together to articulate, develop and advocate for institutionalizing best practices for equitable partnerships throughout the university. METHODS: Findings derive from a collaborative ethnographic process evaluation. RESULTS: The study describes the integral steps proposed to promote equitable community-university research collaboration, the process by which these principles and best practice recommendations were developed, and the institutional change outcomes of this process. CONCLUSIONS: When universities make even small investments toward promoting and nurturing community-engaged research, the quality of the science can be enhanced to advance health equity and community-university relationships can improve, particularly if based on trust, mutual respect, and openness to accomplish a shared vision.

Adapted method for rapid detection and quantification of pathogen Campylobacter jejuni from environmental water samples.

Building on a previously developed workflow for rapid and sensitive pathogen detection by qPCR, this work has established a sample treatment strategy that produces consistent quantification efficiencies (QEs) for Campylobacter jejuni against a complex and highly variable sample matrix from a suburban river. The individual treatments most effective at minimizing the inhibitory effects of the sample matrix were pH buffering with HEPES (50 mM, pH 5.7) and addition of the surfactant Tween 20 (2% v/v). Unexpectedly, sample acidification (pH 4-5) resulting from the use of aged Tween 20 that had undergone partial hydrolysis, appeared to play a key role in enhancing QE. This effect could be replicated by direct pH adjustment with dilute hydrochloric acid and may be linked to the solubilization and removal of inhibitory particles at an acidic pH. While the effectiveness of each individual treatment method varied, a combined treatment of either HEPES buffer + Tween 20, or direct pH adjustment + Tween 20, consistently produced QEs of 60%-70% and up to 100%, respectively, over a sampling period of one year. The consistency and scalability of this workflow make it a suitable alternative to culture-based ISO methods for detecting Campylobacter spp.

Comorbidities and Risk Factors Associated With Insomnia in the Elderly Population.

INTRODUCTION/OBJECTIVES: Sleep disorders affect around 50 to 70 million Americans, with chronic insomnia being the most common, especially in the elderly population. With an 11-fold increase in the US office visits due to insomnia, from 0.8 to 9.4 million, between 1993 and 2015, it is imperative to identify the modifiable risk factors. The aim of our study was to examine the association of risk factors and comorbid medical conditions with insomnia in patients 65 years, and older. METHODS: We performed a retrospective electronic medical record review of the patients aged 65 years and older, who visited our suburban internal medicine office between July 1, 2020 and June 30, 2021. Patients were divided into insomnia group, and the group without insomnia. The associated variables were compared. RESULTS: Among 2431 patients, 247 patients (10.2%) had insomnia. Mean ages of the patients in the insomnia group and the group without insomnia were comparable (77 ± 8.1 year vs 76 ± 7.5 year; P = .211). There was a significantly greater frequency of women in the insomnia group compared to the group without insomnia (63.2% vs 55.5%; P = .022). In the insomnia group, there were significantly higher frequencies of association of certain comorbidities compared to the group without insomnia, such as dementia (6.5% vs 3.4%; P = .015), depression (30.8% vs 14.9%; P < 0.001), anxiety disorder (34.4% vs 17.4%; P < .001), atrial fibrillation (19.4% vs 13.4%; P = .01), and chronic pain disorders (32.8% vs 18.9%; P < .001). Logistic regression analysis showed significantly greater odds of insomnia in patients who had depression (OR = 1.860, 95% CI 1.342-2.576; P < .001), anxiety (OR = 1.845, 95% CI 1.342-2.537; P < .001), and chronic pain disorders (OR = 1.901, 95% CI 1.417-2.549; P < .001). CONCLUSIONS: Female sex, dementia, depression, anxiety, chronic pain disorders, and atrial fibrillation are associated with insomnia in the elderly patients. Presence of depression, anxiety, and chronic pain disorders are associated with greater odds of having insomnia in the elderly patients.

Utilization and Outcomes of Observation for Spontaneous Pneumothorax at an Integrated Health System.

INTRODUCTION: Though limited, recent evidence supports observation rather than intervention for spontaneous pneumothorax management. We sought to compare the utilization and outcomes between observation and intervention for patients with primary and secondary spontaneous pneumothoraces. METHODS: A retrospective cohort study of all adults presenting to Kaiser Permanente Northern California emergency rooms with spontaneous pneumothorax from 2016 to 2020 was performed. Those with prior pneumothoraces, tension physiology, bilateral pneumothoraces, effusions, and prior thoracic procedures or surgery on the affected side were excluded. Groups included observation versus intervention. Baseline clinicodemographic variables and outcomes were compared. Treatment was considered successful if further interventions were not required for pneumothorax resolution. Wilcoxon rank-sum tests, chi-square tests, Fischer exact tests, and multivariable logistic regression models were performed. RESULTS: Of the 386 patients with primary spontaneous pneumothorax, age, race/ethnicity, body mass index, smoking status, and the Charlson comorbidity index were not different between treatment groups. Of 86 patients with secondary spontaneous pneumothorax, age, gender, and smoking status were not different between treatment groups. Among patients with primary pneumothoraces, 83 underwent observation while 303 underwent intervention. The success rate was 92.8% for observation and 60.4% for intervention (P < 0.0001). Among patients with secondary pneumothoraces, 15 underwent observation while 71 underwent intervention, with a successful rate of 73.3% for observation and 32.4% for intervention (P = 0.003). CONCLUSIONS: Given the high success rates for observation of both small and moderate primary and secondary pneumothoraces, observation should be considered for clinically stable patients. Observation may be the superior choice for decreasing morbidity and healthcare costs.

Case report on the role of aggressive palliative surgery in lung NUT carcinoma after induction chemoimmunotherapy.

INTRODUCTION AND IMPORTANCE: NUT (nuclear protein in testis) carcinoma of the lung is an aggressive, poorly differentiated squamous cell carcinoma that has a poor prognosis. Currently, there are no recommended guidelines with limited literature regarding the management of primary NUT carcinoma of the lung. CASE PRESENTATION: A 28-year-old male presented with 2 weeks of intractable chest pain and shortness of breath and was found to have Stage IV pleural NUT carcinoma. After 2 cycles of chemoimmunotherapy, the patient's symptoms persisted with worsening functional status. Palliative surgery was performed via an extrapleural pneumonectomy with significant improvement in symptoms and activities of daily living. CLINICAL DISCUSSION: With no current treatment guidelines, we demonstrate the benefit of surgical resection of advanced pleural NUT carcinoma to improve quality of life. Prognosis is poor with a median survival around 7 months and 3 months with an associated mass. The patient presented pre-operatively with intractable pleuritic chest pain and shortness of breath, limiting activities of daily living that persisted despite chemoimmunotherapy. Our surgical goal was to improve the patient's respiratory status and mitigate pain symptoms via extensive surgical debulking. The patient was able to achieve a higher quality of life and survived longer than the median average, passing away 1 year after diagnosis. CONCLUSION: The management of NUT carcinoma of the lung remains challenging. The role of surgical resection for palliation in advanced tumors has not been previously described and may provide improved quality of life in carefully selected patients.

Using memes to promote student engagement and classroom community during remote learning.

As colleges moved to online teaching during the COVID-19 pandemic, many instructors found it difficult to maintain student engagement and classroom community in the virtual environment. We developed a semester-long activity for a molecular biology research methodology course where students created, and shared original memes related to course content with peers through group chat. Surveys and semi-structured interviews revealed that the exercise was effective in promoting student engagement, a sense of community, and relieving stress.

BAP1 and PTEN mutations shape the immunological landscape of clear cell renal cell carcinoma and reveal the intertumoral heterogeneity of T cell suppression: a proof-of-concept study.

Clear cell renal cell carcinoma (ccRCC) is an immunologically vulnerable tumor entity, and immune checkpoint inhibitors are now widely used to treat patients with advanced disease. Whether and to what extent immune responses in ccRCC are shaped by genetic alterations, however, is only beginning to emerge. In this proof-of-concept study, we performed a detailed correlative analysis of the mutational and immunological landscapes in a series of 23 consecutive kidney cancer patients. We discovered that a high infiltration with CD8 + T cells was not dependent on the number of driver mutations but rather on the presence of specific mutational events, namely pathogenic mutations in PTEN or BAP1. This observation encouraged us to compare mechanisms of T cell suppression in the context of four different genetic patterns, i.e., the presence of multiple drivers, a PTEN or BAP1 mutation, or the absence of detectable driver mutations. We found that ccRCCs harboring a PTEN or BAP1 mutation showed the lowest level of Granzyme B positive tumor-infiltrating lymphocytes (TILs). A multiplex immunofluorescence analysis revealed a significant number of CD8 + TILs in the vicinity of CD68 + macrophages/monocytes in the context of a BAP1 mutation but not in the context of a PTEN mutation. In line with this finding, direct interactions between CD8 + TILs and CD163 + M2-polarized macrophages were found in BAP1-mutated ccRCC but not in tumors with other mutational patterns. While an absence of driver mutations was associated with more CD8 + TILs in the vicinity of FOXP3 + Tregs and CD68 + monocytes/macrophages, the presence of multiple driver mutations was, to our surprise, not found to be strongly associated with immunosuppressive mechanisms. Our results highlight the role of genetic alterations in shaping the immunological landscape of ccRCC. We discovered a remarkable heterogeneity of mechanisms that can lead to T cell suppression, which supports the need for personalized immune oncological approaches.

A rapid and non-invasive proteomic analysis using DBS and buccal swab for multiplexed second-tier screening of Pompe disease and Mucopolysaccharidosis type I.

PURPOSE: Current newborn screening programs for Pompe disease (PD) and mucopolysaccharidosis type I (MPS I) suffer from a high false positive rate and long turnaround time for clinical follow up. This study aimed to develop a novel proteomics-based assay for rapid and accurate second-tier screening of PD and MPS I. A fast turnaround assay would enable the identification of severe cases who need immediate clinical follow up and treatment. METHODS: We developed an immunocapture coupled with mass spectrometry-based proteomics (Immuno-SRM) assay to quantify GAA and IDUA proteins in dried blood spots (DBS) and buccal swabs. Sensitivity, linearity, reproducibility, and protein concentration range in healthy control samples were determined. Clinical performance was evaluated in known PD and MPS I patients as well as pseudodeficiency and carrier cases. RESULTS: Using three 3.2 mm punches (~13.1 µL of blood) of DBS, the assay showed reproducible and sensitive quantification of GAA and IDUA. Both proteins can also be quantified in buccal swabs with high reproducibility and sensitivity. Infantile onset Pompe disease (IOPD) and severe MPS I cases are readily identifiable due to the absence of GAA and IDUA, respectively. In addition, late onset Pompe disease (LOPD) and attenuated MPS I patients showed much reduced levels of the target protein. By contrast, pseudodeficiency and carrier cases exhibited significant higher target protein levels compared to true patients. CONCLUSION: Direct quantification of endogenous GAA and IDUA peptides in DBS by Immuno-SRM can be used for second-tier screening to rapidly identify severe PD and MPS I patients with a turnaround time of <1 week. Such patients could benefit from immediate clinical follow up and possibly earlier treatment.

Targeting the translational machinery in gastrointestinal stromal tumors (GIST): a new therapeutic vulnerability.

Although KIT-mutant GISTs can be effectively treated with tyrosine kinase inhibitors (TKIs), many patients develop resistance to imatinib mesylate (IM) as well as the FDA-approved later-line agents sunitinib, regorafenib and ripretinib. Resistance mechanisms mainly involve secondary mutations in the KIT receptor tyrosine kinase gene indicating continued dependency on the KIT signaling pathway. The fact that the type of secondary mutation confers either sensitivity or resistance towards TKIs and the notion that secondary mutations exhibit intra- and intertumoral heterogeneity complicates the optimal choice of treatment in the imatinib-resistant setting. Therefore, new strategies that target KIT independently of its underlying mutations are urgently needed. Homoharringtonine (HHT) is a first-in-class inhibitor of protein biosynthesis and is FDA-approved for the treatment of chronic myeloid leukemia (CML) that is resistant to at least two TKIs. HHT has also shown activity in KIT-mutant mastocytosis models, which are intrinsically resistant to imatinib and most other TKIs. We hypothesized that HHT could be effective in GIST through downregulation of KIT expression and subsequent decrease of KIT activation and downstream signaling. Testing several GIST cell line models, HHT led to a significant reduction in nascent protein synthesis and was highly effective in the nanomolar range in IM-sensitive and IM-resistant GIST cell lines. HHT treatment resulted in a rapid and complete abolishment of KIT expression and activation, while KIT mRNA levels were minimally affected. The response to HHT involved induction of apoptosis as well as cell cycle arrest. The antitumor activity of HHT was confirmed in a GIST xenograft model. Taken together, inhibition of protein biosynthesis is a promising strategy to overcome TKI resistance in GIST.

APEX-mediated Proximity Labeling of Proteins in Cells Targeted by Extracellular Vesicles.

Extracellular vesicles (EVs) are thought to mediate intercellular communication through the delivery of cargo proteins and RNA to target cells. The uptake of EVs is often followed visually using lipophilic-dyes or fluorescently-tagged proteins to label membrane constituents that are then internalized into recipient cells ( Christianson et al., 2013 ; De Jong et al., 2019 ). However, these methods do not probe the exposure of EV cargo to intracellular compartments, such as the cytoplasm and nucleus, where protein or RNA molecules could elicit functional changes in recipient cells. In this protocol, we employ an EV cargo protein-APEX fusion to detect proximity interactions with recipient cell cytoplasmic/nuclear targets. This approach results in the biotinylation of proteins in close contact with the reporter fusion and thus permits profiling of biotinylated proteins affinity purified on immobilized streptavidin beads. Graphic abstract: Schematic showing three steps of APEX-mediated proximity labeling of proteins in cells targeted by EVs.

Universal Enzyme-Based Field Workflow for Rapid and Sensitive Quantification of Water Pathogens.

A universal filtration and enzyme-based workflow has been established to allow for the rapid and sensitive quantification of leading pathogens Cryptosporidium parvum, Giardia gamblia, Campylobacter jejuni, and Escherichia coli from tap water samples with volumes up to 100 mL, and the potential to scale up to larger volumes. qPCR limits of quantification as low as four oocysts for Cryptosporidium, twelve cysts for Giardia, two cells for C. jejuni, and nineteen cells for E. coli per reaction were achieved. A polycarbonate filter-based sampling method coupled with the prepGEM enzyme-based DNA extraction system created a single-step transfer workflow that required as little as 20 min of incubation time and a 100 µL reaction mix. The quantification via qPCR was performed directly on the prepGEM extract, bypassing time-consuming, labour-intensive conventional culture-based methods. The tap water samples were shown to contain insoluble particles that inhibited detection by reducing the quantification efficiency of a representative pathogen (C. jejuni) to 30-60%. This sample inhibition was effectively removed by an on-filter treatment of 20% (v/v) phosphoric acid wash. Overall, the established workflow was able to achieve quantification efficiencies of 92% and higher for all four leading water pathogens, forming the basis of a rapid, portable, and low-cost solution to water monitoring.

Delineating the molecular and phenotypic spectrum of the SETD1B-related syndrome.

PURPOSE: Pathogenic variants in SETD1B have been associated with a syndromic neurodevelopmental disorder including intellectual disability, language delay, and seizures. To date, clinical features have been described for 11 patients with (likely) pathogenic SETD1B sequence variants. This study aims to further delineate the spectrum of the SETD1B-related syndrome based on characterizing an expanded patient cohort. METHODS: We perform an in-depth clinical characterization of a cohort of 36 unpublished individuals with SETD1B sequence variants, describing their molecular and phenotypic spectrum. Selected variants were functionally tested using in vitro and genome-wide methylation assays. RESULTS: Our data present evidence for a loss-of-function mechanism of SETD1B variants, resulting in a core clinical phenotype of global developmental delay, language delay including regression, intellectual disability, autism and other behavioral issues, and variable epilepsy phenotypes. Developmental delay appeared to precede seizure onset, suggesting SETD1B dysfunction impacts physiological neurodevelopment even in the absence of epileptic activity. Males are significantly overrepresented and more severely affected, and we speculate that sex-linked traits could affect susceptibility to penetrance and the clinical spectrum of SETD1B variants. CONCLUSION: Insights from this extensive cohort will facilitate the counseling regarding the molecular and phenotypic landscape of newly diagnosed patients with the SETD1B-related syndrome.

Targeted long-read sequencing identifies missing disease-causing variation.

Despite widespread clinical genetic testing, many individuals with suspected genetic conditions lack a precise diagnosis, limiting their opportunity to take advantage of state-of-the-art treatments. In some cases, testing reveals difficult-to-evaluate structural differences, candidate variants that do not fully explain the phenotype, single pathogenic variants in recessive disorders, or no variants in genes of interest. Thus, there is a need for better tools to identify a precise genetic diagnosis in individuals when conventional testing approaches have been exhausted. We performed targeted long-read sequencing (T-LRS) using adaptive sampling on the Oxford Nanopore platform on 40 individuals, 10 of whom lacked a complete molecular diagnosis. We computationally targeted up to 151 Mbp of sequence per individual and searched for pathogenic substitutions, structural variants, and methylation differences using a single data source. We detected all genomic aberrations-including single-nucleotide variants, copy number changes, repeat expansions, and methylation differences-identified by prior clinical testing. In 8/8 individuals with complex structural rearrangements, T-LRS enabled more precise resolution of the mutation, leading to changes in clinical management in one case. In ten individuals with suspected Mendelian conditions lacking a precise genetic diagnosis, T-LRS identified pathogenic or likely pathogenic variants in six and variants of uncertain significance in two others. T-LRS accurately identifies pathogenic structural variants, resolves complex rearrangements, and identifies Mendelian variants not detected by other technologies. T-LRS represents an efficient and cost-effective strategy to evaluate high-priority genes and regions or complex clinical testing results.

Family Support and Readiness to Consider Smoking Cessation among Chinese and Vietnamese American Male Smokers.

INTRODUCTION: Smoking prevalence is disproportionately high among Asian American immigrant men with limited English proficiency. Understanding the role of family support may provide insights on culturally acceptable strategies to promote smoking cessation. AIMS: This study examined how family support was associated with readiness to consider smoking cessation among Chinese and Vietnamese American male daily smokers. METHODS: We analyzed baseline data (N=340) from a cluster randomized trial of a family-based healthy lifestyle intervention. We assessed the frequency of receiving family support in various forms (encouraging use of cessation resources; praising efforts; checking-in; reminding of familial role). Multiple regression analysis was used to determine associations between family support areas and readiness to consider smoking cessation, controlling for covariates. RESULTS/FINDINGS: Reporting a higher frequency of receiving praise and encouragement for one's efforts to quit was positively associated with readiness to consider cessation. Other areas of family support were not significant. CONCLUSIONS: These findings provide evidence to explore specific areas of family support in enhancing Asian American smokers' readiness to consider cessation. As there is high interest from Asian American family members to support their smokers for quitting, culturally specific and acceptable strategies are needed to promote smoking cessation among Asian Americans.

Biomonitoring of volatile organic compounds (VOCs) among hairdressers in salons primarily serving women of color: A pilot study.

Hairdressers are exposed to volatile organic compounds (VOCs), many of which have been linked to acute and chronic health effects. Those hairdressers serving an ethnic clientele may potentially experience disproportionate exposures from frequent use of products containing VOCs or different VOC concentrations contained in products which are marketed to the specific needs of their clientele. However, no biomonitoring studies have investigated occupational exposures in this population. In the present pilot study, we sought to characterize concentrations and exposure determinants for 28 VOC biomarkers in post-shift urine samples among 23 hairdressers primarily serving an ethnic clientele. VOC biomarker concentrations among hairdressers of color were compared to concentrations among a comparison group of 17 office workers and a representative sample of women participating in the U.S. National Health and Nutrition Examination Survey. VOC biomarkers were detected in all hairdressers with higher concentrations observed among hairdressers serving a predominantly Black versus Latino clientele, and among hairdressers overall versus office workers and women in the U.S. general population. Median biomarker concentrations for acrolein,1,3-butadiene, and xylene in hairdressers were more than twice as high as those observed among office workers. Median concentrations for 1-bromopropane, acrolein and 1,3-butadiene were more than four times higher among all hairdressers compared to those reported among women in the U.S. general population. Select salon services (e.g., sister locs, flat ironing, permanent hair coloring, permanent waves or texturizing, Brazilian blowout or keratin treatment, etc.) were also associated with higher VOC biomarker concentrations among hairdressers. This pilot study represents the first biomonitoring analysis to characterize VOC exposures among women hairdressers of color and to provide evidence that this occupational population may experience elevated VOC exposures compared to women in the U.S. general population. Results from our study represent an important first step in elucidating occupational VOC exposures in this understudied occupational group. Larger studies among a racially and ethnically diverse cohort of hairdressers are warranted to confirm our findings and inform future exposure interventions in this understudied occupational population.

13C Metabolic Flux Analysis Indicates Endothelial Cells Attenuate Metabolic Perturbations by Modulating TCA Activity.

Disrupted endothelial metabolism is linked to endothelial dysfunction and cardiovascular disease. Targeted metabolic inhibitors are potential therapeutics; however, their systemic impact on endothelial metabolism remains unknown. In this study, we combined stable isotope labeling with 13C metabolic flux analysis (13C MFA) to determine how targeted inhibition of the polyol (fidarestat), pentose phosphate (DHEA), and hexosamine biosynthetic (azaserine) pathways alters endothelial metabolism. Glucose, glutamine, and a four-carbon input to the malate shuttle were important carbon sources in the baseline human umbilical vein endothelial cell (HUVEC) 13C MFA model. We observed two to three times higher glutamine uptake in fidarestat and azaserine-treated cells. Fidarestat and DHEA-treated HUVEC showed decreased 13C enrichment of glycolytic and TCA metabolites and amino acids. Azaserine-treated HUVEC primarily showed 13C enrichment differences in UDP-GlcNAc. 13C MFA estimated decreased pentose phosphate pathway flux and increased TCA activity with reversed malate shuttle direction in fidarestat and DHEA-treated HUVEC. In contrast, 13C MFA estimated increases in both pentose phosphate pathway and TCA activity in azaserine-treated cells. These data show the potential importance of endothelial malate shuttle activity and suggest that inhibiting glycolytic side branch pathways can change the metabolic network, highlighting the need to study systemic metabolic therapeutic effects.