Recurrent dermatomyositis manifesting as a sign of recurrent transitional cell carcinoma of urinary bladder:long-term survival

The association between urological malignancies and paraneoplastic syndromes has been well documented. We report a case of recurrent dermatomyositis manifesting as a sign of metastatic recurrence of non-muscle-invasive transitional cell carcinoma of the bladder, a relationship which has only been referred to in a few reports. The case highlights a few important clinical challenges; firstly, the importance of thorough investigation for underlying malignancy in patients with dermatomyositis, as successful treatment of such malignancy can lead to resolution of paraneoplastic symptoms, and secondly, a high index of suspicion of recurrence in cases where paraneoplastic manifestations recur. Metastatic pulmonary recurrence without local evidence of disease at a follow-up of 4 years makes this case unique. Moreover, in the light of our experience and reported literature, a framework is suggested to approach such a diagnostic dilemma in the future. Description of the case will guide clinicians in the future, in case they encounter such an unusual clinical scenario. This could also serve as a hypothesis-generating source for designing future research as well

Identification of Heme Oxygenase-1 as a Putative DNA-Binding Protein

Heme oxygenase-1 (HO-1) is a rate-limiting enzyme in degrading heme into biliverdin and iron. HO-1 can also enter the nucleus and regulate gene transcription independent of its enzymatic activity. Whether HO-1 can alter gene expression through direct binding to target DNA remains unclear. Here, we performed HO-1 CHIP-seq and then employed 3D structural modeling to reveal putative HO-1 DNA binding domains. We identified three probable DNA binding domains on HO-1. Using the Proteinarium, we identified several genes as the most highly connected nodes in the interactome among the HO-1 gene binding targets. We further demonstrated that HO-1 modulates the expression of these key genes using Hmox1 deficient cells. Finally, mutation of four conserved amino acids (E215, I211, E201, and Q27) within HO-1 DNA binding domain 1 significantly increased expression of Gtpbp3 and Eif1 genes that were identified within the top 10 binding hits normalized by gene length predicted to bind this domain. Based on these data, we conclude that HO-1 protein is a putative DNA binding protein, and regulates targeted gene expression. This provides the foundation for developing specific inhibitors or activators targeting HO-1 DNA binding domains to modulate targeted gene expression and corresponding cellular function

Timing and cell specificity of senescence drives postnatal lung development and injury

Senescence causes age-related diseases and stress-related injury, but it is also physiologically essential during development. Here, Yao et al. show that programmed senescence in mesenchymal cells orchestrates postnatal lung development and that neonatal hyperoxia can induce senescence, particularly in type II, Pdgfra+ mesenchymal and immune cells, during the alveolar stage, resulting in lung injury

Commuting and Sleep: Results From the Hispanic Community Health Study/Study of Latinos Sueño Ancillary Study

Commute time is associated with reduced sleep time, but previous studies have relied on self-reported sleep assessment. The present study investigated the relationships between commute time for employment and objective sleep patterns among non-shift working U.S. Hispanic/Latino adults. From 2010 to 2013, Hispanic/Latino employed, non-shift–working adults (n=760, aged 18–64 years) from the Sueño study, ancillary to the Hispanic Community Health Study/Study of Latinos, reported their total daily commute time to and from work, completed questionnaires on sleep and other health behaviors, and wore wrist actigraphs to record sleep duration, continuity, and variability for 1 week. Survey linear regression models of the actigraphic and self-reported sleep measures regressed on categorized commute time (short: 1–44 minutes; moderate: 45–89 minutes; long: ≥90 minutes) were built adjusting for relevant covariates. For associations that suggested a linear relationship, continuous commute time was modeled as the exposure. Moderation effects by age, sex, income, and depressive symptoms also were explored. Commute time was linearly related to sleep duration on work days such that each additional hour of commute time conferred 15 minutes of sleep loss (p=0.01). Compared with short commutes, individuals with moderate commutes had greater sleep duration variability (p=0.04) and lower interdaily stability (p=0.046, a measure of sleep/wake schedule regularity). No significant associations were detected for self-reported sleep measures. Commute time is significantly associated with actigraphy-measured sleep duration and regularity among Hispanic/Latino adults. Interventions to shorten commute times should be evaluated to help improve sleep habits in this minority population

Phenotypes of obstructive sleep apnea in the Hispanic Community Health Study/Study of Latinos

Study objectivesRecent work on US Whites from clinical samples used obstructive sleep apnea (OSA) symptoms to generate phenotypes for individuals with moderate-severe OSA which suggested 3 to 5 symptom classes. However, it is unknown whether similar classes generalize to diverse Hispanics/Latino adults. Therefore, we sought to fill this gap by empirically deriving sleep phenotypes among a large sample of diverse Hispanics/Latinos.MethodsWe used data from The Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008-2011), a prospective cohort study designed using a multisite multistage probability sample of adults 18-74 years old. The subpopulation of interest included participants with moderate-severe OSA symptoms (≥15 respiratory event index (REI) events per hour; n = 1,605). We performed latent class analysis for complex survey data using 15 common OSA symptoms (e.g. Epworth Sleepiness Scale) and 4 comorbidities to identify phenotype classes.ResultsAverage age was 52.4 ± 13.9 years and 34.0% were female. Mean REI was 33.8 ± 22.5 events per hour. Fit statistics and clinical significance suggested that a three-class solution provided the best fit to the data. The three phenotypes were: (1) Minimally Symptomatic (47.7%), (2) Excessive sleepiness (37.1%), and (3) Disturbed Sleep (15.2%). Sensitivity models were consistent with the main proposed solution.ConclusionsDerived sleep phenotypes among diverse Hispanic/Latinos were consistent with recent findings from the Sleep Apnea Global Interdisciplinary Consortium, but we found notable differences in class prevalence relative to Whites. Further research is needed to link derived sleep phenotypes to health comorbidities in diverse populations

Phenotypes of obstructive sleep apnea in the Hispanic Community Health Study/Study of Latinos

Recent work on US Whites from clinical samples used obstructive sleep apnea (OSA) symptoms to generate phenotypes for individuals with moderate-severe OSA which suggested 3 to 5 symptom classes. However, it is unknown whether similar classes generalize to diverse Hispanics/Latino adults. Therefore, we sought to fill this gap by empirically deriving sleep phenotypes among a large sample of diverse Hispanics/Latinos. We used data from The Hispanic Community Health Study/Study of Latinos (HCHS/SOL; 2008-2011), a prospective cohort study designed using a multisite multistage probability sample of adults 18-74 years old. The subpopulation of interest included participants with moderate-severe OSA symptoms (≥15 respiratory event index (REI) events per hour; n = 1,605). We performed latent class analysis for complex survey data using 15 common OSA symptoms (e.g. Epworth Sleepiness Scale) and 4 comorbidities to identify phenotype classes. Average age was 52.4 ± 13.9 years and 34.0% were female. Mean REI was 33.8 ± 22.5 events per hour. Fit statistics and clinical significance suggested that a three-class solution provided the best fit to the data. The three phenotypes were: (1) Minimally Symptomatic (47.7%), (2) Excessive sleepiness (37.1%), and (3) Disturbed Sleep (15.2%). Sensitivity models were consistent with the main proposed solution. Derived sleep phenotypes among diverse Hispanic/Latinos were consistent with recent findings from the Sleep Apnea Global Interdisciplinary Consortium, but we found notable differences in class prevalence relative to Whites. Further research is needed to link derived sleep phenotypes to health comorbidities in diverse populations