Rigorous benchmarking of T-cell receptor repertoire profiling methods for cancer RNA sequencing.

The ability to identify and track T-cell receptor (TCR) sequences from patient samples is becoming central to the field of cancer research and immunotherapy. Tracking genetically engineered T cells expressing TCRs that target specific tumor antigens is important to determine the persistence of these cells and quantify tumor responses. The available high-throughput method to profile TCR repertoires is generally referred to as TCR sequencing (TCR-Seq). However, the available TCR-Seq data are limited compared with RNA sequencing (RNA-Seq). In this paper, we have benchmarked the ability of RNA-Seq-based methods to profile TCR repertoires by examining 19 bulk RNA-Seq samples across 4 cancer cohorts including both T-cell-rich and T-cell-poor tissue types. We have performed a comprehensive evaluation of the existing RNA-Seq-based repertoire profiling methods using targeted TCR-Seq as the gold standard. We also highlighted scenarios under which the RNA-Seq approach is suitable and can provide comparable accuracy to the TCR-Seq approach. Our results show that RNA-Seq-based methods are able to effectively capture the clonotypes and estimate the diversity of TCR repertoires, as well as provide relative frequencies of clonotypes in T-cell-rich tissues and low-diversity repertoires. However, RNA-Seq-based TCR profiling methods have limited power in T-cell-poor tissues, especially in highly diverse repertoires of T-cell-poor tissues. The results of our benchmarking provide an additional appealing argument to incorporate RNA-Seq into the immune repertoire screening of cancer patients as it offers broader knowledge into the transcriptomic changes that exceed the limited information provided by TCR-Seq.

Sleep insufficiency, circadian rhythms, and metabolomics: the connection between metabolic and sleep disorders.

PURPOSE: US adults who report experiencing insufficient sleep are more likely to suffer from metabolic disorders such as hyperlipidemia, diabetes, and obesity than those with sufficient sleep. Less is understood about the underlying molecular mechanisms connecting these phenomena. A systematic, qualitative review of metabolomics studies exploring metabolic changes in response to sleep insufficiency, sleep deprivation, or circadian disruption was conducted in accordance with PRISMA guidelines. METHODS: An electronic literature review in the PubMed database was performed considering publications through May 2021 and screening and eligibility criteria were applied to articles retrieved. The following keywords were used: "metabolomics" and "sleep disorders" or "sleep deprivation" or "sleep disturbance" or "circadian rhythm." After screening and addition of studies included from reference lists of retrieved studies, 16 records were identified for review. RESULTS: Consistent changes in metabolites were observed across studies between individuals experiencing sleep deprivation compared to non-sleep deprived controls. Significant increases in phosphatidylcholines, acylcarnitines, sphingolipids, and other lipids were consistent across studies. Increased levels of amino acids such as tryptophan and phenylalanine were also noted. However, studies were limited to small samples of young, healthy, mostly male participants conducted in short inpatient sessions, limiting generalizability. CONCLUSION: Changes in lipid and amino acid metabolites accompanying sleep deprivation and/or circadian rhythms may indicate cellular membrane and protein breakdown underlying the connection between sleep disturbance, hyperlipidemia, and other metabolic disorders. Larger epidemiological studies examining changes in the human metabolome in response to chronic insufficient sleep would help elucidate this relationship.

Sphinganine is associated with 24-h MAP in the non-sleepy with OSA.

INTRODUCTION: Excessive daytime sleepiness is a debilitating symptom of obstructive sleep apnea (OSA) linked to cardiovascular disease, and metabolomic mechanisms underlying this relationship remain unknown. We examine whether metabolites from inflammatory and oxidative stress-related pathways that were identified in our prior work could be involved in connecting the two phenomena. METHODS: This study included 57 sleepy (Epworth Sleepiness Scale (ESS) ≥ 10) and 37 non-sleepy (ESS < 10) participants newly diagnosed and untreated for OSA that completed an overnight in-lab or at home sleep study who were recruited from the Emory Mechanisms of Sleepiness Symptoms Study (EMOSS). Differences in fasting blood samples of metabolites were explored in participants with sleepiness versus those without and multiple linear regression models were utilized to examine the association between metabolites and mean arterial pressure (MAP). RESULTS: The 24-h MAP was higher in sleepy 92.8 mmHg (8.4) as compared to non-sleepy 88.8 mmHg (8.1) individuals (P = 0.03). Although targeted metabolites were not significantly associated with MAP, when we stratified by sleepiness group, we found that sphinganine is significantly associated with MAP (Estimate = 8.7, SE = 3.7, P = 0.045) in non-sleepy patients when controlling for age, BMI, smoking status, and apnea-hypopnea index (AHI). CONCLUSION: This is the first study to evaluate the relationship of inflammation and oxidative stress related metabolites in sleepy versus non-sleepy participants with newly diagnosed OSA and their association with 24-h MAP. Our study suggests that Sphinganine is associated with 24 hour MAP in the non-sleepy participants with OSA.

Examining the role of micronutrients on improving long COVID sleep-related symptoms.

AIMS AND OBJECTIVES: Long COVID is defined as the continuation of symptoms for four or more weeks after initial contraction of the virus. This review article examines the role of four select micronutrients (zinc, vitamins C, D and polyphenols) for their anti-inflammatory and therapeutic potential to improve sleep-related symptoms in persons with long COVID. BACKGROUND: Evidence suggests a link between long COVID and increased inflammation. There are currently no therapeutic interventions for common sleep-related symptoms associated with long COVID. Micronutrients, due to their antioxidant and anti-inflammatory properties, may have a role in the treatment of sleep-related symptoms in the context of long COVID. DESIGN: A narrative literature review was conducted and guided by the PRISMA checklist. METHODS: All articles were screened from PubMed, ScienceDirect, NCBI or Google Scholar and were limited to human studies. The following keywords were used: 'COVID-19', 'sleep symptoms', 'zinc', 'vitamin C', 'vitamin D', 'polyphenols' and 'micronutrients'. RESULTS: There are currently no studies that examine the usage of micronutrients and its impacts on long-term, sleep-related symptoms post-COVID-19 infection. We focussed our review on prior studies that examined micronutrients in the context of sleep symptoms and inflammation, while exploring the potential for micronutrients to help improve sleep-related symptoms associated with long COVID. CONCLUSIONS: There is evidence to suggest that sleep-related symptoms associated with long COVID, such as fatigue and poor sleep quality, are associated with inflammation. Zinc, vitamins C, D and polyphenols all have the potential to improve both inflammation and sleep quality to alleviate symptoms. Future research should further examine these micronutrients in the context of long COVID to improve sleep and quality of life. RELEVANCE TO CLINICAL PRACTICE: This article provides implications for clinicians to be at the forefront of research on the usage of micronutrients to improve sleep-related symptoms in persons with long COVID.

Changes in sleepiness and 24-h blood pressure following 4 months of CPAP treatment are not mediated by ICAM-1.

OBJECTIVE: Continuous positive airway pressure (CPAP) therapy reduces circulating intercellular adhesion molecule 1 (ICAM-1) in adults with obstructive sleep apnea (OSA). ICAM-1 levels may affect the daytime sleepiness and elevated blood pressure associated with OSA. We evaluated the association of changes from baseline in ICAM-1 with changes of objective and subjective measures of sleepiness, as well as 24-h ambulatory blood pressure monitoring (ABPM) measures, following 4 months of CPAP treatment. METHODS: The study sample included adults with newly diagnosed OSA. Plasma ICAM-1, 24-h ABPM, Epworth Sleepiness Scale (ESS), and psychomotor vigilance task (PVT) were obtained at baseline and following adequate CPAP treatment. The associations between changes in natural log ICAM-1 and changes in the number of lapses on PVT, ESS score, and 24-h mean arterial blood pressure (MAP) were assessed using multivariate regression models, controlling for a priori baseline covariates of age, sex, BMI, race, site, smoking status, physical activity, anti-hypertensive medications, AHI, and daily hours of CPAP use. RESULTS: Among 140 adults (83% men), mean (± SD) body mass index (BMI) was 31.5 ± 4.2 kg/m2, and apnea-hyopnea index (AHI) was 36.8 ± 15.3 events/h. Sleepiness measures, although not ICAM-1 or ABPM measures, improved significantly following CPAP treatment. We observed no statistically significant associations between the change in ICAM-1 and changes in sleepiness, MAP, or other ABPM measures. CONCLUSION: Changes in ICAM-1 levels were not related to changes in sleepiness or ABPM following CPAP treatment of adults with OSA. Future work should explore whether or not other biomarkers may have a role in mediating these treatment outcomes in adults with OSA.

Metabolomics, sleepiness, and sleep duration in sleep apnea.

PURPOSE: Although the mechanism is unclear, daytime sleepiness, a common sequela of obstructive sleep apnea (OSA), has been found to be correlated with a adverse cardiovascular outcomes. Reviewing metabolomics mechanisms of sleep disturbances and cardiovascular disease may help to explain this correlation. METHODS: This review examines the current literature on the relationships between sleepiness, sleep duration, and metabolites in sleep apnea. RESULTS: Although there is a lack of comprehensive literature in this emerging area, existing studies point to a variety of metabolites in different pathways that are associated with sleepiness and sleep duration. CONCLUSION: Advancing metabolomics research in sleep apnea will guide symptom research and provide alternate and novel opportunities for effective treatment for patients with OSA.

Metabolomics of sleep disorders in HIV: a narrative review.

PURPOSE: Sleep disturbances are prevalent among patients with human immunodeficiency virus (HIV), even those who are being treated on antiretroviral therapy. It is important to understand the metabolomic mechanisms underlying sleep disturbances among people living with HIV (PLWH). METHODS: A review of recent literature was performed to explore the use of metabolomics in understanding sleep among PLWH. RESULTS: We found only two studies that used metabolomics to explore sleep health among PLWH. CONCLUSION: This paper reviews common sleep disorders in HIV, the existing metabolomic studies that may explain the relationship, and implications for future research. The use of metabolomics in exploring sleep disorders among PLWH will help to elucidate mechanistic links to improve patient outcomes.

Role of Supplemental Nutrition Assistance Program in Improving Diet Quality: Implications for Nurses.

The Supplemental Nutrition Assistance Program (SNAP) provides access to healthy food for low-income individuals and households. Food security, however, does not necessarily achieve higher diet quality for beneficiaries. Diet quality is an important consideration for the development and management of chronic illness, a significant public health concern. In this study, we review incentives and disincentives implemented to improve the diet quality, the evidence on SNAP including benefits, challenges, and the politics of funding. New interventions and policies will be needed in order to improve the overall diet quality of SNAP households. SNAP should align with nutritional science to meet national public health goals. Nurses are trusted advocates for patients and the public and are uniquely positioned to aid in this effort. Informed by evidence, nurses willing to leverage their influence, can lead this needed change.

Mechanisms of reduced sleepiness symptoms in heart failure and obstructive sleep apnea.

Patients with both heart failure and obstructive sleep apnea often have poor, repeatedly disrupted sleep, and yet they frequently do not complain of excessive daytime sleepiness. Understanding this lack of perceived sleepiness is crucial for the case identification and treatment of obstructive sleep apnea in the heart failure population at high risk of this disease, especially given the association between untreated obstructive sleep apnea and mortality among patients with heart failure. In this review, we present epidemiologic evidence concerning the lack of sleepiness symptoms in heart failure and obstructive sleep apnea, explore possible mechanistic explanations for this relationship, assess the benefits of treatment in this population, discuss implications for clinical practice and explore directions for future research.

Restless legs syndrome, periodic limb movements of sleep, and subclinical cardiovascular disease.

Restless legs syndrome (RLS) and periodic limb movements of sleep (PLMS) have been variably implicated in risk for cardiovascular disease (CVD), but there is lack of consensus on these relationships. We sought to assess subclinical CVD measures and RLS/PLMS in a large cohort to further evaluate these associations. The Emory Center for Health Discovery and Well Being cohort is composed of employed adults, with subclinical CVD measures including endothelial function (flow-mediated vasodilation), microvascular function (reactive hyperemia index, RHI), arterial stiffness (pulse wave velocity and augmentation index), and carotid intima-media thickness (cIMT). Participants were grouped based on presence (N = 50) or absence (N = 376) of RLS and subclinical CVD measures compared between groups. A subset of participants (n = 40) underwent ambulatory monitoring for PLMS and obstructive sleep apnea. PLMS association with subclinical CVD measures was assessed. RLS status was significantly associated with flow-mediated dilation in univariate analyses but not after controlling for potential confounders; RLS was not associated with other subclinical CVD measures. PLMS were significantly correlated with the RHI, augmentation index, and cIMT in univariate analyses; only the association between PLMS and cIMT remained significant (p = 0.04) after controlling for RLS status, age, apnea-hypopnea index, hyperlipidemia, and hypertension. The observed association between higher PLMS and greater cIMT suggests that PLMS may be a marker of subclinical CVD. Further work is needed to determine the relationship between PLMS and CVD risk. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00497-7.

The effects of time-restricted eating on sleep, cognitive decline, and Alzheimer's disease.

According to the United Nations, by 2050, one in six individuals will be over age 65 globally, and one in four people would be aged 65 and older in western countries. The unprecedented growth of the aging population is associated with increased age-related disorders like Alzheimer's disease (AD) and Mild cognitive impairment (MCI). To date, no cure is known for AD, thus lifestyle interventions including calorie restriction (CR) and time-restricted eating (TRE) are proposed as potential approach to delay the onset and progression of the disease. Sleep disturbances are common in people with MCI and AD. Moreover, accumulating data indicates that pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8 and IL-10 increase in individuals with AD and MCI versus healthy subjects. Thus, the purpose of the present review is to describe the potential effects of TRE on sleep, cognition decline, and neuroinflammatory markers in humans. Preliminary evidence suggests that TRE may produce neuroprotective effects on cognition and reduce neuroinflammatory markers related to AD in humans. To date, no studies investigated the effects of TRE on sleep disturbances and patients with AD. Thereby, the impact of TRE on cognition in individuals with cognitive decline and AD needs to be investigated further in randomized controlled trials (RCTs).

Obesity does not modify the effect of continuous positive airway pressure on insulin resistance in adults with obstructive sleep apnoea.

This study found no evidence that obesity significantly modifies the effect of 4 months of CPAP treatment on HOMA-IR. Longer duration of CPAP treatment may be needed in order to reduce insulin resistance and determine whether obesity modifies the effect. https://bit.ly/3CtX7jZ.

Performance of PROMIS Measures to Assess Fatigue and Sleep Symptom Severity Among African American Patients Newly Diagnosed With Obstructive Sleep Apnea.

This pilot study examined the concurrent validity of Patient-Reported Outcomes Measurement Information System (PROMIS), Short Form, measures with the longer Multidimensional Fatigue Inventory among patients living with obstructive sleep apnea (OSA). A total of 26 African American patients living with prediabetes and newly diagnosed with OSA completed the six-item short form versions of PROMIS Fatigue and PROMIS Sleep Disturbance, and the longer 20-item Multidimensional Fatigue Inventory. Both PROMIS Fatigue and Sleep Disturbance scales demonstrated high reliability with Cronbach's α of .91 and .92, respectively. PROMIS Fatigue scores were significantly correlated with Multidimensional Fatigue Inventory scores (rs = .53; p = .006) and demonstrated concurrent validity. However, PROMIS Sleep Disturbance scores and Multidimensional Fatigue Inventory scores were not associated with one another. The brief PROMIS Fatigue scale is a useful, succinct approach to assess fatigue severity among diverse patient populations living with OSA. This study is among the first to evaluate the performance of PROMIS Fatigue in a sample living with OSA.

Sleep disturbance is associated with cardiovascular and metabolic disorders.

Existing research has demonstrated associations between sleep duration and obesity, diabetes, cardiovascular disease and mortality. Sleep disorders research has shown that sleep apnoea, insomnia and other sleep disorders confer risk for cardiometabolic disease, particularly in the presence of reduced sleep duration. The aim of the present study was to examine the associations between general sleep disturbance, operationalized as 'difficulty falling asleep, staying asleep, or sleeping too much' as measured in a large, nationally representative sample, and self-reported history of myocardial infarction, stroke, coronary artery disease, diabetes and obesity. Data from the Behavioral Risk Factor Surveillance System were analysed. Complete data were available for 138,201 individuals. A hierarchical logistic regression analysis examined associations before and after adjustment for demographic, socioeconomic, medical and psychological factors. After adjusting for demographic, socioeconomic and health risk factors, sleep duration was associated with obesity [odds ratio (OR)=1.18, P<0.0005), diabetes (OR=1.18, P<0.005), myocardial infarction (OR=1.36, P<0.0005), stroke (OR=1.22, P<0.05) and coronary artery disease (OR=1.59, P<0.0005). In fully adjusted models that included physical health, significant relationships remained for obesity (OR=1.14, P<0.0005), myocardial infarction (OR=1.23, P<0.005) and coronary artery disease (OR=1.43, P<0.0005). Sleep disturbance is a significant risk factor for obesity, diabetes, myocardial infarction, stroke and coronary artery disease, and effects for obesity, myocardial infarction and coronary artery disease are the most robust after adjustment. This study demonstrates that sleep disturbance is a novel risk factor that is potentially modifiable. Future research should determine whether sleep intervention could reduce the cardiometabolic consequences of sleep disturbance.

Sleep duration and biomarkers of inflammation in African American and white participants with a parental history of Alzheimer's disease.

Introduction: African Americans (AA)s have worse inflammation, worse sleep, and a greater incidence of Alzheimer's disease (AD) compared to whites; however, no studies have examined associations between biomarkers, sleep, and cognition, and differences by race. Methods: Seventy-six cognitively normal, middle aged (45-65 years) adults with a parental history of AD were included in this study. Associations between biomarkers (tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10], intercellular adhesion molecule-1 [ICAM-1],, and C-reactive protein [CRP]) and self-reported sleep or cognition measures, were assessed. Results: Average sleep duration was significantly lower for AA versus whites (average[SD]) in hours: 6.02(1.18) versus 7.23(0.91), P = .000004). We found a statistically significant association between plasma IL-10 and sleep duration (Spearman's ρ = 0.26, P = .04) and CSF ICAM-1 and sleep quality (Spearman's ρ = 0.30, P = .03). Discussion: Longer sleep duration is positively associated with plasma IL-10 levels irrespective of race. Sleep quality was positively associated with CSF ICAM-1 only in African Americans.

Promoting Caregiver Mastery in Black American Dementia Caregivers.

Over 6 million older Americans live with Alzheimer's disease and related dementias; Black American older adults' prevalence is more than twice that of non-Hispanic White older adults. The Black American dementia caregiving experience can be encapsulated within the Black Family Socioecological Context Model, which provides a conceptual basis for examining social determinants of health at individual, family, community, and societal levels with careful consideration for how the intersection of race, gender, and class of Black American dementia caregivers influences the multiple dimensions of their caregiving experiences. Family dynamics, community setting, and health care systems have a potentially bidirectional influence on these caregivers, which is shaped by historical and ongoing systemic and institutional racism and general disenfranchisement. This Forum article outlines how the Social Cognitive Theory offers ways for Black American dementia caregivers to achieve a sense of mastery within the complicated and fraught ecology within which their caregiving occurs. We propose a research agenda to create programs and interventions for enhancing a sense of mastery among Black American dementia caregivers. Two concepts in particular, "constraints" and "efficacy expectations," provide ways to create a systematic approach to developing successful coping strategies for the constraints perceived by individuals as they undertake and function in the caregiving role. The recognition of the complexity of the caregiving ecosystem and intersectionality of caregivers' experience and identity emphasize the importance of individualization: Each caregiver's experience of this ecosystem-and therefore each Black American dementia caregiver's way to mastery within it-will be uniquely shaped and experienced.

Effects of sample collection and storage conditions on DNA damage in buccal cells from agricultural workers.

Buccal cells are becoming a widely used tissue source for monitoring human exposure to occupational and environmental genotoxicants. A variety of methods exist for collecting buccal cells from the oral cavity, including rinsing with saline, mouthwash, or scraping the oral cavity. Buccal cells are also routinely cryopreserved with dimethyl sulfoxide (DMSO), then examined later for DNA damage by the comet assay. The effects of these different sampling procedures on the integrity of buccal cells for measuring DNA damage are unknown. This study examined the influence of the collection and cryopreservation of buccal cells on cell survival and DNA integrity. In individuals who rinsed with Hank's balanced salt solution (HBSS), the viability of leukocytes (90%) was significantly (p<0.01) greater than that of epithelial cells (12%). Similar survival rates were found for leukocytes (88%) and epithelial cells (10%) after rinsing with Listerine(®) mouthwash. However, the viability of leukocytes after cryopreservation varied significantly (p<0.01) with DMSO concentration. Cell survival was greatest at 5% DMSO. Cryopreservation also influenced the integrity of DNA in the comet assay. Although tail length and tail moment were comparable in fresh or cryopreserved samples, the average head intensity for cryopreserved samples was ∼6 units lower (95% CI: 0.8-12 units lower) than for fresh samples (t(25)=-2.36, p=0.026). These studies suggest that the collection and storage of buccal samples are critical factors for the assessment of DNA damage. Moreover, leukocytes appear to be a more reliable source of human tissue for assessing DNA damage and possibly other biochemical changes.

Phthalate exposures and human health concerns: A review and implications for practice.

High levels of exposure to phthalates have been associated with an increased risk for adverse male fetal reproductive development. Although animal studies have consistently demonstrated reproductive health effects, additional human epidemiological studies are needed to fully understand the potential harm to humans. Recent findings reported for humans have demonstrated endocrine-disrupting action similar to that associated with phthalate exposures in animals. As a result, phthalate exposure is an emerging public health concern that warrants further review. This article explores the state of the science on phthalate exposure, reviews the literature, and provides recommendations occupational health nurses can use to optimize the health of susceptible populations.

How stress, discrimination, acculturation and the gut microbiome affect depression, anxiety and sleep among Chinese and Korean immigrants in the USA: a cross-sectional pilot study protocol.

INTRODUCTION: Although a considerable proportion of Asians in the USA experience depression, anxiety and poor sleep, these health issues have been underestimated due to the model minority myth about Asians, the stigma associated with mental illness, lower rates of treatment seeking and a shortage of culturally tailored mental health services. Indeed, despite emerging evidence of links between psychosocial risk factors, the gut microbiome and depression, anxiety and sleep quality, very few studies have examined how these factors are related in Chinese and Korean immigrants in the USA. The purpose of this pilot study was to address this issue by (a) testing the usability and feasibility of the study's multilingual survey measures and biospecimen collection procedure among Chinese and Korean immigrants in the USA and (b) examining how stress, discrimination, acculturation and the gut microbiome are associated with depression, anxiety and sleep quality in this population. METHOD AND ANALYSIS: This is a cross-sectional pilot study among first and second generations of adult Chinese and Korean immigrants in the greater Atlanta area (Georgia, USA). We collected (a) gut microbiome samples and (b) data on psychosocial risk factors, depression, anxiety and sleep disturbance using validated, online surveys in English, Chinese and Korean. We aim to recruit 60 participants (30 Chinese, 30 Korean). We will profile participants' gut microbiome using 16S rRNA V3-V4 sequencing data, which will be analysed by QIIME 2. Associations of the gut microbiome and psychosocial factors with depression, anxiety and sleep disturbance will be analysed using descriptive and inferential statistics, including linear regression. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Emory University (IRB ID: STUDY00000935). Results will be made available to Chinese and Korean community members, the funder and other researchers and the broader scientific community.