Heterogeneity In Adults Research Articles

Health-related social control among U.S. adults ages 30–80: Associations with alcohol use over four years

Health-related social control (HRSC) includes efforts to regulate or influence others' health behaviors and is an important way interpersonal relationships can affect individual-level health. This study used egocentric network data to describe the size and composition of HRSC networks, identify trajectories of HRSC receipt, and examine how HRSC is related to binge drinking and alcohol-related problems. Data come from a U.S. nationally representative sample of 1235 adults age 30 and older (baseline mean age = 52, 52% female, 64% White) who completed four annual surveys between 2019 and 2022. On average, 30% of adults' network members were HRSC agents who told or reminded them to do things to protect their health. At baseline, 50% of respondents identified a spouse/partner as a HRSC agent, 56% a relative, 46% a friend, and 12% someone else. Respondents' relationships with HRSC agents were generally strong, 93% of agents were described as people “whose opinion matters,” and only 10% were described as hassling or making life difficult for the respondent. Growth mixture modeling identified five trajectories of HRSC receipt over the four-year period: Stable High (36% of sample), Stable Moderate (47%), Stable Low (14%), Decreasing (2%), and Increasing (2%). Binge drinking was relatively consistent for the three Stable HRSC classes (ranging from 11% to 15% of individuals), decreased steadily for the Increasing HRSC class (32%–16%), and fluctuated for the Decreasing HRSC class (decreasing from 10% to 2%, then increasing to 8%). For alcohol problems, the Increasing HRSC class showed the largest increase (2%–21%) before dropping to near-baseline levels (4%), whereas the Decreasing HRSC class fluctuated during the first three waves followed by no individuals reporting alcohol problems at the last wave. Results highlight the importance of examining heterogeneity in adults’ HRSC experiences because of its implications for understanding social influences on health-related behaviors.

0701 Perceived Exercise Response Heterogeneity in Adults with Restless Legs Syndrome

0701 Perceived Exercise Response Heterogeneity in Adults with Restless Legs Syndrome

Gender Differences, Motor Skills and Physical Fitness Heterogeneity in Adults with Down’s Syndrome

Background-Adults with Down's syndrome (DS) present lower physical fitness associated with heightened sedentary behaviors and motor skills impairments. Their etiologies and determinants seem to be heterogeneous. This study aims to evaluate physical fitness in adults with DS and to identify specific physical fitness profiles depending on gender and physical activity levels. Methods-Forty adults with DS (16 women, 24 men, 29.7 ± 7.5 years) performed six tests from the EUROFIT Battery and Motor Assessment Battery for Children (MAB-C). Their maximal aerobic capacity was assessed using an incremental treadmill test to assess (VO2peak). Ecological, physical activity, and sedentary levels were evaluated subjectively (Global Physical Activity Questionnaire) and objectively using an Actigraph GT9X® accelerometer over a seven-day period. Results-VO2peak and isometric strength were significantly lower for women (p < 0.01), whereas men had significantly lower flexibility than women (p < 0.05). Using a principal component analysis and an agglomerative hierarchical analysis, we identified three clusters. Cluster 1 (n = 14; 50% men; Body Mass index = 28.3 ± 4.3) was characterized by significantly poorer physical fitness variables (VO2peak (p < 0.01), strength (p < 0.01) and balance (p < 0.05)) compared to Clusters 2 and 3. Cluster 2 (n = 19; 58% men; Body Mass index = 22.9 ± 2.0) and Cluster 3 (n = 19; 58% men; BMI = 22.9 ± 1.9) were characterized by subjects with comparable physical fitness profiles, except for the balance capacities, which were significantly lower in Cluster 3 (p < 0.05). Conclusions-DS subjects exhibited high heterogeneity in terms of physical fitness, PA, and sedentary levels, with a significant gender effect. The present findings are important to identify subjects at higher risk of sedentary behaviors and impaired motor capacities to develop personalized PA programs.

Chaotic Genetic Patchiness in the Highly Valued Atlantic Stalked Barnacle Pollicipes pollicipes From the Iberian Peninsula: Implications for Fisheries Management

The stalked barnacle Pollicipes pollicipes inhabits rocky shores from the Atlantic coasts of Brittany (France) to Senegal. Because of the culinary traditions of southern Europe, stalked barnacles represent an important target species for local fisheries on the Iberian Peninsula. To manage this fishery sustainably, it is therefore important to assess the dynamics of local populations over the Iberian coast, and how they are interconnected at a wider scale using finely tuned genetic markers. In this work, a new enriched library of GT microsatellites for P. pollicipes was prepared and sequenced using Ion Torrent™ Next Gen-Sequencing Technology. 1,423 adults and juveniles were sampled in 15 localities of three geographic regions: southern Portugal, Galicia and Asturias (both in northern Spain). Twenty polymorphic loci arranged in five multiplex PCRs were then tested and validated as new molecular tools to address the spatial and temporal genetic patterns of P. pollicipes. Our results revealed high genetic diversity among adults. However, juveniles were genetically more structured than their adult counterparts, which alternatively displayed much more connectivity among the three studied regions. The lack of spatial genetic heterogeneity in adults may be due to the overlapping of several generations of settlers coming from different geographic origins, which mainly depends on the orientation of residual currents along the coast during reproduction. The genetic differentiation of juveniles may indeed be congruent with Iberian Peninsula hydrodynamics, which can produce chaotic genetic patchiness (CGP) at small temporal scales due to sweepstake reproductive success, collective dispersal and/or self-recruitment. Remarkably, most of the genetic heterogeneity of juveniles found in this work was located in Galicia, which could represent an admixture between distinct metapopulations or an old refuge for the most northern populations. To conclude, high genetic variation in P. pollicipes can lead to the false impression of population panmixia at the Iberian scale by masking more restricted and current-driven larval exchanges between regions. This possibility should be taken into consideration for further specific management and conservation plans for the species over the Iberian Peninsula.

Panobinostat in adults with H3 K27M-mutant diffuse midline glioma: a single-center experience

Diffuse midline gliomas (DMG) with the H3 K27M-mutation are a well-described entity with most DMG harboring this mutation, with notable heterogeneity in adults. No therapy has been proven to improve survival in this tumor type. Panobinostat is a histone deacetylase inhibitor that may have therapeutic benefit. We report our retrospective experience with use of panobinostat in adults (> 18years) with H3 K27M-mutant DMG treated at Mayo Clinic (Rochester) from January 2016 to August 2020, with follow-up until October 2021. Survival was calculated using the Kaplan-Meier method. 4 patients with H3 K27M-mutant glioma were treated with panobinostat as compassionate use. Patients had a median age of 40years (range 22-62years) and 2 were female. Tumor location was midline for all patients, spinal cord (n = 2), brainstem (n = 1), and thalamus (n = 1). All tumors were IDH1/IDH2 wildtype. 3 patients received radiotherapy followed by adjuvant panobinostat. All patients had no other pharmacologic therapy utilized prior to or during panobinostat therapy aside from concurrent dexamethasone utilized in 3 patients. No patient experienced a grade 2 or higher (per CTCAE grade) adverse effect. The median overall survival was 42months, median progression free survival of 19months, 2 patients were alive at last follow up (both with spinal cord tumors and received radiation). The best response was stable disease in 2 patients and a partial response in 1 patient. This is the first report of clinical outcomes of panobinostat in adults with H3 K27M-mutant DMG. We showed that it is well-tolerated at the dosage schedule that we describe, with no serious adverse effects throughout the study period.

Respiratory Viral and Bacterial Factors That Influence Early Childhood Asthma.

Asthma is a chronic respiratory condition characterised by episodes of shortness of breath due to reduced airway flow. The disease is triggered by a hyperreactive immune response to innocuous allergens, leading to hyper inflammation, mucus production, changes in structural cells lining the airways, and airway hyperresponsiveness. Asthma, although present in adults, is considered as a childhood condition, with a total of about 6.2 million children aged 18 and below affected globally. There has been progress in understanding asthma heterogeneity in adults, which has led to better patient stratification and characterisation of multiple asthma endotypes with distinct, but overlapping inflammatory features. The asthma inflammatory profile in children is not well-defined and heterogeneity of the disease is less described. Although many factors such as genetics, food allergies, antibiotic usage, type of birth, and cigarette smoke exposure can influence asthma development particularly in children, respiratory infections are thought to be the major contributing factor in poor lung function and onset of the disease. In this review, we focus on viral and bacterial respiratory infections in the first 10 years of life that could influence development of asthma in children. We also review literature on inflammatory immune heterogeneity in asthmatic children and how this overlaps with early lung development, poor lung function and respiratory infections. Finally, we review animal studies that model early development of asthma and how these studies could inform future therapies and better understanding of this complex disease.

Blind spot in sepsis management - Tissue level changes in microcirculation.

In sepsis cytokine-mediated inflammation, clotting cascade activation and glycocalyx shedding impair both function and structure of the microcirculation, compromising adequate tissue oxygenation/perfusion. Such mismatch results in "dysoxia", an imbalance in mitochondrial respiration.Microvessel injuries can be grouped into four types: cytotoxic oedema, micro-vessel heterogeneity, sluggish/absent flow, and focal anaemia. Recognition of such diversity in microcirculatory pathology, alongside with the implementation of novel biomarkers might reveal previously unobserved heterogeneity in adults diagnosed with sepsis. Early identification of distinct subtypes may help not only to better stratify disease severity but may also provide explanation to the often seen insufficient/absent response to resuscitative treatment. Experimental evidence suggests that impaired microcirculatory flow may correlate with organ dysfunction and mortality. Therefore, reliable/reproducible diagnostic tools, that provide real-time information about the dynamic state of the microcirculation, might be practice changers in managing the critically ill.The sublingual mucosa and the nailfolds provide easy access to microcirculation via hand-held, point-of-care devices. Accessing these windows, clinicians may recognise, understand and potentially correct the underlying tissue oxygenation/perfusion mismatch. This new clinical information might facilitate an individualised approach vs protocolised care aiming to administer the right balance of intravenous fluids/vasopressors, time/dose auxiliary treatment modalities and, most importantly, might also guide determining the optimal duration of resuscitation to avoid/minimise harm and maximise benefits in sepsis management. However, before every-day clinical use of such point-of-care microcameras, validation studies are needed to establish not only feasibility but reliability and reproducibility as well.

Cardiovascular Risk Heterogeneity in Adults with Diabetes: Selective Use of Coronary Artery Calcium in Statin Use Decision-making

Current American College of Cardiology/American Heart Association and American Diabetes Association guidelines recommend statin therapy for all patients with diabetes between the ages of 40 and 75, including those without cardiovascular disease (CVD). While diabetes is a major CVD risk factor, not all patients with diabetes have an equal risk of CVD. Thus, a more risk-based approach warrants consideration when recommending statin therapy for the primary prevention of CVD. Coronary artery calcium (CAC) is a noninvasive imaging modality that can help risk stratify patients with diabetes for future CVD events. CAC has been extensively studied in large cohorts such as the Multi-Ethnic Study of Atherosclerosis and found to outperform other novel risk stratification tools including carotid intima-media thickness. Moreover, a CAC score of 0 has been shown to be useful in downgrading the estimated risk of a CVD event in patients with diabetes and an intermediate Pooled Cohort Equation score. As clinicians weigh the recommendation for a lifelong therapy and the problem of statin nonadherence and patients weigh concerns about adverse effects of statins, the decision to initiate statin therapy in patients with diabetes is ideally a shared one between patients and providers, and CAC could facilitate this discussion.

Cells of Origin for Prostate Cancer.

Comprehensive knowledge of the normal prostate epithelial lineage hierarchy is a prerequisite to investigate the identity of the cells of origin for prostate cancer. The basal and luminal cells constitute most of the prostate epithelium and have been the major focuses of the study on the cells of origin for prostate cancer. Much progress has been made during the past few decades, mainly using mouse models, to understand the inter-lineage relationship and intra-lineage heterogeneity in adults as well as the lineage plasticity during conditions of stress. These studies have concluded that the adult mouse prostate basal and luminal cells are largely independently sustained under physiological conditions, but both types of cells possess the capacity for bipotent differentiation under stress or artificial experimental conditions. However, the existence or the identity of the putative progenitors within each lineage warrants further investigation. Whether the human prostate lineage hierarchy is completely the same as that of the mouse remains uncertain. Experiments from independent groups have demonstrated that both types of cells in mice and humans can serve as targets for transformation. But controversies remain whether the disease from distinct cells of origin display different clinical behaviors. Further investigation of the intra-lineage heterogeneity will provide new insights into this issue. Understanding the identity of the cells of origin for prostate cancer will help identify novel prognostic markers for early detection of aggressive prostate cancers, provide insights into the therapeutic vulnerability of these tumors, and inspire novel therapeutic strategies.

Strategy for automated metabolic profiling of glioma subtypes from ex-vivo HRMAS spectra

Introduction Infiltrating gliomas are primary brain tumors that express significant biological and clinical heterogeneity in adults, which complicates their treatment and prognosis. Characterization of tumor subtypes using spectroscopic analysis may assist in predicting malignant transformation and quantification of response to therapy.

Does Growing Childhood Socioeconomic Inequality Mean Future Inequality in Adult Health?

Over the past half century, American children have experienced increasingly unequal childhoods. The goal of this article is to begin to understand the implications of recent trends in social and economic inequalities among children for the future of inequalities in health among adults. The relative importance of many of the causal pathways linking childhood social and economic circumstances to adult health remains underexplored, and we know even less about how these causal pathways have changed over time. I combine a series of original analyses with reviews of relevant literature in a number of fields to inform a discussion of what growing childhood inequalities might mean for future inequalities in adult health. In the end, I argue that there is good reason to suppose that growing inequalities in children's social and economic circumstances will lead to greater heterogeneity in adults' morbidity and mortality.

Similar Subgroups Based on Cognitive Performance Parse Heterogeneity in Adults With ADHD and Healthy Controls

Objective: To characterize heterogeneity in adults with ADHD we aimed to identify subgroups within the adult ADHD spectrum, which differ in their cognitive profile. Method: Neuropsychological data from adults with ADHD (n = 133) and healthy control participants (n = 132) were used in a confirmatory factor analysis. The resulting six cognitive factors were correlated across participants to form networks. We used a community detection algorithm to cluster these networks into subgroups. Results: Both the ADHD and control group separated into three profiles that differed in cognitive performance. Profile 1 was characterized by aberrant attention and inhibition, profile 2 by increased delay discounting, and profile 3 by atypical working memory and verbal fluency. Conclusion: Our findings suggest that qualitative differences in neuropsychological performance exist in both control and ADHD adult individuals. This extends prior findings in children with and without ADHD and provides a framework to parse participants into well-defined subgroups.

Parents' Education and Their Adult Offspring's Other-Regarding Behavior

Does socioeconomic background when measured by parental educational attainment explain the heterogeneity in adults' other-regarding preferences? I test this by using data from two online experiments -- a Dictator Game and a Trust Game that were conducted with a broad sample of the Danish adult population. I match the experimental data with high-quality data from the Danish population registers about my subjects and their parents. Whereas previous studies have found socioeconomic status, including parental educational attainment, to be predictive for children's generosity, I find no such evidence among adults.This result is robust across age groups and genders. I provide two explanations for this. First, sociodemographic characteristics in general appear to be poor predictors of adults' other-regarding behavior. Second, by using Danish survey data, I find that Danish parents' educational attainment appears to be uncorrelated with how important they find it to teach their children to think of others. More speculative explanations are also provided.

Bone mineralization is elevated and less heterogeneous in adults with type 2 diabetes and osteoarthritis compared to controls with osteoarthritis alone

PurposeThe purpose of this study was to determine whether trabecular bone mineralization differed in adults with type 2 diabetes compared to adults without type 2 diabetes. MethodsProximal femur specimens were obtained following a total hip replacement procedure from men and women ≥65years of age with and without type 2 diabetes. A scanning electron microscope was used for quantitative backscattered electron imaging (qBEI) analysis of trabecular bone samples from the femoral neck. Gray scale images (pixel size=5.6μm2) were uploaded to ImageJ software and gray level (GL) values were converted to calcium concentrations (weight [wt] % calcium [Ca]) using data obtained with energy dispersive X-ray spectrometry. The following bone mineralization density distribution (BMDD) outcomes were collected: the weighted mean bone calcium concentration (CaMEAN), the most frequently occurring bone calcium concentration (CaPEAK) and mineralization heterogeneity (CaWIDTH). Differences between groups were assessed using the Student's t-test for normally distributed data and Mann–Whitney U-test for non-normally distributed data. An alpha value of <0.05 was considered significant. ResultsThirty-five Caucasian participants were recruited (mean [standard deviation, SD] age, 75.5 [6.5]years): 14 adults with type 2 diabetes (years since type 2 diabetes diagnosis, 13.5 [7.4]years) and 21 adults without type 2 diabetes. In the adults with type 2 diabetes, bone CaMEAN was 4.9% greater (20.36 [0.98]wt.% Ca versus 19.40 [1.07]wt.% Ca, p=0.015) and CaWIDTH was 9.4% lower (median [interquartile range] 3.55 [2.99–4.12]wt.% Ca versus 3.95 [0.71]wt.% Ca, p<0.001) compared to controls. There was no between-group difference in CaPEAK (21.12 [0.97]wt.% Ca for type 2 diabetes versus 20.44 [1.30]wt.% Ca for controls, p=0.121). ConclusionThe combination of elevated mean calcium concentration in bone and lower mineralization heterogeneity in adults with type 2 diabetes may have deleterious effects on the biomechanical properties of bone. These microscopic alterations in bone mineralization, which may be mediated by suppressed bone remodeling, further elucidate higher fracture risk in adults with type 2 diabetes.

Tumor necrosis factor-alpha promoter variants and iron phenotypes in 785 Hemochromatosis and Iron Overload Screening (HEIRS) Study participants

We sought to determine if TNF promoter variants could explain iron phenotype heterogeneity in adults with previous HFE genotyping. HEIRS Study participants genotyped for C282Y and H63D were designated as high transferrin saturation (TS) and/or serum ferritin (SF) (high TS/SF), low TS/SF, or controls. We grouped 191 C282Y homozygotes as high TS/SF, low TS/SF, or controls, and 594 other participants by race/ethnicity as high TS/SF or controls. Using denaturing high-performance liquid chromatography (DHPLC), we screened the TNF promoter region in each participant. We performed multiple regression analyses in C282Y homozygotes using age, sex, HEIRS Study Field Center, and positivity for TNF − 308G→A and − 238G→A to determine if these attributes predicted ln TS or ln SF. DHPLC analyses were successful in 99.3% of 791 participants and detected 9 different variants; TNF − 308G→A and − 238G→A were the most prevalent. Most subjects positive for variants were heterozygous. The phenotype frequencies of each variant did not differ significantly ( p < 0.05) across subgroups of C282Y homozygotes, or across white, black, Hispanic, and Asian non-C282Y homozygotes subgrouped as high TS/SF phenotypes and controls. TNF − 308G→A positivity was a significant predictor of initial screening ln TS but not ln SF; TNF − 238G→A predicted neither ln TS nor ln SF. We conclude that TNF promoter variants have little, if any, effect on initial screening SF values in adults with or without C282Y homozygosity. We cannot exclude a possible association of homozygosity for TNF promoter variants on TS and SF values.

HFE, SLC40A1, HAMP, HJV, TFR2, and FTL mutations detected by denaturing high‐performance liquid chromatography after iron phenotyping and HFE C282Y and H63D genotyping in 785 HEIRS Study participants

We sought to identify mutations that could explain iron phenotype heterogeneity in adults with previous HFE genotyping to detect C282Y and H63D. HEIRS Study participants genotyped for C282Y and H63D were designated as high transferrin saturation (TS) and/or serum ferritin (SF) (high TS/SF), low TS/SF, or controls. We grouped 191 C282Y homozygotes as high TS/SF, low TS/SF, or controls, and 594 other participants by race/ethnicity as high TS/SF or controls. Using denaturing high-performance liquid chromatography (DHPLC), we screened 20 regions of HFE, SLC40A1, HAMP, HJV, TFR2, and FTL in each participant. DHPLC analyses were successful in 99.3% of 791 participants and detected 117 different mutations. In C282Y homozygotes, 4.0% of high TS/SF participants had SLC40A1 Q248H, HAMP -72C>T, or HAMP R59G heterozygosity (0% Controls; P = 0.1200). In whites, 4.1% with high TS/SF and 1.3% of controls had HFE S65C or E168Q (P = 0.3049). HJV c.-6C>G and FTL L55L frequencies were greater in whites with high TS/SF than controls (0.0811 vs. 0.0200, P = 0.0144; 0.5743 vs. 0.4400, P = 0.0204, respectively). One Hispanic with high TS/SF (1.3%) had HAMP G71D heterozygosity. In blacks, SLC40A1 Q248H frequencies did not differ significantly between high TS/SF and control participants. Among Asians, 2.8% with high TS/SF were HFE V295A heterozygotes. Mutations other than HFE C282Y and H63D reported to be pathogenic were infrequently detected in high TS/SF participants. Genetic regions in linkage disequilibrium with HJV c.-6C>G and FTL L55L could partly explain high TS/SF phenotypes in whites. Am. J. Hematol., 2009. Published 2009 Wiley-Liss, Inc.

Oligoclonality of Vδ1 and Vδ2 Cells in Human Peripheral Blood Mononuclear Cells: TCR Selection Is Not Altered by Stimulation with Gram-Negative Bacteria

AbstractDespite the enormous potential repertoire of γδ T cells, there are several observations which suggest that the expressed γδ repertoire in the periphery of normal individuals is often quite restricted. To assess selective expansions among γδ T cells from both adult and newborn blood samples, PBMC from 12 normal adults and cord blood from 15 normal newborns were analyzed for TCRDV1 and TCRDV2 junctional diversity by CDR3 size spectratyping and single-strand conformational polymorphism. Although TCRBV usage showed extensive heterogeneity in adults and newborns, both populations often showed CDR3 region restriction for TCRDV1 and TCRDV2. Analysis of the CDR3 spectratype patterns of newborn twins suggested that clonal selection for TCRDV is independent of genetic background. The possible role of Gram-negative bacteria in driving selective responsiveness of γδ T cells in PBMCs from adults was examined by in vitro stimulation with Escherichia coli and Pseudomonas aeruginosa. Donors whose TCRDV repertoire was highly clonal in the unstimulated blood cells showed the same predominant clones among the bacteria-stimulated cultures. In individuals whose γδ T cells were less restricted, in vitro stimulation did not select for clonality; rather, the TCRDV repertoires were similar before and after bacterial stimulation. Together, these data indicate that γδ T cells are often clonally restricted in adults as well as in newborns and suggest that the prominent stimulatory activity of Gram-negative bacteria does not by itself account for the restriction or diversity of the γδ T cell repertoire.