Multivariate analysis of lifestyle, constitutive and body composition factors influencing bone health in community-dwelling older adults from Madeira, Portugal

This study describes the association between habitual physical activity (PA), other lifestyle/constitutive factors, body composition, and bone health/strength in a large sample of older adults from Madeira, Portugal. This cross-sectional study included 401 males and 401 females aged 60-79 years old. Femoral strength index (FSI) and bone mineral density (BMD) of the whole body, lumbar spine (LS), femoral neck (FN), and total lean tissue mass (TLTM) and total fat mass (TFM) were determined by dual-energy X-ray absorptiometry-DXA. PA was assessed during face-to-face interviews using the Baecke questionnaire and for a sub-sample by Tritrac accelerometer. Demographic and health history information were obtained by telephone interview through questionnaire. The relationship between habitual PA variables and bone health/strength indicators (whole body BMD, FNBMD, LSBMD, and FSI) investigated using Pearson product-moment correlation coefficient was similar for females (0.098≤r≤0.189) and males (0.104≤r≤0.105). Results from standard multiple regression analysis indicated that the primary and most significant predictors for FNBMD in both sexes were age, TLTM, and TFM. For LSBMD, the most significant predictor was TFM in men and TFM, age, and TLTM in females. Our regression model explained 8.3-14.2% and 14.8-29.6% of the total variance in LSBMD and FNBMD for males and females, respectively. This study suggests that habitual PA is minimally but positively associated with BMD and FSI among older adult males and females and that body composition factors like TLTM and TFM are the strongest determinants of BMD and FSI in this population

Ontogeny of Toll-Like Receptor Mediated Cytokine Responses of Human Blood Mononuclear Cells

Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete understanding of the ontogeny of the immune system over the first years of life is thus urgently needed. Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects). We found that innate TLR responses (i) known to support Th17 adaptive immune responses (IL-23, IL-6) peaked around birth and declined over the following 2 years only to increase again by adulthood; (ii) potentially supporting antiviral defense (IFN-α) reached adult level function by 1 year of age; (iii) known to support Th1 type immunity (IL-12p70, IFN-γ) slowly rose from a low at birth but remained far below adult responses even at 2 years of age; (iv) inducing IL-10 production steadily declined from a high around birth to adult levels by 1 or 2 years of age, and; (v) leading to production of TNF-α or IL-1β varied by stimuli. Our data contradict the notion of a linear progression from an ‘immature’ neonatal to a ‘mature’ adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation

Post-COVID symptoms are associated with endotypes reflecting poor inflammatory and hemostatic modulation

IntroductionPersistent symptoms after COVID-19 infection (“long COVID”) negatively affects almost half of COVID-19 survivors. Despite its prevalence, its pathophysiology is poorly understood, with multiple host systems likely affected. Here, we followed patients from hospital to discharge and used a systems-biology approach to identify mechanisms of long COVID.MethodsRNA-seq was performed on whole blood collected early in hospital and 4-12 weeks after discharge from 24 adult COVID-19 patients (10 reported post-COVID symptoms after discharge). Differential gene expression analysis, pathway enrichment, and machine learning methods were used to identify underlying mechanisms for post-COVID symptom development.ResultsCompared to patients with post-COVID symptoms, patients without post-COVID symptoms had larger temporal gene expression changes associated with downregulation of inflammatory and coagulation genes over time. Patients could also be separated into three patient endotypes with differing mechanistic trajectories, which was validated in another published patient cohort. The “Resolved” endotype (lowest rate of post-COVID symptoms) had robust inflammatory and hemostatic responses in hospital that resolved after discharge. Conversely, the inflammatory/hemostatic responses of “Suppressive” and “Unresolved” endotypes (higher rates of patients with post-COVID symptoms) were persistently dampened and activated, respectively. These endotypes were accurately defined by specific blood gene expression signatures (6-7 genes) for potential clinical stratification.DiscussionThis study allowed analysis of long COVID whole blood transcriptomics trajectories while accounting for the issue of patient heterogeneity. Two of the three identified and externally validated endotypes (“Unresolved” and “Suppressive”) were associated with higher rates of post-COVID symptoms and either persistently activated or suppressed inflammation and coagulation processes. Gene biomarkers in blood could potentially be used clinically to stratify patients into different endotypes, paving the way for personalized long COVID treatment

Ontogeny of Toll-Like and NOD-Like Receptor-Mediated Innate Immune Responses in Papua New Guinean Infants

Studies addressing the ontogeny of the innate immune system in early life have reported mainly on Toll-like receptor (TLR) responses in infants living in high-income countries, with little or even no information on other pattern recognition receptors or on early life innate immune responses in children living under very different environmental conditions in less-developed parts of the world. In this study, we describe whole blood innate immune responses to both Toll-like and nucleotide-binding oligomerization domain (NOD)-like receptor agonists including the widely used vaccine adjuvant ‘alum’ in a group of Papua New Guinean infants aged 1–3 (n = 18), 4–6 (n = 18), 7–12 (n = 21) and 13–18 (n = 10) months old. Depending on the ligands and cytokines studied, different age-related patterns were found: alum-induced IL-1β and CXCL8 responses were found to significantly decline with increasing age; inflammatory (IL-6, IL-1β, IFN-γ) responses to TLR2 and TLR3 agonists increased; and IL-10 responses remained constant or increased during infancy, while TNF-α responses either declined or remained the same. We report for the first time that whole blood innate immune responses to the vaccine adjuvant alum decrease with age in infancy; a finding that may imply that the adjuvant effect of alum in pediatric vaccines could be age-related. Our findings further suggest that patterns of innate immune development may vary between geographically diverse populations, which in line with the ‘hygiene hypothesis’ particularly involves persistence of innate IL-10 responses in populations experiencing higher infectious pressure

Multi-Omic Data Integration Allows Baseline Immune Signatures to Predict Hepatitis B Vaccine Response in a Small Cohort

Background: Vaccination remains one of the most effective means of reducing the burden of infectious diseases globally. Improving our understanding of the molecular basis for effective vaccine response is of paramount importance if we are to ensure the success of future vaccine development efforts. Methods: We applied cutting edge multi-omics approaches to extensively characterize temporal molecular responses following vaccination with hepatitis B virus (HBV) vaccine. Data were integrated across cellular, epigenomic, transcriptomic, proteomic, and fecal microbiome profiles, and correlated to final HBV antibody titres. Results: Using both an unsupervised molecular-interaction network integration method (NetworkAnalyst) and a data-driven integration approach (DIABLO), we uncovered baseline molecular patterns and pathways associated with more effective vaccine responses to HBV. Biological associations were unravelled, with signalling pathways such as JAK-STAT and interleukin signalling, Toll-like receptor cascades, interferon signalling, and Th17 cell differentiation emerging as important pre-vaccination modulators of response. Conclusion: This study provides further evidence that baseline cellular and molecular characteristics of an individual’s immune system influence vaccine responses, and highlights the utility of integrating information across many parallel molecular datasets

Adaptations architecturales du tissu osseux en réponse à l\u27exercice physique : intérêts et limites des méthodes non invasives utilisées chez l\u27homme

AimThe purpose of this paper is to give an overview of the imaging techniques that are currently used to study the effects of exercise on bone architecture.Current knowledgeIt is now widely accepted that the prevention of osteoporosis must be initiated in childhood, because the immature skeleton is more responsive to physical loading. Exercise recommendations for bone health promotion must consider the effects of loading not only on the more traditional measures of bone mineral content and macroarchitecture, but also on the microarchitecture and structural properties of the skeleton. The latter requires high precision 3D methods like quantitative computed tomography and magnetic resonance imaging.ProspectsImaging resolutions used most commonly in exercise studies of children have sufficient precision to assess bone density and gross geometry. However, they remain insufficient to clearly depict and quantify the trabecular bone microarchitecture in vivo in humans.<br /