Ethnic differences in calcium, phosphate and bone metabolism

The prevalence of osteoporosis and the incidence of age-related fragility fracture vary by ethnicity. There is greater than 10-fold variation in fracture probabilities between countries across the world. Mineral and bone metabolism are intimately interlinked, and both are known to exhibit patterns of daily variation, known as the diurnal rhythm (DR). Ethnic differences are described for Ca and P metabolism. The importance of these differences is described in detail between select ethnic groups, within the USA between African-Americans and White-Americans, between the Gambia and the UK and between China and the UK. Dietary Ca intake is higher in White-Americans compared with African-Americans, and is higher in White-British compared with Gambian and Chinese adults. Differences are observed also for plasma 25-hydroxy vitamin D, related to lifestyle differences, skin pigmentation and skin exposure to UVB-containing sunshine. Higher plasma 1,25-dihydroxy vitamin D and parathyroid hormone are observed in African-American compared with White-American adults. Plasma parathyroid hormone is also higher in Gambian adults and, in winter, in Chinese compared with White-British adults. There may be ethnic differences in the bone resorptive effects of parathyroid hormone, with a relative skeletal resistance to parathyroid hormone observed in some, but not all ethnic groups. Renal mineral excretion is also influenced by ethnicity; urinary Ca (uCa) and urinary P (uP) excretions are lower in African-Americans compared with White-Americans, and in Gambians compared with their White-British counterparts. Little is known about ethnic differences in the DR of Ca and P metabolism, but differences may be expected due to known differences in lifestyle factors, such as dietary intake and sleep/wake pattern. The ethnic-specific DR of Ca and P metabolism may influence the net balance of Ca and P conservation and bone remodelling. These ethnic differences in Ca, P and the bone metabolism may be important factors in the variation in skeletal health

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Person-Specific Non-shared Environmental Influences in Intra-individual Variability : A Preliminary Case of Daily School Feelings in Monozygotic Twins

Most behavioural genetic studies focus on genetic and environmental influences on inter-individual phenotypic differences at the population level. The growing collection of intensive longitudinal data in social and behavioural science offers a unique opportunity to examine genetic and environmental influences on intra-individual phenotypic variability at the individual level. The current study introduces a novel idiographic approach and one novel method to investigate genetic and environmental influences on intra-individual variability by a simple empirical demonstration. Person-specific non-shared environmental influences on intra-individual variability of daily school feelings were estimated using time series data from twenty-one pairs of monozygotic twins (age = 10 years, 16 female pairs) over two consecutive weeks. Results showed substantial inter-individual heterogeneity in person-specific non-shared environmental influences. The current study represents a first step in investigating environmental influences on intra-individual variability with an idiographic approach, and provides implications for future behavioural genetic studies to examine developmental processes from a microscopic angle

Amorphous carbon nanoparticles: a versatile label for rapid diagnostic (immuno)assays

Carbon nanoparticles (CNPs) labeled with reporter molecules can serve as signaling labels in rapid diagnostic assays as an alternative to gold, colored latex, silica, quantum dots, or up-converting phosphor nanoparticles. Detailed here is the preparation of biomolecule-labeled CNPs and examples of their use as a versatile label. CNPs can be loaded with a range of biomolecules, such as DNA, antibodies, and proteins (e.g., neutravidin or a fusion protein of neutravidin with an enzyme), and the resulting conjugates can be used to detect analytes of high or low molecular mass

Convenience and satisfaction in direct oral anticoagulant-treated patients with atrial fibrillation

Abstract Background Direct oral anticoagulants (DOACs) are the preferred anticoagulants for thromboprophylaxis in atrial fibrillation. We aimed to identify determinants of quality of life related to DOAC treatment to optimize DOAC treatment convenience and satisfaction. Methods We conducted a cross‐sectional study in DOAC users. DOAC treatment–related convenience and satisfaction were measured by Perception of Anticoagulant Treatment Questionnaire. Higher scores are more favorable (range, 0‐100). Patient‐reported outcome measures and drug‐ and organization‐related factors were collected. Multiple regression analyses were used to evaluate the association between these factors (ie, exposure variables) and DOAC treatment–related convenience and treatment satisfaction (ie, outcome variables). Results Of 1598 patients invited, 1035 responded, and 962 were included. The median convenience score was 98.1 (94.2‐100.0), mean satisfaction score 66.5± 14.9. Twenty‐four percent felt not well informed at the start of DOAC; 6.9% did not know who to turn to with questions. Multiple regression analyses showed that lacking sense of security, the predefined composite of receiving insufficient information at start of DOAC and/or not knowing who to turn to with questions was associated with lower convenience (regression coefficient, −1.29; 95% confidence interval [CI], −2.16 to −0.41). Bleeding, gastrointestinal complaints, and lower medication adherence were also associated with lower convenience. Missing sense of security (regression coefficient −6.59; 95% CI, −8.94 to −4.24) and bleeding without consultation were associated with lower treatment satisfaction. Conclusions Accessible interventions to improve DOAC care could be providing more instruction at treatment initiation and ensuring that patients know who to contact in case of problems

Differential family and peer environmental factors are related to severity and comorbidity in childresn with ADHD

Contains fulltext : 70260.pdf (publisher's version ) (Closed access)Behavioral genetic studies imply that salient environmental influences operate within families, making siblings in a family different rather than similar. This study is the first one to examine differential sibling experiences (as measured with the Sibling Inventory of Differential Experience) and its effect on behavioral outcomes within ADHD families. Subjects were 45 Dutch ADHD probands and their unaffected siblings (n = 45) aged 10-18 years. ADHD probands and their unaffected siblings reported differences in sibling interaction, parental treatment, and peer characteristics. These nonshared environmental influences were related to both the severity of ADHD symptoms as well as to comorbid problem behaviors. These findings suggest that environmental influences that operate within ADHD families appear relevant to the severity of problem behaviors of ADHD children and their siblings

A method for exposing rodents to resuspended particles using whole-body plethysmography

BACKGROUND: Epidemiological studies have reported increased risks of cardiopulmonary-related hospitalization and death in association with exposure to elevated levels of particulate matter (PM) across a wide range of urban areas. In response to these findings, researchers have conducted animal inhalation exposures aimed at reproducing the observed toxicologic effects. However, it is technically difficult to quantitate the actual amount of PM delivered to the lung in such studies, and dose is frequently estimated using default respiration parameters. Consequently, the interpretation of PM-induced effects in rodents exposed via whole-body inhalation is often compromised by the inability to determine deposited dose. To address this problem, we have developed an exposure system that merges the generation of dry, aerosolized particles with whole-body plethysmography (WBP), thus permitting inhalation exposures in the unrestrained rat while simultaneously obtaining data on pulmonary function. RESULTS: This system was validated using an oil combustion-derived particle (HP12) at three nominal concentrations (3, 12, and 13 mg/m(3)) for four consecutive exposure days (6 hr/day); a single 6-hour exposure to 13 mg/m(3 )of HP12 was also conducted. These results demonstrated that the system was both reliable and consistent over these exposure protocols, achieving average concentrations that were within 10% of the targeted concentration. In-line filters located on the exhaust outlets of individual WBP chambers showed relative agreement in HP12 mass for each day and were not statistically different when compared to one another (p = 0.16). Temperatures and relative humidities were also similar between chambers during PM and air exposures. Finally, detailed composition analyses of both HP12 filter and bulk samples showed that grinding and aerosolization did not change particle chemistry. CONCLUSION: The results of this study demonstrate that it is possible to expose rodents to resuspended, dry PM via whole-body inhalation while these animals are maintained in WBP chambers. This new methodology should significantly improve the ability to assess dosimetry under minimally stressful exposure conditions

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs) and sickness behavior

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions

Polygenic liability for schizophrenia and childhood adversity influences daily‐life emotion dysregulation and psychosis proneness

Objective To test whether polygenic risk score for schizophrenia (PRS-S) interacts with childhood adversity and daily-life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress-sensitivity measures. Methods The data were retrieved from a general population twin cohort including 593 adolescents and young adults. Childhood adversity was assessed using the Childhood Trauma Questionnaire. Daily-life stressors and momentary mental state domains were measured using ecological momentary assessment. PRS-S was trained on the latest Psychiatric Genetics Consortium schizophrenia meta-analysis. The analyses were conducted using multilevel mixed-effects tobit regression models. Results Both childhood adversity and daily-life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS-S was only associated with increased positive affect. No gene-environment correlation was detected. There is novel evidence for interaction effects between PRS-S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, P = 0.013), positive affect (b = -0.05, P = 0.043), and subtle psychosis expression (b = 0.11, P = 0.007)] and stress-sensitivity measures. Conclusion Exposure to childhood adversities, particularly in individuals with high PRS-S, is pleiotropically associated with emotion dysregulation and psychosis proneness