Comparison between two analytic strategies to detect linkage to obesity with genetically determined age of onset: the Framingham Heart Study

BACKGROUND: Genes have been found to influence the age of onset of several diseases and traits. The occurrence of many chronic diseases, obesity included, appears to be strongly age-dependent. However, an analysis of potential age of onset genes for obesity has yet to be reported. There are at least two analytic methods for determining an age of onset gene. The first is to consider a person affected if they possess the trait before a certain age (an early age of onset phenotype). The second is to define the phenotype based on the residual from a survival analysis. RESULTS: No regions provided evidence for linkage at the more stringent level of p < 0.001. However, five regions showed consistent suggestive evidence for linkage (one marker with p < 0.01 and a second contiguous marker at p < 0.05). These regions were chromosome 1 (280–294 cM) and chromosome 16 (56–64 cM) for overweight using the survival analysis residual method and chromosome 13 (102–122 cM), chromosome 17 (127–138 cM), and chromosome 19 (23–47 cM) for obese before age 35. CONCLUSION: Only one region (chromosome 19 at 23–47 cM) showed somewhat consistent results between the two analytic methods. Potential reasons for inconsistent results between the two methods, as well as their strengths and weaknesses, are discussed. The use of both methods together to explore the genetics of the age of onset of a trait may prove to be beneficial in determining a gene that is linked only to an early age of onset phenotype versus one that determines age of onset through all age groups

The Construction and Validation of an Abridged Version of the Autism-Spectrum Quotient (AQ-Short)

This study reports on the development and validation of an abridged version of the 50-item Autism-Spectrum Quotient (AQ), a self-report measure of autistic traits. We aimed to reduce the number of items whilst retaining high validity and a meaningful factor structure. The item reduction procedure was performed on data from 1,263 Dutch students and general population adults. The resulting 28-item AQ-Short was subsequently validated in 3 independent samples, both clinical and controls, from the Netherlands and the UK. The AQ-Short comprises two higher-order factors assessing ‘social behavioral difficulties’ and ‘a fascination for numbers/patterns’. The clear factor structure of the AQ-Short and its high sensitivity and specificity make the AQ-Short a useful alternative to the full 50-item version

Long-term trial of protection provided by adenovirus-vectored vaccine expressing the PPRV H protein

A recombinant, replication-defective, adenovirus-vectored vaccine expressing the H surface glycoprotein of peste des petits ruminants virus (PPRV) has previously been shown to protect goats from challenge with wild-type PPRV at up to 4 months post vaccination. Here, we present the results of a longer-term trial of the protection provided by such a vaccine, challenging animals at 6, 9, 12 and 15 months post vaccination. Vaccinated animals developed high levels of anti-PPRV H protein antibodies, which were virus-neutralising, and the level of these antibodies was maintained for the duration of the trial. The vaccinated animals were largely protected against overt clinical disease from the challenge virus. Although viral genome was intermittently detected in blood samples, nasal and/or ocular swabs of vaccinated goats post challenge, viral RNA levels were significantly lower compared to unvaccinated control animals and vaccinated goats did not appear to excrete live virus. This protection, like the antibody response, was maintained at the same level for at least 15 months after vaccination. In addition, we showed that animals that have been vaccinated with the adenovirus-based vaccine can be revaccinated with the same vaccine after 12 months and showed an increased anti-PPRV antibody response after this boost vaccination. Such vaccines, which provide a DIVA capability, would therefore be suitable for use when the current live attenuated PPRV vaccines are withdrawn at the end of the ongoing global PPR eradication campaign

Impact of air pollution on hospital patients admitted with ST- and non-ST-segment elevation myocardial infarction in heavily polluted cities within the European Union

Background: Air pollution triggered diseases have become a leading health problem worldwide. The main adverse effects of air pollutants on human health are related to the cardiovascular system and particularly show an increasing prevalence of myocardial infarct and stroke. The aim of the study was to evaluate the influence of main air pollutants on non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI) admissions to local interventionalcardiology centers.Methods: Between 2014 and 2015, a multicenter registry of 1957 patients with acute myocardial infarction (STEMI, NSTEMI) admitted to interventional cardiology departments in three Polish cities were under investigation. The air pollution (PM2.5, PM10, NO2, SO2, O3) and weather conditions (temperature, barometric pressure, humidity) data for each city were collected as daily averages. The case-crossover design and conditional logistic regression were used to explore the association between acute myocardial infarctions and short-term air pollution exposure.Results: Occurrence of NSTEMI on the day of air pollution was triggered by PM2.5 (OR = 1.099, p = 0.01) and PM10 (OR = 1.078, p = 0.03). On the following day after the air pollution was recorded, NSTEMI was induced by: PM2.5 (OR = 1.093, p = 0.025), PM10 (OR = 1.077, p = 0.025) and SO2 (OR = 1.522, p = 0.009). For STEMI, events that occurred on the day in which air pollution was triggered by: PM2.5 (OR = 1.197, p &lt; 0.001), PM10 (OR = 1.163, p &lt; 0.001), SO2 (OR = 1.670, p = 0.001) and NO2 (OR = 1.287, p = 0.011). On the following day after air pollution was recorded, STEMI was induced by: PM2.5 (OR = 1.172, p &lt; 0.001), PM10 (OR = 1.131, p = 0.001), SO2 (OR = 1.550, p = 0.005) and NO2 (OR = 1.265, p = 0.02). None of the weather conditions indicated were statistically significant for acute myocardial infarction occurrence.Conclusions: The most important pollutants triggering acute myocardial infarction occurrence in the population of southern Poland, both on the day of air pollution and the following day are particulate matters (PM2.5, PM10) and gaseous pollutants including NO2 and SO2. These pollutants should be regarded as modifiable risk factors and thus, their reduction is a priority in order to decrease total morbidity and mortality in Poland

Mental Health of Parents and Life Satisfaction of Children: A Within-Family Analysis of Intergenerational Transmission of Well-Being

This paper addresses the extent to which there is an intergenerational transmission of mental health and subjective well-being within families. Specifically it asks whether parents’ own mental distress influences their child’s life satisfaction, and vice versa. Whilst the evidence on daily contagion of stress and strain between members of the same family is substantial, the evidence on the transmission between parental distress and children’s well-being over a longer period of time is sparse. We tested this idea by examining the within-family transmission of mental distress from parent to child’s life satisfaction, and vice versa, using rich longitudinal data on 1,175 British youths. Results show that parental distress at year t-1 is an important determinant of child’s life satisfaction in the current year. This is true for boys and girls, although boys do not appear to be affected by maternal distress levels. The results also indicated that the child’s own life satisfaction is related with their father’s distress levels in the following year, regardless of the gender of the child. Finally, we examined whether the underlying transmission correlation is due to shared social environment, empathic reactions, or transmission via parent-child interaction

Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps and Pathways Forward. An Official American Thoracic Society Research Statement

BACKGROUND: Right ventricular (RV) adaptation to acute and chronic pulmonary hypertensive syndromes is a significant determinant of short- and long-term outcomes. Although remarkable progress has been made in the understanding of RV function and failure since the meeting of the NIH Working Group on Cellular and Molecular Mechanisms of Right Heart Failure in 2005, significant gaps remain at many levels in the understanding of cellular and molecular mechanisms of RV responses to pressure and volume overload, in the validation of diagnostic modalities, and in the development of evidence-based therapies. METHODS: A multidisciplinary working group of 20 international experts from the American Thoracic Society Assemblies on Pulmonary Circulation and Critical Care, as well as external content experts, reviewed the literature, identified important knowledge gaps, and provided recommendations. RESULTS: This document reviews the knowledge in the field of RV failure, identifies and prioritizes the most pertinent research gaps, and provides a prioritized pathway for addressing these preclinical and clinical questions. The group identified knowledge gaps and research opportunities in three major topic areas: 1) optimizing the methodology to assess RV function in acute and chronic conditions in preclinical models, human studies, and clinical trials; 2) analyzing advanced RV hemodynamic parameters at rest and in response to exercise; and 3) deciphering the underlying molecular and pathogenic mechanisms of RV function and failure in diverse pulmonary hypertension syndromes. CONCLUSIONS: This statement provides a roadmap to further advance the state of knowledge, with the ultimate goal of developing RV-targeted therapies for patients with RV failure of any etiology

Hypopituitarism is associated with lower oxytocin concentrations and reduced empathic ability

Purpose Central diabetes insipidus is characterised by arginine vasopressin deficiency. Oxytocin is structurally related to vasopressin and is synthesised in the same hypothalamic nuclei, thus we hypothesised that patients with acquired central diabetes insipidus and anterior hypopituitarism would display an oxytocin deficiency. Moreover, psychological research has demonstrated that oxytocin influences social and emotional behaviours, particularly empathic behaviour. We therefore further hypothesised that central diabetes insipidus patients would perform worse on empathy-related tasks, compared to age-matched and gender-matched clinical control (clinical control-isolated anterior hypopituitarism) and healthy control groups. Method Fifty-six participants (age 46.54 ± 16.30 yrs; central diabetes insipidus: n = 20, 8 males; clinical control: n = 15, 6 males; healthy control: n = 20, 7 males) provided two saliva samples which were analysed for oxytocin and completed two empathy tasks. Results Hypopituitary patients (both central diabetes insipidus and clinical control groups) had significantly lower oxytocin concentrations compared to healthy control participants. Hypopituitary patients also performed significantly worse on both the reading the mind in the eyes task and the facial expression recognition task compared to healthy control participants. Regression analyses further revealed that central diabetes insipidus patients’ oxytocin concentrations significantly predicted their performance on easy items of the reading the mind in the eyes task. Conclusions Hypopituitarism may therefore be associated with reduced oxytocin concentrations and impaired empathic ability. While further studies are needed to replicate these findings, our data suggest that oxytocin replacement may offer a therapeutic approach to improve psychological well-being in patients with hypopituitarism

Are skin disorders related to work strain in hospital workers? A cross-sectional study

To evaluate whether occupational stress factors (high demands, low control, low social support, strain, and iso-strain) are associated with skin disorders in hospital workers and whether psychological problems, such as anxiety and depression, act as potential mechanisms through which occupational stress factors are associated with skin disorders

T Regulatory Cells in Cord Blood—FOXP3 Demethylation as Reliable Quantitative Marker

Regulatory T-cells (Tregs), characterized as CD4+CD25(hi) T-cells expressing FOXP3, play a crucial role in controlling healthy immune development during early immune maturation. Recently, FOXP3 demethylation was suggested to be a novel marker for natural Tregs in adults. In cord blood, the role and function of Tregs and its demethylation is poorly understood. We assessed FOXP3 demethylation in cord blood in relation to previously used Treg markers such as CD4+CD25(hi), FOXP3 mRNA, protein expression, and suppressive Treg function

Interference of functional dual-tasks on gait in untrained people with Parkinson's disease and healthy controls: a cross-sectional study

[EN] Background In Parkinson's disease (PD) population, performing secondary tasks while walking further deteriorates gait and restrict mobility in functional contexts of daily life. This study (1) analyzed the interference of functional cognitive and motor secondary task on untrained people with PD and (2) compared their walking with healthy subjects. Methods Forty people with PD (aged 66.72 [7.5] years, Hoehn and Yahr stage I-II-III, on-medication) composed the PD group (PDG) and 43 participants (aged 66.60 [8.75] years) formed the group of healthy counterparts (HG). Gait was evaluated through spatiotemporal, kinematic and kinetic outcomes in five conditions: single task (ST) and visual, verbal, auditory and motor dual-task (DT). Results The velocity, stride length, and braking force performance of both groups was statistically higher in the ST condition than in verbal, auditory and motor DT (p.05). Conclusions: In untrained participants with PD, verbal and motor secondary tasks affect gait significantly, while auditory and visual tasks interfere to a lesser extent. Untrained people with PD have a poorer gait performance than their healthy counterparts, but in different grades according to the analyzed variables. Trial registration The data in this paper are part of a single-blind, randomized, controlled trial and correspond to the evaluations performed before a physical rehabilitation program, retrospectively registered with the number at clinicaltrial.govNCT04038866.San Martín Valenzuela, C.; Dueñas Moscardó, L.; Lopez Pascual, J.; Serra-Añó, P.; Tomás, JM. (2020). Interference of functional dual-tasks on gait in untrained people with Parkinson's disease and healthy controls: a cross-sectional study. BMC Musculoskeletal Disorders. 21(1):1-11. https://doi.org/10.1186/s12891-020-03431-xS111211Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry. 2008;79:368–76.Soh S-E, McGinley JL, Watts JJ, Iansek R, Murphy AT, Menz HB, et al. Determinants of health-related quality of life in people with Parkinson’s disease: a path analysis. Qual Life Res. 2013;22:1543–53.Tan D, Danoudis M, McGinley J, Morris ME. Relationships between motor aspects of gait impairments and activity limitations in people with Parkinson’s disease: a systematic review. Parkinsonism Relat Disord. 2012;18:117–24.Kelly VE, Eusterbrock AJ, Shumway-Cook A. A review of dual-task walking deficits in people with Parkinson’s disease: motor and cognitive contributions, mechanisms, and clinical implications. Parkinson’s Disease. 2012;918719.Sofuwa O, Nieuwboer A, Desloovere K, Willems A-M, Chavret F, Jonkers I. Quantitative gait analysis in Parkinson’s disease: comparison with a healthy control group. Arch Phys Med Rehabil. 2005;86:1007–13.Beauchet O, Berrut G. Gait and dual-task: definition, interest, and perspectives in the elderly. Psychologie et NeuroPsychiatrie du Vieillissement. 2006;4:215–25.Raffegeau TE, Krehbiel LM, Kang N, Thijs FJ, Altmann LJP, Cauraugh JH, et al. A meta-analysis: Parkinson’s disease and dual-task walking. Parkinsonism Relat Disord. 2019 May;62:28–35.Eric R. Kandel, James H. Schwartz, Thomas M. Jessell, Steven a. Siegelbaum, A. J. Hudspeth. Principles of neural science. Fifth edition. McGraw-Hill Medical: United States of America; 2013.Eisinger RS, Cernera S, Gittis A, Gunduz A, Okun MS. A review of basal ganglia circuits and physiology: application to deep brain stimulation. Parkinsonism Relat Disord. 2019 Feb;59:9–20.Isella V, Mapelli C, Morielli N, De Gaspari D, Siri C, Pezzoli G, et al. Validity and metric of MiniMental Parkinson and MiniMental state examination in Parkinson’s disease. Neurol Sci. 2013;34:1751–8.Morris ME, McGinley J, Huxham F, Collier J, Iansek R. Constraints on the kinetic, kinematic and spatiotemporal parameters of gait in Parkinson’s disease. Hum Mov Sci. 1999;18:461–83.Brauer SG, Morris ME. Can people with Parkinson’s disease improve dual tasking when walking? Gait & Posture. 2010;31:229–33.Baron EI, Miller Koop M, Streicher MC, Rosenfeldt AB, Alberts JL. Altered kinematics of arm swing in Parkinson’s disease patients indicates declines in gait under dual-task conditions. Parkinsonism Relat Disord. 2018;48:61–7.Rochester L, Galna B, Lord S, Burn D. The nature of dual-task interference during gait in incident Parkinson’s disease. Neuroscience. 2014;265:83–94.Logan D, Kiemel T, Dominici N, Cappellini G, Ivanenko Y, Lacquaniti F, et al. The many roles of vision during walking. Exp Brain Res. 2010;206:337–50.de Luna RA, Mihailovic A, Nguyen AM, Friedman DS, Gitlin LN, Ramulu PY. The Association of Glaucomatous Visual Field Loss and Balance. Transl Vis Sci Technol. 2017 May 22;6(3):8.Suarez H, Geisinger D, Ferreira ED, Nogueira S, Arocena S, Roman CS, et al. Balance in Parkinson’s disease patients changing the visual input. Brazilian Journal of Otorhinolaryngology. 2011;77:651–5.Wu T, Hallett M. Neural correlates of dual task performance in patients with Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2008;79:760–6.Canning CG. The effect of directing attention during walking under dual-task conditions in Parkinson’s disease. Parkinsonism Relat Disord. 2005;11:95–9.Wu T, Liu J, Zhang H, Hallett M, Zheng Z, Chan P. Attention to automatic movements in Parkinson’s disease: modified automatic mode in the striatum. Cereb Cortex. 2015;25:3330–42.de Roiz R. M, Cacho EWA, Pazinatto MM, Reis JG, Cliquet a. Barasnevicius-Quagliato EMA Gait analysis comparing Parkinson’s disease with healthy elderly subjects Arq Neuropsiquiatr. 2010;68:81–6.Grabli D, Karachi C, Welter M-L, Lau B, Hirsch EC, Vidailhet M, et al. Normal and pathological gait: what we learn from Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2012 Oct;83(10):979–85.Anna C, Serena F, Maurizio F. Del Sorbo Francesca, Romito Luigi M., Elia Antonio E., et al. quantitative gait analysis in parkin disease: possible role of dystonia. Mov Disord. 2016;31:1720–8.Morris M, Iansek R, McGinley J, Matyas T, Huxham F. Three-dimensional gait biomechanics in Parkinson’s disease: evidence for a centrally mediated amplitude regulation disorder. Mov Disord. 2005;20:40–50.Peterson CL, Kautz SA, Neptune RR. Braking and propulsive impulses increase with speed during accelerated and decelerated walking. Gait Posture. 2011;33:562–7.Chiu M-C, Wang M-J. The effect of gait speed and gender on perceived exertion, muscle activity, joint motion of lower extremity, ground reaction force and heart rate during normal walking. Gait & Posture. 2007;25:385–92.Muniz AMS, Liu H, Lyons KE, Pahwa R, Liu W, Nobre FF, et al. Comparison among probabilistic neural network, support vector machine and logistic regression for evaluating the effect of subthalamic stimulation in Parkinson disease on ground reaction force during gait. J Biomech. 2010;43:720–6.Chastan N, Do MC, Bonneville F, Torny F, Bloch F, Westby GWM, et al. Gait and balance disorders in Parkinson’s disease: impaired active braking of the fall of Centre of gravity. Mov Disord. 2009;24:188–95.Perneger T. What's wrong with Bonferroni adjustments. BMJ. 1998 Apr 18;316(7139):1236–8