Genealogical analyses in open population of Silla Argentino horses belonging to the national police of Colombia

This study aimed to evaluate population parameters, genetic diversity and identify the ancestors with the highest genetic contribution of an open population of Silla Argentino horses in Colombia using pedigree data. 508 horses born between 1998 and 2018 were evaluated, called reference population (RP). The ancestors of the RP were added, defining the total population (TP) whit 1,861 horses born since 1905. Population parameters were estimated, including inbreeding coefficient (F), effective population size (Ne), effective number of founders (fe), ancestors (fa), and founder genomes (fg) and generation interval (GIN). The GIN was 10.1 (TP) and 7.7 (RP) years. The estimate of F for the RP was 0.3%, indicating control in mattings. The Ne was 317 (RP) and 179 (TP). The probability of genes origin indicated values for fe, fa and fg of 386, 187 and 351 (TP), and 161, 64 and 56 (RP), respectively, evidencing a reduction of genetic variability in the RP. Half of the genetic variation in the equine population studied was explained by 40 ancestors. The results show loss of genetic diversity in the RP and the genetic contribution of the ancestors suggests the need to increase the number of stallions for breeding and guide mating to increase genetic diversity in the new generations of Silla Argentino horses of the Colombian National Police

Sex Differences in Association of Depression with Self-Rated Health and Awareness of Cardiovascular Preventive Measures

Aim: To determine gender differences in the relationship between depression and self-rated health and awareness of measures for cardiovascular prevention in an open population of 25-4 years in Russia/Siberia (Novosibirsk). Methods: Under the screening based on the budgetary theme No. AAAA-A17-117112850280-2, a random representative sample of the male and female population who were residents in one of the districts in Novosibirsk was examined in 2013-2016 (n=975, 43.8% males, mean age 34.5±0.4 years). Selfassessment of health and awareness of preventive measures was assessed using the questionnaire "Knowledge and attitude to own health". Depression was assessed using the depression scale based on the adapted MMPI questionnaire. Results: There was a linear increase in the proportion of those who considered themselves "not entirely healthy" or "sick" with an increase in the level of depression in 25-34 and 35-44 years age groups of studied population. Women aged 35-44 years with a moderate level of depression are 15-20% more likely than men to report that they are “not entirely healthy” and “sick” and have health complaints (p <0.05). Men aged 25-34y with major depression were more likely to report negative self-esteem and health complaints but these differences were not statistically significant. In both age groups, with an increase in the level of depression by 20-40%, the proportion of people who “clearly did not take care of their health” among men and women increased. However, the presence of depression eliminate statistical gender differences. In the presence of depression, women are 16% more likely than men to consider it highly likely to develop a serious illness in the next 5-10 years, while they are 10% less likely to have regular health checks. Women were 4-12% more likely than men to doubt the possibilities of preventive medicine, regardless of the level of depression. Conclusions: As depression rises, self-rated health falls and confidence in the effectiveness of preventive measures among both sexes decreases. And while women are more likely to report pessimistic responses to health and prevention, the presence of high levels of depression deletes gender differences.

The effect of sleep duration on the risk of diabetes mellitus in an open population of men aged 45–64 years (international epidemiological studies)

Objective: to study the effect of sleep duration on the 16-year risk of developing type 2 diabetes mellitus (DM) in an open population of men aged 45–64 years living in Novosibirsk.Patients and methods. In 2003–2005 during the IV screening (HAPIEE project), a representative sample of men aged 45–69 years (n=781; mean age – 56.48±0.2 years, response rate – 61%) was examined. A standard clinical and epidemiological examination was carried out: sleep duration was assessed using the Jenkins scale, the level of state-trait anxiety (STA) – using the Spielberger self-assessment scale, depression, life exhaustion, family and workplace stress – with MONICA-MOPSY scales. Social support was assessed with Berkman–Syme Social Network Index. The cohort was followed up for 16 years.Results and discussion. In the studied population of men aged 45–64 years, the most common sleep duration was 7 hours (44.7%), in second place – 8 hours of sleep (27.6%), in third place – 6 hours of sleep (16.4%). Among people with newly diagnosed DM, 7-hour sleep prevailed – 39.2%, 6- and 8-hour sleep – 25.3% each (÷2=7.774; df=5; p>0.05). In men with 5–6 hours of sleep, compared with men sleeping for 7–8 hours, we found a 1.72-fold increased 16-year risk of developing diabetes (95% CI 1.066–2.776; p<0.05), and in men aged 45–54 years – a 1.868-fold increase (95% CI 1.089–3.927; p<0.05). In the Cox-proportional multivariate model, an independent effect on the diabetes risk was observed for: 5–6 hours of sleep at night: hazard ratio (HR) 1.561 (95% CI 1.063–2.83; p<0.001), depression (HR 1.767; 95% CI 1.058–2.952; p<0.05), life exhaustion (HR 1.511; 95% CI 1.266–2.984; p<0.05), and low and medium-1 SNI (HR 1.956; 95% CI 1.074–3.560; p<0.05).Conclusion. Short and very short sleep duration could be defined as a major risk factor of DM.

A comparison of three strategies to reduce the burden of osteoarthritis: A population-based microsimulation study

Objectives The purpose of this study was to compare three strategies for reducing population health burden of osteoarthritis (OA): improved pharmacological treatment of OA-related pain, improved access to joint replacement surgery, and prevention of OA by reducing obesity and overweight. Methods We applied a validated computer microsimulation model of OA in Canada. The model simulated a Canadian-representative open population aged 20 years and older. Variables in the model included demographics, body mass index, OA diagnosis, OA treatment, mortality, and health-related quality of life. Model parameters were derived from analyses of national surveys, population-based administrative data, a hospital-based cohort study, and the literature. We compared 8 what-if intervention scenarios in terms of disability-adjusted life years (DALYs) relative to base-case, over a wide range of time horizons. Results Reductions in DALYs depended on the type of intervention, magnitude of the intervention, and the time horizon. Medical interventions (a targeted increase in the use of painkillers) tended to produce effects quickly and were, therefore, most effective over a short time horizon (a decade). Surgical interventions (increased access to joint replacement) were most effective over a medium time horizon (two decades or longer). Preventive interventions required a substantial change in BMI to generate a significant impact, but produced more reduction in DALYs than treatment strategies over a very long time horizon (several decades). Conclusions In this population-based modeling study we assessed the potential impact of three different burden reduction strategies in OA. Data generated by our model may help inform the implementation of strategies to reduce the burden of OA in Canada and elsewhere.

Opening of a cryptic pocket in β-lactamase increases penicillinase activity

Understanding the functional role of protein-excited states has important implications in protein design and drug discovery. However, because these states are difficult to find and study, it is still unclear if excited states simply result from thermal fluctuations and generally detract from function or if these states can actually enhance protein function. To investigate this question, we consider excited states in β-lactamases and particularly a subset of states containing a cryptic pocket which forms under the Ω-loop. Given the known importance of the Ω-loop and the presence of this pocket in at least two homologs, we hypothesized that these excited states enhance enzyme activity. Using thiol-labeling assays to probe Ω-loop pocket dynamics and kinetic assays to probe activity, we find that while this pocket is not completely conserved across β-lactamase homologs, those with the Ω-loop pocket have a higher activity against the substrate benzylpenicillin. We also find that this is true for TEM β-lactamase variants with greater open Ω-loop pocket populations. We further investigate the open population using a combination of NMR chemical exchange saturation transfer experiments and molecular dynamics simulations. To test our understanding of the Ω-loop pocket’s functional role, we designed mutations to enhance/suppress pocket opening and observed that benzylpenicillin activity is proportional to the probability of pocket opening in our designed variants. The work described here suggests that excited states containing cryptic pockets can be advantageous for function and may be favored by natural selection, increasing the potential utility of such cryptic pockets as drug targets.

Development of a conceptual model of childhood asthma to inform asthma prevention policies

BackgroundThere is no definitive cure for asthma, as prevention remains a major goal. Decision analytic models are routinely used to evaluate the value-for-money proposition of interventions. Following best practice standards in decision-analytic modelling, the objective of this study was to solicit expert opinion to develop a concept map for a policy model for primary prevention of asthma.MethodsWe reviewed currently available decision analytic models for asthma prevention. A steering committee of economic modellers, allergists and respirologists was then convened to draft a conceptual model of paediatric asthma. A modified Delphi method was followed to define the context of the problem at hand (evaluation of asthma prevention strategies) and develop the concept map of the model.ResultsConsensus was achieved after three rounds of discussions, followed by concealed voting. In the final conceptual model, asthma diagnosis was based on three domains of lung function, atopy and their symptoms. The panel recommended several markers for each domain. These domains were in turn affected by several risk factors. The panel clustered all risk factors under three groups of ‘patient characteristic’, ‘family history’ and ‘environmental factors’. To be capable of modelling the interplay among risk factors, the panel recommended the use of microsimulation, with an open-population approach that would enable modelling phased implementation and gradual and incomplete uptake of the intervention.ConclusionsEconomic evaluation of childhood interventions for preventing asthma will require modelling of several codependent risk factors and multiple domains that affect the diagnosis. The conceptual model can inform the development and validation of a policy model for childhood asthma prevention.

Personal Digital Health Assistants

The Aim: To determine gender differences in the dynamic of job stress indicators in an open population of 25-64 years over a long-term period - 29 years in Russia / Siberia (Novosibirsk). Methods: Within the framework of the screening in 1988-89 under the WHO MONICA-psychosocial (MOPSY) program (n=1676, 49.5% males, mean age 44.1±0.4 years), in 2003-2005 under the international project HAPIEE (n=1650, 34.9% males, mean age 54.25±0.2 years), in 2013-2016 (n=975, 43.8% males, mean age 34.5±0,4 years) and 2016-2017 (n=663, 41.3% males, mean age 51.95±0.32 years) within the framework of the budgetary theme No. AAAA-A17-117112850280-2, random representative samples of men and women in one of districts in Novosibirsk were examined. Job stress indicators were assessed using the Karasek’s scale adopted by MONICA-MOPSY. Results: About 40% of male and female population in 1988 reported a change in occupation in the previous 12 years. The highest proportion of such persons was observed in the younger age groups and significant gender differences were also found there. By 2016-17, the proportion of those who changed their specialty decreased but gender differences were not determined. In 2016-17, the proportion of men and women who enjoy their job increased slightly compared to 1988, but the gender difference was insignificant. Responsibility at work increased up to 58.2% and 54.5%, respectively in dynamics among young men and women. In 2016-17, the perception of responsibility at the workplace returned to the semblance of 1988 without gender differences. Regarding changes in the workplace, in 1988, the most frequent were "change of salary" and "change of workplace" for both sexes. Men more often than women indicated conflicts with their superiors and subordinates. In 2013, the change of workplace was reported more often than changes in salary (especially in the youngest group of 25-34 years old) but in 2017 these answers correlated with each other, amounting to 11-12%. No gender differences were observed. In 2013-16, share of men and women who reduced their workload increased to 20%. This proportion decreased in 2016-17. And the trend towards an increase in workload at the workplace moved at a faster pace, especially among middle-aged and older men. The proportion of women who cannot relax and rest after usual working day in the period from 1988 to 2013-16 was stable at 38-39%; but by 2016-2017 it decreased by a third. The proportion of such men has been growing over 29 years and began to exceed women by 10% in 2016-17. Conclusions: Both genders began to perform additional work tasks more often and to assess their responsibility at work as high over 29 years of observations. There is a trend towards eliminating of sex differences.