Common Genetic Variant Association with Altered HLA Expression, Synergy with Pyrethroid Exposure, and Risk for Parkinson's Disease: An Observational and Case-Control Study.

Background/objectivesThe common non-coding single nucleotide polymorphism (SNP) rs3129882 in HLA-DRA is associated with risk for idiopathic Parkinson's disease (PD). The location of the SNP in the major histocompatibility complex class II (MHC-II) locus implicates regulation of antigen presentation as a potential mechanism by which immune responses link genetic susceptibility to environmental factors in conferring lifetime risk for PD.MethodsFor immunophenotyping, blood cells from 81 subjects were analyzed by qRT-PCR and flow cytometry. A case-control study was performed on a separate cohort of 962 subjects to determine association of pesticide exposure and the SNP with risk of PD.ResultsHomozygosity for G at this SNP was associated with heightened baseline expression and inducibility of MHC class II molecules in B cells and monocytes from peripheral blood of healthy controls and PD patients. In addition, exposure to a commonly used class of insecticide, pyrethroids, synergized with the risk conferred by this SNP (OR = 2.48, p = 0.007), thereby identifying a novel gene-environment interaction that promotes risk for PD via alterations in immune responses.ConclusionsIn sum, these novel findings suggest that the MHC-II locus may increase susceptibility to PD through presentation of pathogenic, immunodominant antigens and/or a shift toward a more pro-inflammatory CD4+ T cell response in response to specific environmental exposures, such as pyrethroid exposure through genetic or epigenetic mechanisms that modulate MHC-II gene expression

Pesticide exposure: the hormonal function of the female reproductive system disrupted?

Some pesticides may interfere with the female hormonal function, which may lead to negative effects on the reproductive system through disruption of the hormonal balance necessary for proper functioning. Previous studies primarily focused on interference with the estrogen and/or androgen receptor, but the hormonal function may be disrupted in many more ways through pesticide exposure. The aim of this review is to give an overview of the various ways in which pesticides may disrupt the hormonal function of the female reproductive system and in particular the ovarian cycle. Disruption can occur in all stages of hormonal regulation: 1. hormone synthesis; 2. hormone release and storage; 3. hormone transport and clearance; 4. hormone receptor recognition and binding; 5. hormone postreceptor activation; 6. the thyroid function; and 7. the central nervous system. These mechanisms are described for effects of pesticide exposure in vitro and on experimental animals in vivo. For the latter, potential effects of endocrine disrupting pesticides on the female reproductive system, i.e. modulation of hormone concentrations, ovarian cycle irregularities, and impaired fertility, are also reviewed. In epidemiological studies, exposure to pesticides has been associated with menstrual cycle disturbances, reduced fertility, prolonged time-to-pregnancy, spontaneous abortion, stillbirths, and developmental defects, which may or may not be due to disruption of the female hormonal function. Because pesticides comprise a large number of distinct substances with dissimilar structures and diverse toxicity, it is most likely that several of the above-mentioned mechanisms are involved in the pathophysiological pathways explaining the role of pesticide exposure in ovarian cycle disturbances, ultimately leading to fertility problems and other reproductive effects. In future research, information on the ways in which pesticides may disrupt the hormonal function as described in this review, can be used to generate specific hypotheses for studies on the effects of pesticides on the ovarian cycle, both in toxicological and epidemiological settings

VE-cadherin and claudin-5: it takes two to tango

Endothelial barrier function requires the adhesive activity of VE-cadherin and claudin-5, which are key components of adherens and tight endothelial junctions, respectively. Emerging evidence suggests that VE-cadherin controls claudin-5 expression by preventing the nuclear accumulation of FoxO1 and -catenin, which repress the claudin-5 promoter. This indicates that a crosstalk mechanism operates between these junctional structures

On the dynamics of WKB wave functions whose phase are weak KAM solutions of H-J equation

In the framework of toroidal Pseudodifferential operators on the flat torus $\Bbb T^n := (\Bbb R / 2\pi \Bbb Z)^n$ we begin by proving the closure under composition for the class of Weyl operators $\mathrm{Op}^w_\hbar(b)$ with simbols $b \in S^m (\mathbb{T}^n \times \mathbb{R}^n)$. Subsequently, we consider $\mathrm{Op}^w_\hbar(H)$ when $H=\frac{1}{2} |\eta|^2 + V(x)$ where $V \in C^\infty (\Bbb T^n;\Bbb R)$ and we exhibit the toroidal version of the equation for the Wigner transform of the solution of the Schr\"odinger equation. Moreover, we prove the convergence (in a weak sense) of the Wigner transform of the solution of the Schr\"odinger equation to the solution of the Liouville equation on $\Bbb T^n \times \Bbb R^n$ written in the measure sense. These results are applied to the study of some WKB type wave functions in the Sobolev space $H^{1} (\mathbb{T}^n; \Bbb C)$ with phase functions in the class of Lipschitz continuous weak KAM solutions (of positive and negative type) of the Hamilton-Jacobi equation $\frac{1}{2} |P+ \nabla_x v_\pm (P,x)|^2 + V(x) = \bar{H}(P)$ for $P \in \ell \Bbb Z^n$ with $\ell >0$, and to the study of the backward and forward time propagation of the related Wigner measures supported on the graph of $P+ \nabla_x v_\pm$

Perceptions of values over time and why they matter

Objective: Extant research mostly treats values as being stable over time. Our research examined how people perceive values over time and whether or not these perceptions reflect motivational tensions between theoretically opposing values. We also assessed the viability of examining values over time to predict well-being and future intentions. Method: Four studies (N=934) asked participants to report their values across past, present, and future settings. These temporal trajectories were analysed across the four types of higher-order values: self-transcendence, self-enhancement, openness and conservation (Schwartz, 1992). Studies 3 and 4 assessed associations with well-being. Study 4 assessed associations with self-reported behaviour over time. Results: Across all four studies, participants perceived their values as being dynamic over time. Younger participants’ trajectories did not reflect the motivational conflicts typically reported in values research, but Study 4 showed potential awareness in older age groups. Variability in temporal values correlated with well-being, particularly for openness values. Future values predicted future intentions, even when controlling for present values. Conclusion: This novel method of examining values provides new understanding into how people perceive the pursuit of values over time. Additionally, we show two ways that a temporal values measure can offer new insights into well-being and future intentions

Using public datasets to understand the psychological correlates of smoking, alcohol consumption, and obesity: A country-level analysis

In the present research, we investigate whether cultural value orientations (CVOs) and aggregate personality traits (Big-5) predict actual levels of alcohol consumption, smoking, and obesity across 50 countries using averages derived from millions of data points. Aggregate traits explained variance above and beyond CVOs in obesity (particularly neuroticism and extraversion), while CVOs explained variance beyond aggregate traits in alcohol consumption (particularly harmony and hierarchy). Smoking did not appear to be strongly linked to aggregated traits or CVOs. We conclude that an understanding of the cultural correlates of risky health behaviours may help inform important policies and interventions for meeting international sustainable development goals

The limitations of polling data in understanding public support for COVID-19 lockdown policies

Opinion polls regarding policies designed to tackle COVID-19 have shown public support has remained high throughout the first year of the pandemic in most places around the world; however there is a risk that headline support over-simplifies people’s views. We carried out a two-wave survey with six-month interval on a public sample (N = 212) in the United Kingdom, examining a broad range of perspectives on COVID-19. We find that the majority of people support most public health measures introduced, but that they also see significant side effects of these policies, and that they consider many of these side effects as unacceptable in a cost-benefit analysis. We also find that people judged the threat of COVID-19 via the magnitude of the policy response, and that they do not use their perception of the direct threat to themselves or close others to guide their support for policy. Polling data only offer one simple perspective and do not illustrate the ambivalence people feel around policies relating to COVID-19. There is also a meaningful risk of public opinion and government policy forming a symbiotic relationship, which impacts upon how effectively such policies are implemented both now, and in relation to future threats

Intestinal parasitosis and anemia in children 6 to 60 months of age treated in the period 2015 to 2020, in a health center in the Highlands of Peru

Objetivo: Evaluar la anemia y la parasitosis en niños de 6 a 60 meses de edad, atendidos en un Centro de Salud Alto andina de Perú, durante periodo 2015 al 2020. Método: El estudio fue descriptivo – retrospectivo, se aplicó el método científico, con un diseño no experimental, la población y la muestra fueron compuestos por 1097 niños atendidos en el Centro de Salud de Ascensión, durante los años 2015 al 2020, se incluyó todo niño que padezca anemia y/o parasitosis. Resultado:  515 niñas que componen un 46.9%, y 582 niños que componen 53.1 % padecen de anemia, de los cuales el 83% padecen anemia leve, y un 17 % padecen de anemia moderada; en cuanto a género 83,7% niñas y 82,3% niños presentan anemia, en relación a edad   los de  6 a 12 mes   presentaron anemia  leve en un 37.5%  y moderado 48.1% ; Por otro lado de un total de 240 niños, un 53.3 % fueron niñas y un 46.7 fueron niños que padecen parasitosis intestinal. Conclusión:  En las zonas alto andinas de Perú, de niños y niñas que presentan anemia, predomina la anemia leve, así mismo este problema de salud no diferencia en su afección al género; en relación a la edad predomina de 6 a 12 meses con anemia leve y moderado. Por otro lado, se evidencia un porcentaje considerable de parasitosis intestinal, de igual forma esta enfermedad en cuanto al género no diferencia; sin embargo en cuanto a la edad se evidencia   mayor parasitosis intestinal en niños y niñas de 24, 36 y 60 meses; lo que implica que la parasitosis intestinal no necesariamente es un factor predominante para la anemia.Objective: To evaluate anemia and parasitosis in children from 6 to 60 months of age, attended in a Peruvian High Andean Health Center, during the period 2015 to 2020. Method: The study was descriptive - retrospective, the scientific method was applied, with a non-experimental design, the population and the sample were composed of 1097 children attended at the Ascension Health Center, during the years 2015 to 2020, all children suffering from anemia and/or parasitosis were included. Result: 515 girls comprising 46.9%, and 582 boys comprising 53.1% suffer from anemia, of which 83% suffer from mild anemia, and 17% suffer from moderate anemia; in terms of gender 83.7% girls and 82.3% boys present anemia, in relation to age those from 6 to 12 months presented mild anemia in 37. On the other hand, out of a total of 240 children, 53.3% were girls and 46.7% were boys suffering from intestinal parasitosis. Conclusion: In the high Andean zones of Peru, children with anemia are predominantly mildly anemic, and this health problem does not differentiate between genders; in relation to age, children between 6 and 12 months are predominantly mildly and moderately anemic. On the other hand, there is a considerable percentage of intestinal parasitosis, likewise this disease does not differentiate by gender; however, in terms of age, there is more intestinal parasitosis in children aged 24, 36 and 60 months, which implies that intestinal parasitosis is not necessarily a predominant factor for anemi

Business experience and start-up size: buying more lottery tickets next time around?

This paper explores the determinants of start-up size by focusing on a cohort of 6247 businesses that started trading in 2004, using a unique dataset on customer records at Barclays Bank. Quantile regressions show that prior business experience is significantly related with start-up size, as are a number of other variables such as age, education and bank account activity. Quantile treatment effects (QTE) estimates show similar results, with the effect of business experience on (log) start-up size being roughly constant across the quantiles. Prior personal business experience leads to an increase in expected start-up size of about 50%. Instrumental variable QTE estimates are even higher, although there are concerns about the validity of the instrument