Sex Differences in the Association Between Hypertension and Incident Atrial Fibrillation.

Background Limited evidence is available on sex differences about the association between hypertension and incident atrial fibrillation (AF). Methods and Results We used a nationwide health checkup and claims database to analyze 3 383 738 adults (median age, 43 (36-51) years, 57.4% men). We investigated the relationship between hypertension and incident AF in men and women using a Cox regression model. We used restricted cubic spline functions to identify the association of blood pressure (BP) as a continuous parameter with incident AF. We categorized the men and women into 4 groups according to the 2017 American College of Cardiology/American Heart Association BP guidelines. During a mean follow-up of 1199±950 days, 13 263 AF diagnoses were recorded. The incidence (95% CI) of AF was 15.8 (15.5-16.1) per 10 000 person-years in men and 6.1 (5.9-6.3) per 10 000 person-years in women. Compared with normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension were associated with an increased risk AF in both men and women. However, the hazard ratios were greater in women than in men, and the P value for interactions in the multivariable model was 0.0076. The models using restricted cubic spline showed that the risk of AF associated with elevated systolic BP increased steeply above an approximate threshold of systolic BP of 130 mm Hg in men and 100 mm Hg in women. Although our primary findings were consistent across subgroup analyses, this association was most significant in younger individuals. Conclusions Although the incidence of AF was higher in men, the association between hypertension and incident AF was more pronounced in women than in men, suggesting a potential sex difference in the relationship between hypertension and incident AF.

Pathophysiological conditions induced by SARS-CoV-2 infection reduce ACE2 expression in the lung.

SARS-CoV-2 infection causes a variety of physiological responses in the lung, and understanding how the expression of SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), and its proteolytic activator, transmembrane serine protease 2 (TMPRSS2), are affected in patients with underlying disease such as interstitial pneumonia will be important in considering COVID-19 progression. We examined the expression of ACE2 and TMPRSS2 in an induced usual interstitial pneumonia (iUIP) mouse model and patients with IPF as well as the changes in whole-lung ACE2 and TMPRSS2 expression under physiological conditions caused by viral infection. Histopathological and biochemical characteristics were analyzed using human specimens from patients with IPF and precision-cut lung slices (PCLS) from iUIP mouse model showing UIP with honeycombing and severe fibrosis after non-specific interstitial pneumonia. ACE2 expression decreased with acute lung inflammation and increased in the abnormal lung epithelium of the iUIP mouse model. ACE2 is also expressed in metaplastic epithelial cells. Poly(I:C), interferons, and cytokines associated with fibrosis decreased ACE2 expression in PCLS in the iUIP model. Hypoxia also decreases ACE2 via HIF1α in PCLS. Antifibrotic agent, nintedanib attenuates ACE2 expression in invasive epithelial cells. Patients with IPF are at a higher risk of SARS-CoV-2 infection due to the high expression of ACE2. However, ACE2 and TMPRSS2 expression is decreased by immune intermediaries, including interferons and cytokines that are associated with viral infection and upon administration of antifibrotic agents, suggesting that most of the viral infection-induced pathophysiological responses aid the development of resistance against SARS-CoV-2 infection.

CTLA-4-Ig internalizes CD80 in fibroblast-like synoviocytes from chronic inflammatory arthritis mouse model.

CD80 interact with CD28 and CTLA-4 on antigen-presenting cells, and function in the co-stimulatory signaling that regulates T cell activity. CTLA-4-Ig is used to treat RA by blocking co-stimulatory signaling. Chronic inflammatory arthritis was induced in D1BC mice using low-dose arthritogenic antigens and treated with CTLA-4-Ig. We performed histopathology of the joints and lymph nodes, serological examination for rheumatoid factors, and flow cytometric analysis of isolated synovial cells, including CD45- FLSs and CD45+ synovial macrophages. CTLA-4-Ig treatment ameliorated the chronic inflammatory polyarthritis. There was a decrease in the number of infiltrating lymphoid cells in the joints as well as in the levels of RF-IgG associated with a decrease in the number of B cells in the lymph nodes; more than 15% of CD45- FLSs expressed CD80, and a small number of them expressed PD-L1, indicating the presence of PD-L1/CD80 cis-heterodimers in these cells. CTLA-4-Ig internalized CD80, but not PD-L1, in isolated synovial cells. Gene ontology analysis revealed that CTLA-4-Ig internalization did not significantly alter the expression of inflammation-related genes. The therapeutic effect of CTLA-4-Ig appears to extend beyond the lymph nodes into the inflamed synovial compartment through the synergistic inactivation of T cells by the CD80 and PD-L1 axes.

Complex formation of potassium salt of highly fatty acid with hemagglutinin protein in influenza virus via exothermic interaction.

In our previous study, we found highly fatty acid salts, which are a skin-friendly soaps, had a high ability to inactivate the influenza virus. In order to elucidate the mechanism of inactivation of influenza virus, we investigated interactions and complex formation of potassium tetradecanoate (C14K) as a highly fatty acid salt with a virus particle (VP) derived from avian influenza virus by using isothermal titration calorimetry (ITC) and small-angle X-ray scattering (SAXS). ITC showed C14K attractively interacted with hemagglutinin protein (HA) which exists in the envelop of VP. SAXS analyses revealed C14K formed highly ordered complex with HA through the attractive interaction. Since the HA is responsible for cell entry events, inactivation of influenza viruses by highly fatty acid salts are derived owing to HA inhibition of influenza viruses through the complex formation. Time-resolved SAXS measurements elucidated the complex formation was completed within 40 s after mixing aqueous solutions of C14K and VP. This result strongly suggests that hand-washing with a highly fatty acid salts is an effective measure to prevent infection with influenza virus without causing rough hands.

The evolutionary novelty of childcare by and with strangers.

Alloparenting by and with genetically unrelated individuals is evolutionarily novel; thus, the Savanna-IQ Interaction Hypothesis predicts that more intelligent parents are more likely to resort to paid childcare by strangers. Analyses of individual data (National Child Development Study) in the United Kingdom (Study 1) and macrolevel data from the United States (Study 2) and economically developed Organization for Economic Cooperation and Development (OECD) nations (Study 3) confirmed the hypothesis. Net of education, earnings, sex, current marital status, and number of children, more intelligent British parents were more likely to resort to paid childcare at ages 33 and 42; net of female labor force participation rate, median household income, median cost of childcare, and mean education, U.S. states with higher average intelligence had higher proportions of children (ages 0-4) in paid childcare; and net of maternal employment, gross domestic product (GDP) per capita, cost of childcare, and female educational attainment, OECD nations with higher average intelligence had higher proportions of infants (ages 0-2) in paid childcare. The results were remarkably consistent; both across the 50 U.S. states and 45 economically developed OECD nations, a one IQ point increase in the average intelligence of the population was associated with a 1.8% increase in the proportion of children in paid childcare. Contrary to earlier findings, there was some suggestive evidence that the experience of paid daycare might harm the cognitive development of children. The studies point to the importance of evolutionary perspective in developmental psychology and child development.

Nintedanib induces gene expression changes in the lung of induced-rheumatoid arthritis-associated interstitial lung disease mice.

Nintedanib is a multi-tyrosine kinase inhibitor widely used to treat progressive fibrosing interstitial lung diseases because it slows the reduction in forced vital capacity. However, the prognosis for patients treated with nintedanib remains poor. To improve nintedanib treatment, we examined the effects of nintedanib on gene expression in the lungs of induced-rheumatoid arthritis-associated interstitial lung disease model mice, which develop rheumatoid arthritis and subsequent pulmonary fibrosis. Using next-generation sequencing, we identified 27 upregulated and 130 downregulated genes in the lungs of these mice after treatment with nintedanib. The differentially expressed genes included mucin 5B and heat shock protein 70 family genes, which are related to interstitial lung diseases, as well as genes associated with extracellular components, particularly the myocardial architecture, suggesting unanticipated effects of nintedanib. Of the genes upregulated in the nintedanib-treated lung, expression of regulatory factor X2, which is suspected to be involved in cilia movement, and bone morphogenetic protein receptor type 2, which is involved in the pathology of pulmonary hypertension, was detected by immunohistochemistry and RNA in situ hybridization in peripheral airway epithelium and alveolar cells. Thus, the present findings indicate a set of genes whose expression alteration potentially underlies the effects of nintedanib on pulmonary fibrosis. It is expected that these findings will contribute to the development of improved nintedanib strategies for the treatment of progressive fibrosing interstitial lung diseases.

Sunshine on my shoulders makes me happy. . . especially if I'm less intelligent: how sunlight and intelligence affect happiness in modern society.

The savanna theory of happiness proposes that, due to evolutionary constraints on the human brain, situations and circumstances that would have increased our ancestors' happiness may still increase our happiness today, and those that would have decreased their happiness then may still decrease ours today. It further proposes that, because general intelligence evolved to solve evolutionarily novel problems, this tendency may be stronger among less intelligent individuals. Because humans are a diurnal species that cannot see in the dark, darkness always represented danger to our ancestors and may still decrease our happiness today. Consistent with this prediction, the analysis of the National Longitudinal Study of Adolescent to Adult Health (Add Health) data shows that exposure to sunlight was associated with happiness but the association was significantly weaker among more intelligent individuals.

When intelligence hurts and ignorance is bliss: Global pandemic as an evolutionarily novel threat to happiness.

INTRODUCTION: The savanna theory of happiness posits that it is not only the current consequences of a given situation that affect happiness but also its ancestral consequences, and that the effect of ancestral consequences on happiness is stronger among less intelligent individuals. But what about situations that did not exist in the ancestral environment and thus have no ancestral consequences? Global pandemic is one such situation that has no ancestral analog, and the theory predicts such evolutionarily novel threats to have a negative effect disproportionately on the life satisfaction of more intelligent individuals. METHODS: We analyzed prospectively longitudinal data from population samples from the National Child Development Study (Study 1) and the British Cohort Study (Study 2). RESULTS: Consistent with the theoretical prediction, while more intelligent individuals were generally more satisfied with their lives than less intelligent individuals were throughout adulthood (albeit not because they were more intelligent but because they earned more money, were more likely to be married, and healthier), more intelligent individuals were less satisfied with their lives during the COVID-19 global pandemic because they were more intelligent. CONCLUSION: Higher intelligence may have a downside in the modern world, by allowing life satisfaction to be more vulnerable from being better able to comprehend the severity of problems that did not exist in the ancestral world.

Infertility and same-sex attraction in women.

A polygyny hypothesis of female sexual fluidity proposes that women may have been evolutionarily selected to be sexually fluid, in order to have occasional sex with their cowives in polygynous marriage to reduce tension and conflict inherent in such marriage, while at the same time reproducing children with their husbands. Among others, the hypothesis predicts that women who are biologically (but not surgically) infertile would experience greater same-sex attraction. Biological infertility stems from natural, evolutionarily familiar causes such as menopause, whereas surgical infertility stems from artificial, evolutionarily novel causes such as tubal ligation or hysterectomy. Consistent with the prediction, the analyses of the National Survey of Family Growth data showed that biological infertility, but not surgical infertility, was significantly associated with same-sex self-identified labels, behavior and sexual attraction in women. Biological infertility nearly doubled the odds of women having engaged in same-sex behavior and the number of same-sex partners in the last 12 months and nearly tripled the number of same-sex partners in life. In sharp contrast, biological infertility was not associated (and surgical infertility was significantly negatively associated) with same-sex attraction in men.

Bimodal fibrosis in a novel mouse model of bleomycin-induced usual interstitial pneumonia.

Idiopathic pulmonary fibrosis is pathologically represented by usual interstitial pneumonia (UIP). Conventional bleomycin models used to study pathogenic mechanisms of pulmonary fibrosis display transient inflammation and fibrosis, so their relevance to UIP is limited. We developed a novel chronic induced-UIP (iUIP) model, inducing fibrosis in D1CC×D1BC transgenic mice by intra-tracheal instillation of bleomycin mixed with microbubbles followed by sonoporation (BMS). A bimodal fibrotic lung disease was observed over 14 wk, with an acute phase similar to nonspecific interstitial pneumonia (NSIP), followed by partial remission and a chronic fibrotic phase with honeycombing similar to UIP. In this secondary phase, we observed poor vascularization despite elevated PDGFRß expression. γ2PF- and MMP7-positive epithelial cells, consistent with an invasive phenotype, were predominantly adjacent to fibrotic areas. Most invasive cells were Scgb1a1 and/or Krt5 positive. This iUIP mouse model displays key features of idiopathic pulmonary fibrosis and has identified potential mechanisms contributing to the onset of NSIP and progression to UIP. The model will provide a useful tool for the assessment of therapeutic interventions to oppose acute and chronic fibrosis.

Personality and early susceptibility to COVID-19 in the United Kingdom.

This paper takes advantage of a unique dataset with a prospectively longitudinal, nationally representative sample (n = 5,178) that began in 1958 and has information on COVID-19 health status in 2020 to examine the effect of Big Five personality traits on compliance with social distancing requirements and contraction of COVID-19. The results show some consistency with epidemiological recommendations (Conscientious individuals were more likely to maintain social distance and less likely to contract COVID-19; men were less likely to comply and more likely to contract) but more inconsistency (Agreeable individuals were more likely to comply with social distancing requirements yet more likely to contract COVID-19; Open and Neurotic individuals were no less likely to comply yet more likely to contract COVID-19). The results highlight the importance of Big Five personality factors for behaviour in the global pandemic and may call into question the universal effectiveness of social distancing requirements for all individuals. However, the small number of confirmed cases of COVID-19 during the early months of the pandemic requires caution in interpretation of the results. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.

Suppression of epithelial abnormalities by nintedanib in induced-rheumatoid arthritis-associated interstitial lung disease mouse model.

Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is relevant for the prognosis in patients with RA. Nintedanib, which inhibits both receptor and non-receptor type tyrosine kinases, is an antifibrotic drug for the treatment of progressive fibrosing ILDs, such as idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease. Little is known about the effects of nintedanib on RA-ILD. We examined the characteristics of a novel induced RA-ILD (iRA-ILD) mouse model and the effects of nintedanib on the model. D1CC×D1BC mice are highly susceptible to arthritogenic antigens, such as bovine type II collagen, resulting in severe inflammatory arthritis. ILD develops after joint inflammation is alleviated. Serum surfactant protein D levels were monitored as an ILD marker. Nintedanib was orally administered to iRA-ILD mice for 2 months. The iRA-ILD model showed similar symptoms to those in patients with RA-ILD. The histopathological features of pulmonary disorder resembled nonspecific interstitial pneumonia, but with metaplastic epithelium. Histopathological analysis revealed that in addition to reducing fibrosis, nintedanib suppressed M2 macrophage polarisation and hyperplasia of Type 2 alveolar epithelial cells. The metaplastic epithelium acquired invasiveness because of the expression of E-cadherin, MMP7, Tgf-ß, Col1a1, Padi2 and Padi4. Moreover, citrullinated peptides were detected in these invasive epithelial cells as well as in the bronchiolar epithelium. Administration of nintedanib reduced the expression of Pad4 and citrullinated peptides and eliminated invasive epithelial cells. The broad inhibitory effects of nintedanib on tyrosine kinases may contribute to the overall improvement in RA-ILD, including epithelial abnormalities associated with progressive lung fibrosis.

Economics and Epicycles.

I aver that standard economics as a model of human behavior is as incorrect in 2017 (after Thaler) as geocentrism was as a model of celestial behavior in 1617 (after Galileo). Behavioral economic studies that have exposed the paradoxes and anomalies in standard economics are akin to epicycles on geocentrism. Just as no amount of epicycles could salvage geocentrism as a model of celestial behavior because it was fundamentally incorrect, no amount of behavioral economic adjustments could salvage standard economics as a model of human behavior because it is fundamentally incorrect. Many of the cognitive biases exhibited by humans are shared by other species, so not only are human actors Humans (as opposed to Econs), but nonhuman animals as phylogenetically distant from humans as ants and locusts are also Humans. Evolutionary biology as a model of human behavior can explain many of the hitherto unexplained cognitive biases and provide a unifying model of human behavior currently lacking in behavioral economics.

Not so much rational but rationalizing: Humans evolved as coherence-seeking, fiction-making animals.

The evidence for biased perceptions and judgments in humans coupled with evidence for ecological rationality in nonhuman animals suggest that the claim that humans are the rational animal may be overstated. We instead propose that discussions of human psychology may benefit from viewing ourselves not so much as rational animals but rather as the rationalizing animal. The current article provides evidence that rationalization is unique to humans and argues that rationalization processes (e.g., cognitive dissonance reduction, post hoc justification of choices, confabulation of reasons for moral positions) are aimed at creating the fictions we prefer to believe and maintaining the impression that we are psychologically coherent and rational. Coherence appears to be prioritized at the expense of veridicality, suggesting that distorted perceptions and appraisals can be adaptive for humans-under certain circumstances, we are better off understanding ourselves and reality not so accurately. Rationalization also underlies the various shared beliefs, religions, norms, and ideologies that have enabled humans to organize and coordinate their actions on a grand scale, for better or worse. We conclude with a discussion of the implications of this unique human psychological trait. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Self-Assembly of Surfactin into Nanofibers with Hydrophilic Channels in Nonpolar Organic Media.

We investigated the self-assembly of surfactin (SFNa), a cyclic peptide amphiphile produced by Bacillus subtilis, in a nonpolar organic solvent, namely, cyclohexane (CHx). The CHx solution of SFNa formed a thermoreversible organogel. Transmission electron microscopy and small-angle X-ray scattering (SAXS) analyses showed that gelation of the CHx solution of SFNa was caused by physical cross-linking of SFNa nanofibers. Wide-angle X-ray diffraction and Fourier-transform infrared analyses showed that the SFNa nanofibers were formed by one-dimensional stacking of SFNa rings with a period of 0.48 nm corresponding to the length of inter-ring hydrogen bonds between amide groups. A combination of SAXS and small-angle neutron scattering investigations of CHx and deuterated CHx solutions of SFNa nanofibers containing H2O or D2O showed that the SFNa nanofibers had a hydrophilic interior and formed water channels by water incorporation in this region.

Osteochondrogenesis derived from synovial fibroblasts in inflammatory arthritis model.

Rheumatoid arthritis (RA) is characterized by chronic joint inflammation, which forms pannus with bone destruction. Bony ankylosis is also observed following inflammation; however, the mechanism behind this aberrant bone formation in RA had remained unclear. Based on our recent findings obtained using a novel arthritis model called D1BC mouse, we found that synovial fibroblasts in pannus consist of at least three different populations with the osteochondrogenic lineage being predominant. We also found endochondral ossification like that in embryonic bone development adjacent to invasive synovial fibroblasts. Such ectopic endochondral ossification leads to the failure of bone repair and results in ankylosis. In this review, we describe the character of synovial fibroblasts toward the osteochondrogenic lineage and ectopic endochondral ossification in an inflammatory arthritis mouse model.

Paternal Age is Negatively Associated with Religious Behavior in a Post-60s But Not a Pre-60s US Birth Cohort: Testing a Prediction from the Social Epistasis Amplification Model.

Participation in social behaviors that enhance group-level fitness may be influenced by mutations that affect patterns of social epistasis in human populations. Mutations that cause individuals to not participate in these behaviors may weaken the ability of members of a group to coordinate and regulate behavior, which may in turn negatively affect fitness. To investigate the possibility that de novo mutations degrade these adaptive social behaviors, we examine the effect of paternal age (as a well-established proxy for de novo mutation load) on one such social behavior, namely religious observance, since religiosity may be a group-level cultural adaptation facilitating enhanced social coordination. Using two large samples (Wisconsin Longitudinal Study and AddHealth), each of a different US birth cohort, paternal age was used to hierarchically predict respondent's level of church attendance after controlling for multiple covariates. The effect is absent in WLS (ß = .007, ns, N = 4560); however, it is present in AddHealth (ß = - .046, p < .05, N = 4873) increasing the adjusted model R2 by .005. The WLS respondents were (mostly) born in the 1930s, whereas the AddHealth respondents were (mostly) born in the 1970s. This may indicate that social-epistatic regulation of behavior has weakened historically in the USA, which might stem from and enhance the ability for de novo mutations to influence behavior among more recently born cohorts-paralleling the secular rise in the heritability of age at sexual debut after the sexual revolution.

Father absence, sociosexual orientation, and same-sex sexuality in women and men.

A recent evolutionary theory of female sexual fluidity suggests that women may not have sexual orientations in the same sense that men do, and that women's apparent sexual orientation may instead be a byproduct of their sociosexual orientation. One developmental factor that has consistently been shown to influence sociosexual orientation is father absence in childhood. Consistent with the prediction of the theory, the analyses of the National Longitudinal Study of Adolescent to Adult Health (Add Health) data show that father absence significantly increases women's, but not men's, same-sex sexuality in adulthood, whether it is measured by self identity, sexual behaviour, or romantic attraction. Further consistent with the theory, the association between father absence and same-sex sexuality in women is entirely mediated by their sociosexual orientation.

Does global warming contribute to the obesity epidemic?

Endotherms must expend more energy to digest colder food, so they acquire more calories by eating food at a higher temperature than eating the identical food cold. A recent study shows that ownership of a microwave is associated with a small increase in BMI and obesity. The same logic applies to other substances that endotherms introduce into their bodies, like air. An analysis of the National Longitudinal Study of Adolescent to Adult Health (Add Health) shows that, net of sex, age, race, education, earnings, neighborhood characteristics, and exercise activities, atmospheric temperature is associated with small but statistically significant increases in BMI, weight, overweight, and obesity. Atmospheric temperature is more strongly associated than most exercise activities, and as strongly associated as age and population density. An average American might reduce weight by 15.1 lbs, BMI by 2.52 (half the difference between normal weight and obesity), and the odds of obesity by 54% by moving from Phoenix, AZ, to Barrow, AK, or, less dramatically, 5.7 lbs in weight, .95 in BMI (a fifth of the difference between normal weight and obesity), and 25% in the odds of obesity by moving mere 150 miles north to Flagstaff, AZ. Global warming under the worst-case scenario might produce an increase of 2.2 lbs in weight, .37 in BMI, and 12% in odds of obesity from 1961 to 2081.

Effect of H2 treatment in a mouse model of rheumatoid arthritis-associated interstitial lung disease.

Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD), a primary cause of mortality in patients with RA, has limited treatment options. A previously established RA model in D1CC transgenic mice aberrantly expressed major histocompatibility complex class II genes in joints, developing collagen II-induced polyarthritis and anti-cyclic citrullinated peptide antibodies and interstitial pneumonitis, similar to those in humans. Molecular hydrogen (H2 ) is an efficient antioxidant that permeates cell membranes and alleviates the reactive oxygen species-induced injury implicated in RA pathogenesis. We used D1CC mice to analyse chronic lung fibrosis development and evaluate H2 treatment effects. We injected D1CC mice with type II collagen and supplied them with H2 -rich or control water until analysis. Increased serum surfactant protein D values and lung densities images were observed 10 months after injection. Inflammation was patchy within the perilymphatic stromal area, with increased 8-hydroxy-2'-deoxyguanosine-positive cell numbers and tumour necrosis factor-α, BAX, transforming growth factor-ß, interleukin-6 and soluble collagen levels in the lungs. Inflammatory and fibrotic changes developed diffusely within the perilymphatic stromal area, as observed in humans. H2 treatment decreased these effects in the lungs. Thus, this model is valuable for studying the effects of H2 treatment and chronic interstitial pneumonia pathophysiology in humans. H2 appears to protect against RA-ILD by alleviating oxidative stress.