Psychological Reactance to Mobility Restrictions Due to the COVID-19 Pandemic: A Japanese Population Study

In Japan, mobility restrictions were enforced by the government to abate the spread of COVID-19. The current study examined whether experiences of such mobility restrictions affected motivation for future going-out activities. To this end, we conducted a one-time online survey of 1,000 adults in Tokyo to measure going-out activities in four different time periods at once: before the spread of infection, during and after the emergency declaration, and after the end of the pandemic (future desire). In addition, to examine the impact of preferences for online services that make it easier to stay home, we measured the usage history of online services to obtain food during the mobility restriction period. Results indicated that desire for going-out activities after the end of the pandemic increased compared with those before the pandemic, particularly for leisure-related purposes. In addition, the use of online services to obtain food tended to suppress the increased desire for future going-out activities, although this effect was not significant. In conclusion, mobility restrictions resulted in motivational arousal for going-out activities after the end of the pandemic. Our findings indicate that psychological reactance plays a role in determining going-out activities in the future

Decreased Serum Free Testosterone in Workers Exposed to High Levels of Di-n-butyl Phthalate (DBP) and Di-2-ethylhexyl Phthalate (DEHP): A Cross-Sectional Study in China

BACKGROUND: Observations of adverse developmental and reproductive effects in laboratory animals and wildlife have fueled increasing public concern regarding the potential for various chemicals to impair human fertility. OBJECTIVE: Our objective in this study was to assess the effect of occupational exposure to high levels of phthalate esters on the balance of gonadotropin and gonadal hormones including luteinizing hormone, follicle-stimulating hormone, free testosterone (fT), and estradiol. METHODS: We examined urine and blood samples of 74 male workers at a factory producing unfoamed polyvinyl chloride flooring exposed to di-n-butyl phthalate (DBP) and di-2-ethylhexyl phthalate (DEHP) and compared them with samples from 63 male workers from a construction company, group matched for age and smoking status. RESULTS: Compared to the unexposed workers, the exposed workers had substantially and significantly elevated concentrations of mono-n-butyl phthalate (MBP; 644.3 vs. 129.6 μg/g creatinine, p < 0.001) and mono-2-ethylhexyl phthalate (MEHP; 565.7 vs. 5.7 μg/g creatinine, p < 0.001). fT was significantly lower (8.4 vs. 9.7 μg/g creatinine, p = 0.019) in exposed workers than in unexposed workers. fT was negatively correlated to MBP (r = −0.25, p = 0.03) and MEHP (r = −0.19, p = 0.095) in the exposed worker group. Regression analyses revealed that fT decreases significantly with increasing total phthalate ester score (the sum of quartiles of MBP and MEHP; r = −0.26, p = 0.002). CONCLUSION: We observed a modest and significant reduction of serum fT in workers with higher levels of urinary MBP and MEHP compared with unexposed workers

Agreement between patients' and radiation oncologists' cancer diagnosis and prognosis perceptions: A cross sectional study in Japan

This study assessed agreement between radiation oncologist- and cancer patient-reported perceptions about cancer diagnosis, time since diagnosis, treatment purpose, and whether life expectancy had been discussed; and described preferences for prognosis discussions. Adult cancer patients receiving radiotherapy at a Japanese hospital were invited to complete a touchscreen tablet survey. Patient survey responses were linked and comparisons made with a survey completed by their radiation oncologist. Among 146 cancer patient-oncologist dyads, there was almost perfect agreement on cancer diagnosis (ĸ = 0.88, 95% CI: 0.82–0.94), substantial agreement on time since diagnosis (ĸ = 0.70, 95% CI: 0.57–0.83) and moderate agreement on whether treatment goal was curative or palliative (ĸ = 0.44, 95% CI: 0.28–0.57; all p’s < 0.0001). Agreement about whether a life expectancy discussion had occurred was less than expected by chance (κ = -0.06, p = 0.9). Radiation oncologists reported that they had spoken to over two thirds of patients about this, whilst less than one third of patients stated that this discussion had occurred with their radiation oncologist. Over half of the patients who had not discussed life expectancy wanted to. Patients had variable preferences for whether they (80%), their radiation oncologist (78%) or their partner/family (52%) should decide whether they discuss their life expectancy. Although patient self-reported information about diagnosis and time since diagnosis appears to be reasonably accurate (compared with clinician-reported information), limitations of self-reported data about prognostic discussions were highlighted by poor agreement between patient- and clinician-reported information about whether prognostic discussions have occurred. Additional support is needed to improve prognosis communication and understanding in radiation oncology settings

Lack of a surface layer in Tannerella forsythia mutants deficient in the type IX secretion system

Tannerella forsythia, a Gram-negative anaerobic bacterium, is an important pathogen in periodontal disease. This bacterium possesses genes encoding all known components of the type IX secretion system (T9SS). T. forsythia mutants deficient in genes orthologous to the T9SS-encoding genes porK, porT and sov were constructed. All porK, porT and sov single mutants lacked the surface layer (S-layer) and expressed less-glycosylated versions of the S-layer glycoproteins TfsA and TfsB. In addition, these mutants exhibited decreased haemagglutination and increased biofilm formation. Comparison of the proteins secreted by the porK and WT strains revealed that the secretion of several proteins containing C-terminal domain (CTD)-like sequences is dependent on the porK gene. These results indicate that the T9SS is functional in T. forsythia and contributes to the translocation of CTD proteins to the cell surface or into the extracellular milieu

Photoperiod Regulates Corticosterone Rhythms by Altered Adrenal Sensitivity via Melatonin-Independent Mechanisms in Fischer 344 Rats and C57BL/6J Mice

Most species living in temperate zones adapt their physiology and behavior to seasonal changes in the environment by using the photoperiod as a primary cue. The mechanisms underlying photoperiodic regulation of stress-related functions are not well understood. In this study, we analyzed the effects of photoperiod on the hypothalamic-pituitary-adrenal axis in photoperiod-sensitive Fischer 344 rats. We first examined how photoperiod affects diurnal variations in plasma concentrations of adrenocorticotropic hormone (ACTH) and corticosterone. ACTH levels did not exhibit diurnal variations under long- and short-day conditions. On the other hand, corticosterone levels exhibited a clear rhythm under short-day condition with a peak during dark phase. This peak was not observed under long-day condition in which a significant rhythm was not detected. To analyze the mechanisms responsible for the photoperiodic regulation of corticosterone rhythms, ACTH was intraperitoneally injected at the onset of the light or dark phase in dexamethasone-treated rats maintained under long- and short-day conditions. ACTH induced higher corticosterone levels in rats examined at dark onset under short-day condition than those maintained under long-day condition. Next, we asked whether melatonin signals are involved in photoperiodic regulation of corticosterone rhythms, and rats were intraperitoneally injected with melatonin at late afternoon under long-day condition for 3 weeks. However, melatonin injections did not affect the corticosterone rhythms. In addition, photoperiodic changes in the amplitude of corticosterone rhythms were also observed in melatonin-deficient C57BL/6J mice, in which expression profiles of several clock genes and steroidgenesis genes in adrenal gland were modified by the photoperiod. Our data suggest that photoperiod regulates corticosterone rhythms by altered adrenal sensitivity through melatonin-independent mechanisms that may involve the adrenal clock

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target