Potential of a Novel Chemical Compound Targeting Matrix Metalloprotease-13 for Early Osteoarthritis: An In Vitro Study

Osteoarthritis is a progressive disease characterized by cartilage destruction in the joints. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play key roles in osteoarthritis progression. In this study, we screened a chemical compound library to identify new drug candidates that target MMP and ADAMTS using a cytokine-stimulated OUMS-27 chondrosarcoma cells. By screening PCR-based mRNA expression, we selected 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide as a potential candidate. We found that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated IL-1 beta-induced MMP13 mRNA expression in a dose-dependent manner, without causing serious cytotoxicity. Signaling pathway analysis revealed that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated ERK- and p-38-phosphorylation as well as JNK phosphorylation. We then examined the additive effect of 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide in combination with low-dose betamethasone on IL-1 beta-stimulated cells. Combined treatment with 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide and betamethasone significantly attenuated MMP13 and ADAMTS9 mRNA expression. In conclusion, we identified a potential compound of interest that may help attenuate matrix-degrading enzymes in the early osteoarthritis-affected joints

Individual and Regional Characteristics Associated with Maternal Smoking During Pregnancy in Japan: Healthy Parents and Children 21

Smoking during pregnancy causes various maternal and fetal health problems. Although there are considerable differences in maternal smoking proportions between localities, only a few studies have investigated the effects of regional characteristics on maternal smoking behavior. This study aimed to clarify the association between maternal smoking during pregnancy and individual and regional characteristics. We used data from a large nationwide birth cohort study in Japan that consisted of information on 20,267 women with children aged 3–4 months. The multilevel regression model was used to examine the association between smoking behavior during pregnancy and individual and regional characteristics. On multilevel analysis, late birth order, young age of the mother at birth, low birth weight, low economic status, husband’s smoking during pregnancy, maternal alcohol consumption during pregnancy, absence of a pregnancy counselor, and lack of participation in local events for childrearing were significantly associated with maternal smoking behavior during pregnancy at the individual level. Meanwhile, a high unemployment rate and a high number of nurseries were significantly associated with maternal smoking behavior during pregnancy at the regional level. In conclusion, we showed the relation between maternal smoking during pregnancy and the individual- and regional-level characteristics

Catalyst- and Silane- Controlled Enantioselective Hydrofunctionalization of Alkenes by Cobalt-Catalyzed Hydrogen Atom Transfer and Radical-Polar Crossover

Catalytic enantioselective synthesis of tetrahydrofurans, which are found in the structures of many biologically active natural products, via a transition-metal catalyzed-hydrogen atom transfer (TM-HAT) and radical-polar crossover (RPC) mechanism is described herein. Hydroalkoxylation of non-conjugated alkenes proceeded efficiently with excellent enantioselectivity (up to 94% ee) using a suitable chiral cobalt catalyst, N-fluoro-2,4,6-collidinium tetrafluoroborate, and diethylsilane. Surprisingly, absolute configuration of the product was highly dependent on the steric hindrance of the silane. Slow addition of the silane, the dioxygen effect in the solvent, thermal dependency, and DFT calculation results supported the unprecedented scenario of two competing selective mechanisms. For the less-hindered diethylsilane, a high concentration of diffused carbon-centered radicals invoked diastereoenrichment of an alkylcobalt(III) intermediate by a radical chain reaction, which eventually determined the absolute configuration of the product. On the other hand, a more hindered silane resulted in less opportunity for radical chain reaction, instead facilitating enantioselective kinetic resolution during the late-stage nucleophilic displacement of the alkylcobalt(IV) intermediate

Caregivers' mental distress and child health during the COVID-19 outbreak in Japan.

To clarify the physical and mental conditions of children during the coronavirus disease 2019 pandemic and consequent social distancing in relation to the mental condition of their caregivers. This internet-based nationwide cross-sectional study was conducted between April 30 and May 13, 2020. The participants were 1,200 caregivers of children aged 3-14 years. Child health issues were categorized into "at least one" or "none" according to caregivers' perception. Caregivers' mental status was assessed using the Japanese version of the Kessler Psychological Distress Scale-6. The association between caregivers' mental status and child health issues was analyzed using logistic regression models. Among the participants, 289 (24.1%) had moderate and 352 (29.3%) had severe mental distress and 69.8% of children in their care had health issues. The number of caregivers with mental distress was more than double that reported during the 2016 national survey. After adjusting for covariates, child health issues increased among caregivers with moderate mental distress (odds ratio 2.24, 95% confidence interval 1.59-3.16) and severe mental distress (odds ratio 3.05, 95% confidence interval 2.17-4.29) compared with caregivers with no mental distress. The results highlight parents' psychological stress during the pandemic, suggesting the need for adequate parenting support. However, our study did not consider risk factors of caregivers' mental distress such as socioeconomic background. There is an urgent need for further research to identify vulnerable populations and children's needs to develop sustainable social support programs for those affected by the outbreak

Effect of birth season on allergic rhinitis and cedar pollinosis considering allergen and vitamin D exposure: The Japan Environment and Children's study (JECS)

Background: The relationship between the season of birth, allergen sensitization, and allergic rhinitis have been inconsistent, and there are no studies that simultaneously consider vitamin D and allergen exposure. This study aimed to determine the associations between the season of birth, house dust mite (HDM) and Japanese cedar pollen (JCP) sensitization, and allergic rhinitis and pollinosis, while taking vitamin D levels and allergen exposure into account. Methods: This study included 4323 participants in the Sub-Cohort Study of the Japan Environment and Children's Study. A logistic regression model was used to analyze the association between the season of birth and sensitization to JCP or HDM (judged by specific immunoglobulin E) at age 2 and allergic rhinitis or pollinosis at age 3, adjusted for HDM or JCP exposure and vitamin D levels with potential confounders. Results: Participants born in spring or summer were more likely to have pollinosis than were those born in winter (adjusted odds ratio [aOR]: 2.08, 95% confidence interval [CI]: 1.13–3.82 for spring; aOR: 1.89, 95% CI: 1.03–3.47 for summer). Participants born in summer were more likely to have HDM sensitization than were those born in winter (Der p 1, aOR: 1.53, 95% CI: 1.10–2.15; Der f 1, aOR: 1.44, 95% CI: 1.03–2.01). Exposure to JCP and HDM were associated with pollinosis and HDM sensitization, respectively. Conclusions: Spring and summer births were associated with the development of pollinosis, and summer birth was associated with HDM sensitization, even when vitamin D and allergen exposure were considered. Further studies on mechanisms other than vitamin D and allergen exposure are required

Obesity as a potential risk factor for stillbirth: The Japan Environment and Children’s Study

The relationship between high body mass index (BMI) >25 kg/m2 and risk for stillbirth in the Japanese population remains unclear. This study aimed to estimate the impact of maternal obesity on the risk of stillbirth in a Japanese population. This prospective cohort study used data from the Japan Environment and Children’s Study, which recruited pregnant individuals between 2011 and 2014. A total of 93,772 fetuses were considered eligible for inclusion in this study. Stillbirth (fetal death before or during labor at ≥22 completed weeks of gestation) rates were compared among four pre-pregnancy BMI groups: underweight (<18.5 kg/m2), reference (18.5 to <25.0 kg/m2), overweight (25.0 to <30.0 kg/m2), and obese (≥30.0 kg/m2). The association between pre-pregnancy BMI and the risk of stillbirth was estimated using multiple logistic regression analyses. The overall stillbirth incidence was 0.33% (305/93,722). Compared with the reference group, the risk of stillbirth was significantly higher in the overweight group (adjusted odds ratio [aOR]: 1.55; 95% confidence interval [CI]: 1.08–2.23) and the obese group (aOR: 2.60; 95% CI: 1.59–4.24). The overall incidence of early stillbirth (i.e., <28 weeks) was 0.17% (155/93,722). Similarly, after adjusting for potential confounding factors, the risk of early stillbirth was significantly higher in the obese group (aOR: 4.33; 95% CI: 2.44–7.70). Increased maternal BMI was associated with an increased risk of stillbirth in the Japanese population. Therefore, counselling women planning for pregnancy on the importance of an appropriate pre-pregnancy BMI to minimize the risk of stillbirth is important

Exposure to House Dust Mite Allergen and Endotoxin in Early Life and Sensitization and Allergic Rhinitis: The JECS

The association between endotoxin and allergic rhinitis (AR) is not conclusive. The aim of this study was to determine the association between endotoxin and house dust mite (HDM) allergens in dust, and HDM sensitization and AR among Japanese infants. This study included 4188 participants in the Sub-Cohort Study of the Japan Environment and Children&rsquo;s Study. Dust was collected from children&rsquo;s mattresses at age 18 months and endotoxin and HDM allergen levels were measured. A logistic regression model was used to analyze the association between endotoxin or HDM allergen and the sensitization to HDM (specific-IgE) at age 2 and AR at age 3. The median (interquartile range) endotoxin level was 375.1(186.9&ndash;826.5) EU/m2 and the Der 1 (Der p 1 + Der f 1) level was 51.2 (14.8&ndash;168.6) ng/m2. There were significant positive associations between endotoxin and HDM sensitization (Der f 1, adjusted odds ratio [aOR] quartile [Q] 4 vs. Q1, 1.44, 95% CI, 1.04&ndash;2.00; Der p 1, aOR Q4 vs. Q1, 1.56, 95% CI, 1.12&ndash;2.16). There were also significant positive associations between Der 1 exposure and HDM sensitization (Der f 1, aOR Q3 vs. Q1, 1.75, 95% CI, 1.26&ndash;2.44; aOR Q4 vs. Q1, 2.98, 95% CI, 2.15&ndash;4.13; Der p 1, aOR Q3 vs. Q1, 1.91, 95% CI, 1.37&ndash;2.66; aOR Q4 vs. Q1, 2.91, 95% CI, 2.09&ndash;4.05). There were, however, no associations between endotoxin or Der 1 and AR. In the population residing mostly in non-farming settings, both endotoxin and HDM allergens in dust were associated with an increased risk of HDM allergen sensitization, but not with AR

Appropriate procedures to increase the adherence of children to blood collection: A cross‐sectional study

Abstract Background and Aim Venipuncture for blood collection elicits fear and pain in children. We investigated factors that affect satisfaction with health checkups that included blood collection in healthy 7–8‐year‐old children who underwent blood collection with topical anesthesia. Method Two studies, one questionnaire survey, and the other structured interviews were conducted to gather insights and understand the emotions of 492 and 20 children, respectively. Results We found that the following six points can be applied to encourage children to assess their experience of blood collection positively: (1) prior information using a pamphlet; (2) telling the children that the volume of blood drawn will be small; (3) carefully explaining the risk and benefit of topical anesthesia; (4) conducting the blood collection process swiftly; (5) praising and thanking the children's effort and cooperation; and (6) explaining the results of the research to the children if their blood is going to be used for research. Conclusion The findings indicate that with appropriate measures to reduce pain and fear, children's initial negative feelings toward blood collection can be replaced by positive feelings after the procedure