Comprehensive Assessment of Risk Factors of Cause-Specific Infant Deaths in Japan

Background: Public attention is given to infants with socially high risks of child abuse and neglect, while clinical attention is provided to infants with a biologically high risk of diseases. However, few studies have systematically evaluated how biological or social factors cross over and affect cause-specific infant mortality.Methods: We linked birth data with death data from the Japanese national vital statistics database for all infants born from 2003–2010. Using multivariate logistic regression, we examined the association between biological and social factors and infant mortality due to medical causes (internal causes), abuse (intentional external causes), and accidents (unintentional external causes).Results: Of 8,941,501 births, 23,400 (0.26%) infants died by 1 year of age, with 21,884 (93.5%) due to internal causes, 175 (0.75%) due to intentional external causes, and 1,194 (5.1%) due to unintentional external causes. Infants with high social risk (teenage mothers, non-Japanese mothers, single mothers, unemployed household, four or more children in the household, or birth outside of health care facility) had higher risk of death by intentional, unintentional, and internal causes. Infant born with small for gestational age and preterm had higher risks of deaths by internal and unintentional causes, but not by intentional causes.Conclusions: Both biological as well as social factors were associated with infant deaths due to internal and external causes. Interdisciplinary support from both public health and clinical-care professionals is needed for infants with high social or biological risk to prevent disease and injury

TSLP and IL-7 use two different mechanisms to regulate human CD4+ T cell homeostasis

Whether thymic stromal lymphopoietin (TSLP) directly induces potent human CD4+ T cell proliferation and Th2 differentiation is unknown. We report that resting and activated CD4+ T cells expressed high levels of IL-7 receptor a chain but very low levels of TSLP receptor (TSLPR) when compared with levels expressed in myeloid dendritic cells (mDCs). This was confirmed by immunohistology and flow cytometry analyses showing that only a subset of mDCs, with more activated phenotypes, expressed TSLPR in human tonsils in vivo. IL-7 induced strong STAT1, -3, and -5 activation and promoted the proliferation of naive CD4+ T cells in the presence of anti-CD3 and anti-CD28 monoclonal antibodies, whereas TSLP induced weak STAT5 activation, associated with marginally improved cell survival and proliferation, but failed to induce cell expansion and Th2 differentiation. The effect of TSLP on enhancing strong human T cell proliferation was observed only when sorted naive CD4+ T cells were cultured with mDCs at levels as low as 0.5%. TSLP could only induce naive CD4+ T cells to differentiate into Th2 cells in the presence of allogeneic mDCs. These results demonstrate that IL-7 and TSLP use different mechanisms to regulate human CD4+ T cell homeostasis

Polygenic architecture informs potential vulnerability to drug-induced liver injury

Drug-Induced-Liver-Injury (DILI) is a leading cause of termination in drug development programs and removal of drugs from the market, and this is partially due to the inability to identify patients who are at risk1. Here, we developed a polygenic risk score (PRS) for DILI by aggregating effects of numerous genome-wide loci identified from previous large-scale genome-wide association studies (GWAS)2. The PRS predicted the susceptibility to DILI in patients treated with fasiglifam, amoxicillin-clavulanate or flucloxacillin, and in primary hepatocytes and stem cell-derived organoids from multiple donors treated with over 10 different drugs. Pathway analysis highlighted processes previously implicated in DILI, including unfolded protein responses and oxidative stress. In silico screening identified compounds that elicit transcriptomic signatures present in hepatocytes from individuals with elevated PRS, supporting mechanistic links and suggesting a novel screen for safety of new drug candidates. This genetic-, cellular-, organoid- and human-scale evidence underscored the polygenic architecture underlying DILI vulnerability at the level of hepatocytes, thus facilitating future mechanistic studies. Moreover, the proposed “polygenicity-in-a-dish” strategy might potentially inform designs of safer, more efficient, and robust clinical trials

Oldenlandia diffusa Extract Inhibits Biofilm Formation by Haemophilus influenzae Clinical Isolates.

Oldenlandia diffusa has been empirically used as a therapeutic adjunct for the treatment of respiratory infections. To establish the basic evidence of its clinical usefulness, antimicrobial and biofilm inhibitory activities of an O. diffusa extract were examined against clinical isolates of Haemophilus influenzae, a major causative pathogen of respiratory and sensory organ infections. No significant growth inhibitory activity was observed during incubation for more than 6 h after the extract addition into a culture of H. influenzae. On the other hand, biofilm formation by H. influenzae, evaluated by a crystal violet method, was significantly and dose-dependently inhibited by the O. diffusa extract. Furthermore, the mRNA level of the biofilm-associated gene luxS of H. influenzae significantly decreased soon after the extract addition, and the suppressive effect continued for at least 2 h. At 2 h after the addition of the O. diffusa extract, the autoinducer in the culture supernatant was also significantly reduced by the O. diffusa extract in a dose-dependent manner. These results revealed that O. diffusa extract shows inhibitory activity against luxS-dependent biofilm formation but has no antimicrobial activity against planktonic cells of H. influenzae. Thus, O. diffusa extract might be useful as an adjunctive therapy for the treatment of respiratory infections caused by H. influenzae

Comprehensive Assessment of Risk Factors of Cause-Specific Infant Deaths in Japan

Background: Public attention is given to infants with socially high risks of child abuse and neglect, while clinical attention is provided to infants with a biologically high risk of diseases. However, few studies have systematically evaluated how biological or social factors cross over and affect cause-specific infant mortality. Methods: We linked birth data with death data from the Japanese national vital statistics database for all infants born from 2003–2010. Using multivariate logistic regression, we examined the association between biological and social factors and infant mortality due to medical causes (internal causes), abuse (intentional external causes), and accidents (unintentional external causes). Results: Of 8,941,501 births, 23,400 (0.26%) infants died by 1 year of age, with 21,884 (93.5%) due to internal causes, 175 (0.75%) due to intentional external causes, and 1,194 (5.1%) due to unintentional external causes. Infants with high social risk (teenage mothers, non-Japanese mothers, single mothers, unemployed household, four or more children in the household, or birth outside of health care facility) had higher risk of death by intentional, unintentional, and internal causes. Infant born with small for gestational age and preterm had higher risks of deaths by internal and unintentional causes, but not by intentional causes. Conclusions: Both biological as well as social factors were associated with infant deaths due to internal and external causes. Interdisciplinary support from both public health and clinical-care professionals is needed for infants with high social or biological risk to prevent disease and injury

The relationship between raising a child with a disability and the mental health of mothers compared to raising a child without disability in japan

AbstractObjectivePrevious studies conducted in Japan targeted only mothers who cared for children with disabilities, and lacked reference subjects, such as mothers of children without disabilities. The aim of this study was to examine the association between raising one or two children with a disability and maternal psychological distress compared to mothers of children without a disability, and to assess differences among partnered mothers living with grandparent(s), partnered mothers without grandparent(s), and single mothers.MethodsThis study utilized data from the Comprehensive Survey of Living Conditions (CSLC) in 2010. We merged the data of the children (aged six and over), mothers, and fathers. This study obtained 33,739 study subjects as a triad of a child (33,110 children without disabilities and 629 children with disabilities), mother, and father. The Japanese version of Kessler 6 (K6) was used to assess the psychological distress of mothers. Multivariate logistic regression was performed to assess the independent association of a child with a disability on maternal psychological distress after controlling for the basic characteristics of the children, mothers, and households.ResultsThis study reported that raising one or two children with disabilities was significantly related to maternal psychological distress (odds ratio: 1.72 for one child, 2.85 for two children) compared to mothers of children without disability. After stratifying the analyses by family structure, significant associations remained among mothers in two-parent families but not for mothers in three-generation families and single mothers due to a small number of children with disabilities in these families.ConclusionsThis study reported the significant association between raising a child with a disability and maternal psychological distress in comparison to mothers of children without disabilities. Attention should be paid to not only single mothers, but also partnered mothers in two-parent families who have a child with a disability. It is important for health professionals to focus on the mental health of every mother of a child with a disability and to assess their needs for psychological support

Direct observation of pressure-induced amorphization of methane/ethane hydrates using Raman and infrared spectroscopy

The pressure-induced amorphization (PIA) of ice and clathrate hydrates occurs at temperatures significantly below their melting and decomposition points. The PIA of type I clathrate hydrates containing methane and ethane as guest molecules was investigated using Raman and infrared (IR) spectroscopy. With isothermal compression at 100 K, methane hydrate (MH) underwent PIA at 2–3.5 GPa, whereas ethane hydrate (EH) underwent PIA at 4.0–5.5 GPa. The type I clathrate structure consists of small (512) and large (51262) cages. The Raman results revealed that the collapsed small and large cages in the amorphous forms of MH and EH were not distinguishable. The collapsed cages, including the methane and ethane molecules, were similar to the small and large cages, respectively. Their water networks were folded or expanded during the PIA process so that the cavity sizes of the collapsed cages were compatible with those of the guest molecules. Peaks in the IR spectra of crystalline MH assignable to the ro-vibrational transition of methane in large cages were observed in the C–H stretching wavenumber region below 40 K. The ro-vibrational IR band disappeared after amorphization, suggesting that the rotational motion of the methane molecule in the large cage was frozen by the collapse, as reported in previous dielectric spectroscopic and simulation studies. This study contributes to a better understanding of the changes in the local structure around guest molecules during PIA and the dynamics of the guest molecules

Mental Health of Parents as Caregivers of Children with Disabilities: Based on Japanese Nationwide Survey.

The number of children with disability is increasing gradually in Japan. Previous researches in other countries have reported that parents as caregivers (CGs) of children with disability have mental health problems, but the actual situation has not been examined nationwide in Japan so far. The aim of this study was to evaluate the association between mental health of CGs who had children with disability and characteristics of children, CGs, and household based on the nation-wide survey. This study utilized data from 2010 Comprehensive Survey of the Living Conditions, and defined children with disability aged 6 to 17. Individual data of children and CGs were linked, and 549 pairs of them were extracted. The Japanese version of Kessler 6 (K6) was used to assess mental health status of caregiver, scored 5 and over represented to general psychological distress. Logistic regression was used to evaluate the associations of interest. The almost half (44.4%) of CGs had psychological distress (k6 score; 5 +) in nationwide, and 8.9% of CGs might have serious mental illness (K6 score; 13 +). After adjusting covariates of child, CG, and household factors, CG having a current symptom (OR, 95% CI: 3.26, 1.97-5.39), CG's activity restriction (OR, 95% CI: 2.95, 1.38-6.32), low social support (OR, 95%CI: 9.31, 1.85-46.8), three generation family (OR, 95% CI: 0.49, 0.26-0.92), and lower 25% tile group of monthly household expenditure (OR, 95% CI:1.92, 1.05-3.54), were significantly associated with psychological distress of CGs. This study encourages health care providers to pay more attentions toward parent's mental health, especially for in case of having low social support, and lower income family. Further research should examine the detailed information of child's disease and disability, medical service use, and quality and quantity of social support in nationwide to straighten the system for supporting services of both children with disabilities and their CGs