Rates of out-of-home care among children in Canada: an analysis of national administrative child welfare data. / Taux de placement des enfants hors de leur foyer familial : analyse des données administratives nationales du système de protection de l'enfance au Canada.

INTRODUCTION: As a part of the public health approach to child welfare, data about children placed in out-of-home care are needed to assess population trends, understand drivers of social and health inequities, and examine outcomes for children and families. We analyzed administrative data from Canada to describe the population of children in out-of-home care, and estimate and compare rates of out-of-home care by province/territory, year, sex/gender, age group and placement type. METHODS: We conducted a cross-sectional analysis of point-in-time data from all provinces and territories for the period 2013/2014 to 2021/2022. We used frequencies and percentages to describe the population of children (and youth up to age 21 years) in out-of-home care and estimated overall and stratified rates and rate ratios. RESULTS: An estimated 61 104 children in Canada were in out-of-home care on 31 March 2022. The national rate of out-of-home care was 8.24 children per 1000 population. Rate variations by province/territory were substantial and changed over time. Rates were highest among males and children aged 1 to 3 and 16 to 17 years. Foster homes were the most common type of placement, although kinship homes accounted for an increasing share. CONCLUSION: This analysis demonstrated that administrative data can be used to generate national indicators about children involved in the child welfare system. These data can be used for tracking progress towards health and social equity for children and youth in Canada.

[Sixth wave of COVID-19 pandemic: Epidemiological survey in children].

Objectives　At the beginning of the COVID-19 pandemic, the number of infected children was lower than that of adults. Most cases were transmitted in the family, asymptomatic, and severe cases were rare. In the sixth wave in Japan the number of infected children increased sharply after the Omicron variant had been replaced in December 2021, which had a substantial influence in maintaining social and medical functions. Furthermore, few reports on child death in the country have raised concerns among parents. However, no literature has elucidated the epidemiological characteristics of the Omicron variant in children. In this study, we aimed to clarify them during the sixth wave in Japan.Methods　We analyzed the data of 28,086 COVID-19-infected patients those were registered in the Yamashirokita Public Health Center between January 15, 2022 and May 31, 2022. The cumulative incidence and hospitalization rate were compared between the age groups <15 and those >15 years based on the databases compiled by our public health center and the Kyoto prefecture government. In addition, we analyzed the background, length of hospitalization, and clinical symptoms of 24 patients based on active epidemiological investigation, health observations, and discharge reports submitted from medical facilities.Results　Of the 52,897 residents <15 years (pediatric population is 12.3%), 15.1% (7,980 cases) were infected, and children accounted for 28.4% of all-age infected patients. Among them, 24 were hospitalized (0.3% of children with COVID-19, 0.04% of the child population). Conversely, of the 377,093 residents aged ≥15 years, 5.3% (20,106 patients) were infected. Among them, 1,088 were hospitalized (5.4% of COVID-19 patients, 0.28% of the adult population). For 24 hospitalized children, 22 (91.6%) had mild cases and 2 (8.3%) had moderate cases, and no severe case was noted based on the criteria of severity in Japan's COVID-19 medical care guidelines. Two patients (8.3%) were hospitalized for treatment of other diseases. The median of hospital stay was 3.5 days, and 20 patients (83.3%) were discharged home during the recuperation period.Conclusions　The cumulative incidence of children with COVID-19 in the sixth wave was 15.1%, approximately three times higher than that of the older patients; however, no severe case was observed in children.

Asking youth and adults about child maltreatment: a review of government surveys.

OBJECTIVES: In this review we: (1) identify and describe nationally representative surveys with child maltreatment (CM) questions conducted by governments in low-income, middle-income and high-income countries and (2) describe procedures implemented to address respondents' safety and minimise potential distress. DESIGN: We conducted a systematic search across eight databases from 1 January 2000 to 5 July 2021 to identify original studies with information about relevant surveys. Additional information about surveys was obtained through survey methods studies, survey reports, survey websites or by identifying full questionnaires (when available). RESULTS: Forty-six studies representing 139 surveys (98 youth and 41 adult) conducted by governments from 105 countries were identified. Surveys implemented a variety of procedures to maximise the safety and/or reduce distress for respondents including providing the option to withdraw from the survey and/or securing confidentiality and privacy for the respondent. In many surveys, further steps were taken such as providing information for support services, providing sensitivity training to survey administrators when interviews were conducted, among others. A minority of surveys took additional steps to empirically assess potential distress experienced by respondents. CONCLUSIONS: Assessing risk and protective factors and developing effective interventions and policies are essential to reduce the burden of violence against children. While asking about experiences of CM requires careful consideration, procedures to maximise the safety and minimise potential distress to respondents have been successfully implemented globally, although practices differ across surveys. Further analysis is required to assist governments to implement the best possible safety protocols to protect respondents in future surveys.

Child Welfare Reform: A Scoping Review.

While there have been ongoing calls to reform child welfare so that it better meets children's and families' needs, to date there have been no comprehensive summaries of child welfare reform strategies. For this systematic scoping review, we summarized authors' recommendations for improving child welfare. We conducted a systematic search (2010 to 2021) and included published reviews that addressed authors' recommendations for improving child welfare for children, youth, and families coming into contact with child welfare in high-income countries. A total of 4758 records was identified by the systematic search, 685 full-text articles were screened for eligibility, and 433 reviews were found to be eligible for this scoping review. Reviews were theoretically divided, with some review authors recommending reform efforts at the macro level (e.g., addressing poverty) and others recommending reform efforts at the practice level (e.g., implementing evidence-based parenting programs). Reform efforts across socioecological levels were summarized in this scoping review. An important next step is to formulate what policy solutions are likely to lead to the greatest improvement in safety and well-being for children and families involved in child welfare.

Suppression of the doxorubicin response by hypoxia-inducible factor-1α is strictly dependent on oxygen concentrations under hypoxic conditions.

Hypoxia-inducible factor-1α (HIF-1α) and p53 are involved in anticancer drug resistance under hypoxic conditions. Here, we found that the cytotoxicity of anticancer drugs (doxorubicin, gemcitabine, and cisplatin) was lower at 1% O2 than at 5% O2. We examined the effects of these drugs on HIF-1α and p53 expression under different hypoxic oxygen concentrations. At 5% O2, the drugs decreased HIF-1α expression and increased p53 levels. At 1% O2, the drugs increased HIF-1α expression but did not alter p53 levels. When the HIF-1α protein was stabilized by DMOG under normoxic conditions, doxorubicin did not increase the level of p53 expression. These results show that the maintenance of HIF-1α expression blocked doxorubicin-dependent increases in p53 expression. We hypothesized the mechanism of HIF-1α protein translation might be different between at 5% and at 1% O2, because many reports indicate that the same mechanism of HIF-1α protein stabilization occurs under hypoxic conditions, such as 5% and 1% O2. The level of phosphorylated-4E-BP1, which causes translation of HIF-1α, was higher at 1% O2 than at 5% O2. Our results suggest that the sensitivity of tumor cells to anticancer drugs is dependent oxygen concentrations under hypoxic conditions, and involves 4E-BP1-dependent stabilization of the HIF-1α protein.

Examining the unique contributions of parental and youth maltreatment in association with youth mental health problems.

BACKGROUND: Extensive research seeks to understand the intergenerational impact of child maltreatment. However, it remains unclear how parent's history of child maltreatment (PCM) is associated with child mental health, after accounting for children's experiences of maltreatment and other proximal risk factors. OBJECTIVE: This study examines the associations between PCM and youth internalizing and externalizing problems, while accounting for youth experiences of maltreatment (YM), and parent mental health and positive parenting. PARTICIPANTS AND SETTING: Youth aged 14 to 17 years (N = 2266) participated in the 2014 Ontario Child Heath Study. METHODS: Parents and youth reported their experiences of child maltreatment. Parent-report and self-reports of youth internalizing and externalizing problems were also collected. Number of subtypes of maltreatment and specific subtypes of maltreatment were examined. Parents reported their own mental health problems and positive parenting practices. RESULTS: Regarding number of maltreatment subtypes, initially PCM was associated with parent-reported, but not self-reported, youth internalizing and externalizing problems. After accounting for YM, parent mental health problems and positive parenting, only YM remained significant. Regarding specific subtypes of maltreatment, both parent and youth emotional abuse were related to parent- and youth-reported internalizing and externalizing problems, after controlling for other maltreatment subtypes. However, the effects of parent emotional abuse became nonsignificant after accounting for YM and proximal risk factors. CONCLUSIONS: Findings indicate: 1) the unique associations between specific PCM and YM subtypes and youth mental health problems; 2) the role of proximal risk factors in explaining the association between PCM and youth mental health; and 3) the importance of multiple informants of youth mental health problems.

Developmental Evolution of Hypaxial Muscles: Insights From Cyclostomes and Chondrichthyans.

Jawed vertebrates possess two distinct groups of muscles in the trunk (epaxial and hypaxial muscles) primarily defined by the pattern of motor innervation from the spinal cord. Of these, the hypaxial group includes muscles with highly differentiated morphology and function, such as the muscles associated with paired limbs, shoulder girdles and tongue/infrahyoid (hypobranchial) muscles. Here we summarize the latest findings on the evolutionary mechanisms underlying the morphological variety of hypaxial musculature, with special reference to the molecular insights obtained from several living species that diverged early in vertebrate evolution. Lampreys, extant jawless vertebrates, lack many of derived traits characteristic of the gnathostomes, such as jaws, paired fins and epaxial/hypaxial distinction of the trunk skeletal musculatures. However, these animals possess the primitive form of the hypobranchial muscle. Of the gnathostomes, the elasmobranchs exhibit developmental mode of hypaxial muscles that is not identical to that of other gnathostomes in that the muscle primordia relocate as coherent cell aggregates. Comparison of expression of developmental genes, including Lbx genes, has delineated the temporal order of differentiation of various skeletal muscles, such as the hypobranchial, posterior pharyngeal and cucullaris (trapezius) muscles. We have proposed that the sequential addition of distal muscles, associated with expression of duplicated Lbx genes, promoted the elaboration of skeletal musculature. These analyses have revealed the framework of an evolutionary pathway that gave rise to the morphological complexity and diversity of vertebrate body patterns.

Nurse-Family Partnership nurses' attitudes and confidence in identifying and responding to intimate partner violence: An explanatory sequential mixed methods evaluation.

AIMS: To evaluate the effect of an intimate partner violence intervention education component on nurses' attitudes in addressing intimate partner violence; complementary aims included understanding nurses' perceptions of the education and how it influenced their attitudes and confidence to address intimate partner violence in practice. DESIGN: An explanatory sequential mixed methods design embedded within a 15-site cluster randomized clinical trial that evaluated an intimate partner violence intervention within the Nurse-Family Partnership programme. METHODS: Data were collected between February 2011 and September 2016. Quantitative assessment of nurses' attitudes about addressing intimate partner violence was completed by nurses in the intervention (n = 77) and control groups (n = 101) at baseline, 12 months and at study closure using the Public Health Nurses' Responses to Women Who Are Abused Scale. Qualitative data were collected from nurses in the intervention group at two timepoints (n = 14 focus groups) and focused on their perceptions of the education component. Data were analysed using content analysis. RESULTS: Nurses in the intervention group reported large improvements in their thoughts, feelings and perceived behaviours related to addressing intimate partner violence; a strong effect of the education was found from baseline to 12 months and baseline to study closure timepoints. Nurses reported that the education component was acceptable and increased their confidence to address intimate partner violence. CONCLUSION: Nurses reported improved attitudes about and confidence in addressing intimate partner violence after receiving the education component. However, these findings need to be considered together with trial results showing no main effects for clients, and a low level of intervention fidelity. IMPACT: These evaluation findings underscore that improvement in nurses' self-reported educational outcomes about addressing intimate partner violence cannot be assumed to result in adherence to intervention implementation or improvement in client outcomes. These are important considerations for developing nurse education on intimate partner violence.

Allergic contact dermatitis due to the liquid skin adhesive Dermabond® predominantly occurs after the first exposure.

BACKGROUND: The clinical characteristics of patients with allergic contact dermatitis (ACD) due to a skin adhesive containing 2-octyl cyanoacrylate, Dermabond®, have not yet been elucidated. OBJECTIVE: To investigate the clinical characteristics of patients with ACD caused by Dermabond® application. METHODS: In this retrospective study, 577 patch tested patients were included. We identified patients with positive patch test results for Dermabond® and evaluated their results concerning (meth)acrylates and ethyl cyanoacrylate adhesive. RESULTS: Nine patients had positive patch test results to Dermabond®; six had developed secondary generalization.The mean time between Dermabond® application and ACD onset was 34 days (range, 27-44) in six patients with ACD after the first use, whereas, in the other three patients, it was 5.6 days (range, 4-8) after the second use. The time was significantly different between the two groups (P < .01). Positive reactions to ethyl cyanoacrylate adhesive (Aron Alpha) occurred in seven of nine patients, to ethyl cyanoacrylate 10% pet. in four of eight patients tested, and to 2-hydroxyethyl methacrylate in one of eight patients tested. CONCLUSIONS: Dermabond®-induced ACD is apparently characterized by a high prevalence of primary sensitization at first exposure to Dermabond®, secondary generalization is frequent, and most patients show cross-reactivity to ethyl cyanoacrylate.

Novel developmental bases for the evolution of hypobranchial muscles in vertebrates.

BACKGROUND: Vertebrates are characterized by possession of hypobranchial muscles (HBMs). Cyclostomes, or modern jawless vertebrates, possess a rudimentary and superficial HBM lateral to the pharynx, whereas the HBM in jawed vertebrates is internalized and anteroposteriorly specified. Precursor cells of the HBM, marked by expression of Lbx1, originate from somites and undergo extensive migration before becoming innervated by the hypoglossal nerve. How the complex form of HBM arose in evolution is relevant to the establishment of the vertebrate body plan, but despite having long been assumed to be similar to that of limb muscles, modification of developmental mechanisms of HBM remains enigmatic. RESULTS: Here we characterize the expression of Lbx genes in lamprey and hagfish (cyclostomes) and catshark (gnathostome; jawed vertebrates). We show that the expression patterns of the single cyclostome Lbx homologue, Lbx-A, do not resemble the somitic expression of mammalian Lbx1. Disruption of Lbx-A revealed that LjLbx-A is required for the formation of both HBM and body wall muscles, likely due to the insufficient extension of precursor cells rather than to hindered muscle differentiation. Both homologues of Lbx in the catshark were expressed in the somitic muscle primordia, unlike in amniotes. During catshark embryogenesis, Lbx2 is expressed in the caudal HBM as well as in the abdominal rectus muscle, similar to lamprey Lbx-A, whereas Lbx1 marks the rostral HBM and pectoral fin muscle. CONCLUSIONS: We conclude that the vertebrate HBM primarily emerged as a specialized somatic muscle to cover the pharynx, and the anterior internalized HBM of the gnathostomes is likely a novelty added rostral to the cyclostome-like HBM, for which duplication and functionalization of Lbx genes would have been a prerequisite.

Generation of Rat Monoclonal Antibodies Specific for Human Stromal Cell-Derived Factor-2.

Stromal cell-derived factor-2 (SDF-2) is reportedly involved in multiple endoplasmic reticulum (ER) functions, including the misfolded protein catabolic process, protein glycosylation, and ER protein quality control. However, the precise molecular and cellular functions of SDF-2 remain unknown. Previously, we discovered that SDF-2 mediates acquired resistance to oxaliplatin in human gastric cancer cells. In this study, we have generated SDF-2-specific monoclonal antibodies (mAbs), using the rat medial iliac lymph node method, as a tool to explore novel mechanisms of oxaliplatin resistance. The antibodies detected endogenous human SDF-2 in immunoblotting analyses. In addition, immunoprecipitation analyses revealed the availability of these antibodies for human SDF-2. Thus, these mAbs will be available to elucidate molecular and cellular functions of SDF-2 in cancer cells.

Child Welfare Responses Linked to Subtypes of Exposure to Intimate Partner Violence: Evidence From the Canadian Incidence Study of Reported Child Abuse and Neglect.

Children exposed to intimate partner violence (CE-IPV) are at increased risk for later health and social difficulties. To date, studies have primarily focused on CE-IPV as a unitary construct; this may lead to the mistaken assumption that all subtypes of CE-IPV (i.e., exposure to direct or indirect physical abuse, or exposure to emotional abuse) are equally harmful requiring similar responses from child welfare services. The purpose of this study was to examine child welfare responses by CE-IPV subtype in a large Canadian child welfare sample. Using data from the Canadian Incidence Study of Reported Child Abuse and Neglect-2008 (N = 2,184), we examined child welfare responses to CE-IPV subtypes or their co-occurrence. Information was obtained from child welfare workers' reports. Cases with co-occurring subtypes of CE-IPV were more likely to be substantiated and involved multiple incidents compared with that with single CE-IPV subtypes. Cases with direct physical CE-IPV and co-occurring CE-IPV were also more likely to remain open and have an application considered or made to child welfare court. Exposure to emotional IPV was the least likely to warrant interventions by welfare services, including referrals to specialized services. These results suggest that within CE-IPV subtypes, there is evidence of different responses (recommendations and services) once a case has been opened by a worker. Future research is needed to examine the effectiveness of the responses and outcomes for children following child welfare interventions.

Psychophysiological influences on personality trajectories in adolescent females exposed to child maltreatment.

Although child maltreatment is a major public health concern, which adversely affects psychological and physical development, we know relatively little concerning psychophysiological and personality factors that may modify risk in children exposed to maltreatment. Using a three-wave, short-term prospective design, we examined the influence of individual differences in two disparate psychophysiological measures of risk (i.e., resting frontal brain electrical activity and respiratory sinus arrhythmia) on the trajectories of extraversion and neuroticism in a sample of female adolescents (N = 55; M age = 14.02 years) exposed to child maltreatment. Adolescents exposed to child maltreatment with relatively higher left frontal absolute alpha power (i.e., lower brain activity) at rest exhibited increasing trajectories of extraversion, and adolescents exposed to child maltreatment with relatively lower respiratory sinus arrhythmia at rest displayed increasing trajectories of neuroticism over 1 year. Individual differences in psychophysiological measures indexing resting central and peripheral nervous system activity may therefore differentially influence personality characteristics in adolescent females exposed to child maltreatment.

The Autophagy-Related Protein GABARAP Is Induced during Overwintering in the Bean Bug (Hemiptera: Alydidae).

In most insects dependent on food resources that deplete seasonally, mechanisms exist to protect against starvation. Insects overcome periods of food depletion using diapause-associated physiological mechanisms, such as increased energy resources in fat bodies and suppression of metabolism. Because autophagy supplies energy resources through the degradation of intracellular components, we hypothesized that it might be an additional strategy to combat starvation during overwintering. In this study, we measured the abundance of the proteins involved in the signaling pathway of autophagy during overwintering in adults of the bean bug Riptortus pedestris (Fabricius) (Hemiptera: Alydidae), which must withstand the periodic depletion of its host plants from late fall to early spring. Although the levels of gamma-aminobutyric acid receptor-associated protein (GABARAP) markedly increased after the cessation of food supply, AMP-activated protein kinase (AMPK) and target of rapamycin (TOR) were not found to be associated with food depletion. Thus, food depletion appears to induce autophagy independent of AMPK and TOR. The GABARAP levels significantly increased universally when the food supply ceased, irrespective of the diapause status of adults and low-temperature conditions. In overwintering diapause adults under seminatural conditions, the GABARAP levels significantly increased during early spring. Thus, autophagy appears to assist the survival of the bean bugs under natural conditions of food deficiency.

Effect of Yokukansan and Yokukansankachimpihange on Aggressive Behavior, 5-HT Receptors and Arginine Vasopressin Expression in Social Isolation-Reared Mice.

The traditional herbal medicines yokukansan (YKS) and yokukansankachimpihange (YKSCH) are prescribed for neurosis, insomnia or night crying and irritability in children. YKSCH comprises YKS and two additional herbs, a chimpi and a hange, and is used to treat digestive function deficiencies. However, the differences between the effects of YKS and YKSCH on brain function are unclear. The present study examined the effects of YKS and YKSCH on aggressive behavior in mice reared under a social isolation (SI) condition. Mice were housed individually for 6 weeks. YKS and YKSCH were administered orally for 2 weeks before aggression tests. SI increased aggressive behavior against naïve mice, and YKS, but not YKSCH, significantly attenuated this aggressive behavior. Because serotonin (5-HT)2A and 5-HT3A receptor antagonists are reported to have anti-aggressive effects, the mRNA levels of these receptors were examined. YKS attenuated the SI-induced increase in 5-HT2A and 5-HT3A receptor mRNA in the amygdala. On the other hand, YKSCH attenuated the SI-induced increase in 5-HT1A receptor mRNA. YKS and YKSCH did not affect 5-HT and its metabolite 5-hydroxyindoleacetic acid content in the amygdala. However, YKSCH increased the mRNA level of arginine vasopressin (AVP), which is a neuropeptide that has been implicated in aggression, in the amygdala. These results suggest that YKS ameliorates aggressive behavior by decreasing 5-HT2A and 5-HT3A receptor expression. The YKSCH-induced increase in AVP may disrupt the anti-aggressive effect of YKS. YKS may be more effective than YKSCH for treating irritability if digestive function deficiencies are not considered.

Effect of Addition of an Intimate Partner Violence Intervention to a Nurse Home Visitation Program on Maternal Quality of Life: A Randomized Clinical Trial.

Importance: Intimate partner violence (IPV) is a public health problem with significant adverse consequences for women and children. Past evaluations of a nurse home visitation program for pregnant women and first-time mothers experiencing social and economic disadvantage have not consistently shown reductions in IPV. Objective: To determine the effect on maternal quality of life of a nurse home visitation program augmented by an IPV intervention, compared with the nurse home visitation program alone. Design, Setting, and Participants: Cluster-based, single-blind, randomized clinical trial at 15 sites in 8 US states (May 2011-May 2015) enrolling 492 socially disadvantaged pregnant women (≥16 years) participating in a 2.5-year nurse home visitation program. Interventions: In augmented program sites (n = 229 participants across 7 sites), nurses received intensive IPV education and delivered an IPV intervention that included a clinical pathway to guide assessment and tailor care focused on safety planning, violence awareness, self-efficacy, and referral to social supports. The standard program (n = 263 participants across 8 sites) included limited questions about violence exposure and information for abused women but no standardized IPV training for nurses. Main Outcomes and Measures: The primary outcome was quality of life (WHOQOL-BREF; range, 0-400; higher score indicates better quality of life) obtained through interviews at baseline and every 6 months until 24 months after delivery. From 17 prespecified secondary outcomes, 7 secondary end points are reported, including scores on the Composite Abuse Scale, SPAN (Startle, Physiological Arousal, Anger, and Numbness), Prime-MD Patient Health Questionnaire, TWEAK (Tolerance/Worry About Drinking/Eye-Opener/Amnesia/C[K]ut Down on Drinking), Drug Abuse Severity Test, and the 12-Item Short-Form Health Survey (physical and mental health), version 2. Results: Among 492 participants enrolled (mean age, 20.4 years), 421 (86%) completed the trial. Quality of life improved from baseline to 24 months in both groups (change in WHOQOL-BREF scores from 299.5 [SD, 54.4] to 308.2 [SD, 52.6] in the augmented program group vs from 293.6 [SD, 56.4] to 316.4 [SD, 57.5] in the standard program group). Based on multilevel growth curve analysis, there was no statistically significant difference between groups (modeled score difference, -4.9 [95% CI, -16.5 to 6.7]). There were no statistically significant differences between study groups in any of the secondary participant end points. There were no adverse events recorded in either group. Conclusions and Relevance: Among pregnant women experiencing social and economic disadvantage and preparing to parent for the first time, augmentation of a nurse home visitation program with a comprehensive IPV intervention, compared with the home visitation program alone, did not significantly improve quality of life at 24 months after delivery. These findings do not support the use of this intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT01372098.

A dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, attenuates cardiac dysfunction after myocardial infarction independently of DPP-4.

Dipeptidyl peptidase-4 (DPP-4) inhibitors not only improve impaired glucose tolerance in diabetes, but also have pleiotropic extra-pancreatic effects such as preconditioning effect for myocardial ischemia-reperfusion injury. Here, we investigated the anti-remodeling effects of linagliptin, a DPP-4 inhibitor, by use of DPP-4-deficient rats. After the induction of myocardial infarction (MI), Fischer 344 rats with inactivating mutation of DPP-4 were orally administrated with a DPP-4 inhibitor, linagliptin (5 mg kg-1·day-1), or vehicle in drinking water for 4 weeks. Linagliptin did not affect hemodynamic status, body weight, and infarct size. In echocardiography, linagliptin tended to improve left ventricular (LV) systolic function, and significantly improved LV diastolic function, surprisingly. Interstitial fibrosis in marginal region and macrophage infiltration were significantly lower in the linagliptin group than those in the vehicle group. Fibrosis-related gene expressions, such as collagen I and transforming growth factor-ß1 (TGF-ß1), and inflammation-related expressions, such as macrophage chemotactic protein 1 and matrix metalloproteinase-2 (MMP-2), were significantly suppressed in marginal area of the linagliptin-treated rats compared with the vehicle rats. The TGF-ß1 and MMP-2 protein levels were attenuated by linagliptin in DPP-4-deficient cardiac fibroblasts. Linagliptin can attenuate MI-induced cardiac remodeling via a DPP-4-independent pathway.

HIF-1-dependent lipin1 induction prevents excessive lipid accumulation in choline-deficient diet-induced fatty liver.

Adaptive responses to hypoxia regulate hepatic lipid metabolism, but their consequences in nonalcoholic fatty liver disease (NAFLD) are largely unknown. Here, we show that hypoxia inducible factor-1 (HIF-1), a key determinant of hypoxic adaptations, prevents excessive hepatic lipid accumulation in the progression of NAFLD. When exposed to a choline-deficient diet (CDD) for 4 weeks, the loss of hepatic Hif-1α gene accelerated liver steatosis with enhanced triglyceride accumulation in the liver compared to wild-type (WT) livers. Expression of genes involved in peroxisomal fatty acid oxidation was suppressed significantly in CDD-treated WT livers, whereas this reduction was further enhanced in Hif-1α-deficient livers. A lack of induction and nuclear accumulation of lipin1, a key regulator of the PPARα/PGC-1α pathway, could be attributed to impaired peroxisomal ß-oxidation in Hif-1α-deficient livers. The lipin1-mediated binding of PPARα to the acyl CoA oxidase promoter was markedly reduced in Hif-1α-deficient mice exposed to a CDD. Moreover, forced Lipin1 expression restored the aberrant lipid accumulation caused by Hif-1α deletion in cells incubated in a choline-deficient medium. These results strongly suggest that HIF-1 plays a crucial role in the regulation of peroxisomal lipid metabolism by activating the expression and nuclear accumulation of lipin1 in NAFLD.

Nepalese migrants in Japan: What is holding them back in getting access to healthcare?

INTRODUCTION: Migrants are one of the most deprived and vulnerable groups who receive the least health services in the society. Only a few studies have been conducted on access to healthcare among migrants in Asia, despite hosting 75 million migrants. In Japan, Nepalese migrants constitute the largest South Asian community. Their number increased by three folds from 2011 to 2016. However, little is known about their access to health care in Japan. Based on Andersen's model, we examined the factors associated with access to healthcare among Nepalese migrants in Japan. METHODS: We conducted a cross-sectional study among 642 Nepalese migrants residing in 10 prefectures of Japan. We used multivariable logistic regression model to explore the key predisposing, enabling, and need factors associated with access to healthcare among the migrants. RESULTS: The migrants who had stayed in Japan longer were more likely to perceive better access to a doctor/health worker (AOR = 1.11, 95% CI 1.03-1.19).The migrants were more likely to perceive better access to a doctor/health worker (AOR = 1.79, 95% CI 1.17-2.73) when they did not need Japanese language interpreter during visit to health facilities. They were also less likely not to see a doctor/health worker when needed (AOR = 0.34, 95% CI 0.21-0.56). The migrants were less likely to perceive better access to a doctor/health worker when they had not paid the health insurance premium regularly (AOR = 0.21, 95% CI 0.13-0.33).Their low perception of better access to a doctor/health worker was also associated with self-rated health status as poor or fair (AOR = 0.60, 95% CI 0.41-0.89). CONCLUSION: Nepalese migrants have poor access to health care in Japan. The key factors associated with their access to health care are the length of stay (predisposing factor), Japanese language skill and health insurance (enabling factors) and self-rated health status (need factor).