[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.

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.

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.

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.

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.

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.

Role of hypoxia-inducible factor-1 in the development of renal fibrosis in mouse obstructed kidney: Special references to HIF-1 dependent gene expression of profibrogenic molecules.

The aim of the study is to clarify the role of hypoxia-inducible factor-1 (HIF-1) in the development of renal fibrosis in mouse obstructive nephropathy. We used mice with floxed HIF-1α alleles and tamoxifen-inducible Cre/ERT2 recombinase under ubiquitin C promoter to induce global HIF-1α deletion. Following tamoxifen administration, mice were subjected to unilateral ureteral obstruction (UUO). At 3, 7 and 14 days after UUO, renal gene expression profiles and interstitial fibrosis were assessed. HIF-1 dependent up-regulation of prolyl hydroxylase 3 and glucose transporter-1 was observed in the obstructed kidney at 3 and 7 days but not at 14 days after UUO. Various factors promoting fibrosis were up-regulated during the development of fibrosis. HIF-1 dependent gene expression of profibrotic molecules, plasminogen activator inhibitor 1, connective tissue growth factor, lysyl oxidase like 2 and transglutaminase 2 was observed in the obstructed kidney but such HIF-1 dependency was limited to the early onset of renal fibrosis. Global HIF-1 deletion tended to attenuate interstitial collagen I deposition at 3 days but had no effects thereafter. It is suggested that HIF-1 dependent profibrogenic mechanisms are operating at the early onset of renal fibrosis but its contribution declines with the progression in mouse UUO model.

Longitudinal Associations Among Child Maltreatment, Resting Frontal Electroencephalogram Asymmetry, and Adolescent Shyness.

Child maltreatment is linked to distinct neurophysiological patterns and social-emotional vulnerability. Relations among maltreatment, relative resting frontal alpha asymmetry, shyness, and psychopathology were examined prospectively. Adolescent girls (age 14-16) who experienced child maltreatment (N = 55) were compared to nonmaltreated controls (N = 25), and returned for 6- and 12-month follow-ups. Among participants exhibiting relative right frontal asymmetry, maltreated adolescents reported higher shyness than controls at Time 1. Low-stable and high-stable shyness trajectories were observed for maltreated participants. Compared to low shy, participants in high-shy trajectory reported at Time 3: higher neuroticism and generalized anxiety; and lower extraversion if they also exhibited relative right frontal asymmetry. Thus, right frontal brain activity and shyness are involved in social-emotional vulnerability of adolescents who experienced child maltreatment.

Trajectories of resting frontal brain activity and psychopathology in female adolescents exposed to child maltreatment.

Resting frontal electroencephalogram (EEG) alpha asymmetry patterns reflecting different affective and motivational tendencies have been proposed as a putative mechanism underlying resilience among maltreated youth. This 2-year prospective study examined whether developmental stability of resting frontal alpha asymmetry moderated the relation between child maltreatment severity and psychopathology in female adolescents (n = 43; ages 12-16) recruited from child protection agencies. Results identified two trajectories of resting frontal asymmetry: 60.5% displayed stable right and 39.5% displayed stable left frontal alpha asymmetry. Although individuals with these alpha asymmetry profiles experienced comparable childhood trauma severity, adolescents with stable left alpha asymmetry and lower levels of trauma were less likely to present symptoms or an episode of posttraumatic stress disorder (PTSD) and depression over 2 years than those with stable right alpha asymmetry and lower levels of trauma. These findings suggest that developmental patterns of resting left frontal brain activity may buffer against psychopathology in maltreated female youth.

Heat shock protein 70 inhibitors suppress androgen receptor expression in LNCaP95 prostate cancer cells.

Androgen deprivation therapy is initially effective for treating patients with advanced prostate cancer; however, the prostate cancer gradually becomes resistant to androgen deprivation therapy, which is termed castration-resistant prostate cancer (CRPC). Androgen receptor splice variant 7 (AR-V7), one of the causes of CRPC, is correlated with resistance to a new-generation AR antagonist (enzalutamide) and poor prognosis. Heat shock protein 70 (Hsp70) inhibitor is known to decrease the levels of full-length AR (AR-FL), but little is known about its effects against CRPC cells expressing AR-V7. In this study, we investigated the effect of the Hsp70 inhibitors quercetin and VER155008 in the prostate cancer cell line LNCaP95 that expresses AR-V7, and explored the mechanism by which Hsp70 regulates AR-FL and AR-V7 expression. Quercetin and VER155008 decreased cell proliferation, increased the proportion of apoptotic cells, and decreased the protein levels of AR-FL and AR-V7. Furthermore, VER155008 decreased AR-FL and AR-V7 mRNA levels. Immunoprecipitation with Hsp70 antibody and mass spectrometry identified Y-box binding protein 1 (YB-1) as one of the molecules regulating AR-FL and AR-V7 at the transcription level through interaction with Hsp70. VER155008 decreased the phosphorylation of YB-1 and its localization in the nucleus, indicating that the involvement of Hsp70 in AR regulation might be mediated through the activation and nuclear translocation of YB-1. Collectively, these results suggest that Hsp70 inhibitors have potential anti-tumor activity against CRPC by decreasing AR-FL and AR-V7 expression through YB-1 suppression.

Global research priorities for interpersonal violence prevention: a modified Delphi study.

OBJECTIVE: To establish global research priorities for interpersonal violence prevention using a systematic approach. METHODS: Research priorities were identified in a three-round process involving two surveys. In round 1, 95 global experts in violence prevention proposed research questions to be ranked in round 2. Questions were collated and organized according to the four-step public health approach to violence prevention. In round 2, 280 international experts ranked the importance of research in the four steps, and the various substeps, of the public health approach. In round 3, 131 international experts ranked the importance of detailed research questions on the public health step awarded the highest priority in round 2. FINDINGS: In round 2, "developing, implementing and evaluating interventions" was the step of the public health approach awarded the highest priority for four of the six types of violence considered (i.e. child maltreatment, intimate partner violence, armed violence and sexual violence) but not for youth violence or elder abuse. In contrast, "scaling up interventions and evaluating their cost-effectiveness" was ranked lowest for all types of violence. In round 3, research into "developing, implementing and evaluating interventions" that addressed parenting or laws to regulate the use of firearms was awarded the highest priority. The key limitations of the study were response and attrition rates among survey respondents. However, these rates were in line with similar priority-setting exercises. CONCLUSION: These findings suggest it is premature to scale up violence prevention interventions. Developing and evaluating smaller-scale interventions should be the funding priority.

Myeloid HIF-1 attenuates the progression of renal fibrosis in murine obstructive nephropathy.

Hypoxia-inducible factors (HIFs) play an important role in the pathogenesis of renal fibrosis. Although the role of macrophage infiltration in the progression of renal fibrosis is well known, the role of macrophage HIF-1 remains to be revealed. To address this question, myeloid specific conditional HIF-1 knock out mice were subjected to unilateral ureteral obstruction (UUO). Renal interstitial deposition of collagen Ⅲ and mRNA expressions of collagen Ⅰ and collagen Ⅲ were markedly increased at 7 days after UUO and myeloid HIF-1 depletion significantly accelerated these increases. Immunohistochemistry and flow cytometric analysis revealed that renal infiltrating macrophages were increased with duration of UUO but myeloid HIF-1 depletion did not affect these changes. Myeloid HIF-1 depletion did not affect M1 and M2 macrophage phenotype polarization in obstructed kidneys. Renal connective tissue growth factor (CTGF) expression was markedly increased and myeloid HIF-1 depletion further enhanced this increase. Immunomagnetic separation of renal cells revealed that renal CTGF was expressed predominantly in renal cells other than macrophages. It is suggested that myeloid HIF-1 attenuates the progression of renal fibrosis in murine obstructive kidney. Alteration of CTGF expression in renal cells other than macrophages is one of possible mechanisms by which myeloid HIF-1 protected renal fibrosis.

Lipid synthesis is promoted by hypoxic adipocyte-derived exosomes in 3T3-L1 cells.

Hypoxia occurs within adipose tissues as a result of adipocyte hypertrophy and is associated with adipocyte dysfunction in obesity. Here, we examined whether hypoxia affects the characteristics of adipocyte-derived exosomes. Exosomes are nanovesicles secreted from most cell types as an information carrier between donor and recipient cells, containing a variety of proteins as well as genetic materials. Cultured differentiated 3T3-L1 adipocytes were exposed to hypoxic conditions and the protein content of the exosomes produced from these cells was compared by quantitative proteomic analysis. A total of 231 proteins were identified in the adipocyte-derived exosomes. Some of these proteins showed altered expression levels under hypoxic conditions. These results were confirmed by immunoblot analysis. Especially, hypoxic adipocyte-released exosomes were enriched in enzymes related to de novo lipogenesis such as acetyl-CoA carboxylase, glucose-6-phosphate dehydrogenase, and fatty acid synthase (FASN). The total amount of proteins secreted from exosomes increased by 3-4-fold under hypoxic conditions. Moreover, hypoxia-derived exosomes promoted lipid accumulation in recipient 3T3-L1 adipocytes, compared with those produced under normoxic conditions. FASN levels were increased in undifferentiated 3T3-L1 cells treated with FASN-containing hypoxic adipocytes-derived exosomes. This is a study to characterize the proteomic profiles of adipocyte-derived exosomes. Exosomal proteins derived from hypoxic adipocytes may affect lipogenic activity in neighboring preadipocytes and adipocytes.

[A case of anaphylaxis induced by gelatin-contained gel capsule cold medicine].

We report here a 20-year old woman who referred to our clinic for identify the responsible antigen of anaphylaxis. Five days before the reaction, she had a cold and had taken a gel capsule cold medicine, Stona IB Gel®. On the day of the reaction, she took a dose of Stona IB Gel® after eating yogurt. Five minutes after oral administration, she developed a heat sensation and pruritus on her neck, with flushing, abdominal pains, breathing difficulties, and syncope. The specific IgE antibodies measured by ImmunoCAP® were all negative except for gelatin. Prick-prick skin testing revealed positive responses to Stona IB Gel®, gelatin KS and gelatin RP600, of which the latter two were included in the Stona IB Gel® capsule. From these test results, she was diagnosed with anaphylaxis due to gelatin, and to date she has had no further allergic symptoms since avoiding foods containing gelatin. In infancy she had received four vaccinations against diphtheria, pertussis and tetanus, which contained gelatin as a stabilizer. However, she had not developed allergic symptoms until this time. We hypothesize that she might be sensitized to gelatin by taking Stona IB Gel® during the preceding 4 days. This is the first case of anaphylaxis from the ingestion of an oral medication containing gelatin in Japan. Allergic reactions to gelatin are comparatively rare, but according to the past reports, the reactions were severe. Since many kinds of foods, cosmetics, pharmaceutical products, and medication contain gelatin, it is important to be aware of gelatin allergy.

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.

Pravastatin-induced proangiogenic effects depend upon extracellular FGF-2.

The HMG-CoA reductase inhibitors (statins) have been shown to exert several protective effects on the vasculature that are unrelated to changes in the cholesterol profile, and to induce angiogenesis. The proangiogenic effect exerted by statins has been attributed to the activation of the PI3K/Akt pathway in endothelial cells; however, it is unclear how statins activate this pathway. Pravastatin-mediated activation of Akt and MAPK occurs rapidly (within 10 min.) and at low doses (10 nM). Here, we hypothesized that FGF-2 contributes to the proangiogenic effect of statins. We found that pravastatin, a hydrophilic statin, induced phosphorylation of the FGF receptor (FGFR) in human umbilical vein endothelial cells. SU5402, an inhibitor of FGFR, abolished pravastatin-induced PI3K/Akt and MAPK activity. Likewise, anti-FGF-2 function-blocking antibodies inhibited Akt and MAPK activity. Moreover, depletion of extracellular FGF-2 by heparin prevented pravastatin-induced phosphorylation of Akt and MAPK. Treatment with FGF-2 antibody inhibited pravastatin-enhanced endothelial cell proliferation, migration and tube formation. These observations indicate that pravastatin exerts proangiogenic effects in endothelial cells depending upon the extracellular FGF-2.

[Oral capecitabine as postoperative adjuvant chemotherapy in stage III colon cancer patients].

Capecitabine(Xeloda®)has been a global standard drug for the treatment of colon cancer since large randomized controlled trials demonstrated its efficacy and safety in treating patients suffering from the disease. Few studies have been conducted to assess the effects of oral capecitabine treatment on Japanese patients. Therefore, we conducted this study to evaluate oral capecitabine as postoperative adjuvant chemotherapy in 50 patients who underwent surgery for stage III colon cancer at our department. Patients received an 8 courses treatment with capecitabine during the study, and the incidence of adverse events, treatment completion rate, and treatment compliance were assessed. Adverse events were reported in a total of 46 patients(92%). The most common adverse event was hand foot syndrome(HFS), reported in 39 patients(78%), whereas bone-marrow toxicity and diarrhea were reported in as few as 2(4%)and 3(6%)patients, respectively. Both these events were mild in severity, and no patients required hospitalization, nor were they associated with treatment-related deaths. The median treatment duration was 8 courses ranging from 3 to 8 courses, and the 8 courses treatment completion rate was 96%. The relative dose intensity, which was used as a treatment compliance index, is expressed as the actual dose taken by the patient divided by the dose planned at baseline. The median and mean of the relative dose intensity were 100%(ranging from 37% to 100%)and 93%, respectively. The results of this study showed that the safety profile of oral capecitabine therapy was generally favorable, with a lower incidence and lesser severity of life-threatening bone-marrow toxicity and diarrhea, although the treatment is still associated with frequent HFS. This is the great advantage of capecitabine when it is used as postoperative adjuvant chemotherapy for gastrointestinal cancer. Indeed, a satisfactory treatment completion rate was achieved in this study while maintaining a sufficient dose and treating HFS, by reducing the dose, interrupting treatment, or providing appropriate corrective measures.

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.