Unintentional Injury Deaths among Children: A Descriptive Study Using Medico-legal Documents in Okayama Prefecture, Japan (2001−2015)

According to the World Health Organization’s World Report, approx. 950,000 children and young people < 18 years old die from an injury each year, and unintentional injury deaths account for a large portion of these cases. Here we used medico-legal documents to epidemiologically analyze the cases of unintentional injury deaths among children < 5 years old in Okayama Prefecture, Japan from 2001 to 2015. Age, sex, manner/cause of death, and various circumstances of the incident were investigated. There were 73 unintentional injury deaths during the study period. Drowning (n=29), suffocation (n=24), and transport accidents (n=13) were the major categories of unintentional injury deaths. Twenty-two cases (30.1%) were autopsied. Differences in the characteristics of the unintentional injury deaths by age were observed. Information which cannot be obtained from Vital Statistics was available from medico-legal documents, and detailed characteristics of unintentional injury deaths among children < 5 years old were elucidated. Investigating medico-legal information is one of the meaningful measures for the prevention of unintentional injury deaths among children in Japan

Predictors of volunteerism: A study of older adults in Japan

Volunteerism has risen steadily as a viable activity at old age in Japan for it gives older adults ways to contribute to society as well as enhancing their quality of life. It has also been addressed by the national government and adopted by many local municipalities under the long-term care insurance program as a health promotion and preventive care activity. However, studies examining why older adults volunteer and why some don’t are limited. Using a modified version of Baltes and colleagues’ model of competence, this study examines the predictors of volunteerism among older adults in Japan. Data from a city located northeast of Tokyo was used (n=703). Results indicated that basic competence does not predict volunteerism, but rather competence gained from experiences. To increase the number of older volunteers, the study suggests that civic engagement must start at an earlier age coupled with financial stability. Keywords: volunteerism, older adults, Japan, competence, long-term care insuranc

Bullous Pemphigoid IgG Induces Cell Dysfunction and Enhances the Motility of Epidermal Keratinocytes via Rac1/Proteasome Activation

Bullous pemphigoid (BP) is an autoimmune disease characterized by the formation of blisters, in which autoantibodies mainly target type XVII collagen (ColXVII) expressed in basal keratinocytes. BP IgG is known to induce the internalization of ColXVII from the plasma membrane of keratinocytes through macropinocytosis. However, the cellular dynamics following ColXVII internalization have not been completely elucidated. BP IgG exerts a precise effect on cultured keratinocytes, and the morphological/functional changes in BP IgG-stimulated cells lead to the subepidermal blistering associated with BP pathogenesis. Based on the electron microscopy examination, BP IgG-stimulated cells exhibit alterations in the cell membrane structure and the accumulation of intracellular vesicles. These morphological changes in the BP IgG-stimulated cells are accompanied by dysfunctional mitochondria, increased production of reactive oxygen species, increased motility, and detachment. BP IgG triggers the cascade leading to metabolic impairments and stimulates cell migration in the treated keratinocytes. These cellular alterations are reversed by pharmacological inhibitors of Rac1 or the proteasome pathway, suggesting that Rac1 and proteasome activation are involved in the effects of BP IgG on cultured keratinocytes. Our study highlights the role of keratinocyte kinetics in the direct functions of IgG in patients with BP

Mutual Effects of Orexin and Bone Morphogenetic Proteins on Gonadotropin Expression by Mouse Gonadotrope Cells

Orexin plays a key role in the regulation of sleep and wakefulness and in feeding behavior in the central nervous system, but its receptors are expressed in various peripheral tissues including endocrine tissues. In the present study, we elucidated the effects of orexin on pituitary gonadotropin regulation by focusing on the functional involvement of bone morphogenetic proteins (BMPs) and clock genes using mouse gonadotrope L beta T2 cells that express orexin type 1 (OX1R) and type 2 (OX2R) receptors. Treatments with orexin A enhanced LH beta and FSH beta mRNA expression in a dose-dependent manner in the absence of GnRH, whereas orexin A in turn suppressed GnRH-induced gonadotropin expression in L beta T2 cells. Orexin A downregulated GnRH receptor expression, while GnRH enhanced OX1R and OX2R mRNA expression. Treatments with orexin A as well as GnRH increased the mRNA levels of Bmal1 and Clock, which are oscillational regulators for gonadotropin expression. Of note, treatments with BMP-6 and -15 enhanced OX1R and OX2R mRNA expression with upregulation of clock gene expression. On the other hand, orexin A enhanced BMP receptor signaling of Smad1/5/9 phosphorylation through upregulation of ALK-2/BMPRII among the BMP receptors expressed in L beta T2 cells. Collectively, the results indicate that orexin regulates gonadotropin expression via clock gene expression by mutually interacting with GnRH action and the pituitary BMP system in gonadotrope cells

Clinical Effects of Probiotic Bifidobacterium breve Supplementation in Adult Patients with Atopic Dermatitis

Probiotics (live microbial food supplements) have been shown to be effective in allergic diseases, but the potential of probiotics for treatment of adult atopic dermatitis is not clear. The effect of probiotic Bifidobacterium breve (B. breve) for atopic dermatitis was assessed in this study. A total of 24 patients were given either B. breve strain YY or a placebo for 8 weeks. Clinical severity was evaluated by using the severity scoring of atopic dermatitis and quality of life was assessed by Skindex-29-J. In addition, blood and fecal samples were taken before and after the study. The objective severity scoring for atopic dermatitis significantly improved in the probiotic group compared with the placebo group. In the quality of life assessment, the total score showed significant improvement in the probiotic group. The proportion of B. breve in intestinal microflora was increased in the probiotic group. However, no significant change in thymus and activation-regulated chemokine (TARC/CCL17), immunoglobulin E or the number of eosinophils was found. Our results suggest that B. breve may be beneficial for the treatment of atopic dermatitis. However, since the severity of disease symptoms in the placebo group at the beginning of the study was milder than those in the probiotic group because the number of patients in the present pilot study was relatively small, further study is needed to determine the clinical value of B. breve in adult patients with atopic dermatitis

Anomalous negative excursion of carbon isotope in organic carbon after the last Paleoproterozoic glaciation in North America

Early Paleoproterozoic time (2.5–2.0 Ga) spanned a critical phase in Earth's history, characterized by repeated glaciations and an increase in atmospheric oxygen (the Great Oxidation Event (GOE)). Following the last and most intense glaciation of this period, marine carbonates record a large positive excursion of δ^(13)C value (termed the “Lomagundi event”) between about 2.2 and 2.1 Ga coinciding with the global appearances of red beds and sulfates, which suggest an accumulation of high levels of atmospheric oxygen. Here we report the discovery of large negative excursions of δ^(13)C in organic matter (down to −55‰) from quartzose sandstones (of the Marquette Range and the Huronian Supergroups, North America) intermediate in age between the last Paleoproterozoic glaciation and the possible onset of the Lomagundi event. The negative excursion is concomitant with the appearance of intensely weathered quartzose sandstones, which may represent hot and humid conditions. There are some interpretations that potentially explain the negative excursions: (1) redeposition of older ^(13)C-depleted kerogen, (2) later post-depositional infiltration of oil, (3) active methane productions by methanogens in shallow-marine environments, or (4) dissociation of methane hydrate. If the latter two were the case, they would provide clues for understanding the environmental change connecting the intense glaciation and an increase in oxygen

ADAR1 is a promising risk stratification biomarker of remnant liver recurrence after hepatic metastasectomy for colorectal cancer

Adenosine-to-inosine RNA editing is a process mediated by adenosine deaminases that act on the RNA (ADAR) gene family. It has been discovered recently as an epigenetic modification dysregulated in human cancers. However, the clinical significance of RNA editing in patients with liver metastasis from colorectal cancer (CRC) remains unclear. The current study aimed to systematically and comprehensively investigate the significance of adenosine deaminase acting on RNA 1 (ADAR1) expression status in 83 liver metastatic tissue samples collected from 36 patients with CRC. The ADAR1 expression level was significantly elevated in liver metastatic tissue samples obtained from patients with right-sided, synchronous, or RAS mutant-type CRC. ADAR1-high liver metastasis was significantly correlated with remnant liver recurrence after hepatic metastasectomy. A high ADAR1 expression was a predictive factor of remnant liver recurrence (area under the curve = 0.72). Results showed that the ADAR1 expression level could be a clinically relevant predictive indicator of remnant liver recurrence. Patients with liver metastases who have a high ADAR1 expression requires adjuvant chemotherapy after hepatic metastasectomy

Evolution of Developmental Programs for the Midline Structures in Chordates: Insights From Gene Regulation in the Floor Plate and Hypochord Homologues of Ciona Embryos

In vertebrate embryos, dorsal midline tissues, including the notochord, the prechordal plate, and the floor plate, play important roles in patterning of the central nervous system, somites, and endodermal tissues by producing extracellular signaling molecules, such as Sonic hedgehog (Shh). In Ciona, hedgehog.b, one of the two hedgehog genes, is expressed in the floor plate of the embryonic neural tube, while none of the hedgehog genes are expressed in the notochord. We have identified a cis-regulatory region of hedgehog.b that was sufficient to drive a reporter gene expression in the floor plate. The hedgehog.b cis-regulatory region also drove ectopic expression of the reporter gene in the endodermal strand, suggesting that the floor plate and the endodermal strand share a part of their gene regulatory programs. The endodermal strand occupies the same topographic position of the embryo as does the vertebrate hypochord, which consists of a row of single cells lined up immediately ventral to the notochord. The hypochord shares expression of several genes with the floor plate, including Shh and FoxA, and play a role in dorsal aorta development. Whole-embryo single-cell transcriptome analysis identified a number of genes specifically expressed in both the floor plate and the endodermal strand in Ciona tailbud embryos. A Ciona FoxA ortholog FoxA.a is shown to be a candidate transcriptional activator for the midline gene battery. The present findings suggest an ancient evolutionary origin of a common developmental program for the midline structures in Olfactores

A prospective compound screening contest identified broader inhibitors for Sirtuin 1

Potential inhibitors of a target biomolecule, NAD-dependent deacetylase Sirtuin 1, were identified by a contest-based approach, in which participants were asked to propose a prioritized list of 400 compounds from a designated compound library containing 2.5 million compounds using in silico methods and scoring. Our aim was to identify target enzyme inhibitors and to benchmark computer-aided drug discovery methods under the same experimental conditions. Collecting compound lists derived from various methods is advantageous for aggregating compounds with structurally diversified properties compared with the use of a single method. The inhibitory action on Sirtuin 1 of approximately half of the proposed compounds was experimentally accessed. Ultimately, seven structurally diverse compounds were identified