Reduction in Anti-Dengue Virus IgG Antibody Levels with the Use of a Larvicide for Vector Control in Rural Lao People's Democratic Republic.

The Lao People's Democratic Republic is an endemic area of dengue, with cases reported in urban and rural areas every year. In this study, we indirectly evaluated the efficacy of a larvicide (SumiLarvTM 2MR discs) that was used for vector control against Aedes mosquitoes. Villages in a rural area of Lao PDR were selected as study areas, non-intervention and intervention villages. At the intervention village, the larvicide was used to treat refillable water containers for 27 months (October 2017 to February 2020), while at the non-intervention villages were no treatment. The serum samples of villagers from both villages were randomized to collect in the pre-intervention and in post-intervention periods. An enzyme-linked immunosorbent assay (ELISA) was used to examine anti-dengue virus (DENV) IgG antibody levels in serum samples. Recombinant DENV serotype 2 non-structural protein1 was used as an antigen for the ELISA, the optical density (OD) values were analyzed for comparison. The results showed that the OD values decreased significantly (p < 0.01) between the pre-intervention and post-intervention periods at the intervention site. The treatment of water storage containers in rural areas with SumiLarvTM 2MR discs may help to protect residents from Aedes mosquito bites, and hence, reduce DENV infections.

Systemic treatment with a novel basic fibroblast growth factor mimic small-molecule compound boosts functional recovery after spinal cord injury.

Neurotrophic factors have been regarded having promising potentials for neuronal protection and regeneration, and thus promoting beneficial effects of kinesiological functions. They can be suspected to play important roles in cell/tissue grafting for various neural diseases. The clinical applications of such trophic factors to the central nervous system (CNS), however, have caused problematic side effects on account of the distinctive bioactive properties. In the course of developing synthetic compounds reflecting beneficial properties of basic fibroblast growth factor (bFGF), we conducted screening candidates that stimulate to trigger the intracellular tyrosine phosphorylation of FGF receptor and lead to the subsequent intracellular signaling in neurons. A small synthetic molecule SUN13837 was characterized by mimicking the beneficial properties of bFGF, which have been known as its specific activities when applied to CNS. What is more remarkable is that SUN13837 is eliminated the bioactivity to induce cell proliferation of non-neuronal somatic cells. On the bases of studies of pharmacology, behavior, physiology and histology, the present study reports that SUN13837 is characterized as a promising synthetic compound for treatment of devastating damages onto the rat spinal cord.

[Preparations made and considered by parents of children with mental illness for their children's lives in the community after their own death].

Objectives　To examine how parents of children with mental illness prepare for their children's lives in the community after their own death.Methods　Twenty-two parents living in the Kanto region, who have children with mental illness, were interviewed from December 2016 to February 2017. Through qualitative inductive analysis, codes were identified from the narrative data that showed the preparation of parents and compared their similarities and differences. Similar codes were collected and subcategories and categories were created with increasing abstraction levels. Each category was considered with respect to the purpose and the reason why each preparation was done.Results　Participants were 9 fathers (40.9%) and 13 mothers (59.1%). Their ages were as follows: in their sixties (n=9; 40.9%), seventies (n=10; 45.5%), and eighties (n=3; 13.6%).　Ten categories emerged regarding parental preparation for their children's life after their death: 1) Forecasting their own death and recognizing the limitations of support; 2) Trying to share with their children about their own death; 3) With consideration of after their own death, organizing the necessary information for their children and their own belongings; 4) Consulting with their relatives about the lives of their children and inheritance, and considering the use of the social resources; 5) Trying to secure a residence and living expenses for their children; 6) Connecting with social resources, searching for recovery methods for their children, and their own health maintenance; 7) Stabilizing and recovering disease conditions of their children, supporting to take medication and outpatient visits; 8) Assessing the ability of their children to live considering their independent life; 9) Developing their abilities to live and sociality, and making reliable supporters other than parents; 10) Encouraging to have fun in their children's lives and considering their employment. Parents were preparing to hope their child would cope with difficulties in their lives after their own death, and maintain a stable life in the community by him/herself.Conclusions　The results suggested that parents should recognize the need of an independent life for their children in the community, to promote concrete preparations toward their children living in the community after their own death.

Effectiveness of an educational program for mid-level Japanese public health nurses to improve program planning competencies: A preliminary randomized control trial.

OBJECTIVE: To evaluate the effectiveness of an education program for mid-level Japanese public health nurses (PHNs) to improve their competencies in program planning, which will fulfill community health needs. DESIGN: Randomized control trial. SAMPLE: During 2017, 103 PHNs with 5-20 years of PHN work experience in Japan were enrolled and randomly allocated to the intervention (n = 51) or control group (n = 52). MEASUREMENTS: The primary outcome measured competency in program planning based on Competency Measurement of Creativity for PHNs (CMC), knowledge, and skills regarding program planning. INTERVENTION: Six web-based learning modules followed by two face-to-face group sessions. RESULTS: The PHN participants averaged about 12 years of experience. In the intervention group, 25 PHNs completed all modules (49.0%). Post intervention, there were no statistically significant differences among any between-group CMC scores. However, the intervention group's CMC 3 score was significantly higher than that of the control group of ≥12 years of experience. Total knowledge and skill scores also improved significantly in the intervention group compared with the control group. CONCLUSIONS: The results suggest that PHNs with ≥12 years of experience are a suitable target of this educational program, and should play a key role in program planning.

Difficulties of fathers whose families evacuated voluntarily after the Fukushima nuclear disaster.

The Fukushima nuclear disaster in 2011 resulted in radiation exposure, and many evacuees felt anxious of its health risks. However, little is known about the difficulties faced by fathers whose families evacuated voluntarily. Therefore, the aim of the present case study was to clarify the difficulties and concerns of fathers whose families evacuated voluntarily after the Fukushima nuclear disaster. Eleven fathers in Fukushima were interviewed between 14 December 2014 and 25 February 2015. Four themes emerged: (i) seeking a safe place away from radiation exposure; (ii) burdens of a double life; (iii) feelings of isolation and perceived deterioration of health; and (iv) deciding on whether to continue voluntary evacuation. Fathers were anxious about radiation exposure, similar to mothers, and faced work-family conflicts from the voluntary evacuation of their families, including financial, physical, and mental sacrifice. Half of the fathers did not express their difficulties to others. Our findings identified a new type of conflict between people of a community who did/did not choose voluntary evacuation. Occupational health nurses should understand fathers' feelings of isolation and monitor their health to prevent the development of stress-related diseases.

Synthesis and evaluation of N-(4-benzylphenyl)piperazines as VGF inducers.

A series of compounds was discovered that induce the production of VGF mRNA in SH-SY5Y cells and exhibit cytoprotection under tunicamycin induced endoplasmic reticulum (ER) stress. The aminophenol ring and linker chain of the template SUN N8075 (1) was modified to yield compounds with higher efficacy and lower propensity for adverse effects.

Extracellular Lactate Dehydrogenase A Release From Damaged Neurons Drives Central Nervous System Angiogenesis.

Angiogenesis, a prominent feature of pathology, is known to be guided by factors secreted by living cells around a lesion. Although many cells are disrupted in a response to injury, the relevance of degenerating cells in pathological angiogenesis is unclear. Here, we show that the release of lactate dehydrogenase A (LDHA) from degenerating neurons drives central nervous system (CNS) angiogenesis. Silencing neuronal LDHA expression suppressed angiogenesis around experimental autoimmune encephalomyelitis (EAE)- and controlled cortical impact-induced lesions. Extracellular LDHA-mediated angiogenesis was dependent on surface vimentin expression and vascular endothelial growth factor receptor (VEGFR) phosphorylation in vascular endothelial cells. Silencing vimentin expression in vascular endothelial cells prevented angiogenesis around EAE lesions and improved survival in a mouse model of glioblastoma. These results elucidate novel mechanisms that may mediate pathologic angiogenesis and identify a potential molecular target for the treatment of CNS diseases involving angiogenesis.

Peripherally derived FGF21 promotes remyelination in the central nervous system.

Demyelination in the central nervous system (CNS) leads to severe neurological deficits that can be partially reversed by spontaneous remyelination. Because the CNS is isolated from the peripheral milieu by the blood-brain barrier, remyelination is thought to be controlled by the CNS microenvironment. However, in this work we found that factors derived from peripheral tissue leak into the CNS after injury and promote remyelination in a murine model of toxin-induced demyelination. Mechanistically, leakage of circulating fibroblast growth factor 21 (FGF21), which is predominantly expressed by the pancreas, drives proliferation of oligodendrocyte precursor cells (OPCs) through interactions with ß-klotho, an essential coreceptor of FGF21. We further confirmed that human OPCs expressed ß-klotho and proliferated in response to FGF21 in vitro. Vascular barrier disruption is a common feature of many CNS disorders; thus, our findings reveal a potentially important role for the peripheral milieu in promoting CNS regeneration.

Characteristics and related factors of Japanese mothers who have faced difficulties with childrearing.

OBJECTIVE: To identify characteristics of mothers who face difficulties with childrearing. DESIGN AND SAMPLE: Cross-sectional study. During 2014, 221 mothers and 248 children living in City A within the Tokyo metropolis were registered as requiring help with childrearing. Nursing records of 205 mothers (92.8%) and their 227 children (91.5%) were available. We excluded 29 mothers and children owing to incomplete data for a final sample of 176 mothers (79.6%) and 198 children (79.8%). MEASURES: Difficulties with childrearing were assessed by self-reported questionnaires at the newborn child's 4-month health checkups. Data on maternal and child variables were collected from nursing records. RESULTS: The "Difficulties group" included 59 mothers (35.4%) and their 70 children. Logistic regression analysis showed that mothers who were aged 40 years or older, who had a total score on the Edinburgh Postnatal Depression Scale of 9 or greater, who used more child-care support services, and who were monitored more frequently by public health nurses had a high risk of facing difficulties with childrearing. CONCLUSIONS: Periodic monitoring by PHNs is a key strategy to improve the impact of the difficulties of childrearing for mothers of yoshien jido and their children.

Cardiomyocyte-released factors stimulate oligodendrocyte precursor cells proliferation.

The heart produces multiple diffusible factors that are involved in a number of physiological processes, but the action of these factors on the central nervous system is not well understood. In this study, we found that one or more factors released by cardiomyocytes promote oligodendrocyte precursor cell (OPC) proliferation in vitro. Mouse OPCs co-cultured with mouse cardiomyocytes showed higher proliferative ability than OPCs cultured alone. In addition, cardiomyocyte-conditioned media was sufficient to promote OPC proliferation. The phosphorylation of phosphatidylinositol (PI) 3-kinase and extracellular signal-regulated kinase (ERK) in OPCs is necessary for the enhancement of OPC proliferation by cardiomyocyte-conditioned media. These data indicate that heart-derived factors have the ability to directly regulate the function of central nervous system (CNS) cells.

Caesarean section by maternal age group among singleton deliveries and primiparous Japanese women: a secondary analysis of the WHO Global Survey on Maternal and Perinatal Health.

BACKGROUND: The rising caesarean section rate is an important public health concern that in turn increases maternal and perinatal risks of adverse effects, unnecessary medical consumption, and inequities in worldwide access. The aim of this study was to investigate caesarean section indications by maternal age group and examine the association between age and caesarean section in primiparous Japanese women with singleton births. METHODS: We analyzed the Japanese data of primiparous women with singleton births from the WHO Global Survey on Maternal and Perinatal Health to compare maternal and neonatal characteristics and outcomes between groups with and without caesarean section. Women were divided into 3 maternal age groups (≤29, 30 to 34 and ≥35 years). We performed multivariable logistic-regression analysis to identify characteristics associated with caesarean section. RESULTS: Of the 3245 women with singleton births were included in the Japanese data, 610 women (18.8%) delivered by caesarean section, half of whom (n = 305) were nulliparous. We included singleton nulliparous women (1747 deliveries) in our analysis. The maternal age 35 years old was associated with higher risks for all caesarean section (adjusted odds ratio [AOR] 1.89, 95% CI 1.28-2.78) and emergency antepartum caesarean section (AOR 2.26, 95% CI 1.49-3.40). Intrapartum caesarean section, which is mainly performed for obstetric indications, was not higher among the older maternal age group. CONCLUSION: In Japan, advanced maternal age significantly increased the risk for caesarean section; however, intrapartum caesarean section was not higher risk among the older age group. Management of maternal complications would help to reduce the rate of caesarean sections and associated unnecessary medical consumption.

Prostacyclin prevents pericyte loss and demyelination induced by lysophosphatidylcholine in the central nervous system.

Pericytes play pivotal roles in physiological and pathophysiological conditions in the central nervous system. As pericytes prevent vascular leakage, they can halt neuronal damage stemming from a compromised blood-brain barrier. Therefore, pericytes may be a good target for the treatment of neurodegenerative disorders, although evidence is lacking. In this study, we show that prostacyclin attenuates lysophosphatidylcholine (LPC)-mediated vascular dysfunction through pericyte protection in the adult mouse spinal cord. LPC decreased the number of pericytes in an in vitro blood-brain barrier model, and this decrease was prevented by iloprost treatment, a prostacyclin analog. Intrathecal administration of iloprost attenuated vascular barrier disruption after LPC injection in the mouse spinal cord. Furthermore, iloprost treatment diminished demyelination and motor function deficits in mice injected with LPC. These results support the notion that prostacyclin acts on pericytes to maintain vascular barrier integrity.

[Characteristics and related factors of individuals who refuse the support of health and welfare professionals].

OBJECTIVES: Health and welfare professionals experience difficulties during their casework on individuals in the community. The purpose of this study was to identify the characteristics and related factors of those in the community who refuse the support of health and welfare professionals. METHODS: Since 2006, based on a signed research agreement between researchers and local government office A, the series of psychiatric consultation services was initiated for healthcare professionals who experienced difficulties in carrying out their casework on individuals in the community. Data were acquired from local government office A and included the patient's basic attributes, family-related factors, psychiatric factors, and problematic behaviors. Additionally, information on whether individuals refused support was obtained. The data did not include private information. To investigate risk factors for refusing healthcare professional support, 372 profiles of patients who underwent consultation services from 2006 to 2012, were analyzed by logistic regression analysis. RESULTS: Among 309 persons, only 102 (33.0%) accepted support from health and welfare professionals, and 207 (67.0%) persons refused support. Logistic regression analysis revealed that individuals in the community who received welfare benefits (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.02-3.39), refused medication (OR=2.07, 95%CI=1.10-3.90), or used abusive language towards healthcare professionals (OR=1.97, 95%CI=1.09-3.55) were more likely to refuse support from health and welfare professionals. CONCLUSION: The results indicate that individuals in the community who refused support of health and welfare professionals tend to have a worsening condition and a greater need for crisis intervention than those who did not refuse support.

SUN11602, a novel aniline compound, mimics the neuroprotective mechanisms of basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) offers some measure of protection against excitotoxic neuronal injuries by upregulating the expression of the calcium-binding protein calbindin-D28k (Calb). The newly synthesized small molecule 4-({4-[[(4-amino-2,3,5,6-tetramethylanilino)acetyl](methyl)amino]-1-piperidinyl}methyl)benzamide (SUN11602) mimics the neuroprotective effects of bFGF, and thus, we examined how SUN11602 exerts its actions on neurons in toxic conditions of glutamate. In primary cultures of rat cerebrocortical neurons, SUN11602 and bFGF prevented glutamate-induced neuronal death. This neuroprotection, which occurred in association with the augmented phosphorylation of the bFGF receptor-1 (FGFR-1) and the extracellular signal-regulated kinase-1/2 (ERK-1/2), was abolished by pretreatment with PD166866 (a FGFR-1 tyrosine kinase-specific inhibitor) and PD98059 (a mitogen-activated protein kinase [MAPK]/[ERK-1/2] kinase [MEK] inhibitor). In addition, SUN11602 and bFGF increased the levels of CALB1 gene expression in cerebrocortical neurons. Whether this neuroprotection was linked to Calb was investigated with primary cultures of cerebrocortical neurons from homozygous knockout (Calb(-/-)) and wild-type (WT) mice. In WT mice, SUN11602 and bFGF increased the levels of newly synthesized Calb in cerebrocortical neurons and suppressed the glutamate-induced rise in intracellular Ca(2+). This Ca(2+)-capturing ability of Calb allowed the neurons to survive severe toxic conditions of glutamate. In contrast, Calb levels remained unchanged in Calb(-/-) mice after exposure to SUN11602 or bFGF, and due to a loss of function of the gene, these neurons were no longer resistant to toxic conditions of glutamate. These findings indicated that SUN11602 activated a number of cellular molecules (FGFR-1, MEK/ERK intermediates, and Calb) and consequently contributed to intracellular Ca(2+) homeostasis as observed in the case of bFGF.

Metabolite profiles correlate closely with neurobehavioral function in experimental spinal cord injury in rats.

Traumatic spinal cord injury (SCI) results in direct physical damage and the generation of local factors contributing to secondary pathogenesis. Untargeted metabolomic profiling was used to uncover metabolic changes and to identify relationships between metabolites and neurobehavioral functions in the spinal cord after injury in rats. In the early metabolic phase, neuronal signaling, stress, and inflammation-associated metabolites were strongly altered. A dynamic inflammatory response consisting of elevated levels of prostaglandin E2 and palmitoyl ethanolamide as well as pro- and anti-inflammatory polyunsaturated fatty acids was observed. N-acetyl-aspartyl-glutamate (NAAG) and N-acetyl-aspartate (NAA) were significantly decreased possibly reflecting neuronal cell death. A second metabolic phase was also seen, consistent with membrane remodeling and antioxidant defense response. These metabolomic changes were consistent with the pathology and progression of SCI. Several metabolites, including NAA, NAAG, and the ω-3 fatty acids docosapentaenoate and docosahexaenoate correlated greatly with the established Basso, Beattie and Bresnahan locomotive score (BBB score). Our findings suggest the possibility of a biochemical basis for BBB score and illustrate that metabolites may correlate with neurobehavior. In particular the NAA level in the spinal cord might provide a meaningful biomarker that could help to determine the degree of injury severity and prognosticate neurologic recovery.

Inhibitory effects of osemozotan, a serotonin 1A-receptor agonist, on methamphetamine-induced c-Fos expression in prefrontal cortical neurons.

Psychostimulants induce hyperlocomotion in normal subjects, although, they are effective in producing a calming effect in hyperactive subjects. This paradoxical effect has been related to changes in serotonin (5-HT) neurotransmission in hyperactive dopamine transporter-knockout mice. In addition, we observed that hyperlocomotion in mice lacking pituitary adenylate cyclase-activating polypeptide was attenuated by amphetamine dependent on 5-HT(1A) receptor signaling and that amphetamine, when co-administered with a 5-HT(1A) agonist, produced a calming effect in wild-type mice. Here, in an attempt to address how 5-HT(1A) receptor signaling exerts the calming action of psychostimulants, we examined c-Fos expression in several brain regions after administration of methamphetamine and osemozotan, a selective 5-HT(1A) receptor agonist. The number of c-Fos-positive cells was increased in the medial prefrontal cortex, striatum and nucleus accumbens in methamphetamine (3 mg/kg body weight)-injected mice. Osemozotan (1 mg/kg) significantly reduced the methamphetamine-induced c-Fos expression in the medial prefrontal cortex and striatum, but not in the nucleus accumbens. This osemozotan action was completely blocked by the 5-HT(1A) receptor antagonist WAY-100635 (1 mg/kg). As the prefrontal cortex is considered to be involved in the beneficial actions of psychostimulant medications for attention-deficit/hyperactivity disorder, the present result showing 5-HT(1A)-mediated inhibition of corticostriatal activity may partly be related to this psychostimulant action.

An antihyperkinetic action by the serotonin 1A-receptor agonist osemozotan co-administered with psychostimulants or the non-stimulant atomoxetine in mice.

It has been demonstrated that treatment of hyperactive mice with psychostimulants produced a calming effect depending on serotonergic neurotransmission. Our previous study also showed that hyperactivity in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP) was ameliorated by amphetamine in a serotonin (5-HT)(1A)-dependent manner and that amphetamine calmed wild-type mice given the 5-HT(1A) agonist 8-OH-DPAT. Here, we examined if 5-HT(1A)-mediated pathways can be a determinant of the action of other psychostimulants as well as the non-stimulant atomoxetine by examining locomotor activity in mice co-administered with the 5-HT(1A) agonist osemozotan. Co-administration of osemozotan with either methamphetamine or amphetamine was not only antihyperkinetic, but also decreased locomotion to below basal levels. In contrast, osemozotan just nullified methylphenidate-induced hyperactivity. The non-stimulant atomoxetine did not induce hyperactivity, but co-administration of atomoxetine with osemozotan produced a calming effect. The adjunctive effect of osemozotan added to the psychostimulants was blocked by the 5-HT(1A) antagonist WAY-100635 at a low dose (0.1 mg/kg), suggesting the involvement of a presynaptic 5-HT(1A)-mediated mechanism. However, WAY-100635 (up to 1 mg/kg) did not block the effect of atomoxetine plus osemozotan. The present results may provide insights into the therapeutic mechanisms of the psychostimulants and atomoxetine for hyperkinetic disorders.