[Comparison and clarification of public health and public health nursing competencies: A report of the Committee on Public Health Nursing (2017-2018)].

Objectives　The Committee on Public Health Nursing (2017-2018) of the Japanese Society of Public Health aimed to elucidate the competencies of public health and public health nursing to provide basic materials for public health, public health nursing education, practice, and research.Methods　We studied the core competencies of public health professionals and public health nursing in the United States and examined similarities to and differences from those in Japan.Results　The United States and Japan shared similar public health and public health nursing competencies in that they targeted populations, identified health problems, and clarified health challenges for effective actions. However, differences were noted in the understanding of target groups, perspectives for identifying health problems and overcoming health challenges, and conceptualization of individuals in populations. In public health, the target population practiced clear boundaries, such as residing in certain geographical areas and ethnic groups, among others. In health challenges, the top-down approach was employed to resolve health problems in certain populations. The individual was recognized as a part of a population composed of a certain group. In public health nursing, target population (e.g., from individuals/families to groups/communities/social groups) were understood in a continuous and multilayered manner. Individual/family health problems were associated with the characteristics of groups, communities, and social groups that encompass the continuum. Moreover, health challenges were addressed in a manner oriented toward the transformation of social groups as a whole. Public health nursing competencies in both countries, which share many similarities, were developed to achieve the objectives of public health. In the United States, the competencies and skills considered necessary, such as analytical/assessment and cultural competency skills, were clearly expressed and constructed in line with the core competencies of public health professionals. However, in Japan, skills and abilities necessary as competencies in public health nursing mentioned above were not specified.Conclusion　Elucidating the core competencies of public health professionals in Japan is essential to develop human resources that can contribute to effective practices in public health and public health nursing. Toward this end, skills and abilities necessary as competencies in public health nursing in Japan, which were not previously verbalized, should be described in detail.

Suppression of RNF213, a susceptibility gene for moyamoya disease, inhibits endoplasmic reticulum stress through SEL1L upregulation.

RNF213, a susceptibility gene for moyamoya disease, is associated with stress responses to various stressors. We previously reported that Rnf213 knockout (KO) mitigated endoplasmic reticulum (ER) stress-induced diabetes in the Akita mouse model of diabetes. However, the role of RNF213 in ER stress regulation remains unknown. In the present study, RNF213 knockdown significantly inhibited the upregulation of ER stress markers (CHOP and spliced XBP1) by chemical ER stress-inducers in HeLa cells. Levels of SEL1L, a critical molecule in ER-associated degradation (ERAD), were increased by RNF213 knockdown, and SEL1L knockdown prevented the inhibitory effect of RNF213 suppression on ER stress in HeLa cells, indicating SEL1L involvement in this inhibition of ER stress. SEL1L upregulation was also confirmed in pancreatic islets of Rnf213 KO/Akita mice and in Rnf213 KO mouse embryonic fibroblasts. Additionally, RNF213 suppression increased levels of HRD1, which forms a complex with SEL1L to degrade misfolded protein in cells under ER stress. In conclusion, we demonstrate that RNF213 depletion inhibits ER stress possibly through elevation of the SEL1L-HRD1 complex, thereby promoting ERAD in vitro and in vivo.

Culturally sensitive disaster nursing by Public health nurses in Japan.

OBJECTIVE: To clarify culturally sensitive disaster nursing by public health nurses (PHNs) in Japan, an island nation located on the Pacific Rim, with regard to PHNs' intentions and comforting supports for affected people. DESIGN: Qualitative descriptive study. SAMPLE: Participants were 17 local PHNs and 13 affected people in nine disaster-affected municipalities throughout Japan. MEASUREMENTS: Semi-structured interviews were conducted between October 2018 and July 2019. Two types of categories were qualitatively created: categories for PHNs' culturally sensitive disaster nursing actions, including their intentions; and categories for comforting supports that PHNs provided for affected people through the four phases of disaster. The relationship between these two types of categories was determined. Cultural factors were extracted from the culturally sensitive disaster nursing actions of PHNs and categorized. RESULTS: Regarding intentions, in the acute phase, PHNs utilized culture. In the sub-acute phase, they utilized, acted based on, followed, thought of, and balanced cultural knowledge. In the mid-term-phase, they utilized, thought of, followed, and balanced with local culture. In the long-term phase, they merged, thought of, balanced, utilized, and followed local cultural practices. The actions associated with these intentions corresponded to comforting supports for affected people. Cultural factors, such as transportation style, were obtained in each phase. CONCLUSION: To enhance the resilience of a community affected by disaster, PHNs should focus on maximizing, preserving, and accommodating culture to maintain familiar life patterns when people's circumstances are totally disrupted by powerful forces of nature.

Graft flow predictive equation in distal bypass grafting for critical limb ischemia.

OBJECTIVE: Graft flow (GF) seems to be an important prognostic predictor in distal bypass for critical limb ischemia, but previous studies have failed to clarify the association between GF and the graft prognosis. GF differs significantly among grafts, and each graft seems to have an optimal GF depending on various factors. We hypothesized that comparison between the measured GF (mGF) and optimal estimated GF (eGF) would be important in predicting graft prognosis. Herein, we aimed to develop a GF predictive equation by assessing GF determinants and to validate the equation against a clinical dataset. METHODS: A total of 198 distal bypasses with vein grafts for critical limb ischemia from 2011 to 2016 were enrolled. Of these grafts, 135 normal grafts without any abnormalities on early postoperative ultrasound examination were used to develop and validate the equation. Various anatomic and patient-related factors were analyzed to detect GF determinants with stepwise selection, and the GF predictive equation was developed with multiple linear regression analysis. After developing the equation, all 198 grafts were categorized into two groups according to the equation developed based on data from the 135 normal grafts as follows: optimal flow grafts (OFGs), in which mGF > eGF - 14.6, and suboptimal flow grafts (SFGs), in which mGF < eGF - 14.6. The cutoff value of 14.6 was determined using receiver operating characteristic curves to detect graft abnormalities. By comparing OFGs and SFGs, the efficacy of the equation in predicting bypass abnormalities and graft prognosis was assessed. RESULTS: The GF determinants were runoff, hemodialysis (HD), diabetes mellitus (DM), and graft quality (GQ). The predictive equation was estimated as follows: GF(ml/min)=(32.9×run-off)+(9.9×GQ)-(13.0×DM)-(35.1×HD)+12.1 (R2 = 0.71, coefficient: runoff and GQ, 3 [good], 2 [fair], 1 [poor]; DM and HD, 1 [yes], 0 [no]). In the efficacy assessment of the equation, SFGs showed a significantly higher rate of bypass abnormalities (64.0% vs 12.2%; P < .0001), graft intermediate stenosis (10.7% vs 1.6%; P = .0071), graft critical stenosis (28.0% vs 3.2%; P < .0001), and early graft occlusion (17.3% vs 4.3%; P = .0037) than OFGs and were associated with a higher rate of revision surgery within 2 years after surgery (50.7% vs 34.2%; P = .026). SFGs also showed significantly lower primary patency rates (P < .0001) and secondary patency rates (P = .0005). CONCLUSIONS: GF was well-estimated with runoff, GQ, and the presence of DM and HD. A comparison between mGF and eGF, calculated with the equation, will help to detect bypass abnormalities and determine the necessity of additional intraoperative procedures and, thus, achieve optimal outcomes.

Direct Interaction between the Voltage Sensors Produces Cooperative Sustained Deactivation in Voltage-gated H+ Channel Dimers.

The voltage-gated H(+) channel (Hv) is a voltage sensor domain-like protein consisting of four transmembrane segments (S1-S4). The native Hv structure is a homodimer, with the two channel subunits functioning cooperatively. Here we show that the two voltage sensor S4 helices within the dimer directly cooperate via a π-stacking interaction between Trp residues at the middle of each segment. Scanning mutagenesis showed that Trp situated around the original position provides the slow gating kinetics characteristic of the dimer's cooperativity. Analyses of the Trp mutation on the dimeric and monomeric channel backgrounds and analyses with tandem channel constructs suggested that the two Trp residues within the dimer are functionally coupled during Hv deactivation but are less so during activation. Molecular dynamics simulation also showed direct π-stacking of the two Trp residues. These results provide new insight into the cooperative function of voltage-gated channels, where adjacent voltage sensor helices make direct physical contact and work as a single unit according to the gating process.

Paroxysmal limb intolerable pain (infantile pain episodes associated with novel Nav1.9 mutations in familial episodic pain syndrome).

Painful peripheral neuropathy has been correlated with various voltage-gated sodium channel mutations in sensory neurons. Recently Navl.9, a voltage-gated sodium channel sub- type, has been established as a genetic influence for certain peripheral pain syndromes. Herein, we performed a genetic study in six unrelated, multigenerational Japanese families with episodic pain syndrome. Affected participants were characterized by infantile recurrent pain episodes, with spontaneous mitigation around adolescence. The affected joints, in an in- creasing order of frequency, include those in the knees, ankles, wrists, and elbows. The pain typically lasts for 15-30 min and recurs several times a day. The pain is often induced by fa- tigue and is a prelude of bad weather. The affected regions feel cold in the patients, and warming the lesions relieves the symptoms. This unique phenotype was inherited in an autosomal-dominant mode. Two missense var- iants, p.R222S and p.R222H, were identified in SCN11A by linkage analysis and exome analy- sis. Next, we generated a knock-in mouse model harboring one of the mutations (p.R222S). Behavioral tests showed that p.R222S mice were significantly more hypersensitive to hot and cold stimuli. Electrophysiological studies using dorsal ganglion neurons showed significant increase of input impedance and firing frequency of evoked action potentials in p.R222S mice. These results suggest that the novel mutation reported herein is a gain-of-function mu- tation that causes infantile familial episodic pain.

Genetic study of intracranial aneurysms.

BACKGROUND AND PURPOSE: Rupture of intracranial aneurysms (IAs) causes subarachnoid hemorrhage, leading to immediate death or severe disability. Identification of the genetic factors involved is critical for disease prevention and treatment. We aimed to identify the susceptibility genes for IAs. METHODS: Exome sequencing was performed in 12 families with histories of multiple cases of IA (number of cases per family ≥3), with a total of 42 cases. Various filtering strategies were used to select the candidate variants. Replicate association studies of several candidate variants were performed in probands of 24 additional IA families and 426 sporadic IA cases. Functional analysis for the mutations was conducted. RESULTS: After sequencing and filtering, 78 variants were selected for the following reasons: allele frequencies of variants in 42 patients was significantly (P<0.05) larger than expected; variants were completely shared by all patients with IA within ≥1 family; variants predicted damage to the structure or function of the protein by PolyPhen-2 (Polymorphism Phenotyping V2) and SIFT (Sorting Intolerance From Tolerant). We selected 10 variants from 9 genes (GPR63, ADAMST15, MLL2, IL10RA, PAFAH2, THBD, IL11RA, FILIP1L, and ZNF222) to form 78 candidate variants by considering commonness in families, known disease genes, or ontology association with angiogenesis. Replicate association studies revealed that only p.E133Q in ADAMTS15 was aggregated in the familial IA cases (odds ratio, 5.96; 95% confidence interval, 2.40-14.82; P=0.0001; significant after the Bonferroni correction [P=0.05/78=0.0006]). Silencing ADAMTS15 and overexpression of ADAMTS15 p.E133Q accelerated endothelial cell migration, suggesting that ADAMTS15 may have antiangiogenic activity. CONCLUSIONS: ADAMTS15 is a candidate gene for IAs.

The cooperation of sustained and phasic inhibitions increases the contrast of ITD-tuning in low-frequency neurons of the chick nucleus laminaris.

Neurons in the nucleus laminaris (NL) of birds detect the coincidence of binaural excitatory inputs from the nucleus magnocellularis (NM) on both sides and process the interaural time differences (ITDs) for sound localization. Sustained inhibition from the superior olivary nucleus is known to control the gain of coincidence detection, which allows the sensitivity of NL neurons to ITD tolerate strong-intensity sound. Here, we found a phasic inhibition in chicken brain slices that follows the ipsilateral NM inputs after a short time delay, sharpens coincidence detection, and may enhance ITD sensitivity in low-frequency NL neurons. GABA-positive small neurons are distributed in and near the NL. These neurons generate IPSCs in NL neurons when photoactivated by a caged glutamate compound, suggesting that these GABAergic neurons are interneurons that mediate phasic inhibition. These IPSCs have fast decay kinetics that is attributable to the α1-subunit of the GABAA receptor, the expression of which dominates in the low-frequency region of the NL. Model simulations demonstrate that phasic IPSCs narrow the time window of coincidence detection and increase the contrast of ITD-tuning during low-level, low-frequency excitatory input. Furthermore, cooperation of the phasic and sustained inhibitions effectively increases the contrast of ITD-tuning over a wide range of excitatory input levels. We propose that the complementary interaction between phasic and sustained inhibitions is the neural mechanism that regulates ITD sensitivity for low-frequency sound in the NL.

Expansion of intronic GGCCTG hexanucleotide repeat in NOP56 causes SCA36, a type of spinocerebellar ataxia accompanied by motor neuron involvement.

Autosomal-dominant spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders. In this study, we performed genetic analysis of a unique form of SCA (SCA36) that is accompanied by motor neuron involvement. Genome-wide linkage analysis and subsequent fine mapping for three unrelated Japanese families in a cohort of SCA cases, in whom molecular diagnosis had never been performed, mapped the disease locus to the region of a 1.8 Mb stretch (LOD score of 4.60) on 20p13 (D20S906-D20S193) harboring 37 genes with definitive open reading frames. We sequenced 33 of these and observed a large expansion of an intronic GGCCTG hexanucleotide repeat in NOP56 and an unregistered missense variant (Phe265Leu) in C20orf194, but we found no mutations in PDYN and TGM6. The expansion showed complete segregation with the SCA phenotype in family studies, whereas Phe265Leu in C20orf194 did not. Screening of the expansions in the SCA cohort cases revealed four additional occurrences, but none were revealed in the cohort of 27 Alzheimer disease cases, 154 amyotrophic lateral sclerosis cases, or 300 controls. In total, nine unrelated cases were found in 251 cohort SCA patients (3.6%). A founder haplotype was confirmed in these cases. RNA foci formation was detected in lymphoblastoid cells from affected subjects by fluorescence in situ hybridization. Double staining and gel-shift assay showed that (GGCCUG)n binds the RNA-binding protein SRSF2 but that (CUG)(6) does not. In addition, transcription of MIR1292, a neighboring miRNA, was significantly decreased in lymphoblastoid cells of SCA patients. Our finding suggests that SCA36 is caused by hexanucleotide repeat expansions through RNA gain of function.

Activation of metabotropic glutamate receptors improves the accuracy of coincidence detection by presynaptic mechanisms in the nucleus laminaris of the chick.

Interaural time difference (ITD) is a major cue for localizing a sound source and is processed in the nucleus laminaris (NL) in birds. Coincidence detection (CD) is a crucial step for processing ITD and critically depends on the size and time course of excitatory postsynaptic potentials (EPSPs). Here, we investigated a role of metabotropic glutamate receptors (mGluRs) in the regulation of EPSP amplitude and CD in the NL of chicks. A non-specific agonist of mGluRs ((±)-1-aminocyclopentane-trans-1,3-dicarboxylic acid; t-ACPD) reduced the amplitude and extent of depression of excitatory postsynaptic currents (EPSCs) during a stimulus train, while the paired pulse ratio and coefficient of variation of EPSC amplitude were increased. In contrast, the amplitudes of spontaneous EPSCs were not affected, but the frequency was reduced. Thus, the effects of t-ACPD were presynaptic and reduced the release of neurotransmitter from terminals in the NL. Expression of group II mGluRs was graded along the tonotopic axis and was stronger towards the low frequency region in the NL. Both group II (DCG-IV) and group III (l-AP4) specific agonists reduced EPSC amplitude by presynaptic mechanisms, and the reduction was larger in the low frequency region; however, we could not find any effects of group I-specific agonists on EPSCs. The reduced EPSP amplitude in DCG-IV improved CD. A specific antagonist of group II mGluRs (LY341495) increased the amplitude of both EPSCs and EPSPs and enhanced the depression during a stimulus train, indicating constitutive activation of mGluRs in the NL. These observations indicate that mGluRs may work as autoreceptors and regulate EPSP size to improve CD in the NL.

Ablation of Rnf213 retards progression of diabetes in the Akita mouse.

Moyamoya disease (MMD) and moyamoya syndrome are vasculopathies characterized by progressive stenosis in the circle of Willis and its branches. The RNF213 gene, which encodes a novel class of proteins, characterized by both E3 ligase and AAA+ATPase activities, has been identified as the susceptibility gene for MMD. However, its physiological functions remain unknown. MMD and moyamoya syndrome are often accompanied by diabetes mellitus. In this study, we generated Rnf213 knockout (KO) C57BL/6 mice (Rnf213(-/-); Ins2(+/+)), which were mated with Akita (C57BL/6 Rnf213(+/+); Ins2(+/C96Y)) mice, a strain that develops diabetes spontaneously by 5 weeks of age, to obtain mice lacking Rnf213 and carrying the Akita mutation (KO/Akita, Rnf213(-/-); Ins2(+/C96Y)). Body weight and blood glucose concentration were measured from 6 to 20 weeks. Glucose tolerance, insulin resistance, plasma insulin and leptin concentrations, food consumption, pancreatic insulin content and histopathology were evaluated at 18 weeks of age. We found that glucose tolerance, as indicated by AUC, was 20% lower (p<0.05) and insulin contents in pancreas were 150% higher (p<0.05), in KO/Akita than in Akita mice. The number of CHOP positive ß-cells assayed by histopathological examination was 30% lower and food consumption was 34% lower in KO/Akita than in Akita mice (p<0.05 each). These findings indicated that the disruption of Rnf213 improved glucose tolerance by protecting islet ß cells.

The moyamoya disease susceptibility variant RNF213 R4810K (rs112735431) induces genomic instability by mitotic abnormality.

Moyamoya disease (MMD) is a cerebrovascular disease characterized by occlusive lesions in the Circle of Willis. The RNF213 R4810K polymorphism increases susceptibility to MMD. In the present study, we characterized phenotypes caused by overexpression of RNF213 wild type and R4810K variant in the cell cycle to investigate the mechanism of proliferation inhibition. Overexpression of RNF213 R4810K in HeLa cells inhibited cell proliferation and extended the time of mitosis 4-fold. Ablation of spindle checkpoint by depletion of mitotic arrest deficiency 2 (MAD2) did not shorten the time of mitosis. Mitotic morphology in HeLa cells revealed that MAD2 colocalized with RNF213 R4810K. Immunoprecipitation revealed an RNF213/MAD2 complex: R4810K formed a complex with MAD2 more readily than RNF213 wild-type. Desynchronized localization of MAD2 was observed more frequently during mitosis in fibroblasts from patients (n=3, 61.0 ± 8.2%) compared with wild-type subjects (n=6, 13.1 ± 7.7%; p<0.01). Aneuploidy was observed more frequently in fibroblasts (p<0.01) and induced pluripotent stem cells (iPSCs) (p<0.03) from patients than from wild-type subjects. Vascular endothelial cells differentiated from iPSCs (iPSECs) of patients and an unaffected carrier had a longer time from prometaphase to metaphase than those from controls (p<0.05). iPSECs from the patients and unaffected carrier had significantly increased mitotic failure rates compared with controls (p<0.05). Thus, RNF213 R4810K induced mitotic abnormalities and increased risk of genomic instability.

Downregulation of Securin by the variant RNF213 R4810K (rs112735431, G>A) reduces angiogenic activity of induced pluripotent stem cell-derived vascular endothelial cells from moyamoya patients.

Moyamoya disease (MMD) is a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The RNF213 R4810K polymorphism increases susceptibility to MMD. Induced pluripotent stem cells (iPSCs) were established from unaffected fibroblast donors with wild-type RNF213 alleles, and from carriers/patients with one or two RNF213 R4810K alleles. Angiogenic activities of iPSC-derived vascular endothelial cells (iPSECs) from patients and carriers were lower (49.0 ± 19.4%) than from wild-type subjects (p<0.01). Gene expression profiles in iPSECs showed that Securin was down-regulated (p<0.01) in carriers and patients. Overexpression of RNF213 R4810K downregulated Securin, inhibited angiogenic activity (36.0 ± 16.9%) and proliferation of humanumbilical vein endothelial cells (HUVECs) while overexpression of RNF213 wild type did not. Securin expression was downregulated using RNA interference techniques, which reduced the level of tube formation in iPSECs and HUVECs without inhibition of proliferation. RNF213 R4810K reduced angiogenic activities of iPSECs from patients with MMD, suggesting that it is a promising in vitro model for MMD.

Combined linkage analysis and exome sequencing identifies novel genes for familial goiter.

Familial goiter is a genetic disease showing heterogeneous expression. To identify causative genes, we investigated three multigenerational goiter families with an autosomal dominant inheritance pattern. We performed genome-wide linkage analysis on all the families, combined with whole-exome sequencing in two affected individuals from each family. For linkage analysis, we considered loci with logarithm of odds (LOD) scores >1.5 as candidate regions for identification of rare variants. In one of the families, we found two rare heterozygous missense variants, p.V56M in RGS12 and p.G37D in GRPEL1, which segregate with goiter and are both located within the same haplotype on 4p16. This haplotype was not observed in 150 controls. In the other two families, we identified two additional rare missense variants segregating with goiter, p.A551T in CLIC6 on 21q22.12 and p.V412A in WFS1 on 4p16. In controls, the minor allele frequency (MAF) of p.V412A in WFS1 was 0.017 while p.A551T in CLIC6 was not detected. All identified genes (RGS12, GRPEL1, CLIC6 and WFS1) show expression in the human thyroid gland, suggesting that they may play a role in thyroid gland function. Moreover, these four genes are novel with regard to their involvement in familial goiter, supporting genetic heterogeneity of this disease.

P.R4810K, a polymorphism of RNF213, the susceptibility gene for moyamoya disease, is associated with blood pressure.

BACKGROUND: Moyamoya disease-an idiopathic vascular disorder of intracranial arteries-is often accompanied by hypertension. RNF213 has been identified as a susceptibility gene for moyamoya disease. In the present study, the association of p.R4810K (G>A) with blood pressure (BP) was investigated in a Japanese population. METHODOLOGY/PRINCIPAL FINDINGS: Three independent study populations, the Nyukawa (n = 984), Noshiro (n = 2,443) and Field (n = 881) studies, joined this study. BP, body weight and height were measured. Past and present symptoms and disease and medication histories were assessed by interview. Associations of p.R4810K (rs112735431, ss179362673) of RNF213 with BP were investigated. Two linkage disequilibrium blocks were constructed for moyamoya patients with p.R4810K (n = 140) and the general population (n = 384) using 39 single nucleotide polymorphisms (SNPs) spanning 390 kb around RNF213. A total of 60 carriers (3 for AA genotype and 57 for GA genotype) were found in these samples, and the minor allele frequencies were 1.4 % in the Nyukawa and Field studies and 0.2 % in the Noshiro study. Regression analyses adjusted for age, sex and body mass index based on an additive model demonstrated significant associations with systolic BP (mmHg/allele): ß (standard error) was 8.2 (2.9) in the Nyukawa study (P = 4.7 × 10(-3)), 18.7 (5.4) in the Noshiro study (P = 4.6 × 10(-4)) and 8.9 (2.0) (P = 1.0 × 10(-5)) in the three populations. In contrast, diastolic BP showed significant associations only in the Noshiro study. Linkage disequilibrium blocks contained none of the BP-associated proxy SNPs reported by previous studies. CONCLUSIONS/SIGNIFICANCE: Our study suggests that p.R4810K of RNF213 is associated strongly with systolic BP.

Reduced pain sensitivity of episodic pain syndrome model mice carrying a Nav1.9 mutation by ANP-230, a novel sodium channel blocker.

The sodium channel Nav1.9 is expressed in the sensory neurons of small diameter dorsal root ganglia that transmit pain signals, and gain-of-function Nav1.9 mutations have been associated with both painful and painless disorders. We initially determined that some Nav1.9 mutations are responsible for familial episodic pain syndrome observed in the Japanese population. We therefore generated model mice harboring one of the more painful Japanese mutations, R222S, and determined that dorsal root ganglia hyperexcitability was the cause of the associated pain. ANP-230 is a novel non-opioid drug with strong inhibitory effects on Nav1.7, 1.8 and 1.9, and is currently under clinical trials for patients suffering from familial episodic pain syndrome. However, little is known about its mechanism of action and effects on pain sensitivity. In this study, we therefore investigated the inhibitory effects of ANP-230 on the hypersensitivity of Nav1.9 p.R222S mutant model mouse to pain. In behavioral tests, ANP-230 reduced the pain response of the mice, particularly to heat or mechanical stimuli, in a concentration- and time-dependent manner. Furthermore, ANP-230 suppressed the repetitive firing of dorsal root ganglion neurons of these mutant mice. Our results clearly demonstrate that ANP-230 is an effective analgesic for familial episodic pain syndrome resulting from DRG neuron hyperexcitability, and that such analgesic effects are likely to be of clinical significance.

Venous Screening Activities at the Site of Hokkaido East Iburi Earthquake: Report from the Result of Venous Screening in Preventive Awareness Activities.

After previous earthquakes, high prevalence of cardiovascular diseases including venous thromboembolism (VTE) has been reported. We performed venous screening at the site of Hokkaido East Iburi Earthquake which happened at 6th September 2018. VTE screening using ultrasound sonography was performed for total 7 days at Atsuma town, Mukawa town and Abira town (total 9 shelters). Deep vein thrombosis (DVT) was found in 19 of 195 evacuees (9.7%), including 8 fresh thrombus cases (4.1%). On multivariable analysis of evacuees and shelter environment factors, systolic blood pressure, use of cardboard bed and toilet environment were significant predictor of DVT. Introduction and setting-up of cardboard beds were found as an important shelter environment factor. (This is secondary publication from Jpn J Phlebol 2021; 32(1): 5-10.).