Interprofessional Collaborative Practice for Child Maltreatment Prevention in Japan: A Literature Review.

This literature review explored the factors promoting interprofessional collaborative practice for the child maltreatment prevention in Japan. We searched the Japanese database of ICHUSHI-web, focusing on studies published between 1990 and 2015. The studies were examined for methodological quality using the critical appraisal checklists. We initially identified 161 articles and finally selected eight studies that met the selection criteria and were analyzed. The Collaborative Practice Circle based on the Interprofessional Education for Collaborative Patient-Centered Practice framework, was used as a conceptual framework to analyze the data and to discuss the review findings. Data analysis continued until categories were saturated using content analysis. Five categories as interactional factors, two categories as organizational factors and three categories as systemic factors were identified. The findings revealed that interactional factors were composed of practical competencies and experiences of professionals. Our findings also indicate that educational programs for improving practical competencies of professionals at the individual level and establishing a system of training and human resource development at the organizational level are required. Further research is warranted to examine the impact the challenges outlined in the interactional factors, the organizational interventions and support for clients.

Maternal perceptions of family-centred support and their associations with the mother-nurse relationship in the neonatal intensive care unit.

AIMS AND OBJECTIVES: To evaluate maternal perceptions of family-centred support with hospitalised preterm infants and their relationship between mothers and nurses in the neonatal intensive care unit (NICU). BACKGROUND: Mothers who gave birth to preterm infants tend to suffer more stress and need individual support based on family-centred care. However, there may be a shortage of support for mothers to obtain parent-crafting skills before bringing their infants home. DESIGN: This cross-sectional study used path analysis and multiple group analysis to evaluate a structural equation model of the relationship between maternal perception based on family-centred support in parent-crafting training and the mothers-nurses collaboration. METHODS: We analysed data from 98 mothers (valid response proportion, 41.0%) whose infants were hospitalised in the NICU of two types of perinatal centres in Japan. We used three revised standardised questionnaires in Japanese: Measure of Process of Care in the NICU (Neo-MPOC 20), Enabling Practice Scale in the NICU (Neo-EPS) and the author-developed Mother and Infant Questionnaire. RESULTS: Path analysis revealed that the relationship between mothers and nurses was linked to three factors related to the perinatal centres' support: consideration of parents' feelings, ability to deal with specific needs and coordination in dealing with situations that interact with provision of parent-friendly visual information. Separate path analyses for each perinatal centre showed the same pattern, although the standard coefficients were different. CONCLUSIONS: Maternal perceptions of family-centred support with hospitalised preterm infants promoted better collaboration between mothers and nurses to obtain parent-crafting skills at two types of perinatal units in Japan. RELEVANCE TO CLINICAL PRACTICE: Clear visual information materials might promote better maternal understanding of their infants, help in acquisition of parent-crafting skills and improve mother-nurse collaboration, with the result that mothers are better able to care for their infants autonomously at home.

Sound Environments Surrounding Preterm Infants Within an Occupied Closed Incubator.

UNLABELLED: Preterm infants often exhibit functional disorders due to the stressful environment in the neonatal intensive care unit (NICU). The sound pressure level (SPL) in the NICU is often much higher than the levels recommended by the American Academy of Pediatrics. Our study aims to describe the SPL and sound frequency levels surrounding preterm infants within closed incubators that utilize high frequency oscillation (HFO) or nasal directional positive airway pressure (nasal-DPAP) respiratory settings. DESIGN AND METHODS: This is a descriptive research study of eight preterm infants (corrected age<33 weeks) exposed to the equipment when placed in an incubator. The actual noise levels were observed and the results were compared to the recommendations made by neonatal experts. RESULTS: Increased noise levels, which have reported to affect neonates' ability to self-regulate, could increase the risk of developing attention deficit disorder, and may result in tachycardia, bradycardia, increased intracranial pressure, and hypoxia. CONCLUSION AND PRACTICE IMPLICATIONS: The care provider should closely assess for adverse effects of higher sound levels generated by different modes of respiratory support and take measures to ensure that preterm infants are protected from exposure to noise exceeding the optimal safe levels.

Depressive symptoms and changes in physiological and social factors 1 week to 4 months postpartum in Japan.

BACKGROUND: Postpartum depression (PPD) is a common condition and may be exacerbated unless treated. There is, however, a lack of longitudinal studies about the relationship between PPD and changes in physiological status and social role postpartum. METHODS: We enrolled longitudinally 65 Japanese mothers (36 primiparas) and measured their psychological responses at 1 week, 1 month, and 4 months postpartum. The physiological indicators were three urine catecholamine fraction levels, cortisol levels, and heart-rate variability. We used the Edinburgh Postnatal Depression Scale (EPDS) and 28-item General Health Questionnaire (GHQ) for psychological evaluation. RESULTS: Eleven participants had an EPDS score ≥9 (cutoff point) at 1 month and five at 4 months. With GHQ total score, 32 participants had ≥6 (cutoff point) at 1 month and 17 at 4 months. The psychological indicators underwent change from childbirth to 4 months postpartum. However, there was no correlation between the psychological and physiological indicators. We likewise found EPDS and GHQ scores were not influenced by parity or undertaking of social activities. LIMITATIONS: The mothers׳ high education level may mean that the results are not generalizable to Japan overall. We were unable to evaluate the status of 11 mothers who dropped out. The participants may have lacked sufficient time to complete questionnaires, resulting in diminished accuracy. We could not determine the prevalence of PPD. CONCLUSIONS: Irrespective of parity status, postpartum mothers showed physiological and mental changes caused by childrearing-related stress. To prevent PPD, postnatal mothers need continuous screening with appropriate evaluating indicators and individualized advice.

Maintenance of stereocilia and apical junctional complexes by Cdc42 in cochlear hair cells.

Cdc42 is a key regulator of dynamic actin organization. However, little is known about how Cdc42-dependent actin regulation influences steady-state actin structures in differentiated epithelia. We employed inner ear hair-cell-specific conditional knockout to analyze the role of Cdc42 in hair cells possessing highly elaborate stable actin protrusions (stereocilia). Hair cells of Atoh1-Cre;Cdc42(flox/flox) mice developed normally but progressively degenerated after maturation, resulting in progressive hearing loss particularly at high frequencies. Cochlear hair cell degeneration was more robust in inner hair cells than in outer hair cells, and began as stereocilia fusion and depletion, accompanied by a thinning and waving circumferential actin belt at apical junctional complexes (AJCs). Adenovirus-encoded GFP-Cdc42 expression in hair cells and fluorescence resonance energy transfer (FRET) imaging of hair cells from transgenic mice expressing a Cdc42-FRET biosensor indicated Cdc42 presence and activation at stereociliary membranes and AJCs in cochlear hair cells. Cdc42-knockdown in MDCK cells produced phenotypes similar to those of Cdc42-deleted hair cells, including abnormal microvilli and disrupted AJCs, and downregulated actin turnover represented by enhanced levels of phosphorylated cofilin. Thus, Cdc42 influenced the maintenance of stable actin structures through elaborate tuning of actin turnover, and maintained function and viability of cochlear hair cells.

Actinoplanes rishiriensis sp. nov., a novel motile actinomycete isolated by rehydration and centrifugation method.

The motile actinomycete strain RI50-RCA114(T) was isolated using rehydration and centrifugation method from a soil sample obtained from Rishiri Island in Japan. The taxonomic status of this organism was established using a polyphasic approach. Cells of strain RI50-RCA114(T) were Gram positive, aerobic, motile and formed irregular sporangia. The strain grew in the presence of 0-2% (w/v) NaCl, between pH 5 and 8, and over a temperature range of 20-37°C, with optimal growth at 30°C. Whole-cell hydrolysates of the strain contained meso-diaminopimelic acid, galactose, glucose and mannose, in addition to one unidentified O-methyl-hexose. The predominant menaquinone was MK-9(H(4)), and the major polar lipids comprised phosphatidylethanolamine, diphosphatidylglycerol and phosphatidyl-N-methylethylethanolamine. The major cellular fatty acids were iso-C(16:0), iso-C(15:0) and anteiso-C(17:0). Comparative 16S ribosomal RNA gene sequence analysis revealed that strain RI50-RCA114(T) had the closest sequence similarity with Actinoplanes globisporus JCM 3186(T) (97.6%). However, DNA-DNA hybridization assays as well as physiological and biochemical analyses differentiated strain RI50-RCA114(T) from its closest phylogenetic relative. On the basis of these data, we propose that strain RI50-RCA114(T) (=NBRC 108556(T)=BCC 49184(T)) be classified as the type strain of a novel Actinoplanes species and named Actinoplanes rishiriensis sp. nov.

Sequential binding of cytosolic Phox complex to phagosomes through regulated adaptor proteins: evaluation using the novel monomeric Kusabira-Green System and live imaging of phagocytosis.

We engineered a method for detecting intramolecular and intermolecular phox protein interactions in cells by fluorescence microscopy using fusion proteins of complementary fragments of a coral fluorescent reporter protein (monomeric Kusabira-Green). We confirmed the efficacy of the monomeric Kusabira-Green system by showing that the PX and PB1 domains of p40phox interact in intact cells, which we suggested maintains this protein in an inactive closed conformation. Using this system, we also explored intramolecular interactions within p47phox and showed that the PX domain interacts with the autoinhibited tandem Src homology 3 domains maintained in contact with the autoinhibitory region, along with residues 341-360. Furthermore, we demonstrated sequential interactions of p67phox with phagosomes involving adaptor proteins, p47phox and p40phox, during FcgammaR-mediated phagocytosis. Although p67phox is not targeted to phagosomes by itself, p47phox functions as an adaptor for the ternary complex (p47phox-p67phox-p40phox) in early stages of phagocytosis before phagosome closure, while p40phox functions in later stages after phagosomal closure. Interestingly, a mutated "open" form of p40phox linked p47phox to closed phagosomes and prolonged p47phox and p67phox retention on phagosomes. These results indicate that binding of the ternary complex to phagosomes can be temporally regulated by switching between adaptor proteins that have PX domains with distinct lipid-binding specificities.

A novel dominant-negative mutation in Gdf5 generated by ENU mutagenesis impairs joint formation and causes osteoarthritis in mice.

Growth and differentiation factor 5 (GDF5) has been implicated in chondrogenesis and joint formation, and an association of GDF5 and osteoarthritis (OA) has been reported recently. However, the in vivo function of GDF5 remains mostly unclarified. Although various human GDF5 mutations and their phenotypic consequences have been described, only loss-of-function mutations that cause brachypodism (shortening and joint ankylosis of the digits) have been reported in mice. Here, we report a new Gdf5 allele derived from a large-scale N-ethyl-N-nitrosourea mutagenesis screen. This allele carries an amino acid substitution (W408R) in a highly conserved region of the active signaling domain of the GDF5 protein. The mutation is semi-dominant, showing brachypodism and ankylosis in heterozygotes and much more severe brachypodism, ankylosis of the knee joint and malformation with early-onset OA of the elbow joint in homozygotes. The mutant GDF5 protein is secreted and dimerizes normally, but inhibits the function of the wild-type GDF5 protein in a dominant-negative fashion. This study further highlights a critical role of GDF5 in joint formation and the development of OA, and this mouse should serve as a good model for OA.

Increased basal platelet activity, plasma adiponectin levels, and diabetes mellitus are associated with poor platelet responsiveness to in vitro effect of aspirin.

INTRODUCTION: Aspirin is one of the most effective antiplatelet agents and is now commonly used to prevent vascular events. In some patients, however, recurrent vascular events have been demonstrated despite aspirin therapy. Our objective was to characterize individuals showing poor response to in vitro effect of aspirin, using PFA-100. METHODS: One hundred sixty-eight healthy male subjects were analyzed. We assessed platelet function tests, including PFA-100, whole blood aggregation, and optical platelet aggregation. Also measured were hemostatic and other parameters including von Willebrand factor (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), soluble vascular adhesion molecule-1 (sVCAM-1), high sensitive C-reactive protein (hs-CRP), and adiponectin. Poor responders were defined as having a collagen/epinephrine-induced closure time (CEPI-CT) under 250 s with PFA-100 when incubated with 10 microM aspirin, whereas good responders were defined as having a CEPI-CT of more than 250 s. RESULTS AND CONCLUSIONS: PFA-100 tests revealed that 40 subjects (24%) were poor responders (PR) and 128 (76%) were good responders (GR). Poor responsiveness was significantly associated with (1) higher basal platelet activities in PFA-100, as well as in whole blood aggregation and aggregometer;(2) increased level of adiponectin (8.8+/-4.1 micro g/mL [PR] vs 7.3+/-2.9 micro g/mL [GR], p=0.010);and (3) the presence of diabetes mellitus (17.5% [PR] vs 4.7% [GR], p=0.009). Importantly, whereas 24% of the subjects showed insufficient inhibition in PFA-100 when incubated with 10 microM aspirin, almost all subjects showed maximum inhibition with 30 microM aspirin. These observations suggest that higher doses of aspirin might overcome aspirin resistance.

A series of ENU-induced single-base substitutions in a long-range cis-element altering Sonic hedgehog expression in the developing mouse limb bud.

Mammal-fish-conserved-sequence 1 (MFCS1) is a highly conserved sequence that acts as a limb-specific cis-acting regulator of Sonic hedgehog (Shh) expression, residing 1 Mb away from the Shh coding sequence in mouse. Using gene-driven screening of an ENU-mutagenized mouse archive, we obtained mice with three new point mutations in MFCS1: M101116, M101117, and M101192. Phenotype analysis revealed that M101116 mice exhibit preaxial polydactyly and ectopic Shh expression at the anterior margin of the limb buds like a previously identified mutant, M100081. In contrast, M101117 and M101192 show no marked abnormalities in limb morphology. Furthermore, transgenic analysis revealed that the M101116 and M100081 sequences drive ectopic reporter gene expression at the anterior margin of the limb bud, in addition to the normal posterior expression. Such ectopic expression was not observed in the embryos carrying a reporter transgene driven by M101117. These results suggest that M101116 and M100081 affect the negative regulatory activity of MFCS1, which suppresses anterior Shh expression in developing limb buds. Thus, this study shows that gene-driven screening for ENU-induced mutations is an effective approach for exploring the function of conserved, noncoding sequences and potential cis-regulatory elements.

Implementation of the modified-SHIRPA protocol for screening of dominant phenotypes in a large-scale ENU mutagenesis program.

SHIRPA is a three-stage protocol for the comprehensive assessment of primarily mouse behavior. The first stage consists of high-throughput phenotyping of 33 behavioral observations and 7 metabolic or disease observations. We modified this part of the protocol by integrating new morphologic observations into the initial phenotype assay of behavior and dysmorphology. Behavioral observations assessed by this protocol, now referred to as the "modified-SHIRPA," are compatible with the original "SHIRPA" protocol. Using modified-SHIRPA, we screened dominant phenotypes of more than 10,000 G(1) progeny generated by crossing DBA/2J females with ENU-treated C57BL/6J males. To date, we have obtained 136 hereditary-confirmed mutants that exhibit behavioral and morphologic defects. Some independent mutant lines exhibited similar phenotypes, suggesting that they may represent alleles of the same gene or mutations in the same genetic pathway. They could hold great potential for the unraveling of the molecular mechanisms of certain phenotypes.

Enamelin (Enam) is essential for amelogenesis: ENU-induced mouse mutants as models for different clinical subtypes of human amelogenesis imperfecta (AI).

Amelogenesis imperfecta (AI) is a group of commonly inherited defects of dental enamel formation, which exhibits marked genetic and clinical heterogeneity. The genetic basis of this heterogeneity is still poorly understood. Enamelin, the affected gene product in one form of AI (AIH2), is an extracellular matrix protein that is one of the components of enamel. We isolated three ENU-induced dominant mouse mutations, M100395, M100514 and M100521, which caused AI-like phenotypes in the incisors and molars of the affected individuals. Linkage analyses mapped each of the three mutations to a region of chromosome 5 that contained the genes encoding enamelin (Enam) and ameloblastin (Ambn). Sequence analysis revealed that each mutation was a single-base substitution in Enam. M100395 (Enam(Rgsc395)) and M100514 (Enam(Rgsc514)) were putative missense mutations that caused S to I and E to G substitutions at positions 55 and 57 of the translated protein, respectively. Enam(Rgsc395) and Enam(Rgsc514) heterozygotes showed severe breakage of the enamel surface, a phenotype that resembled local hypoplastic AI. The M100521 mutation (Enam(Rgsc521)) was a T to A substitution at the splicing donor site in intron 4. This mutation resulted in a frameshift that gave rise to a premature stop codon. The transcript of the Enam(Rgsc521) mutant allele was degraded, indicating that Enam(Rgsc521) is a loss-of-function mutation. Enam(Rgsc521) heterozygotes showed a hypomaturation-type AI phenotype in the incisors, possibly due to haploinsufficiency of Enam. Enam(Rgsc521) homozygotes showed complete loss of enamel on the incisors and the molars. Thus, we report here that the Enam gene is essential for amelogenesis, and that mice with different point mutations at Enam may provide good animal models to study the different clinical subtypes of AI.

Structure--activity relationships of 1beta-methyl-2-(5-phenylpyrrolidin-3-ylthio)carbapenems.

Structure--activity relationship studies of 1beta-methyl-2-[(3S,5R)-5-(4-aminomethylphenyl)pyrrolidin-3-ylthio]carbapenems, especially those pertaining to the relationship between antibacterial activity and side-chain structure were conducted. These studies suggested that the trans-(3S,5R)-5-phenylpyrrolidin-3-ylthio side-chain and the aminomethyl group at the 4-position of the phenyl ring play a key role in enhancing the antibacterial activity against the MRSA and Pseudomonas aeruginosa strains. In particular, the basicity of a substituent at the 4-position of the phenyl ring were shown to greatly contribute to the antibacterial activity against MRSA and methicillin-resistant Staphyloccocus epidermidis strains. In contrast, the amidine group was shown to lead to potent antibacterial activity against P. aeruginosa strains comparable to that of imipenem, however, a good correlation between the basicity of the 4-substituent and antipseudomonal activity was not observed. In conclusion, the 4-aminomethyl or methylaminomethyl group on the phenyl ring was the best substituent for antipseudomonal activity.