Non-efficacy of early intervention strategy for non-obese patients with early-onset gestational diabetes mellitus: solely based on the short-term outcomes.

INTRODUCTION: To verify the effectiveness of intervention in early pregnancy for women with early-onset gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: This study included women with a singleton pregnancy who were diagnosed with early-onset GDM by 20 weeks of gestation according to the International Association of Diabetes and Pregnancy Study Group (IADPSG) threshold. We retrospectively evaluated the pregnancy outcomes in pregnant women with early-onset GDM. In the treatment from early pregnancy group (n=286), patients were diagnosed with early-onset GDM at the Yokohama City University Medical Center (YCU-MC) in 2015-2017 and were treated for GDM from early pregnancy. Concerning the treatment from mid-pregnancy group (n=248), participants were diagnosed with early-onset GDM at five sites, including the YCU-MC in 2018-2019, and were followed up without treatment until the second 75 g oral glucose tolerance test (OGTT) at 24-28 weeks of gestation. Treatment for GDM was given only if the GDM pattern was still present in the second OGTT. RESULTS: There were no significant differences in maternal backgrounds, including GDM risk factors and gestational weight gain, between the groups. Among the treatment from mid-pregnancy group, the false-positive early GDM was 124/248 (50%). Regarding pregnancy outcome, the rate of large for gestational age (LGA) was 8.8% in the treatment from early pregnancy group and 10% in the treatment from mid-pregnancy group, with no significant difference, whereas small for gestational age (SGA) was significantly higher in the treatment from early pregnancy group (9.4%) than in the treatment from mid-pregnancy group (4.8%) (p=0.046). There were no significant differences in maternal adverse events and neonatal outcomes between the groups. In a subanalysis limited to body mass index >25 kg/m2, LGA was significantly lower in the treatment from early pregnancy group than in the treatment from mid-pregnancy group. CONCLUSIONS: The strategy for diagnosing GDM by IADPSG thresholds in early pregnancy and providing treatment to all patients from early pregnancy did not improve the pregnancy outcomes, but rather increased the SGA rate.

The interactive effects of traffic sound and window views on indoor soundscape perceptions in the residential area.

Environmental noise has long been considered one of the unwelcome aspects of urban life at home. An increasing number of scholars have studied improving indoor acoustic comfort by using the soundscape approach. However, much uncertainty still exists about the relationship between the audio-visual environment and indoor soundscape perception. The current study investigates the interaction effects of traffic sound and window views on indoor soundscape perceptions in residential contexts. Thirty-two participants were presented with 51 scenarios (a combination of 17 window views and three aural stimuli) and requested to assess their soundscape perceptions in a VR experiment. Results showed that traffic noise could moderate the impact of nature, road, and building views on pleasantness, while it can also moderate the effect of water sound and road view on eventfulness. In particular, natural window views were found not to lead to a more pleasant indoor soundscape necessarily; natural window views even decrease the pleasantness of indoor soundscape in the case of heavy traffic noise outside the window. Besides, overall visual indicators, including complexity and openness, have an interactive effect with traffic sound on pleasantness. Last, pleasantness is found to be associated with the appropriateness of indoor soundscape.

Awareness of Infectious Disease Screening During Early Pregnancy and Knowledge About its Vertical Transmission in Japan: A Report from the Pregnant Women Health Initiative.

OBJECTIVES: We aimed to clarify the accuracy of pregnant women's knowledge and understanding regarding infectious disease screening in early pregnancy and clarify the roles that should be played by health care providers in promoting the health of pregnant women and their children. METHODS: A cross-sectional questionnaire survey was conducted in 25 hospitals across Japan from May 2018 to September 2019. We compared the agreement rates regarding screening results for hepatitis B virus (HBV), hepatitis C virus (HCV), syphilis, human T-cell leukemia virus-1 (HTLV-1), and cervical cytology in the medical records and understanding of their results by pregnant women. We then investigated whether participants had knowledge regarding the risk of mother-to child transmission in these diseases and factors associated with their knowledge. RESULTS: We enrolled 2,838 respondents in this study. The rates of agreement for HBV and cervical cancer screening related to human papillomavirus infection were "substantial," those for syphilis was "moderate," and those for HCV and HTLV-1 were "fair," according to the Kappa coefficient. The rate of knowledge regarding mother-to-child transmission of syphilis was highest (37.0%); this rate for the other items was approximately 30%. Increased knowledge was associated with higher educational level and higher annual income. CONCLUSIONS FOR PRACTICE: Pregnant women in Japan had generally good levels of understanding regarding their results in early-pregnancy infectious disease screening. However, they had insufficient knowledge regarding mother-to-child transmission of these diseases. Health care providers should raise awareness in infectious disease prevention among pregnant women and the general public, providing appropriate measures and implementing effective perinatal checkups and follow-ups for infectious diseases.

A qualitative and quantitative synthesis of the impacts of COVID-19 on soundscapes: A systematic review and meta-analysis.

The current prolonged coronavirus disease (COVID-19) pandemic has substantially influenced numerous facets of our daily lives for over two years. Although a number of studies have explored the pandemic impacts on soundscapes worldwide, their works have not been reviewed comprehensively nor systematically, hence a lack of prospective soundscape goals based upon global evidence. This review study examines evidence of the COVID-19 crisis impacts on soundscapes and quantifies the prevalence of unprecedented changes in acoustic environments. Two key-research classes were identified based on a systematic content analysis of the 119 included studies: (1) auditory perceptual change and (2) noise level change due to the COVID-19 pandemic/lockdown. Our qualitative synthesis ascertained the substantial adverse consequences of pandemic soundscapes on human health and well-being while beneficial aspects of the COVID-19 pandemic on soundscapes were yet identified. Furthermore, meta-analysis results highlight that the observed average noise-level reduction (148 averaged samples derived from 31 studies) varied as a function of the stringency level of the COVID-19 confinement policies imposed by the governments, which would be further moderated by urban morphology and main noise sources. Given these collective findings, we propose soundscape materiality, its nexus with related the United Nations' sustainable development goals (SDGs), and prospective approaches to support resilient soundscapes during and after the pandemic, which should be achieved to enhance healthy living and human well-being.

Clustering acoustical measurement data in pediatric hospital units.

The previous hospital acoustic literature has highlighted some important considerations and various complexities regarding objective noise measurements. However, extensive use of conventional acoustical metrics such as logarithmically averaged equivalent sound pressure levels (Leq) do not sufficiently describe hospital acoustical environments and often lack considerations of the room-based activity status that can significantly influence the soundscape. The goal of this study was to explore utilizing statistical clustering techniques in healthcare settings with a particular aim of identifying room-activity conditions. The acoustic measurements were conducted in the patient rooms of two pediatric hospital units and subsequently classified based on two room-activity conditions-active and non-active conditions-by applying statistical clustering analyses with standard k-means and fuzzy c-means algorithms. The results of this study demonstrate the most probable noise levels and degree of associations of the measured noise levels for the two room-activity conditions. The results were further validated in terms of the clustered levels, the number of conditions, and parameter dependency. The clustering approach allows for a more thorough soundscape characterization than single-number level descriptors alone by providing a method of identifying and describing the noise levels associated with typical, intrinsic activity conditions experienced by occupants.

High probability of false-positive gestational diabetes mellitus diagnosis during early pregnancy.

INTRODUCTION: This study aimed to assess the validity of applying the International Association of Diabetes and Pregnancy Study Group (IADPSG) criteria for the diagnosis of gestational diabetes mellitus (GDM) at any time during pregnancy. RESEARCH DESIGN AND METHODS: This multicenter cohort study was conducted at five Japanese facilities from January 2018 to April 2019. The study cohort included women at a high risk of GDM who met one or more of the following IADPSG criteria during early pregnancy: fasting plasma glucose (FPG) ≥92 mg/dL and 75 g oral glucose tolerance test (OGTT) value of ≥180 mg/dL at 1 hour, or ≥153 mg/dL at 2 hour (hereafter early-onset GDM). Women diagnosed with early-onset GDM were followed up without therapeutic intervention and underwent the 75 g OGTT again during 24-28 weeks of gestation. Those exhibiting the GDM patterns on the second 75 g OGTT were diagnosed with true GDM and treated, whereas those exhibiting the normal patterns were diagnosed with false positive early GDM and received no therapeutic intervention. RESULTS: Of the 146 women diagnosed with early-onset GDM, 69 (47%) had normal 75 g OGTT values at 24-28 weeks of gestation, indicating a false-positive result. FPG levels were significantly higher in the first 75 g-OGTT test than in the second 75 g-OGTT test (93 mg/dL and 87.5 mg/dL, respectively; p<0.001). FPG levels were high in 86 (59%) women with early-onset GDM during early pregnancy but in only 39 (27%) women during mid-pregnancy. Compared with false positive early GDM, true GDM was more frequently associated with adverse pregnancy outcomes. CONCLUSIONS: Although women with early-onset GDM were followed up without treatment, the results of repeated 75 g OGTT during mid-pregnancy were normal in about 50%. Our data did not support the adoption of IADPSG thresholds for the diagnosis of GDM prior to 20 weeks of gestation.

Examining the Utility of Perceptual Noise Categorization in Pediatric and Neonatal Hospital Units.

Medical and nursing staff working in hospitals often experience exposure to extreme sound environments, and there is growing evidence of the negative impacts. Previous research highlighted various complexities regarding noise sources in hospitals; however, identifications of intrinsic noise categories that can reveal the complex mixture of existing hospital noise is still limited. The objective of this work was to identify intrinsic categories of the noise sources based on staff perceived annoyance and explore clear associations of these categorized noise sources with psychological perceptions. The staff perceptual responses regarding hospital noise were assessed by conducting surveys at the three pediatric and neonatal care units in two hospitals. Using principle component analysis (PCA), the psychological annoyance responses of 94 participants were used to derive the inherent structural patterns of the existing noise sources. The derived PCA categorization was validated on mixed-model analysis of variances, and employed on regression models to explore potential associations between the categorized noise factors and the staff's psychological perceptions. The results highlighted three intrinsic noise categories and their negative impacts on staff's psychological perceptions including work/rest disturbance and noisiness. Taken as a whole, the findings better reveal problematic noise source categories and establish a framework for hospital noise control that is less source-specific and more broadly generalizable.

Association between chronological depressive changes and physical symptoms in postoperative pancreatic cancer patients.

BACKGROUND: Pancreatic cancer (PC) has poorer prognosis and higher surgical invasiveness than many other cancers, with associated psychiatric symptoms including depression and anxiety. Perioperative depression has not been investigated in PC patients regarding surgical stress and relevant interventions. METHODS: We evaluated chronological depressive changes and subjective physical symptoms in surgically treated PC patients preoperatively and at 3 and 6 months postoperatively.Enrolled patients undergoing pancreatic tumor surgery completed questionnaires based on the Self-Rating Depression Scale (SDS) and Functional Assessment of Cancer Therapy for Patients with Hepatobiliary Cancer (FACT-Hep) preoperatively, and at 3 and 6 months postoperatively. Responses were analyzed with JMP® Pro using one-way and two-way ANOVA, Spearman's rank correlation coefficient, and multiple regression analysis. RESULTS: Malignancy was diagnosed in 73 of 101 patients postoperatively; SDS score was significantly higher in these patients than in those with benign tumors at all timepoints: malignant/benign, 41.8/37.9 preoperatively (p = 0.004); 43.5/37.8 3 months postoperatively (p = 0.006); and 42.9/37.7 6 months postoperatively (p = 0.020). SDS scores were significantly higher in patients < 65 years old with malignancy at 3 months than at 6 months postoperatively (44.6/42.5, p = 0.046) and in patients with malignancy who underwent pancreaticoduodenectomy at 3 months postoperatively than preoperatively (43.4/41.1; p = 0.028). SDS scores moderately correlated with 8 physical symptom-related FACT-Hep items 3 months postoperatively (p < 0.05), showing low-to-moderate correlation with 16 physical symptom-related FACT-Hep items at 6 months postoperatively (p < 0.05). Multiple regression analysis of FACT-Hep symptoms significantly correlated with SDS scores revealed the following significant variables: "lack of energy" (p < 0.000) and "pain" (p = 0.018) preoperatively (R2 = 0.43); "able to perform usual activities" (p = 0.031) and "lack of energy" (p < 0.000) at 3 months postoperatively (R2 = 0.51); and "stomach swelling or cramps" (p = 0.034) and "bowel control" (p = 0.049) at 6 months postoperatively (R2 = 0.52). CONCLUSIONS: PC patients experience persistently high levels of depression preoperatively through 6 months postoperatively, with associated subjective symptoms including pain and gastrointestinal symptoms. TRIAL REGISTRATION: UMIN Clinical Trials Registry 000009592, Registered 20 December 2012.

Spontaneous reduction of an incarcerated gravid uterus in the third trimester.

An incarcerated gravid uterus is an uncommon complication of pregnancy. On rare occasions, an incarcerated gravid uterus resolves spontaneously even in the third trimester of pregnancy. Severe abdominal pain might be caused by spontaneous reduction and should be considered as a possible cause.

Phenotypic changes of AADC-only-immunoreactive cells in the alimentary canal of the laboratory shrew, Suncus murinus, induced by systemic administration of monoamine precursors.

In order to elucidate the function of anti-aromatic acid decarboxylase (AADC)-only-positive cells in the alimentary canal, 5-hydroxy-L-tryptophan (5-HTP) or L-3,4-dihydroxyphenylalanine (L-DOPA) was intraperitoneally injected into the laboratory shrew, Suncus murinus, and immunohistochemical studies were conducted on continuous sections of the alimentary canal using specific antisera against tyrosine hydroxylase (TH), AADC, dopamine (DA), and serotonin (5-HT). AADC-only-positive cells localized to the epithelial layer of the alimentary canal from the stomach to the large intestine. These AADC-only-positive cells became DA- and AADC-positive cells after L-DOPA injection, and 5-HT- and AADC-positive cells after 5-HTP injection. These results strongly indicate that the AADC-only-positive cells in the alimentary canal of Suncus murinus are capable of synthesizing DA and 5-HT simultaneously upon administration of L-DOPA and 5-HTP.

Association of biparietal diameter growth rate with neurodevelopment in infants with fetal growth restriction.

OBJECTIVE: To investigate the association between neurodevelopmental complications and biparietal diameter (BPD) growth rate. MATERIALS AND METHODS: The patients were pregnant women with severe fetal growth restriction (< 5(th) percentile) before 30 weeks who delivered after 24 gestational weeks. We defined poor BPD growth as being at least 50% below the mean growth rate for at least 1 week. We analyzed maternal characteristics, neonatal complication morbidities, perinatal mortality rate, and neurodevelopmental complications in the child at age 2 years (corrected). RESULTS: BPD growth was categorized as normal or poor. Out of 8254 infants, 26 met the above criteria. The poor BPD growth group included 17 infants and the normal BPD growth group included nine infants. The gestational age at delivery was 28.7 (24.7-31.7) weeks in the poor BPD growth group and 28.5 (26.1-32.4) weeks in the normal BPD growth group, showing no significant difference. However, death or neurodevelopmental complications occurred in eight of the 17 infants in the poor BPD growth group, whereas neither death nor neurodevelopmental complications were observed in the normal BPD growth group (p = 0.009). Moreover, in those with poor outcomes, BPD growth rates were consistently below 40% and birth weights were < 700 g. CONCLUSION: BPD growth was associated with neurodevelopmental outcomes, and growth delay as compared with the mean growth rate is a risk factor for poor neurodevelopment.

Requirement of DLG1 for cardiovascular development and tissue elongation during cochlear, enteric, and skeletal development: possible role in convergent extension.

The Dlg1 gene encodes a member of the MAGUK protein family involved in the polarization of epithelial cells. Null mutant mice for the Dlg1 gene (Dlg1-/- mice) exhibit respiratory failure and cyanosis, and die soon after birth. However, the cause of this neonatal lethality has not been determined. In the present study, we further examined Dlg1-/- mice and found severe defects in the cardiovascular system, including ventricular septal defect, persistent truncus arteriosus, and double outlet right ventricle, which would cause the neonatal lethality. These cardiovascular phenotypes resemble those of mutant mice lacking planar cell polarity (PCP) genes and support a recent notion that DLG1 is involved in the PCP pathway. We assessed the degree of involvement of DLG1 in the development of other organs, as the cochlea, intestine, and skeleton, in which PCP signaling has been suggested to play a role. In the organ of Corti, tissue elongation was inhibited accompanied by disorganized arrangement of the hair cell rows, while the orientation of the stereocilia bundle was normal. In the sternum, cleft sternum, abnormal calcification pattern of cartilage, and disorganization of chondrocytes were observed. Furthermore, shortening of the intestine, sternum, and long bones of the limbs was observed. These phenotypes of Dlg1-/- mice involving cellular disorganization and insufficient tissue elongation strongly suggest a defect in the convergent extension movements in these mice. Thus, our present results provide a possibility that DLG1 is particularly required for convergent extension among PCP signaling-dependent processes.

Clinical features of gestational thrombocytopenia difficult to differentiate from immune thrombocytopenia diagnosed during pregnancy.

AIM: To investigate the clinical features of gestational thrombocytopenia (GT) difficult to differentiate from immune thrombocytopenia (ITP) during pregnancy. METHODS: The January 2000-December 2012 hospital database was analyzed to identify women with ITP or GT (after excluding other possible causes of thrombocytopenia) among those first noted to have platelet counts of less than 100 000/µL during pregnancy. The maternal characteristics, platelet count fluctuations and pregnancy outcomes were compared between women with ITP and GT. RESULTS: There were 23 pregnancies (22 women) with thrombocytopenia (GT, 13; ITP, 10). The GT group included five twin pregnancies (38.5%), whereas all pregnancies of the ITP group were singleton pregnancies, with significantly more twin pregnancies in the GT group (P = 0.046). Thrombocytopenia in the first trimester occurred in 70% (7/10) of ITP cases and 23.1% (3/13) of even GT cases. The nadir platelet count was less than 70 000/µL in 100% (10/10) of ITP cases and 30.8% (4/13) of GT cases (P < 0.001). Maternal treatment was required in 80% (8/10) of ITP cases, but in none of the GT cases. The pregnancy outcomes were favorable in both groups, and no case required fetal treatment. CONCLUSION: Gestational thrombocytopenia with platelet counts of less than 10 0000/µL occurred more frequently in twin pregnancies. Although onset of thrombocytopenia in the first trimester and a platelet count of less than 70 000/µL is more common in ITP, these findings were not uncommon in GT. Differentiation between ITP and GT may be feasible only with post-partum changes in the platelet count.

High expression of Pitx-2 in the ICAT-deficient metanephros leads to developmental arrest.

ICAT (Inhibitor of ß-catenin and T cell factor) inhibits the interaction between ß-catenin and TCF/LEF transcription factor and serves as a negative regulator of Wnt signaling. In a subset of ICAT knockout mice, significant delay in the ureteric bud branching and renal agenesis are observed. In order to examine the process of this developmental defect, molecular changes were analyzed in fetal ICAT-/- kidneys with a focus on Wnt-signaling associated factors. The protein level of active ß-catenin was elevated in ICAT-/- kidneys. DNA microarray and immunohistochemical analyses revealed that the expression of a Wnt target gene Pitx-2 was enhanced in ICAT-/- kidneys. There was no genotypic difference in the expression level of another Wnt target gene, c-Ret. These results suggest that the enhancement of Pitx-2 expression induced by activated Wnt signaling leads to delays in ureteric bud branching and subsequent renal agenesis. In the ICAT-/- kidneys which developed to E18.5 without any apparent defect, renal glomeruli, convoluted tubules and collecting ducts were decreased in density and showed abnormal structure. ICAT may be required for various developmental stages during renal development.

[Prophylaxis with acyclovir for herpes zoster infection during bortezomib-dexamethasone combination therapy].

A novel molecular targeting drug, a proteasome inhibitor, bortezomib (Bor), has been reported to be highly effective for relapsed/refractory, as well as for newly diagnosed multiple myeloma, but is also associated with a high frequency of herpes zoster (HZ) infection (13%). We conducted a retrospective survey on HZ infection (profile) after Bor therapy in our hospital. Six of 30 patients developed HZ infection during bortezomib-dexamethasone treatment (BD therapy). Age, performance status, and stem cell transplantation were not related risk factors for HZ infection. HZ developed when acyclovir (ACV) was not administrated to all six cases. Continuous administration of ACV decreased the incidence of HZ infection. Based on these results, we started an anti- HZ prophylaxis program using ACV for all patients receiving BD therapy. Further study is warranted to establish the optimal dose and duration of ACV for appropriate prophylaxis of HZ infection.

Loss of ICAT gene function leads to arrest of ureteric bud branching and renal agenesis.

ICAT, inhibitor of beta-catenin and T cell factor, or Ctnnbip1, is a negative regulator of the Wnt signaling pathway that interferes with the interaction between beta-catenin and T cell factor. Some ICAT-deficient (ICAT-/-) embryos exhibit unilateral or bilateral renal agenesis. In this study, we investigated developmental processes in the ICAT-/- kidney. ICAT was highly expressed in both the ureteric bud (UB) and the surrounding metanephric mesenchymal (MM) cells in the metanephros of embryonic day E11.5-E13.5 wild-type (ICAT+/+) mouse. In the E12.5-ICAT-/- metanephros, UB branching was delayed, and a T-shaped, bifurcated UB was frequently seen; this was never seen in the E12.5-ICAT+/+ metanephros. More apoptotic MM cells were detected in the ICAT-/- metanephros than in the ICAT+/+ metanephros. These results suggest that the loss of ICAT gene function causes the arrest of UB branching and the apoptotic death of MM cells, resulting in renal agenesis.

Role of the Rho GTPase-activating protein RICS in neurite outgrowth.

The Rho family of small GTPases, including RhoA, Rac1 and Cdc42, are critical regulators of the actin cytoskeleton. In neuronal systems, Rho GTPase-activating proteins (RhoGAPs) and their substrates, Rho GTPases, have been implicated in regulating multiple processes in the morphological development of neurons, including axonal growth and guidance, dendritic elaboration and formation of synapses. RICS is mainly expressed in the brain and functions as a RhoGAP protein for Cdc42 and Rac1 in vitro. To examine the biological function of RICS, we disrupted the RICS gene in mice. RICS knockout mice developed normally and were fertile. However, when cultured in vitro, Cdc42 activity in RICS(-/-) neurons was higher than that in wild-type neurons. Consistent with this finding, hippocampal and cerebellar granule neurons derived from RICS(-/-) mice bore longer neurites than those from wild-type mice. These findings suggest that RICS plays an important role in neurite extension by regulating Cdc42 in vivo.

Anteriorization of neural fate by inhibitor of beta-catenin and T cell factor (ICAT), a negative regulator of Wnt signaling.

Inhibitor of beta-catenin and T cell factor (ICAT) inhibits Wnt signaling by interfering with the interaction between beta-catenin and T cell factor. Here we show that ICAT(-/-) embryos exhibit malformation of the forebrain and craniofacial bones and lack the kidney. Analysis of the neuronal differentiation of embryonic stem cells revealed that Wnt3a redirects the fate of neural progenitors to a posterior character, whereas ICAT induces forebrain cells by inhibiting Wnt signaling. Furthermore, ICAT(-/-) embryonic stem cells were found to differentiate into neuronal cells possessing a posterior character. These results suggest that ICAT plays an important role in the anteriorization of neural cells by inhibiting the posteriorizing activity of Wnt signaling.

Calmodulin overexpression causes Ca(2+)-dependent apoptosis of pancreatic beta cells, which can be prevented by inhibition of nitric oxide synthase.

We investigated the mechanism of beta-cell loss in transgenic mice with elevated levels of beta cell calmodulin. The transgenic mice experienced a sudden rise in blood glucose levels between 21 and 28 days of age. This change was associated with development of severe hypoinsulinemia and loss of beta cells from the islets. Ultrastructural analysis revealed that compromised granule formation and apoptotic changes in the transgenic beta cells preceded the onset of hyperglycemia. Intraperitoneal injection of tolbutamide, an antidiabetic sulfonylurea, decreased blood glucose levels but increased the number of apoptotic beta cells. Finally, injection of transgenic mice with N(omega)-nitro-L-arginine methyl ester, which inhibits nitric oxide synthase activity, prevented hyperglycemia and lessened the changes in number and size of beta cells. Because immunofluorescent staining revealed preferential distribution of neural nitric oxide synthase in pancreatic beta cells, we speculate that overexpression of calmodulin sensitizes the beta cells to Ca(2+)-dependent activation of neural nitric oxide synthase, which mediates apoptosis.