Endlessly single-mode holey fibers: the influence of core design

In this paper we evaluate the cut-off properties of holey fibers (HFs) with a triangular lattice of air holes and the core formed by the removal of a single (HF1) or more air holes (HF3 and HF7). With the aid of finite-element simulations we determine the single-mode and multi-mode phases and also find the air hole diameters limiting the endlessly single-mode regime. From calculations of V and W parameters we find that in general HF1 is less susceptible to longitudinal non-uniformities compared to the other designs for equivalent effective areas. As an example we illustrate this general property for the particular case of a macro-bending induced loss.Comment: 7 pages including 4 figures. Accepted for Opt. Expres

CD38 genotype (rs1800561 (4693C > T): R140W)は新生児集中治療室への入院のリスク増加に関連する

BACKGROUNDS:Preterm birth (PTB)/admission to the neonatal intensive care unit (NICU) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. AIM:Given the role of CD38 in term delivery through oxytocin (OXT) release, we hypothesized that OXT signaling may play a role in the etiology of PTB/admission to the NICU. This study was designed to identify genetic variation in the CD38-oxytocin pathway associated with PTB/admission to the NICU. METHODS:To identify common genetic variants predisposing individuals to PTB/admission to the NICU, we genotyped two single nucleotide polymorphisms (SNPs) in the CD38-oxytocin pathway in 63 case mothers, 55 control mothers, and 188 female volunteers in Nara Medical University Hospital, Japan. RESULTS:Maternal genetic effect analysis of the SNP genotype data revealed a significant association between an SNP in CD38 (rs1800561 (4693C>T): R140W), which was reported to be correlated with diabetes and autism, and the risk of NICU admission. On the other hand, an SNP in the oxytocin receptor (OXTR) (rs2254298) showed no correlation with the risk of NICU admission. CONCLUSION:Our study points to an association between maternal common polymorphisms in the CD38 (rs1800561) gene in Japanese women and susceptibility to PTB/admission to the NICU. Future studies with larger sample sizes are needed to confirm the findings of this study.博士（医学）・甲第639号・平成27年11月27日Copyright © 2015 Elsevier B.V. All rights reserved

Intradermal hepatitis B virus vaccination for low- or non-responded health-care workers.

Immune responses to hepatitis B virus (HBV) vaccine in six low- or non-responded health-care workers were tested with an intradermal low dose (5 micrograms) of the recombinant vaccine. The injection was repeated three or four times at fortnightly intervals. These successive doses of the vaccine induced a high concentration of antibodies with delayed-type hypersensitivity (DTH) skin reactions in all six subjects. A few minor temporary side effects, such as irritation and itching at the injection site, were reported by some of the vaccinees. The results suggest low-dose of intradermal HBV vaccinations for low- or non-responders are safe and readily effective.</p

Dual-time-point 18F-FDG PET imaging for diagnosis of disease type and disease activity in patients with idiopathic interstitial pneumonia

Purpose Individual clinical courses of idiopathic interstitial pneumonia (IIP) are variable and difficult to predict because the pathology and disease activity are contingent, and chest computed tomography (CT) provides little information about disease activity. In this study, we applied dual-time-point [18F]-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET), commonly used for diagnosis of malignant tumors, to the differential diagnosis and prediction of disease progression in IIP patients. Methods Fifty patients with IIP, including idiopathic pulmonary fibrosis (IPF, n=21), nonspecific interstitial pneumonia (NSIP, n=18), and cryptogenic organizing pneumonia (COP, n=11), underwent 18F-FDG PET examinations at two time points: Scan 1 at 60 min (early imaging) and Scan 2 at 180 min (delayed imaging) after 18F-FDG injection. The standardized uptake values (SUV) at the two points and the retention index (RI-SUV) calculated from them were evaluated and compared with chest CT findings, disease progression, and disease types. To evaluate short term disease progression, all patients were examined pulmonary function test every 3 months for 1 year after 18F-FDG PET scanning. Results The early SUV for COP (2.47±0.74) was significantly higher than that for IPF (0.99±0.29, P=0.0002) or NSIP (1.22±0.44, P=0.0025). When an early SUV cut-off value of 1.5 and greater was used to distinguish COP from IPF and NSIP, the sensitivity, specificity, and accuracy were 90.9%, 94.3%, and 93.5%, respectively. The RI-SUV for IPF and NSIP lesions was significantly greater in patients with deteriorated pulmonary function after 1-year of follow-up (progressive group, 13.0±8.9%) than in cases without deterioration during the 1-year observation period (stable group, -16.8±5.9%, P<0.0001). However, the early SUV for all IIP types provided no additional information of disease progression. When an RI-SUV cut-off value of 0% and greater was used to distinguish progressive IIPs from stable IIPs, the sensitivity, specificity, and accuracy were 95.5%, 100%, and 97.8%, respectively. Conclusion Early-SUV and RI-SUV obtained from dual-time point 18F-FDG PET are useful parameter for the differential diagnosis and prediction of disease progression in patients with IIP

Influence of genetic factors on the ephedrine alkaloid composition ratio of Ephedra plants

We investigated the ephedrine alkaloid [(-)-ephedrine and (+)-pseudoephedrine] composition ratio of a crude Chinese herbal drug described in the Japanese Pharmacopoeia \u27Ephedra herb (Chinese name: Mahuang)\u27. There were marked changes in the alkaloid composition ratio of wild plants in areas where both male and female clusters coexisted. However, in genetically homogeneous areas with the growth of male or female clusters alone, all of the coefficients of the regression lines were positive, but each gradient varied. This suggests that the alkaloid composition ratio has a clear tendency in each individual. Based on this, we cultivated individuals for vegetative propagation, and evaluated the alkaloid content ratio. Those propagated by separating the roots showed a specific tendency regardless of the cultivation area (Wakayama, Tanegashima). Those propagated by separating the herbaceous stem showed a specific tendency regardless of the soil or harvest time. In addition, we surveyed the (-)-ephedrine content ratio of 3- to 6-year-old strains. There was a high positive correlation coefficient between the previous and subsequent years. These findings suggest that the ephedrine alkaloid composition ratio of Ephedra herb depends on genetic factors, but not on environmental factors or the growth period

産後うつとボンディングの関連の経産による変化: 子どもの健康と環境に関する全国調査からの経時的な結果より

富山大学・富医薬博乙77号・土田 暁子・2020/11/25関連論文Tsuchida A, Hamazaki K, Matsumura K, Miura K, Kasamatsu H, Inadera H; Japan Environment and Children\u27s Study (JECS) Group. Changes in the association between postpartum depression and mother-infant bonding by parity: Longitudinal results from the Japan Environment and Children\u27s Study. J Psychiatr Res. 2019 Mar;110:110-116. doi: 10.1016/j.jpsychires.2018.11.022. Epub 2018 Nov 28. PMID: 30616158.富山大

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362