Direct anti glycolate aldol reaction of protected chiral N-hydroxyacetyl thiazolidinethiones with acetals catalyzed by a nickel(II) complex

The direct and stereocontrolled addition of (S)‐4‐isopropyl‐N‐(2‐pivaloyloxyacetyl)‐1,3‐thiazolidine‐2‐thione to dialkyl acetals of aromatic and α,β‐unsaturated aldehydes catalyzed by 2.5-5 mol‐% of a nickel(II) complex permits the synthesis of diastereomerically pure and fully protected anti aldol adducts in good to high yields. The catalytic species is formed in situ from commercially available and easy to handle (Me3P)2NiCl2, which makes this reaction a direct, catalytic, and experimentally simple approach to the asymmetric anti glycolate aldol reaction

The effect of duration of illness and antipsychotics on subcortical volumes in schizophrenia: Analysis of 778 subjects

BackgroundThe effect of duration of illness and antipsychotic medication on the volumes of subcortical structures in schizophrenia is inconsistent among previous reports. We implemented a large sample analysis utilizing clinical data from 11 institutions in a previous meta-analysis.MethodsImaging and clinical data of 778 schizophrenia subjects were taken from a prospective meta-analysis conducted by the COCORO consortium in Japan. The effect of duration of illness and daily dose and type of antipsychotics were assessed using the linear mixed effect model where the volumes of subcortical structures computed by FreeSurfer were used as a dependent variable and age, sex, duration of illness, daily dose of antipsychotics and intracranial volume were used as independent variables, and the type of protocol was incorporated as a random effect for intercept. The statistical significance of fixed-effect of dependent variable was assessed.ResultsDaily dose of antipsychotics was positively associated with left globus pallidus volume and negatively associated with right hippocampus. It was also positively associated with laterality index of globus pallidus. Duration of illness was positively associated with bilateral globus pallidus volumes. Type of antipsychotics did not have any effect on the subcortical volumes.DiscussionA large sample size, uniform data collection methodology and robust statistical analysis are strengths of the current study. This result suggests that we need special attention to discuss about relationship between subcortical regional brain volumes and pathophysiology of schizophrenia because regional brain volumes may be affected by antipsychotic medication

The deglacial history of surface and intermediate water of the Bering Sea

Author Posting. © The Authors, 2005. This is the author's version of the work. It is posted here by permission of Elsevier B. V. for personal use, not for redistribution. The definitive version was published in Deep Sea Research Part II: Topical Studies in Oceanography 52 (2005): 2163-2173, doi:10.1016/j.dsr2.2005.07.004.The lithology of deglacial sediments from the Bering Sea includes intervals of laminated or dysaerobic sediments. These intervals are contemporaneous with the occurrence of laminated sediments from the California margin and Gulf of California, which suggests widespread low-oxygen conditions at intermediate depths in the North Pacific Ocean. The cause could be reduced intermediate water ventilation, increased organic carbon flux, or a combination of the two. We infer abrupt decreases of planktonic foraminifer δ18O at 14,400 y BP and 11,650 y BP, which may be a combination of both freshening and warming. On the Shirshov Ridge, the abundance of sea-ice diatoms of the genus Nitzschia reach local maxima twice during the deglaciation, the latter of which may be an expression of the Younger Dryas. These findings expand the extent of the expression of deglacial millennial-scale climate events to include the northernmost Pacific.The Oak Foundation of Boston, Massachusetts, and the WHOI Academic Programs Office provided support for Mea Cook. This project was funded by NSF grant OPP-9912122

PETREL for Astrophysics and Carbon Business

A multi-purpose 50kg class microsatellite hosting astrophysical mission and earth remote sensing, PETREL , will be launched in 2023. In the night side, PETREL observe the ultra-violet sky with a wide-field telescope covering 50 deg^2 for surveying transient objects related to supernovae, tidal disruption events, and gravitational wave events. Our UV telescope can detect the early phase UV emission from a neutron star merger occurred within 150 Mpc. In addition to the satellite observation, PETREL sends a detection alert including the coordinate and brightness of the UV transient to the ground via the real time communication network within several minutes after detection to conduct follow-up observations with the collaborating ground based observatories over the world. In the day side, PETREL observes the surface of the earth by using the tunable multi-spectral cameras and a ultra-compact hyperspectral camera. Our potential targets are the tropical forests (Green Carbon) and coastal zones (Blue Carbon) in the tropical areas to evaluating the global biological carbon strages. For this purpose PETREL will conduct multiple scale mapping collaborating with drones and small aircraft not only satellite. The obtained data will be used for academical research and for business applications. The technical difficulty of this satellite is that carries out multi-purpose with different requirements, such as astronomical observations which requires a quite high attitude stability and the earth observations requiring a high pointing accuracy, with limited resources. If it is possible, a novel small satellite system or a business style can be realized that can share the payload with academia and industry. PETREL has been adopted as Innovative Satellite Technology Demonstration Program No.3 led by JAXA, and development is underway with the aim of launching in FY2023

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Use of the index of pulmonary vascular disease for predicting long-term outcome of pulmonary arterial hypertension associated with congenital heart disease

AimsLimited data exist on risk factors for the long-term outcome of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD-PAH). We focused on the index of pulmonary vascular disease (IPVD), an assessment system for pulmonary artery pathology specimens. The IPVD classifies pulmonary vascular lesions into four categories based on severity: (1) no intimal thickening, (2) cellular thickening of the intima, (3) fibrous thickening of the intima, and (4) destruction of the tunica media, with the overall grade expressed as an additive mean of these scores. This study aimed to investigate the relationship between IPVD and the long-term outcome of CHD-PAH.MethodsThis retrospective study examined lung pathology images of 764 patients with CHD-PAH aged &lt;20 years whose lung specimens were submitted to the Japanese Research Institute of Pulmonary Vasculature for pulmonary pathological review between 2001 and 2020. Clinical information was collected retrospectively by each attending physician. The primary endpoint was cardiovascular death.ResultsThe 5-year, 10-year, 15-year, and 20-year cardiovascular death-free survival rates for all patients were 92.0%, 90.4%, 87.3%, and 86.1%, respectively. The group with an IPVD of ≥2.0 had significantly poorer survival than the group with an IPVD &lt;2.0 (P = .037). The Cox proportional hazards model adjusted for the presence of congenital anomaly syndromes associated with pulmonary hypertension, and age at lung biopsy showed similar results (hazard ratio 4.46; 95% confidence interval: 1.45–13.73; P = .009).ConclusionsThe IPVD scoring system is useful for predicting the long-term outcome of CHD-PAH. For patients with an IPVD of ≥2.0, treatment strategies, including choosing palliative procedures such as pulmonary artery banding to restrict pulmonary blood flow and postponement of intracardiac repair, should be more carefully considered

ヒト乳癌におけるエストロゲン依存性の検討 : Ⅱ. 進行又は再発乳癌に対するタモキシフェンの臨床的評価

An antiestrogen (tamoxifen) was given to 17 patients with advanced breast cancer (both recurrent and primary cancers) during a period from June 1981 to September 1983. The response rate to the antiestrogen was 47.8% (8/17). Sixty percent (6/10) of patients with estrogen receptor positive (ER +) responded, compared with 16.7% (1/6) of patients with estrogen receptor negative (ER －). Forty percent of patients with soft tissue/lymph nodes involvement responded, compared with 27.2% in patients with bone metastasis, and 25.0% in patients with visceral involvement. Postmenopausal patients responded more than premenopausal ones. In recurrent cases, the response rate increased with the prolongation of disease free interval. Eight out of 17 patients are still alive, and the longest survival case has been in a condition of partial response for 23 months so far. The mean survival period in 9 deaths was 13±9 months, with longest 32 months. As shown here, some patients with advanced breast cancer respond very well to the therapy. From these results, we think the tamoxifen-containing endocrinotherapy in combination with chemotherapy is effective in treatment of · advanced cancer and its active application may enable patients to live longer in the rehabilitated situation

ヒト乳癌におけるエストローゲン依存性の検討 : I. ヒト乳癌組織におけるエストローゲンレセプターの細胞化学的研究

We have had an opportunity to determine estrogen receptor (ER) in cytoplasmic fractions of primary breast cancer specimens taken from 79 patients under a fluorescent microscope using fluorescent estradiol conjugate as a tracer. In this study, an estrogen receptor is reported as positive when not less than 10% of carcinoma cells incorporate fluorescent estradiol conjugate into cytoplasma. The ER positive rate was 61% in the total cases, varying by age: 70% in 40s and younger, 43% in 50s, and 60% in 60s and older patients. Sixty-eight % of premenopausal breast cancers conpared to 54% of postmenopausal ones were ER positive. Broken down by the histological type, the rates were 70% in papilla-tubular carinoma, 59 % in medullary tubular carcinoma, and 57 % in scirrhous type. The rates by tumor size according to the clinical TNM classification were 70 % in T1, 59% in T2, 91% in T3, and 34% in T4. The rates by stage difined by the pathological TNM classification were 65 % in Stage I, 50% in Stage II, 87% in Stage III, and 45% in Stage IV. We discuss our findings and review others, as well