DNA methylation (DNAm) is one of the most studied epigenetic modifications. DNAm has emerged as a key biological mechanism and biomarkers to test associations between environmental exposure and ...outcomes in epidemiological studies. Although previous studies have focused on associations between DNAm and either exposure/outcomes, it is useful to test for mediation of the association between exposure and outcome by DNAm. The purpose of this scoping review is to introduce the methodological essence of statistical mediation analysis and to examine emerging epidemiological research applying mediation analyses. We conducted this scoping review for published peer-reviewed journals on this topic using online databases (PubMed, Scopus, Cochrane, and CINAHL) ending in December 2020. We extracted a total of 219 articles by initial screening. After reviewing titles, abstracts, and full texts, a total of 69 articles were eligible for this review. The breakdown of studies assigned to each category was 13 for smoking (18.8%), 8 for dietary intake and famine (11.6%), 6 for other lifestyle factors (8.7%), 8 for clinical endpoints (11.6%), 22 for environmental chemical exposures (31.9%), 2 for socioeconomic status (SES) (2.9%), and 10 for genetic factors and race (14.5%). In this review, we provide an exposure-wide summary for the mediation analysis using DNAm levels. However, we found heterogenous methods and interpretations in mediation analysis with typical issues such as different cell compositions and tissue-specificity. Further accumulation of evidence with diverse exposures, populations and with rigorous methodology will be expected to provide further insight in the role of DNAm in disease susceptibility.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
The proposed structure of glaucoposterol A, a strophastane-type steroid of mushroom origin, has been synthesized from an aldol obtained in our previous synthesis of strophasterol F, a diastereomer of ...the proposed structure of glaucoposterol A. Based on the fact that the NMR data of natural glaucoposterol A are distinctly different from those of the synthetic material, but matches those of strophasterol F, we put forward a proposal that glaucoposterol A and strophasterol F are actually the same compound. In addition, the hitherto unknown stereochemistry of strophasterol D has been elucidated through synthesis of its two diastereomeric structures.
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•The originally proposed structure of glaucoposterol A was synthesized.•Two diastereomeric structures of strophasterol D were synthesized.•Glaucoposterol A and strophasterol F were suggested to be the same compound.•Strophasterol D was determined to be the C7-epimer of strophasterol C.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Multisystem inflammatory syndrome (MIS) is a hyperinflammatory shock associated with cardiac dysfunction and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. ...However, there are no reports on using MIS criteria, such as multisystemic inflammation (MSI) in fulminant myocarditis, without SARS-CoV-2 infection. This study investigated the differences in clinical characteristics and course between patients with fulminant lymphocytic myocarditis (FLM) plus MSI and those without MSI.Methods and Results: This multicenter retrospective cohort study included 273 patients with FLM registered in the JROAD-DPC database between April 2014 and March 2017. We evaluated the presence of MSI using criteria modified from previously reported MIS criteria and compared the characteristics and risk of mortality or heart transplantation between FLM patients with MSI and without MSI. Of the 273 patients with FLM, 107 (39%) were diagnosed with MSI. The MSI group was younger (44 vs. 57 years; P<0.0001) and had more females (50% vs. 36%; P=0.0236), a higher incidence of pericardial effusion (58% vs. 40%; P=0.0073), and a lower 90-day mortality rate (19% vs. 33%; P=0.0185) than the non-MSI group. The risk of mortality at 90 days was lower in FLM patients aged <50 years with MSI aged <50 years than in those without MSI (P=0.0463).Conclusions: These results suggest that MSI may influence the prognosis of FLM, especially in patients aged <50 years.
Aneurysm rebleeding is a major cause of death and morbidity in patients with aneurysmal subarachnoid hemorrhage (SAH). Recognizing the predictors of rebleeding might help to identify patients who ...will benefit from acute management. This study was performed to investigate the predictors of aneurysm rebleeding and their impact on clinical outcomes in the preoperative, intraoperative, and postoperative periods.
The incidence of rebleeding, demographic data, and clinical data from 4933 patients with aneurysmal SAH beginning in the year 2000 were retrospectively analyzed in the Nagasaki SAH Registry Study. The authors performed multiple logistic regression analyses to identify the risk factors contributing to rebleeding and outcome after SAH.
Preoperative rebleeding occurred in 7.2% of patients. Patient age (p = 0.01), multiple aneurysms (p < 0.01), aneurysm size (p < 0.0001), and heart disease (p = 0.03) were significantly associated with preoperative rebleeding. Conversely, intraoperative rebleeding occurred in 11.2% of patients. Aneurysm location (anterior communicating artery ACoA), family history (p = 0.02), preoperative rebleeding (p < 0.01), and clipping/coiling (p < 0.0001) were significantly associated with intraoperative rebleeding. Interaction analysis showed that clipping significantly affected intraoperative rebleeding at the ACoA (OR 4.00; 95% CI 1.82-8.80; p < 0.001). Postoperative rebleeding occurred in 2.4% of patients. Coiling/clipping (p < 0.0001) and intraoperative rebleeding (p < 0.01) were significantly associated with postoperative rebleeding. Rebleeding in all time periods examined significantly contributed to the clinical outcome after SAH.
Aneurysm rebleeding after SAH has specific characteristics in the preoperative, intraoperative, and postoperative periods, and all of these characteristics contribute to the clinical outcome. The ACoA has a higher risk of intraoperative rebleeding, and endovascular coiling could be a good candidate in terms of techniques for preventing intraoperative rebleeding, although complete aneurysm obliteration should be accomplished.
Background: We evaluated the effectiveness of the BNT162b2 vaccine against infection, symptomatic infection, and hospitalization in older people during the Delta-predominant period (July 1 to ...September 30, 2021).Methods: We performed a population-based cohort study in an older adult population aged ≥65 years using data from the Vaccine Effectiveness, Networking, and Universal Safety Study conducted from January 1, 2019, to September 30, 2021, in Japan. We matched BNT162b2-vaccinated and -unvaccinated individuals in a 1:1 ratio on the date of vaccination of the vaccinated individual. We evaluated the effectiveness of the vaccine against infection, symptomatic infection, and coronavirus disease (COVID-19)-related hospitalization by comparing the vaccinated and unvaccinated groups. We estimated the risk ratio and risk difference using the Kaplan–Meier method with inverse probability weighting. The vaccine effectiveness was calculated as (1 − risk ratio) × 100%.Results: The study included 203,574 matched pairs aged ≥65 years. At 7 days after the second dose, the vaccine effectiveness of BNT162b2 against infection, symptomatic infection, and hospitalization was 78.1% (95% confidence interval CI, 65.2–87.8%), 79.1% (95% CI, 64.6–88.9%), and 93.5% (95% CI, 83.7–100%), respectively.Conclusion: BNT162b2 was highly effective against infection, symptomatic infection, and hospitalization in Japan’s older adult population aged ≥65 years during the Delta-predominant period.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Post-authorization safety studies (PASSs) of vaccines are important. PASSs enable the evaluation of association between vaccination and adverse events following immunization through common study ...designs. Clinical trials during vaccine development typically include a few thousand to 10,000 participants while a PASS might aim to detect a few adverse events per 100,000 vaccine recipients. While all available data may be utilized, prior consideration of power analyses are nonetheless crucial for interpretation in cases where statistically significant differences are not found.
This research primarily examined cohort study design and self-controlled case series (SCCS) design, estimating the power of a PASS under plausible conditions.
Both the cohort study and SCCS designs necessitated large sample sizes or high event counts to guarantee adequate power. The SCCS design is particularly suited to evaluating rare adverse events. However, extremely rare events may not yield sufficient occurrences, thereby resulting in low power. Although the SCCS design can more efficiently control for time-invariant confounding in principle, it solely estimates relative measures. A cohort study design might be preferred if confounding can be adequately managed as it also estimates absolute measures. It may be an easy decision to use all the data at hand for either design. We found it necessary to estimate the sample size and number of events to be used in the study based on
information and anticipated results.
A diastereo- and enantioselective total synthesis of diocollettines A with an unusual oxygen-containing tricyclic ring system has been achieved in 63% overall yield from commercially available ...3-phenylpropanal via four steps. The key feature of the present synthesis is an exclusively diastereoselective cascade sequence composed of a trans-selective oxa-Michael addition of 1,3-dihydroxyacetone to a 2,3-dihydropyrylium ion intermediate, intramolecular aldol-type reaction, and intramolecular acetalization.
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IJS, KILJ, NUK, PNG, UL, UM
Two epimeric rearranged ergostanes, strophasterols A and B, with an unprecedented carbon skeleton were synthesized from ergosterol, both in 17 steps via a common secosteroidal intermediate. The ...conversion of ergosterol into the pivotal intermediate involved an efficient acid‐catalyzed double‐bond migration from ring B to ring D, oxidative cleavage of the double bond, and a completely diastereoselective acyl radical cyclization to form an isolated cyclopentanone ring unique to this recently discovered family of steroidal compounds produced by mushrooms. The intermediate was transformed stereodivergently into two epimeric cyclopentane derivatives through hydrogenation using two types of catalysts. One epimer was elaborated into strophasterol B by utilizing peracid oxidation of an iodide to provide an epoxide directly, and the other epimer was elaborated into strophasterol A, which is known to be a suppressor of endoplasmic reticulum stress.
Two for one: Two epimeric secosteroids of mushroom origin, strophasterols A and B, were synthesized from ergosterol in a stereodivergent manner by using two types of hydrogenation. An isolated cyclopentane ring unit unique to the strophastane family of natural products was installed through an acyl radical cyclization, and the B‐ring functionalization was achieved through peracid oxidation of an iodide to deliver an epoxide directly.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abnormal peripheral perfusion (PP) worsens the prognosis of patients with septic shock. Polymyxin B-direct hemoperfusion (PMX-DHP) increases blood pressure and reduces vasopressor doses. However, the ...modification of PP following administration of PMX-DHP in patients with vasopressor-dependent septic shock have not yet been elucidated. A retrospective exploratory observational study was conducted in patients with septic shock treated with PMX-DHP. Pulse-amplitude index (PAI), vasoactive inotropic score (VIS), and cumulative fluid balance data were extracted at PMX-DHP initiation (T0) and after 24 (T24) and 48 (T48) h. Changes in these data were analyzed in all patients and two subgroups (abnormal PP PAI < 1 and normal PP PAI ≥ 1) based on the PAI at PMX-DHP initiation. Overall, 122 patients (abnormal PP group, n = 67; normal PP group, n = 55) were evaluated. Overall and in the abnormal PP group, PAI increased significantly at T24 and T48 compared with that at T0, with a significant decrease in VIS. Cumulative 24-h fluid balance after PMX-DHP initiation was significantly higher in the abnormal PP group. PMX-DHP may be an effective intervention to improve PP in patients with abnormal PP; however, caution should be exercised as fluid requirements may differ from that of patients with normal PP.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
The anatomical site of resected lobes may influence postoperative cerebral infarction. The objective of the current study was to determine if left upper pulmonary lobectomy is a risk factor ...for postoperative cerebral infarction.
Methods
This was a retrospective case–control study in patients undergoing pulmonary lobectomy from 2004 to 2013 in Japan. We retrospectively identified 610 patients from 153 institutions who had developed postoperative cerebral infarction following pulmonary lobectomy. The control group consisted of 773 patients who underwent lobectomy without cerebral infarction during a randomly selected single month in 2009 at the same institutions.
Results
Factors associated with cerebral infarction were age 10-year intervals, odds ratio (OR): 1.46; 95% confidence interval (CI): 1.23–1.73;
p
< 0.001, male sex (OR 1.92; 95% CI 1.29–2.86;
p
= 0.001), presence of comorbidities (OR 1.82; 95% CI 1.35–2.44;
p
< 0.001), perioperative anti-platelet or anti-coagulant drug use (OR 1.71; 95% CI 1.20–2.45;
p
= 0.003), and lobectomy. Subgroup analyses revealed that cerebral infarction was strongly associated with left upper lobectomy.
Conclusions
Our findings suggest that left upper lobectomy is associated with a higher risk of cerebral infarction than other types of lobectomy, particularly in the early postoperative period.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
