Robust antibody response after a third BNT162b2 vaccine compared to the second among immunocompromised and healthy individuals,a prospective longitudinal cohort study

PurposeAs protection from COVID-19 following two doses of the BNT162b2 vaccine showed a time dependent waning, a third (booster) dose was administrated. This study aims to compare the antibody response following the third dose versus the second and to evaluate post-booster seroconversion.MethodsA prospective observational study conducted in Maccabi Healthcare Services. Serial SARS-CoV-2 Spike IgG tests, 1,2,3 and 6 months following the second vaccine dose and one month following the third were obtained. Neutralizing antibody levels were measured in a subset of participants. Per individual SARS-CoV-2 Spike IgG titer ratios were calculated one month after the booster administration compared to titers one month following the second dose and prior to booster.ResultsAmong 110 participants, 56 (51%) were women. Mean age was 61.7 ± 1.9 years and 66 (60%) were immunocompromised. One month after third dose, IgG titers were induced 7.83 (95 %CI 5.25–11.67) folds and 2.40 (95 %CI 1.90–3.03) folds compared to one month after the second, in the immunocompromised and immunocompetent groups, respectively. Of the 17 immunocompromised participants who were seronegative after the second dose, 4 (24%) became seropositive following the third. Comparing the titers prior to the third dose, an increase of 50.7 (95 %CI 32.5–79.1) fold in the immunocompromised group and 25.7 (95 %CI 19.1–34.7) fold in and immunocompetent group, was observed.ConclusionA third BNT162b2 vaccine elicited robust humoral response, superior to the response observed following the second, among immunocompetent and immunocompromised individuals.     

The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy

In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography–tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030–0.973] and 0.003 ± 0.002 [0.001–0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

毛霉目病原真菌的实验室鉴定及体外抗真菌药物敏感 性分析

摘要:目的以分子测序为参考 ,评估形态学、基质辅助激光解吸电离飞行时间质谱对毛霉目真菌的鉴定能力,分析毛霉目真菌对两性霉素B、泊沙康唑的体外药敏特点。方法收集 2018年1月-2022年2月广东省人民医院25例毛霉病住院患者标 本,进行镜检并对培养的茵落行形态学鉴定、质谱鉴定、分子测序和体外药敏试验。结果KOH 湿片法阳性率(76%)高于革兰染色法(32%),差异有统计学意义(P<0.05);形态学鉴定可将68%的菌株鉴定到属水平,3株鉴定错误,2株无法鉴定;将所 有菌株进行质谱鉴定,单用IVD和RUO数据库鉴定率分别为56%和44%,两库联合可将鉴定率提高为64%。毛霉目真菌对两性霉素B的抑制50%菌株生长的最小抑菌浓度(MIC3o)为1μg/mL,根霉属相比其他属对两性霉素B表现出较高的MIC 值,其中2株MIC>32 μg/mL,另2株MIC为8 μg/mL;根霉属对泊沙康唑的MICso为0.5 μg/mL,横梗霉属MICgo为4 μg/ mL,小克银汉霉属MICg0为2 μg/mL,有部分菌株表现出较低MIC值,同样亦有部分菌株对泊沙康唑表现出较高的MIC 值。结论 将传统镜检、培养与质谱技术和分子技术相结合,尽量将毛霉目真菌准确鉴定到种,并积极开展毛霉体外药敏试验,可为临床治疗提供参考依据。     

Triceps skinfold thickness and body mass index and the risk of gestational diabetes mellitus: Evidence from a multigenerational cohort study

BackgroundPre-pregnancy obesity is a well-recognized risk factor for gestational diabetes mellitus (GDM). There is a continuity of obesity from childhood to adolescence and then adulthood. However, it is unknown whether early childhood obesity predicts GDM.MethodsWe investigated the prospective association of childhood triceps skinfold thickness and body mass index (BMI) with GDM risk among women from the Mater-University of Queensland Study of Pregnancy (MUSP), a multigenerational cohort study. A multiple logistic regression model was applied to estimate the odds of experiencing GDM by childhood skinfold thickness and BMI.ResultsOut of 552 women in the study for whom data were available on triceps skinfold thickness and BMI at average age 5 (range 3–7) years old, 52 (9.42%) developed GDM by average age 30 (range 28–33) years. We found that the risk of developing GDM was greater among women who had greater skinfold thickness but not greater BMI at age 5 years. Women who were classified as overweight or obese based on skinfold thickness at age 5 years had an increased odds ratio of GDM compared to women who had normal skinfold thickness. This association remained significant after adjustment for the potential confounders (OR 2.74; 95% confidence interval = 1.28–5.86).ConclusionThe risk of developing GDM was associated with higher skinfold thickness at age 5 years.     

Pan-cancer proteomic map of 949 human cell lines

1. Download : Download high-res image (220KB)
2. Download : Download full-size image

     

Body mass index is a predictor of discharge to a postacute care facility following total shoulder arthroplasty

BackgroundThe purpose of this study is to evaluate the effect of body mass index (BMI) on discharge to a postacute care (PAC) facility following elective total shoulder arthroplasty (TSA).MethodsThe National Surgical Quality Improvement Program database was queried to identify adult patients (>18 years old) who underwent inpatient TSA for primary osteoarthritis between 2005 and 2018. Hemiarthroplasty, revision TSA, trauma indications, and outpatient procedures were excluded. Patient and perioperative data were identified. Univariate analysis and multivariate logistic regression were used to assess the relationship between BMI and discharge to PAC facilities.ResultsA total of 10,198 patients with a primary TSA were identified. The majority (93%) of patients were discharged home vs. 7% to PAC facilities. Patients discharged to PAC had significantly higher mean BMI (P = .006). After controlling for demographic and comorbid factors, BMI was the only modifiable risk factor that was independently associated with an increased risk of discharge to a PAC. For every increase in BMI point, there was an increased risk of discharge to a PAC by 2.9% (odds ratio [OR] 1.029, confidence interval [CI] 1.016-1.041, P < .001). Additional covariates associated with PAC discharge were older age (OR 1.113, CI 1.099-1.127, P < .001), female gender (OR 3.037, CI 2.489-3.705, P < .001), and dependent functional status (OR 8.322, CI 5.544-12.492, P < .001).ConclusionMost patients undergoing TSA were discharged home following surgery. While age, sex, and functional status also affect disposition, elevated BMI is the only modifiable risk factor that independently predicts PAC discharge. Consideration of patient BMI prior to elective TSA may greatly improve discharge planning and management of patient expectations.