Aim
This paper describes the emergency, compassionate use of the COVID‐19 vaccination for high‐risk adolescents aged 12–15 years prior to approval by the American Food and Drugs Administration in May ...2021. The target audience had underlying health conditions associated with severe disease and multisystem inflammatory syndrome in children (MIS‐C) or severely immunosuppressed household members.
Methods
An orderly approval system was established in Israel for adolescents aged 12–15 years, based on a professional position paper and compassionate treatment regulations. From 12 February 2021, eligible adolescents were referred to the Israeli Ministry of Health for permission to vaccinate, via four health maintenance organisations. Data were collected about adverse events after vaccinations and the incidence of any cases of COVID‐19.
Results
By 15 March 2021, the vaccine had been approved for 607 adolescents: 333 had received one dose, and 92 had received two doses. The median age was 14.6 years, and the major indication was obesity. Only one child tested positive for the virus, 4 days after vaccination, and no adverse effects were recorded.
Conclusion
The emergency use of COVID‐19 vaccination for 333 adolescents aged 12–15, 92 of them with 2 doses, based on a position paper and compassionate treatment regulations, did not result in any adverse effects. Since 27 July 2021, the same process was further applied in Israel among younger children, aged 5–11, preceding formal release of the clinical trial.
To examine the association between systemic inflammation measured during midlife and 20-year cognitive decline.
Within the Atherosclerosis Risk in Communities cohort study, inflammatory biomarkers ...were measured during middle adulthood. We created an inflammation composite score using 4 blood biomarkers measured at visit 1 (fibrinogen, white blood cell count, von Willebrand factor, and factor VIII); we measured C-reactive protein (CRP) at visit 2. Cognition was assessed over 3 visits spanning 20 years using measures of memory, executive function, and language.
A total of 12,336 participants (baseline age 56.8 5.7, 21% black, 56% women) were included. After adjusting for demographic variables, vascular risk factors, and comorbidities, each standard deviation (SD) increase in midlife inflammation composite score was associated with an additional 20-year decline of -0.035 SD (95% confidence interval: -0.062 to -0.007) on the cognitive composite score. We found a similar association between each SD increase in midlife CRP level and additional 20-year cognitive decline (-0.038 SD, 95% confidence interval: -0.057 to -0.019). Participants with a midlife inflammation composite score in the top quartile had a 7.8% steeper cognitive decline, compared to participants in the lowest quartile; CRP in the top quartile was associated with an 11.6% steeper cognitive decline. In cognitive domain-specific analyses, elevated midlife inflammatory markers were most consistently associated with declines in memory. Results were similar after adjusting for attrition using inverse probability weighting.
Our findings highlight what may be an early pathogenic role for systemic inflammation as a driver of cognitive decline in the decades leading up to older adulthood.
Sex differences in dementia risk are unclear, but some studies have found greater risk for women.
To determine associations between sex and cognitive decline in order to better understand sex ...differences in dementia risk.
This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020.
Sex.
The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean SD, 50 10); a 1-point difference represents a 0.1-SD difference in cognition.
Among 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median interquartile range age, 58 51-66 years at first cognitive assessment; 2229 18.9% Black) and 14 313 women (median interquartile range age, 58 51-67 years at first cognitive assessment; 3636 25.4% Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95% CI, -0.08 to -0.05 points/y; P < .001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P < .001). Men and women had similar declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P = .61).
The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.
We sought to determine whether the use of carotid revascularization procedures after stroke due to carotid stenosis differs between minority-serving hospitals and hospitals serving predominantly ...white patients.
We identified ischemic stroke cases due to carotid disease, identified by ICD-9-CM codes, from 2007 to 2011 in the Nationwide Inpatient Sample. The use of carotid endarterectomy (CEA) and carotid artery stenting (CAS) was recorded. Hospitals with ≥40% racial/ethnic minority patients (minority-serving hospitals) were compared to hospitals with <40% minority patients (predominantly white hospitals hereafter, abbreviated to white). Logistic regression was used to evaluate the use of CEA/CAS among minority-serving and white hospitals.
Of the 26,189 ischemic stroke cases meeting inclusion criteria, 20,870 (79.7%) were treated at 1,113 white hospitals and 5,319 (20.3%) received care at 325 minority-serving hospitals. Compared to patients in white hospitals, patients in minority-serving hospitals were less likely to undergo CEA/CAS (17.6%, 95% confidence interval CI 16.6%-18.6%, in minority-serving vs 21.2%, 95% CI 20.7%-21.8%, in white hospitals;
< 0.001). In fully adjusted logistic regression models, the odds of CEA/CAS were lower in minority-serving compared to white hospitals (odds ratio 0.81, 95% CI 0.70-0.93), independent of individual patient race/ethnicity and other measured hospital characteristics. White and Hispanic individuals had significantly lower odds of CEA/CAS in minority-serving compared to white hospitals. Patient-level racial/ethnic differences in the use of carotid revascularization procedures remained within each hospital stratum.
The odds of carotid revascularization after stroke is lower in minority- compared to white-serving hospitals, suggesting system-level factors as a major contributor to explain race disparities in the use of carotid revascularization.
NusE:NusG Complex Links Transcription and Translation Burmann, Björn M; Schweimer, Kristian; Luo, Xiao ...
Science (American Association for the Advancement of Science),
04/2010, Letnik:
328, Številka:
5977
Journal Article
Recenzirano
Bacterial NusG is a highly conserved transcription factor that is required for most Rho activity in vivo. We show by nuclear magnetic resonance spectroscopy that Escherichia coli NusG ...carboxyl-terminal domain forms a complex alternatively with Rho or with transcription factor NusE, a protein identical to 30S ribosomal protein S10. Because NusG amino-terminal domain contacts RNA polymerase and the NusG carboxy-terminal domain interaction site of NusE is accessible in the ribosomal 30S subunit, NusG may act as a link between transcription and translation. Uncoupling of transcription and translation at the ends of bacterial operons enables transcription termination by Rho factor, and competition between ribosomal NusE and Rho for NusG helps to explain why Rho cannot terminate translated transcripts.
Two-dimensional observation of biological samples at hundreds of nanometers resolution or even below is of high interest for many sensitive medical applications. Recent advances have been obtained ...over the last ten years with computational imaging. Among them, Fourier Ptychographic Microscopy is of particular interest because of its important super-resolution factor. In complement to traditional intensity images, phase images are also produced. A large set of N raw images (with typically N = 225) is, however, required because of the reconstruction process that is involved. In this paper, we address the problem of FPM image reconstruction using a few raw images only (here, N = 37) as is highly desirable to increase microscope throughput. In contrast to previous approaches, we develop an algorithmic approach based on a physics-informed optimization deep neural network and statistical reconstruction learning. We demonstrate its efficiency with the help of simulations. The forward microscope image formation model is explicitly introduced in the deep neural network model to optimize its weights starting from an initialization that is based on statistical learning. The simulation results that are presented demonstrate the conceptual benefits of the approach. We show that high-quality images are effectively reconstructed without any appreciable resolution degradation. The learning step is also shown to be mandatory.
Bacterial small RNAs (sRNAs) have been implicated in various aspects of post-transcriptional gene regulation. Here, we demonstrate that sRNAs also act at the level of transcription termination. We ...use the rpoS gene, which encodes a general stress sigma factor σS, as a model system, and show that sRNAs DsrA, ArcZ, and RprA bind the rpoS 5′UTR to suppress premature Rho-dependent transcription termination, both in vitro and in vivo. sRNA-mediated antitermination markedly stimulates transcription of rpoS during the transition to the stationary phase of growth, thereby facilitating a rapid adjustment of bacteria to global metabolic changes. Next generation RNA sequencing and bioinformatic analysis indicate that Rho functions as a global “attenuator” of transcription, acting at the 5′UTR of hundreds of bacterial genes, and that its suppression by sRNAs is a widespread mode of bacterial gene regulation.
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•Rho termination factor acts within 5′UTRs of many bacterial genes•Rho functions as a global attenuator of gene expression•Small RNAs interfere with Rho-mediated termination by base-paring within 5′UTRs•sRNA-mediated antitermination is a widespread mode of bacterial gene regulation
Bacterial small RNAs balance the Rho-dependent termination pathway to prevent premature transcription termination, extending the role of these RNA regulators beyond post-transcriptional control.
Presence of coronary artery calcium (CAC), carotid plaque, and increased carotid intima-media thickness (IMT) may indicate elevated cardiovascular disease (CVD) risk; however, no large studies have ...compared them directly. This study compares predictive uses of CAC presence, carotid artery plaque presence, and high IMT for incident CVD events.
Participants were from the Multi-Ethnic Study of Atherosclerosis (MESA). Predictive values of carotid plaque, IMT, and CAC presence were compared using Cox proportional hazards models, c-statistics, and net reclassification indices. The 6779 participants were mean (SD) 62.2 (10.2) years old; 49.9% had CAC, and 46.7% had carotid plaque. The mean left and right IMT were 0.754 (0.210) mm and 0.751 (0.187) mm, respectively. After 9.5 years (mean), 538 CVD events, 388 coronary heart disease (CHD) events, and 196 stroke/transient ischemic attacks were observed. CAC presence was a stronger predictor of incident CVD and CHD than carotid ultrasound measures. Mean IMT≥75th percentile (for age, sex, and race) alone did not predict events. Compared with traditional risk factors, c-statistics for CVD (c=0.756) and CHD (c=0.752) increased the most by the addition of CAC presence (CVD, 0.776; CHD, 0.784; P<0.001) followed by carotid plaque presence (CVD, c=0.760; CHD, c=0.757; P<0.05). Compared with risk factors (c=0.782), carotid plaque presence (c=0.787; P=0.045) but not CAC (c=0.785; P=0.438) improved prediction of stroke/transient ischemic attacks.
In adults without CVD, CAC presence improves prediction of CVD and CHD more than carotid plaque presence or high IMT. CAC and carotid ultrasound parameters performed similarly for stroke/transient ischemic attack event prediction.
Type 2 diabetes (T2D) is a heterogeneous complex disease affecting more than 29 million Americans alone with a rising prevalence trending toward steady increases in the coming decades. Thus, there is ...a pressing clinical need to improve early prevention and clinical management of T2D and its complications. Clinicians have understood that patients who carry the T2D diagnosis have a variety of phenotypes and susceptibilities to diabetes-related complications. We used a precision medicine approach to characterize the complexity of T2D patient populations based on high-dimensional electronic medical records (EMRs) and genotype data from 11,210 individuals. We successfully identified three distinct subgroups of T2D from topology-based patient-patient networks. Subtype 1 was characterized by T2D complications diabetic nephropathy and diabetic retinopathy; subtype 2 was enriched for cancer malignancy and cardiovascular diseases; and subtype 3 was associated most strongly with cardiovascular diseases, neurological diseases, allergies, and HIV infections. We performed a genetic association analysis of the emergent T2D subtypes to identify subtype-specific genetic markers and identified 1279, 1227, and 1338 single-nucleotide polymorphisms (SNPs) that mapped to 425, 322, and 437 unique genes specific to subtypes 1, 2, and 3, respectively. By assessing the human disease-SNP association for each subtype, the enriched phenotypes and biological functions at the gene level for each subtype matched with the disease comorbidities and clinical differences that we identified through EMRs. Our approach demonstrates the utility of applying the precision medicine paradigm in T2D and the promise of extending the approach to the study of other complex, multifactorial diseases.
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