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About 80% of persons with chronic hepatitis B virus (HBV) infection in the United States are non‐US‐born. Despite improvements in infant hepatitis B vaccination globally since 2000, work remains to attain the World Health Organization's (WHO) global 2030 goal of 90% vaccination. We explore the impacts on the United States of global progress in hepatitis B vaccination since 2000 and of achieving WHO hepatitis B vaccination goals. We simulated immigrants with HBV infection arriving to the United States from 2000 to 2070 using models of the 10 countries from which the largest numbers of individuals with HBV infection were born. We estimated costs in the United States among these cohorts using a disease simulation model. We simulated three scenarios: a scenario with no progress in infant vaccination for hepatitis B since 2000 (baseline), current (2020) progress and achieving WHO 2030 goals for hepatitis B vaccination. We estimate current hepatitis B vaccination progress since the 2000 baseline in these 10 countries will lead to 468,686 fewer HBV infections, avoid 35,582 hepatitis B‐related deaths and save $4.2 billion in the United States through 2070. Achieving the WHO 2030 90% hepatitis B infant vaccination targets could lead to an additional 16,762 fewer HBV infections, 989 fewer hepatitis B‐related deaths and save $143 million through 2070. Global hepatitis B vaccination since 2000 reduced prevalence of HBV infection in the United States. Achieving the WHO 2030 infant vaccination goals globally could lead to over one hundred million dollars in additional savings. [ABSTRACT FROM AUTHOR]

Background and aims: Pre‐clinical studies suggest that the simultaneous blockade of the α1b and 5HT2A receptors may be effective in reducing alcohol consumption. This study aimed to assess the efficacy and safety of prazosin (α1b blocker) and cyproheptadine (5HT2A blocker) combination in decreasing total alcohol consumption (TAC) in alcohol use disorder (AUD). Design, setting and participants: This was a double‐blind, parallel group, placebo‐controlled, Phase 2, randomized clinical trial conducted in 32 addiction treatment centres in France. A total of 108 men and 46 women with severe AUD took part. Intervention: Participants were randomly assigned to one of the following 3‐month treatments: (1) low‐dose group (LDG) receiving 8 mg cyproheptadine and 5 mg prazosin extended‐release (ER) formulation daily; (2) high‐dose group (HDG) receiving 12 mg cyproheptadine and 10 mg prazosin ER daily; and (3) placebo group (PG) receiving placebo of cyproheptadine and prazosin ER. A total of 154 patients were randomized: 54 in the PG, 54 in the LDG and 46 in the HDG. Measurements The primary outcome was TAC change from baseline to month 3. Findings: A significant main treatment effect in the change in TAC was found in the intent‐to‐treat population (P = 0.039). The HDG and LDG showed a benefit in the change in TAC from baseline to month 3 compared with PG: −23.6 g/day, P = 0.016, Cohen's d = −0.44; −18.4 g/day, P = 0.048 (Bonferroni correction P < 0.025), Cohen's d = −0.36. In a subgroup of very high‐risk drinking‐level participants (> 100 g/day of pure alcohol for men and > 60 g/day for women), the difference between the HDG and the PG in the primary outcome was −29.8 g/day (P = 0.031, Cohen's d = −0.51). The high and low doses were well‐tolerated with a similar safety profile. Conclusions: A randomized controlled trial of treatment of severe alcohol use disorder with a cyproheptadine−prazosin combination for 3 months reduced drinking by more than 23 g per day compared with placebo. A higher dose combination was associated with a larger magnitude of drinking reduction than a lower dose combination while showing similar safety profile. [ABSTRACT FROM AUTHOR]

Genome‐wide analysis of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) strains is essential to better understand infectivity and virulence and to track coronavirus disease 2019 (COVID‐19) cases and outbreaks. We performed whole‐genome sequencing of 27 SARS‐CoV‐2 strains isolated between January 2020 and April 2020. A total of 54 mutations in different genomic regions was found. The D614G mutation, first detected in March 2020, was identified in 18 strains and was more likely associated with a lower cycle threshold (<25) in real‐time reverse‐transcription polymerase chain reaction diagnostic tests than the original D614 (prevalence ratio = 2.75; 95% confidence interval, 1.19–6.38). The integration of sequencing and epidemiological data suggests that SARS‐CoV‐2 transmission in both quarantine areas and in the community in Vietnam occur at the beginning of the epidemic although the country implemented strict quarantine quite early, with strict contact tracing, and testing. These findings provide insights into the nature of the epidemic, as well as shape strategies for COVID‐19 prevention and control in Vietnam. [ABSTRACT FROM AUTHOR]

Eight different stationary phases based on two aminopropyl silicas of different brands suitable for multimodal chromatography applications have been prepared by a four‐component Ugi reaction. The intention was to synthesize stationary phases significantly differing in their properties hereby demonstrating flexibility of the Ugi synthetic protocol. Diverse functional groups including a nonpolar long aliphatic chain, phenyl moiety, cholic acid scaffold, phenylboronic and monosaccharide units, charged betaine, and arginine moieties were immobilized on a silica surface. The novel sorbents were extensively characterized by elemental analysis, Raman spectroscopy, and chromatography. Considering the anchored chemical structures covalently bonded to the silica surface, reversed‐phase, hydrophilic, and ion‐exchange separation modes were expected. The chromatographic evaluation was performed directed to map the potential of the individual columns specifically in the mentioned chromatographic modes. The Ugi synthetic protocol has proven to be a simple, feasible, and versatile tool for the synthesis of sorbents of variable properties. The newly prepared stationary phases differed considerably in hydrophobicity and ion‐exchange ability. A significant influence of the supporting aminopropyl silica on the final chromatographic behavior was observed. Finally, one practical example confirming applicability of the newly prepared sorbents was demonstrated in separation of cytarabine. [ABSTRACT FROM AUTHOR]

In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS‐CoV‐2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human‐to‐human transmission of SARS‐CoV‐2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi‐morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies. Highlights: Transmission of SARS‐CoV‐2 is a global public health and clinical concern.This report describes clinical features, virus isolation, and complete genome sequences from the first two SARS‐CoV‐2 infections in Vietnam.Epidemiological and phylogenetic analysis suggested evidence of human‐to‐human transmission of SARS‐CoV‐2. Comparison of SARS‐CoV‐2 strains isolated from these two patients with those from Wuhan showed high similarities.Nonsynonymous substitutions existed in the ORF1ab region of the viral sequence.Compared with mild clinical and virological manifestations in the younger patient, the elderly suffered from pneumonia, prolonged viral shedding, and residual lung damage. [ABSTRACT FROM AUTHOR]

New SARS-CoV-2 variant of concern imported from the United Kingdom to Vietnam, December 2020 Here, we describe clinical, epidemiological characteristics, and sequencing of the B.1.1.7 variant from a patient with pneumonia imported from the United Kingdom to Vietnam. On December 14, 2020, the United Kingdom reported a newly identified variant of SARS-CoV-2 (known as VOC 202012/01 or B.1.1.7 lineage).1,2 This carries several mutations, including the spike protein N501Y substitution and 69-70del, resulting in substantially increased transmission rates of 50-74% greater than other variants3; the variant rapidly circulates worldwide.4 In such a context, a full characterization of this variant is essential for a further development of response strategies to COVID-19. [Extracted from the article]

Abstract: We have previously reported that silica nanoparticles (SiNPs) of nominal size 50 nm (Si50) induce the pro‐inflammatory cytokines CXCL8 and IL‐6 in BEAS‐2B cells, via mechanisms involving MAPK p38, TACE‐mediated TGF‐α release and the NF‐κB pathway. In this study, we examined whether these findings are cell specific or might be extended to another epithelial lung cell model, HBEC3‐KT, and also to SiNPs of a smaller size (nominal size of 10 nm; Si10). The TEM average size of Si10 and Si50 was 10.9 and 34.7 nm, respectively. The surface area (BET) of Si10 was three times higher than for Si50 per mass unit. With respect to hydrodynamic size (DLS), Si10 in exposure medium showed a higher z‐average for the main peak than Si50, indicating more excessive agglomeration. Si10 strongly induced CXCL8 and IL‐6, as assessed by ELISA and RT‐PCR, and was markedly more potent than Si50, even when adjusted to equal surface area. Furthermore, Si10 was far more cytotoxic, measured as lactate dehydrogenase (LDH) release, than Si50 in both epithelial cell cultures. With respect to signalling pathways, Western analysis and experiments with and without inhibition of MAPK, TACE and NF‐κB (synthetic inhibitors) revealed that p38‐phosphorylation, TACE‐mediated TGF‐α release and NF‐κB activation seem to be important triggering mechanisms for both Si50 and Si10 in the two different lung epithelial cell cultures. In conclusion, the identified signalling pathways are suggested to be important in inducing cytokine responses in different epithelial cell types and also for various sizes of silica nanoparticles. [ABSTRACT FROM AUTHOR]

This study examines the impact of having a credit rating on earnings management (EM) through accruals and real activities manipulation by initial public offering (IPO) firms. We find that firms going public with a credit rating are less likely to engage in income-enhancing accrual-based and real EM in the offering year. The monitoring by a credit rating agency (CRA) and the reduced information asymmetry due to the provision of a credit rating disincentivise rated issuers from managing earnings. We also suggest that the participation of a reputable auditing firm is crucial for CRAs to effectively restrain EM. Moreover, we document that for unrated issuers, at-issue income-increasing EM is not linked to future earnings and is negatively related to post-issue long-run stock performance. However, for rated issuers, at-issue income-increasing EM is positively associated with subsequent accounting performance and is unrelated to long-run stock performance following the offering. The evidence indicates that managers in unrated firms generally manipulate earnings to mislead investors, while managers in rated firms tend to exercise their accounting and operating discretion for informative purposes. [ABSTRACT FROM AUTHOR]

In humanized mice, the T-cell repertoire is derived from genetically identical human progenitors in distinct animals. Thus, careful comparison of the T-cell repertoires of humanized mice with those of humans may reveal the contribution of genetic determinism on T-cell repertoire formation. Here, we performed a comprehensive assessment of the distribution of V-J combinations of the human β chain of the T-cell receptor (hTRBV) in NOD.SCID.γc−/− (NSG) humanized mice. We observed that numerous V-J combinations were equally distributed in the thymus and in the periphery of humanized mice compared with human references. A global analysis of the data, comparing repertoire perturbation indices in humanized NSG mice and unrelated human PBMCs, reveals that 50% of the hTRBV families significantly overlapped. Using multivariate ranking and bootstrap analyses, we found that 18% of all possible V-J combinations contributed close to 50% of the expressed diversity, with significant over-representation of BV5-J1.1+1.2 and BV6-J1.1+1.2 rearrangements. Finally, comparison of CD3− and CD3+ thymocyte repertoires indicated that the observed V-J combination overlap was already present before TCR-MHC selection in the thymus. Altogether, our results show that half of the T-cell repertoire combinatorial diversity in humans is genetically determined. [ABSTRACT FROM AUTHOR]