A stem-loop RNA RIG-I agonist protects against acute and chronic SARS-CoV-2 infection in mice

As SARS-CoV-2 continues to cause morbidity and mortality around the world, there is an urgent need for the development of effective medical countermeasures. Here, we assessed the antiviral capacity of a minimal RIG-I agonist, stem-loop RNA 14 (SLR14), in viral control, disease prevention, post-infection therapy, and cross-variant protection in mouse models of SARS-CoV-2 infection. A single dose of SLR14 prevented viral infection in the lower respiratory tract and development of severe disease in a type I interferon (IFN-I)–dependent manner. SLR14 demonstrated remarkable prophylactic protective capacity against lethal SARS-CoV-2 infection and retained considerable efficacy as a therapeutic agent. In immunodeficient mice carrying chronic SARS-CoV-2 infection, SLR14 elicited near-sterilizing innate immunity in the absence of the adaptive immune system. In the context of infection with variants of concern (VOCs), SLR14 conferred broad protection against emerging VOCs. These findings demonstrate the therapeutic potential of SLR14 as a host-directed, broad-spectrum antiviral for early post-exposure treatment and treatment of chronically infected immunosuppressed patients.     

Gender effects in diagnosing alcohol abuse and dependence

Using a national population sample of 43,809 adults, male and female responses were compared for 41 indicators of alcohol abuse and dependence. While men reported all indicators more often than did women, the male to female ratio of positive responses varied according to both the construct represented by the item and its underlying prevalence. Items that might be construed as signs of weakness — physical effects, psychological effects, and loss of control or powerlessness — had lower male/female ratios than other items. Excess male prevalence was greatest for the least prevalent indicators. The paper presents alternative interpretations of these findings and discusses their implications for diagnostic classification.     

The first prenatal diagnosis for veno-occlusive disease and immunodeficiency syndrome, an autosomal recessive condition associated with mutations in SP110

OBJECTIVES: We present the first prenatal diagnosis of familial hepatic veno-occlusive disease with immunodeficiency (VODI). Homozygous mutations in the gene SP110 are the genetic basis of VODI. The proband in this report presented at three months of age with hepatomegaly hepatic failure and was found to have hypogammaglobulinemia. He died one month after hepatic transplant at eight months of age due to hemophagocytic syndrome. DNA testing detected a homozygous truncating mutation in exon 5; SP110 c.642delC. Prenatal testing was offered to this family in a subsequent pregnancy. METHODS: Chorion villus was sampled at 12 weeks' gestation. DNA was extracted using standard techniques, and sequencing of SP110 exon 5 was performed using flanking primers. Maternal contamination was excluded by examining STR markers in CVS and maternal DNA. RESULTS: A heterozygous SP110 c.642delC mutation was detected in exon 5. This mutation was present in heterozygous form in both parents. CONCLUSIONS: The prenatal test result is predictive of a child with a normal immune and hepatic phenotype. This report presents the first prenatal molecular diagnosis for VODI and shows the importance of molecular genetic research in not only defining the aetiology of syndromes but also in assisting reproductive choices through the collaboration of genetic and feto-maternal services.     

Effect of left ventricular ejection fraction (LVEF) on mortality of total arch replacement in subacute/chronic type A aortic dissection

BackgroundPreoperative reduced left ventricular ejection fraction (LVEF) is a prognostic factor for postoperative mortality following cardiovascular surgery. We investigated the relationship between the LVEF and the outcome of total arch replacement (TAR) in patients with subacute/chronic type A aortic dissection (TAAD).MethodsA total of 136 patients with subacute/chronic TAAD who received a TAR at Beijing Anzhen hospital from January 2015 to January 2018 were included in the analysis. Univariable and multivariable Cox proportional hazards regression analyses were performed to assess the relationship between the LVEF and the surgical outcome in this subset of patients.ResultsThe in-hospital mortality rate 4.4%, and 6.6% of patients experienced neurologic complications. During the median follow-up period of 3.97 years [interquartile range (IQR) 3.20–4.67 years], the all-cause mortality was 10.3% (14/136). The multivariable Cox proportional hazards analysis demonstrated that reduced LVEF was an independent predictor of mid-term mortality (hazards ratio =0.93, 95% CI: 0.86–0.99, P=0.03). The Kaplan-Meier survival analysis showed that patients with a LVEF <55% had a significantly worse prognosis than those with a LVEF ≥55%.ConclusionsDuring the mid-term follow-up period, subacute/chronic TAAD patients had a satisfactory surgical survival rate following TAR. Patients with a reduced LVEF had higher postoperative mortality following TAR. Thus, subacute/chronic TAAD patients with LVEF <55% should be carefully evaluated to determine their suitability for elective repair with TAR.     

Learning Through Service: Student Perceptions on Volunteering at Interprofessional Hepatitis B Student-run Clinics

Student-run clinics (SRCs) are widespread, but studies on their educational impact are limited. We surveyed preclinical medical, nursing, and pharmacy students about their experiences in a hepatitis B elective which provided opportunities to they could volunteer at hepatitis B screening and vaccination SRCs. Student responses revealed positive perceptions of the volunteer experience. Benefits included interacting with patients, developing clinical skills, providing service to disadvantaged populations, and collaborating with health professional peers. Students who participated in clinic reported enhanced skills compared to those who did not attend. SRCs play a valuable role in instilling positive attitudes and improving skills.     

Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation?

The Banff schema incorporates a semiquantitative scoring system for grading of acute cellular rejection (ACR) of the liver allograft. The Banff rejection activity index (RAI) comprises 3 components scored from 0 to 3: venous endothelial inflammation (E); bile duct damage (B); and portal inflammation (P); the scores are combined to an overall score (the RAI). The purpose of this research was to determine the prognostic value of the Banff RAI score in predicting the response to increased immunosuppression and the long-term outcome of the graft. A retrospective study was done of patients undergoing primary liver transplantation between January 2000 and October 2004 with tacrolimus-based immunosuppression; 495 patients were included, 231 had histologically-confirmed ACR, 193 responded to 1 cycle of high-dose steroids. There was no correlation between the total RAI score and response to steroids, resistant rejection, development of chronic rejection, or graft survival. The E score was related to patient survival, a lower score being associated with a worse outcome (P = 0.048). In multivariable analysis, serum bilirubin, serum aspartate aminotransferase, and E score were significant predictors of death (P = 0.012). In univariable analysis, B score and bilirubin were significantly related to "resistant rejection" (P = 0.018 and 0.002, respectively), but only bilirubin was significant in multivariable analysis (logistic regression). In conclusion, although the Banff RAI score is a useful marker of the severity of rejection, neither the total RAI score nor any of the individual components correlated with response to steroids or graft survival.     

Interventions to increase influenza vaccination rates in veterans with spinal cord injuries and disorders

OBJECTIVE: To increase the percentage of veterans with spinal cord injuries and disorders (SCI&D) who receive annual influenza vaccinations. DESIGN: A repeated measures quality improvement project using several integrated evidence-based interventions. SETTING: 23 Veterans Affairs (VA) SCI Centers. PATIENTS: Veterans with SCI&D average age = 57.3 years (range 21-102 y). INTERVENTIONS: Patient reminder letters and education; provider reminders and posters; computerized clinical reminders for vaccination targeted to SCI & D; standing orders. MAIN OUTCOME MEASURES: Patient self-reported vaccination status. RESULTS: Baseline vaccination rate was 33% in fiscal year (FY) 2001. The percentage of veterans with SCI&D who reported receiving vaccinations increased from 62.5% in year 1 (FY2002) to 67.4% in FY2003 (P = 0.004); for individuals younger than 50 years of age, rates increased from 50% to 54%. Predictors of vaccination were age 65 years of age or older, VA health care visit in past year, nonsmoker, believing vaccination is important, having a health condition that may contribute to respiratory complications, and self-reported influenza in prior year. CONCLUSIONS: Vaccination rates were higher than baseline and higher than reported for other high-risk groups. Interventions that incorporate system-wide approaches plus patient and provider education and reminders were moderately effective in increasing vaccination rates. Targeting younger persons, smokers, and those who do not use VA care may further improve rates.