Improving public health training and research capacity in Africa: a replicable model for linking training to health and socio-demographic surveillance data

Background: Research training for public health professionals is key to the future of public health and policy in Africa. A growing number of schools of public health are connected to health and socio-demographic surveillance system field sites in developing countries, in Africa and Asia in particular. Linking training programs with these sites provides important opportunities to improve training, build local research capacity, foreground local health priorities, and increase the relevance of research to local health policy. Objective: To increase research training capacity in public health programs by providing targeted training to students and increasing the accessibility of existing data. Design: This report is a case study of an approach to linking public health research and training at the University of the Witwatersrand. We discuss the development of a sample training database from the Agincourt Health and Socio-demographic Surveillance System in South Africa and outline a concordant transnational intensive short course on longitudinal data analysis offered by the University of the Witwatersrand and the University of Colorado-Boulder. This case study highlights ways common barriers to linking research and training can be overcome. Results and Conclusions: This collaborative effort demonstrates that linking training to ongoing data collection can improve student research, accelerate student training, and connect students to an international network of scholars. Importantly, the approach can be adapted to other partnerships between schools of public health and longitudinal research sites

Real-time imaging of hepatitis C virus infection using a fluorescent cell-based reporter system

Author Manuscript 2010 August 1Hepatitis C virus (HCV), which infects 2–3% of the world population, is a causative agent of chronic hepatitis and the leading indication for liver transplantation1. The ability to propagate HCV in cell culture (HCVcc) is a relatively recent breakthrough and a key tool in the quest for specific antiviral therapeutics. Monitoring HCV infection in culture generally involves bulk population assays, use of genetically modified viruses and/or terminal processing of potentially precious samples. Here we develop a cell-based fluorescent reporter system that allows sensitive distinction of individual HCV-infected cells in live or fixed samples. We demonstrate use of this technology for several previously intractable applications, including live-cell imaging of viral propagation and host response, as well as visualizing infection of primary hepatocyte cultures. Integration of this reporter with modern image-based analysis methods could open new doors for HCV research.New York (State). Dept. of Health (Empire State Stem Cell Fund Contract C023046)United States. Public Health Service (Grant R01 DK56966)National Institutes of Health (U.S.) (Roadmap for Medical Research Grant 1 R01 DK085713-01)Howard Hughes Medical Institute (Investigator

Updated overall survival from the MONALEESA-3 trial in postmenopausal women with HR+/HER2− advanced breast cancer receiving first-line ribociclib plus fulvestrant

Background The phase III MONALEESA-3 trial included first- (1L) and second-line (2L) patients and demonstrated a significant overall survival (OS) benefit for ribociclib + fulvestrant in patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative (HR+/HER2−) advanced breast cancer (ABC) in the final protocol-specified and exploratory (longer follow-up) OS analyses. At the time of these analyses, the full OS benefit of 1L ribociclib was not completely characterized because the median OS (mOS) was not reached. As CDK4/6 inhibitor (CDK4/6i) + endocrine therapy (ET) is now a preferred option for 1L HR+/HER2− ABC, we report an exploratory analysis (median follow-up, 70.8 months; 14.5 months longer than the prior analysis) to fully elucidate the OS benefit in the MONALEESA-3 1L population. Methods Postmenopausal patients with HR+/HER2− ABC were randomized 2:1 to 1L/2L fulvestrant + ribociclib or placebo. OS in 1L patients (de novo disease or relapse > 12 months from completion of [neo]adjuvant ET) was assessed by Cox proportional hazards model and Kaplan–Meier methods. Progression-free survival 2 (PFS2) and chemotherapy-free survival (CFS) were analyzed. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615). Results At data cutoff (January 12, 2022; median follow-up time, 70.8 months), mOS was 67.6 versus 51.8 months with 1L ribociclib versus placebo (hazard ratio (HR) 0.67; 95% CI 0.50–0.90); 16.5% and 8.6% of ribociclib and placebo patients, respectively, were still receiving treatment. PFS2 (HR 0.64) and CFS (HR 0.62) favored ribociclib versus placebo. Among those who discontinued treatment, 16.7% and 35.0% on ribociclib or placebo, respectively, received a subsequent CDK4/6i. No new safety signals were observed. Conclusions This analysis of MONALEESA-3 reports the longest mOS thus far (67.6 months) for 1L patients in a phase III ABC trial. These results in a 1L population show that the OS benefit of ribociclib was maintained through extended follow-up, further supporting its use in HR+/HER2− ABC.This work was supported by Novartis Pharmaceuticals Corporation. The funder of this study, in agreement with the authors and the study steering committee members, designed this study. Representatives of the trial sponsor performed data collection and the subsequent analysis

Corrigendum to ‘Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival’: [Annals of Oncology Volume 32, Issue 8, August 2021, Pages 1015-1024](S0923753421015532)(10.1016/j.annonc.2021.05.353)

peer reviewedThe authors regret that at the time the article was published, Supplementary Table S2 contained errors. This has now been corrected. The authors would like to apologise for any inconvenience caused

Stability of Yellow Fever Virus under Recombinatory Pressure as Compared with Chikungunya Virus

Recombination is a mechanism whereby positive sense single stranded RNA viruses exchange segments of genetic information. Recent phylogenetic analyses of naturally occurring recombinant flaviviruses have raised concerns regarding the potential for the emergence of virulent recombinants either post-vaccination or following co-infection with two distinct wild-type viruses. To characterize the conditions and sequences that favor RNA arthropod-borne virus recombination we constructed yellow fever virus (YFV) 17D recombinant crosses containing complementary deletions in the envelope protein coding sequence. These constructs were designed to strongly favor recombination, and the detection conditions were optimized to achieve high sensitivity recovery of putative recombinants. Full length recombinant YFV 17D virus was never detected under any of the experimental conditions examined, despite achieving estimated YFV replicon co-infection levels of ∼2.4×106 in BHK-21 (vertebrate) cells and ∼1.05×105 in C710 (arthropod) cells. Additionally YFV 17D superinfection resistance was observed in vertebrate and arthropod cells harboring a primary infection with wild-type YFV Asibi strain. Furthermore recombination potential was also evaluated using similarly designed chikungunya virus (CHIKV) replicons towards validation of this strategy for recombination detection. Non-homologus recombination was observed for CHIKV within the structural gene coding sequence resulting in an in-frame duplication of capsid and E3 gene. Based on these data, it is concluded that even in the unlikely event of a high level acute co-infection of two distinct YFV genomes in an arthropod or vertebrate host, the generation of viable flavivirus recombinants is extremely unlikely

The effect of basic fibroblast growth factor on regeneration in a surgical wound model of rat submandibular glands

This study developed an animal model of surgically wounded submandibular glands (SMGs) and investigated the effects of collagen gel with basic fibroblast growth factor (bFGF) on tissue regeneration of surgically wounded SMGs in vivo. The animal model was produced by creating a surgical wound using a 3-mm diameter biopsy punch in SMGs. The wound was filled with collagen gel with bFGF (bFGF group) or without bFGF (control group). In the animal model of surgically wounded SMGs, salivary glands without scar tissue around the wound area were observed with smaller areas of collagen gel. Small round and spindle-shape cells invaded the collagen gel in both groups after operation day (AOD) 5, and this invasion dramatically increased at AOD 7. Host tissue completely replaced the collagen gel at AOD 21. The invading immune cells in the group treated with collagen gel with bFGF were positive for vimentin, α-smooth muscle actin (αSMA), CD49f, c-kit and AQP5 at AOD 7. Similarly, the mRNA expression of vimentin, αSMA, CD49f, keratin19 and AQP5 was also increased. This study suggests that the use of collagen gels with bFGF improves salivary gland regeneration

TREATMENT OF ANXIODEPRESSIVE DISORDERS IN PATIENTS WITH CARDIOVASCULAR DISEASES

Sixty patients at the age of 43 to 79 years with anxiodepressive symptoms with comorbid cardiovascular disease have been examined after admission to psychotherapeutic department. Patients have been divided into two groups. The first group including 30 patients were treated by the tricyclic antidepressant amitriptyline with the average daily dose of 34.4 ± 12.9 mg. The 30 patients from the second group were treated by antidepressants of the selective serotonin reuptake inhibitors group. The sociodemographic characteristics in both groups did not differ significantly; the severity of cardiovascular disease, additional somatic and other diseases were certainty lower in the first group than in the second (p < 0.05). Examination of the patients with the use of Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale (HDRS and HARS) was carried out three times: at admission, in 1 week and in 4 weeks. At the time of admission, anxiety and depression in the first group were more expressed (p < 0.05) than in the second due to frequent psychogeny. The treatment scheme included tranquilizers, neuroleptics, neurometabolic drugs, basic cardiotropic therapy and psychotherapy. After 4 weeks anxiodepressive symptoms were more than 50 % reduced in both groups: 61 % in the first group and 50.7 % in the second group by the HDRC scale; 65.9 % in the first group and 59.8 % in the second group by the HARS scale. It has been shown that the small doses of antidepressant including amitriptyline involved in the complex treatment scheme were efficient and did not cause cardiotoxic effect