Development of a glycoconjugate vaccine to prevent invasive Salmonella Typhimurium infections in sub-Saharan Africa

Invasive infections associated with non-typhoidal Salmonella (NTS) serovars Enteritidis (SE), Typhimurium (STm) and monophasic variant 1,4,[5],12:i:- are a major health problem in infants and young children in sub-Saharan Africa, and currently, there are no approved human NTS vaccines. NTS O-polysaccharides and flagellin proteins are protective antigens in animal models of invasive NTS infection. Conjugates of SE core and O-polysaccharide (COPS) chemically linked to SE flagellin have enhanced the anti-COPS immune response and protected mice against fatal challenge with a Malian SE blood isolate. We report herein the development of a STm glycoconjugate vaccine comprised of STm COPS conjugated to the homologous serovar phase 1 flagellin protein (FliC) with assessment of the role of COPS O-acetyls for functional immunity. Sun-type COPS conjugates linked through the polysaccharide reducing end to FliC were more immunogenic and protective in mice challenged with a Malian STm blood isolate than multipoint lattice conjugates (>95% vaccine efficacy [VE] versus 30-43% VE). Immunization with de-O-acetylated STm-COPS conjugated to CRM197 provided significant but reduced protection against STm challenge compared to mice immunized with native STm-COPS:CRM197 (63-74% VE versus 100% VE). Although OPS O-acetyls were highly immunogenic, post-vaccination sera that contained various O-acetyl epitope-specific antibody profiles displayed similar in vitro bactericidal activity when equivalent titers of anti-COPS IgG were assayed. In-silico molecular modeling further indicated that STm OPS forms a single dominant conformation, irrespective of O-acetylation, in which O-acetyls extend outward and are highly solvent exposed. These preclinical results establish important quality attributes for an STm vaccine that could be co-formulated with an SE-COPS:FliC glycoconjugate as a bivalent NTS vaccine for use in sub-Saharan Africa

AI’s potential for Artificial Phantom Mimicking Tissue of the Human Breast Electrical Properties

National audienceIn this study, we present an assessment method of Early Breast Cancer Detection based on Artificial Intelligence (AI). This method includes prediction, setting and measurement of several human breast phantom mixtures for Microwave Imaging (MWI). These developed Breast Phantoms have realistic dielectric properties (important for Radar Microwave Imaging Systems & Ethical Non-Animal-Testing). We Developed Heterogeneous mimicking tissue architecture for mimicking Breast Tissues (Fat, Regular Fat, Gland, Body Fluid, Blood, Muscle-Tumor, Skin Dry, and Skin Wet) and tested using ultrawideband frequency (0.2 GHz-4.5 GHz) by a modern Vector Network Analyzer. Our qualitative and quantitative research includes the methodology and results for using the material's dielectric parameters and AI algorithms for emulation of real Breast Tissues for Microwave Imaging Pre-clinical trials

Pre-implementation Assessment of Tobacco Cessation Interventions in Substance Use Disorder Residential Programs in California

BackgroundAcross the United States, substance use disorder (SUD) treatment programs vary in terms of tobacco-related policies and cessation services offered. Implementation of tobacco-related policies within this setting can face several barriers. Little is known about how program leadership anticipate such barriers at the pre-implementation phase. This study used the Consolidated Framework for Implementation Research (CFIR) during the pre-implementation stage to identify factors that may influence the implementation stage of tobacco-related cessation policies and services in residential SUD programs.MethodsWe conducted semi-structured qualitative interviews with sixteen residential treatment program directors in California. The analysis was guided by a deductive approach using CFIR domains and constructs to develop codes and identify themes. ATLAS.ti software was used to facilitate thematic analysis of interview transcripts.FindingsThemes that arose as anticipated facilitators for implementation included the relative advantage of the intervention vs. current practice, external policies/incentives to support tobacco-related policy, program directors' strong commitment and high self-efficacy to incorporate cessation into SUD treatment, and recognizing the importance of planning and engaging opinion leaders. Potential barriers included the SUD recovery culture, low stakeholder engagement, organizational culture, lack of workforce expertise, and lack of reimbursement for smoking cessation services.ConclusionTo support successful implementation of tobacco-related organizational change interventions, staff and clients of residential SUD programs require extensive education about the effectiveness of evidence-based medications and behavioral therapies for treating tobacco dependence. Publicly funded SUD treatment programs should receive support to address tobacco dependence among their clients through expanded reimbursement for tobacco cessation services

Comparative analysis of hatcheries contribution to poor development of day-old chicks based on biological and immunological performance

Background and Aim: The quality of day-old chicks is a cornerstone to successful poultry production. Chicks with a poor quality start slowly in the field and may have high feed intake, poor growth rate, and poor feed conversion ratio. The current study aimed to assess chick quality challenges encountered from day-old chicks hatched in most commercial hatcheries in Ghana. Materials and Methods: A total of 300 day-old chicks each were obtained from commercial hatcheries in Ghana and Europe. The chicks were labeled as locally hatched broiler day-old chicks (LBDOC) and foreign hatched broiler day-old chicks (FBDOC), respectively. Chicks were reared and monitored from day old to 21 days post-hatch. Sample of chicks (n=25) from each hatchery was euthanized weekly at 1, 7, 14, and 21 days and blood samples collected for analysis. The parameters measured included physical, hematological, immunological, histological, and bacteriological characteristics. All data were analyzed by SAS Proc GLM at p<0.05. Results: The live weight of chicks was higher in FBDOC compared to LBDOC on the 1st day. The chick length and shank length of FBDOC were longer than the LBDOC. The 7-day chick mortality was 6% in LBDOC as compared to 1.5% in FBDOC. The LBDOC also had a higher wet and dry residual yolk sac percentages as well as higher residual yolk sac fluid volume than the FBDOC. The rate of yolk sac disappearance of the FBDOC was higher than the LBDOC. More than half of the LBDOC had developed navel strings and leaky navel compared to FBDOC. The LBDOC recorded Escherichia coli, Proteus, Streptococcus spp., and Gram-negative bacteria in the residual yolk sac isolated through the 21 days while FBDOC recorded E. coli, Proteus, and Gram-negative bacteria. The intestinal villi count, lengths, width, and surface area were all not significantly different. The blood monocyte levels appeared higher in FBDOC than LBDOC, which give evidence of higher immunity in FBDOC than LBDOC. Conclusion: The results indicate a challenging situation in maintaining the quality of locally hatched broiler day-old-chicks compared to foreign hatched broiler-day-old-chicks. The study demonstrates that chick quality impact goes beyond the physical characteristics of chick weight and chick length, and the higher performance of FBDOC may be influenced by compliance with international hatchery standards and vaccination protocols

Wolbachia endobacteria depletion by doxycycline as antifilarial therapy is macrofilaridical in onchocerciasis

In Tanzania malaria is the leading cause of morbidity and mortality, especially in children under 5 years. The disease ranks number one in both outpatient and inpatient statistics. The socio-economic impact of malaria is so high that it contributes highly to poverty and underdevelopment. Efforts made during the past century to combat and control malaria have not been successful. The prospects of achieving the Abuja declaration targets are uncertain within the remaining period of time. Currently, the Ministry of Health through a 5-year strategic plan advocates four main approaches in the fight against the disease. These include improved case management, vector control using insecticide treated mosquito nets, prevention and control of malaria in pregnancy and epidemic preparedness, prevention and control. However, these strategies face various challenges including inadequate human, financial, and material resources; inefficiency in the healthcare system that is incapable of providing quality health services and access to prompt diagnosis and treatment; lack of an effective disease surveillance system; and an inefficient health education communication mechanism. Tanzania is at the crossroads and is challenged with the need to introduce a new antimalarial treatment regimen and the reintroduction of DDT for indoor residual spray. Unless malaria control strategy adopts an integrated approach its success is far from being realized. This article reviews the current malaria control strategies and its challenges in Tanzania and proposes new strategies. Copyrigh

High-dose testosterone treatment reduces monoamine oxidase A levels in the human brain : a preliminary report

202202 bcvcVersion of RecordOthersThis study was supported by a grant from the Austrian Science Fund to R. Lanzenberger (FWF grant number K LI 50 4 ). M. Murgas is funded by the Austrian Science Fund (FWF), D OC 33-B2 7 . L. Rischka was a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Department of Psychiatry and Psychotherapy, Medical University of Vienna.Publishe