Infectious diseases modelling

BACKGROUND AIMS: HCV infection continues to be a major global health burden, despite effective antiviral treatments. The urgent need for a protective vaccine is hindered by the scarcity of suitable HCV permissive animal models tractable in vaccination and challenge studies. Currently, only antibody neutralization studies in infectious cell culture systems or studies of protection by passive immunization of human-liver chimeric mice offer the possibility to evaluate the effect of vaccine-induced antibodies...

The discovery of safe and efficient inhibitors against efflux pumps as well as metallo-β-lactamases (MBL) is one of the main challenges in the development of multidrug-resistant (MDR) reversal agents which can be utilized in the treatment of carbapenem-resistant Gram-negative bacteria. In this study, we have identified that introduction of an ethylene-linked sterically demanding group at the 3-OH position of the previously reported MDR reversal agent di-F-Q endows the resulting compounds with hereto unknown multitarget inhibitory activity against both efflux pumps and broad-spectrum β-lactamases including difficult-to-inhibit MBLs...

As one of the leading causes of global mortality and morbidity, various neurological diseases cause social and economic burdens. Despite significant advances in the treatment of neurological diseases, establishing a proper disease model, especially for degenerative and infectious diseases, remains a major challenging issue. For long, mice were the model of choice but suffered from serious drawbacks of differences in anatomical and functional aspects of the nervous system. Furthermore, the collection of post-mortem brain tissues limits their usage in cultured cell lines...

Growing evidence demonstrates the key role of the gut microbiota in human health and disease. The recent success of microbiotherapy products to treat recurrent Clostridioides difficile infection has shed light on its potential in conditions associated with gut dysbiosis, such as acute graft-versus-host disease, intestinal bowel diseases, neurodegenerative diseases, or even cancer. However, the difficulty in defining a "good" donor as well as the intrinsic variability of donor-derived products' taxonomic composition limits the translatability and reproducibility of these studies...

BACKGROUND: Mental health (MH) is extremely relevant when referring to people living with a chronic disease, such as people living with HIV (PLWH). In fact - although life expectancy and quality have increased since the advent of antiretroviral therapy (ART) - PLWH carry a high incidence of mental disorders, and this burden has been exacerbated during the COVID-19 pandemic. In this scenario, UNAIDS has set new objectives for 2025, such as the linkage of at least 90% of PLWH to people-centered, context-specific MH services...

Zoonoses such as ZIKV and SARS-CoV-2 pose a severe risk to global health. There is urgent need for broad antiviral strategies based on host-targets filling gaps between pathogen emergence and availability of therapeutic or preventive strategies. Significant reduction of pathogen titers decreases spread of infections and thereby ensures health systems not being overloaded and public life to continue. Based on previously observed interference with FGFR1/2-signaling dependent impact on interferon stimulated genes (ISGs)-expression, we identified Pim kinases as promising druggable cellular target...

INTRODUCTION: Oral corticosteroids are the primary treatment for several autoimmune conditions. The risk of long-term implant, bone health, and infectious-related complications in patients taking chronic oral corticosteroids before total knee arthroplasty (TKA) is unknown. We compared the 10-year cumulative incidence of revision, periprosthetic joint infection (PJI), fragility fracture (FF), and periprosthetic fracture (PPF) following TKA in patients who had and did not have preoperative chronic oral corticosteroid use...

OBJECTIVE: To determine the incidence of mortality and its predictors among pulmonary TB (PTB) survivors treated at a rural Ugandan tertiary hospital. METHODS: We conducted a retrospective chart review of data between 2013 and 2023. We included all people that met the WHO's definition of tuberculosis cure and traced them or their next of kin to determine vital status (alive/deceased). We estimated the cumulative incidence of mortality per 1,000 population, crude all-cause mortality rate per 1,000 person-years, and median years of potential life lost (YPLL) for deceased individuals...

Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota...

BACKGROUND: No national study has evaluated changes in the appropriateness of US outpatient antibiotic prescribing across all conditions and age groups after the coronavirus disease 2019 (COVID-19) outbreak in March 2020. METHODS: This was an interrupted time series analysis of Optum's de-identified Clinformatics Data Mart Database, a national commercial and Medicare Advantage claims database. Analyses included prescriptions for antibiotics dispensed to children and adults enrolled during each month during 2017-2021...

BACKGROUND: Primary care physicians played an important role in the global response during the COVID-19 pandemic, but with the absence of laboratory and diagnostics services, the move to telehealth and the focus on respiratory assessment, they faced increased uncertainty when making clinical decisions. OBJECTIVES: This paper aims to examine the impact of the pandemic on decisions made by primary care physicians, as measured by referrals to chest X-ray and laboratory tests and by prescriptions of antibiotics...

Rationale: A mature tissue resident macrophage (TRM) population residing in the peritoneal cavity has been known for its unique ability to migrate to peritoneally located injured tissues and impart wound healing properties. Here, we sought to expand on this unique ability of large peritoneal macrophages (LPMs) by investigating whether these GATA6+ LPMs could also intravasate into systemic circulation and migrate to extra-peritoneally located lungs upon ablating lung-resident alveolar macrophages (AMs) by intranasally administered clodronate liposomes in mice...

BACKGROUND: Throughout the SARS-CoV-2 pandemic, policymakers have had to navigate between recommending voluntary behaviour change and policy-driven behaviour change to mitigate the impact of the virus. While individuals will voluntarily engage in self-protective behaviour when there is an increasing infectious disease risk, the extent to which this occurs and its impact on an epidemic is not known. METHODS: This paper describes a deterministic disease transmission model exploring the impact of individual avoidance behaviour and policy-mediated avoidance behaviour on epidemic outcomes during the second wave of SARS-CoV-2 infections in Ontario, Canada (September 1, 2020 to February 28, 2021)...

The complex interactions were performed among non-pharmaceutical interventions, vaccinations, and hosts for all epidemics in mainland China during the spread of COVID-19. Specially, the small-scale epidemic in the city described by SVEIR model was less found in the current studies. The SVEIR model with control was established to analyze the dynamical and epidemiological features of two epidemics in Jinzhou City led by Omicron variants before and after Twenty Measures. In this study, the total population ( N ) of Jinzhou City was divided into five compartments: the susceptible ( S ), the vaccinated ( V ), the exposed ( E ), the infected ( I ), and the recovered ( R )...

This opinion piece emphasies the critical role of translational research in enhancing the UK's resilience against future pandemics. The COVID-19 pandemic demonstrated the lifesaving potential of scientific innovation, including genomic tracking of SARS-CoV-2, vaccine development, data linkage, modelling, and new treatments. These advances, achieved through collaborations between academic institutions, industry, government, public health bodies, and the NHS, occurred at an unprecedented pace. However, the UK's pandemic preparedness planning, as reflected in the 2016 Exercise Cygnus report, notably lacked provision for scientific innovation...

BACKGROUND: Within Laos, the vaccination coverage rates with the monovalent hepatitis B birth dose vaccine and hepatitis B antigen-containing combination vaccines remain stagnant with 75% and 64%, respectively, in 2021. In this study, we used data from the Multiple Indicator Cluster Surveys to identify possible factors that represent barriers for receiving these childhood vaccinations. METHODS: Data from the Multiple Indicator Cluster Surveys in 2011/12 and 2017 were analysed to examine factors associated with receiving the hepatitis B-containing vaccines using regression modelling...

RATIONALE & OBJECTIVE: Long pentraxin-3 (PTX-3) serves as a biomarker for prognosticating adverse clinical outcomes in individuals with chronic kidney disease (CKD). The objective of the current meta-analysis was to evaluate the prognostic efficacy of PTX-3 in patients with CKD. In addition, we compared the prognostic effectiveness of PTX-3 and the short pentraxin C-reactive protein (CRP) in the identical cohort of patients with CKD. STUDY DESIGN: A systematic review and meta-analysis...

The rapid acceleration of global warming has led to an increased burden of high temperature-related diseases (HTDs), highlighting the need for advanced evidence-based management strategies. We have developed a conceptual framework aimed at alleviating the global burden of HTDs, grounded in the One Health concept. This framework refines the impact pathway and establishes systematic data-driven models to inform the adoption of evidence-based decision-making, tailored to distinct contexts. We collected extensive national-level data from authoritative public databases for the years 2010-2019...

INTRODUCTION: Differences in control measures and response speeds between regions may be responsible for the differences in the number of infections of global infectious diseases. Therefore, this article aims to examine the decay stage of global infectious diseases. We demonstrate our method by considering the first wave of the COVID-19 epidemic in 2020. METHODS: We introduce the concept of the attenuation rate into the varying coefficient SEIR model to measure the effect of different cities on epidemic control, and make inferences through the integrated adjusted Kalman filter algorithm...

CPPs, or Cell-Penetrating Peptides, offer invaluable utility in disease treatment due to their ability to transport various therapeutic molecules across cellular membranes. Their unique characteristics, such as biocompatibility and low immunogenicity, make them ideal candidates for delivering drugs, genes, or imaging agents directly into cells. This targeted delivery enhances treatment efficacy while minimizing systemic side effects. CPPs exhibit versatility, crossing biological barriers and reaching intracellular targets that conventional drugs struggle to access...