resensitization of multidrug-resistant clinical isolates of and through phage-antibiotic synergy.

Bacteriophages are an increasingly attractive option for the treatment of antibiotic-resistant infections, but their efficacy is difficult to discern due to the confounding effects of antibiotics. Phages are generally delivered in conjunction with antibiotics, and thus, when patients improve, it is unclear whether the phages, antibiotics, or both are responsible. This question is particularly relevant for enterococcus infections, as limited data suggest phages might restore antibiotic efficacy against resistant strains.

Transforming the Health Research Workforce in Mozambique: Achievements of the Mozambique Institute for Health Education and Research (MIHER) over a 13‑Year Journey.

African research capacity is challenged by insufficient infrastructure to solicit and manage grants from local and international funding agencies. The manuscript provides an overview and discusses lessons learned about the pioneering role of the Mozambique Institute for Health Education and Research (MIHER) as the first research support center (RSC) in supporting the management of research grants in Mozambique, emphasizing its impact on research capacity development. Using mixed methods, data were comprehensively collected to identify MIHER's primary achievements from 2010 to 2023.

Considerations for prioritising clinical research using bacteriophage.

Antimicrobial resistance (AMR) poses a significant global health threat, as it contributes to prolonged illness, higher mortality rates and increased healthcare costs. As traditional antibiotics become less effective, treatments such as bacteriophage therapy offer potential solutions. The question remains, however, on how to set research priorities in the face of a growing number of antibiotic-resistant pathogens, some common and/or dangerous.

Effects of multiple mammalian herbivores and climate on grassland-shrubland transitions in the Chihuahuan Desert.

The replacement of grasses by shrubs or bare ground (xerification) is a primary form of landscape change in drylands globally with consequences for ecosystem services. The potential for wild herbivores to trigger or reinforce shrubland states may be underappreciated, however, and comparative analyses across herbivore taxa are sparse. We sought to clarify the relative effects of domestic cattle, native rodents, native lagomorphs, and exotic African oryx (Oryx gazella) on a Chihuahuan Desert grassland undergoing shrub encroachment.

Translational research priorities for bacteriophage therapeutics.

The growing threat of antimicrobial resistant (AMR) bacterial pathogens coupled with the relative dearth of promising novel antibiotics requires the discovery and development additional medical interventions. Over the past decade bacteriophages have emerged one of the most promising new tools to combat AMR pathogens. Anecdotal clinical experiences under so-called 'compassionate use' regulatory pathways as well as a limited number of clinical trials have provided ample evidence of safety and early evidence of efficacy.

Dryland state transitions alter trophic interactions in a predator-prey system.

Environmental change is expected to alter trophic interactions and food web dynamics with consequences for ecosystem structure, function and stability. However, the mechanisms by which environmental change influences top-down and bottom-up processes are poorly documented. Here, we examined how environmental change caused by shrub encroachment affects trophic interactions in a dryland.

Oral pharmacokinetics and efficacy of oral phospholipid remdesivir nucleoside prodrugs against SARS-CoV-2 in mice.

Oral broad-spectrum antivirals are urgently needed for the treatment of many emerging and contemporary RNA viruses. We previously synthesized 1--octadecyl-2--benzyl--glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug of GS-441524 (remdesivir nucleoside, RVn), and demonstrated its efficacy in a SARS-CoV-2 mouse model. Structure-activity relationship studies focusing on the prodrug scaffold identified two modifications, 3-fluoro-4-methoxy-benzyl (V2053) and 4-cyano-benzyl (V2067), that significantly enhanced the broad-spectrum antiviral activity against multiple RNA viruses when compared to V2043.

Phylogenetic assessment within a species complex of a subterranean rodent (Geomys bursarius) with conservation implications for isolated subspecies.

Range contraction and expansion from glaciation have led to genetic divergence that may be particularly pronounced in fossorial species with low dispersal. The plains pocket gopher (Geomys bursarius) is a fossorial species that ranges widely across North America but has a poorly understood phylogeny. We used mitogenomes (14,996 base pairs) from 56 individuals across seven subspecies, plus two outgroup species, to assess genetic divergence from minimum spanning trees, measure genetic distances, and infer phylogenetic trees using BEAST.

A simple solid media assay for detection of synergy between bacteriophages and antibiotics.

The emergence of antibiotic-resistant bacteria (ARB) has necessitated the development of alternative therapies to deal with this global threat. Bacteriophages (viruses that target bacteria) that kill ARB are one such alternative. Although phages have been used clinically for decades with inconsistent results, a number of recent advances in phage selection, propagation, and purification have enabled a reevaluation of their utility in contemporary clinical medicine.

Phage resistance in Klebsiella pneumoniae and bidirectional effects impacting antibiotic susceptibility.

Objectives: Bacteriophage (phage) therapy is a promising anti-infective option to combat antimicrobial resistance. However, the clinical utilization of phage therapy has been severely compromised by the potential emergence of phage resistance. Although certain phage resistance mechanisms can restore bacterial susceptibility to certain antibiotics, a lack of knowledge of phage resistance mechanisms hinders optimal use of phages and their combination with antibiotics.

ventricular assist device infections: findings from ineffective phage therapies in five cases.

Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular LVAD infection.

A Cross Sectional Study on the Bidirectional Interactions Between Leptospirosis and HIV Infection Among Patients from Maputo Central Hospital, Mozambique.

Introduction: This study aims to determine the baseline seroprevalence of leptospirosis, a zoonotic and neglected disease, in people living with HIV (PWH) in Maputo, Mozambique, and to evaluate the relationship between selected HIV-related factors that might influence risk of coinfection with leptospirosis, such as degree of immunosuppression, as assessed by CD4 cell count, World Health Organization (WHO) HIV/AIDS clinical stage and antiretroviral therapy (ART) intake.

Methods: This was a descriptive cross-sectional analysis of 157 PWH, aged over 18 years old, admitted to the Maputo Central Hospital, in Maputo, Mozambique, between March 2020 and October 2021. The study participants were recruited as a convenience sample regardless of the reasons for their admission.

Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics.

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions.

Optimizing campus-wide COVID-19 test notifications with interpretable wastewater time-series features using machine learning models.

During the COVID-19 pandemic, wastewater surveillance of the SARS CoV-2 virus has been demonstrated to be effective for population surveillance at the county level down to the building level. At the University of California, San Diego, daily high-resolution wastewater surveillance conducted at the building level is being used to identify potential undiagnosed infections and trigger notification of residents and responsive testing, but the optimal determinants for notifications are unknown. To fill this gap, we propose a pipeline for data processing and identifying features of a series of wastewater test results that can predict the presence of COVID-19 in residences associated with the test sites.

Jumbo phages are active against extensively drug-resistant eyedrop-associated infections.

Antibiotic-resistant bacteria present an emerging challenge to human health. Their prevalence has been increasing across the globe due in part to the liberal use of antibiotics that has pressured them to develop resistance. Those bacteria that acquire mobile genetic elements are especially concerning because those plasmids may be shared readily with other microbes that can then also become antibiotic resistant.

Enhanced broad spectrum in vitro antiviral efficacy of 3-F-4-MeO-Bn, 3-CN, and 4-CN derivatives of lipid remdesivir nucleoside monophosphate prodrugs.

Broad spectrum oral antivirals are urgently needed for the early treatment of many RNA viruses of clinical concern. We previously described the synthesis of 1-O-octadecyl-2-O-benzyl-glycero-3-phospho-RVn (V2043), an orally bioavailable lipid prodrug of remdesivir nucleoside (RVn, GS-441524) with broad spectrum antiviral activity against viruses with pandemic potential. Here we compared the relative activity of V2043 with new RVn lipid prodrugs containing sn-1 alkyl ether or sn-2 glycerol modifications.

Whole-genome surveillance identifies markers of drug resistance and novel genomic regions under selection in Mozambique.

Malaria is a devastating disease caused by parasites. The evolution of parasite drug resistance continues to hamper progress toward malaria elimination, and despite extensive efforts to control malaria, it remains a leading cause of death in Mozambique and other countries in the region. The development of successful vaccines and identification of molecular markers to track drug efficacy are essential for managing the disease burden.

A simple solid media assay for detection of synergy between bacteriophages and antibiotics.

The emergence of antibiotic resistant bacteria (ARB) has necessitated the development of alternative therapies to deal with this global threat. Bacteriophages (viruses that target bacteria) that kill ARB are one such alternative. While phages have been used clinically for decades with inconsistent results, a number of recent advances in phage selection, propagation and purification have enabled a reevaluation of their utility in contemporary clinical medicine.

Container Profiler: Profiling resource utilization of containerized big data pipelines.

Background: This article presents the Container Profiler, a software tool that measures and records the resource usage of any containerized task. Our tool profiles the CPU, memory, disk, and network utilization of containerized tasks collecting over 60 Linux operating system metrics at the virtual machine, container, and process levels. The Container Profiler supports performing time-series profiling at a configurable sampling interval to enable continuous monitoring of the resources consumed by containerized tasks and pipelines.

Patients' views on HCC biospecimen research: Understanding the role of race and culture through interviews.

Background: HCC is a leading cause of cancer-related mortality; there are significant racial and ethnic disparities in HCC risk and survival. Our knowledge regarding whether molecular and genetic factors contribute to these observed differences is limited by scarcity of biospecimens, which are especially scarce in minority populations. Because biospecimens are not needed for HCC diagnosis or treatment, patients are less likely to provide biospecimens solely for research purposes.

Microbiological assessment reveals that Salmonella, Shigella and Campylobacter infections are widespread in HIV infected and uninfected patients with diarrhea in Mozambique.

Diarrhea is an important cause of hospitalizations in Mozambique. However, little attention has been paid to the impact HIV infection on the prevalence or clinical manifestations of enteric bacterial infections. This study aimed to determine the prevalence of Salmonella spp.

Susceptibility antibiotic screening reveals high rates of multidrug resistance of Salmonella, Shigella and Campylobacter in HIV infected and uninfected patients from Mozambique.

Background: Antibacterial resistance is a growing concern worldwide, including in Mozambique. Diarrhea is an important cause of mortality in Mozambique, yet few local studies have reported on the resistance of bacterial pathogens in this context. Therefore, this study aims to characterize antibiotic susceptibility patterns of Salmonella, Shigella and Campylobacter spp.