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Background: In low- to middle-income countries, malnutrition is a major contributing factor in children failing to achieve their developmental potential. The prevention of malnutrition requires, among others, nutritious, diverse and safe foods in early childhood. Aim: The study aimed to determine primary caregivers’ choices and motivation for the foods they fed their children. Setting: The study was conducted among early childhood development centres in the Xhariep District, Free State. Methods: A qualitative study was undertaken. Twelve participants who met the inclusion criteria were conveniently sampled. Semi-structured interviews were conducted to find out the primary caregivers’ choices and motivation for foods they fed their children until data saturation was reached. Results: The mean age of the participants was 31 years. Nine of the participants relied on social grants as a source of income. The participants reported feeding their children mainly maize porridge, milk, juice, and water. Vegetables and meat were fed to the children once a week. Fruits were fed to the children at the beginning of the month. Conclusion: The level of education, employment status, and community support influenced the primary caregivers’ feeding practices. The content of the diets of their children was insufficient in vegetables and fruit, not only placing the children at risk of undernutrition but also at risk of obesity and micronutrient deficiencies. Primary caregivers ensured their children were fed, although limited foods were offered. Contribution: This research creates awareness of the level of social progress and access to resources within rural communities in the Xhariep district, and gives the opportunity to extend this research to confirm these findings in other poverty-stricken areas.

Abstract The objective of this study is to define CT imaging derived phenotypes for patients with hepatic steatosis, a common metabolic liver condition, and determine its association with patient data from a medical biobank. There is a need to further characterize hepatic steatosis in lean patients, as its epidemiology may differ from that in overweight patients. A deep learning method determined the spleen-hepatic attenuation difference (SHAD) in Hounsfield Units (HU) on abdominal CT scans as a quantitative measure of hepatic steatosis. The patient cohort was stratified by BMI with a threshold of 25 kg/m2 and hepatic steatosis with threshold SHAD ≥ − 1 HU or liver mean attenuation ≤ 40 HU. Patient characteristics, diagnoses, and laboratory results representing metabolism and liver function were investigated. A phenome-wide association study (PheWAS) was performed for the statistical interaction between SHAD and the binary characteristic LEAN. The cohort contained 8914 patients—lean patients with (N = 278, 3.1%) and without (N = 1867, 20.9%) steatosis, and overweight patients with (N = 1863, 20.9%) and without (N = 4906, 55.0%) steatosis. Among all lean patients, those with steatosis had increased rates of cardiovascular disease (41.7 vs 27.8%), hypertension (86.7 vs 49.8%), and type 2 diabetes mellitus (29.1 vs 15.7%) (all p

Since May 2022, mpox has been identified in 108 countries without endemic disease; most cases have been in gay, bisexual, or other men who have sex with men. To determine number of missed cases, we conducted 2 studies during June–September 2022: a prospective serologic survey detecting orthopoxvirus antibodies among men who have sex with men in San Francisco, California, and a retrospective monkeypox virus PCR testing of swab specimens submitted for other infectious disease testing among all patients across the United States. The serosurvey of 225 participants (median age 34 years) detected 18 (8.0%) who were orthopoxvirus IgG positive and 3 (1.3%) who were also orthopoxvirus IgM positive. The retrospective PCR study of 1,196 patients (median age 30 years; 54.8% male) detected 67 (5.6%) specimens positive for monkeypox virus. There are likely few undiagnosed cases of mpox in regions where sexual healthcare is accessible and patient and clinician awareness about mpox is increased.

Traditional approaches employing natural plant products to treat a wide array of ailments have been documented and described for thousands of years. However, there remains limited scientific study of the therapeutic potential or effectiveness of ethnobotanical applications. Increases in the incidence of cancer and emerging infectious diseases demonstrate a growing need for advances in the development of therapeutic options. In this study, we evaluate the therapeutic potential of aqueous extracts prepared from four plants, purple aster (Symphyotrichum novae-angliae (L.) Nemsom), common sage (Salvia lyrata (L.)), northern spicebush (Lindera benzoin (L.) Blume), and lamb’s ear (Stachys byzantina (K.) Koch)) traditionally used in Native American medicine in Indiana, USA. Using a combination of cytotoxicity assays, immunofluorescence microscopy, and antiviral assays, we found that sage and spicebush extracts exhibit cytotoxic and antiproliferative effects on HeLa cell proliferation and that sage, spicebush, and aster extracts were capable of significantly inhibiting human respiratory syncytial virus (hRSV), a major respiratory pathogen of infants and the elderly. Chemical analysis of the four extracts identified four major compounds which were subsequently evaluated to identify the responsible constituents in the extracts. While none of the identified compounds were shown to induce significant impacts on HeLa cell proliferation, two of the compounds, (1S)-(-)-Borneol and 5-(hydroxymethyl)-furfural, identified in sage and spicebush, respectively, were shown to have antiviral activities. Our data suggest that several of the extracts tested exhibited either anti-proliferative or antiviral activity supporting future further analysis.

Abstract Glioblastomas are highly aggressive brain tumors for which therapeutic options are very limited. In a quest for new anti-glioblastoma drugs, we focused on specific structural modifications to the benzoyl-phenoxy-acetamide (BPA) structure present in a common lipid-lowering drug, fenofibrate, and in our first prototype glioblastoma drug, PP1. Here, we propose extensive computational analyses to improve the selection of the most effective glioblastoma drug candidates. Initially, over 100 structural BPA variations were analyzed and their physicochemical properties, such as water solubility (− logS), calculated partition coefficient (ClogP), probability for BBB crossing (BBB_SCORE), probability for CNS penetration (CNS-MPO) and calculated cardiotoxicity (hERG), were evaluated. This integrated approach allowed us to select pyridine variants of BPA that show improved BBB penetration, water solubility, and low cardiotoxicity. Herein the top 24 compounds were synthesized and analyzed in cell culture. Six of them demonstrated glioblastoma toxicity with IC50 ranging from 0.59 to 3.24 µM. Importantly, one of the compounds, HR68, accumulated in the brain tumor tissue at 3.7 ± 0.5 µM, which exceeds its glioblastoma IC50 (1.17 µM) by over threefold.

Abstract Human rabies remains a globally significant public health problem. Replacement of polyclonal anti-rabies immunoglobulin (RIG), a passive component of rabies post-exposure prophylaxis (PEP), with a monoclonal antibody (MAb), would eliminate the cost and availability constraints associated with RIG. Our team has developed and licensed a human monoclonal antibody RAB1 (Rabishield©), as the replacement for RIG where canine rabies is enzootic. However, for the highly diverse rabies viruses of North America, a cocktail containing two or more MAbs targeting different antigenic sites of the rabies glycoprotein should be included to ensure neutralization of all variants of the virus. In this study, two MAb cocktails, R172 (RAB1-RAB2) and R173 (RAB1-CR57), were identified and evaluated against a broad range of rabies variants from North America. R173 was found to be the most potent cocktail, as it neutralized all the tested North American RABV isolates and demonstrated broad coverage of isolates from both terrestrial and bat species. R173 could be a promising candidate as an alternative or replacement for RIG PEP in North America.

Abstract Glioblastomas are the most aggressive brain tumors for which therapeutic options are limited. Current therapies against glioblastoma include surgical resection, followed by radiotherapy plus concomitant treatment and maintenance with temozolomide (TMZ), however, these standard therapies are often ineffective, and average survival time for glioblastoma patients is between 12 and 18 months. We have previously reported a strong anti-glioblastoma activity of several metabolic compounds, which were synthetized based compounds, which were synthetized based on the chemical structure of a common lipid-lowering drug, fenofibrate, and share a general molecular skeleton of benzoylphenoxyacetamide (BPA). Extensive computational analyses of phenol and naphthol moieties added to the BPA skeleton were performed in this study with the objective of selecting new BPA variants for subsequent compound preparation and anti-glioblastoma testing. Initially, 81 structural variations were considered and their physical properties such as solubility (logS), blood–brain partitioning (logBB), and probability of entering the CNS calculated by the Central Nervous System—Multiparameter Optimization (MPO-CNS) algorithm were evaluated. From this initial list, 18 compounds were further evaluated for anti-glioblastoma activity in vitro. Nine compounds demonstrated desirable glioblastoma cell toxicity in cell culture, and two of them, HR51, and HR59 demonstrated significantly improved capability of crossing the model blood–brain-barrier (BBB) composed of endothelial cells, astrocytes and pericytes.

Purpose: Antimicrobial resistance (AMR) is a global One Health issue. Simulation modelling is used to understand AMR in many contexts but there is lack of integration of models across sectors. The purpose of our research is to explore whether it is possible to quantify an existing model consisting of 92 compartments deemed important to the emergence and transmission of AMR in different parts of the One Health spectrum relevant to the food system of a high-income country (Sweden). Methods & Materials: We performed a literature scan to address 2 research objectives: (1) to identify current models of AMR representing different parts of the One Health system, and (2) to identify existing evidence to inform such models in a high-income (specifically Swedish) context. Searches were conducted in Google, Google Scholar, and Pubmed and articles that fit pre-determined criteria were read, models were categorized by type in an excel database. Results: Of the 140 simulation models identified (Objective 1), the majority of the models were deterministic (48%), compartmental (69%), and limited to one sector (57%). The majority of the AMR-specific models were human-focussed (54%) and were either at a macroscopic-level (transfers of patients between hospitals and community members; 22%) or microscopic (pathogen) level (within-host models of gene transfer and AMR emergence; 27%), with very few multi-level models including both mechanisms (2%). A total of 376 data sources were included to inform the models (Objective 2). These sources provided quantitative and qualitative data that addressed 79 of the 92 compartments from peer-reviewed (138 citations) and grey literature (72 web pages, 72 reports, and 94 other sources). Major data gaps included the environmental sector, wildlife, and nodes that are broad, ill-defined, or abstract in nature (e.g. human experience and knowledge). Conclusion: The number of models that address AMR beyond one context or sector is limited. Existing models addressing different parts of the system have the potential to be integrated together into a more holistic model. Mixed methods may be useful to incorporate a variety of data sources to fill current gaps.

Purpose: Our study purpose was to identify (1) the underlying causal system of factors influencing antimicrobial resistance (AMR) development and spread in South East Asia (SEA) and (2) places to intervene by integrating diverse perspectives to find context-specific solutions. Methods & Materials: Using a complex adaptive systems lens and participatory, qualitative, systems modelling approach, we conducted 2 participatory workshops and 2 interviews involving AMR experts and other disciplinary experts to brainstorm factors influencing AMR and identify leverage points for intervention. Transcripts were thematically analyzed for factors, connections, and leverage points for interventions, which were then transcribed into a causal loop diagram (CLD) using Vensim 8.0.4 and validated via participant feedback. Results: Seventeen participants representing diverse perspectives across the One Health spectrum (e.g., animal welfare, pharmaceutical industry, food industry, water and sanitation, pest control) constructed a CLD that identified 98 factors, interlinked by 393 arrows, that influenced AMR in SEA. Seven themes explained the AMR dynamics illustrated in the CLD: consumer demand; agricultural food production systems; antimicrobial and pesticide/chemical misuse and AMR spread in the environment; inequitable access to quality antibiotics and health care; poor food safety practices; poor knowledge; and a need for research and innovation. Eight ‘overarching factors’, not included in the CLD because they impact the entire AMR system, emerged as underpinning the AMR dynamics described in each theme: leadership priorities and investments (e.g., privatized health care); poor regulations and enforcement; social and cultural norms; infectious disease prevalence; the drive to survive (e.g., due to food insecurity, poverty); increasing wealth and urbanization; climate change; and the underlying goal of economic prosperity that drives system behaviour. Fifteen leverage points representing different ‘overarching’ and CLD factors were identified as places to intervene with potential to change AMU and AMR directly (e.g., via setting AMU standards) or indirectly (e.g., via improving food security) in SEA. Conclusion: Our study illustrates AMR as the product of actions across the One Health spectrum and identifies the need for multi-pronged and multi-level interventions, including actions relevant to achieving the sustainable development goals, to transform our reliance on AMU and mitigate AMR sustainably.