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New Trypanosoma brucei acting derivatives incorporating 1-(4-phenyl)adamantane and 1-(4-phenoxyphenyl)adamantane.
Get PDFIn this work, we describe the design, synthesis and evaluation of novel functionalised 1-(4-phenyl)adamantane and 1-(4-phenoxyphenyl)adamantane derivatives. Based on previous findings, we incorporated a phenyl ring between the adamantane core and the pharmacophoric side chain to enhance the activity and selectivity index (SI). The aromatic imidazolines 1a-d and the linear amidines 2a,b and 3a,b exhibited notable activity against T. brucei. The 1-(4-phenyl)adamantane 1-(4-phenoxyphenyl)adamantane core was further functionalized with the aminoguanylhydrazone and thiosemicarbazone moieties. 2-[(E)-4-(1-adamantyl)benzylidene]hydrazine-1-carbothioamide 4c emerged as a promising trypanocidal agent with an EC50 of 0.16 μM and an SI of 17. Future studies will focus on optimizing the length and the distance of the side chain between the aromatic ring and the chromophores to further enhance the activity and selectivity of these molecules
Socio-cultural and structural barriers influencing parents' knowledge and access to information on schistosomiasis in children around Ugandan Lakes.
Get PDFBACKGROUND: In Uganda, the national prevalence of schistosomiasis is 36.1% among the two-to-four-year age group. Knowledge about schistosomiasis and socio-cultural factors have been reported to influence adult participation in mass drug administrations of praziquantel, the standard medication used to treat the disease. In advance and support of the (pilot) introduction of the recently developed paediatric praziquantel formulation (arpraziquantel), we conducted research on parent and other community members' knowledge about paediatric schistosomiasis, their information sources, and potential perceived barriers that influence knowledge and access to information on schistosomiasis. METHODS: This cross-sectional qualitative study consisted of 65 in-depth interviews and ten focus group discussions with parents/guardians of preschool-aged children (PSAC), Village Health Teams (VHTs), health professionals, community leading persons and district officials, in addition to direct observations. We collected data concurrently in Hoima District at Lake Albert and Bugiri at Lake Victoria, Uganda, in 2022. The analysis followed both an inductive and a deductive thematic approach. RESULTS: Despite high parental awareness of the disease and knowledge of signs and symptoms, we identified less familiarity with its transmission and prevention. With limited communication channels, VHTs emerged as the primary information sources but reflected varied local understandings of schistosomiasis. Parents expressed a desire to be informed about the new paediatric treatment through VHTs, health professionals, and community leaders, and partly through the radio. Other mentioned socio-cultural and structural barriers to information flow included language barriers, illiteracy, high population movement, fears, and resentment from restrictive government fishing laws. CONCLUSIONS: Carefully designed information campaigns tailored to local circumstances and health literacy needs should be carried out by trained VHTs and preferably supported by health professionals and the local leadership structure. These components are essential to inform parents/guardians of PSAC, enabling them to make well-informed decisions for their children's health
Use of Household Apparent Food Intake Data to Estimate Micronutrient Inadequacy in Comparison to the 24-h Recall Data Among Women of Reproductive Age in Kasungu District, Malawi.
Get PDFOBJECTIVE: The aim of this study was to compare micronutrient intake and inadequacy estimates using household consumption and expenditure survey (HCES) and quantitative 24-h recall (24HR) data among women of reproductive age (WRA) in Kasungu district, Malawi. METHODS: We conducted a secondary data analysis utilizing HCES dietary data from a subsample of households in rural areas of Kasungu district, which were sourced from the 2019/20 Malawi Fifth Integrated Household Survey (n = 183); and 24HR data were obtained from WRA in a community-based Addressing Hidden Hunger with Agronomy (AHHA) trial in the same district (n = 177). Micronutrient intakes and inadequacy were estimated under two alternative scenarios of large-scale food fortification (LSFF). We standardized apparent nutrient intakes from the HCES data using the adult female equivalent metric. RESULTS: Estimated prevalence of micronutrient inadequacy fell within 20 percentage points between HCES and 24HR for iron (Fe), zinc (Zn), vitamins B2 and B9 under both no fortification and fortification scenarios. There were some discrepancies for the remaining B vitamins, being consistently large for vitamin B3. CONCLUSIONS: In the absence of 24HR data, HCES data can be used to make inferences about some micronutrient intakes and inadequacies among rural WRA in Malawi and to inform decisions regarding LSFF, including vehicle selection and coverage. However, additional efforts are needed to improve HCES for dietary nutrient surveillance given existing limitations
Integrating anticipatory action in disease outbreak preparedness and response in the humanitarian sector.
Get PDFIn the humanitarian sector, anticipatory action entails acting ahead of predicted hazardous events to prevent or mitigate potential impacts and needs. It leverages early warnings to bridge preparedness and response, with a core principle being the provision of ex-ante emergency funding for preagreed early actions. Traditionally applied to extreme climatic events, there is growing interest in integrating anticipatory action into disease outbreak preparedness and response. We present an analytical framework for trigger development for climate-sensitive infectious disease outbreaks based on a review of existing and emerging practices from the Red Cross Red Crescent Movement, United Nations agencies and Médecins Sans Frontières since 2014. We propose that, depending on data availability, there are four broad approaches for trigger development. First, the humanitarian sector could scale up the release of prearranged funding based on real-time surveillance data (eg, suspected cases) while other emergency funding is secured. Second, the humanitarian sector could take advantage of weather forecasts and seasonal climate forecasts to anticipate outbreaks linked to extreme climatic events, anomalous climatic conditions or highly suitable climatic conditions. Third, to extend the lead time available for intervention, the humanitarian sector could use observed environmental and socioeconomic transmission risk factors (eg, population displacement, overcrowding, presence of vectors, weather changes) in combination with real-time surveillance data to improve early detection or curb a rapid increase in cases, while other emergency funding is secured. Fourth, data-driven outbreak forecasting using seasonal forecasts can help extend the lead time further to make informed decisions about future risks. We present examples and discuss the trade-offs between approaches. As anticipatory action for outbreaks becomes established, we expect that future applications will integrate all four approaches
Diagnostic accuracy of convolutional neural networks in classifying hepatic steatosis from B-mode ultrasound images: a systematic review with meta-analysis and novel validation in a community setting in Telangana, India.
Get PDFBACKGROUND: Ultrasound is a widely available, inexpensive, and non-invasive modality for evaluating hepatic steatosis (HS). However, the scarcity of radiological expertise limits its utility. Convolutional Neural Networks (CNNs) have potential for automated classification of HS using B-mode ultrasound images. We aimed to assess their diagnostic accuracy and generalisability across diverse study settings and populations. METHODS: We systematically reviewed two biomedical databases up to Dec 12, 2023, to identify studies that applied CNNs in the classification of HS using B-mode ultrasound images as input (PROSPERO: CRD42024501483). We supplemented this review with a novel analysis of the community-based Andhra Pradesh Children and Parents' Study (APCAPS) in India to address the overrepresentation of hospital samples and lack of data on South Asian populations who exhibit a distinct central adiposity phenotype that could influence CNN performance. We quantitatively synthesised diagnostic accuracy metrics for eligible studies using random-effects meta-analyses. FINDINGS: Our search returned 289 studies, of which 17 were eligible. All but one of the 17 studies were based in hospital or clinical outpatient settings with curated cases and controls. Studies were conducted exclusively in East Asian, European, or North American populations. Studies employed varying gold standards: seven studies (41.18%) used liver biopsy, three (17.64%) used MRI proton density fat fraction, and seven (41.18%) used clinician-evaluated ultrasound-based HS grades. The APCAPS sample included 219 participants with radiologist-assigned HS grades. Across the range of study settings and populations, CNNs demonstrated good diagnostic accuracy. Meta-analysis of studies with low risk of bias reporting on five unique datasets showed a pooled area under the receiver operating characteristic curve of 0.93 (95% CI 0.73-0.98) for detecting any severity and 0.86 (95% CI 0.77-0.92) for detecting moderate-to-severe HS severity grades, respectively. INTERPRETATION: CNNs have good diagnostic accuracy and generalisability for HS classification, suggesting potential for real-world application. FUNDING: Medical Research Council, UK (MR/T038292/1, MR/V001221/1)
Predicting the risks of stroke, cardiovascular disease, and peripheral vascular disease among people with type 2 diabetes with artificial intelligence models: A systematic review and meta-analysis
Get PDFMacrovascular complications, including stroke, cardiovascular disease (CVD), and peripheral vascular disease (PVD), significantly contribute to morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to evaluate the performance of artificial intelligence (AI) models in predicting these complications, emphasizing applicability in diverse healthcare settings. Following PRISMA guidelines, a systematic search of six databases was conducted, yielding 46 eligible studies with 184 AI models. Predictive performance was assessed using the area under the receiver operating characteristic curve (AUROC). Subgroup analyses examined model performance by outcome type, predictor data (lab-only, non-lab, mixed), and algorithm type. Heterogeneity was evaluated using I2 statistics, and sensitivity analyses addressed outliers and study biases. The pooled AUROC for all AI models was 0.753 (95%CI: 0.740–0.766; I2=99.99%). Models predicting PVD achieved the highest AUROC (0.794), followed by cerebrovascular diseases (0.770) and CVD (0.741). Gradient-boosting algorithms outperformed others (AUROC: 0.789). Models with lab-only predictors had superior performance (AUROC: 0.837) compared to mixed (0.759) and non-lab predictors (0.714). External validations reported reduced AUROC (0.725), underscoring limitations in generalizability. AI models show moderate predictive accuracy for T2DM macrovascular complications, with laboratory-based predictors being key to performance. However, the limited external validation and reliance on high-resource data restrict implementation in low-resource settings. Future efforts should focus on non-lab predictors, external validation, and context-appropriate AI solutions to enhance global applicability
Female Genital Schistosomiasis (FGS) in a Nonendemic Setting: Retrospective Case-Notes Review of Schistosoma haematobium-Positive FGS Cases at the Hospital for Tropical Diseases, London, With a Pragmatic Clinical Pathway for Nonendemic Settings.
Get PDFBACKGROUND: Female genital schistosomiasis (FGS), the genital manifestation of S. haematobium infection in women, results in protean gynecological symptoms and longer-term complications. FGS affects an estimated 75% of women with S. haematobium, totaling 56 million women, mainly in Sub-Saharan Africa. With increasing migration, FGS will be encountered more frequently in nonendemic settings. Despite this, evaluation of FGS diagnosis and management and guidelines for these settings are lacking. METHODS: A retrospective case-notes review was undertaken of patients presenting to the Hospital for Tropical Diseases, London, from 1998 to 2018 with S. haematobium ova in terminal urine or on biopsy. Descriptive and outcome variables were collected. Specific FGS variables included documented gynecological symptoms and referrals to sexual health and gynecology specialists. Results informed a clinical pathway aiding diagnosis and management of FGS. RESULTS: Overall, 186 patients with S. haematobium ova in terminal urine or biopsy were included, 62 (33.3%) of whom were women. Four women had documented gynecological symptoms (4/62, 6.5%). Two symptomatic women were referred to gynecology (2/4, 50%), and 2 were lost to follow-up (2/4, 50%). Gynecological symptoms were not documented for many women, despite proven S. haematobium infection. CONCLUSIONS: Given that 75% of women with S. haematobium infection may have FGS, there is a gap in diagnosis in this nonendemic setting. We developed a clinical pathway to improve diagnosis and management of FGS, including inquiry about gynecological symptoms, followed by targeted referrals to gynecology, sexual health, and urological imaging. By formalizing a pathway, we aim to improve FGS care in this nonendemic setting
Estimating historical PFAS exposures in Ronneby, Sweden using biobanked dried blood spots from newborns.
Get PDFBACKGROUND: In 2013, it was discovered that a subset of the population in Ronneby, Sweden was exposed to high levels of perfluorinated compounds (PFAS) from drinking water that had been provided by the local Brantafors waterworks and was contaminated by fire-fighting foam from a nearby airport. The start and time-course of population exposures are not known. OBJECTIVE: To investigate the start of PFAS exposures in the Ronneby population and changes over time by measuring PFAS in dried blood spots (DBS) collected from infants after birth and biobanked at the Swedish Phenylketonuria (PKU) Biobank. METHODS: We measured PFAS in DBS from 288 infants born between 1985 and 2013 using liquid chromatography-tandem mass spectrometry. Brantafors subjects (N = 246) were infants whose mothers lived at an address that received Brantafors water, while non-Brantafors subjects (N = 42) were infants whose mothers lived in the same county but never lived in Ronneby. We compared PFAS concentrations between the two groups using Welch's t-tests for unequal variance and investigated trends in PFAS concentration over time using generalized additive models with a non-linear term for year of birth. RESULTS: Mean PFAS concentrations were significantly higher in Brantafors subjects born in 1985 (N = 10) compared to non-Brantafors subjects born 1985-1989 (N = 19) for all PFAS. The concentration of all PFAS measured in Brantafors subjects increased from 1985, with most PFAS reaching an expected maximum in 2007. For example, non-Brantafors subjects born between 1985 and 1995 had a median PFOS concentration of 4.0 ng/mL (IQR: 3.6-4.3), while Brantafors subjects born 1985-1995 had a median concentration of 18 ng/mL (IQR: 14-26) and Brantafors subjects born 1996-2013 had a median concentration of 42 ng/mL (IQR: 29-64). DISCUSSION: These results suggest that population-wide PFAS exposures were already present in Ronneby in 1985 and increased over the subsequent 30 years, and demonstrate how DBS can be used for historical exposure assessment
“We are Kind of Nurses on the Cheap”: A Study of the Devaluation of England’s Feminised Social Care Workforce
Get PDFFast and accurate in silico antigen typing with Kaptive 3.
Get PDFSurface polysaccharides are common antigens in priority pathogens and therefore attractive targets for novel control strategies such as vaccines, monoclonal antibody and phage therapies. Distinct serotypes correspond to diverse polysaccharide structures that are encoded by distinct biosynthesis gene clusters; e.g. the Klebsiella pneumoniae species complex (KpSC) K- and O-loci encode the synthesis machinery for the capsule (K) and outer-lipopolysaccharides (O), respectively. We previously presented Kaptive and Kaptive 2, programmes to identify K- and O-loci directly from KpSC genome assemblies (later adapted for Acinetobacter baumannii), enabling sero-epidemiological analyses to guide vaccine and phage therapy development. However, for some KpSC genome collections, Kaptive (v≤2) was unable to type a high proportion of K-loci. Here, we identify the cause of this issue as assembly fragmentation and present a new version of Kaptive (v3) to circumvent this problem, reduce processing times and simplify output interpretation. We compared the performance of Kaptive v2 and Kaptive v3 for typing genome assemblies generated from subsampled Illumina read sets (decrements of 10× depth), for which a corresponding high-quality completed genome was also available to determine the 'true' loci (n=549 KpSC, n=198 A. baumannii). Both versions of Kaptive showed high rates of agreement to the matched true locus amongst 'typeable' locus calls (≥96% for ≥20× read depth), but Kaptive v3 was more sensitive, particularly for low-depth assemblies (at 1 order of magnitude faster than Kaptive v2, making it easy to analyse thousands of assemblies on a desktop computer, facilitating broadly accessible in silico serotyping that is both accurate and sensitive. The Kaptive v3 source code is freely available on GitHub (https://github.com/klebgenomics/Kaptive), and has been implemented in Kaptive Web (https://kaptive-web.erc.monash.edu/)