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PURPOSE OF REVIEW: This opinion piece aims to explore the transformative potential of integrating artificial intelligence with digital microscopy to enhance diagnostics for soil-transmitted helminthiasis (STH) and schistosomiasis (SCH), two pervasive neglected tropical diseases (NTDs). By aligning innovative artificial intelligence-driven solutions with WHO's strategic objectives and calls for better, more accessible, and more integrated diagnostics, we highlight the latest advancements that may support improved health outcomes in affected communities. RECENT FINDINGS: The review covers recent advancements in artificial intelligence-based diagnostic technologies, emphasizing automated egg detection and quantification. These technologies promise to mitigate challenges such as human error and the need for skilled technicians. SUMMARY: The findings have significant implications for public health, ethical considerations and regulatory pathways, particularly in resource-limited settings. The authors advocate for interdisciplinary collaboration and a strategic focus on meeting WHO target product profiles to ensure uptake, ultimately to support reaching WHO NTD targets.
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In polymicrobial sepsis, the extracellular histones, mainly released from activated neutrophils, significantly contribute to cardiac dysfunction (septic cardiomyopathy), as demonstrated in our previous studies using Echo-Doppler measurements. This study aims to elucidate the roles of extracellular histones and their interactions with Toll-like receptors (TLRs) in cardiac dysfunction. Through ex vivo assessments of ECG, left ventricle (LV) function parameters, and in vivo Echo-Doppler studies in mice perfused with extracellular histones, we aim to provide comprehensive insights into the mechanisms underlying sepsis-induced cardiac dysfunction. Langendorff-perfused hearts from both wild-type and TLR2, TLR3, or TLR4 knockout (KO) mice were examined. Paced mouse hearts were perfused with histones to assess contractility and relaxation. Echo-Doppler studies evaluated cardiac dysfunction after intravenous histone injection. Histone perfusion caused defects in contractility and relaxation, with TLR2 and TLR3 KO mice being partially protected. Specifically, TLR2 KO mice exhibited the greatest reduction in Echo-Doppler abnormalities, while TLR4 KO exacerbated cardiac dysfunction. Among individual histones, H1 induced the most pronounced abnormalities in cardiac function, apoptosis of cardiomyocytes, and LDH release. Our data highlight significant interactions between histones and TLRs, providing insights into histones especially H1 as potential therapeutic targets for septic cardiomyopathy. Further studies are needed to explore specific histone-TLR interactions and their mechanisms.
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Histonas , Camundongos Knockout , Animais , Histonas/metabolismo , Camundongos , Receptores Toll-Like/metabolismo , Masculino , Sepse/metabolismo , Sepse/complicações , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Coração/fisiopatologiaRESUMO
In 2009, Massachusetts General Hospital and the Red Sox Foundation launched Home Base, a nonprofit dedicated to providing care to veterans, service members, and their loved ones who struggle with the invisible wounds of war free of charge. Significant needs exist for mental health services in each of these populations, and a need for innovative approaches to address shortcomings in existing treatment models. Three inventive components of our programming are highlighted herein: a Veteran Outreach Team, which helps to engage patients in care, programming, and services specifically for family members, and an intensive outpatient substance use treatment program. More than 4,000 patients, 3,031 veterans and service members, and 1,025 family members have engaged in treatment at Home Base. Patients were asked to complete post-treatment self-measures, including a satisfaction questionnaire via an electronic data collection system. The vast majority of individuals who engaged in our treatment model were satisfied with the care they received (>92%) and would refer their peers to the Home Base program (>75%). Data from 78 individuals who completed the dual diagnosis services demonstrated large effect sizes in reductions in alcohol use and comorbid mental health symptoms. These data suggest that novel components to the standard outpatient mental health model might provide substantive benefits for the patients served. While internal data is prone to a lack of generalizability, these additional offerings help ameliorate patients' expressed shortcomings with existing models; present literature that describes the benefits that these additions provide is also reviewed. The lessons learned and limitations are discussed.
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Adherence is vital for medicine to have an effect, yet adherence is considered to be low, with approximately half of the patients not fully adherent. However, research into adherence tends to focus on quantitative analysis of performance, which fails to perceive how people are adherent in their many different environments. As a contribution to gaining a deeper understanding, interviews were held with thirty individuals in the UK, Egypt, Kazakhstan, and six countries in sub-Saharan Africa to understand their perceptions on adherence to a range of drugs, and these were compared with an existing well-regarded list. New or undocumented reasons for non-adherence were discovered. Reasons for non-adherence were consistent across both developing and developed worlds. A new viewpoint on adherence is suggested, which considers adherence to be a single act and therefore as an individual opportunity to be adherent, permitting greater focus on the enablers and inhibitors of adherence at any given point in time.
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The reorientation of Earth through rotation of its solid shell relative to its spin axis is known as True polar wander (TPW). It is well-documented at present, but the occurrence of TPW in the geologic past remains controversial. This is especially so for Late Jurassic TPW, where the veracity and dynamics of a particularly large shift remain debated. Here, we report three palaeomagnetic poles at 153, 147, and 141 million years (Myr) ago from the North China craton that document an ~ 12° southward shift in palaeolatitude from 155-147 Myr ago (~1.5° Myr-1), immediately followed by an ~ 10° northward displacement between 147-141 Myr ago (~1.6° Myr-1). Our data support a large round-trip TPW oscillation in the past 200 Myr and we suggest that the shifting back-and-forth of the continents may contribute to the biota evolution in East Asia and the global Jurassic-Cretaceous extinction and endemism.
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Cephalopods are among many marine animals that through some combination of habit and/or habitat have proven difficult to study, especially understanding their trophic positions in marine communities. Stable isotope analyses have provided powerful tools for discovering quantitative aspects about the ecology and food sources of many cephalopod species. Here, we present new gut content and isotopic data (carbon and nitrogen isotopes) from phragmocone-bearing cephalopods (both ectocochleates, as well as those with internal, hard part buoyancy maintenance apparatuses). To this, we also include observations from baited remote underwater video systems to describe feeding habits and potential prey types to correlate with gut contents analyses. These data come from extant Allonautilus, Nautilus, and Sepia species, as well as from extinct nautiloids and ammonites. Extant nautiloids occupy a different isotopic niche than all other cephalopod groups where such data have been published to date. We conclude that these species are obligate scavengers rather than predators on any living species in their environments. Extant Nautilus and Allonautilus also demonstrate different patterns of functional allometry of nitrogen isotope values over ontogeny than do most other cephalopods (or animals in general), by showing decreasing nitrogen isotope levels during ontogeny. This pattern is shown to be different in Sepia and the yet small number of ammonite cephalopods studied to date, supporting the increasingly accepted view that ammonites were far closer to coleoids in basic biology than nautiloids. Overall, phragmocone-bearing cephalopods appear fundamentally different ecologically than cephalopods without this kind of buoyancy system. Of these groups, nautiloids appear to live a low-energy existence that allows them to subsist on energy-poor food sources, such as crustacean molts, as well as being able to scavenge in low oxygen basins where rare food falls, such as dead fish, remain unobtainable by most other animals.
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Cefalópodes , Animais , Ecologia , Ecossistema , Isótopos de Nitrogênio , Estado Nutricional , PeixesRESUMO
Biological age captures physiological deterioration better than chronological age and is amenable to interventions. Blood-based biomarkers have been identified as suitable candidates for biological age estimation. This study aims to improve biological age estimation using machine learning models and a feature-set of 60 circulating biomarkers available from the UK Biobank (n = 306,116). We implement an Elastic-Net derived Cox model with 25 selected biomarkers to predict mortality risk (C-Index = 0.778; 95% CI [0.767-0.788]), which outperforms the well-known blood-biomarker based PhenoAge model (C-Index = 0.750; 95% CI [0.739-0.761]), providing a C-Index lift of 0.028 representing an 11% relative increase in predictive value. Importantly, we then show that using common clinical assay panels, with few biomarkers, alongside imputation and the model derived on the full set of biomarkers, does not substantially degrade predictive accuracy from the theoretical maximum achievable for the available biomarkers. Biological age is estimated as the equivalent age within the same-sex population which corresponds to an individual's mortality risk. Values ranged between 20-years younger and 20-years older than individuals' chronological age, exposing the magnitude of ageing signals contained in blood markers. Thus, we demonstrate a practical and cost-efficient method of estimating an improved measure of Biological Age, available to the general population.
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Envelhecimento , Humanos , Envelhecimento/fisiologia , BiomarcadoresRESUMO
Externalized histones erupt from the nucleus as extracellular traps, are associated with several acute and chronic lung disorders, but their implications in the molecular pathogenesis of interstitial lung disease are incompletely defined. To investigate the role and molecular mechanisms of externalized histones within the immunologic networks of pulmonary fibrosis, we studied externalized histones in human and animal bronchoalveolar lavage (BAL) samples of lung fibrosis. Neutralizing anti-histone antibodies were administered in bleomycin-induced fibrosis of C57BL/6 J mice, and subsequent studies used conditional/constitutive knockout mouse strains for TGFß and IL-27 signaling along with isolated platelets and cultured macrophages. We found that externalized histones (citH3) were significantly (P < 0.01) increased in cell-free BAL fluids of patients with idiopathic pulmonary fibrosis (IPF; n = 29) as compared to healthy controls (n = 10). The pulmonary sources of externalized histones were Ly6G+CD11b+ neutrophils and nonhematopoietic cells after bleomycin in mice. Neutralizing monoclonal anti-histone H2A/H4 antibodies reduced the pulmonary collagen accumulation and hydroxyproline concentration. Histones activated platelets to release TGFß1, which signaled through the TGFbRI/TGFbRII receptor complex on LysM+ cells to antagonize macrophage-derived IL-27 production. TGFß1 evoked multiple downstream mechanisms in macrophages, including p38 MAPK, tristetraprolin, IL-10, and binding of SMAD3 to the IL-27 promotor regions. IL-27RA-deficient mice displayed more severe collagen depositions suggesting that intact IL-27 signaling limits fibrosis. In conclusion, externalized histones inactivate a safety switch of antifibrotic, macrophage-derived IL-27 by boosting platelet-derived TGFß1. Externalized histones are accessible to neutralizing antibodies for improving the severity of experimental pulmonary fibrosis.
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Fibrose Pulmonar Idiopática , Interleucina-27 , Humanos , Camundongos , Animais , Camundongos Endogâmicos C57BL , Histonas , Plaquetas , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genéticaRESUMO
Nautiloids are a charismatic group of marine molluscs best known for their rich fossil record, but today they are restricted to a handful of species in the family Nautilidae from around the Coral Triangle. Recent genetic work has shown a disconnect between traditional species, originally defined on shell characters, but now with new findings from genetic structure of various Nautilus populations. Here, three new species of Nautilus from the Coral Sea and South Pacific region are formally named using observations of shell and soft anatomical data augmented by genetic information: N.samoaensissp. nov. (from American Samoa), N.vitiensissp. nov. (from Fiji), and N.vanuatuensissp. nov. (from Vanuatu). The formal naming of these three species is timely considering the new and recently published information on genetic structure, geographic occurrence, and new morphological characters, including color patterns of shell and soft part morphology of hood, and will aid in managing these possibly endangered animals. As recently proposed from genetic analyses, there is a strong geographic component affecting taxonomy, with the new species coming from larger island groups that are separated by at least 200 km of deep water (greater than 800 m) from other Nautilus populations and potential habitats. Nautilid shells implode at depths greater than 800 m and depth therefore acts as a biogeographical barrier separating these species. This isolation, coupled with the unique, endemic species in each locale, are important considerations for the conservation management of the extant Nautilus species and populations.
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OBJECTIVES: To assess the appropriate preanalytical process for storage of plasma for renin concentration analysis. This study was initiated due to the wide variation in preanalytical handling of samples observed within our network, particularly with respect to freezing for longer term storage. METHODS: Pooled plasma from patient samples was analysed immediately post separation for renin concentration (n=30, concentration 4.0-204 mIU/L). Aliquots from these samples were frozen in a -20 °C freezer and then analysed, with the renin concentration compared to the respective baseline concentration. Comparisons were also made to: aliquots snap frozen using a dry ice/acetone bath, aliquots stored at room temperature, and aliquots stored at 4 °C. Subsequent experiments investigated the potential sources of cryoactivation observed in these initial studies. RESULTS: Substantial and highly variable cryoactivation was observed in samples frozen using a -20 °C freezer, with renin concentration increasing over 300% from baseline in some samples (median 21.3%). This cryoactivation could be prevented by snap freezing samples. Subsequent experiments determined that long term storage in a -20 °C freezer could prevent cryoactivation provided samples were initially frozen rapidly in a -70 °C freezer. Rapid defrosting of samples was not required to prevent cryoactivation. CONCLUSIONS: Standard -20 °C freezers may not be appropriate for freezing samples for renin analysis. Laboratories should consider snap freezing their samples using a -70 °C freezer or similar to avoid cryoactivation of renin.
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Plasma , Renina , Humanos , CongelamentoRESUMO
The latest Permian mass extinction (LPME) was triggered by magmatism of the Siberian Traps Large Igneous Province (STLIP), which left an extensive record of sedimentary Hg anomalies at Northern Hemisphere and tropical sites. Here, we present Hg records from terrestrial sites in southern Pangea, nearly antipodal to contemporaneous STLIP activity, providing insights into the global distribution of volcanogenic Hg during this event and its environmental processing. These profiles (two from Karoo Basin, South Africa; two from Sydney Basin, Australia) exhibit significant Hg enrichments within the uppermost Permian extinction interval as well as positive Δ199Hg excursions (to ~0.3), providing evidence of long-distance atmospheric transfer of volcanogenic Hg. These results demonstrate the far-reaching effects of the Siberian Traps as well as refine stratigraphic placement of the LPME interval in the Karoo Basin at a temporal resolution of ~105 years based on global isochronism of volcanogenic Hg anomalies.
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Mercúrio , Mercúrio/análise , Extinção Biológica , África do Sul , AustráliaRESUMO
OBJECTIVE: Older people experience high rates of adverse outcomes following emergency department (ED) presentation. There is growing evidence to support alternative care pathways for certain types of emergency medical services (EMS) calls. Pathfinder is one such service and targets patients aged 65 years and over, whose presenting issues can be safely managed at home by immediate paramedic, occupational therapy, and/or physiotherapy interventions. The aim of this service evaluation was to understand how older people feel about being treated at home as a result of EMS calls and to understand their experiences of the Pathfinder service. METHODS: This was a thematic analysis of open-ended responses recorded from telephone interviews during routine service evaluation with service users (patients or their next-of-kin). RESULTS: Of 573 service users, telephone interviews were conducted with 429 (75%). Five primary themes were identified: (1) professionalism of the multidisciplinary clinical team; (2) "the right service, in the right place, at the right time"; (3) role of Pathfinder in "getting the ball rolling"; (4) lasting effects of the experience on the patient and his or her next-of-kin; (5) value of skilled communication with the older person. CONCLUSION: Older people and their next-of-kin voiced a clear preference for hospital avoidance, and strongly valued the opportunity to be treated in their homes at the time of an EMS call rather than default conveyance to the ED. They appreciated the importance of a skilled multidisciplinary team with a follow-up service that effectively positions itself between the acute hospital and community services.
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Serviços Médicos de Emergência , Auxiliares de Emergência , Masculino , Feminino , Humanos , Idoso , Cuidadores , Retroalimentação , Serviço Hospitalar de EmergênciaRESUMO
ABSTRACT: This report deals with the advances made in the areas of complement and its role in sepsis, both in mice and in humans. The study relates to work over the past 25 years (late 1990s to October 2022). During this period, there has been very rapid progress in understanding the activation pathways of complement and the activation products of complement, especially the anaphylatoxin C5a and its receptors, C5aR1 and C5aR2. Much has also been learned about these pathways of activation that trigger activation of the innate immune system and the array of strong proinflammatory cytokines that can cause cell and organ dysfunction, as well as complement products that cause immunosuppression. The work in septic humans and mice, along with patients who develop lung dysfunction caused by COVID-19, has taught us that there are many strategies for treatment of humans who are septic or develop COVID-19-related lung dysfunction. To date, treatments in humans with these disorders suggest that we are in the midst of a new and exciting area related to the complement system.
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COVID-19 , Sepse , Humanos , Camundongos , Animais , Citocinas , Proteínas do Sistema Complemento , Complemento C5a/metabolismo , Receptor da Anafilatoxina C5aRESUMO
To improve birth outcomes, all pregnant women without known diabetes are recommended for an oral glucose tolerance test (OGTT) to screen for hyperglycaemia in pregnancy (diabetes in pregnancy or gestational diabetes mellitus (GDM)). This narrative review presents contemporary approaches to minimise preanalytical glycolysis in OGTT samples with a focus on GDM diagnosis using criteria derived from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. The challenges of implementing each approach across a diverse Australian healthcare setting were explored. Many Australian sites currently collect and transport OGTT samples at ambient temperature in sodium fluoride (NaF) tubes which is likely to lead to missed diagnosis of GDM in a significant proportion of cases. Alternative preanalytical solutions should be pragmatic and tailored to individual settings and as close as possible to the preanalytical conditions of the HAPO study for correct interpretation of OGTT results. Rapid centrifugation of barrier tubes to separate plasma could be suitable in urban settings provided time to centrifugation is strictly controlled. Tubes containing NaF and citrate could be useful for remote or resource poor settings with long delays to analysis but the impact on the interpretation of OGTT results should be carefully considered. Testing venous blood glucose at the point-of-care bypasses the need for glycolytic inhibition but requires careful selection of devices with robust analytical performance. Studies to evaluate the potential error of each solution compared to the HAPO protocol are required to assess the magnitude of misdiagnosis and inform clinicians regarding the potential impact on patient safety and healthcare costs.
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Diabetes Gestacional , Hiperglicemia , Gravidez , Feminino , Humanos , Diabetes Gestacional/diagnóstico , Teste de Tolerância a Glucose , Austrália , Glicemia/análise , Manejo de EspécimesAssuntos
COVID-19 , Humanos , SARS-CoV-2 , Atenção Primária à Saúde , Síndrome de COVID-19 Pós-AgudaRESUMO
Scientific sampling of zooplankton in the Atlantic sector of the Southern Ocean has been undertaken since the 1920s, but few analyzed datasets are available to the research community. We provide a database of standardized data derived from samples collected by Bongo nets in this sector between 1996 and 2013, amounting to almost 94,000 individual records. The study region contains some of the highest levels of pelagic biomass in the Southern Ocean and is also undergoing rapid ocean warming and changing seasonality in sea-ice distribution. Data from a single expedition to the sub-Arctic where the same sampling methodology was used are also included. Atlantic water is an increasing influence in that region, as is the prevalence of boreal plankton taxa within Arctic plankton communities. These data will be of value in supporting studies assessing the impacts of climate change on the structure and function of polar pelagic systems.
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Global access to accurate biodiversity data is a prerequisite to our progress in understanding biodiversity dynamics in ecosystems and any changes that are occurring. Despite recent major advancements in sharing data on the world's species, one of the remaining challenges relates to the mechanics of guiding data systematically from its provenance to end users. It can take considerable effort to orchestrate a successful sampling campaign, manage samples obtained in often extreme, remote conditions and to secure preservation of, and access to, the acquired data. Here, we briefly describe biodiversity data flow from a polar ship to a national data repository and onward to a global data portal. This paper highlights a few crucial points in this process, which aims to provide information systematically into the mosaic of our polar species biodiversity knowledge. This flexible workflow can be modified for other data types and adopted by other data repositories.