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OBJECTIVES: Inappropriate prescribing of antibiotics is a key driver of antimicrobial resistance. This study aimed to describe urine sampling rates and antibiotic prescribing for patients with lower urinary tract infections (UTIs) in English general practice. DESIGN: A retrospective population-based study using administrative data. SETTING: IQVIA Medical Research Database (IMRD) data from general practices in England, 2015-2022. PARTICIPANTS: Patients who have consulted with an uncomplicated UTI in England general practices captured in the IMRD. OUTCOME MEASURES: Trends in UTI episodes (episodes were defined as UTI diagnosis codes occurring within 14 days of each other), testing and antibiotic prescribing on the same day as initial UTI consultation were assessed from January 2015 to December 2022. Associations, using univariate and multivariate logistic regressions, were examined between consultation and demographic factors on the odds of a urine test. RESULTS: There were 743 350 UTI episodes; 50.8% had a urine test. Testing rates fluctuated with an upward trend and large decline in 2020. Same-day UTI antibiotic prescribing occurred in 78.2% of episodes. In multivariate modelling, factors found to decrease odds of a urine test included age ≥85 years (0.83, 95% CI 0.82 to 0.84), consultation type (remote vs face to face, 0.45, 95% CI 0.45 to 0.46), episodes in London compared with the South (0.74, 95% CI 0.72 to 0.75) and increasing practice size (0.77, 95% CI 0.76 to 0.78). Odds of urine tests increased in males (OR 1.11, 95% CI 1.10 to 1.13), for those episodes without a same-day UTI antibiotic (1.10, 95% CI 1.04 to 1.16) for episodes for those with higher deprivation status (Indices of Multiple Deprivation 8 vs 1, 1.51, 95% CI 1.48 to 1.54). Compared with 2015, 2016-2019 saw increased odds of testing while 2020 and 2021 saw decreases, with 2022 showing increased odds. CONCLUSION: Urine testing for UTI in general practice in England showed an upward trend, with same-day antibiotic prescribing remaining consistent, suggesting greater alignment to national guidelines. The COVID-19 pandemic impacted testing rates, though as of 2022, they began to recover.
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Antibacterianos , Medicina General , Pautas de la Práctica en Medicina , Urinálisis , Infecciones Urinarias , Humanos , Inglaterra/epidemiología , Infecciones Urinarias/diagnóstico , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/orina , Infecciones Urinarias/epidemiología , Masculino , Femenino , Estudios Retrospectivos , Medicina General/tendencias , Antibacterianos/uso terapéutico , Persona de Mediana Edad , Anciano , Urinálisis/métodos , Pautas de la Práctica en Medicina/tendencias , Pautas de la Práctica en Medicina/estadística & datos numéricos , Anciano de 80 o más Años , Adulto , Prescripción Inadecuada/estadística & datos numéricos , Adolescente , Adulto Joven , Modelos LogísticosRESUMEN
Since November 2023, the absolute number of attendances at emergency departments for pneumonia among children aged 5-14 years in England have been above expected levels for the time of year. This increased signal peaked during March 2024 but then persisted into early summer 2024 despite decreases in prevalence of seasonal respiratory pathogens. Record linkage between emergency department and laboratory databases points to this unusual activity being driven largely by Mycoplasma pneumoniae.
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Servicio de Urgencia en Hospital , Mycoplasma pneumoniae , Neumonía , Humanos , Niño , Inglaterra/epidemiología , Preescolar , Adolescente , Incidencia , Neumonía/epidemiología , Masculino , Femenino , Mycoplasma pneumoniae/aislamiento & purificación , Servicio de Urgencia en Hospital/estadística & datos numéricos , Prevalencia , Neumonía por Mycoplasma/epidemiología , Neumonía por Mycoplasma/diagnóstico , Estaciones del Año , Vigilancia de la PoblaciónRESUMEN
Combat sports athletes often undergo rapid body mass loss (BML), which presents health risks. Hydration testing has been proposed as a possible solution to reduce or eliminate rapid BML. However, combat sports athletes may exhibit distinct physiological characteristics due to repeated exposure to BML. Thus, traditional and emerging hydration biomarkers should be investigated to determine their potential suitability for field use in this cohort. This study examined whether BML can explain changes in serum and urine osmolality (SosmΔ, UosmΔ), tear osmolarity (TosmΔ), hematocrit (HctΔ), and urine-specific gravity (USGΔ) after mild-moderate passive dehydration. Biomarker reliability was also assessed across two trials. Fifteen male and female combat sports athletes (age: 26.3 ± 5.3 years, body mass: 67.7 ± 9.9 kg) underwent a sauna protocol twice (5-28 days apart) aiming for 4% BML. The average BML in Trials 1 and 2 was 3.0 ± 0.7%. Regression analysis revealed that BML explained HctΔ (R2 = 0.22, p = 0.009) but not SosmΔ (R2 = 0.11, p = 0.079) or other biomarkers. Intraclass correlation coefficients (ICCs) were significant for all biomarkers except TosmΔ (ICC = 0.06, p = 0.37) and post-Tosm (ICC = 0.04, p = 0.42); post-Hct performed best (ICC = 0.82, p < 0.001). Contingency tables with post-Sosm (295 mOsm/kg) and post-USG (1.020) cutoffs revealed an 80% true negative rate (TNR) and a 62% true positive rate (TPR). Increasing the Sosm cutoff to 301 mOsm/kg decreased the TNR to 52% but increased the TPR to 83%. Although blood parameters were most sensitive to BML, they could only explain 11%-22% of biomarker variation. The typical USG cutoff misclassified 42% of athletes postdehydration, and reliability was generally poor-moderate. Alternative strategies should be pursued to manage rapid BML in combat sports.
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Biomarcadores , Deshidratación , Sudor , Lágrimas , Humanos , Masculino , Biomarcadores/sangre , Adulto , Deshidratación/diagnóstico , Femenino , Concentración Osmolar , Adulto Joven , Sudor/química , Gravedad Específica , Hematócrito , Artes Marciales/fisiología , Baño de Vapor , Reproducibilidad de los Resultados , Pérdida de Peso , Atletas , Orina/químicaRESUMEN
We describe an outbreak of Ralstonia pickettii in the United Kingdom, with isolates genetically indistinguishable from a 2023 Australian outbreak linked to internationally distributed saline solutions. Confirmed cases (n = 3) had bacteraemia, clinically relevant infection, indwelling venous lines and frequent healthcare contact. Multi-stakeholder intervention was required including product recall and risk communications. We recommend a low threshold for investigating clusters of Ralstonia species and similar opportunistic pathogens, considering contaminated product sources. Effective mitigation requires multi-agency partnership and international collaboration.
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Brotes de Enfermedades , Infecciones por Bacterias Gramnegativas , Ralstonia pickettii , Humanos , Reino Unido/epidemiología , Ralstonia pickettii/aislamiento & purificación , Ralstonia pickettii/genética , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Solución Salina , Bacteriemia/epidemiología , Bacteriemia/microbiología , Australia/epidemiología , Contaminación de Medicamentos , MasculinoRESUMEN
Introduction: Robotics uptake in the aerospace industry is low, mainly due to the low-volume/high-accuracy production that aerospace manufacturers require. Furthermore, aerospace manufacturing and assembly sites are often unstructured environments not specifically suitable for robots to operate in. Methods: This paper introduces a robotic visual inspection system using off-the-shelf components able to inspect the mounting holes for wing slat actuators without the need for fixed-coordinate programming; the part just needs to be left within reach of the robot. Our system sets one of the opposed pairs of mounting holes as a reference (the "datum") and then compares the tilt of all other pairs of mounting holes with respect to it. Under the assumption that any deviation in the mounting hole tilt is not systematic but due to normal manufacturing tolerances, our system will either guarantee the correct alignment of all mounting holes or highlight the existence of misaligned holes. Results and Discussion: Computer-vision tilt measurements are performed with an error of below 0.03° using custom optimization for the sub-pixel determination of the center and radius of the mounting holes. The error introduced by the robot's motion from the datum to each of the remaining hole pairs is compensated by moving back to the datum and fixing the orientation again before moving to inspect the next hole pair. This error is estimated to be approximately 0.05°, taking the total tilt error estimation for any mounting hole pair to be 0.08° with respect to the datum. This is confirmed by manually measuring the tilt of the hole pairs using a clock gauge on a calibrated table (not used during normal operation).
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OBJECTIVES: To compare prevalence and change scores of disordered eating (DE) in combat sport athletes by sex and explore the potential relationship between rapid weight loss (RWL) and DE scores. DESIGN: Prospective study based on 24 events (September 2022-2023). METHODS: A body mass (BM) questionnaire was completed at ~1â¯day post-competition providing pre-competition BM data for -7â¯days, -24â¯h, and weigh-in. The Athletic Disordered Eating (ADE) online questionnaire was completed at ~7 and ~28â¯days post-competition, providing overall DE and four subscale scores (food and energy control, bingeing, body control, and body discontent). RESULTS: There were 122, 132, and 89 respondents for the BM (77â¯% male), and ADE questionnaires at 7 (79â¯% male), and 28â¯days (74â¯% male). A large proportion of males' (83â¯%) and females' (89â¯%) DE scores were moderate to very high; minimal (17â¯% vs. 11â¯%), moderate (36â¯% vs. 32â¯%), high (37â¯% vs. 36â¯%), and very high (11â¯% vs. 21â¯%). Comparing DE change scores in males and females indicated deterioration (5â¯% vs. 0â¯%), improvement (3â¯% vs. 25â¯%, pâ¯=â¯0.013), and no difference (92â¯% vs. 75â¯%). Body discontent change score showed a significant sex difference (pâ¯=â¯0.014), with females improving (42â¯% vs. 17â¯%, pâ¯=â¯0.035) and males deteriorating (35â¯% vs. 4â¯%, pâ¯=â¯0.008). Correlation analyses were significant for RWL -7â¯days and males' food control score (Râ¯=â¯0.22, pâ¯=â¯0.031). CONCLUSIONS: Moderate to very high DE indications were identified in 4 of every 5 combat sport competitors. A sex-specific change in body discontent is evident, and most competitors struggle with their food-body relationship post-competition, irrespective of RWL magnitude.
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The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris. This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris. A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.
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Antifúngicos , COVID-19 , Candida auris , Candidiasis , Control de Infecciones , Humanos , Candidiasis/prevención & control , Candidiasis/epidemiología , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Control de Infecciones/métodos , Candida auris/efectos de los fármacos , COVID-19/prevención & control , COVID-19/epidemiología , Antifúngicos/uso terapéutico , Antifúngicos/farmacología , Inglaterra/epidemiología , Infección Hospitalaria/prevención & control , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , SARS-CoV-2 , Farmacorresistencia Fúngica , Candida/efectos de los fármacos , Candida/clasificación , Candida/aislamiento & purificación , Brotes de Enfermedades/prevención & controlRESUMEN
The UK observed a marked increase in scarlet fever and invasive group A streptococcal infection in 2022 with severe outcomes in children and similar trends worldwide. Here we report lineage M1UK to be the dominant source of invasive infections in this upsurge. Compared with ancestral M1global strains, invasive M1UK strains exhibit reduced genomic diversity and fewer mutations in two-component regulator genes covRS. The emergence of M1UK is dated to 2008. Following a bottleneck coinciding with the COVID-19 pandemic, three emergent M1UK clades underwent rapid nationwide expansion, despite lack of detection in previous years. All M1UK isolates thus-far sequenced globally have a phylogenetic origin in the UK, with dispersal of the new clades in Europe. While waning immunity may promote streptococcal epidemics, the genetic features of M1UK point to a fitness advantage in pathogenicity, and a striking ability to persist through population bottlenecks.
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COVID-19 , Filogenia , Infecciones Estreptocócicas , Streptococcus pyogenes , Streptococcus pyogenes/genética , Streptococcus pyogenes/patogenicidad , Streptococcus pyogenes/aislamiento & purificación , Reino Unido/epidemiología , Humanos , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , COVID-19/epidemiología , Pandemias , Escarlatina/epidemiología , Escarlatina/microbiología , Mutación , Proteínas Represoras/genética , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Genoma Bacteriano , Europa (Continente)/epidemiología , Proteínas BacterianasRESUMEN
Water constitutes an indispensable resource crucial for the sustenance of humanity, as it plays an integral role in various sectors such as agriculture, industrial processes, and domestic consumption. Even though water covers 71% of the global land surface, governments have been grappling with the challenge of ensuring the provision of safe water for domestic use. A contributing factor to this situation is the persistent contamination of available water sources rendering them unfit for human consumption. A common contaminant, pesticides are not frequently tested for despite their serious effects on biodiversity. Pesticide determination in water quality assessment is a challenging task because the procedures involved in the extraction and detection are complex. This reduces their popularity in many monitoring campaigns despite their harmful effects. If the existing methods of pesticide analysis are adapted by leveraging new technologies, then information concerning their presence in water ecosystems can be exposed. Furthermore, beyond the advantages conferred by the integration of wireless sensor networks (WSNs), the Internet of Things (IoT), Machine Learning (ML), and big data analytics, a notable outcome is the attainment of a heightened degree of granularity in the information of water ecosystems. This paper discusses methods of pesticide detection in water, emphasizing the possible use of electrochemical sensors, biosensors, and paper-based sensors in wireless sensing. It also explores the application of WSNs in water, the IoT, computing models, ML, and big data analytics, and their potential for integration as technologies useful for pesticide monitoring in water.
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Prostate cancer is the most common non-cutaneous cancer among men in the UK, causing significant health and economic burdens. Diagnosis and risk prognostication can be challenging due to the genetic and clinical heterogeneity of prostate cancer as well as uncertainties in our knowledge of the underlying biology and natural history of disease development. Urinary extracellular vesicles (EVs) are microscopic, lipid bilayer defined particles released by cells that carry a variety of molecular cargoes including nucleic acids, proteins and other molecules. Urine is a plentiful source of prostate-derived EVs. In this narrative review, we summarise the evidence on the function of urinary EVs and their applications in the evolving field of prostate cancer diagnostics and active surveillance. EVs are implicated in the development of all hallmarks of prostate cancer, and this knowledge has been applied to the development of multiple diagnostic tests, which are largely based on RNA and miRNA. Common gene probes included in multi-probe tests include PCA3 and ERG, and the miRNAs miR-21 and miR-141. The next decade will likely bring further improvements in the diagnostic accuracy of biomarkers as well as insights into molecular biological mechanisms of action that can be translated into opportunities in precision uro-oncology.
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While considerable progress has been made in understanding the neuronal circuits that underlie the patterning of locomotor behaviours such as walking, less is known about the circuits that amplify motoneuron output to enable adaptable increases in muscle force across different locomotor intensities. Here, we demonstrate that an excitatory propriospinal neuron population (V3 neurons, Sim1 + ) forms a large part of the total excitatory interneuron input to motoneurons (â¼20%) across all hindlimb muscles. Additionally, V3 neurons make extensive connections among themselves and with other excitatory premotor neurons (such as V2a neurons). These circuits allow local activation of V3 neurons at just one segment (via optogenetics) to rapidly depolarize and amplify locomotor-related motoneuron output at all lumbar segments in both the in vitro spinal cord and the awake adult mouse. Interestingly, despite similar innervation from V3 neurons to flexor and extensor motoneuron pools, functionally, V3 neurons exhibit a pronounced bias towards activating extensor muscles. Furthermore, the V3 neurons appear essential to extensor activity during locomotion because genetically silencing them leads to slower and weaker mice with a poor ability to increase force with locomotor intensity, without much change in the timing of locomotion. Overall, V3 neurons increase the excitability of motoneurons and premotor neurons, thereby serving as global command neurons that amplify the locomotion intensity.
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PURPOSE: Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. The purpose of the study was to measure the associations of specific exposures (deprivation, ethnicity, and clinical characteristics) with incident sepsis and case fatality. METHODS: Two research databases in England were used including anonymized patient-level records from primary care linked to hospital admission, death certificate, and small-area deprivation. Sepsis cases aged 65-100 years were matched to up to six controls. Predictors for sepsis (including 60 clinical conditions) were evaluated using logistic and random forest models; case fatality rates were analyzed using logistic models. RESULTS: 108,317 community-acquired sepsis cases were analyzed. Severe frailty was strongly associated with the risk of developing sepsis (crude odds ratio [OR] 14.93; 95% confidence interval [CI] 14.37-15.52). The quintile with most deprived patients showed an increased sepsis risk (crude OR 1.48; 95% CI 1.45-1.51) compared to least deprived quintile. Strong predictors for sepsis included antibiotic exposure in prior 2 months, being house bound, having cancer, learning disability, and diabetes mellitus. Severely frail patients had a case fatality rate of 42.0% compared to 24.0% in non-frail patients (adjusted OR 1.53; 95% CI 1.41-1.65). Sepsis cases with recent prior antibiotic exposure died less frequently compared to non-users (adjusted OR 0.7; 95% CI 0.72-0.76). Case fatality strongly decreased over calendar time. CONCLUSION: Given the variety of predictors and their level of associations for developing sepsis, there is a need for prediction models for risk of developing sepsis that can help to target preventative antibiotic therapy.
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Atención Primaria de Salud , Sepsis , Humanos , Sepsis/mortalidad , Sepsis/epidemiología , Anciano , Inglaterra/epidemiología , Masculino , Femenino , Estudios de Casos y Controles , Anciano de 80 o más Años , Atención Primaria de Salud/estadística & datos numéricos , Factores de Riesgo , Etnicidad/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Infecciones Comunitarias Adquiridas/mortalidad , Infecciones Comunitarias Adquiridas/epidemiologíaAsunto(s)
Recurrencia , Tonsilectomía , Tonsilitis , Humanos , Tonsilitis/cirugía , Niño , Resultado del TratamientoRESUMEN
Reading is a primary concern of patients with central field loss (CFL) because it is typically performed with foveal vision. Spatial remapping offers one potential avenue to aid in reading; it entails shifting occluded letters to retinal areas where vision is functional. Here, we introduce a method of creating and testing different remapping strategies-ways to remap text-customized for CFL of different shapes. By simulating CFL in typically-sighted individuals, we tested the customization hypothesis-that the benefits of different remapping strategies will depend on the properties of the CFL. That is, remapping strategies will aid reading differentially in the presence of differently shaped CFL. In Experiment 1, letter recognition in the presence of differently shaped CFL was assessed in and around central vision. Using these letter recognition "maps" different spatial remappings were created and tested in Experiment 2 using a word recognition task. Results showed that the horizontal gap remapping, which did not remap any letters vertically, resulted in the best word recognition. Results were also consistent with the customization hypothesis; the benefits of different remappings on word recognition depended on the different CFL shapes. Although the horizontal gap remapping resulted in very good word recognition, tailoring remapping strategies to the shape of patients' CFL may aid reading with the wide range of sizes and shapes encountered by patients with CFL.
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Fóvea Central , Lectura , Humanos , Reconocimiento en Psicología , RetinaRESUMEN
There is growing evidence that altered microbiota abundance of a range of specific anaerobic bacteria are associated with cancer, including Peptoniphilus spp., Porphyromonas spp., Fusobacterium spp., Fenollaria spp., Prevotella spp., Sneathia spp., Veillonella spp. and Anaerococcus spp. linked to multiple cancer types. In this review we explore these pathogenic associations. The mechanisms by which bacteria are known or predicted to interact with human cells are reviewed and we present an overview of the interlinked mechanisms and hypotheses of how multiple intracellular anaerobic bacterial pathogens may act together to cause host cell and tissue microenvironment changes associated with carcinogenesis and cancer cell invasion. These include combined effects on changes in cell signalling, DNA damage, cellular metabolism and immune evasion. Strategies for early detection and eradication of anaerobic cancer-associated bacterial pathogens that may prevent cancer progression are proposed.
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Bacterias Anaerobias , Carcinogénesis , Humanos , Evasión Inmune , Porphyromonas , Transducción de Señal , Microambiente TumoralRESUMEN
The development of cancer is an evolutionary process involving the sequential acquisition of genetic alterations that disrupt normal biological processes, enabling tumor cells to rapidly proliferate and eventually invade and metastasize to other tissues. We investigated the genomic evolution of prostate cancer through the application of three separate classification methods, each designed to investigate a different aspect of tumor evolution. Integrating the results revealed the existence of two distinct types of prostate cancer that arise from divergent evolutionary trajectories, designated as the Canonical and Alternative evolutionary disease types. We therefore propose the evotype model for prostate cancer evolution wherein Alternative-evotype tumors diverge from those of the Canonical-evotype through the stochastic accumulation of genetic alterations associated with disruptions to androgen receptor DNA binding. Our model unifies many previous molecular observations, providing a powerful new framework to investigate prostate cancer disease progression.
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Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/genética , Próstata/metabolismo , Mutación , Genómica , Evolución MolecularRESUMEN
Colorectal cancer (CRC) is a heterogenous malignancy underpinned by dysregulation of cellular signaling pathways. Previous literature has implicated aberrant JAK/STAT3 signal transduction in the development and progression of solid tumors. In this study we investigate the effectiveness of inhibiting JAK/STAT3 in diverse CRC models, establish in which contexts high pathway expression is prognostic and perform in depth analysis underlying phenotypes. In this study we investigated the use of JAK inhibitors for anti-cancer activity in CRC cell lines, mouse model organoids and patient-derived organoids. Immunohistochemical staining of the TransSCOT clinical trial cohort, and 2 independent large retrospective CRC patient cohorts was performed to assess the prognostic value of JAK/STAT3 expression. We performed mutational profiling, bulk RNASeq and NanoString GeoMx® spatial transcriptomics to unravel the underlying biology of aberrant signaling. Inhibition of signal transduction with JAK1/2 but not JAK2/3 inhibitors reduced cell viability in CRC cell lines, mouse, and patient derived organoids (PDOs). In PDOs, reduced Ki67 expression was observed post-treatment. A highly significant association between high JAK/STAT3 expression within tumor cells and reduced cancer-specific survival in patients with high stromal invasion (TSPhigh) was identified across 3 independent CRC patient cohorts, including the TrasnSCOT clinical trial cohort. Patients with high phosphorylated STAT3 (pSTAT3) within the TSPhigh group had higher influx of CD66b + cells and higher tumoral expression of PDL1. Bulk RNAseq of full section tumors showed enrichment of NFκB signaling and hypoxia in these cases. Spatial deconvolution through GeoMx® demonstrated higher expression of checkpoint and hypoxia-associated genes in the tumor (pan-cytokeratin positive) regions, and reduced lymphocyte receptor signaling in the TME (pan-cytokeratin- and αSMA-) and αSMA (pan-cytokeratin- and αSMA +) areas. Non-classical fibroblast signatures were detected across αSMA + regions in cases with high pSTAT3. Therefore, in this study we have shown that inhibition of JAK/STAT3 represents a promising therapeutic strategy for patients with stromal-rich CRC tumors. High expression of JAK/STAT3 proteins within both tumor and stromal cells predicts poor outcomes in CRC, and aberrant signaling is associated with distinct spatially-dependant differential gene expression.
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Neoplasias Colorrectales , Humanos , Animales , Ratones , Estudios Retrospectivos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Transducción de Señal , Hipoxia , Queratinas/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Línea Celular TumoralRESUMEN
In 2022, there were global reports of increased numbers of acute hepatitis not explained by hepatitis A-E virus infection in children. This manuscript summarises histopathology results from 20 patients in the United Kingdom who underwent liver transplant or had a liver biopsy as part of aetiological investigations. All available histopathological samples were reviewed centrally as part of the outbreak investigation. A working group comprised of infection specialists, hepatologists and histopathologists met virtually to review the cases, presentation, investigations and histopathology. All 20 liver samples had evidence of inflammation without significant interface activity, and submassive confluent pan-lobular or multilobular hepatocellular necrosis. Overall, the predominant histopathological findings were of acute nonspecific hepatitis with submassive hepatic necrosis and central vein perivenulitis and endothelitis. Histopathological findings were a poor indicator of aetiology.
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Hepatitis , Hepatopatías , Trasplante de Hígado , Humanos , Niño , Hígado/patología , Hepatitis/patología , Hepatopatías/patología , BiopsiaRESUMEN
In most holometabolous insects, sex differentiation occurs via a hierarchical cascade of transcription factors, with doublesex (dsx) regulating genes that control sex-specific traits. Although less is known in hemimetabolous insects, early evidence suggests that substantial differences exist from more evolutionarily advanced insects. Here, we identified and characterized dsx in Lygus hesperus (western tarnished plant bug), a hemipteran pest of many agricultural crops in western North America. The full-length transcript for L. hesperus dsx (Lhdsx) and several variants encode proteins with conserved DNA binding and oligomerization domains. Transcript profiling revealed that Lhdsx is ubiquitously expressed, likely undergoes alternative pre-mRNA splicing, and, unlike several model insects, is sex-biased rather than sex-specific. Embryonic RNA interference (RNAi) of Lhdsx only impacted sex development in adult males, which lacked both internal reproductive organs and external genitalia. No discernible impacts on adult female development or reproductivity were observed. RNAi knockdown of Lhdsx in nymphs likewise only affected adult males, which lacked the characteristic dimorphic coloration but had dramatically elevated vitellogenin transcripts. Gene knockout of Lhdsx by CRISPR/Cas9 editing yielded only females in G0 and strongly biased heterozygous G1 offspring to females with the few surviving males showing severely impaired genital development. These results indicate that L. hesperus male development requires Lhdsx, whereas female development proceeds via a basal pathway that functions independently of dsx. A fundamental understanding of sex differentiation in L. hesperus could be important for future gene-based management strategies of this important agricultural pest.
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Escarabajos , Heterópteros , Femenino , Masculino , Animales , Heterópteros/genética , Diferenciación Sexual , Desarrollo SexualRESUMEN
BACKGROUND AND AIMS: Sepsis is a serious and life-threatening condition caused by a dysregulated immune response to an infection. Recent guidance issued in the UK gave recommendations around recognition and antibiotic treatment of sepsis, but did not consider factors relating to health inequalities. The aim of this study was to summarise the literature investigating associations between health inequalities and sepsis. METHODS: Searches were conducted in Embase for peer-reviewed articles published since 2010 that included sepsis in combination with one of the following five areas: socioeconomic status, race/ethnicity, community factors, medical needs and pregnancy/maternity. RESULTS: Five searches identified 1,402 studies, with 50 unique studies included in the review after screening (13 sociodemographic, 14 race/ethnicity, 3 community, 3 care/medical needs and 20 pregnancy/maternity; 3 papers examined multiple health inequalities). Most of the studies were conducted in the USA (31/50), with only four studies using UK data (all pregnancy related). Socioeconomic factors associated with increased sepsis incidence included lower socioeconomic status, unemployment and lower education level, although findings were not consistent across studies. For ethnicity, mixed results were reported. Living in a medically underserved area or being resident in a nursing home increased risk of sepsis. Mortality rates after sepsis were found to be higher in people living in rural areas or in those discharged to skilled nursing facilities while associations with ethnicity were mixed. Complications during delivery, caesarean-section delivery, increased deprivation and black and other ethnic minority race were associated with post-partum sepsis. CONCLUSION: There are clear correlations between sepsis morbidity and mortality and the presence of factors associated with health inequalities. To inform local guidance and drive public health measures, there is a need for studies conducted across more diverse setting and countries.