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Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22-which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu's arteritis3-6-we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.
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Inflamación , Macrófagos , Proteína Proto-Oncogénica c-ets-2 , Femenino , Humanos , Masculino , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Células Cultivadas , Cromosomas Humanos Par 21/genética , Bases de Datos Factuales , Regulación de la Expresión Génica , Estudio de Asociación del Genoma Completo , Genómica , Haplotipos/genética , Inflamación/genética , Enfermedades Inflamatorias del Intestino/genética , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/patología , Proteína Proto-Oncogénica c-ets-2/genética , Proteína Proto-Oncogénica c-ets-2/metabolismo , Reproducibilidad de los Resultados , Factores de Necrosis Tumoral/metabolismo , Interleucina-23/metabolismoRESUMEN
Objective: This study aims to develop and validate the Futile Recanalization Prediction Score (FRPS), a novel tool designed to predict the severity risk of FR and aid in pre- and post-EVT risk assessments. Methods: The FRPS was developed using a rigorous process involving the selection of predictor variables based on clinical relevance and potential impact. Initial equations were derived from previous meta-analyses and refined using various statistical techniques. We employed machine learning algorithms, specifically random forest regression, to capture nonlinear relationships and enhance model performance. Cross-validation with five folds was used to assess generalizability and model fit. Results: The final FRPS model included variables such as age, sex, atrial fibrillation (AF), hypertension (HTN), diabetes mellitus (DM), hyperlipidemia, cognitive impairment, pre-stroke modified Rankin Scale (mRS), systolic blood pressure (SBP), onset-to-puncture time, sICH, and NIHSS score. The random forest model achieved a mean R-squared value of approximately 0.992. Severity ranges for FRPS scores were defined as mild (FRPS < 66), moderate (FRPS 66-80), and severe (FRPS > 80). Conclusions: The FRPS provides valuable insights for treatment planning and patient management by predicting the severity risk of FR. This tool may improve the identification of candidates most likely to benefit from EVT and enhance prognostic accuracy post-EVT. Further clinical validation in diverse settings is warranted to assess its effectiveness and reliability.
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BACKGROUND: Posterior circulation stroke (PCS) accounts for approximately 20% of all acute ischemic strokes. The optimal reperfusion therapy for PCS management remains uncertain. PURPOSE: To evaluate the prevalence and outcomes of intravenous thrombolysis (IVT), endovascular thrombectomy (EVT), and bridging therapy in PCS patients. MATERIAL AND METHODS: We conducted a meta-analysis of 19 studies examining reperfusion therapy outcomes in PCS patients, including 9765 individuals. We pooled prevalence data and assessed associations between reperfusion therapies and clinical, safety, and recanalization outcomes using random-effects models. RESULTS: The pooled prevalence of reperfusion therapies post-acute PCS was 39% for IVT, 54% for EVT, and 48% for bridging therapy. EVT was associated with significantly higher odds of favorable functional outcomes (modified Rankin Score [mRS] 0-3) at 90 days compared to standard medical therapy (odds ratio [OR] = 5.68; 95% confidence interval [CI]=2.07-15.59; P = 0.001). Conversely, bridging therapy was linked to reduced odds of favorable functional outcomes at 90 days compared to EVT (OR = 0.35; 95% CI=0.26-0.47; P < 0.001). Bridging therapy was also significantly associated with lower odds of good functional outcomes (mRS 0-2) (OR = 0.25; 95% CI=0.11-0.54; P < 0.001), reduced risk of symptomatic intracranial hemorrhage (OR = 0.26; 95% CI=0.07-0.68; P = 0.009), lower mortality (OR = 0.13; 95% CI=0.04-0.44; P = 0.001), and less successful recanalization (OR = 0.35; 95% CI=0.13-0.94; P = 0.038) relative to EVT. CONCLUSION: Our meta-analysis underscores the favorable outcomes associated with EVT in PCS cases. With notable reperfusion rates, understanding factors influencing PCS outcomes can inform patient selection and prognostic considerations.
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Trombectomía , Terapia Trombolítica , Humanos , Terapia Trombolítica/métodos , Trombectomía/métodos , Procedimientos Endovasculares/métodos , Reperfusión/métodos , Accidente Cerebrovascular Isquémico/terapia , Accidente Cerebrovascular Isquémico/cirugía , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Resultado del Tratamiento , Accidente Cerebrovascular/terapiaRESUMEN
We report a review examining the psychological wellbeing of parents of children with Down syndrome (DS) relative to that of parents of typically developing (TD) children. A systematic search identified 57 relevant studies, which were synthesised meta-analytically. Relative to their counterparts with TD children, mothers and fathers of children with DS reported higher levels of parenting stress (mothers: g = 0.57, 95% CI [0.33, 0.81]; fathers: g = 0.40, [0.24, 0.56]), depressive symptoms (mothers: g = 0.42, [0.23, 0.61]; fathers: g = 0.25, [0.02, 0.48]) and psychological distress (mothers: g = 0.45, [0.30, 0.60]; fathers: g = 0.63, [0.26, 0.99]). Small effects were found for anxiety for mothers (g = 0.16, [0.03, 0.29]), with no differences for fathers (g = 0.03, [-0.25, 0.32]). No group differences were found for positive impact of parenting (mothers: g = -0.09, [-0.25, 0.07]; fathers: g = -0.04, [-0.30, 0.22]), while evidence concerning other positive wellbeing outcomes was limited. No significant moderating effects of child age range, country income level, or group differences in parental education level were identified, but limited subgroup analyses were possible. Raising a child with DS may be associated with elevated stress, depressive symptoms, and psychological distress for mothers and fathers. However, levels of parenting reward appear equivalent to those experienced by parents raising TD children.
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Síndrome de Down , Responsabilidad Parental , Padres , Estrés Psicológico , Humanos , Síndrome de Down/psicología , Responsabilidad Parental/psicología , Estrés Psicológico/psicología , Niño , Padres/psicología , Depresión/psicología , Ansiedad/psicología , Adulto , Distrés PsicológicoRESUMEN
III-V colloidal quantum dots (QDs) promise Pb and Hg-free QD compositions with which to build short-wavelength infrared (SWIR) optoelectronic devices. However, their synthesis is limited by the availability of group-V precursors with controllable reactivities to prepare monodisperse, SWIR-absorbing III-V QDs. Here, we report a one-pot heat-up method to synthesize â¼8 nm edge length (â¼6.5 nm in height) tetrahedral, SWIR-absorbing InAs QDs by increasing the [In3+]:[As3+] ratio introduced using commercially available InCl3 and AsCl3 precursors and by decreasing the concentration and optimizing the volume of the reducing reagent superhydride to control the concentration of In(0) and As(0) intermediates through QD nucleation and growth. InAs QDs are treated with NOBF4, and their deposited films are exchanged with Na2S to yield n-type InAs QD films. We realize the only colloidal InAs QD photoconductors with responsivity at the technologically important wavelength of 1.55 µm.
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BACKGROUND: Futile recanalization (FR) continues to raise concern despite the success of endovascular thrombectomy (EVT) in acute ischemic stroke (AIS). Understanding the prevalence of FR and identifying associated factors are crucial for refining patient prognoses and optimizing management strategies. OBJECTIVES: This study aims to comprehensively assess the pooled prevalence of FR, explore the diverse factors connected with FR, and establish the association of FR with long-term clinical outcomes among AIS patients undergoing EVT. MATERIALS AND METHODS: Incorporating studies focusing on FR following EVT in AIS patients, we conducted a random-effect meta-analysis to assess the pooled prevalence and its association with various clinical and imaging risk factors linked to FR. Summary estimates were compiled and study heterogeneity was explored. RESULTS: Our comprehensive meta-analysis, involving 11,700 AIS patients undergoing EVT, revealed a significant pooled prevalence of FR at 51%, with a range of 48% to 54% (Effect Size [ES]: 51%; 95% Confidence Interval [CI]: 48-54%; z = 47.66; p < 0.001). Numerous clinical factors demonstrated robust correlations with FR, including atrial fibrillation (Odds Ratio [OR]: 1.39, 95% CI 1.22 1.59; p < 0.001), hypertension (OR 1.65, 95% CI 1.41 1.92; p < 0.001), diabetes mellitus (OR 1.71, 95% CI 1.47 1.99; p < 0.001), previous stroke or transient ischemic attack (OR 1.298, 95% CI 1.06 1.59; p = 0.012), prior anticoagulant usage (OR 1.33, 95% CI 1.08 1.63; p = 0.007), cardioembolic strokes (OR 1.34, 95% CI 1.10 1.63; p = 0.003), and general anesthesia (OR 1.53, 95% CI 1.35 1.74; p < 0.001). Conversely, FR exhibited reduced likelihoods of smoking (OR 0.66, 95% CI 0.57 0.77; p < 0.001), good collaterals (OR 0.33, 95% CI 0.23 0.49; p < 0.001), male sex (OR 0.87, 95% CI 0.77 0.97; p = 0.016), and intravenous thrombolysis (IVT) (OR 0.75, 95% CI 0.66 0.86; p < 0.001). FR was strongly associated with increasing age (standardized mean difference [SMD] 0.49, 95% CI 0.42 0.56; p < 0.0001), baseline systolic blood pressure (SMD 0.20, 95% CI 0.13 0.27; p < 0.001), baseline National Institute of Health Stroke Severity Score (SMD 0.75, 95% CI: 0.65 0.86; p < 0.001), onset-to-treatment time (SMD 0.217, 95% CI 0.13 0.30; p < 0.001), onset-to-recanalization time (SMD 0.38, 95% CI 0.19; 0.57; p < 0.001), and baseline blood glucose (SMD 0.31, 95% CI 0.22 0.41; p < 0.001), while displaying a negative association with reduced baseline Alberta Stroke Program Early CT Score (ASPECTS) (SMD -0.37, 95% CI -0.46 -0.27; p < 0.001). Regarding clinical outcomes, FR was significantly associated with increased odds of symptomatic intracranial hemorrhages (OR 7.37, 95% CI 4.89 11.12; p < 0.001), hemorrhagic transformations (OR 2.98, 95% CI 2.37 3.75; p < 0.001), and 90-day mortality (OR 19.24, 95% CI 1.57 235.18; p = 0.021). CONCLUSIONS: The substantial prevalence of FR, standing at approximately 51%, warrants clinical consideration. These findings underscore the complexity of FR in AIS patients and highlight the importance of tailoring management strategies based on individual risk factors and clinical profiles.
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AIMS: Atherosclerosis is driven by multiple processes across multiple body systems. For example, the innate immune system drives both atherogenesis and plaque rupture via inflammation, while coronary artery-occluding thrombi formed by the coagulation system cause myocardial infarction and death. However, the interplay between these systems during atherogenesis is understudied. We recently showed that coagulation and immunity are fundamentally linked by the activation of interleukin-1α (IL-1α) by thrombin, and generated a novel knock-in mouse in which thrombin cannot activate endogenous IL-1α [IL-1α thrombin mutant (IL-1αTM)]. METHODS AND RESULTS: Here, we show significantly reduced atherosclerotic plaque formation in IL-1αTM/Apoe-/- mice compared with Apoe-/- and reduced T-cell infiltration. However, IL-1αTM/Apoe-/- plaques have reduced vascular smooth muscle cells, collagen, and fibrous caps, indicative of a more unstable phenotype. Interestingly, the reduced atherogenesis seen with thrombin inhibition was absent in IL-1αTM/Apoe-/- mice, suggesting that thrombin inhibitors can affect atherosclerosis via reduced IL-1α activation. Finally, bone marrow chimeras show that thrombin-activated IL-1α is derived from both vessel wall and myeloid cells. CONCLUSIONS: Together, we reveal that the atherogenic effect of ongoing coagulation is, in part, mediated via thrombin cleavage of IL-1α. This not only highlights the importance of interplay between systems during disease and the potential for therapeutically targeting IL-1α and/or thrombin, but also forewarns that IL-1 may have a role in plaque stabilization.
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Aterosclerosis , Placa Aterosclerótica , Trombina , Animales , Ratones , Apolipoproteínas E/genética , Aterosclerosis/genética , Aterosclerosis/prevención & control , Proliferación Celular , Colágeno/metabolismo , Interleucina-1alfa/genética , Interleucina-1alfa/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Noqueados para ApoE , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Placa Aterosclerótica/metabolismo , Trombina/metabolismoRESUMEN
Background: A well-coordinated adaptive immune response is crucial for limiting COVID-19 disease. Some individuals with immunodeficiency are at a high risk of developing severe COVID-19. Therefore, the development of standardized methods for measuring different arms of the vaccine response in the setting of immunodeficiency is of particular interest. In this study, we compared the vaccine response of individuals living with immunodeficiency with healthy controls in terms of interferon gamma (IFN-γ) production and spike protein-specific antibody level post primary COVID-19 vaccination and booster vaccines. Additionally, the disease severity of those individuals who contracted COVID-19 was assessed. Methods: Whole blood was stimulated overnight from 71 participants and 99 healthy controls. Commercially available PepTivator® peptide pool and trimeric spike protein stimulation were used. ELISA was used to analyze IFN-γ levels. The total SARS-CoV-2 spike protein antibody titre was measured using a Roche Elecsys® S total antibody assay. Patient characteristics, COVID-19 infection status and IDDA 2.1 'Kaleidoscope' scores were recorded. Vaccine responses were scored from zero to three. Results: 99% of healthy controls, 89% of individuals with IEI and 76% with secondary immunodeficiency (SID) had an IFN-γ level above the validated reference range after peptide mix stimulation following primary vaccination. There was an increase in IFN-γ levels in patients with inborn errors of immunity (IEI) following the booster vaccine (p = 0.0156). 100% of healthy controls, 70% of individuals living with IEI and 64% of individuals living with SID had detectable spike protein-specific antibody levels following the primary vaccination. 55% of immunodeficiency patients who had mild COVID-19 and 10% with moderate/severe COVID-19 had detectable antibody and IFN-γ levels post vaccine. The mean pre-infection IDDA 2.1 scores were higher in individuals who developed moderate/severe COVID-19 (25.2 compared to 9.41). Conclusions: Covid whole-blood IGRA is a highly accurate, straightforward and robust assay and can be easily adapted to measure cellular response to COVID-19. A complete evaluation of the vaccine response may be particularly important for individuals living with immunodeficiency. A clinical immunodeficiency score and a validated vaccine response score may be valuable tools in estimating COVID-19 disease risk and identifying individuals living with immunodeficiency who may benefit from enhanced vaccination schedules.
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COVID-19 , Síndromes de Inmunodeficiencia , Humanos , Vacunas contra la COVID-19 , COVID-19/prevención & control , Glicoproteína de la Espiga del Coronavirus , SARS-CoV-2 , Gravedad del Paciente , Interferón gammaRESUMEN
The frequency, duration, and intensity of heat waves in Australia are increasing. To reduce the impact of heat waves on milk production, novel management strategies are required. Altering the forage type and amount offered affect the heat load on dairy cows and offer potential strategies to ameliorate the effects of hot weather. Thirty-two multiparous, lactating Holstein-Friesian cows were assigned one of four dietary treatments: chicory high amount, chicory low amount, pasture silage high amount, or pasture silage low amount. These cows were exposed to a heat wave in controlled-environment chambers. Cows that were offered fresh chicory had similar feed intake to cows that were offered pasture silage (15.3 kg DM/d). However, cows that were offered chicory produced greater energy-corrected milk (21.9 vs. 17.2 kg/d) and had a lower maximum body temperature (39.4 vs. 39.6 °C) than cows that were offered pasture silage overall. Cows that were offered the high amount of forage had greater feed intake (16.5 vs. 14.1 kg DM/d) and energy corrected milk yield (20.0 vs. 17.9 kg/d) than cows that were offered the low amount, as intended, but with no difference in maximum body temperature (39.5 °C). We conclude that feeding chicory instead of pasture silage to dairy cows shows promise as a dietary strategy to ameliorate the effect of heat exposure, and there was no advantage in restricting feed amount.
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Understanding the cumulative effects of multiple stressors is a research priority in environmental science. Ecological models are a key component of tackling this challenge because they can simulate interactions between the components of an ecosystem. Here, we ask, how has the popular modeling platform Ecopath with Ecosim (EwE) been used to model human impacts related to climate change, land and sea use, pollution, and invasive species? We conducted a literature review encompassing 166 studies covering stressors other than fishing mostly in aquatic ecosystems. The most modeled stressors were physical climate change (60 studies), species introductions (22), habitat loss (21), and eutrophication (20), using a range of modeling techniques. Despite this comprehensive coverage, we identified four gaps that must be filled to harness the potential of EwE for studying multiple stressor effects. First, only 12% of studies investigated three or more stressors, with most studies focusing on single stressors. Furthermore, many studies modeled only one of many pathways through which each stressor is known to affect ecosystems. Second, various methods have been applied to define environmental response functions representing the effects of single stressors on species groups. These functions can have a large effect on the simulated ecological changes, but best practices for deriving them are yet to emerge. Third, human dimensions of environmental change - except for fisheries - were rarely considered. Fourth, only 3% of studies used statistical research designs that allow attribution of simulated ecosystem changes to stressors' direct effects and interactions, such as factorial (computational) experiments. None made full use of the statistical possibilities that arise when simulations can be repeated many times with controlled changes to the inputs. We argue that all four gaps are feasibly filled by integrating ecological modeling with advances in other subfields of environmental science and in computational statistics.
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Ecosistema , Proyectos de Investigación , Humanos , Modelos Teóricos , Especies Introducidas , Cambio ClimáticoRESUMEN
BACKGROUND: Cerebral collateral status has a potential role in mediating postreperfusion clinical and safety outcomes in acute ischemic stroke (AIS). PURPOSE: To investigate the prognostic accuracy and impact of collateral status on clinical and safety outcomes in patients with AIS receiving reperfusion therapy. MATERIAL AND METHODS: Studies with AIS patients treated with reperfusion therapy, collateral status assessed using Tan, ASITN/SIR, or similar collateral grading methods and data stratified according to collateral status were included. Relevant data on clinical outcomes, such as functional outcome at 90 days, mortality at 90 days, angiographic reperfusion, symptomatic intracerebral hemorrhage (sICH) and hemorrhagic transformation (HT), were collated and analyzed. RESULTS: A meta-analysis of 18 studies involving 4132 patients with AIS was conducted. Good collateral status was significantly associated with angiographic reperfusion (odds ratio [OR]=1.97, 95% confidence interval [CI]=1.38-2.80; P < 0.0001), sICH (OR=0.67, 95% CI=0.46-0.99; P = 0.042), and 90-day functional outcome (OR=3.05, 95% CI=1.78-5.24; P < 0.0001). However, its association with HT (OR=0.76, 95% CI=0.38-1.51; P = 0.425) and three-month mortality (OR=0.53, 95% CI=0.17-1.69; P = 0.280) did not reach statistical significance. The prognostic accuracy of collaterals for predicting angiographic reperfusion, HT, functional outcome (at 90 days), and mortality (at 90 days) were 63%, 49%, 66%, and 48%, respectively. CONCLUSION: Cerebral collaterals are significantly associated with clinical and safety outcomes, albeit with a prognostic accuracy range of 48%-66%; thus, evaluation of their patency is a useful prognostic tool in patients with AIS receiving reperfusion therapy.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/tratamiento farmacológico , Pronóstico , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapia , Isquemia Encefálica/complicaciones , Terapia Trombolítica/métodos , Resultado del Tratamiento , Circulación Colateral , Hemorragia Cerebral/etiología , Reperfusión/métodos , Angiografía Cerebral/métodosRESUMEN
Background: The impact of lesion topography (LT), characterised by the Alberta Stroke Programme Early CT Score (ASPECTS), on outcomes after reperfusion therapy in acute ischemic stroke (AIS) is poorly elucidated. We investigated the prognostic accuracy of ASPECTS-based LT assessment and its association with clinical outcomes in AIS patients considered for reperfusion therapy or receiving intravenous thrombolysis (IVT), endovascular thrombectomy (EVT), or none or both. Methods: Studies were identified from PubMed with additional studies added from Google Scholar. The prevalence of individual ASPECTS regions will also be determined. The association of individual ASPECTS regions with the functional outcome at 90 days will be assessed using random-effects modelling for various cut-offs, such as 6, 7 and 8. The association of continuous ASPECTS with the functional outcome at 90 days will also be undertaken. Forest plots of odds ratios (ORs) will be generated. Results: A total of 25 studies have been included in the final analysis, encompassing 11,404 patients. Pooled estimates indicate that the highest prevalence rates were in cases involving the insula and lentiform nucleus. Subgroup analysis for ASPECTS < 6 (OR 6.10; 95% CI 2.50−14.90; p < 0.0001), ASPECTS < 7 (OR 4.58; 95% CI 1.18−17.86; p < 0.0001) and ASPECTS < 8 (OR 2.26; 95% CI 1.32−3.89; p < 0.0001) revealed a significant association with poor functional outcome at 90 days. Decreasing ASPECTS significantly increased the odds of poor functional outcomes at 90 days (SMD −1.15; 95% CI −1.77−−0.52; p < 0.0001). Conclusions: Our meta-analysis demonstrates that decreasing ASPECTS is significantly associated with poor functional outcomes. Individual ASPECTS regions associated with the highest odds of poor functional outcomes were identified. Future studies on the association of LT and clinical outcomes specific to EVT are required.
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Background: Brain clots retrieved following endovascular thrombectomy in acute ischemic stroke patients may offer unique opportunities to characterise stroke aetiology and aid stroke decision-making in select groups of patients. However, the evidence around the putative association of clot morphology with stroke aetiology is limited and remains inconclusive. This study aims to perform a systematic review and meta-analysis to delineate the association of brain clot composition with stroke aetiology and post-reperfusion outcomes in patients receiving endovascular thrombectomy. Methods: The authors conducted a systematic literature review and meta-analysis by extracting data from several research databases (MEDLINE/PubMed, Cochrane, and Google Scholar) published since 2010. We used appropriate key search terms to identify clinical studies concerning stroke thrombus composition, aetiology, and clinical outcomes, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: The authors identified 30 articles reporting on the relationship between stroke thrombus composition or morphology and aetiology, imaging, or clinical outcomes, of which 21 were included in the meta-analysis. The study found that strokes of cardioembolic origin (SMD = 0.388; 95% CI, 0.032-0.745) and cryptogenic origin (SMD = 0.468; 95% CI, 0.172-0.765) had significantly higher fibrin content than strokes of non-cardioembolic origin. Large artery atherosclerosis strokes had significantly lower fibrin content than cardioembolic (SMD = 0.552; 95% CI, 0.099-1.004) or cryptogenic (SMD = 0.455; 95% CI, 0.137-0.774) strokes. Greater red blood cell content was also significantly associated with a thrombolysis in cerebral infarction score of 2b-3 (SMD = 0.450; 95% CI, 0.177-0.722), and a positive hyperdense middle cerebral artery sign (SMD = 0.827; 95% CI, 0.472-1.183). No significant associations were found between red blood cell, platelet, or white blood cell content and aetiology, or between clot composition and bridging thrombolysis. Conclusions: This meta-analysis found that fibrin composition is significantly higher in strokes of cardioembolic and cryptogenic origin, and that red blood cell content is positively associated with the hyperdense middle cerebral artery sign and better reperfusion outcomes. Important advances to stroke clinical workup can be derived from these findings, in which many aspects of stroke workflow remain to be optimised. As data are still limited in terms of the association of various thrombus components with stroke aetiology as well as a standardised method of analysis, further studies are required to validate these findings to guide their use in clinical decision-making.
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Cereal grains that differ in the rate and extent of ruminal fermentation differ in heat increment and may be used to improve thermoregulation during heat stress. This experiment investigated the responses of dairy cows in late lactation to a heat challenge when offered wheat-grain or corn-grain. Eighteen lactating cows, 220 ± 94 (mean ± standard deviation) days in milk, 3.7 ± 0.17 years of age and 558 ± 37 kg bodyweight, were allocated treatments containing 6 kg dry matter (DM)/day of wheat grain or 6 kg DM/day corn grain (9 per treatment) plus 14 kg DM/day of alfalfa hay. Measurements were made during a 7-day pre-challenge period at ambient conditions in individual stalls, during a 4-day heat challenge (temperature humidity index of 74 to 84) in individual controlled-climate chambers, then during a 7-day recovery period at ambient conditions in individual stalls. During the heat challenge, cows offered corn had lower respiration rates (p = 0.017) and greater feed intake (p = 0.021) but energy-corrected milk (p = 0.097) was not different to that of cows offered wheat. Feeding corn grain to dairy cows during a heat challenge reduced some of the negative impacts of heat stress, enabling the cows to consume more forage compared with supplementing with wheat grain.
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Aim To describe the effect of the Covid pandemic on the general practice workplace based learning of GP training in Ireland. Methods A prospective national survey of GP trainees who were in their GP practice placements on three separate occasions throughout the winter pandemic of 2020/2021 Results The average response rate to the three surveys was 19.4%. As the pandemic worsened, the number of face to face consultations dropped so that 51% (n=41) of trainees were seeing less than 5 patients face to face by the third survey. Conversely, the number of telephone/video consultations rose so that by the third survey 54% (n=44) of trainees were conducting more than 16 consultations per day remotely. Examinations and GP presentations expected to be daily occurrences diminished as the pandemic grew more severe, such that by the third survey 24-25% of trainees had not conducted a respiratory examination or dealt with new/unexpected hypertension in the previous month. Conclusion This study demonstrates abrupt change to the normal course of their training which was experienced by Irish GP trainees as a result of Covid, with examples from clinical practice. Adaptions of the training programme helped mitigate against the effects of the pandemic.
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COVID-19 , Medicina General , Medicina Familiar y Comunitaria , Humanos , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND: In a population-based birth cohort, we aimed to identify longitudinal trajectories of atopic dermatitis (AD) during childhood using data from different sources (validated questionnaires and healthcare records). We investigated the impact of different AD definitions on such trajectories and their relationships with various risk factors. METHODS: Of the 1184 children born into the study, 1083 had information on current AD for at least three follow-ups from birth to age 11 years and were included in the analysis for parentally reported AD (PRAD). Data were transcribed from healthcare records for 916 of 1184 children for the analysis of doctor-diagnosed AD (DDAD). We also derived a composite definition of AD (CDAD) (at least two of the following: PRAD, DDAD, current use of AD treatment). Using latent class analysis (LCA), we determined longitudinal profiles of AD using the three definitions. Filaggrin (FLG) genotype data were available for 803 white participants. RESULTS: For PRAD, LCA identified four AD classes ('no AD', 'persistent', 'early-onset remitting' and 'late-onset'). For DDAD and CDAD, the optimal number of phenotypes was three ('no AD', 'persistent' and 'early-onset remitting'). Although AD classes at population level appeared similar in different models, a considerable proportion of children (n = 485, 45%) moved between classes. The association with FLG genotype, atopic diseases and early-life risk factors was inconsistent across different definitions, but the association with oral food challenge-confirmed peanut allergy was similar, with a nine- to 11-fold increase among children in the persistent AD class. In a CDAD model, compared with the early-onset remitting class, those with persistent AD were significantly more likely to have (at age 3 years) moderate/severe AD, polysensitization and current wheeze, and were less likely to have been breastfed. CONCLUSIONS: Standardized composite definitions of AD may help to define AD cases with more precision and identify more consistent long-term trajectories.