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1.
J Clin Microbiol ; : e0102224, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382308

RESUMO

The BioFire Joint Infection (JI) Panel offers a significant advancement in the rapid diagnosis of joint infections by facilitating the simultaneous detection of multiple bacterial and fungal pathogens, as well as resistance markers, directly from synovial fluid samples. An article published in the Journal of Clinical Microbiology by Moran et al. (J Clin Microbiol 62:e00182-24, 2024, https://doi.org/10.1128/jcm.00182-24) presents both prospective and retrospective analyses of the panel's real-world clinical application. The study highlights the panel's benefits, such as its rapid turnaround time and ability to identify challenging pathogens, while also discussing its limitations, particularly in detecting certain off-panel organisms.

2.
Patient Educ Couns ; 130: 108456, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39393327

RESUMO

OBJECTIVE: This study examines the way healthcare staff describe challenging patients and perceive responsibility for follow-up of patients with chronic conditions. METHODS: Interviews were conducted with 46 healthcare staff (15 primary care physicians/12 nurses/15 administrative staff/4 pharmacists) at 12 clinics in Israel. They were audiotaped, transcribed, and thematically analyzed using Atlas qualitative data analysis software. RESULTS: Participants defined patients as "challenging" either because they are less likely to follow medical recommendations or are felt to overconsume care. Staff believed that patients did not follow medical recommendations because they were indifferent, unaware, in denial about deteriorating medical condition, or fear of the unknown. Participants generally perceived a shared responsibility for follow-up between the staff and the patient. Staff who endorsed closer relationships with staff members expressed empathy toward challenging patients and felt responsible for follow-up. CONCLUSIONS: Healthcare staff perceive themselves as partially responsible for helping patients follow up with medical recommendations. Cohesive staff relationships may promote higher levels of empathy toward challenging patients and may contribute to helping patients follow up with recommended care. Practice implications To improve follow-up with medical recommendations, there is a need to develop and test interventions to promote more cohesive ties among clinic staff.

3.
J Infect ; 89(4): 106260, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39218309

RESUMO

BACKGROUND: Though observational evidence supports indirect effects of SARS-CoV-2 vaccines, randomised experiments are lacking. To address this gap, the double-blinded, prospective follow-up of the household contacts (HHCs) of Philippine participants of the individually-randomised, placebo-controlled trial of the adjuvanted-subunit protein COVID-19 vaccine, SCB-2019, (EudraCT, 2020-004272-17; ClinicalTrials.gov, NCT04672395) was analyzed in a cluster-randomised fashion. METHODS: Over an eight-week period, HHCs were followed by rRT-PCR and paired rapid antibody tests (RATs) to detect symptomatic (SCI, primary) and all (ACI, secondary) SARS-CoV-2 infection. A standard analysis estimated the indirect effectiveness of SCB-2019 for each endpoint, excluding HHC RAT-positive at enrollment. A secondary analysis employed enzyme-linked immunosorbent assay (ELISA) results to correct for suspected bias. FINDINGS: SCB-2019 (N = 3470) and placebo (N = 3225) exposed HHCs contributed to at least one analysis. The standard analysis estimated that SCB-2019 reduced the risk of SCI by 83% (95% confidence/credible interval [CI: 32% to 96%), with no effect against ACI. The bias-corrected relative risk reduction was 97% (95% CI: 74% to 100%) for SCI and 79% (95% CI: 14% to 96%) for ACI, with an estimated one SARS-CoV-2 infection prevented per 4.8 households where one member received SCB-2019. INTERPRETATION: SCB-2019 demonstrated bias-corrected indirect effectiveness against SARS-CoV-2 infection among HHC, even at a modest coverage level in the household (approximately 25%). Further research into the indirect effects of SARS-CoV-2 vaccines is needed to optimize the impact of limited doses in low and middle-income settings.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Características da Família , SARS-CoV-2 , Humanos , Filipinas/epidemiologia , COVID-19/prevenção & controle , COVID-19/epidemiologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , SARS-CoV-2/imunologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Anticorpos Antivirais/sangue , Adulto Jovem , Adolescente , Método Duplo-Cego , Estudos Prospectivos , Criança , Pré-Escolar , Análise por Conglomerados , Idoso , Eficácia de Vacinas , Vacinas de Subunidades Antigênicas
4.
Sci Rep ; 14(1): 22489, 2024 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-39341937

RESUMO

Current human population growth along Earth's coasts is on a collision path with anticipated consequences of increasing natural and anthropogenic induced coastal hazards. Using recently-available ambient, dasymetric data, we developed methods to estimate annual continental and global coastal populations from (2000-2018) measured horizontally from the shoreline inward. We found: (1) large concentrations of population in relatively small bands and regions along the coast (~ 2 billion within 50 km and ~ 1 billion within 10 km); (2) higher growth rates of coastal population than inland population (an addition of 463 million within 50 km and 233 million within 10 km); (3) strong influence of distance from the coast to predict population distribution; and (4) that macro population patterns and growth could be expressed and modeled as a power function at continental and global levels. Findings point to emerging macro population patterns along the coast as contributing to increasing anthropogenic effects on Earth systems and increasing human risks associated with sea-level rise, land subsidence, extreme weather, and public health. Reliable data tracking of the magnitude, spatial distribution and change of human populations in the coastal regions is essential for comprehensive coastal monitoring.


Assuntos
Crescimento Demográfico , Humanos , Elevação do Nível do Mar
5.
J Autism Dev Disord ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39230781

RESUMO

The purpose of this study was to examine the effects of using adapted science eBooks within shared reading on comprehension and task engagement of high school students with autism spectrum disorder (ASD). A grade-level science textbook was selected and converted into an eBook format, incorporating various visual and auditory features (e.g., text-to-speech, summarized sentences, highlighted keywords) and presented on an iPad. The shared reading intervention included before, during, and after reading strategies (i.e., pre-teaching target vocabulary words, sharing information, retelling), with direct instruction on locating literal information. The intervention effects on reading comprehension and task engagement were evaluated using a single-case multiple probe design. The results of this study indicated that all participants demonstrated improvements in reading comprehension. Despite the longer intervention sessions compared to the baseline, all participants exhibited similar or enhanced levels of task engagement during the intervention sessions. The findings of this study provide empirical evidence supporting the use of adapted eBooks within shared reading as a means to increase access to grade-level science texts for high school students with ASD while maintaining a high level of task engagement. This intervention holds promise for improving the learning outcomes for students with ASD in science content area.

6.
Cell Rep Med ; 5(9): 101715, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39241772

RESUMO

Progression of acute traumatic brain injury (TBI) into chronic neurodegeneration is a major health problem with no protective treatments. Here, we report that acutely elevated mitochondrial fission after TBI in mice triggers chronic neurodegeneration persisting 17 months later, equivalent to many human decades. We show that increased mitochondrial fission after mouse TBI is related to increased brain levels of mitochondrial fission 1 protein (Fis1) and that brain Fis1 is also elevated in human TBI. Pharmacologically preventing Fis1 from binding its mitochondrial partner, dynamin-related protein 1 (Drp1), for 2 weeks after TBI normalizes the balance of mitochondrial fission/fusion and prevents chronically impaired mitochondrial bioenergetics, oxidative damage, microglial activation and lipid droplet formation, blood-brain barrier deterioration, neurodegeneration, and cognitive impairment. Delaying treatment until 8 months after TBI offers no protection. Thus, time-sensitive inhibition of acutely elevated mitochondrial fission may represent a strategy to protect human TBI patients from chronic neurodegeneration.


Assuntos
Lesões Encefálicas Traumáticas , Dinaminas , Mitocôndrias , Dinâmica Mitocondrial , Proteínas Mitocondriais , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Animais , Dinaminas/metabolismo , Dinaminas/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Humanos , Camundongos , Mitocôndrias/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Estresse Oxidativo , Encéfalo/patologia , Encéfalo/metabolismo , Microglia/metabolismo , Microglia/patologia , Doença Crônica , Modelos Animais de Doenças , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia
7.
JAMA Ophthalmol ; 142(9): 856-863, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39145984

RESUMO

Importance: High concordance in diabetic retinopathy (DR) outcomes between 7-field (7F) and ultra-widefield (UWF) images would allow for combining longitudinal assessments based on the 2 modalities both in clinical studies and clinical care. Objective: To compare 7F and UWF imaging with regard to DR severity and the associations of DR severity with risk factors, such as hemoglobin A1c, age, diabetes duration, and sex. Design, Setting, and Participants: This cross-sectional study describes the outcomes of the randomized clinical Diabetes Control and Complications Trial (DCCT) and its subsequent observational study, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. Of the 1441 participants with type 1 diabetes in the DCCT, 1375 were enrolled in the EDIC study. Of the 1171 participants who were active between March 2019 and December 2021, 200° UWF color imaging and 7F fundus photographs were obtained for 785 participants once at the same visit. Central graders assessed 7F-UWF with a 7F template masking the retinal periphery and the full UWF image (UWF-global). Data were analyzed from January 2022 to March 2023. Exposures: Hemoglobin A1c was assessed quarterly during the DCCT and annually during the EDIC study using high-performance liquid chromatography. Main Outcomes and Measures: Retinopathy was determined independently for all imaging as mild, moderate, or severe nonproliferative DR (SNPDR) using the Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale for the 7F images and the global ETDRS grading scale for the UWF images. Panretinal and focal photocoagulation were self-reported or based on scarring location and pattern observed during grading. Proliferative DR (PDR) was defined by observed neovascularization or evidence of panretinal photocoagulation. Results: Among the 785 participants included in this study, 420 (53%) were male and 365 (47%) were female. The mean (SD) age was 61 (7) years. DR grading between UWF-7F and 7F imaging was correlated for all outcomes, including for severe outcomes, such as SNPDR (κ, 0.73; concordance, 96%), PDR (κ, 0.74; concordance, 97%), scatter photocoagulation (κ, 0.97; concordance, 99%), and focal photocoagulation (κ, 0.71; concordance, 98%). Most DR severity scores were within 1 step (1410 of 1529 [92%]), and 3% (51 of 1529) were more than 2 steps apart (κ, 0.45; 95% CI, 0.42-0.49; weighted κ, 0.63; 95% CI, 0.60-0.67) on the ETDRS severity scale. DR severity assessed within the UWF-global area was higher compared to 7F (median [IQR] UWF-global score, 3 [2-3] vs median 7F level score, 2.0 [1-3]; P < .001), although the 2 modalities were correlated (1225 of 1508 [81%] 1-step agreement; weighted κ, 0.41). Conclusions and Relevance: Standard ETDRS 7F and UWF evaluations of DR were comparable for ETDRS severity levels as previously reported by Diabetic Retinopathy Clinical Research Retina Network reports. In addition, these evaluations of DR were comparable for DCCT/EDIT study outcomes and major study conclusions, suggesting that use of UWF imaging is not likely to introduce relevant measurement biases in future longitudinal studies. Trial Registration: ClinicalTrials.gov Identifiers: NCT00360815.


Assuntos
Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Feminino , Masculino , Estudos Transversais , Adulto , Diabetes Mellitus Tipo 1/complicações , Hemoglobinas Glicadas/metabolismo , Índice de Gravidade de Doença , Pessoa de Meia-Idade
8.
J Ultrasound Med ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39115150

RESUMO

OBJECTIVE: Determine if knowledge of a third-trimester ultrasound diagnosis of large for gestational age (LGA) independently increases the risk of cesarean delivery (CD). STUDY DESIGN: Historical cohort comparing CD rate among patients diagnosed with an LGA fetus on a clinically indicated ultrasound from January 2017 to July 2021 with those without an LGA diagnosis at 34 weeks or later. LGA was defined as an ultrasound-estimated fetal weight greater than or equal to the 90th percentile for the gestational age. Univariate analysis was performed to identify significant confounding variables and was utilized as covariates for binary regression with CD rate as the primary outcome, and adjusted odds ratios (AOR) with 95% confidence intervals (CI) were calculated. Nulliparous term singleton vertex (NTSV) and multiparous CD rates were also compared. RESULTS: There were 447 patients diagnosed with an LGA fetus and 1971 patients without an LGA diagnosis on third-trimester ultrasound. The positive predictive value of LGA diagnosis was 50.1% and the false positive rate was 10.6%. Patients with a diagnosis of LGA had higher AOR of CD (OR 2.11, 95% CI 1.56-2.83), and higher AOR of NTSV CD (OR 1.88, 95% CI 1.14-3.13) compared with those without an LGA diagnosis. There was no difference in the rates of non-medically indicated CD, multiparous primary CD, and attempted and successful TOLAC. CONCLUSION: Our results suggest third-trimester ultrasound diagnosis of LGA independently increases odds of CD, specifically among nulliparous patients, and the potential bias may be one factor contributing to excessive CDs and NTSV CDs.

9.
J Appl Res Intellect Disabil ; 37(5): e13281, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39104041

RESUMO

BACKGROUND: Culinary nutrition education can support improved diet-related health and wellbeing. This pre-post pilot study aimed to assess feasibility and acceptability of an eight-session culinary nutrition programme, the Food and Lifestyle Information Programme (FLIP), for adults with mild-to-moderate intellectual disability. A secondary aim was to evaluate preliminary programme effectiveness. METHOD: Participants were recruited through a disability service provider. Feasibility measures were: recruitment and retention; implementation; engagement and participation; adverse outcomes; and feasibility of outcome measures. Acceptability was assessed using an interactive process evaluation. Effectiveness measures included cooking frequency, cooking and food skill confidence and diet quality. RESULTS: Six of eight participants completed the intervention with high attendance and programme engagement. FLIP was well received by participants and support workers. No adverse outcomes occurred. Diet quality was feasible to assess. CONCLUSIONS: Findings can inform content, delivery and evaluation of future culinary nutrition programmes for adults with mild-to-moderate intellectual disability.


Assuntos
Estudos de Viabilidade , Deficiência Intelectual , Humanos , Deficiência Intelectual/reabilitação , Adulto , Masculino , Feminino , Projetos Piloto , Pessoa de Meia-Idade , Culinária , Aceitação pelo Paciente de Cuidados de Saúde , Educação de Pacientes como Assunto/métodos
10.
Toxicol Appl Pharmacol ; 491: 117046, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39084266

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease, affecting 38% of adults globally. If left untreated, NAFLD may progress to more advanced forms of the disease, including non-alcoholic steatohepatitis (NASH), liver cirrhosis, and fibrosis. Early NAFLD detection is critical to prevent disease progression. Using an obesogenic high-fat and high-sucrose (HF/HS) diet, we characterized the progression of NAFLD in male and female Collaborative Cross CC042 mice after 20-, 40-, and 60-week intervals of chronic HF/HS diet feeding. The incidence and severity of liver steatosis, inflammation, and fibrosis increased in both sexes over time, with male mice progressing to a NASH-like disease state faster than female mice, as indicated by earlier and more pronounced changes in liver steatosis. Histopathological indication of macrovesicular steatosis and gene expression changes of key lipid metabolism genes were found to be elevated in both sexes after 20 weeks of HF/HS diet. Measurement of circulating markers of inflammation (CXCL10 and TNF-α), histopathological analysis of immune cell infiltrates, and gene expression changes in inflammation-related genes indicated significant liver inflammation after 40 and 60 weeks of HF/HS diet exposure in both sexes. Liver fibrosis, as assessed by Picosirius red and Masson's trichrome staining and changes in expression of key fibrosis related genes indicated significant changes after 40 and 60 weeks of HF/HS diet exposure. In conclusion, we present a preclinical animal model of dietary NAFLD progression, which recapitulates human pathophysiological and pathomorphological changes, that could be used to better understand the progression of NAFLD and support development of new therapeutics.


Assuntos
Dieta Hiperlipídica , Modelos Animais de Doenças , Fígado , Hepatopatia Gordurosa não Alcoólica , Animais , Hepatopatia Gordurosa não Alcoólica/patologia , Dieta Hiperlipídica/efeitos adversos , Masculino , Feminino , Camundongos , Fígado/patologia , Fígado/metabolismo , Fígado/efeitos dos fármacos , Progressão da Doença , Sacarose Alimentar/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Cirrose Hepática/patologia , Cirrose Hepática/induzido quimicamente
11.
J Chem Phys ; 161(1)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38958156

RESUMO

Force Field X (FFX) is an open-source software package for atomic resolution modeling of genetic variants and organic crystals that leverages advanced potential energy functions and experimental data. FFX currently consists of nine modular packages with novel algorithms that include global optimization via a many-body expansion, acid-base chemistry using polarizable constant-pH molecular dynamics, estimation of free energy differences, generalized Kirkwood implicit solvent models, and many more. Applications of FFX focus on the use and development of a crystal structure prediction pipeline, biomolecular structure refinement against experimental datasets, and estimation of the thermodynamic effects of genetic variants on both proteins and nucleic acids. The use of Parallel Java and OpenMM combines to offer shared memory, message passing, and graphics processing unit parallelization for high performance simulations. Overall, the FFX platform serves as a computational microscope to study systems ranging from organic crystals to solvated biomolecular systems.


Assuntos
Software , Simulação de Dinâmica Molecular , Variação Genética , Algoritmos , Termodinâmica , Proteínas/química , Cristalização , Ácidos Nucleicos/química
12.
Diabetes Care ; 47(9): 1530-1538, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38861647

RESUMO

OBJECTIVE: To evaluate associations between plasma biomarkers of brain injury and MRI and cognitive measures in participants with type 1 diabetes (T1D) from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. RESEARCH DESIGN AND METHODS: Plasma amyloid-ß-40, amyloid-ß-42, neurofilament light chain (NfL), phosphorylated Tau-181 (pTau-181), and glial fibrillary acidic protein (GFAP) were measured in 373 adults who participated in the DCCT/EDIC study. MRI assessments included total brain and white matter hyperintensity volumes, white matter mean fractional anisotropy, and indices of Alzheimer disease (AD)-like atrophy and predicted brain age. Cognitive measures included memory and psychomotor and mental efficiency tests and assessments of cognitive impairment. RESULTS: Participants were 60 (range 44-74) years old with 38 (30-51) years' T1D duration. Higher NfL was associated with an increase in predicted brain age (0.51 years per 20% increase in NfL; P < 0.001) and a 19.5% increase in the odds of impaired cognition (P < 0.01). Higher NfL and pTau-181 were associated with lower psychomotor and mental efficiency (P < 0.001) but not poorer memory. Amyloid-ß measures were not associated with study measures. A 1% increase in mean HbA1c was associated with a 14.6% higher NfL and 12.8% higher pTau-181 (P < 0.0001). CONCLUSIONS: In this aging T1D cohort, biomarkers of brain injury did not demonstrate an AD-like profile. NfL emerged as a biomarker of interest in T1D because of its association with higher HbA1c, accelerated brain aging on MRI, and cognitive dysfunction. Our study suggests that early neurodegeneration in adults with T1D is likely due to non-AD/nonamyloid mechanisms.


Assuntos
Peptídeos beta-Amiloides , Biomarcadores , Cognição , Diabetes Mellitus Tipo 1 , Imageamento por Ressonância Magnética , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/sangue , Pessoa de Meia-Idade , Masculino , Adulto , Feminino , Biomarcadores/sangue , Idoso , Peptídeos beta-Amiloides/sangue , Cognição/fisiologia , Proteínas tau/sangue , Lesões Encefálicas/sangue , Lesões Encefálicas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Proteínas de Neurofilamentos/sangue , Proteína Glial Fibrilar Ácida/sangue
13.
Nat Plants ; 10(7): 1112-1125, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38906996

RESUMO

Desiccation tolerance has evolved repeatedly in plants as an adaptation to survive extreme environments. Plants use similar biophysical and cellular mechanisms to survive life without water, but convergence at the molecular, gene and regulatory levels remains to be tested. Here we explore the evolutionary mechanisms underlying the recurrent evolution of desiccation tolerance across grasses. We observed substantial convergence in gene duplication and expression patterns associated with desiccation. Syntenic genes of shared origin are activated across species, indicative of parallel evolution. In other cases, similar metabolic pathways are induced but using different gene sets, pointing towards phenotypic convergence. Species-specific mechanisms supplement these shared core mechanisms, underlining the complexity and diversity of evolutionary adaptations to drought. Our findings provide insight into the evolutionary processes driving desiccation tolerance and highlight the roles of parallel and convergent evolution in response to environmental challenges.


Assuntos
Adaptação Fisiológica , Poaceae , Poaceae/genética , Poaceae/fisiologia , Adaptação Fisiológica/genética , Dessecação , Secas , Evolução Molecular , Evolução Biológica , Regulação da Expressão Gênica de Plantas , Duplicação Gênica
14.
Circ Cardiovasc Qual Outcomes ; 17(7): e010561, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38828563

RESUMO

BACKGROUND: Cardiovascular trials often use a composite end point and a time-to-first event model. We sought to compare edoxaban versus warfarin using the win ratio, which offers data complementary to time-to-first event analysis, emphasizing the most severe clinical events. METHODS: ENGAGE AF-TIMI 48 (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) was a double-blind, randomized trial in which patients with atrial fibrillation were assigned 1:1:1 to a higher dose edoxaban regimen (60/30 mg daily), a lower dose edoxaban regimen (30/15 mg daily), or warfarin. In an exploratory analysis, we analyzed the trial outcomes using an unmatched win ratio approach. The win ratio for each edoxaban regimen was the total number of edoxaban wins divided by the number of warfarin wins for the following ranked clinical outcomes: 1: death; 2: hemorrhagic stroke; 3: ischemic stroke/systemic embolic event/epidural or subdural bleeding; 4: noncerebral International Society on Thrombosis and Haemostasis major bleeding; and 5: cardiovascular hospitalization. RESULTS: 21 105 patients were randomized to higher dose edoxaban regimen (N=7035), lower dose edoxaban regimen (N=7034), or warfarin (N=7046), yielding >49 million pairs for each treatment comparison. The median age was 72 years, 38% were women, and 59% had prior vitamin K antagonist use. The win ratio was 1.11 (95% CI, 1.05-1.18) for higher dose edoxaban regimen versus warfarin and 1.11 (95% CI, 1.05-1.18) for lower dose edoxaban regimen versus warfarin. The favorable impacts of edoxaban on death (34% of wins) and cardiovascular hospitalization (41% of wins) were the major contributors to the win ratio. Results consistently favored edoxaban in subgroups based on creatine clearance and dose reduction at baseline, with heightened benefit among those without prior vitamin K antagonist use. CONCLUSIONS: In a win ratio analysis of the ENGAGE AF-TIMI 48 trial, both dose regimens of edoxaban were superior to warfarin for the net clinical outcome incorporating ischemic and bleeding events. As the win ratio emphasizes the most severe clinical events, this analysis supports the superiority of edoxaban over warfarin in patients with atrial fibrillation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00781391.


Assuntos
Anticoagulantes , Fibrilação Atrial , Inibidores do Fator Xa , Hemorragia , Piridinas , Tiazóis , Varfarina , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/mortalidade , Fibrilação Atrial/complicações , Varfarina/efeitos adversos , Varfarina/administração & dosagem , Piridinas/efeitos adversos , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Tiazóis/administração & dosagem , Tiazóis/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Método Duplo-Cego , Feminino , Masculino , Resultado do Tratamento , Idoso , Hemorragia/induzido quimicamente , Anticoagulantes/efeitos adversos , Anticoagulantes/administração & dosagem , Fatores de Tempo , Fatores de Risco , Pessoa de Meia-Idade , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/mortalidade , Idoso de 80 Anos ou mais , Medição de Risco
15.
Children (Basel) ; 11(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38929252

RESUMO

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of mortality among term newborns globally. Infants born through meconium-stained amniotic fluid are at risk of developing meconium aspiration syndrome (MAS) and HIE. Simultaneous occurrence of MAS and HIE is a perilous combination for newborns due to the risk of persistent pulmonary hypertension of the newborn (PPHN). Moreover, therapeutic hypothermia (TH), which is the current standard of care for the management of HIE, may increase pulmonary vascular resistance (PVR) and worsen PPHN. Infants with MAS and HIE require close cardiorespiratory and hemodynamic monitoring for PPHN. Therapeutic strategies, including oxygen supplementation, ventilation, use of surfactant, inhaled nitric oxide and other pulmonary vasodilators, and systemic vasopressors, play a critical role in the management of PPHN in MAS, HIE, and TH. While TH reduces death or disability in infants with HIE, infants with MAS and HIE undergoing TH need close hemodynamic monitoring for PPHN.

16.
Reprod Sci ; 31(9): 2771-2782, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38777947

RESUMO

Preeclampsia (PE) is a leading cause of maternal and fetal mortality and morbidity. While placental dysfunction is a core underlying issue, the pathogenesis of this disorder is thought to differ between early-onset (EOPE) and late-onset (LOPE) subtypes. As recent reports suggest that small extracellular vesicles (sEVs) contribute to the development of PE, we have compared systemic sEV concentrations between normotensive, EOPE, and LOPE pregnancies. To circumvent lengthy isolation techniques and intermediate filtration steps, a streamlined approach was developed to evaluate circulating plasma sEVs from maternal plasma. Polymer-based precipitation and purification were used to isolate total systemic circulating maternal sEVs, free from bias toward specific surface marker expression or extensive subpurification. Immediate Nanoparticle Tracking Analysis (NTA) of freshly isolated sEV samples afforded a comprehensive analysis that can be completed within hours, avoiding confounding freeze-thaw effects of particle aggregation and degradation.Rather than exosomal subpopulations, our findings indicate a significant elevation in the total number of circulating maternal sEVs in patients with EOPE. This streamlined approach also preserves sEV-bound protein and microRNA (miRNA) that can be used for potential biomarker analysis. This study is one of the first to demonstrate that maternal plasma sEVs harbor full-length hypoxia inducible factor 1 alpha (HIF-1α) protein, with EOPE sEVs carrying higher levels of HIF-1α compared to control sEVs. The detection of HIF-1α and its direct signaling partner microRNA-210 (miR-210) within systemic maternal sEVs lays the groundwork for identifying how sEV signaling contributes to the development of preeclampsia. When taken together, our quantitative and qualitative results provide compelling evidence to support the translational potential of streamlined sEV analysis for future use in the clinical management of patients with EOPE.


Assuntos
Vesículas Extracelulares , Pré-Eclâmpsia , Humanos , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Feminino , Gravidez , Vesículas Extracelulares/metabolismo , Adulto , MicroRNAs/sangue , Biomarcadores/sangue
17.
Pest Manag Sci ; 80(9): 4770-4778, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38801186

RESUMO

BACKGROUND: The Varroa mite (Varroa destructor) is considered to be the greatest threat to apiculture worldwide. RNA interference (RNAi) using double-stranded RNA (dsRNA) as a gene silencing mechanism has emerged as a next-generation strategy for mite control. RESULTS: We explored the impact of a dsRNA biopesticide, named vadescana, designed to silence the calmodulin gene in Varroa, on mite fitness in mini-hives housed in a laboratory. Two dosages were tested: 2 g/L dsRNA and 8 g/L dsRNA. Vadescana appeared to have no effect on mite survival, however, mite fertility was substantially reduced. The majority of foundress mites exposed to vadescana failed to produce any offspring. No dose-dependent effect of vadescana was observed, as both the low and high doses inhibited mite reproduction equally well in the mini-hives and neither dose impacted pupal survival of the honey bee. Approximately 95% of bee pupae were alive at uncapping across all treatment groups. CONCLUSION: These findings suggest that vadescana has significant potential as an effective alternative to conventional methods for Varroa control, with broader implications for the utilization of RNAi as a next-generation tool in the management of pest species. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Interferência de RNA , Reprodução , Varroidae , Animais , Abelhas/parasitologia , Varroidae/fisiologia , Varroidae/genética , RNA de Cadeia Dupla , Controle Biológico de Vetores/métodos , Criação de Abelhas/métodos
18.
Mhealth ; 10: 15, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38689611

RESUMO

Background: Evidence-based mobile health (mHealth) interventions have been successful for an array of physical and mental health conditions. Children with developmental disorders (DD) often have secondary speech and language disorders. The lack of high-quality medical and educational services in low- and middle-income countries limits the opportunities for children with DD to succeed in life. South Africa currently offers limited access to education, social, and health services. Methods: Twelve caregivers of twelve children with DD between the ages of 3 and 6 years who already received monthly early childhood therapy participated in this study. A mHealth app, called Nna'Le'wena, a Setswana phrase meaning "Me and You", was designed, developed, installed, and tested on tablets. The app provided a systematic framework and guidance to the caregivers in order to use evidence-based communication interaction strategies with the children over a twelve-week period. The app could be used offline and provided audio instructions in English and Setswana, two dominant languages in South Africa. The app automatically generated log files and collected answers to weekly surveys. At the end of the study, caregivers were asked to evaluate the app by using relevant portions of the Mobile App Rating Scale (MARS). Results: Caregivers were able to successfully interact and use the app. The app was well-received and liked by the caregivers. Caregivers listened to the instructional audios in English and Setswana during the 12-week period. They were able to provide communication opportunities to their children during daily living activities, especially during play- and mealtime activities. Conclusions: The Nna'Le'wena app was successfully deployed and used by caregivers of children with DD. mHealth solutions can be effective and are relatively affordable solutions that can enhance health care and educational delivery in different settings, including in low-and middle-income countries with limited Internet capabilities.

19.
Nurs Educ Perspect ; 45(4): E25-E27, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38625709

RESUMO

ABSTRACT: This study used a quantitative descriptive survey with a sample of 92 participants to assess perceived nurse faculty competency in their role at Saudi Arabian universities. Participants' perceptions overall were highly positive in the areas of teaching, scholarship, and service competencies. Participants reported less competence in the areas of scholarship and service when they started in their role. Orientation and a mentor relationship with senior faculty were reported to aid in their transition to the faculty role. The findings of the study identify strategies to support the new nurse educator.


Assuntos
Docentes de Enfermagem , Humanos , Arábia Saudita , Docentes de Enfermagem/psicologia , Feminino , Masculino , Adulto , Inquéritos e Questionários , Competência Profissional/normas , Pessoa de Meia-Idade
20.
Diabetes Care ; 47(9): 1522-1529, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38551949

RESUMO

OBJECTIVE: To investigate quantitative and qualitative changes in retinal structure using optical coherence tomography (OCT) and their associations with systemic or other risk factors in individuals with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In the Epidemiology of Diabetes Interventions and Complications (EDIC) study, OCT images were obtained during study years 25-28 (2019-2022) in 937 participants; 54% and 46% were from the original intensive (INT) and conventional (CONV) glycemic management treatment groups, respectively. RESULTS: Average age for participants was 61 years old, diabetes duration 39 years, and HbA1c 7.6%. Participants originally in the CONV group were more likely to have disorganization of retinal inner layers (DRIL) (CONV 27.3% vs. INT 18.7%; P = 0.0003), intraretinal fluid (CONV 24.4% vs. INT 19.2%; P = 0.0222), and intraretinal cysts (CONV 20.8% vs. INT 16.6%; P = 0.0471). In multivariable models, sex, age, smoking, mean updated systolic blood pressure, and history of "clinically significant" macular edema (CSME) and of anti-VEGF treatment were independently associated with changes in central subfield thickness, while HbA1c, BMI, and history of CSME and of ocular surgery were associated with DRIL. Visual acuity (VA) decline was associated with significant thinning of all retinal subfields except for the central and inner nasal subfields. CONCLUSIONS: Early intensive glycemic management in T1D is associated with a decreased risk of DRIL. This important morphological abnormality was associated with a history of macular edema, a history of ocular surgery, and worse VA. This study reveals benefits of intensive glycemic management on the retina beyond features detected by fundus photographs and ophthalmoscopy.


Assuntos
Retinopatia Diabética , Retina , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Pessoa de Meia-Idade , Masculino , Feminino , Retina/diagnóstico por imagem , Retina/patologia , Retinopatia Diabética/epidemiologia , Adulto , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico/métodos , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Idoso
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