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BACKGROUND: BMS-986141 is a novel potent highly selective antagonist of PAR (protease-activated receptor) type 4. PAR4 antagonism has been demonstrated to reduce thrombus formation in isolation and in combination with factor Xa inhibition in high shear conditions in healthy people. We sought to determine whether PAR4 antagonism had additive antithrombotic effects in patients with coronary artery disease who were receiving antiplatelet therapy. METHODS: Forty-five patients with stable coronary heart disease and 10 healthy volunteers completed a phase 2a open-label 4-arm single-center study. Patients were allocated to 1 of 3 treatment arms for 7 days: (1) ticagrelor (90 mg BID), (2) aspirin (75 mg QD), or (3) the combination of ticagrelor and aspirin. Agonist-induced platelet aggregation, platelet activation, and ex vivo thrombus formation were measured before and 2 and 24 hours after a single oral 4-mg dose of BMS-986141 on the first study visit day in all participants. RESULTS: BMS-986141 demonstrated highly selective inhibition of PAR4-AP (agonist peptide)-induced platelet aggregation, P-selectin expression, and platelet-monocyte aggregate expression (P≤0.001 for all), which were unaffected by concomitant antiplatelet therapies. PAR4 antagonism reduced ex vivo thrombus area in high shear conditions in healthy volunteers (-21%; P=0.001) and in patients receiving ticagrelor alone (-28%; P=0.001), aspirin alone (-23%; P=0.018), or both in combination (-24%; P≤0.001). Plasma concentration of BMS-986141 correlated with PAR4-AP-induced platelet responses (P≤0.001 for all) and total thrombus area under high shear stress conditions (P≤0.01 for all). CONCLUSIONS: PAR4 antagonism has additive antithrombotic effects when used in addition to ticagrelor, aspirin, or their combination, in patients with stable coronary heart disease. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05093790.
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Enfermedad de la Arteria Coronaria , Trombosis , Humanos , Inhibidores de Agregación Plaquetaria/farmacología , Ticagrelor/uso terapéutico , Fibrinolíticos/uso terapéutico , Enfermedad de la Arteria Coronaria/metabolismo , Aspirina , Agregación Plaquetaria , Plaquetas/metabolismoRESUMEN
INTRODUCTION: Non-invasive detection of pathological changes in thoracic aortic disease remains an unmet clinical need particularly for patients with congenital heart disease. Positron emission tomography combined with magnetic resonance imaging (PET-MRI) could provide a valuable low-radiation method of aortic surveillance in high-risk groups. Quantification of aortic microcalcification activity using sodium [18F]fluoride holds promise in the assessment of thoracic aortopathies. We sought to evaluate aortic sodium [18F]fluoride uptake in PET-MRI using three methods of attenuation correction compared to positron emission tomography computed tomography (PET-CT) in patients with bicuspid aortic valve, METHODS: Thirty asymptomatic patients under surveillance for bicuspid aortic valve disease underwent sodium [18F]fluoride PET-CT and PET-MRI of the ascending thoracic aorta during a single visit. PET-MRI data were reconstructed using three iterations of attenuation correction (Dixon, radial gradient recalled echo with two [RadialVIBE-2] or four [RadialVIBE-4] tissue segmentation). Images were qualitatively and quantitatively analysed for aortic sodium [18F]fluoride uptake on PET-CT and PET-MRI. RESULTS: Aortic sodium [18F]fluoride uptake on PET-MRI was visually comparable with PET-CT using each reconstruction and total aortic standardised uptake values on PET-CT strongly correlated with each PET-MRI attenuation correction method (Dixon R = 0.70; RadialVIBE-2 R = 0.63; RadialVIBE-4 R = 0.64; p < 0.001 for all). Breathing related artefact between soft tissue and lung were detected using Dixon and RadialVIBE-4 but not RadialVIBE-2 reconstructions, with the presence of this artefact adjacent to the atria leading to variations in blood pool activity estimates. Consequently, quantitative agreements between radiotracer activity on PET-CT and PET-MRI were most consistent with RadialVIBE-2. CONCLUSION: Ascending aortic microcalcification analysis in PET-MRI is feasible with comparable findings to PET-CT. RadialVIBE-2 tissue attenuation correction correlates best with the reference standard of PET-CT and is less susceptible to artefact. There remain challenges in segmenting tissue types in PET-MRI reconstructions, and improved attenuation correction methods are required.
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Aorta Torácica , Imagen por Resonancia Magnética , Imagen Multimodal , Humanos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Imagen Multimodal/métodos , Aorta Torácica/diagnóstico por imagen , Adulto , Calcinosis/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Anciano , Válvula Aórtica/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodosRESUMEN
BACKGROUND: 18F-GP1 is a novel positron-emitting radiotracer that is highly specific for activated platelets and thrombus. In a proof-of-concept study, we aimed to determine its potential clinical application in establishing the role and origin of thrombus in ischemic stroke. METHODS: Eleven patients with recent ischemic stroke (n=9) or transient ischemic attack (n=2) underwent 18F-GP1 positron emission tomography and computed tomography angiography at a median of 11 (range, 2-21) days from symptom onset. 18F-GP1 uptake (maximum target-to-background ratio) was assessed in the carotid arteries and brain. RESULTS: 18F-GP1 uptake was identified in 10 of 11 patients: 4 in the carotid arteries only, 3 in the brain only, and 3 in both the brain and carotid arteries. In those with carotid uptake, 4 participants had >50% stenosis and 3 had nonstenotic disease. One case had bilateral stenotic disease (>70%), but only the culprit carotid artery demonstrated 18F-GP1 uptake. The average uptake was higher in the culprit (median maximum target-to-background ratio, 1.55 [interquartile range, 1.26-1.82]) compared with the contralateral nonculprit carotid artery (maximum target-to-background ratio, 1.22 [1.19-1.6]). In those with brain 18F-GP1 uptake (maximum target-to-background ratio, 6.45 [4.89-7.65]), areas of acute infarction on computed tomography correlated with brain 18F-GP1 uptake in 6 cases. Ex vivo autoradiography of postmortem infarcted brain tissue showed focal uptake corresponding to intraluminal thrombus within the culprit vessel and downstream microvasculature. There was also evidence of diffuse uptake within some of the infarcted brain tissue reflecting parenchymal petechial hemorrhage. CONCLUSIONS: 18F-GP1 positron emission tomography and computed tomography angiography is a novel noninvasive method of identifying in vivo cerebrovascular thrombosis, which holds major promise in understanding the role and origin of thrombosis in stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03943966.
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Estenosis Carotídea , Ataque Isquémico Transitorio , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Trombosis , Humanos , Arterias Carótidas , Ataque Isquémico Transitorio/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagenRESUMEN
Injury surveillance data indicate that collegiate athletes are at greater risk for lower extremity (LE) injuries following sports-related concussion (SRC). While the association between SRC and LE injury appears to be clinically relevant up to 1-year post-SRC, little evidence has been provided to determine possible mechanistic rationales. Thus, we aimed to compare collegiate athletes with a history of SRC to matched controls on biomechanical and cognitive performance measures associated with LE injury risk. Athletes with a history of SRC (n = 20) and matched controls (n = 20) performed unanticipated bilateral land-and-cut tasks and cognitive assessments. Group-based analyses (ANOVA) and predictive modeling (C5.0 decision tree algorithm) were used to compare group differences on biomechanical and cognitive measures. Collegiate athletes with a history of SRC demonstrated approximately six degrees less peak knee flexion on both dominant (p = 0.03, d = 0.71) and nondominant (p = 0.02, d = 0.78) limbs during the land-and-cut tasks compared to controls. Verbal Memory, knee flexion, and Go/No Go total score (C5.0 decision tree algorithm) were identified as the strongest indicators of previous SRC injury history. Reduced knee flexion during sport-specific land-and-cut tasks may be a mechanism for increased LE injury risk in athletes with a history of SRC. There appears to be multiple biomechanical and cognitive predictors for identifying previous SRC in collegiate athletes, providing evidence to support a multifactorial SRC management strategy to reduce future injury risk.
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Traumatismos en Atletas , Conmoción Encefálica , Cognición , Extremidad Inferior , Humanos , Conmoción Encefálica/fisiopatología , Traumatismos en Atletas/fisiopatología , Fenómenos Biomecánicos , Masculino , Cognición/fisiología , Adulto Joven , Femenino , Extremidad Inferior/lesiones , Atletas , Estudios de Casos y Controles , AdolescenteRESUMEN
BACKGROUND: Patients with thoracic aortopathy are at increased risk of catastrophic aortic dissection, carrying with it substantial mortality and morbidity. Although granular medial calcinosis (medial microcalcification) has been associated with thoracic aortopathy, its relationship to disease severity has yet to be established. METHODS: One hundred one thoracic aortic specimens were collected from 57 patients with thoracic aortopathy and 18 control subjects. Standardized histopathologic scores, immunohistochemistry, and nanoindentation (tissue elastic modulus) were compared with the extent of microcalcification on von Kossa histology and 18F-sodium fluoride autoradiography. RESULTS: Microcalcification content was higher in thoracic aortopathy samples with mild (n=28; 6.17 [2.71-10.39]; P≤0.00010) or moderate histopathologic degeneration (n=30; 3.74 [0.87-11.80]; P<0.042) compared with control samples (n=18; 0.79 [0.36-1.90]). Alkaline phosphatase (n=26; P=0.0019) and OPN (osteopontin; n=26; P=0.0045) staining were increased in tissue with early aortopathy. Increasingly severe histopathologic degeneration was related to reduced microcalcification (n=82; Spearman ρ, -0.51; P<0.0001)-a process closely linked with elastin loss (n=82; Spearman ρ, -0.43; P<0.0001) and lower tissue elastic modulus (n=28; Spearman ρ, 0.43; P=0.026).18F-sodium fluoride autoradiography demonstrated good correlation with histologically quantified microcalcification (n=66; r=0.76; P<0.001) and identified areas of focal weakness in vivo. CONCLUSIONS: Medial microcalcification is a marker of aortopathy, although progression to severe aortopathy is associated with loss of both elastin fibers and microcalcification.18F-sodium fluoride positron emission tomography quantifies medial microcalcification and is a feasible noninvasive imaging modality for identifying aortic wall disruption with major translational promise.
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Calcinosis , Elastina , Aorta , Calcinosis/diagnóstico por imagen , Humanos , Índice de Severidad de la Enfermedad , Fluoruro de SodioRESUMEN
Recent work in biosensors has shown promise to enable high throughput searches through large genetic libraries. However, just as physiological limitations and lack of in-depth mechanistic knowledge can prevent us from achieving high titers in microbial systems; similar roadblocks can appear in the application of biosensors. Here, we characterized a previously developed transcription-factor (ExuR) based galacturonate biosensor for its other cognate ligand, glucuronate. Though we saw an ideal response to glucuronate from the biosensor in controlled and ideal experimental circumstances, these results began to deviate from a well-behaved system when we explored the application of the sensor to different MIOX homologs. Through modifications to circuit architecture and culture conditions, we were able to decrease this variation and use these more optimal conditions to apply the biosensor for the separation of two closely related MIOX homologs. ONE-SENTENCE SUMMARY: In this work, a transcription-factor biosensor was investigated for its potential to screen a library of myo -inositol oxygenase variants while seeking to mitigate the impact the production pathway appeared to have on the biosensor.
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Técnicas Biosensibles , Factores de Transcripción , Ácido Glucurónico , Factores de Transcripción/genética , Regulación de la Expresión Génica , Inositol-Oxigenasa/genética , Inositol-Oxigenasa/metabolismo , Glucuronatos , Técnicas Biosensibles/métodosRESUMEN
OBJECTIVE: The purpose of this review was to examine the reporting in chiropractic mixed methods research using Good Reporting of A Mixed Methods Study (GRAMMS) criteria. METHODS: In this methodological review, we searched MEDLINE, Embase, CINAHL, and the Index to Chiropractic Literature from the inception of each database to December 31, 2020, for chiropractic studies reporting the use of both qualitative and quantitative methods or mixed qualitative methods. Pairs of reviewers independently screened titles, abstracts, and full-text studies, extracted data, and appraised reporting using the GRAMMS criteria and risk of bias with the Mixed Methods Appraisal Tool (MMAT). Generalized estimating equations were used to explore factors associated with reporting using GRAMMS criteria. RESULTS: Of 1040 citations, 55 studies were eligible for review. Thirty-seven of these 55 articles employed either a multistage or convergent mixed methods design, and, on average, 3 of 6 GRAMMS items were reported among included studies. We found a strong positive correlation in scores between the GRAMMS and MMAT instruments (r = 0.78; 95% CI, 0.66-0.87). In our adjusted analysis, publications in journals indexed in Web of Science (adjusted odds ratio = 2.71; 95% CI, 1.48-4.95) were associated with higher reporting using GRAMMS criteria. Three of the 55 studies fully adhered to all 6 GRAMMS criteria, 4 studies adhered to 5 criteria, 10 studies adhered to 4 criteria, and the remaining 38 adhered to 3 criteria or fewer. CONCLUSION: Our findings suggest that reporting in chiropractic mixed methods research using GRAMMS criteria was poor, particularly among studies with a higher risk of bias.
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Quiropráctica , HumanosRESUMEN
OBJECTIVES: A standardized non-occupational post-exposure prophylaxis (nPEP) programme was implemented to improve guideline compliance for treatment of post-sexual assault patients within an emergency department (ED). METHODS: A single-centre, retrospective, observational study of adult patients evaluated in the ED for sexual assault was performed following nPEP programme implementation. A comprehensive nPEP programme consisting of a standardized order set, real-time multidisciplinary consultation, on-site pharmacy and close post-discharge follow-up was implemented between July 2017 and June 2018. Laboratory, treatment, vaccination, prescription and follow-up data during the pre- (July 2016 to June 2017) and post-intervention (July 2018 to August 2019) periods were compared. RESULTS: Of the 147 post-sexual assault patients included in this study (59 pre-intervention, 88 post-intervention), 133 (90.5%) were eligible for nPEP. Patient demographics and rate of those eligible for nPEP were similar in both cohorts. Antiretroviral therapy (ART) was offered (72.2% vs. 100%; p < 0.005) and ultimately prescribed (51.9% vs. 86.1%; p < 0.005) more frequently following nPEP programme implementation. Patients were more likely to have appropriate screening for renal function, liver function, pregnancy, syphilis, hepatitis B, hepatitis C and HIV in the post-intervention period (all p < 0.005). Hepatitis B vaccination was more commonly administered post-intervention (8.5% vs. 22.7%; p < 0.024). In-person 28-day follow-up was rare in both pre- (3.5%) and post-intervention (11.3%) cohorts (p = 0.278). CONCLUSIONS: Implementation of a comprehensive nPEP programme resulted in improved guideline compliance with more frequent and appropriate ART administration. Recommended screening laboratories and hepatitis B vaccinations were more commonly performed, but in-person follow-up remained low. The nPEP programmes should be implemented to standardize efforts that decrease the risk of HIV transmission.
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Infecciones por VIH , Delitos Sexuales , Adulto , Cuidados Posteriores , Servicio de Urgencia en Hospital , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Humanos , Alta del Paciente , Profilaxis Posexposición/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: Standard methods for quantifying positron emission tomography (PET) uptake in the aorta are time consuming and may not reflect overall vessel activity. We describe aortic microcalcification activity (AMA), a novel method for quantifying 18F-sodium fluoride (18F-NaF) uptake in the thoracic aorta. METHODS: Twenty patients underwent two hybrid 18F-NaF PET and computed tomography (CT) scans of the thoracic aorta less than three weeks apart. AMA, as well as maximum (TBRmax) and mean (TBRmean) tissue to background ratios, were calculated by two trained operators. Intra-observer repeatability, inter-observer repeatability and scan-rescan reproducibility were assessed. Each 18F-NaF quantification method was compared to validated cardiovascular risk scores. RESULTS: Aortic microcalcification activity demonstrated excellent intra-observer (intraclass correlation coefficient 0.98) and inter-observer (intraclass correlation coefficient 0.97) repeatability with very good scan-rescan reproducibility (intraclass correlation coefficient 0.86) which were similar to previously described TBRmean and TBRmax methods. AMA analysis was much quicker to perform than standard TBR assessment (3.4min versus 15.1min, P<0.0001). AMA was correlated with Framingham stroke risk scores and Framingham risk score for hard cononary heart disease. CONCLUSIONS: AMA is a simple, rapid and reproducible method of quantifying global 18F-NaF uptake across the ascending aorta and aortic arch that correlates with cardiovascular risk scores.
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Calcinosis , Radioisótopos de Flúor , Aorta Torácica/diagnóstico por imagen , Calcinosis/diagnóstico por imagen , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Reproducibilidad de los Resultados , Fluoruro de SodioRESUMEN
OBJECTIVE: This UK multicenter study aims to report early- and medium-term results following covered endovascular reconstruction of aortic bifurcation (CERAB) for the treatment of aortoiliac occlusive disease (AIOD) in patients with chronic limb threatening ischemia (CLTI) or intermittent claudication (IC). MATERIALS AND METHODS: Retrospective case analysis was performed of patients who underwent CERAB between November 1, 2012 and March 31, 2020 in 6 centers across the United Kingdom. Anatomical data, including degree of plaque calcification, were assessed using preoperative imaging. Outcome measures included mortality, perioperative complications, target lesion reintervention (TLR), and major limb amputation. Primary, assisted primary, and secondary patencies were calculated at set intervals. RESULTS: A total of 116 patients underwent CERAB over the study period for the following reasons [48% presenting with CLTI (Rutherford 4-6) and 52% with IC (Rutherford 1-3)]; 82% presented had Trans-Atlantic Inter-Society Consensus (TASC) D AIOD disease. Median age was 65 years (range 42-90 years); 76% of the cohort were male. Severely calcified aortic and iliac lesions were noted in 90% and 80% of patients, respectively. Over a median follow-up of 18 months (range 1-91 months), 2 (1.7%) patients were lost to follow up. In total 5, (4.3%) patients died and 2 (1.7%) had a major amputation. Endovascular TLR was required in 14 (12.1%) patients at last follow up. Surgical TLR was performed in 4 (3.4%) patients at last follow-up. Seven (6%) patients developed an aortic/iliac stent occlusion at last follow-up. The Kaplan-Meier (KM) freedom from TLR at 1 year was 94% and KM 1-year primary patency, assisted primary patency, and secondary patency were 88%, 94%, and 98% respectively. Subanalysis found the following features were associated with need for TLR; TASC D disease (OR = 2.45, 95% CI 1.44 to 3.71), severe aortic calcification (OR = 2.01, 95% CI 1.03 to 2.20), and presence of tissue loss at baseline (OR = 1.43, 95% CI 1.01 to 4.63). CONCLUSION: Perioperative (<30 days) and medium-term morbidity, mortality, and patency rates in this pragmatic cohort of patients with severe AIOD lesions show that CERAB is a valid revascularization option. A direct comparison with surgical treatments for AIOD in a randomized controlled trial is justified.
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Enfermedades de la Aorta , Arteriopatías Oclusivas , Procedimientos Endovasculares , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades de la Aorta/diagnóstico por imagen , Enfermedades de la Aorta/cirugía , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/cirugía , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Arteria Ilíaca/diagnóstico por imagen , Arteria Ilíaca/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Resultado del Tratamiento , Reino Unido , Grado de Desobstrucción VascularRESUMEN
BACKGROUND: Pseudoaneurysm formation is common in standard thin-walled polytetrafluoroethylene (sPTFE) grafts, occurring in up to 10% of grafts, and is reported as the most common cause of graft loss for grafts more than 2 years old. The Gore® Acuseal™ graft is an early cannulation graft, needled before incorporation, and thus may be especially prone to pseudoaneurysm formation. In addition, as this is a relatively new product, there are limited data on long-term outcomes such as pseudoaneurysm. We report one center's experience of the incidence and etiological factors associated with pseudoaneurysm formation over 5 years and 265 grafts. METHODS: A total of 265 Acuseal grafts were placed in the last 5 years. All patients had prospective data entered into an electronic searchable patient record. Surveillance was performed with 3 monthly imaging (digital subtraction angiography or ultrasound), clinical examination, and hemodynamic performance. Data examined included the incidence, causative factors, and outcomes of pseudoaneurysm. RESULTS: Eleven grafts (4.15%) developed a pseudoaneurysm, with 2 patients developing significant hemorrhage. The median time to development of a pseudoaneurysm was 25 months interquartile range (IQR, 20-28 months). Several common etiological factors were identified. All but one patient had overuse of needling sites (n = 10; 90.9%). Other factors associated with pseudoaneurysm formation were inadequate surveillance (n = 9; 81.8%), venous outflow stenosis (n = 9; 81.8%), and anticoagulation/dual antiplatelet therapy (n = 7; 63.6%). Management included observation and needle rotation (n = 5; 45.5%), stent grafting (n = 3; 27.3%), or excision (n = 1; 9.1%) of the pseudoaneurysm. Surgical or endovascular augmentation of the venous outflow was required in 9 patients (81.8%). Graft ligation and explantation were required in 5 patients (45.5%) with graft preservation achieved in 6/11 patients (54.5%). CONCLUSIONS: Pseudoaneurysm formation occurs less frequently in Acuseal grafts compared with historical data for standard PTFE grafts. Pseudoaneurysm formation did not occur in any graft within the first 13 months after implantation, suggesting early cannulation before incorporation is not by itself a risk factor for pseudoaneurysm development. Poor needling, venous stenosis, inadequate surveillance, and anticoagulation/dual antiplatelet therapy are remediable factors, and graft preservation is possible. Acuseal is a robust graft with lower rates of pseudoaneurysm formation on long-term follow-up than standard PTFE grafts.
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Aneurisma Falso/epidemiología , Derivación Arteriovenosa Quirúrgica/instrumentación , Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Cateterismo , Politetrafluoroetileno , Diálisis Renal , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/cirugía , Derivación Arteriovenosa Quirúrgica/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Cateterismo/efectos adversos , Bases de Datos Factuales , Remoción de Dispositivos , Femenino , Humanos , Incidencia , Masculino , Diseño de Prótesis , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Escocia/epidemiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this preliminary study was to determine the differences in abdominal musculature thickness, within 1 month of delivery, in women who experienced back pain during pregnancy compared with those who did not. METHODS: B-mode ultrasound imaging was used to measure abdominal muscle thickness on 76 postpartum participants who participated in a larger study; 47 women experienced back pain during pregnancy, and 29 did not. Participant data were stratified by group, and primary comparisons were based on these grouping across the abdominal muscles, including rectus abdominis (upper and lower fibers), external oblique, internal oblique, and transversus abdominis. Means and standard deviations were also used to set parameters for future studies. RESULTS: In the present study, there was no difference in any abdominal muscle thickness between groups. Women with low back pain were significantly shorter (165.19 ± 6.64 cm) than women who did not have from back pain during pregnancy (169.38 ± 7.58 cm). All other demographics, such as age, weight, and date tested postpartum, were not significantly different between groups. CONCLUSION: The results of this study showed no variation in abdominal muscle thickness in women who had back pain during pregnancy and those who did not.
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Músculos Abdominales/diagnóstico por imagen , Dolor de la Región Lumbar/diagnóstico por imagen , Complicaciones del Embarazo/diagnóstico por imagen , Resultado del Embarazo , Ultrasonografía Doppler/métodos , Músculos Abdominales/anatomía & histología , Adulto , Estudios de Casos y Controles , Femenino , Edad Gestacional , Humanos , Dolor de la Región Lumbar/fisiopatología , Dimensión del Dolor , Periodo Posparto , Embarazo , Valores de Referencia , Medición de RiesgoRESUMEN
The personal care industry is focused on developing safe, more efficacious, and increasingly milder products, that are routinely undergoing preclinical and clinical testing before becoming available for consumer use on skin. In vitro systems based on skin reconstructed equivalents are now established for the preclinical assessment of product irritation potential and as alternative testing methods to the classic Draize rabbit skin irritation test. We have used the 3-D EpiDerm™ model system to evaluate tissue viability and primary cytokine interleukin-1α release as a way to evaluate the potential dermal irritation of 224 non-ionic, amphoteric and/or anionic surfactant-containing formulations, or individual raw materials. As part of our testing programme, two representative benchmark materials with known clinical skin irritation potential were qualified through repeated testing, for use as references for the skin irritation evaluation of formulations containing new surfactant ingredients. We have established a correlation between the in vitro screening approach and clinical testing, and are continually expanding our database to enhance this correlation. This testing programme integrates the efforts of global manufacturers of personal care products that focus on the development of increasingly milder formulations to be applied to the skin, without the use of animal testing.
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Alternativas al Uso de Animales , Cosméticos/toxicidad , Interleucina-1alfa/análisis , Cuidados de la Piel , Pruebas de Irritación de la Piel , Tensoactivos/toxicidad , HumanosAsunto(s)
Países en Desarrollo , Hospitales de Distrito/organización & administración , Servicios de Salud Rural/organización & administración , Procedimientos Quirúrgicos Operativos/estadística & datos numéricos , Atención de Salud Universal , África del Sur del Sahara , Creación de Capacidad , Comunicación , Urgencias Médicas , Fuerza Laboral en Salud , Humanos , Aceptación de la Atención de Salud , Desarrollo de Personal/organización & administraciónRESUMEN
A broad assessment is provided of the current state of knowledge regarding the risks associated with shale gas development and their governance. For the principal domains of risk, we identify observed and potential hazards and promising mitigation options to address them, characterizing current knowledge and research needs. Important unresolved research questions are identified for each area of risk; however, certain domains exhibit especially acute deficits of knowledge and attention, including integrated studies of public health, ecosystems, air quality, socioeconomic impacts on communities, and climate change. For these, current research and analysis are insufficient to either confirm or preclude important impacts. The rapidly evolving landscape of shale gas governance in the U.S. is also assessed, noting challenges and opportunities associated with the current decentralized (state-focused) system of regulation. We briefly review emerging approaches to shale gas governance in other nations, and consider new governance initiatives and options in the U.S. involving voluntary industry certification, comprehensive development plans, financial instruments, and possible future federal roles. In order to encompass the multiple relevant disciplines, address the complexities of the evolving shale gas system and reduce the many key uncertainties needed for improved management, a coordinated multiagency federal research effort will need to be implemented.
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Industria Procesadora y de Extracción , Gas Natural , Riesgo , Cambio Climático , Regulación Gubernamental , Humanos , Salud Pública , Estados UnidosRESUMEN
Purpose To assess periaortic adipose tissue attenuation at CT angiography in different abdominal aortic aneurysm disease states. Materials and Methods In a retrospective observational study from January 2018 to December 2022, periaortic adipose tissue attenuation was assessed at CT angiography in patients with asymptomatic or symptomatic (including rupture) abdominal aortic aneurysms and controls without aneurysms. Adipose tissue attenuation was measured using semiautomated software in periaortic aneurysmal and nonaneurysmal segments of the abdominal aorta and in subcutaneous and visceral adipose tissue. Periaortic adipose tissue attenuation values between the three groups were assessed using Student t tests and Wilcoxon rank sum tests followed by a multiregression model. Results Eighty-eight individuals (median age, 70 years [IQR, 65-78]; 78 male and 10 female patients) were included: 70 patients with abdominal aortic aneurysms (40 asymptomatic and 30 symptomatic, including 24 with rupture) and 18 controls. There was no evidence of differences in the periaortic adipose tissue attenuation in the aneurysmal segment in asymptomatic patients versus controls (-81.44 HU ± 7 [SD] vs -83.27 HU ± 9; P = .43) and attenuation in nonaneurysmal segments between asymptomatic patients versus controls (-75.43 HU ± 8 vs -78.81 HU ± 6; P = .08). However, symptomatic patients demonstrated higher periaortic adipose tissue attenuation in both aneurysmal (-57.85 HU ± 7; P < .0001) and nonaneurysmal segments (-58.16 HU ± 8; P < .0001) when compared with the other two groups. Conclusion Periaortic adipose tissue CT attenuation was not increased in stable abdominal aortic aneurysm disease. There was a generalized increase in attenuation in patients with symptomatic disease, likely reflecting the systemic consequences of acute rupture. Keywords: Abdominal Aortic Aneurysm, Periaortic Adipose Tissue Attenuation, CT Angiography ClinicalTrials.gov registration no. NCT02229006 © RSNA, 2024.
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Aneurisma de la Aorta Abdominal , Anciano , Femenino , Humanos , Masculino , Tejido Adiposo/diagnóstico por imagen , Adiposidad , Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Obesidad , Estudios RetrospectivosRESUMEN
In April of 2018, an optical gas imaging (OGI) and full flow sampler (FFS) emissions measurement study of pneumatic controllers (PCs) was conducted at 15 oil and natural gas production sites in West Virginia. The objective of the study was to identify and characterize PC systems with excessive emissions caused by maintenance issues or nonoptimized process conditions. A total of 391 PC systems were found on the sites and all were classified by the operator as snap-acting (on/off) intermittent venting PCs (IPCs) that should exhibit little gas release while the PC is closed between actuation events. The population was comprised of two groups, 259 infrequently actuating, lower emitting (LE) IPCs and 132 gas processing unit (GPU) liquid level IPCs and associated dump valve actuators that vent more frequently and have larger emission volumes. Using a PC-specific OGI inspection protocol with an assumed whole gas OGI detection threshold of 2.0 scfh, only 2 out of 259 LE-IPCs exhibited OGI detectable emissions indicating good inspection and maintenance practices for this category. Due to combined (ganged) GPU exhaust vents, the OGI inspection of the GPU liquid level IPCs was comparatively less informative and determination of single component IPC emissions by the FFS was more difficult. The time resolved FFS measurements of GPU IPCs defined three categories of operation: one that indicated proper function and two associated with higher emissions that may result from an IPC maintenance or process issues. The overall GPU IPC emission distribution was heavy tailed, with a median value of 12.8 scfh, similar to the 13.5 scfh whole gas IPC emission factor (EF). Total emissions were dominated by non-optimal temporal profile high-emitter IPC cases with the top 20% of IPC systems accounting for between 51.3% and 70.7% of GPU liquid level IPC emissions by volume. The uncertainty in the estimate was due to the ganged nature of the GPU exhaust vents. The highest GPU IPC emission came from a single malfunctioning unit with a measured whole gas value of 157 scfh. Up to six IPCs exceeded 100 scfh. An analysis of FFS emission measurements compared to liquids production per IPC unit employed indicated that production sites operating at a high level of liquids production test the limits of the site engineering, likely resulting in higher IPC emissions. Overall, this study found that the LE-IPCs with OGI-verified low closed bleed rates may emit well below the IPC EF while GPU liquid level IPC systems are likely well represented by the current IPC EF. IPCs that are experiencing a maintenance or process issue or that are operating at sites with a very high product throughput per IPC employed can emit at rates exceeding ten times IPC EF.
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OBJECTIVE: In patients with abdominal aortic aneurysms, sodium [18F]fluoride positron emission tomography identifies aortic microcalcification and disease activity. Increased uptake is associated with aneurysm expansion and adverse clinical events. The effect of endovascular aneurysm repair (EVAR) on aortic disease activity and sodium [18F]fluoride uptake is unknown. This study aimed to compare aortic sodium [18F]fluoride uptake before and after treatment with EVAR. METHODS: In a preliminary proof-of-concept cohort study, preoperative and post-operative sodium [18F]fluoride positron emission tomography-computed tomography angiography was performed in patients with an infrarenal abdominal aortic aneurysm undergoing EVAR according to current guideline-directed size treatment thresholds. Regional aortic sodium [18F]fluoride uptake was assessed using aortic microcalcification activity (AMA): a summary measure of mean aortic sodium [18F]fluoride uptake. RESULTS: Ten participants were recruited (76±6 years) with a mean aortic diameter of 57±2 mm at time of EVAR. Mean time from EVAR to repeat scan was 62±21 months. Prior to EVAR, there was higher abdominal aortic AMA when compared with the thoracic aorta (AMA 1.88 vs 1.2; p<0.001). Following EVAR, sodium [18F]fluoride uptake was markedly reduced in the suprarenal (ΔAMA 0.62, p=0.03), neck (ΔAMA 0.72, p=0.02) and body of the aneurysm (ΔAMA 0.69, p=0.02) while it remained unchanged in the thoracic aorta (ΔAMA 0.11, p=0.41). CONCLUSIONS: EVAR is associated with a reduction in AMA within the stented aortic segment. This suggests that EVAR can modify aortic disease activity and aortic sodium [18F]fluoride uptake is a promising non-invasive surrogate measure of aneurysm disease activity.
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Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Calcinosis , Procedimientos Endovasculares , Humanos , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/etiología , Fluoruros , Reparación Endovascular de Aneurismas , Estudios de Cohortes , Implantación de Prótesis Vascular/métodos , Resultado del Tratamiento , Procedimientos Endovasculares/efectos adversos , Calcinosis/cirugía , Estudios Retrospectivos , Factores de Riesgo , Prótesis VascularRESUMEN
Introduction: Tracheotomy is one of the most commonly performed procedure by otolaryngologists, but no consensus exists on the effect of suturing techniques on postoperative complications. Stay sutures and Bjork flaps are utilized frequently for securing the tracheal incision to the neck skin in order to create a tract for recannulation. Methods: Retrospective cohort study of tracheotomies performed by Otolaryngology-Head and Neck Surgery providers (May 2014 to August 2020) was conducted to determine the effect of suturing technique on postoperative complications and patient outcomes. Patient demographics, medical comorbidities, indication for tracheostomy, and postoperative complications were analyzed with a statistical alpha set of .05. Results: Out of 1395 total tracheostomies performed at our institution during the study period, 518 met inclusion criteria for this study. Three hundred and seventeen tracheostomies were secured by utilizing a Bjork flap, while 201 were secured with up and down stay sutures. Neither technique was noted to be more commonly associated with tracheal bleeding, infection, mucus plugging, pneumothorax, or false passage of the tracheostomy tube. One mortality was noted following decannulation during the study period. Conclusion: Though various techniques exist; adverse outcomes are not associated with the manner in which a new tracheostomy stoma is secured. Medical comorbidities and the indications for tracheostomy likely play a more significant role in postoperative outcomes and complications. Level of evidence: Level 3.
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BACKGROUND: The diagnosis and management of myocardial infarction are increasingly complex, and establishing the presence of intracoronary thrombosis has major implications for both the classification and treatment of myocardial infarction. OBJECTIVES: The aim of this study was to investigate whether positron emission tomographic (PET) and computed tomographic (CT) imaging could noninvasively detect in vivo thrombus formation in human coronary arteries using a novel glycoprotein IIb/IIIa receptor antagonist-based radiotracer, 18F-GP1. METHODS: In a single-center observational case-control study, patients with or without acute myocardial infarction underwent coronary 18F-GP1 PET/CT angiography. Coronary artery 18F-GP1 uptake was assessed visually and quantified using maximum target-to-background ratios. RESULTS: 18F-GP1 PET/CT angiography was performed in 49 patients with and 50 patients without acute myocardial infarction (mean age: 61 ± 9 years, 75% men). Coronary 18F-GP1 uptake was apparent in 39 of the 49 culprit lesions (80%) in patients with acute myocardial infarction. False negative results appeared to relate to time delays to scan performance and low thrombus burden in small-caliber distal arteries. On multivariable regression analysis, culprit vessel status was the only independent variable associated with higher 18F-GP1 uptake. Extracoronary cardiac 18F-GP1 findings included a high frequency of infarct-related intramyocardial uptake (35%) as well as left ventricular (8%) or left atrial (2%) thrombus. CONCLUSIONS: Coronary 18F-GP1 PET/CT angiography is the first noninvasive selective technique to identify in vivo coronary thrombosis in patients with acute myocardial infarction. This novel approach can further define the role and location of thrombosis within the heart and has the potential to inform the diagnosis, management, and treatment of patients with acute myocardial infarction. (In-Vivo Thrombus Imaging With 18F-GP1, a Novel Platelet PET Radiotracer [iThrombus]; NCT03943966).