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1.
J Am Coll Radiol ; 21(6S): S286-S291, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38823950

RESUMO

Abdominal aortic aneurysm (AAA) is a significant vascular disease found in 4% to 8% of the screening population. If ruptured, its mortality rate is between 75% and 90%, and it accounts for up to 5% of sudden deaths in the United States. Therefore, screening of AAA while asymptomatic has been a crucial portion of preventive health care worldwide. Ultrasound of the abdominal aorta is the primary imaging modality for screening of AAA recommended for asymptomatic adults regardless of their family history or smoking history. Alternatively, duplex ultrasound and CT abdomen and pelvis without contrast may be appropriate for screening. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.


Assuntos
Aneurisma da Aorta Abdominal , Medicina Baseada em Evidências , Programas de Rastreamento , Sociedades Médicas , Humanos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Estados Unidos , Programas de Rastreamento/métodos , Programas de Rastreamento/normas
2.
Circulation ; 149(24): e1313-e1410, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38743805

RESUMO

AIM: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia). METHODS: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate. STRUCTURE: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.


Assuntos
American Heart Association , Extremidade Inferior , Doença Arterial Periférica , Humanos , Doença Arterial Periférica/terapia , Doença Arterial Periférica/diagnóstico , Extremidade Inferior/irrigação sanguínea , Estados Unidos , Cardiologia/normas
3.
J Am Coll Cardiol ; 83(24): 2497-2604, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38752899

RESUMO

AIM: The "2024 ACC/AHA/AACVPR/APMA/ABC/SCAI/SVM/SVN/SVS/SIR/VESS Guideline for the Management of Lower Extremity Peripheral Artery Disease" provides recommendations to guide clinicians in the treatment of patients with lower extremity peripheral artery disease across its multiple clinical presentation subsets (ie, asymptomatic, chronic symptomatic, chronic limb-threatening ischemia, and acute limb ischemia). METHODS: A comprehensive literature search was conducted from October 2020 to June 2022, encompassing studies, reviews, and other evidence conducted on human subjects that was published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through May 2023 during the peer review process, were also considered by the writing committee and added to the evidence tables where appropriate. STRUCTURE: Recommendations from the "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with peripheral artery disease have been developed.


Assuntos
American Heart Association , Extremidade Inferior , Doença Arterial Periférica , Humanos , Doença Arterial Periférica/terapia , Doença Arterial Periférica/diagnóstico , Extremidade Inferior/irrigação sanguínea , Estados Unidos , Cardiologia/normas , Sociedades Médicas/normas
4.
Front Cardiovasc Med ; 11: 1352700, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38572306

RESUMO

Spontaneous coronary artery dissection (SCAD) is an uncommon condition which is increasingly recognized as a cause of significant morbidity. SCAD can cause acute coronary syndrome and myocardial infarction (MI), as well as sudden cardiac death. It presents similarly to atherosclerotic MI although typically in patients with few or no atherosclerotic risk factors, and particularly in women. As more patients are recognized to have this condition, there is a great need for clinician familiarity with diagnostic criteria, as well as with contemporary treatment approaches, and with appropriate patient-centered counseling, including genetic testing, exercise recommendations, and psychological care. The standard of care for patients with SCAD is rapidly evolving. This review therefore summarizes the diagnosis of SCAD, epidemiology, modern treatment, cardiac rehabilitation and preconception counseling, and the current approach to genetic testing, exercise recommendations, and psychological care, all of which are crucial to the vascular medicine specialist.

5.
J Am Heart Assoc ; 13(7): e032819, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38533943

RESUMO

BACKGROUND: Myocardial infarction secondary to spontaneous coronary artery dissection (SCAD) can be traumatic and potentially trigger posttraumatic stress disorder (PTSD). In a large, multicenter, registry-based cohort, we documented prevalence of lifetime and past-month SCAD-induced PTSD, as well as related treatment seeking, and examined a range of health-relevant correlates of SCAD-induced PTSD. METHODS AND RESULTS: Patients with SCAD were enrolled in the iSCAD (International SCAD) Registry. At baseline, site investigators completed medical report forms, and patients reported demographics, medical/SCAD history, psychosocial factors (including SCAD-induced PTSD symptoms), health behaviors, and health status via online questionnaires. Of 1156 registry patients, 859 patients (93.9% women; mean age, 52.3 years) completed questionnaires querying SCAD-induced PTSD. Nearly 35% (n=298) of patients met diagnostic criteria for probable SCAD-induced PTSD in their lifetime, and 6.4% (n=55) met criteria for probable past-month PTSD. Of 811 patients ever reporting any SCAD-induced PTSD symptoms, 34.8% indicated seeking treatment for this distress. However, 46.0% of the 298 patients with lifetime probable SCAD-induced PTSD diagnoses reported never receiving trauma-related treatment. Younger age at first SCAD, fewer years since SCAD, being single, unemployed status, more lifetime trauma, and history of anxiety were associated with greater past-month PTSD symptom severity in multivariable regression models. Greater past-month SCAD-induced PTSD symptoms were associated with greater past-week sleep disturbance and worse past-month disease-specific health status when adjusting for various risk factors. CONCLUSIONS: Given the high prevalence of SCAD-induced PTSD symptoms, efforts to support screening for these symptoms and connecting patients experiencing distress with empirically supported treatments are critical next steps. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04496687.


Assuntos
Anomalias dos Vasos Coronários , Transtornos de Estresse Pós-Traumáticos , Doenças Vasculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Angiografia Coronária , Vasos Coronários , Sistema de Registros , Fatores de Risco , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Doenças Vasculares/epidemiologia , Doenças Vasculares/congênito
6.
Appl Nurs Res ; 74: 151747, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38007247

RESUMO

AIM: The aim of this study is to explore experiences and perspectives of nurses and providers (e.g., physicians, medical directors, fellows, and nurse practitioners) on reducing preventable hospitalizations of nursing home (NH) residents in relation to interprofessional relationship and hospitalization decision-making process. BACKGROUND: Preventable NH resident hospitalization continues to be a pressing public health issue. Studies show that improved interprofessional relationship may help reduce hospitalization, yet research on communication processes and interactions among different NH staff remains limited. METHODS: This is a qualitative descriptive study. Two focus groups were held with fourteen nurses and thirteen in-depth, qualitative interviews were conducted with providers from two Chicagoland NHs. Focus group sessions and interviews were transcribed, coded, and analyzed for common themes based on qualitative description method. RESULTS: All study participants agreed that providers have the ultimate responsibility for hospitalization decisions. However, nurses believed they could influence those decisions, depending on provider characteristics, trust, and resident conditions. Nurses and providers differed in the way they experienced and conveyed emotions, and differed in key elements affecting hospitalization decisions such as structural or environmental factors (e.g., lacking staff and equipment at the facility, poor communication between the NH and hospitals) and interpersonal factors (e.g., characteristics of effective nurses or providers and the effective interactions between them). CONCLUSIONS: Interpersonal factors, including perceived competence, respect, and trust, may influence NH hospitalization decisions and be targeted for reducing preventable hospitalizations of residents.


Assuntos
Recursos Humanos de Enfermagem , Médicos , Humanos , Hospitalização , Casas de Saúde , Hospitais , Pesquisa Qualitativa
7.
Pediatr Ann ; 52(8): e303-e308, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37561825

RESUMO

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness. ROP occurs in infants who are born very preterm. In ROP, retinal blood vessel development, which is prematurely arrested in preterm infants, is altered by perinatal exposures like oxygen and inflammation. Optimizing nutritional practices for preterm infants may mitigate the risk of ROP. In this article, we review the evidence that postnatal growth, hyperglycemia, polyunsaturated fatty acids, and breast milk provision may affect ROP risk. We also outline the current management strategies for ROP and describe the vision outcomes of children affected by ROP. [Pediatr Ann. 2023;52(8):e303-e308.].


Assuntos
Recém-Nascido Prematuro , Retinopatia da Prematuridade , Lactente , Feminino , Criança , Recém-Nascido , Humanos , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/etiologia , Retinopatia da Prematuridade/prevenção & controle , Leite Humano , Estado Nutricional , Inflamação
8.
Am J Alzheimers Dis Other Demen ; 38: 15333175231160010, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36896819

RESUMO

Pupil dilation functions as a proxy for cognitive effort and can be measured through automated pupillometry. The aim of this scoping review is to examine how individuals with cognitive impairment differ in task-evoked pupillary responses relative to cognitively healthy individuals. A systematic literature search across six databases was conducted to identify studies examining changes in pupillary responses evoked by cognitive tasks comparing patients with dementia to healthy controls. Eight articles met inclusion criteria and were included for review. Differences in task-evoked pupillary response between cognitively impaired and cognitively healthy participants were observed across studies. Pupil dilation is decreased in patients with Alzheimer's Disease compared to controls, with no difference observed in patients with mild cognitive impairment. A mild, non-significant trend towards reduced pupil dilation in patients with either Parkinson's Disease or Dementia with Lewy Bodies suggests a similar but less pronounced effect than in AD patients. Further research is required to examine the utility of task-evoked pupillary responses as a potential biomarker indexing cognitive decline in individuals transitioning to mild cognitive impairment and/or dementia.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Parkinson , Humanos , Pupila/fisiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Biomarcadores
9.
Behav Brain Res ; 443: 114343, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-36787866

RESUMO

Transcranial direct current stimulation (tDCS) has been explored as a potential method for cognitive enhancement. tDCS may induce a cascade of neurophysiological changes including alterations in cerebral oxygenation. However, the effects of tDCS on the cognitive-cerebral oxygenation interaction remains unclear. Further, oxygenation variability across individuals remains minimally controlled for. The purpose of this sham-controlled study was to test the effects of anodal tDCS over the right dorsolateral prefrontal cortex (DLPFC) on the interaction between working memory and cerebral oxygenation while controlling for individual oxygenation variability. Thirty-three adults received resting-state functional near-infrared spectroscopy (fNIRS) recordings over bilateral prefrontal cortices. Following this, working memory was tested using a Toulouse n-back task concurrently paired with fNIRS, with measurements taken before and after 20 min of anodal or sham tDCS at 1.5 mA. With individual oxygenation controlled for, anodal tDCS was found to increase the oxyhemoglobin concentration over the right DLPFC during the 2-back (q = .015) and 3-back (q = .008) conditions. Additionally, anodal tDCS was found to improve accuracy during the 3-back task by 13.4 % (p = .028) and decrease latency by 250 ms (p = .013). The increase in oxyhemoglobin was strongly correlated with increases in accuracy (p = .041) and decreases in latency during the 3-back span (p = .017). Taken together, anodal tDCS over the right DLPFC was found to regionally increase oxyhemoglobin concentrations and improve working memory performance in higher cognitive load conditions.


Assuntos
Estimulação Transcraniana por Corrente Contínua , Adulto , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Córtex Pré-Frontal Dorsolateral , Oxiemoglobinas , Memória de Curto Prazo/fisiologia , Córtex Pré-Frontal/fisiologia , Cognição
10.
JPEN J Parenter Enteral Nutr ; 47(3): 354-363, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36398422

RESUMO

BACKGROUND: 100% soybean oil emulsions (SO100) are associated with poor docosahexaenoic acid (DHA) and arachidonic acid (ARA) status in extremely low birth weight (ELBW) infants. A multi-oil emulsion with 15% fish oil (FO15) contains more DHA and ARA than SO100. This study compares clinical outcomes, namely growth and fatty acids, in ELBW infants who received S0100 or FO15. METHODS: This observational study included ELBW infants born between 2014 and 2019 who received SO100 or FO15 for >7 days. Gas chromatography/mass spectrometry was used to measure erythrocyte fatty acids. RESULTS: The mean ± SD gestational age was 27 ± 3 and 26 ± 2 weeks for SO100 (n = 43) and FO15 (n = 43), respectively (P = 0.2). DHA (-0.3 ± 0.10% per week, P = 0.026, for FO15 vs -0.2 ± 0.05% per week, P < 0.001, for SO100) and ARA (-0.8 ± 0.21% per week for FO15 vs -0.9 ± 0.17% per week for SO100; P < 0.001 for both) declined in both groups with no difference between groups (P interaction > 0.7 for both). After controlling for days to reach full feeds, the mean difference in weight z score trajectories was similar (Est = -0.08; 95% CI, -0.82 to 0.04; P = 0.2), and SO100 was associated with a nonsignificant increased odds for cholestasis (odds ratio, 3.1; 95% CI, 0.96-10.2; P = 0.059). There was no difference in other clinical comorbidities. CONCLUSIONS: In comparison with ELBW infants who received SO100, infants who received FO15 still demonstrated a decline in DHA and ARA. Growth and other clinical outcomes were unchanged.


Assuntos
Óleos de Peixe , Nutrição Parenteral , Recém-Nascido , Humanos , Emulsões/química , Nutrição Parenteral/métodos , Recém-Nascido Prematuro , Óleo de Soja , Ácidos Docosa-Hexaenoicos , Ácido Araquidônico
11.
Invest Ophthalmol Vis Sci ; 63(12): 23, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36383353

RESUMO

Purpose: Retinopathy of prematurity (ROP) can lead to blindness. Arachidonic acid (ARA) and docosahexaenoic acid (DHA) regulate retinal inflammation and angiogenesis. The aim of this study was to investigate red blood cell membrane (RBCM) ARA and DHA in preterm infants. Methods: This prospective observational study divided infants into groups by ROP severity and RBCM ARA and DHA means and terciles. Results: Although the mean ± SD RBCM ARA was different between groups (no ROP, 17.9% ± 0.7%, vs. type 2 ROP, 17.4% ± 0.8%, vs. type 1 ROP, 16.7% ± 1.0%; P < 0.001), the mean RBCM DHA was similar (P = 0.161). Infants with type 1 ROP were more likely to be in the lowest ARA and DHA terciles than in the highest (ARA, 44% vs. 5.6%; DHA, 22% vs. 5.6%). ARA and DHA declined over the first month of life in all ROP groups. At week 1, ARA was lower in the type 1 and type 2 ROP groups compared with the no-ROP group (18% ± 2% and 19% ± 3% vs. 21% ± 2%, respectively; P < 0.05 for all). At week 2, DHA and ARA were lower in the type I ROP group compared with the no-ROP group (3% ± 1% vs. 4% ± 1%, P = 0.03 and 16% ± 1% vs. 19% ± 1%, respectively; P < 0.01). A RBCM ARA% ≥ 17 was associated with a 45% reduction in any ROP. As the estimated 4-week ARA% mean increased by 1%, the odds of ROP decreased by 70% (odds ratio = 0.30; 95% confidence interval, 0.1-0.7). Conclusions: Infants with severe ROP have lower ARA and DHA levels than infants without ROP. ARA and DHA may act synergistically to protect against ROP.


Assuntos
Ácidos Docosa-Hexaenoicos , Retinopatia da Prematuridade , Lactente , Recém-Nascido , Humanos , Membrana Eritrocítica , Recém-Nascido Prematuro , Ácido Araquidônico
12.
Sci Rep ; 12(1): 19432, 2022 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-36371458

RESUMO

Pathologic retinal neovascularization is a potentially blinding consequence seen in many common diseases including diabetic retinopathy, retinopathy of prematurity, and retinal vaso-occlusive diseases. This study investigates epithelial membrane protein 2 (EMP2) and its role as a possible modulator of angiogenesis in human retinal pigment epithelium (RPE) under hypoxic conditions. To study its effects, the RPE cell line ARPE-19 was genetically modified to either overexpress EMP2 or knock down its levels, and RNA sequencing and western blot analysis was performed to confirm the changes in expression at the RNA and protein level, respectively. Protein expression was evaluated under both normoxic conditions or hypoxic stress. Capillary tube formation assays with human umbilical vein endothelial cells (HUVEC) were used to evaluate functional responses. EMP2 expression was found to positively correlate with expression of pro-angiogenic factors HIF1α and VEGF at both mRNA and protein levels under hypoxic conditions. Mechanistically, EMP2 stabilized HIF1α expression through downregulation of von Hippel Lindau protein (pVHL). EMP2 mediated changes in ARPE-19 cells were also found to alter the secretion of a paracrine factor(s) in conditioned media that can regulate HUVEC migration and capillary tube formation in in vitro functional angiogenesis assays. This study identifies EMP2 as a potential mediator of angiogenesis in a human RPE cell line. EMP2 levels positively correlate with pro-angiogenic mediators HIF1α and VEGF, and mechanistically, EMP2 regulates HIF1α through downregulation of pVHL. This study supports further investigation of EMP2 as a promising novel target for therapeutic treatment of pathologic neovascularization in the retina.


Assuntos
Neovascularização Patológica , Fator A de Crescimento do Endotélio Vascular , Recém-Nascido , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Neovascularização Patológica/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Hipóxia/genética , Hipóxia/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Proteínas de Membrana/metabolismo , Pigmentos da Retina/metabolismo , Glicoproteínas de Membrana/metabolismo
13.
Front Rehabil Sci ; 3: 997531, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386776

RESUMO

Background: Patients with depression and/or anxiety are commonly seen in inpatient geriatric settings. Both disorders are associated with an increased risk of cognitive impairments, notably in executive functioning. Transcranial direct current stimulation (tDCS), a type of non-invasive brain stimulation, involves the administration of a low-dose electrical current to induce neuromodulation, which ultimately may act on downstream cognitive processing. Objective: The purpose of this study was to determine the effects of tDCS on executive functioning in geriatric inpatients with symptoms of depression and/or anxiety. Design: Pilot Randomized Controlled Trial. Setting: Specialized geriatric wards in a tertiary rehabilitation hospital. Methods: Thirty older-aged adults were recruited, of which twenty completed ten-to-fifteen sessions of 1.5 mA anodal or sham tDCS over the left dorsolateral prefrontal cortex. Cognitive assessments were administered at baseline and following the tDCS protocol; analyses examined the effects of tDCS on cognitive performance between groups (anodal or sham tDCS). Results: tDCS was found to increase inhibitory processing and cognitive flexibility in the anodal tDCS group, with significant changes on the Stroop test and Trail Making Test-Part B. No significant changes were observed on measures of attention or working memory. Discussion: These results provide preliminary evidence that tDCS-induced neuromodulation may selectively improve cognitive processing in older adults with symptoms of depression and/or anxiety. Clinical Trials Registration: www.clinicaltrials.gov, NCT04558177.

14.
Hypertension ; 79(8): e128-e143, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35708012

RESUMO

Renovascular disease is a major causal factor for secondary hypertension and renal ischemic disease. However, several prospective, randomized trials for atherosclerotic disease failed to demonstrate that renal revascularization is more effective than medical therapy for most patients. These results have greatly reduced the generalized diagnostic workup and use of renal revascularization. Most guidelines and review articles emphasize the limited average improvement and fail to identify those clinical populations that do benefit from revascularization. On the basis of the clinical experience of hypertension centers, specialists have continued selective revascularization, albeit without a summary statement by a major, multidisciplinary, national organization that identifies specific populations that may benefit. In this scientific statement for health care professionals and the public-at-large, we review the strengths and weaknesses of randomized trials in revascularization and highlight (1) when referral for consideration of diagnostic workup and therapy may be warranted, (2) the evidence/rationale for these selective scenarios, (3) interventional and surgical techniques for effective revascularization, and (4) areas of research with unmet need.


Assuntos
Hipertensão Renovascular , Hipertensão , Obstrução da Artéria Renal , American Heart Association , Humanos , Hipertensão Renovascular/diagnóstico , Hipertensão Renovascular/etiologia , Hipertensão Renovascular/cirurgia , Estudos Prospectivos , Obstrução da Artéria Renal/diagnóstico , Obstrução da Artéria Renal/cirurgia , Procedimentos Cirúrgicos Vasculares
15.
Cogn Behav Neurol ; 35(1): 76-82, 2022 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-35239601

RESUMO

The behavioral variant of frontotemporal dementia (bvFTD) is a neurodegenerative disease that is diagnosed by progressive neuropsychiatric changes and supportive neuroimaging. Making an accurate diagnosis of bvFTD is a challenging process that can be complicated by the presence of a subset of nonprogressive, or phenocopy, cases whose symptoms remain stable. Our patient, who presented with neuropsychiatric symptoms that are characteristic of bvFTD, improved and stabilized after thorough neuropsychiatric and neuropsychological evaluation and treatment. Our case illustrates that, despite diagnostic uncertainties, appropriate evaluation and treatment can lead to improvement and stabilization of neuropsychiatric symptoms in individuals presumed to have bvFTD.


Assuntos
Demência Frontotemporal , Doenças Neurodegenerativas , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/psicologia , Humanos , Neuroimagem , Testes Neuropsicológicos
17.
Nature ; 597(7876): 420-425, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34471290

RESUMO

Oxygen is critical for a multitude of metabolic processes that are essential for human life. Biological processes can be identified by treating cells with 18O2 or other isotopically labelled gases and systematically identifying biomolecules incorporating labeled atoms. Here we labelled cell lines of distinct tissue origins with 18O2 to identify the polar oxy-metabolome, defined as polar metabolites labelled with 18O under different physiological O2 tensions. The most highly 18O-labelled feature was 4-hydroxymandelate (4-HMA). We demonstrate that 4-HMA is produced by hydroxyphenylpyruvate dioxygenase-like (HPDL), a protein of previously unknown function in human cells. We identify 4-HMA as an intermediate involved in the biosynthesis of the coenzyme Q10 (CoQ10) headgroup in human cells. The connection of HPDL to CoQ10 biosynthesis provides crucial insights into the mechanisms underlying recently described neurological diseases related to HPDL deficiencies1-4 and cancers with HPDL overexpression5.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase/metabolismo , Ácidos Mandélicos/metabolismo , Metaboloma , Ubiquinona/análogos & derivados , Animais , Linhagem Celular , Feminino , Humanos , Ácidos Mandélicos/análise , Camundongos , Camundongos Nus , Tirosina/metabolismo , Ubiquinona/biossíntese
18.
J Am Heart Assoc ; 10(17): e021962, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34459232

RESUMO

Background Fibromuscular dysplasia (FMD) is a nonatherosclerotic arterial disease that has a variable presentation including pulsatile tinnitus (PT). The frequency and characteristics of PT in FMD are not well understood. The objective of this study was to evaluate the frequency of PT in FMD and compare characteristics between patients with and without PT. Methods and Results Data were queried from the US Registry for FMD from 2009 to 2020. The primary outcomes were frequency of PT among the FMD population and prevalence of baseline characteristics, signs/symptoms, and vascular bed involvement in patients with and without PT. Of 2613 patients with FMD who were included in the analysis, 972 (37.2%) reported PT. Univariable analysis and multivariable logistic regression were performed to explore factors associated with PT. Compared with those without PT, patients with PT were more likely to have involvement of the extracranial carotid artery (90.0% versus 78.6%; odds ratio, 1.49; P=0.005) and to have higher prevalence of other neurovascular signs/symptoms including headache (82.5% versus 62.7%; odds ratio, 1.82; P<0.001), dizziness (44.9% versus 22.9%; odds ratio, 2.01; P<0.001), and cervical bruit (37.5% versus 15.8%; odds ratio, 2.73; P<0.001) compared with those without PT. Conclusions PT is common among patients with FMD. Patients with FMD who present with PT have higher rates of neurovascular signs/symptoms, cervical bruit, and involvement of the extracranial carotid arteries. The coexistence of the 2 conditions should be recognized, and providers who evaluate patients with PT should be aware of FMD as a potential cause.


Assuntos
Displasia Fibromuscular , Zumbido , Artérias Carótidas , Displasia Fibromuscular/diagnóstico por imagem , Displasia Fibromuscular/epidemiologia , Humanos , Sistema de Registros , Zumbido/diagnóstico , Zumbido/epidemiologia , Estados Unidos
19.
JMIR Res Protoc ; 10(7): e30621, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34255727

RESUMO

BACKGROUND: Mobile app-based therapies are increasingly being employed by speech-language pathologists in the rehabilitation of people with aphasia as adjuncts or substitutes for traditional in-person therapy approaches. These apps can increase the intensity of treatment and have resulted in meaningful outcomes across several domains. OBJECTIVE: VoiceAdapt is a mobile therapy app designed with user and stakeholder feedback within a user-centered design framework. VoiceAdapt uses two evidence-based lexical retrieval treatments to help people with aphasia in improving their naming abilities through interactions with the app. The purpose of the randomized controlled trial (RCT) proposed here is to examine the feasibility and clinical efficacy of training with VoiceAdapt on the language and communication outcomes of people with aphasia. METHODS: A multicenter RCT is being conducted at two locations within Canada. A total of 80 people with aphasia will be recruited to participate in a two-arm, waitlist-controlled, crossover group RCT. After baseline assessment, participants will be randomized into an intervention group or a waitlist control group. The intervention group participants will engage in 5 weeks of training with the app, followed by posttreatment and follow-up assessments after an additional 5 weeks. Those in the waitlist control group will have no training for 5 weeks; this is followed by pretreatment assessment, training for 5 weeks, and posttreatment assessment. All trial procedures are being conducted remotely given the COVID-19 pandemic. RESULTS: Recruitment of participants started in September 2020, and the study is expected to be completed by March 2022. Publication of results is expected within 6 months of study completion. CONCLUSIONS: The results of the RCT will provide information on evidence-based practice using technology-based solutions to treat aphasia. If positive results are obtained from this RCT, the VoiceAdapt app can be recommended as an efficacious means of improving lexical retrieval and communicative functioning in people with aphasia in an easily accessible and a cost-effective manner. Moreover, the implementation of this RCT through remote assessment and delivery can provide information to therapists on telerehabilitation practices and monitoring of app-based home therapy programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT04108364; https://clinicaltrials.gov/ct2/show/NCT04108364. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30621.

20.
Clin Drug Investig ; 41(8): 741-749, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34304373

RESUMO

Filgotinib (Jyseleca®), an oral Janus kinase (JAK) inhibitor, is approved as monotherapy or in combination with methotrexate to treat moderate to severe active rheumatoid arthritis (RA) in adults who have an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs (DMARDs). In phase 3 trials, once-daily filgotinib was generally well tolerated and associated with an improvement in RA signs and symptoms as well as physical function in patients with an inadequate response to ongoing methotrexate, an inadequate response to ongoing conventional synthetic DMARDs plus an inadequate response or intolerance to prior biologic DMARDs, or limited or no prior exposure to methotrexate. In addition, filgotinib was noninferior to adalimumab in terms of low disease activity response rate (DAS28-CRP ≤ 3.2) in patients with an inadequate response to methotrexate. Filgotinib also appeared to inhibit the radiographic progression of joint damage and led to low disease activity or disease remission (DAS28-CRP < 2.6). Filgotinib showed sustained efficacy, and the safety profile of filgotinib longer term was similar to that in the phase 2 and 3 trials.


Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease mainly affecting the small joints of the hands and feet. While there is no cure for RA, biologic disease-modifying antirheumatic drugs (DMARDs), which target the inflammatory cytokines (and their receptors) involved in RA, can achieve low disease activity or disease remission. However, these drugs are not always effective or well tolerated and their administration routes (intravenous or subcutaneous) can be a barrier to use. More recently, oral drugs that act on pathways downstream of cytokine receptors have been developed. These drugs, the Janus kinase (JAK) inhibitors, are targeted synthetic DMARDs. Filgotinib (Jyseleca®), a second-generation JAK inhibitor, improves joint swelling, disease activity, pain, and physical functioning and reduces progression of joint damage in adults with moderate to severe active RA and is generally well tolerated. Like other JAK inhibitors, filgotinib is recommended in treatment guidelines as an effective alternative to biologic DMARDs in adults with moderate to severe active RA who have not responded adequately to or who do not tolerate other DMARDs.


Assuntos
Antirreumáticos , Artrite Reumatoide , Adulto , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Quimioterapia Combinada , Humanos , Piridinas/uso terapêutico , Triazóis
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