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1.
Small ; : e2311448, 2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38326094

RESUMEN

The development of a cost-effective, ultra-selective, and room temperature gas sensor is the need of an hour, owing to the rapid industrialization. Here, a new 2D semiconducting Cu(I) coordination polymer (CP) with 1,4-di(1H-1,2,4-triazol-1-yl)benzene (1,4-TzB) ligand is reported. The CP1 consists of a Cu2 I2 secondary building unit bridged by 1,4-TzB, and has high stability as well as semiconducting properties. The chemiresistive sensor, developed by a facile drop-casting method derived from CP1, demonstrates a response value of 66.7 at 100 ppm on methanol exposure, accompanied by swift transient (response and recovery time 17.5 and 34.2 s, respectively) behavior. In addition, the developed sensor displays ultra-high selectivity toward methanol over other volatile organic compounds , boasting LOD and LOQ values of 1.22 and 4.02 ppb, respectively. The CP is found to be a state-of-the-art chemiresistive sensor with ultra-high sensitivity and selectivity toward methanol at room temperature.

2.
J Neurointerv Surg ; 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38171611

RESUMEN

BACKGROUND: Mechanical thrombectomy has become the standard of care for acute ischemic stroke due to large vessel occlusions. Racial differences in outcomes after mechanical thrombectomy for acute ischemic stroke have not been extensively studied. We evaluate the real-world evidence for differences between races in the outcomes of thrombectomy for large vessel occlusions using the NeuroVascular Quality Initiative-Quality Outcomes Database (NVQI-QOD). METHODS: Data from the NVQI-QOD acute ischemic stroke registry were analyzed and compared for racial differences in outcomes after mechanical thrombectomy in 4507 patients from 28 US centers (17 states) between January 2014 and April 2021. Race was dichotomized into non-Hispanic White (NHW, n=3649) and non-Hispanic Black (NHB, n=858). We performed 1:1 propensity score matching resulting in a subsample of matched groups (n=761 each for NHB and NHW) to compare study endpoints using Welch's two-sided t-tests and Χ2 test for continuous and categorical outcomes, respectively. RESULTS: Prior to matching, NHW and NHB patients significantly differed in age, comorbidities, medication use, smoking status, and presenting stroke severity. No significant difference in functional outcomes or mortality, at discharge or follow-up, were revealed. NHB patients had higher average postprocedure length of stay than NHW patients, which persisted following matching (11.2 vs 9.1 days, P=0.004). CONCLUSION: Evidence from the NVQI-QOD acute ischemic stroke registry showed that outcome metrics, such as modified Rankin Scale score and mortality, did not differ significantly between racial groups; however, disparity between NHW and NHB patients in postprocedure length of stay following mechanical thrombectomy was revealed.

3.
Epilepsy Behav ; 149: 109484, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37988904

RESUMEN

BACKGROUND AND PURPOSE: Antiseizure medications (ASM) effectively prevent seizures in about 70% of adult epilepsy patients, but nonadherence to medication is the primary cause of breakthrough seizures, accounting for 26% to 79% of cases. Factors such as age, education, dosing frequency, forgetfulness, fear of side effects, and socioeconomic status contribute to poor adherence, especially among underserved populations. This study aimed to assess medication adherence during routine follow-up visits and identify the role of education in reducing non adherence in an underserved patient population. METHODS: The study involved a retrospective chart review of adult epilepsy patients seen at the University of Illinois Hospital between December 2016 and April 2020. Data on patient demographics, epilepsy and seizure classification, medication details, emergency visits, and adherence were collected from electronic medical records using the RedCap system. Descriptive statistics and statistical tests were conducted using STATA 17.0 for data analysis, including chi-squared analysis for categorical data and t-tests for continuous data. RESULTS: The study enrolled a total of 286 adult epilepsy patients who met the eligibility criteria. Among them, 111 patients (38.81 %) were classified as nonadherent based on ASM levels. Caucasian/white race and income > $50,000 per year, were significantly associated with adherence (p = 0.009 and p = 0.006 respectively). Moreover, patients with weekly seizures were more likely to be adherent (p = 0.042). No significant differences were found regarding medication adherence and sex, education, employment, epilepsy type, age at diagnosis, seizure type or number of current ASM medications. Even though not significant, a trend towards college educated patients being more adherent was observed (70.37 %). Of self-reported adherent patients, 33.33 % were found to be nonadherent based on ASM levels. Nurse phone calls reminding 70 non adherent patients about adherence increased the chances of becoming adherent by 80.39 %. Finally, although not statistically significant, the majority of adherent patients had no history of hospitalizations for breakthrough seizures (73.89 %). CONCLUSION: More than a third of our patients were found to be non-adherent during routine follow-up visits. Lower socio-economic status and lower education were associated with increased chances of being non adherent. Rates of adherence were improved by nurse's phone calls discussing the importance of adherence and risks of SUDEP. The findings emphasize the importance of education in improving medication adherence among these populations, suggesting the need for social interventions, community outreach programs, and targeted educational initiatives.


Asunto(s)
Epilepsia , Poblaciones Vulnerables , Adulto , Humanos , Estudios Retrospectivos , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Convulsiones/tratamiento farmacológico , Convulsiones/epidemiología , Cumplimiento de la Medicación
4.
Dalton Trans ; 52(39): 14151-14159, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37750312

RESUMEN

Cu(I)-based coordination polymers (CPs) are known as efficient emissive materials providing an eco-friendly and cost-effective platform for the development of various functional materials and sensors. In addition to the nature of the metal center, organic ligands also play a crucial role in controlling the emissive properties of coordination polymers. Herein, we report on the synthesis of dithiane- and dithiolane-substituted triphenylamine ligands L1 and L2. These ligands were found to be emissive both in the solid state and in solution. In addition, these ligands exhibit solvatochromic behaviour due to the twisted intramolecular charge transfer (TICT) phenomenon. Next, coordination behaviour of these ligands was explored with Cu(I)X salts (X = Br and Cl) and four new 1D coordination polymers [{Cu(µ2-X)2Cu}(µ2-L)]n, CP1 (X = Br, L = L1), CP2 (X = Cl, L = L1), CP3 (X = Br, L = L2), and CP4 (X = Cl, L = L2) were synthesized and crystallographically characterized. The emission behaviour of all the CPs suggests ligand-centered transitions. On mechanical grinding, emission maxima (λem) for CP1 and CP2 were blue-shifted, whereas for CP3 and CP4 red-shifts were observed. All CPs were found to emit at 448 nm with increased intensity after grinding. It is supposed that grinding is responsible for a change in the spatial arrangement (dihedral angles) of the phenyl groups of triphenylamine, causing the observed emission shifts. Furthermore, the higher emission intensity after grinding suggests the occurrence of a similar phenomenon as an aggregation-induced quenching in these CPs.

5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 3459-3463, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-36086190

RESUMEN

Subarachnoid hemorrhage (SAH) is a devastating neurological injury that can lead to many downstream complications including epilepsy. Predicting who will get epilepsy in order to find ways to prevent it as well as stratify patients for future interventions is a major challenge given the large number of variables not only related to the injury itself, but also to what happens after the injury. Extensive multimodal data are generated during the process of SAH patient care. In parallel, preclinical models are under development that attempt to imitate the variables observed in patients. Computational tools that consider all variables from both human data and animal models are lacking and demand an integrated, time-dependent platform where researchers can aggregate, store, visualize, analyze, and share the extensive integrated multimodal information. We developed a multi-tier web-based application that is secure, extensible, and adaptable to all available data modalities using flask micro-web framework, python, and PostgreSQL database. The system supports data visualization, data sharing and downloading for offline processing. The system is currently hosted inside the institutional private network and holds [Formula: see text] of data from 164 patients and 71 rodents. Clinical Relevance-Our platform supports clinical and preclinical data management. It allows users to comprehensively visualize patient data and perform visual analytics. These utilities can improve research and clinical practice for subarachnoid hemorrhage and other brain injuries.


Asunto(s)
Lesiones Encefálicas , Epilepsia , Hemorragia Subaracnoidea , Animales , Lesiones Encefálicas/complicaciones , Bases de Datos Factuales , Epilepsia/complicaciones , Humanos , Modelos Animales , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico
6.
Eur J Pharmacol ; 927: 175054, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35636524

RESUMEN

PI3Kδ plays a critical role in adaptive immune cell activation and function. Suppression of PI3Kδ has been shown to counter excessive triggering of immune responses which has led to delineating the role of this isoform in the pathophysiology of autoimmune disorders. In the current study, we have described preclinical characterization of PI3Kδ specific inhibitor LL-00071210 in various rheumatoid arthritis models. LL-00071210 displayed excellent in vitro potency in biochemical and cellular assay against PI3Kδ with IC50 values of 24.6 nM and 9.4 nM, respectively. LL-00071210 showed higher selectivity over PI3Kγ and PI3Kß as compared to available PI3K inhibitors. LL-00071210 had good stability in liver microsomes and plasma across species and showed low clearance, low-to-moderate Vss, with bioavailability of >50% in preclinical species. LL-00071210 demonstrated excellent in vivo efficacy in adjuvant-induced and collagen-induced arthritis models. Co-administration of LL-00071210 and methotrexate at subtherapeutic dose regimen in collagen induced arthritis model led to additive effects, indicating the combination potential of LL-00071210 along with available disease modifying anti-rheumatic drugs (DMARD). In conclusion, we have described a specific PI3Kδ inhibitor with ∼100-fold selectivity over other PI3K isoforms. LL-00071210 has good drug-like properties and thus warrants testing in the clinic for the treatment of autoimmune diseases.


Asunto(s)
Artritis Reumatoide , Fosfatidilinositol 3-Quinasas , Artritis Reumatoide/tratamiento farmacológico , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Relación Estructura-Actividad
8.
J Med Chem ; 64(23): 17004-17030, 2021 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-34843241

RESUMEN

The role of calcium release-activated calcium (CRAC) channels is well characterized and is of particular importance in T-cell function. CRAC channels are involved in the pathogenesis of several autoimmune diseases, making it an attractive therapeutic target for treating inflammatory diseases, like rheumatoid arthritis (RA). A systematic structure-activity relationship study with the goal of optimizing lipophilicity successfully yielded two lead compounds, 36 and 37. Both compounds showed decent potency and selectivity and a remarkable pharmacokinetic profile. Further characterization in in vivo RA models and subsequent histopathological evaluation of tissues led to the identification of 36 as a clinical candidate. Compound 36 displayed an excellent safety profile and had a sufficient safety margin to qualify it for use in human testing. Oral administration of 36 in Phase 1 clinical study in healthy volunteers established favorable safety, tolerability, and good target engagement as measured by levels of IL-2 and TNF-α.


Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Activados por la Liberación de Calcio/antagonistas & inhibidores , Calcio/metabolismo , Descubrimiento de Drogas , Administración Oral , Animales , Área Bajo la Curva , Artritis Reumatoide/tratamiento farmacológico , Bloqueadores de los Canales de Calcio/farmacocinética , Ensayos Clínicos Fase I como Asunto , Humanos , Células Jurkat , Masculino , Ratones , Ratones Endogámicos BALB C , Ratas , Ratas Endogámicas Lew , Relación Estructura-Actividad
9.
Neurosurgery ; 89(6): 1071-1079, 2021 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-34560777

RESUMEN

BACKGROUND: Delayed cerebral vasospasm is a feared complication of aneurysmal subarachnoid hemorrhage (SAH). OBJECTIVE: To investigate the relationship of systemic inflammation, measured using the systemic immune-inflammation (SII) index, with delayed angiographic or sonographic vasospasm. We hypothesize that early elevations in SII index serve as an independent predictor of vasospasm. METHODS: We retrospectively reviewed the medical records of 289 SAH patients for angiographic or sonographic evidence of delayed cerebral vasospasm. SII index [(neutrophils × platelets/lymphocytes)/1000] was calculated from laboratory data at admission and dichotomized based on whether or not the patient developed vasospasm. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to determine the ability of SII index to predict the development of vasospasm. RESULTS: A total of 246 patients were included in our study, of which 166 (67.5%) developed angiographic or sonographic evidence of cerebral vasospasm. Admission SII index was elevated for SAH in patients with vasospasm compared to those without (P < .001). In univariate logistic regression, leukocytes, neutrophils, lymphocytes, neutrophil-lymphocyte ratio (NLR), and SII index were associated with vasospasm. After adjustment for age, aneurysm location, diabetes mellitus, hyperlipidemia, and modified Fisher scale, SII index remained an independent predictor of vasospasm (odds ratio 1.386, P = .003). ROC analysis revealed that SII index accurately distinguished between patients who develop vasospasm vs those who do not (area under the curve = 0.767, P < .001). CONCLUSION: Early elevation in SII index can independently predict the development of delayed cerebral vasospasm in aneurysmal SAH.


Asunto(s)
Hemorragia Subaracnoidea , Vasoespasmo Intracraneal , Humanos , Inflamación/complicaciones , Linfocitos , Estudios Retrospectivos , Hemorragia Subaracnoidea/complicaciones , Vasoespasmo Intracraneal/diagnóstico por imagen , Vasoespasmo Intracraneal/etiología
10.
Stroke ; 52(4): 1339-1346, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33657859

RESUMEN

BACKGROUND AND PURPOSE: We investigated the prevalence, awareness, and control of vascular risk factors (VRFs) and the use of antithrombotic and statin agents in HCHS (Hispanic Community Health Study)/SOL (Study of Latinos) participants with self-reported history of stroke or transient ischemic attack. METHODS: Sociodemographic characteristics, medications, and prevalence of different VRFs were recorded. VRF diagnoses and goals were based on the recommendations of professional organizations. Factors associated with optimal VRF control and use of antithrombotic and statin agents were investigated using multivariate logistic regression. RESULTS: The analysis included 404 participants (39% men). The prevalences of hypertension, dyslipidemia, and diabetes were 59%, 65%, and 39%, respectively. Among those who met the diagnostic criteria for these diagnoses, the frequencies of awareness were 90%, 75%, and 83%, respectively. In participants who were aware of their VRFs, the prevalences of controlled hypertension, dyslipidemia, and diabetes were 46%, 32%, and 54%. Approximately 46% of the participants were on antithrombotics, 39% on statins, and 26% on both. Only 38% of those with atrial fibrillation received anticoagulation. In multivariate analyses adjusted for baseline sociodemographic characteristics, older age was associated with uncontrolled hypertension and diabetes. Residing in the United States for ≥10 years and born in the United States were associated with uncontrolled diabetes, female sex with uncontrolled dyslipidemia, and lack of health insurance with decreased use of statins and hyperlipidemia. CONCLUSIONS: Hispanic/Latino adults in the United States have high prevalence and awareness of VRFs but low adherence to secondary stroke prevention strategies. Older adults, women, and uninsured people are vulnerable groups that may benefit from targeted interventions. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060344.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Fibrinolíticos/uso terapéutico , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Prevención Secundaria , Accidente Cerebrovascular/prevención & control , Anciano , Enfermedades Cardiovasculares/complicaciones , Estudios de Cohortes , Femenino , Hispánicos o Latinos , Humanos , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Prevención Secundaria/métodos , Prevención Secundaria/estadística & datos numéricos , Accidente Cerebrovascular/etiología , Estados Unidos
11.
Stroke ; 51(11): 3295-3301, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33032489

RESUMEN

BACKGROUND AND PURPOSE: The role of regional hypoperfusion as a contributor to stroke risk in atherosclerotic vertebrobasilar disease has recently been confirmed by the observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) Study. We examined the stability of hemodynamic status over time and its relationship to stroke risk in patients from this prospective cohort. METHODS: VERiTAS enrolled patients with recently symptomatic ≥50% atherosclerotic stenosis/occlusion of vertebral and/or basilar arteries. Large vessel flow in the vertebrobasilar territory was assessed using quantitative magnetic resonance angiography, and patients were designated as low or normal flow based on distal territory regional flow, incorporating collateral capacity. Patients underwent standard medical management and follow-up for primary outcome event of vertebrobasilar territory stroke. Quantitative magnetic resonance angiography imaging was repeated at 6, 12, and 24 months. Flow status over time was examined relative to baseline and relative to subsequent stroke risk using a cause-specific proportional hazard model, with flow status treated as a time-varying covariate. Mean blood pressure was examined to assess for association with changes in flow status. RESULTS: Over 19±8 months of follow-up, 132 follow-up quantitative magnetic resonance angiography studies were performed in 58 of the 72 enrolled patients. Of the 13 patients with serial imaging who had low flow at baseline, 7 (54%) had improvement to normal flow at the last follow-up. Of the 45 patients who had normal flow at baseline, 3 (7%) converted to low flow at the last follow-up. The mean blood pressure did not differ in patients with or without changes in flow status. The time-varying flow status remained a strong predictor of subsequent stroke (hazard ratio, 10.3 [95% CI, 2.2-48.7]). CONCLUSIONS: There is potential both for improvement and worsening of hemodynamics in patients with atherosclerotic vertebrobasilar disease. Flow status, both at baseline and over time, is a risk factor for subsequent stroke, thus serving as an important prognostic marker. Registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00590980.


Asunto(s)
Circulación Cerebrovascular , Hemodinámica , Arteriosclerosis Intracraneal/fisiopatología , Accidente Cerebrovascular Isquémico/epidemiología , Insuficiencia Vertebrobasilar/fisiopatología , Anciano , Estudios de Cohortes , Femenino , Humanos , Arteriosclerosis Intracraneal/diagnóstico por imagen , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Insuficiencia Vertebrobasilar/diagnóstico por imagen
12.
Muscle Nerve ; 62(6): 717-721, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32856738

RESUMEN

INTRODUCTION: Ulnar neuropathy at the elbow (UNE) is the second most common entrapment neuropathy. Our goal was to create and analyze a grading system for UNE electrodiagnostic severity. METHODS: We retrospectively analyzed EMG reports with UNE. We then classified 112 limbs as having mild, moderate, or severe grade UNE based on electrodiagnostic findings. The association between presenting symptoms and signs, EMG findings, treatment type, and electrodiagnostic grade was statistically analyzed. RESULTS: Seventeen limbs (15.2%) had mild, 80 (71.4%) had moderate, and 15 (13.4%) had severe UNE. Symptoms (P = .016), exam findings (P < .001), and treatment type (P = .043) were significantly associated with electrodiagnostic grade. DISCUSSION: Our UNE grading system was significantly related to symptoms, physical exam, and treatment selection and may be useful to measure electrodiagnostic severity.


Asunto(s)
Potenciales de Acción , Electromiografía , Conducción Nerviosa , Síndromes de Compresión del Nervio Cubital/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Codo , Electrodiagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Síndromes de Compresión del Nervio Cubital/diagnóstico , Neuropatías Cubitales/diagnóstico , Neuropatías Cubitales/fisiopatología
13.
J Am Heart Assoc ; 9(12): e016406, 2020 06 16.
Artículo en Inglés | MEDLINE | ID: mdl-32500810

RESUMEN

Background Atherosclerotic vertebrobasilar disease is a significant etiology of posterior circulation stroke. The prospective observational VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) study demonstrated that distal hemodynamic status is a robust predictor of subsequent vertebrobasilar stroke risk. We sought to compare predictive models using thresholds for posterior circulation vessel flows standardized to age and vascular anatomy to optimize risk prediction. Methods and Results VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis/occlusion in vertebral and/or basilar arteries. Quantitative magnetic resonance angiography measured large-vessel vertebrobasilar territory flow, and patients were designated as low or normal flow based on a prespecified empiric algorithm considering distal territory regional flow and collateral capacity. For the present study, post hoc analysis was performed to generate additional predictive models using age-specific normalized flow measurements. Sensitivity, specificity, and time-to-event analyses were compared between the algorithms. The original prespecified algorithm had 50% sensitivity and 79% specificity for future stroke risk prediction; using a predictive model based on age-normalized flows in the basilar and posterior cerebral arteries, standardized to vascular anatomy, optimized flow status thresholds were identified. The optimized algorithm maintained sensitivity and increased specificity to 84%, while demonstrating a larger and more significant hazard ratio for stroke on time-to-event analysis. Conclusions These results indicate that flow remains a strong predictor of stroke across different predictive models, and suggest that prediction of future stroke risk can be optimized by use of vascular anatomy and age-specific normalized flows.


Asunto(s)
Angiografía Cerebral , Circulación Cerebrovascular , Hemodinámica , Ataque Isquémico Transitorio/etiología , Accidente Cerebrovascular Isquémico/etiología , Angiografía por Resonancia Magnética , Insuficiencia Vertebrobasilar/diagnóstico por imagen , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Velocidad del Flujo Sanguíneo , Femenino , Humanos , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/fisiopatología , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/fisiopatología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Estados Unidos , Insuficiencia Vertebrobasilar/complicaciones , Insuficiencia Vertebrobasilar/fisiopatología
14.
Epilepsy Behav ; 111: 107228, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32599431

RESUMEN

PURPOSE: People with epilepsy (PWE) come from a wide variety of social backgrounds and educational skillsets, making self-management (SM) education for improving their condition challenging. Here, we evaluated whether a mobile technology-based personalized epilepsy SM education intervention, PAUSE to Learn Your Epilepsy (PAUSE), improves SM measures such as self-efficacy, epilepsy SM behaviors, epilepsy outcome expectations, quality of life (QOL), and personal impact of epilepsy in adults with epilepsy. METHODS: Recruitment for the PAUSE study occurred from October 2015 to March 2019. Ninety-one PWE were educated using an Internet-enabled computer tablet application that downloads custom, patient-specific educational programs from Epilepsy.com. Validated self-reported questionnaires were used for outcome measures. Participants were assessed at baseline (T0), the first follow-up at completion of the PWE-paced 8-12-week SM education intervention (T1), and the second follow-up at least 3 months after the first follow-up (T2). Multiple linear regression was used to assess within-subject significant changes in outcome measures between these time points. RESULTS: The study population was diverse and included individuals with a wide variety of SM educational needs and abilities. The median time for the first follow-up assessment (T1) was approximately 4 months following the baseline (T0) and 8 months following baseline for the second follow-up assessment (T2). Participants showed significant improvement in all SM behaviors, self-efficacy, outcome expectancy, QOL, and personal impact of epilepsy measures from T0 to T1. Participants who scored lower at baseline tended to show greater improvement at T1. Similarly, results showed that participant improvement was sustained in the majority of SM measures from T1 to T2. CONCLUSION: This study demonstrated that a mobile technology-based personalized SM intervention is feasible to implement. The results provide evidence that epilepsy SM behavior and practices, QOL, outcome expectation for epilepsy treatment and management, self-efficacy, and outcome expectation and impact of epilepsy significantly improve following a personalized SM education intervention. This underscores a greater need for a pragmatic trial to test the effectiveness of personalized SM education, such as PAUSE to Learn Your Epilepsy, in broader settings specifically for the unique needs of the hard-to-reach and hard-to-treat population of PWE.


Asunto(s)
Escolaridad , Epilepsia/psicología , Calidad de Vida/psicología , Automanejo/psicología , Clase Social , Telemedicina/métodos , Adulto , Epilepsia/terapia , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Autoeficacia , Automanejo/métodos , Encuestas y Cuestionarios
15.
J Med Chem ; 63(11): 6107-6133, 2020 06 11.
Artículo en Inglés | MEDLINE | ID: mdl-32368909

RESUMEN

Voltage-gated sodium channel NaV1.7 is a genetically validated target for pain. Identification of NaV1.7 inhibitors with all of the desired properties to develop as an oral therapeutic for pain has been a major challenge. Herein, we report systematic structure-activity relationship (SAR) studies carried out to identify novel sulfonamide derivatives as potent, selective, and state-dependent NaV1.7 inhibitors for pain. Scaffold hopping from benzoxazine to chroman and indane bicyclic system followed by thiazole replacement on sulfonamide led to identification of lead molecules with significant improvement in solubility, selectivity over NaV1.5, and CYP2C9 inhibition. The lead molecules 13, 29, 32, 43, and 51 showed a favorable pharmacokinetics (PK) profile across different species and robust efficacy in veratridine and formalin-induced inflammatory pain models in mice. Compound 51 also showed significant effects on the CCI-induced neuropathic pain model. The profile of 51 indicated that it has the potential for further evaluation as a therapeutic for pain.


Asunto(s)
Cromanos/química , Canal de Sodio Activado por Voltaje NAV1.7/metabolismo , Sulfonamidas/química , Bloqueadores del Canal de Sodio Activado por Voltaje/química , Animales , Cromanos/farmacocinética , Cromanos/uso terapéutico , Citocromo P-450 CYP2C9/química , Citocromo P-450 CYP2C9/metabolismo , Citocromo P-450 CYP3A/química , Citocromo P-450 CYP3A/metabolismo , Modelos Animales de Enfermedad , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Semivida , Masculino , Ratones , Ratones Endogámicos BALB C , Canal de Sodio Activado por Voltaje NAV1.7/química , Neuralgia/inducido químicamente , Neuralgia/tratamiento farmacológico , Neuralgia/patología , Isoformas de Proteínas/antagonistas & inhibidores , Isoformas de Proteínas/metabolismo , Relación Estructura-Actividad , Sulfonamidas/farmacocinética , Sulfonamidas/uso terapéutico , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacocinética , Bloqueadores del Canal de Sodio Activado por Voltaje/uso terapéutico
16.
Cerebrovasc Dis Extra ; 9(3): 123-128, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31618729

RESUMEN

INTRODUCTION: Distal territory blood flow is independently associated with subsequent strokes in symptomatic vertebrobasilar atherosclerotic disease. We aimed to assess infarct patterns in relation to hemodynamic status in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study. METHODS: Distal territory blood flow was measured using quantitative magnetic resonance angiography (MRA) in 72 patients with symptomatic atherosclerotic vertebrobasilar disease, and then dichotomized into normal (n = 54) and low (n = 18) flow. Patients were followed longitudinally on standard medical management. Two observers blinded to flow status independently reviewed the imaging performed at the time of subsequent strokes, in order to adjudicate the likely mechanism based on infarct patterns. The frequency of stroke mechanisms was qualitatively compared based on flow status. RESULTS: During a median follow-up period of 23 months, 10/72 patients had a subsequent stroke; 5 of these had low distal flow. Infarct patterns were adjudicated to be consistent with hemodynamic (n = 2), embolic (n = 4), and junctional plaque/perforator (n = 4) infarcts. Hemodynamic infarcts were seen in 40% (2/5) low-flow patients, in comparison to 0% (0/5) normal-flow patients. CONCLUSION: In contrast to normal-flow patients, those with low distal flow seem to be uniquely susceptible to hemodynamic infarctions, although other patterns of infarction can also be seen in these hemodynamically impaired patients.


Asunto(s)
Aterosclerosis/complicaciones , Infarto Encefálico/etiología , Circulación Cerebrovascular , Hemodinámica , Insuficiencia Vertebrobasilar/complicaciones , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/fisiopatología , Velocidad del Flujo Sanguíneo , Infarto Encefálico/diagnóstico por imagen , Infarto Encefálico/fisiopatología , Angiografía Cerebral/métodos , Femenino , Humanos , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Estados Unidos , Insuficiencia Vertebrobasilar/diagnóstico por imagen , Insuficiencia Vertebrobasilar/fisiopatología
17.
Epilepsia ; 60(9): 1921-1931, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31486072

RESUMEN

OBJECTIVE: To assess depressive symptom outcomes in a pooled sample of epilepsy self-management randomized controlled trials (RCTs) from the Managing Epilepsy Well (MEW) Network integrated research database (MEW DB). METHODS: Five prospective RCTs involving 453 adults with epilepsy compared self-management intervention (n = 232) versus treatment as usual or wait-list control outcomes (n = 221). Depression was assessed with the nine-item Patient Health Questionnaire. Other variables included age, gender, race, ethnicity, education, income, marital status, seizure frequency, and quality of life. Follow-up assessments were collapsed into a visit 2 and a visit 3; these were conducted postbaseline. RESULTS: Mean age was 43.5 years (SD = 12.6), nearly two-thirds were women, and nearly one-third were African American. Baseline sample characteristics were mostly similar in the self-management intervention group versus controls. At follow-up, the self-management group had a significantly greater reduction in depression compared to controls at visit 2 (P < .0001) and visit 3 (P = .0002). Quality of life also significantly improved in the self-management group at visit 2 (P = .001) and visit 3 (P = .005). SIGNIFICANCE: Aggregate MEW DB analysis of five RCTs found depressive symptom severity and quality of life significantly improved in individuals randomized to self-management intervention versus controls. Evidence-based epilepsy self-management programs should be made more broadly available in neurology practices.


Asunto(s)
Adaptación Psicológica/fisiología , Depresión/complicaciones , Depresión/diagnóstico , Epilepsia/complicaciones , Calidad de Vida , Automanejo , Adulto , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
18.
Epilepsy Behav ; 98(Pt A): 258-265, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31398690

RESUMEN

PURPOSE: People with epilepsy (PWE) from underserved populations face significant barriers to epilepsy management and therefore may lack knowledge about epilepsy and self-management (SM) of epilepsy. This paper evaluates SM practices, self-efficacy, outcome expectancy, quality of life, and personal impact of epilepsy in PWE from underserved populations as compared with all PWE. METHODS: Recruitment for the Managing Epilepsy Well (MEW) Network PAUSE to Learn Your Epilepsy study occurred from October 2015 to March 2019. Participants were assessed at baseline; after SM education intervention; and 6-, 9-, and 15-month postbaseline assessment. Baseline data from 112 PWE were analyzed for this report. RESULTS: Study population was diverse: 63% were women, 47.3% were non-Hispanic black, 24.1% were Hispanic, and 57.4% had public healthcare coverage. Participants on average had epilepsy for 14 years, and 49.1% reported at least one seizure within the past month, but only 27% reported having used a seizure diary or calendar for seizure tracking. Self-management practices & behaviors were significantly lower among PWE from underserved populations than all PWE, though self-efficacy among PWE from underserved populations was significantly higher. CONCLUSION: This study identifies the unique epilepsy SM needs of PWE from underserved populations. We discuss the need for a personalized approach for developing SM skills and behaviors among these PWE.


Asunto(s)
Epilepsia/psicología , Medicina de Precisión/psicología , Calidad de Vida/psicología , Autoeficacia , Automanejo/psicología , Poblaciones Vulnerables/psicología , Adolescente , Adulto , Anciano , Epilepsia/economía , Epilepsia/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Medicina de Precisión/economía , Medicina de Precisión/métodos , Automanejo/economía , Automanejo/métodos , Adulto Joven
19.
J Org Chem ; 84(20): 12800-12808, 2019 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-31321982

RESUMEN

Nickel-catalyzed regioselective C(2)-H arylation of indoles and pyrroles with aryl chlorides is achieved under neat conditions. This method allows the efficient coupling of diverse aryl chlorides employing a user-friendly and inexpensive Ni(OAc)2/dppf catalyst system at 80 °C. Numerous functionalities, such as halides, alkyl ether, fluoro-alkyl ether, and thioether, and substituted amines, including heteroarenes like benzothiazolyl, pyrrolyl, indolyl, and carbazolyl, are well tolerated under the reaction conditions. The preliminary mechanistic study highlights a single-electron transfer (SET) pathway for the arylation reaction.

20.
Stroke ; 50(2): 495-497, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30580717

RESUMEN

Background and Purpose- Cerebral hypoperfusion symptoms (defined as symptoms related to change in position, effort or exertion, or recent change in antihypertensive medication) have been used in stroke studies as a surrogate for detecting hemodynamic compromise. However, the validity of these symptoms in identifying flow compromise in patients has not been well established. We examined whether hypoperfusion symptoms correlated with quantitative measurements of flow compromise in the prospective, observational VERiTAS study (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke). Methods- VERiTAS enrolled patients with recent vertebrobasilar transient ischemic attack or stroke and ≥50% atherosclerotic stenosis or occlusion in vertebral or basilar arteries. Hemodynamic status using vertebrobasilar large vessel flow was measured using quantitative magnetic resonance angiography, and patients were designated as low, borderline, or normal flow based on distal territory regional flow, incorporating collateral capacity. The presence of qualifying event hypoperfusion symptoms was assessed relative to the quantitatively determined flow status (normal versus borderline/low) and also examined as a predictor of subsequent stroke risk. Results- Of the 72 enrolled subjects, 66 had data on hypoperfusion symptoms available. On initial quantitative magnetic resonance angiography designation, 43 subjects were designated as normal flow versus 23 subjects designated as low flow (n=16) or borderline flow (n=7). Of these, 5 (11.6%) normal flow and 3 (13.0%) low/borderline flow subjects reported at least one qualifying event hypoperfusion symptom ( P=0.99, Fisher exact test). Hypoperfusion symptoms had a positive predictive value of 37.5% and negative predictive value of 65.5% for low/borderline flow status. Compared with flow status, which strongly predicted subsequent stroke risk, hypoperfusion symptoms were not associated with stroke outcome ( P=0.87, log-rank test). Conclusions- These results suggest that hypoperfusion symptoms alone correlate poorly with actual hemodynamic compromise as assessed by quantitative magnetic resonance angiography and subsequent stroke risk in vertebrobasilar disease, and are not a reliable surrogate for flow measurement. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00590980.


Asunto(s)
Arteria Basilar , Angiografía por Resonancia Magnética , Accidente Cerebrovascular , Arteria Vertebral , Insuficiencia Vertebrobasilar , Adulto , Anciano , Anciano de 80 o más Años , Arteria Basilar/diagnóstico por imagen , Arteria Basilar/fisiopatología , Velocidad del Flujo Sanguíneo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/fisiopatología , Arteria Vertebral/diagnóstico por imagen , Arteria Vertebral/fisiopatología , Insuficiencia Vertebrobasilar/complicaciones , Insuficiencia Vertebrobasilar/diagnóstico por imagen , Insuficiencia Vertebrobasilar/fisiopatología
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