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AIM: Links between autism spectrum disorder (ASD) and autoimmune diseases, including Type 1 diabetes have been proposed. This study assessed the frequency of ASD in children with Type 1 diabetes in the T1D Exchange (T1DX) registry and the impact of ASD on characteristics of children with Type 1 diabetes. METHODS: Analysis included 10 032 participants aged < 18 years (median Type 1 diabetes duration 6.5 years, 48% female, 77% non-Hispanic White). Diagnosis of ASD was defined as autism, Asperger's or pervasive developmental disorder. RESULTS: A diagnosis of ASD was recorded for 159 (1.58%) participants. Those with ASD were predominantly male (88% vs. 51% of those without ASD, P < 0.001) and slightly older (median 14 vs. 13 years, P = 0.022). Occurrence of diabetic ketoacidosis at Type 1 diabetes diagnosis was similar (35% vs. 41%, P = 0.161). Pump use was lower in those with ASD (51% vs. 63%, P = 0.005) but continuous glucose monitor use was similar (24% vs. 27%, P = 0.351). Median HbA1c was slightly lower in those with ASD [68 vs. 69 mmol/mol (8.4% vs. 8.5%), P = 0.006]. This difference was more pronounced after adjusting for confounders. CONCLUSIONS: The frequency of ASD in the T1DX registry was similar to that in the general population. These data show that despite deficits in communication, occurrence of diabetic ketoacidosis was similar in youth with and without ASD. Pump use was less frequent in those with ASD, possibly due to sensory issues, although CGM use did not differ. The lower HbA1c may be due to a more regimented routine with ASD. Because comorbidities such as ASD complicate care of patients with Type 1 diabetes, further research is needed to support these children.
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Transtorno do Espectro Autista/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Adolescente , Automonitorização da Glicemia/estatística & dados numéricos , Criança , Comorbidade , Cetoacidose Diabética/epidemiologia , Feminino , Hemoglobinas Glicadas/análise , Humanos , Sistemas de Infusão de Insulina/estatística & dados numéricos , Masculino , Sistema de RegistrosRESUMO
3,7-Dihydroxytropolones (3,7-dHTs) are highly oxygenated troponoids that have been identified as lead compounds for several human diseases. To date, structure-function studies on these molecules have been limited due to a scarcity of synthetic methods for their preparation. New synthetic strategies towards structurally novel 3,7-dHTs would be valuable in further studying their therapeutic potential. Here we describe the successful adaptation of a [5 + 2] oxidopyrilium cycloaddition/ring-opening for 3,7-dHT synthesis, which we apply in the synthesis of a plausible biosynthetic intermediate to the natural products puberulic and puberulonic acid. We have also tested these new compounds in several biological assays related to human immunodeficiency virus (HIV), hepatitis B virus (HBV) and herpes simplex virus (HSV) in order to gain insight into structure-functional analysis related to antiviral troponoid development.
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Antivirais/farmacologia , HIV/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Simplexvirus/efeitos dos fármacos , Tropolona/análogos & derivados , Antivirais/síntese química , Antivirais/química , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Tropolona/síntese química , Tropolona/química , Tropolona/farmacologiaRESUMO
OBJECTIVES: As a developing country, Iran is experiencing the increasing burden of cancers, which are currently the third leading cause of mortality in Iran. This study aims to demonstrate that cancer research in Iran concentrates on the cancer research priorities based on the global burden of disease (GBD) reports. STUDY DESIGN: Descriptive evaluation of all cancers disability-adjusted life years (DALYs) was performed using GBD data. Also a comprehensive search was conducted using cancer-associated keywords to obtain all cancer-related publications from Iran, indexed in Web of Science. METHOD: Multiple regression analysis and correlation coefficients (R2) were used to evaluate the possible associations between cancer research publications and GBD. RESULTS: During 1996-2014, the majority of cancer-related publications in Iran focused on breast cancer, leukaemia and stomach cancer, respectively. This study found hypothetical correlations between cancer publications in Iran in line with the burden of cancer as reported by GBD. Particularly, correlations between years lived with disability (YLD) and cancer-related publications were more obvious. CONCLUSION: This study introduces a new outline in setting cancer research priorities in the region.
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Pessoas com Deficiência/estatística & dados numéricos , Carga Global da Doença/tendências , Neoplasias/mortalidade , Pesquisa , Efeitos Psicossociais da Doença , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Neoplasias/etnologia , Anos de Vida Ajustados por Qualidade de Vida , Análise de RegressãoRESUMO
In this study melt rheological behavior of lactose-filled polyethylene glycol (PEG) composites as a low melting polymeric carrier for controlled release drugs was investigated using a capillary rheometer. The effect of lactose concentration and process variables such as temperature and ram speed on the flow behavior of PEG has been studied. The composites were found to be shear thinning in behavior when extruded, and the results were well described by power-law model in each case. Stronger shear thinning behavior was observed by raising the filler concentration and decreasing the temperature, while the flow index has been decreased. In all compositions a significant increase in shear viscosity was found by an increase in the filler content. In fact, shear viscosity increased linearly by weight fraction of filler, but there was a dramatic increase after the filler content raised above 20 wt% of lactose which might be the result of the strong interaction among filler particles. Furthermore, decreasing the process temperature resulted in an increase in shear viscosity, and the temperature dependence of shear viscosity decreased as the shear rate increased. The extensional viscosity of composites was calculated in each case. The results showed that the ratio of the extensional viscosity to shear viscosity was in the range of 500-1200.
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Portadores de Fármacos/química , Composição de Medicamentos/métodos , Lactose/química , Polietilenoglicóis/química , Preparações de Ação Retardada , Formas de Dosagem , Modelos Teóricos , Polímeros/química , Reologia , Resistência ao Cisalhamento , Temperatura , Temperatura de Transição , ViscosidadeRESUMO
Rhabdomyosarcoma of the cervix is among the rare histological types of cervical cancers, which are usually seen in young girls or women in the general active period. The usual circumstances of diagnosis are dominated by recurrent metrorrhagia. At the initial stage, the lesions may be asymptomatic or take on the appearance of a benign polyp. In the case reported here, the clinical symptomatology was recurrent metrorrhagia with a cervical implanted polyp occurring 28 months after resection of a benign polyp. RMS is one of the malignant tumors of mesenchymal origin. Typically, it is a malignant tumor proliferation of cells with morphological and/or phenotypic striated muscle differentiation. The characteristic cells of this tumor are rhabdomyoblasts rhabdomyosarcomas are classified into three histological subtypes: embryonal, alveolar, and anaplastic. Within embryonal RMS, it is possible to distinguish between botryoid, leiomyomatous and anaplastic forms. Botryoid and leiomyomatous forms are classically described as having a more favorable prognosis. Treatment is based on a multidisciplinary approach that includes indications for conservative surgery, chemotherapy, radiotherapy and brachytherapy.
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BACKGROUND: The chicken infectious anemia virus (CIAV) is an important pathogen that causes severe immunosuppression in young chickens. AIMS: The study aims to characterize the genotype and full-length sequencing of CIAV strains in Iran. METHODS: First, the collected thymus samples were investigated by conventional PCR for CIAV detection. Second, one of the CIAV positive samples (UT-Zahraee) was chosen for full genome sequencing. RESULTS: Throughout 2017, we detected 13 CIAVs isolated from 40 broiler flocks of different provinces of Iran. A comparison of the complete sequences of the genome and homologies of the nucleotides revealed that UT-Zahraee had a high similarity with American and Egyptian CIAV isolates. Moreover, VP1 sequence analysis showed that UT-Zahraee shared high homology with previously reported Iranian CIAV strains, Chinese, and Egyptian isolates. CONCLUSION: This study is the first report of full genome sequencing of CIAV strain from Iran. It will be beneficial to understand better the epidemiology and molecular characteristics of CIAV circulating in Iran.
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BACKGROUND AND PURPOSE: In recent years, the transradial approach has become more widely adopted for neuroendovascular procedures. The purpose of this study was to evaluate the safety and feasibility of a transradial approach and distal transradial access for neuroendovascular procedures in a single center. MATERIALS AND METHODS: Retrospective analysis was performed for all patients who underwent transradial approach or distal transradial access neuroendovascular procedures from January 2016 to August 2019 at a single center. Exclusion criteria included a Barbeau D waveform, a radial artery of <2 mm on sonographic evaluation, and known radial artery occlusion. Procedures were evaluated for technical success (defined as successful radial artery access and completion of the intended procedure without crossover to an auxiliary access site), complications, and adverse events during follow-up at 30 days. RESULTS: The transradial approach or distal transradial access was attempted in 279 consecutive patients (58.1% women; median age, 57.7 years) who underwent 328 standard or distal transradial approach procedures. Two-hundred seventy-nine transradial approach and 49 distal transradial approach procedures were performed (cerebral angiography [n = 213], intracranial intervention [n = 64], head and neck intervention [n = 30], and stroke intervention [n = 21]). Technical success was 92.1%. Immediate adverse events (2.1%) included radial access site hematoma (n = 5), radial artery occlusion (n = 1), and acute severe radial artery spasm (n = 1). Thirty-day adverse events (0.3%) included a radial artery pseudoaneurysm (n = 1). Twenty-six cases (7.9%) required crossover to transfemoral access. CONCLUSIONS: The transradial approach for neuroendovascular procedures is safe and feasible across a wide range of neuroendovascular interventions.
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Procedimentos Endovasculares/métodos , Neuroendoscopia/métodos , Artéria Radial/cirurgia , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND AND PURPOSE: Racial and socioeconomic disparities in the incidence, treatment, and outcomes of acute ischemic stroke exist and have been described. We aimed to characterize disparities in the use of endovascular thrombectomy in a nationally representative analysis. MATERIALS AND METHODS: Discharge data from the Nationwide Inpatient Sample between 2006 and 2016 were queried using validated International Classification of Disease codes. Patients admitted to US hospitals with acute ischemic stroke were included and stratified on the basis of race, income, and primary payer. Trends in endovascular thrombectomy use, good outcome (discharge to home/acute rehabilitation), and poor outcome (discharge to skilled nursing facility, hospice, in-hospital mortality) were studied using univariate and multivariable analyses. RESULTS: In this analysis of 1,322,162 patients, endovascular thrombectomy use increased from 53/111,829 (0.05%) to 3054/146,650 (2.08%) between 2006 and 2016, respectively. Less increase was observed in black patients from 4/12,733 (0.03%) to 401/23,836 (1.68%) and those in the lowest income quartile from 10/819 (0.03%) to 819/44,984 (1.49%). Greater increase was observed in the highest income quartile from 18/22,138 (0.08%) to 669/27,991 (2.39%). Black race predicted less endovascular thrombectomy use (OR = 0.79; 95% CI, 0.72-0.86). The highest income group predicted endovascular thrombectomy use (OR = 1.24; 95% CI, 1.13-1.36) as did private insurance (OR = 1.30; 95% CI, 1.23-1.38). High income predicted good outcome (OR = 1.10; 95% CI. 1.06-1.14), as did private insurance (OR = 1.36; 95% CI, 1.31-1.39). Black race predicted poor outcome (OR = 1.33; 95% CI, 1.30-1.36). All results were statistically significant (P < .01). CONCLUSIONS: Despite a widespread increase in endovascular thrombectomy use, black and low-income patients may be less likely to receive endovascular thrombectomy. Future effort should attempt to better understand the causes of these disparities and develop strategies to ensure equitable access to potentially life-saving treatment.
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Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/cirurgia , Humanos , Fatores Socioeconômicos , Acidente Vascular Cerebral/cirurgia , Trombectomia , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) is an active worldwide pandemic with diverse complications. Stroke as a presentation has not been strongly associated with COVID-19. The authors aimed to retrospectively review a link between COVID-19 and acute stroke. MATERIALS AND METHODS: We conducted a retrospective case-control study of 41 cases and 82 control subjects matched by age, sex, and risk factors. Cases were patients who underwent stroke alert imaging with confirmed acute stroke on imaging between March 16 and April 5, 2020, at 6 hospitals across New York City. Control subjects were those who underwent stroke alertimaging during the same timeframe without imaging evidence of acute infarction. Data pertaining to diagnosis of COVID-19 infection, patient demographics, and risk factors were collected. A univariate analysis was performed to assess the covariate effect of risk factors and COVID-19 status on stroke imaging with positive findings. RESULTS: The mean age for cases and controls was 65.5 ± 15.3 years and 68.8 ± 13.2 years, respectively. Of patients with acute ischemic stroke, 46.3% had COVID-19 infection compared with 18.3% of controls (P = .001). After adjusting for age, sex, and risk factors, COVID-19 infection had a significant independent association with acute ischemic stroke compared with control subjects (OR, 3.9; 95% CI, 1.7-8.9; P = .001). CONCLUSIONS: We demonstrated that COVID-19 infection is significantly associated with imaging confirmation of acute ischemic stroke, and patients with COVID-19 should undergo more aggressive monitoring for stroke.
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Betacoronavirus , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/etiologia , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2RESUMO
New York City has become the global epicenter of the coronavirus 2019 (COVID-19) pandemic. Despite a massive shift in health care resources, cerebrovascular disease continues to be a substantial burden. We review the first 10 patients undergoing thrombectomy following a series of governmental and institutional policy changes diverting resources to the care of critically ill patients with COVID-19. Ten patients with emergent large-vessel occlusion underwent thrombectomy between March 23 and April 1, 2020. Five patients tested positive for the COVID-19 virus. Successful reperfusion was achieved in 9 of 10 patients, at a median time of 37 minutes from vascular access. The postprocedural NIHSS score improved by an average of 7.7 points. Of the 5 patients positive for COVID-19, none have experienced a critical respiratory illness. We report the early incidence of COVID-19 positivity in patients with emergent large-vessel occlusion and demonstrate that thrombectomy continues to be an efficacious option, as well as safe for health care providers.
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Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Acidente Vascular Cerebral/cirurgia , Trombectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Reperfusão , Estudos Retrospectivos , SARS-CoV-2 , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
CONTEXT: Estrogen deprivation therapy with aromatase inhibitors has been hypothesized to paradoxically sensitize hormone-receptor-positive breast cancer tumor cells to low-dose estradiol therapy. OBJECTIVE: To determine whether 6 mg of estradiol (daily) is a viable therapy for postmenopausal women with advanced aromatase inhibitor-resistant hormone receptor-positive breast cancer. DESIGN, SETTING, AND PATIENTS: A phase 2 randomized trial of 6 mg vs 30 mg of oral estradiol used daily (April 2004-February 2008 [enrollment closed]). Eligible patients (66 randomized) had metastatic breast cancer treated with an aromatase inhibitor with progression-free survival (> or = 24 wk) or relapse (after > or = 2 y) of adjuvant aromatase inhibitor use. Patients at high risk of estradiol-related adverse events were excluded. Patients were examined after 1 and 2 weeks for clinical and laboratory toxicities and flare reactions and thereafter every 4 weeks. Tumor radiological assessment occurred every 12 weeks. At least 1 measurable lesion or 4 measurable lesions (bone-only disease) were evaluated for tumor response. INTERVENTION: Randomization to receive 1 oral 2-mg generic estradiol tablet 3 times daily or five 2-mg tablets 3 times daily. MAIN OUTCOME MEASURES: Primary end point: clinical benefit rate (response plus stable disease at 24 weeks). SECONDARY OUTCOMES: toxicity, progression-free survival, time to treatment failure, quality of life, and the predictive properties of the metabolic flare reaction detected by positron emission tomography/computed tomography with fluorodeoxyglucose F 18. RESULTS: The adverse event rate (> or = grade 3) in the 30-mg group (11/32 [34%]; 95% confidence interval [CI], 23%-47%) was higher than in the 6-mg group (4/34 [18%]; 95% CI, 5%-22%; P = .03). Clinical benefit rates were 9 of 32 (28%; 95% CI, 18%-41%) in the 30-mg group and 10 of 34 (29%; 95% CI, 19%-42%) in the 6-mg group. An estradiol-stimulated increase in fluorodeoxyglucose F 18 uptake (> or = 12% prospectively defined) was predictive of response (positive predictive value, 80%; 95% CI, 61%-92%). Seven patients with estradiol-sensitive disease were re-treated with aromatase inhibitors at estradiol progression, among which 2 had partial response and 1 had stable disease, suggesting resensitization to estrogen deprivation. CONCLUSIONS: In women with advanced breast cancer and acquired resistance to aromatase inhibitors, a daily dose of 6 mg of estradiol provided a similar clinical benefit rate as 30 mg, with fewer serious adverse events. The efficacy of treatment with the lower dose should be further examined in phase 3 clinical trials. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00324259.
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Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Receptores de Estrogênio/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/mortalidade , Resistencia a Medicamentos Antineoplásicos , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Pós-Menopausa , Valor Preditivo dos Testes , Qualidade de Vida , Compostos Radiofarmacêuticos , Análise de SobrevidaRESUMO
BACKGROUND AND PURPOSE: Atherosclerotic plaque composition and structure contribute to the risk of plaque rupture and embolization. Virtual histology by intravascular ultrasonography and high-resolution MR imaging are new imaging modalities that have been used to characterize plaque morphology and composition in peripheral arteries. MATERIALS AND METHODS: The objectives of this study were 1) to determine the correlation between virtual histology-intravascular ultrasonography and histopathologic analysis (reference standard) and 2) to explore the comparative results of 7T MR imaging (versus histopathologic analysis), both to be performed in vitro by use of intracranial arterial segments with atherosclerotic plaques. Thirty sets of postmortem samples of intracranial circulation were prepared for the study. These samples included the middle cerebral artery (n = 20), basilar artery (n = 8), and anterior cerebral artery (n = 2). Virtual histology-intravascular ultrasonography and 7T MR imaging were performed in 34 and 10 points of interest, respectively. The formalin-fixed arteries underwent tissue processing and hematoxylin-eosin staining. The plaques were independently categorized according to revised Stary classification after review of plaque morphology and characteristics obtained from 3 modalities. The proportion of fibrous, fibrofatty, attenuated calcium, and necrotic components in the plaques were determined in histology slides and compared with virtual histology-intravascular ultrasonography and MR imaging. RESULTS: Of 34 points of interest in the vessels, 32 had atherosclerotic plaques under direct visualization. Plaques were visualized in gray-scale intravascular ultrasonography as increased wall thickness, outer wall irregularity, and protrusion. The positive predictive value of virtual histology-intravascular ultrasonography for identifying fibroatheroma was 80%. Overall, virtual histology-intravascular ultrasonography accurately diagnosed the type of the plaque in 25 of 34 samples, and κ agreement was 0.58 (moderate agreement). The sensitivity and specificity of virtual histology-intravascular ultrasonography readings for fibroatheroma were 78.9% and 73.3%, respectively. The overall sensitivity and specificity for virtual histology-intravascular ultrasonography were 73.5% and 96.6%, respectively. Plaques were identified in 7T MR imaging as increased wall thickness, luminal stenosis, or outer wall protrusion. The positive predictive value of 7T MR imaging for detecting fibrous and attenuated calcium deposits was 88% and 93%, respectively. CONCLUSIONS: This in vitro study demonstrated that virtual histology-intravascular ultrasonography and high-resolution MR imaging are reliable imaging tools to detect atherosclerotic plaques within the intracranial arterial wall, though both imaging modalities have some limitations in accurate characterization of the plaque components. Further clinical studies are needed to determine the clinical utility of plaque morphology and composition assessment by noninvasive tests.