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Sulfonyl fluorides have emerged as powerful "click" electrophiles to access sulfonylated derivatives. Yet, they are relatively inert towards C-C bond forming transformations, notably under transition-metal catalysis. Here, we describe conditions under which aryl sulfonyl fluorides act as electrophiles for the Pd-catalyzed Suzuki-Miyaura cross-coupling. This desulfonative cross-coupling occurs selectively in the absence of base and, unusually, even in the presence of strong acids. Divergent one-step syntheses of two analogues of bioactive compounds showcase the expanded reactivity of sulfonyl fluorides to encompass both S-Nu and C-C bond formation. Mechanistic experiments and DFT calculations suggest oxidative addition occurs at the C-S bond followed by desulfonation to form a Pd-F intermediate that facilitates transmetalation.
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Up to now, numerous peptides/hydrolysates derived from casein and whey protein have shown angiotensin-I-converting enzyme (ACE) inhibitory. In this research, quantum topological molecular similarity (QTMS) indices of amino acids were utilized in quantitative sequence-activity modeling (QSAM) to predict the activity of a set of milk-driven peptides with ACE inhibition. Since the derived peptides have not the same number of residues, we overcame this issue by auto cross covariance (ACC) methodology. Then, some QSAMs were built to predict the pIC50 value of ACE peptides derived from Bovine Casein and Whey. The model established an acceptable relationship between the selected variables and the pIC50 of the peptides. To estimate the performance of the developed models, casein and whey proteins from human, goat, bovine and sheep were virtually broken by trypsin and chymotrypsin enzymes and the ACE activity of the resultant virtual peptides were predicted and some new ACE peptides were proposed.
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Aminoácidos/análisis , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Caseínas/farmacología , Leche/química , Fragmentos de Péptidos/farmacología , Peptidil-Dipeptidasa A/química , Proteína de Suero de Leche/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Animales , Caseínas/química , Bovinos , Cabras , Humanos , Hidrólisis , Modelos Moleculares , Fragmentos de Péptidos/química , Ovinos , Proteína de Suero de Leche/químicaAsunto(s)
Isquemia Encefálica , Accidente Cerebrovascular , Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Humanos , Accidente Cerebrovascular/tratamiento farmacológico , Tenecteplasa/uso terapéutico , Terapia Trombolítica , Activador de Tejido Plasminógeno/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: Evaluating the degree of extracranial stenosis is important in predicting the risk of cerebrovascular events and to assess if the patient can benefit from any intervention. Non-invasive methods, like Doppler Ultrasonography (DUS) are preferred to invasive methods such as Digital Subtraction Angiography (DSA). METHODS: In this retrospective study, the level of agreement between DUS and DSA regarding the degree of stenosis of Internal Carotid Arteries (ICAs) and Vertebral Arteries (VAs) was assessed. The degree of ICA stenosis was classified into 5 groups. DSA was assumed as the gold standard. VA stenosis was classified into two groups of more or less than 50% stenosis. RESULTS: A total of 428 ICAs were assessed. Based on DSA results, DUS could estimate the degree of arterial stenosis in groups of 0-15% stenosis and 100% stenosis most accurately, and the least accuracy was in groups of 50-69% and 70-99% stenosis. The overall agreement between DUS and DSA in the classified ICA stenosis was moderate (Weighted Kappa = 0.565, P < 0.001). Also, the agreement of DUS and DSA when classifying ICA stenosis into two groups of above and below 50%, was moderate (Kappa = 0.583, P < 0.001). DUS was most sensitive and specific in the group of 100% stenosis (Sensitivity: 0.75 Specificity: 0.99) as well as the group of 1-15% stenosis (Sensitivity: 0.80 Specificity: 0.76). Also, DUS was least sensitive in group of 50-69% stenosis (Sensitivity: 0.11 Specificity: 0.94). Regarding VAS, 108 arteries were assessed and the agreement between DUS and DSA was fair (Kappa = 0.248, CI95 = -0.013 - 0.509, P < 0.01). CONCLUSIONS: DUS can be used as the first-line screening tool for detecting extra cranial arteries stenosis. The practicality of the DUS as a screening tool for extracranial VAs stenosis appears to be limited.
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BACKGROUND: Hispanics are one of the largest and fastest-growing population in the United States. Having been reported as one of the high-risk ethnicities to develop Alzheimer's Disease (AD) makes elder Hispanics one of the significant groups of AD in the country, indicating a need to study the disparities in Hispanics vs. non-Hispanics patients. We aimed to determine the prevalence, morbidity, and mortality outcomes of AD in Hispanics. METHODS: We surveyed Healthcare Cost and Utilization Project (HCUP) from 2005 to 2015 to identify patients older than 50 years who were admitted for any reason and had AD diagnosis. Prevalence, demographics, age brackets, in-hospital deaths, disease severity, and hospital length of stay (LOS) were compared between the Hispanics and Non-Hispanics. RESULTS: Among 14,135,560 Hispanic discharges, 2.76% had AD, compared with 207,515,260 discharges in Non-Hispanic with 2.61% AD, p < 0.001. Hispanics had significantly more AD in all age brackets, especially over 90 years of age, p < 0.001. A significantly higher prevalence of AD in both Hispanic Females (3.27% vs. 3.10%) and Males (2.17% vs. 2.04%) was noticed, p < 0.001. In northeast and south regions of the country and urban hospitals, AD was more among Hispanics (p < 0.001). Hispanic patients were younger (81.8 ± 7.77 vs. 82.6 ± 7.50, p < 0.001), had longer LOS (6.41 ± 7.72 vs. 6.08 ± 7.05, p < 0.001), had higher hospital charges ($45,989 vs. $37,688, p < 0.001). Hispanic AD patients had higher disease severity and mortality risk (p < 0.001). However, the inpatient mortality was not different between the Hispanic and non-Hispanics. Multivariate analysis showed that Hispanics had the highest AD prevalence in the inpatient setting (OR, 1.38; 95% CI, 1.37-1.39, p < 0.001). CONCLUSION: The prevalence of AD was significantly higher in inpatient Hispanics than non-Hispanics. Hispanic AD patients had a younger age compared with non-Hispanic AD. Disease severity and mortality risks were higher in Hispanics with AD than non-Hispanics with AD. However, no difference was seen in mortality rate during admission in Hispanics vs. non-Hispanics.
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Enfermedad de Alzheimer/epidemiología , Mortalidad Hospitalaria/etnología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/etnología , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estados Unidos/epidemiologíaRESUMEN
Objectives Health insurance is associated with better outcomes in the admitted patient population, even after adjusting for other factors such as race and socioeconomic status. However, the literature is limited on the relationship between insurance status and hospital outcomes in patients hospitalized with the disease of nervous system. Methods This cross-sectional study used the Nationwide Inpatient Sample (NIS) database to achieve the results. All Major Diagnostic Category (MDC) codes from patients discharged for disease and disorders of nervous system between the years 2005 to 2014 were queried and analyzed for the impact of lack of insurance on patient outcome. Results Among 4,737,999 discharges, 5.6% had no insurance. The hospital mortality rate among uninsured and insured patients was 4.1% and 3.7%, respectively (P<0.001). In the multivariate analysis, hospital mortality of uninsured patients was higher in the elderly (aOR: 4.74[CI:4.52-4.97], P<0.001), those with comorbidities (aOR: 2.23[CI:2.18-2.27], P<0.001), Asians (aOR: 1.16[CI:1.12-1.20]. P<0.001), in rural areas (aOR: 1.44[ 95%CI:1.41-1.48], P<0.001) and those in the lowest household income quartile (aOR: 1.03[CI:1.01-1.05], P<0.001). The average length of stay (LOS) was shorter for the uninsured (4.79±8.26 vs 4.96±7.55 days, P<0.001). Conclusions The findings suggest that lack of health insurance is correlated with hospital mortality in patients hospitalized with disease and disorders of nervous system, with an increased disparity in vulnerable populations.
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Background: Amyotrophic Lateral Sclerosis-Specific Quality of Life-Revised (ALSSQOL-R) encompasses 50 items which assess quality of life (QOL) in patients with amyotrophic lateral sclerosis (ALS) in six major domains. This study aims to translate the ALSSQOL-R into Persian and evaluate its reliability and validity among Iranian patients. Methods: ALSSQOL-R was translated by the standard multi-step forward-backward method. Content validity was calculated using item content validity index (I-CVI). Three items in the "intimacy" domain were deleted considering Iranian culture. Cronbach's alpha was used for all 6 dimensions to calculate the internal consistency reliability. Test-retest reliability was evaluated using intraclass correlation coefficient (ICC) with one-month interval. Concurrent validity was measured by the validated version of 36-Item Short Form Health Survey (SF-36) questionnaire. Results: Sixty-three patients with ALS were enrolled in the study. I-CVI was 70%, promoted to 85% after modifications (acceptable). Regarding internal consistency reliability, Cronbach's alpha in all six domains was 0.70 and total Cronbach's alpha was 0.89 which is assumed as good. In terms of test-retest reliability, ICC [95% confidence interval (CI)] was 0.91 (91%) and Pearson correlation coefficient (r) was 0.90 (P < 0.001), all indicating an excellent reliability. The concurrent validity was established based on a strong correlation with SF-36 (r = 0.744, P < 0.001). Conclusion: The findings show that the modified Persian version of ALSSQOL-R is a valid and reliable QOL questionnaire which can be used for Iranian patients with ALS in both clinical and research settings.
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BACKGROUND: Myxoma may cause systemic embolization and frequently presents as ischemic stroke. CASE PRESENTATION: There have been debates about whether it is safe to use recombinant tissue plasminogen activator (rt-PA) in patients with cardiac myxoma who referred with ischemic stroke to the hospital's emergency. RESULTS: The patient was a young case of atrial myxoma with initial presentation of acute cerebral infarction symptoms who was treated with intravenous rt-PA with no complications. CONCLUSION: The case provides an evidence of the efficacy and safety of intravenous rt-PA in cases of cardiac myxoma. However, we cannot always expect thrombolytic therapy to be effective, especially in tumor emboli.
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BACKGROUND: Knowledge of variations in the origin of vertebral artery (VA) is indispensable to vascular surgeons. Aberrant origin of vertebral artery on either side is an uncommon finding. There are unilateral and bilateral variability in VA origin. CASE PRESENTATION: We present a case of vertebral artery dissection who was found to have bilateral VAs aberrant origin. The right VA took origin from the right common carotid artery (CCA) which is a completely a rare finding, and the left VA originated from the arch of aorta. CONCLUSION: Unlike most similar reported cases, the VA diameter at origin was larger on the left than on the right side. The possible embryological mechanism is discussed.
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Coronavirus disease 2019 (COVID-19) disease caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with many neurological symptoms. The purpose of this article is to describe the neurological manifestations so far reported and their probable pathogenesis. We conducted a literature review on EMBASE, MEDLINE and SCIELO databases using the terms "COVID-19", "COVID", "neurological", "neurologic", "manifestations", "implications", "Guillain-Barre syndrome", "encephalopathy". A total of 33 articles including clinical series, retrospective studies, and case reports were selected and thoroughly reviewed to describe neurological manifestations of COVID-19. There are several neurological manifestations of SARS-CoV-2 infection with different clinical presentations, severity, and prevalence. The most critical ones, such as cerebrovascular disease, encephalopathy, and Guillain-Barre syndrome, were less common and usually associated with previous medical history, known risk factors for cerebrovascular disease or advanced age. The main hypotheses for the spread of the virus are through the hematogenous route or the cribriform plate of the ethmoid bone or a disseminated severe immune response by a cytokine storm. The presence of neurological disturbances associated with laboratory tests alterations is an important clue for the physicians to promptly recognize neurological manifestations of SARS-CoV-2.
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Background: A number of patients with symptoms of acute cerebral ischemia may have other causes called stroke mimics (SM). The prevalence of SM can be as high as 31% in some reports, and these patients are potentially at the risk of intravenous thrombolysis (IVT) therapy and its complications. This study was designed to determine the prevalence of our center's SM (Firoozgar Hospital) among patients who received IVT, their baseline characteristics, final diagnoses, and outcomes. Methods: We reviewed the medical records of all patients who received IVT between June 2015 and May 2018. The following variables were collected: demographic characteristics, past medical history, onset-to-needle (OTN) time, door-to-needle (DTN) time, National Institutes of Health Stroke Scale (NIHSS) score at admission, brain imaging, and all paraclinic findings. Functional outcome at discharge based on modified Rankin Scale (mRS) was also assessed. Results: 10 out of 165 (6.0%) patients including 8 men and 4 women were finally diagnosed with SM. The median age and NIHSS score at presentation were 60 years and 7, respectively. Final diagnoses were seizure (n = 6), hemiplegic migraine (n = 2), conversion (n = 1), and alcohol intoxication (n = 1). All patients were discharged with a mRS score of 0 and 1 without experiencing any thrombolytic adverse effects. Conclusion: None of the patients with SM experienced any adverse effect of tissue plasminogen activator (tPA) including hemorrhage and all of them reached good mRS score. This shows that tPA is generally safe and the risk of treating patients with SM is very low and making a vital treatment decision may outweigh the risk of neglected cases in a time-sensitive setting.
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It is common knowledge that fecal microbiota is a primary source of Escherichia coli causing urinary tract infections (UTIs) via the fecal-perineal-urethral route. But, it is still unknown whether E. coli UTI is mainly caused by dominant fecal E. coli isolates (prevalence hypothesis) or the isolates that possess more virulence factors (special pathogenicity hypothesis). In the present study, the urine E. coli isolates of 30 women with UTI were compared with the fecal E. coli isolates of the same patients and healthy control individuals according to the phylogenetic group, virulence genotype, and antibiotic susceptibility pattern. The genetic relatedness of the isolates was specified and compared by pulsed-field gel electrophoresis (PFGE). PFGE analysis showed that most patients (73.3%) had distinct urine isolates which were not similar to any of their fecal isolates. Based on the phylogenetic analysis, most of the urine and fecal isolates of healthy women were assigned to phylogenetic group B2, followed by D. The distribution of phylogenetic groups was significantly different between the urine and the fecal isolates of patients (p < 0.05). The prevalence of fimH and ompT among urine isolates was significantly more than that among fecal isolates. The level of multidrug resistance was higher among urine isolates. Although more in-depth researches are required, the present study could be supported by pathogenicity hypothesis. Furthermore, concerning the antibiotic resistance pattern among uropathogenic E. coli should be highly considered.
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Infecciones por Escherichia coli/microbiología , Heces/microbiología , Infecciones Urinarias/microbiología , Escherichia coli Uropatógena/genética , Adhesinas de Escherichia coli/genética , Adhesinas de Escherichia coli/metabolismo , Adulto , Antibacterianos/farmacología , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Femenino , Proteínas Fimbrias/genética , Proteínas Fimbrias/metabolismo , Genotipo , Humanos , Péptido Hidrolasas/genética , Péptido Hidrolasas/metabolismo , Filogenia , Orina/microbiología , Escherichia coli Uropatógena/clasificación , Escherichia coli Uropatógena/efectos de los fármacos , Escherichia coli Uropatógena/aislamiento & purificaciónRESUMEN
BACKGROUND: To determine whether it is possible to predict intravenous thrombolytic therapy (IVT) outcome after 3 months in acute ischemic stroke patients who are candidate to receive recombinant tissue plasminogen activator (rt-PA), before rt-PA administration based on their risk factors and some available laboratory results. METHODS: We enrolled 118 ischemic stroke patients who were treated with standard dose of Alteplase in our hospital. Baseline characteristics, door-to-needle time (DTN), onset-to-treatment time (OTT), the National Institute Health Stroke Scale (NIHSS), systolic and diastolic blood pressure on admission, history of diabetes, hypertension, dyslipidemia, coronary artery disease (CAD), previous ischemic stroke, atrial fibrillation (AF), laboratory results were retrospectively collected. The modified Rankin Scale (mRS) was recorded after 3 months of admission and patients were divided into good (mRS 2) and poor (mRS>2) outcome groups. Chi-square test and t-test were used for categorical and continuous variables, respectively. Predictors for outcome after 3 months were studied by multivariable logistic regression. RESULTS: Good outcome was seen in 60 (51%) patients and poor outcome was seen in 58 (49%) patients. Significant predictors for outcome at 3 months according to multivariable regression analysis were NIHSS score (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.498-0.750; p<0.001), SBP (OR, 0.95; 95% CI, 0.925-0.991; P=0.01), AF (OR, 0.09; 95% CI, 0.013- 0.708; P=0.02), CAD (OR, 17.08; 95% CI, 0.013-0.708; p=0.003). CONCLUSION: Higher NIHSS score, higher SBP on admission, AF and history of CAD could be the independent predictors of outcome after IVT in acute ischemic stroke patients.
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The aim of this study was to determine the resistance patterns of uropathogenic Escherichia coli (UPEC) isolates and to investigate the frequency of several virulence genes, including fimH, papA, hlyD, cnf-1, sitA, and tsh, among various phylogenetic groups of UPEC isolates. A total of 85 E. coli isolates were recovered from urine samples from outpatients with a clinical diagnosis of uncomplicated urinary tract infections. A molecular approach to examine the antimicrobial resistance patterns was employed using PCR and the disc diffusion method. The detected frequencies of the virulence factor genes determined using PCR were: fimH (34.1%), papA (9.4%), hlyD (21.2%), cnf-1 (3.5%), sitA (15.3%), and tsh (27.1%). These results revealed that the isolates were resistant to trimethoprim-sulfamethoxazole (SXT) (74.1%), cefotaxime (CTX) (68.2%), and amoxicillin-clavulanic acid (AMC) (94.1%), and they were relatively less resistant to N (56.5%). According to these results, further investigation is needed to determine exactly whether or not SXT, CTX, and AMC are appropriate antibiotics for the treatment of UPEC infections in southern Iran. Although these results demonstrate that fimH is the most frequent virulence gene among UPEC isolates, the high prevalence of isolates that do not encode fimH (75.9%) and the relatively low frequency of isolates that carry other virulence genes require further investigation to clarify the role of the other potential virulence factors in the pathogenesis of these isolates.