BE-FAST (Balance, Eyes, Face, Arm, Speech, Time): Reducing the Proportion of Strokes Missed Using the FAST Mnemonic.

BACKGROUND AND PURPOSE: The FAST algorithm (Face, Arm, Speech, Time) helps identify persons having an acute stroke. We determined the proportion of patients with acute ischemic stroke not captured by FAST and evaluated a revised mnemonic. METHODS: Records of all patients admitted to the University of Kentucky Stroke Center between January and December 2014 with a discharge International Classification of Diseases, Ninth Revision, Clinical Modification code for acute ischemic stroke were reviewed. Those misclassified, having missing National Institutes of Health Stroke Scale data, or were comatose or intubated were excluded. Presenting symptoms, demographics, and examination findings based on the National Institutes of Health Stroke Scale data were abstracted. RESULTS: Of 858 consecutive records identified, 736 met inclusion criteria; 14.1% did not have any FAST symptoms at presentation. Of these, 42% had gait imbalance or leg weakness, 40% visual symptoms, and 70% either symptom. With their addition, the proportion of stroke patients not identified was reduced to 4.4% (P<0.0001). In a sensitivity analysis, if face weakness, arm weakness, or speech impairment on admission examination were considered in addition to a history of FAST symptoms, the proportion missed was reduced to 9.9% (P=0.0010). The proportion of stroke patients not identified was also reduced (2.6%) with the addition of a history of gait imbalance/leg weakness or visual symptoms (P<0.0001). CONCLUSIONS: Of patients with ischemic stroke with deficits potentially amenable to acute intervention, 14% are not identified using FAST. The inclusion of gait/leg and visual symptoms leads to a reduction in missed strokes. If validated in a prospective study, a revision of public educational programs may be warranted.

Comparative antioxidant and bioavailability studies of Vitamin C in Phyllanthus emblica Linn. and its combinations with Piper nigrum Linn. and Zingiber officinale Roscoe

ABSTRACT Phyllanthus emblica Linn. (amla) is used in Ayurveda, the ancient Indian system of medicine and its major constituent is vitamin C which has effective free radical scavenging property. The purpose of this study was to evaluate the in vitro antioxidant activity and the bioavailability profile of vitamin C in amla and its combinations with piperine and ginger in comparison to synthetic vitamin C using New Zealand rabbits. In vitro antioxidant activity studies of synthetic vitamin C, amla, amla with piperine and amla with ginger were carried out using different models such as 2,2-Diphenyl-1-picrylhydrazyl, Nitric Oxide, Hydrogen peroxide scavenging methods, Total reductive capability and Oxygen Radical Absorbance Capacity estimation. The study results showed that synthetic vitamin C, amla, amla with piperine and amla with ginger possess significant in vitro antioxidant activity. For bioavailability studies, synthetic vitamin C, amla, amla with piperine and amla with ginger 100 mg/kg, were administered orally and the serum samples were analyzed by HPLC at 0, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours. Bioavailability studies revealed that amla with piperine combination has higher concentration of vitamin C when compared to synthetic vitamin C. This is probably due to presence of piperine, which is a bioavailability enhancer. The present study supports the fact that amla with piperine combination can be an alternative to synthetic vitamin C.

RESUMO Phyllanthus emblica Linn. (amla) é utilizada na medicina Ayurveda, medicina da Índia antiga e seu principal constituinte é a vitamina C, que possui propriedade sequestrante de radicais livres. O propósito deste estudo foi avaliar a atividade antioxidante in vitro e o perfil de biodisponibilidade da vitamina C na amla e suas combinações com piperina e gengibre em comparação com a vitamina C sintética, utilizando coelhos da Nova Zelândia. Os estudos de atividade antioxidante in vitro de vitamina C sintética, amla, amla com piperina e amla com gengibre foram realizados utilizando-se diferentes modelos para sequestrantes, como 2,2-difenil-1-picrilidrazil, óxido nítrico, peróxido de hidrogênio, capacidade redutiva total e a estimativa da capacidade de absorvância do radical oxigênio. Os resultados do estudo mostraram que vitamina C sintética, amla, amla com piperina e amla com gengibre possuem atividade antioxidante in vitro significativa. Para os estudos de biodisponibilidade, administraram-se oralmente vitamina C sintética, amla, amla com piperina e amla com gengibre 100 mg/kg e as amostras de soro foram analisadas por CLAE em 0, 1, 2, 3, 4, 6, 8, 10, 12 e 24 horas. Os estudos de biodisponibilidade revelaram que a associação de amla com piperina tem maior concentração de vitamina C, quando comparada com a vitamina C sintética. Este efeito é provavelmente devido à presença de piperina, que é intensificador de biodisponibilidade. O presente estudo apoia o fato de que a associação de amla e piperina pode ser uma alternativa para a vitamina C sintética.

Autoimmune diseases and autoantibodies in the first degree relatives of patients with systemic sclerosis.

OBJECTIVE: To determine aggregation of autoimmune diseases in the first degree relatives (FDR) of patients with systemic sclerosis (SSc) and to investigate frequencies of antinuclear antibodies (ANA) and other autoantibodies in the FDRs and spouses of patients with SSc. METHODS: Information on FDRs including history of autoimmune disease was obtained from unrelated SSc probands in the Scleroderma Family Registry and DNA Repository. FDRs were contacted to verify any reported autoimmune diseases. The prevalence of autoimmune disease in probands' families was compared with the corresponding prevalence in controls' families as reported in the literature. Furthermore, sera from probands' FDRs and spouses in addition to unrelated controls were investigated for the presence of autoantibodies (ANA). RESULTS: We investigated 4612 FDRs of 1071 SSc probands. SSc probands with anti-centromere antibodies (ACA) and limited disease type were more likely to report familial autoimmunity (p=0.022 and p=0.041, respectively). The four most prevalent autoimmune diseases among SSc probands' FDRs were hypothyroidism (4%), Rheumatoid arthritis (1.5%), hyperthyroidism (1.3%) and systemic lupus erythematosus-SLE (0.4%). Compared to control families, SLE, hypothyroidism and hyperthyroidism were more common in SSc probands' families. The most striking increase for familial prevalence was observed in SLE (OR=16.98, 95% CI=1.02-227.82, p=0.004). ANA was present in 14.2% of probands' FDR's and 8.6% of spouses and did not differ from the prevalence of ANA among controls (p=0.124 and p=0.477, respectively). Only two FDRs of probands had ACA while none had anti-topoisomerase antibodies. CONCLUSION: Our study implies varying degrees of risk for familial autoimmunity among subtypes of SSc and provides further support for common genetic and potentially environmental factors leading to SSc and SLE.

Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis: evidence of possible gene-gene interaction and alterations in Th1/Th2 cytokines.

OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Dysregulation of the immune system, including the Th1/Th2 cytokine balance, is central to the pathogenesis of SSc. This study was undertaken to investigate the hypothesis that single-nucleotide polymorphisms (SNPs) in TBX21 and STAT4, both of which are critical transcription factors that regulate the Th1/Th2 balance, are associated with SSc susceptibility. METHODS: We tested SNPs in TBX21 and STAT4 for association with SSc in 2 independent cohorts, the SSc Registry cohort (880 SSc cases and 507 controls) and the University of Texas SSc cohort (522 cases and 531 controls). Additional white control genotypes were obtained from public repositories. We also investigated for gene-gene interactions. Plasma cytokines and whole blood gene expression profiles were examined to determine functional effects of these SNPs. RESULTS: Multiple SNPs in TBX21 and STAT4 were found to be associated with SSc. In a combined analysis of 902 SSc patients and 4,745 controls, TT genotyping of the TBX21 rs11650354 variant revealed a recessive pattern for disease susceptibility (Pcorr=1.4x10(-15), odds ratio 3.37, 95% confidence interval 2.4-4.6). In an analysis of 1,039 SSc patients and 3,322 controls, the A allele of the STAT4 variant rs11889341 was associated with increased SSc susceptibility in a dominant pattern (Pcorr=2.4x10(-5), odds ratio 1.29, 95% confidence interval 1.2-1.5). Furthermore, we identified gene-gene interaction among the TBX21 and STAT4 variants, such that the STAT4 genotype increased the risk of SSc only in the TBX21 CC genotype group. SSc patients carrying the TBX21 CC genotype had higher interleukin-6 (IL-6) and tumor necrosis factor alpha levels, and those with the TT genotype had elevated IL-2, IL-5, IL-4, and IL-13 (Th2) levels, compared with controls. Whole blood expression profiles revealed dysregulation of type I interferon pathways in the CC group and T cell pathways in the TT group of the TBX21 SNP. CONCLUSION: The present results, from studies of 2 independent cohorts, indicate that SNPs in TBX21 and STAT4 contribute uniquely and interactively to SSc susceptibility, leading to altered cytokine balance and immune dysregulation.