The Octonions

The octonions are the largest of the four normed division algebras. While somewhat neglected due to their nonassociativity, they stand at the crossroads of many interesting fields of mathematics. Here we describe them and their relation to Clifford algebras and spinors, Bott periodicity, projective and Lorentzian geometry, Jordan algebras, and the exceptional Lie groups. We also touch upon their applications in quantum logic, special relativity and supersymmetry.Comment: 56 pages LaTeX, 11 Postscript Figures, some small correction

Salinomycin enhances doxorubicin-induced cytotoxicity in multidrug resistant MCF-7/MDR human breast cancer cells via decreased efflux of doxorubicin

Salinomycin is a monocarboxylic polyether antibiotic, which is widely used as an anticoccidial agent. The anticancer property of salinomycin has been recognized and is based on its ability to induce apoptosis in human multidrug resistance (MDR). The present study investigated whether salinomycin reverses MDR towards chemotherapeutic agents in doxorubicin-resistant MCF-7/MDR human breast cancer cells. The results demonstrated that doxorubicin-mediated cytotoxicity was significantly enhanced by salinomycin in the MCF-7/MDR cells, and this occurred in a dose-dependent manner. This finding was consistent with subsequent observations made under a confocal microscope, in which the doxorubicin fluorescence signals of the salinomycin-treated cells were higher compared with the cells treated with doxorubicin alone. In addition, flow cytometric analysis revealed that salinomycin significantly increased the net cellular uptake and decreased the efflux of doxorubicin. The expression levels of MDR-1 and MRP-1 were not altered at either the mRNA or protein levels in the cells treated with salinomycin. These results indicated that salinomycin was mediated by its ability to increase the uptake and decrease the efflux of doxorubicin in MCF-7/MDR cells. Salinomycin reversed the resistance of doxorubicin, suggesting that chemotherapy in combination with salinomycin may benefit MDR cancer therapyopen

Edematous and painful external hemorrhoids following intersphincteric resection for low rectal cancer

Intersphincteric resection (ISR) is the ultimate sphincter saving procedure for low rectal cancer. Hemorrhoids are a common benign condition. We present and discuss a case of ISR which developed painful edematous hemorrhoids after ISR. A 62-year-old female with low rectal cancer received neoadjuvant chemoradiotherapy with successful down staging of tumor before undergoing robot assisted ISR with coloanal hand-sewn anastomosis. She had pre-existing external hemorrhoids which were not excised. She developed painful and edematous external hemorrhoids 4 days after surgery. These were treated conservatively before discharge. Many colorectal surgeons performing ISR have experienced similar situations in their patients, but none have reported on this phenomenon. We discuss the possible factors that may contribute to this situation. A possible solution is prophylactic excision of the hemorrhoids during coloanal anastomosis. Painful hemorrhoids may occur after ISR and if managed conservatively, the outcome is skin tags

Relationship between the hepatic venous pressure gradient and first variceal hemorrhage in patients with cirrhosis: a multicenter retrospective study in Korea

Background/AimsVariceal hemorrhage is one of the major complications of cirrhosis and is associated with significant mortality and morbidity. The development of gastroesophageal varices and variceal hemorrhage is the most direct consequence of portal hypertension. Correlations between the hepatic venous pressure gradient (HVPG) and first variceal hemorrhage were examined.MethodsPatients with cirrhosis who underwent HVPG measurement between July 2009 and September 2010 were enrolled (n=535). All patients underwent esophagogastroduodenoscopy to enable the evaluation of gastroesophageal varices.ResultsThe HVPG for all patients was 16.46±7.05 mmHg (mean±SD), and was significantly higher among those with first variceal hemorrhage than in those without it. The HVPG was significantly correlated with both Child-Turcotte-Pugh (r=0.488, P<0.001) and Model for End-stage Liver Disease (r=0.478, P<0.001) scores. An HVPG value of 11 mmHg was predictive of first variceal hemorrhage with a sensitivity of 92.4% and a specificity of 27.7%.ConclusionsThe HVPG was higher in patients with first variceal hemorrhage than in those without it

Prognostic indicators in primary biliary cirrhosis: significance of revised IAHG (International Autoimmune Hepatitis Group) score

Background/AimsPrimary biliary cirrhosis (PBC) is a slowly progressing autoimmune disease of the liver that is characterized by portal inflammation and immune-mediated destruction of the intrahepatic bile ducts. Serum total bilirubin is one of the various prognostic factors that have been proposed. A recent study found that PBC with accompanying autoimmune hepatitis (AIH) carries a negative prognosis. This study examined the clinical characteristics of PBC and analyzed the factors that affect its prognosis.MethodsPatients diagnosed with PBC between January 1998 and December 2010 based on clinical and histopathological findings were compiled and analyzed retrospectively.ResultsAmong 27 patients, 24 (1 male and 23 females, ages 50.0±9.3 years) were followed up. The follow-up period was 8.6±0.9 years. Of the 24 patients, 9 patients progressed to liver cirrhosis (LC). Comparison between patients who did and did not progress to LC revealed statistically significant differences in the patients' serum total bilirubin (2.7±1.8 vs. 0.8±0.4, P=0.012), the Mayo risk score (5.1±0.7 vs. 3.9±0.6, P=0.001), the revised IAHG (International Autoimmune Hepatitis Group) score (9.2±2.3 vs. 5.4±3.0, P=0.004) and frequency of AIH overlap (5/9 [55.6%] vs. 0/15 [0%], P=0.001) at the time of diagnosis.ConclusionsWe propose that serum total bilirubin, the Mayo risk score, and the revised IAHG score at the time of diagnosis are helpful for predicting PBC prognosis. In particular, since all of the patients with accompanying AIH progressed to LC, the presence of overlap syndrome at the time of diagnosis is helpful for predicting PBC prognosis and providing an adequate treatment

CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimers disease as an indicator of tau phosphorylation

Abstract Background Recently, several studies suggested potential involvements of α-synuclein in Alzheimers disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α-synuclein could be an additional supported biomarker in AD diagnosis. Methods In this cross-sectional study, CSF samples of 71 early-onset AD, 34 late-onset AD, 11 mild cognitive impairment, 17 subjective cognitive decline, 45 Parkinsons disease, and 32 healthy control (HC) were collected. CSF amyloid-β1-42 (A), total tau (N), and phosphorylated tau181 (T) were measured by commercial ELISA kits, and in-house ELISA kit was developed to quantify α-synuclein. The cognitive assessments and amyloid-PET imaging were also performed. Results CSF α-synuclein manifested a tendency to increase in AD and to decreased in Parkinsons disease compared to HC. The equilibrium states of total tau and α-synuclein concentrations were changed significantly in AD, and the ratio of total tau/α-synuclein (N/αS) was dramatically increased in AD than HC. Remarkably, N/αS revealed a strong positive correlation with tau phosphorylation rate. Also, the combination of N/αS with amyloid-β1-42/phosphorylated tau181ratio had the best diagnosis performance (AUC = 0.956, sensitivity = 96%, specificity = 87%). In concordance analysis, N/αS showed the higher diagnostic agreement with amyloid-β1-42 and amyloid-PET. Analysis of biomarker profiling with N/αS had distinctive characteristics and clustering of each group. Especially, among the group of suspected non-Alzheimers disease pathophysiology, all A−T+N+ patients with N/αS+ were reintegrated into AD. Conclusions The high correlation of α-synuclein with tau and the elevated N/αS in AD supported the involvement of α-synuclein in AD pathophysiology. Importantly, N/αS improved the diagnostic performance, confirming the needs of incorporating α-synuclein as a biomarker for neurodegenerative disorders. The incorporation of a biomarker group [N/αS] could contribute to provide better understanding and diagnosis of neurodegenerative disorders

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Impact of sputum gross appearance and volume on smear positivity of pulmonary tuberculosis: a prospective cohort study

Abstract Background Although checking specimen quality upon sputum collection for acid-fast smear of suspected tuberculosis (TB) cases is recommended, this procedure is based on expert opinion. The purpose of this study was to elucidate the impact of sputum gross appearance and volume on smear positivity among patients with suspected pulmonary TB, according to sex. Methods From November 2010 through June 2011, we enrolled consecutive patients suspected to have active pulmonary TB. The association of sputum gross appearance and volume with smear positivity, along with other variables possibly affecting smear positivity such as symptoms, disease extent, and cavity on chest radiograph, were investigated. Results Among 2,439 patients undergoing TB examination, 170 (113 men, 57 women) with active pulmonary TB were enrolled. They submitted 492 sputa. There were 73 smear-positive patients (42.9%) and 164 smear-positive sputa (33.3%). While gross appearance was associated with smear positivity in both sexes (purulent or blood-tinged sputum (rather than mucoid sputum or saliva); odds ratio (OR), 2.05, 95% confidence interval (CI), 1.21–3.47 in men; OR, 2.78, 95% CI, 1.23–6.26 in women), the amount of sputum specimens was associated with smear positivity in only female patients (≥4 ml versus Conclusions Sputum gross appearance and volume were associated with smear positivity. A volume of 4 ml seems to be the the minimum sputum volume acceptable for smear microscopy in females suspected of TB. Those suspected of TB should be encouraged to expectorate grossly qualified sputum specimens.</p