Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Pathogen-Mediated Proteolysis of the Cell Death Regulator RIPK1 and the Host Defense Modulator RIPK2 in Human Aortic Endothelial Cells

Porphyromonas gingivalis is the primary etiologic agent of periodontal disease that is associated with other human chronic inflammatory diseases, including atherosclerosis. The ability of P. gingivalis to invade and persist within human aortic endothelial cells (HAEC) has been postulated to contribute to a low to moderate chronic state of inflammation, although how this is specifically achieved has not been well defined. In this study, we demonstrate that P. gingivalis infection of HAEC resulted in the rapid cleavage of receptor interacting protein 1 (RIPK1), a mediator of tumor necrosis factor (TNF) receptor-1 (TNF-R1)-induced cell activation or death, and RIPK2, a key mediator of both innate immune signaling and adaptive immunity. The cleavage of RIPK1 or RIPK2 was not observed in cells treated with apoptotic stimuli, or cells stimulated with agonists to TNF-R1, nucleotide oligomerization domain receptor 1(NOD1), NOD2, Toll-like receptor 2 (TLR2) or TLR4. P. gingivalis-induced cleavage of RIPK1 and RIPK2 was inhibited in the presence of a lysine-specific gingipain (Kgp) inhibitor. RIPK1 and RIPK2 cleavage was not observed in HAEC treated with an isogenic mutant deficient in the lysine-specific gingipain, confirming a role for Kgp in the cleavage of RIPK1 and RIPK2. Similar proteolysis of poly (ADP-ribose) polymerase (PARP) was observed. We also demonstrated direct proteolysis of RIPK2 by P. gingivalis in a cell-free system which was abrogated in the presence of a Kgp-specific protease inhibitor. Our studies thus reveal an important role for pathogen-mediated modification of cellular kinases as a potential strategy for bacterial persistence within target host cells, which is associated with low-grade chronic inflammation, a hallmark of pathogen-mediated chronic inflammatory disorders

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Hepatocellular carcinoma in patients undergoing orthotopic liver transplantation: radiological findings with anatomopathological correlation in Brazil Carcinoma hepatocelular em pacientes submetidos a transplante hepático: achados radiológicos com correlação anatomopatológica no Brasil

BACKGROUND: Hepatocellular carcinoma is one of the most common malignant tumors worldwide. Imaging techniques, specially computed tomography and ultrasound, are among the most useful diagnostic tools, although the accuracy of these methods may have a significant variability. AIMS: To determine the prevalence of hepatocellular carcinoma in cirrhotic patients undergoing orthotopic liver transplantation at "Santa Casa de Misericórdia" of Porto Alegre, RS, Brazil; to estimate the sensitivity of computed tomography and ultrasound in pretransplantation detection of hepatocellular carcinoma in this population; to correlate the radiological characteristics with anatomopathological findings. MATERIALS AND METHODS: Retrospective prevalence study. Population: adult, cirrhotic patients undergoing orthotopic liver transplantation from January 1990 to July 2003. Among the 292 transplanted patients, 31 cases of hepatocellular carcinoma were diagnosed, of which 29 were included in the study. Tumor characteristics in both ultrasound and computed tomography were compared to those observed in anatomopathological examination. RESULTS: Prevalence of hepatitis C virus infection among patients with diagnosis of hepatocellular carcinoma was 93.5%, and the prevalence of hepatocellular carcinoma among transplanted patients was 10.6%. The overall sensitivity of the imaging techniques was 70.3% for computed tomography and 72% for ultrasound. CONCLUSION: The prevalence of hepatocellular carcinoma at our institution, as well as the sensitivity of both ultrasound and computed tomography to detect such tumors at pretransplantation screening were similar to those found by other authors, while the prevalence of hepatitis C virus infection, the most common etiological agent for liver disease in our patients, is one of the highest ever reported in literature. Factors influencing hepatocellular carcinoma detection rates were: time from examination to liver transplantation; acquisition of computed tomography images during arterial phase; lesion size. Arterial phase proved to be the most useful part of computed tomography examination in this study.<br>RACIONAL: O carcinoma hepatocelular é um dos tumores malignos mais comuns em todo o mundo. Exames de imagens, especialmente tomografia computadorizada e ultra-sonografia, estão entre as principais técnicas diagnósticas, embora a acurácia destes métodos possa apresentar significativa variabilidade. OBJETIVOS: Determinar a prevalência de carcinoma hepatocelular em pacientes cirróticos submetidos a transplante hepático na Santa Casa de Misericórdia de Porto Alegre, RS; estimar a sensibilidade da tomografia computadorizada e da ultra-sonografia na detecção pré-transplante de carcinoma hepatocelular nesse grupo de pacientes; correlacionar características radiológicas com achados anatomopatológicos. MATERIAIS E MÉTODOS: Estudo de prevalência retrospectivo. População: pacientes adultos, cirróticos, submetidos a transplante hepático de janeiro de 1990 a julho de 2003. Entre os 292 pacientes transplantados, foi diagnosticado 31 casos de carcinoma hepatocelular, dos quais 29 foram incluídos no estudo. As características tomográficas e ecográficas dos tumores diagnosticados pré-transplante foram comparadas com as observadas em exame anatomopatológico. RESULTADOS: A prevalência da infecção pelo vírus da hepatite C nos pacientes com diagnóstico de carcinoma hepatocelular foi de 93,5% e a prevalência deste entre os pacientes transplantados foi de 10,6%. A sensibilidade dos métodos de imagem na detecção de casos de carcinoma hepatocelular foi de 70,3% para tomografia computadorizada e de 72% para ecografia. CONCLUSÃO: A prevalência de carcinoma hepatocelular na instituição onde foi desenvolvido o estudo, bem como a sensibilidade da ultra-sonografia e da tomografia computadorizada para detecção dessa neoplasia na avaliação pré-transplante foi semelhante à relatada na literatura. Em contrapartida, a prevalência de infecção pelo vírus da hepatite C, fator etiológico de hepatopatia mais freqüente nos pacientes desta série, é das maiores já relatadas. Os fatores que influenciaram as taxas de detecção de carcinoma hepatocelular foram: tempo decorrido entre realização do exame e transplante; realização de tomografia computadorizada com fase arterial; tamanho da lesão. A fase arterial provou ser a mais importante no diagnóstico de carcinoma hepatocelular neste estudo