Review of Heavy Quark Physics - theory

Recent progress in the theory of B-meson decays is reviewed with emphasis on the aspects related to the B-factory data.Comment: 15 pages; Invited Plenary Talk at the 32nd International Conference on High Energy Physics (ICHEP'04), Beijing, China, Aug. 16-22, 200

Antihyperlipidemic effects of Pleurotus ostreatus (oyster mushrooms) in HIV-infected individuals taking antiretroviral therapy

<p>Abstract</p> <p>Background</p> <p>Antiretroviral treatment (ART) regimens in HIV patients commonly cause significant lipid elevations, including increases in both triglycerides and cholesterol. Standard treatments for hypercholesterolemia include the HMG CoA reductase inhibitors, or "statins." Because many ART agents and statins share a common metabolic pathway that uses the cytochrome P450 enzyme system, coadministration of ART with statins could increase statin plasma levels significantly. The oyster mushroom, <it>Pleurotus ostreatus</it>, has been shown in animal models to decrease lipid levels - a finding that has been supported by preliminary data in a small human trial.</p> <p>Methods</p> <p>To assess the safety and efficacy of <it>P. ostreatus </it>in patients with HIV and ART-induced hyperlipidemia, a single-arm, open-label, proof-of-concept study of 8 weeks' duration with a target enrollment of 20 subjects was conducted. Study patients with ART-induced elevated non-HDL cholesterol levels (> 160 mg/dL) were enrolled. Participants received packets of freeze-dried <it>P. ostreatus </it>(15 gm/day) to be administered orally for the 8 week trial period. Lipid levels were drawn every two weeks to assess efficacy. Safety assessments included self-reported incidence of muscle aches and measurement of liver and muscle enzymes. Mean within-person change in lipid levels were estimated using generalized estimating equations to account for repeated observations on individuals. A 30 mg/dL decrease in non-HDL cholesterol was deemed clinically significant.</p> <p>Results</p> <p>126 patients were screened to enroll 25, of which 20 completed the 8-week study. The mean age was 46.4 years (36-60). Patients had a mean 13.7 yrs of HIV infection. Mean non-HDL cholesterol was 204.5 mg/dL at day 0 and 200.2 mg/dL at day 56 (mean within-person change = -1.70; 95% confidence interval (CI) = -17.4, 14.0). HDL cholesterol levels increased from 37.8 mg/dL at day 0 to 40.4 mg/dL on day 56 (mean within-person change = 2.6; 95% CI = -0.1, 5.2). Triglycerides dropped from 336.4 mg/dL on day 0 to 273.4 mg/dL on day 56 (mean within-person change = -63.0; 95% CI = -120.9, -5.1). Only 3 individuals achieved a sustained clinically significant (30 mg/dL) decline in non-HDL cholesterol after 8 weeks of therapy. There were no adverse experiences reported other than patients' distaste for the preparation. Liver function tests and muscle enzymes were not affected by the 8 weeks of treatment.</p> <p>Conclusions</p> <p><it>Pleurotus ostreatus </it>as administered in this experiment did not lower non-HDL cholesterol in HIV patients with ART-induced hypercholesterolemia. Small changes in HDL and triglycerides were not of a clinical magnitude to warrant further study.</p> <p>Trial Registration</p> <p>clinicaltrials.gov Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00069524">NCT00069524</a></p

Cystatin C and lactoferrin concentrations in biological fluids as possible prognostic factors in eye tumor development

Objectives. To investigate the possible role of cystatin C in eye biological fluids locally and in serum and lactoferrin revealing anti-tumor activity in eye tumor development. Background. The increased number of eye tumors was registered recently not only in the countries with high insolation, but also in the northern countries including Russia (11 cases per million of population). Search for new biological markers is important for diagnosis and prognosis in eye tumors. Cystatin C, an endogenous inhibitor of cysteine proteases, plays an important protective role in several tumors. Lactoferrin was shown to express anti-tumor and antiviral activities. It was hypothesized that cystatin C and lactoferrin could serve as possible biomarkers in the diagnosis of malignant and benign eye tumors. Study design. A total of 54 patients with choroidal melanoma and benign eye tumors were examined (part of them undergoing surgical treatment). Serum, tear fluid and intraocular fluid samples obtained from the anterior chamber of eyes in patients with choroidal melanoma were studied. Methods. Cystatin C concentration in serum and eye biological fluids was measured by commercial ELISA kits for human (BioVendor, Czechia); lactoferrin concentration &#x2013; by Lactoferrin-strip D 4106 ELISA test systems (Vector-BEST, Novosibirsk Region, Russia). Results. Cystatin C concentration in serum of healthy persons was significantly higher as compared to tear and intraocular fluids. In patients with choroidal melanoma, increased cystatin C concentration was similar in tear fluid of both the eyes. Lactoferrin level in tear fluid of healthy persons was significantly higher than its serum level. Significantly increased lactoferrin concentration in tear fluid was noted in patients with benign and malignant eye tumors. Conclusion. Increased level of cystatin C in tear fluid seems to be a possible diagnostic factor in the eye tumors studied. However, it does not allow us to differentiate between malignant and benign eye tumors. Similar changes were noted for lactoferrin in tear fluid

A case of carotid body paraganglioma and haemangioblastoma of the spinal cord in a patient with the N131K missense mutation in the VHL gene

The article describes paraganglioma case in woman with von Hippel–Lindau disease. She was found to be a carrier of a rare germline mutation in the VHL gene (393C>A; N131K). The patient developed large, untypical for von Hippel–Lindau disease, carotid body paraganglioma at the common carotid artery bifurcation. The carotid body paraganglioma coexisted with the haemangioblastoma situated intramedullary in region C5/C6. The haemangioblastoma reached the right-sided dorsal part of the spinal cord in section C5/C6. It produced radicular symptoms within C5/C6, followed by the later paresis of the right limbs. The haemangioblastoma was resected completely. Twelve months after the operation, the spinal symptoms receded and the carotid body paraganglioma still was asymptomatic. The current case of carotid body paraganglioma in patient with the 393C>A (N131K) missense mutation in the VHL gene, supports association of this specific mutation and VHL disease type 2, and suggests its correlation with susceptibility to paragangliomas

Genome-wide association study of survival from sepsis due to pneumonia: an observational cohort study

BACKGROUND: Sepsis continues to be a major cause of death, disability, and health-care expenditure worldwide. Despite evidence suggesting that host genetics can influence sepsis outcomes, no specific loci have yet been convincingly replicated. The aim of this study was to identify genetic variants that influence sepsis survival. METHODS: We did a genome-wide association study in three independent cohorts of white adult patients admitted to intensive care units with sepsis, severe sepsis, or septic shock (as defined by the International Consensus Criteria) due to pneumonia or intra-abdominal infection (cohorts 1-3, n=2534 patients). The primary outcome was 28 day survival. Results for the cohort of patients with sepsis due to pneumonia were combined in a meta-analysis of 1553 patients from all three cohorts, of whom 359 died within 28 days of admission to the intensive-care unit. The most significantly associated single nucleotide polymorphisms (SNPs) were genotyped in a further 538 white patients with sepsis due to pneumonia (cohort 4), of whom 106 died. FINDINGS: In the genome-wide meta-analysis of three independent pneumonia cohorts (cohorts 1-3), common variants in the FER gene were strongly associated with survival (p=9·7 × 10(-8)). Further genotyping of the top associated SNP (rs4957796) in the additional cohort (cohort 4) resulted in a combined p value of 5·6 × 10(-8) (odds ratio 0·56, 95% CI 0·45-0·69). In a time-to-event analysis, each allele reduced the mortality over 28 days by 44% (hazard ratio for death 0·56, 95% CI 0·45-0·69; likelihood ratio test p=3·4 × 10(-9), after adjustment for age and stratification by cohort). Mortality was 9·5% in patients carrying the CC genotype, 15·2% in those carrying the TC genotype, and 25·3% in those carrying the TT genotype. No significant genetic associations were identified when patients with sepsis due to pneumonia and intra-abdominal infection were combined. INTERPRETATION: We have identified common variants in the FER gene that associate with a reduced risk of death from sepsis due to pneumonia. The FER gene and associated molecular pathways are potential novel targets for therapy or prevention and candidates for the development of biomarkers for risk stratification. FUNDING: European Commission and the Wellcome Trust

Calcium Sulfate and Platelet-Rich Plasma make a novel osteoinductive biomaterial for bone regeneration

BACKGROUND: With the present study we introduce a novel and simple biomaterial able to induce regeneration of bone. We theorized that nourishing a bone defect with calcium and with a large amount of activated platelets may initiate a series of biological processes that culminate in bone regeneration. Thus, we engineered CS-Platelet, a biomaterial based on the combination of Calcium Sulfate and Platelet-Rich Plasma in which Calcium Sulfate also acts as an activator of the platelets, therefore avoiding the need to activate the platelets with an agonist. METHODS: First, we tested CS-Platelet in heterotopic (muscle) and orthotopic (bone) bone regeneration bioassays. We then utilized CS-Platelet in a variety of dental and craniofacial clinical cases, where regeneration of bone was needed. RESULTS: The heterotopic bioassay showed formation of bone within the muscular tissue at the site of the implantation of CS-Platelet. Results of a quantitative orthotopic bioassay based on the rat calvaria critical size defect showed that only CS-Platelet and recombinant human BMP2 were able to induce a significant regeneration of bone. A non-human primate orthotopic bioassay also showed that CS-Platelet is completely resorbable. In all human clinical cases where CS-Platelet was used, a complete bone repair was achieved. CONCLUSION: This study showed that CS-Platelet is a novel biomaterial able to induce formation of bone in heterotopic and orthotopic sites, in orthotopic critical size bone defects, and in various clinical situations. The discovery of CS-Platelet may represent a cost-effective breakthrough in bone regenerative therapy and an alternative or an adjuvant to the current treatments