Experimental modulation of capsule size in Cryptococcus neoformans

Experimental modulation of capsule size is an important technique for the study of the virulence of the encapsulated pathogen Cryptococcus neoformans. In this paper, we summarize the techniques available for experimental modulation of capsule size in this yeast and describe improved methods to induce capsule size changes. The response of the yeast to the various stimuli is highly dependent on the cryptococcal strain. A high CO(2) atmosphere and a low iron concentration have been used classically to increase capsule size. Unfortunately, these stimuli are not reliable for inducing capsular enlargement in all strains. Recently we have identified new and simpler conditions for inducing capsule enlargement that consistently elicited this effect. Specifically, we noted that mammalian serum or diluted Sabouraud broth in MOPS buffer pH 7.3 efficiently induced capsule growth. Media that slowed the growth rate of the yeast correlated with an increase in capsule size. Finally, we summarize the most commonly used media that induce capsule growth in C. neoformans

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels

Get screened: a pragmatic randomized controlled trial to increase mammography and colorectal cancer screening in a large, safety net practice

Abstract Background Most randomized controlled trials of interventions designed to promote cancer screening, particularly those targeting poor and minority patients, enroll selected patients. Relatively little is known about the benefits of these interventions among unselected patients. Methods/Design "Get Screened" is an American Cancer Society-sponsored randomized controlled trial designed to promote mammography and colorectal cancer screening in a primary care practice serving low-income patients. Eligible patients who are past due for mammography or colorectal cancer screening are entered into a tracking registry and randomly assigned to early or delayed intervention. This 6-month intervention is multimodal, involving patient prompts, clinician prompts, and outreach. At the time of the patient visit, eligible patients receive a low-literacy patient education tool. At the same time, clinicians receive a prompt to remind them to order the test and, when appropriate, a tool designed to simplify colorectal cancer screening decision-making. Patient outreach consists of personalized letters, automated telephone reminders, assistance with scheduling, and linkage of uninsured patients to the local National Breast and Cervical Cancer Early Detection program. Interventions are repeated for patients who fail to respond to early interventions. We will compare rates of screening between randomized groups, as well as planned secondary analyses of minority patients and uninsured patients. Data from the pilot phase show that this multimodal intervention triples rates of cancer screening (adjusted odds ratio 3.63; 95% CI 2.35 - 5.61). Discussion This study protocol is designed to assess a multimodal approach to promotion of breast and colorectal cancer screening among underserved patients. We hypothesize that a multimodal approach will significantly improve cancer screening rates. The trial was registered at Clinical Trials.gov NCT00818857http://deepblue.lib.umich.edu/bitstream/2027.42/78264/1/1472-6963-10-280.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78264/2/1472-6963-10-280.pdfPeer Reviewe

Corner contributions to holographic entanglement entropy

The entanglement entropy of three-dimensional conformal field theories contains a universal contribution coming from corners in the entangling surface. We study these contributions in a holographic framework and, in particular, we consider the effects of higher curvature interactions in the bulk gravity theory. We find that for all of our holographic models, the corner contribution is only modified by an overall factor but the functional dependence on the opening angle is not modified by the new gravitational interactions. We also compare the dependence of the corner term on the new gravitational couplings to that for a number of other physical quantities, and we show that the ratio of the corner contribution over the central charge appearing in the two-point function of the stress tensor is a universal function for all of the holographic theories studied here. Comparing this holographic result to the analogous functions for free CFT's, we find fairly good agreement across the full range of the opening angle. However, there is a precise match in the limit where the entangling surface becomes smooth, i.e., the angle approaches $\pi$, and we conjecture the corresponding ratio is a universal constant for all three-dimensional conformal field theories. In this paper, we expand on the holographic calculations in our previous letter arXiv:1505.04804, where this conjecture was first introduced.Comment: 62 pages, 6 figures, 1 table; v2: minor modifications to match published version, typos fixe

Comments on Holographic Entanglement Entropy and RG Flows

Using holographic entanglement entropy for strip geometry, we construct a candidate for a c-function in arbitrary dimensions. For holographic theories dual to Einstein gravity, this c-function is shown to decrease monotonically along RG flows. A sufficient condition required for this monotonic flow is that the stress tensor of the matter fields driving the holographic RG flow must satisfy the null energy condition over the holographic surface used to calculate the entanglement entropy. In the case where the bulk theory is described by Gauss-Bonnet gravity, the latter condition alone is not sufficient to establish the monotonic flow of the c-function. We also observe that for certain holographic RG flows, the entanglement entropy undergoes a 'phase transition' as the size of the system grows and as a result, evolution of the c-function may exhibit a discontinuous drop.Comment: References adde

Radiation-induced malignancies following radiotherapy for breast cancer

With advances in diagnosis and treatment, breast cancer is becoming an increasingly survivable disease resulting in a large population of long-term survivors. Factors affecting the quality of life of such patients include the consequences of breast cancer treatment, which may have involved radiotherapy. In this study, we compare the incidence of second primary cancers in women who received breast radiotherapy with that in those who did not (non-radiotherapy). All women studied received surgery for their first breast cancer. Second cancers of the lung, colon, oesophagus and thyroid gland, malignant melanomas, myeloid leukaemias and second primary breast cancers were studied. Comparing radiotherapy and non-radiotherapy cohorts, elevated relative risks (RR) were observed for lung cancer at 10-14 years and 15 or more (15+) years after initial breast cancer diagnosis (RR 1.62, 95% confidence interval [CI] 1.05-2.54 and RR 1.49, 95% CI 1.05-2.14, respectively), and for myeloid leukaemia at 1-5 years (RR 2.99, 95% CI 1.13-9.33), for second breast cancer at 5-10 years (RR 1.34, 95% CI 1.10-1.63) and 15+ years (RR 1.26, 95% CI 1.00-1.59) and oesophageal cancer at 15+ years (RR 2.19, 95% CI 1.10-4.62)

IL28B genotype is associated with cirrhosis or transition to cirrhosis in treatment-naive patients with chronic HCV genotype 1 infection: the international observational Gen-C study

Background and purpose: Contradictory data exist on the association between host interleukin-28B (IL28B) rs12979860 genotype and liver fibrosis in patients with chronic hepatitis C (CHC). This large, international, observational study (NCT01675427/MV25600) investigated relationships between IL28B rs12979860 genotype and liver fibrosis stage in CHC patients. Methods: A total of 3003 adult, treatment-naive CHC patients were enrolled into the study. Patients made one study visit to provide a blood sample for genotyping; other data were obtained from medical records. Results: 2916 patients comprised the analysis population; the majority were enrolled in Europe (n = 2119), were Caucasian (n = 2582) and had hepatitis C virus (HCV) genotype (G) 1 infection (n = 1702) (G2 = 323, G3 = 574, G4 = 260). Distribution of IL28B genotypes varied according to region of enrolment, patient ethnicity and HCV genotype. A significant association was observed between increasing number of IL28B T alleles and the prevalence of cirrhosis/transition to cirrhosis (based on biopsy or non-invasive assessments) in G1-infected patients (CC = 22.2% [111/499], CT = 27.5% [255/928], TT = 32.3% [87/269]; p = 0.0018). The association was significant in the large subgroup of European Caucasian G1 patients (n = 1245) but not in the smaller Asian (n = 25), Latin American (n = 137) or Middle Eastern (n = 289) G1 subgroups. IL28B genotype was not associated with liver fibrosis stage in patients with HCV G2, G3 or G4 infection. Conclusion: This large, international study found that IL28B rs12979860 genotype is significantly associated with liver fibrosis stage in CHC patients with HCV G1 infection. This association was evident in European Caucasians but not in G1-infected patients from Asia, Latin America or the Middle EastF. Hoffmann-La Roche Ltd, Basel, Switzerlan

Gravitational physics with antimatter

The production of low-energy antimatter provides unique opportunities to search for new physics in an unexplored regime. Testing gravitational interactions with antimatter is one such opportunity. Here a scenario based on Lorentz and CPT violation in the Standard- Model Extension is considered in which anomalous gravitational effects in antimatter could arise.Comment: 5 pages, presented at the International Conference on Exotic Atoms (EXA 2008) and the 9th International Conference on Low Energy Antiproton Physics (LEAP 2008), Vienna, Austria, September 200

Autoimmune hepatitis in India: profile of an uncommon disease

BACKGROUND: Autoimmune hepatitis (AIH) has been reported to show considerable geographical variation in frequency and clinical manifestations. It is considered a rare cause of liver disease in India. The present study was undertaken to determine the incidence, clinical, biochemical and histological profile of AIH in this part of the world. METHODS: Patients presenting with acute or chronic liver disease between January 1999 and June 2002 were evaluated prospectively. AIH was diagnosed using the international autoimmune hepatitis group criteria. Workup included clinical, biochemical, USG, viral markers, UGI endoscopy, AI markers (ANA, SMA, Anti-LKM, AMA, RF, p-ANCA) using indirect immunofluorescence and liver biopsy if possible. RESULTS: Forty-one of 2401 (1.70%) patients were diagnosed to have autoimmune liver disease. Out of these, 38 had autoimmune hepatitis and the rest 3 had primary biliary cirrhosis. The mean age of the patients of autoimmune hepatitis was 36.2 (15.9) years, 34 (89.4%) were females, and the duration of symptoms was 20.3 (20.5) months. Nineteen (50%) of them presented with chronic hepatitis, 13 (34.2%) as cirrhosis, 5 (13.1%) with acute hepatitis and 1 (2.6%) with cholestatic hepatitis. The presentations were jaundice in 21 (55.2%), pedal edema and hepatomegaly in 17 (44.7%), splenomegaly in 13 (34.2%), encephalopathy, abdominal pain in 9 (23.6%) and fever in 8 (21%). Twelve had esophageal varices and 3 had bled. Biochemical parameters were ALT 187 (360) U/L, AST 157 (193) U/L, ALP 246 (254) U/L, globulin 4.1 (1.6) g/dL, albumin 2.8 (0.9) g/dL, bilirubin 5.2 (7.4) mg/dL, prothrombin time 17 (7) sec and ESR 47 (17) sec. The autoimmune markers were SMA (24), ANA (15), both SMA and ANA (4), AMA (1), rheumatoid factor (2), pANCA (1), and Anti-LKM in none. Thirty (79%) patients had definite AIH and eight (21%) had probable AI hepatitis. Associated autoimmune diseases was seen in 15/38 (39.4%), diabetes 4, hypothyroidism 3, vitiligo 2, thrombocytopenia 2, rheumatoid arthritis 2, Sjogren's syndrome 1 and autoimmune polyglandular syndrome III in 1. Viral markers were positive in two patients, one presenting as acute hepatitis and HEV-IgM positive and another anti-HCV positive. CONCLUSION: In India, autoimmune hepatitis is uncommon and usually presents with chronic hepatitis or cirrhosis, acute hepatitis being less common. Age at presentation was earlier but clinical parameters and associated autoimmune diseases were similar to that reported from the west. Primary biliary cirrhosis is rare. Type II AIH was not observed