The presence of resistance mutations to protease and polymerase inhibitors in Hepatitis C virus sequences from the Los Alamos databank

Several new direct‐acting antiviral (DAA) drugs are in development for chronic hepatitis C viral (HCV) infection, and NS3‐NS4A serine protease and the NS5B RNA‐dependent RNA polymerase have been the major targets. HCV variants displaying drug‐resistant phenotypes have been observed both in vitro and during clinical trials. Our aim was to characterize amino acid changes at positions previously associated with resistance in protease (NS3) and polymerase (NS5B) regions from treatment‐naïve HCV patients infected with genotypes 1a, 1b and 3a. All 1383 NS3 protease sequences (genotype 1a = 680, 1b = 498 and 3a = 205) and 806 NS5B polymerase sequences (genotypes 1a = 471, 1b = 329, 3a = 6) were collected from Los Alamos databank. Genotype 3a protease sequences showed the typical low‐level resistance mutation V36L. NS3 sequences from other genotypes presented mutations on positions 36, 39, 41, 43, 54, 80, 109, 155 and 168 in a frequency lower than 2%, except for the mutation Q80R found in 35% of genotype 1a isolates. Polymerase sequences from genotype 3a patients showed five typical mutations: L419I, I424V, I482L, V499A and S556G. Two positions presented high polymorphism in the NS5B region from genotype 1a (V499A) and genotype 1b (C316N) subjects. Our results demonstrated a natural profile of genotype 3a that can be associated with the pre‐existence of HCV variants resistant to first‐generation protease inhibitors and to non‐nucleoside polymerase inhibitors. Likewise, genotype 1b isolates and genotype 1a sequences exhibited pre‐existing mutations associated with resistance to Palm II and Thumb I polymerase inhibitors, respectively.     

Comparison of Parasitological,Serological, and Molecular Tests for Visceral Leishmaniasis in HIV-Infected Patients: A Cross-Sectional Delayed-Type Study

The aim of this study was to evaluate the accuracy of invasive and non-invasive tests for diagnosis of visceral leishmaniasis (VL) in a large series of human immunodeficiency virus (HIV)-infected patients. In this delayed-type cross-sectional study, 113 HIV-infected symptomatic patients were evaluated by an adjudication committee after clinical follow-up to establish the presence or absence of VL as the target condition (reference test). The index tests were recombinant K39 antigen-based immunochromatographic test (rK39), indirect fluorescent antibody test (IFAT), prototype kit of direct agglutination test (DAT-LPC), and real-time polymerase chain reaction (qPCR) in peripheral blood. Compared with parasitological test and adjudication committee diagnosis or latent class model analyses, IFAT and rk39 dipstick test presented the lowest sensitivity. DAT-LPC exhibited good overall performance, and there was no statistical difference between DAT-LPC and qPCR diagnosis accuracy. Real-time PCR emerges as a less invasive alternative to parasitological examination for confirmation of cases not identified by DAT.     

Cardiac tamponade in juvenile chronic arthritis: report of two cases and review of publications.

Two cases of systemic juvenile chronic arthritis, complicated by cardiac tamponade and eight previously reported cases are described. The clinical features and radiological, electrocardiographic, and echocardiographic findings were similar for all cases. One patient in this series was treated with corticosteroids and underwent pericardiectomy, dying of sepsis 30 days after surgery. The other patient was also treated with corticosteroids, underwent pericardiocentesis and developed fatal ventricular tachycardia. Of the 10 cases, only six were successfully treated. Early diagnosis and appropriate treatment are essential for a favourable outcome.     

The value of non-prefixed marking in reduction mammoplasty

The advantages of non-prefixed marking for breast reduction are discussed in this paper. The authors use a curved incision modification of the Pitanguy technique, stressing the value of changing the demarcation depending on the skin-gland relationship of each patient.     

The effect of blue light exposure and use of intraocular lenses on human uveal melanoma cell lines

Little is known about the effect of blue light on inducing melanocytic malignant transformation. We chose to investigate the effect of blue light (475 nm wavelength) on the proliferation rates of uveal melanoma cells. In addition, we tested two different intraocular lenses to determine the possible effects of ultraviolet absorbing and blue light filtering intraocular lenses on the changes in proliferation. Four human uveal melanoma cell lines (92.1, MKT-BR, OCM-1, SP6.5) were exposed to blue light with and without the presence of ultraviolet absorbing and blue light filtering intraocular lenses. Cells covered by aluminum foil were used as a control. The proliferation rate of the cells compared with the control was then assessed using the Sulforhodamine-B proliferation assay. Cells exposed to blue light showed a statistically significant (P<0.05) increase in proliferation. Those exposed to blue light through a standard ultraviolet absorbing intraocular lens showed a smaller increase in proliferation, whereas those exposed with a blue light filtering intraocular lens showed no increase in proliferation than the control in all four cell lines. The exposure of cells to blue light led to an increase in proliferation in all cell lines compared with the control. The use of blue light filtering intraocular lenses abolished these increases in proliferation in the four cell lines. These results indicate that blue light filtering intraocular lenses may have a protective effect on the proliferation rates of uveal melanoma cells exposed to blue light.     

Problem-solving capacity for vitreoretinal diseases in a university health center

PURPOSE: To evaluate the effectiveness of the tertiary care delivered to patients with vitreoretinal diseases in a defined urban population; to substantiate the planning and allocation of resources in order to improve the tertiary eye care delivery system in a specific area. METHODS: Data were collected from consecutive first-time patients between June 1, 2003 and July 31, 2004 in the Department of Ophthalmology, State University of Campinas, S?o Paulo, Brazil. Problem-solving capacity values were calculated for vitreoretinal surgery and photocoagulation. Data were entered into the Statistical Package for the Social Sciences (version 10.0). RESULTS: Of the 7500 patients referred to the Department, 641 were deemed suitable for analysis. The diagnoses analyzed were retinal detachment (26.0%), diabetic retinopathy (21.0%), and vitreous hemorrhage (7.7%). The median ages were 52, 59 and 57.5, respectively. Of all patients referred for retinal detachment, 26.5% were inoperable. The values obtained for the problem-solving capacity (PSC) showed that 38.1%, 33.0% and 93.5% of those eligible for an ophthalmic intervention (for retinal detachment, vitreous hemorrhage and diabetic retinopathy) had obtained treatment. The main reason for not giving treatment was the unavailability of operating room time and photocoagulation time (87.1%). CONCLUSIONS: This was the first study of tertiary eye care service performance in Latin America. Sight-threatening conditions such as retinal detachment and diabetic retinopathy are not thoroughly covered by the health system in this area. Various ways to reduce the problem are considered. The study has provided valuable information on planning high-complexity eye services in the population in question.     

Target visibility and visual awareness modulate amygdala responses to fearful faces

The goals of the present study were twofold. First, we wished to investigate the neural correlates of aware and unaware emotional face perception after characterizing each subject's behavioral performance via signal detection theory methods. Second, we wished to investigate the extent to which amygdala responses to fearful faces depend on the physical characteristics of the stimulus independently of the percept. We show that amygdala responses depend on visual awareness. Under conditions in which subjects were not aware of fearful faces flashed for 33 ms, no differential activation was observed in the amygdala. On the other hand, differential activation was observed for 67 ms fearful targets that the subjects could reliably detect. When trials were divided into hits, misses, correct rejects, and false alarms, we show that target visibility is an important factor in determining amygdala responses to fearful faces. Taken together, our results further challenge the view that amygdala responses occur automatically.