Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

Methods. We studied participants with acute and/or early HIV infection and TDR in 2 cohorts (San Francisco, California, and Sao Paulo, Brazil). We followed baseline mutations longitudinally and compared replacement rates between mutation classes with use of a parametric proportional hazards model. Results. Among 75 individuals with 195 TDR mutations, M184V/I became undetectable markedly faster than did nonnucleoside reverse-transcriptase inhibitor (NNRTI) mutations (hazard ratio, 77.5; 95% confidence interval [CI], 14.7-408.2; P < .0001), while protease inhibitor and NNRTI replacement rates were similar. Higher plasma HIV-1 RNA level predicted faster mutation replacement, but this was not statistically significant (hazard ratio, 1.71 log(10) copies/mL; 95% CI, .90-3.25 log(10) copies/mL; P = .11). We found substantial person-to-person variability in mutation replacement rates not accounted for by viral load or mutation class (P < .0001). Conclusions. The rapid replacement of M184V/I mutations is consistent with known fitness costs. The long-term persistence of NNRTI and protease inhibitor mutations suggests a risk for person-to-person propagation. Host and/or viral factors not accounted for by viral load or mutation class are likely influencing mutation replacement and warrant further study.

Lower cytokine secretion ex vivo by natural killer T cells in HIV-infected individuals is associated with higher CD161 expression

Objective: Natural killer T (NKT) cells are efficiently targeted by HIV and severely reduced in numbers in the circulation of infected individuals. The functional capacity of the remaining NKT cells in HIV-infected individuals is poorly characterized. This study measured NKT cell cytokine production directly ex vivo and compared these responses with both the disease status and NKT subset distribution of individual patients. Methods: NKT cell frequencies, subsets, and ex-vivo effector functions were measured in the peripheral blood mononuclear cells of HIV-infected patients and healthy controls by flow cytometry. We measured cytokines from NKT cells after stimulation with either a-galactosyl ceramide-loaded CD1d dimers (DimerX-alpha GalCer) or phorbol myristate acetate and ionomycin. Results: The frequencies of NKT cells secreting interferon-gamma and tumor necrosis factor-alpha were significantly lower in HIV-infected patients than healthy controls after DimerX-alpha GalCer treatment, but responses were similar after treatment with phorbol myristate acetate and ionomycin. The magnitude of the interferon-gamma response to DimerX-alpha GalCer correlated inversely with the number of years of infection. Both interferon-gamma and tumor necrosis factor-alpha production in response to DimerX-alpha GalCer correlated inversely with CD161 expression. Conclusion: The ex-vivo Th1 responses of circulating NKT cells to CD1d-glycolipid complexes are impaired in HIV-infected patients. NKT cell functions may be progressively lost over time in HIV infection, and CD161 is implicated in the regulation of NKT cell responsiveness. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Transcriptional Errors in Human Immunodeficiency Virus Type 1 Generate Targets for T-Cell Responses

We measured T-cell responses to human immunodeficiency virus type 1 (HIV-1) cryptic epitopes encoded by regions of the viral genome not normally translated into viral proteins. T-cell responses to cryptic epitopes and to regions normally spliced out of the HIV-1 viral proteins Rev and Tat were detected in HIV-1-infected subjects.

Factors Related to the Selection of Surgical Versus Percutaneous Revascularization in Diabetic Patients With Multivessel Coronary Artery Disease in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) Trial

Objectives We evaluated demographic, clinical, and angiographic factors influencing the selection of coronary artery bypass graft (CABG) surgery versus percutaneous coronary intervention (PCI) in diabetic patients with multivessel coronary artery disease (CAD) in the BARI 2D (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes) trial. Background Factors guiding selection of mode of revascularization for patients with diabetes mellitus and multivessel CAD are not clearly defined. Methods In the BARI 2D trial, the selected revascularization strategy, CABG or PCI, was based on physician discretion, declared independent of randomization to either immediate or deferred revascularization if clinically warranted. We analyzed factors favoring selection of CABG versus PCI in 1,593 diabetic patients with multivessel CAD enrolled between 2001 and 2005. Results Selection of CABG over PCI was declared in 44% of patients and was driven by angiographic factors including triple vessel disease (odds ratio [OR]: 4.43), left anterior descending stenosis >= 70% (OR: 2.86), proximal left anterior descending stenosis >= 50% (OR: 1.78), total occlusion (OR: 2.35), and multiple class C lesions (OR: 2.06) (all p < 0.005). Nonangiographic predictors of CABG included age >= 65 years (OR: 1.43, p = 0.011) and non-U.S. region (OR: 2.89, p = 0.017). Absence of prior PCI (OR: 0.45, p < 0.001) and the availability of drug-eluting stents conferred a lower probability of choosing CABG (OR: 0.60, p = 0.003). Conclusions The majority of diabetic patients with multivessel disease were selected for PCI rather than CABG. Preference for CABG over PCI was largely based on angiographic features related to the extent, location, and nature of CAD, as well as geographic, demographic, and clinical factors. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT00006305) (J Am Coll Cardiol Intv 2009;2:384-92) (C) 2009 by the American College of Cardiology Foundation

Insulin-like peptide genes in honey bee fat body respond differently to manipulation of social behavioral physiology

Nutrient sensitive insulin-like peptides (ILPs) have profound effects on invertebrate metabolism, nutrient storage, fertility and aging. Many insects transcribe ILPs in specialized neurosecretory cells at changing levels correlated with life history. However, the major site of insect metabolism and nutrient storage is not the brain, but rather the fat body, where functions of ILP expression are rarely studied and poorly understood. Fat body is analogous to mammalian liver and adipose tissue, with nutrient stores that often correlate with behavior. We used the honey bee (Apis mellifera), an insect with complex behavior, to test whether ILP genes in fat body respond to experimentally induced changes of behavioral physiology. Honey bee fat body influences endocrine state and behavior by secreting the yolk protein precursor vitellogenin (Vg), which suppresses lipophilic juvenile hormone and social foraging behavior. In a two-factorial experiment, we used RNA interference (RNAi)-mediated vg gene knockdown and amino acid nutrient enrichment of hemolymph (blood) to perturb this regulatory module. We document factor-specific changes in fat body ilp1 and ilp2 mRNA, the bee`s ILP-encoding genes, and confirm that our protocol affects social behavior. We show that ilp1 and ilp2 are regulated independently and differently and diverge in their specific expression-localization between fat body oenocyte and trophocyte cells. Insect ilp functions may be better understood by broadening research to account for expression in fat body and not only brain.

Multiple recurrent genetic events converge on control of histone lysine methylation in medulloblastoma

We used high-resolution SNP genotyping to identify regions of genomic gain and loss in the genomes of 212 medulloblastomas, malignant pediatric brain tumors. We found focal amplifications of 15 known oncogenes and focal deletions of 20 known tumor suppressor genes (TSG), most not previously implicated in medulloblastoma. Notably, we identified previously unknown amplifications and homozygous deletions, including recurrent, mutually exclusive, highly focal genetic events in genes targeting histone lysine methylation, particularly that of histone 3, lysine 9 (H3K9). Post-translational modification of histone proteins is critical for regulation of gene expression, can participate in determination of stem cell fates and has been implicated in carcinogenesis. Consistent with our genetic data, restoration of expression of genes controlling H3K9 methylation greatly diminishes proliferation of medulloblastoma in vitro. Copy number aberrations of genes with critical roles in writing, reading, removing and blocking the state of histone lysine methylation, particularly at H3K9, suggest that defective control of the histone code contributes to the pathogenesis of medulloblastoma.

Micromorphology of Resin-Dentin Interfaces Using One-Bottle Etch&Rinse and Self-Etching Adhesive Systems on Laser-Treated Dentin Surfaces: A Confocal Laser Scanning Microscope Analysis

Background and Objectives: This study evaluated the hybrid layer (HL) morphology created by three adhesive systems (AS) on dentin surfaces treated with Er:YAG laser using two irradiation parameters. Study Design: Occlusal flat dentin surfaces of 36 human third molars were assigned into nine groups (n = 4) according to the following ASs: one bottle etch&rinse Single Bond Plus (3M ESPE), two-step Clearfil Protect Bond (Kuraray), and all-in-one S3 Bond (Kuraray) self-etching, which were labeled with rhodamine B or fluorescein isothiocyanate dextran and were applied to dentin surfaces that were irradiated with Er:YAG laser at either 120 (38.7 J/cm(2)) or 200 mJ/pulse (64.5 J/cm(2)), or were applied to untreated dentin surfaces (control group). The ASs were light-activated following MI and the bonded surfaces were restored with resin composite Z250 (3M ESPE). After 24 hours of storage in vegetable oil, the restored teeth were vertically, serially sectioned into 1-mm thick slabs, which had the adhesive interfaces analyzed with confocal laser microscope (CLSM-LSM 510 Meta). CLSM images were recorded in the fluorescent mode from three different regions along each bonded interface. Results: Non-uniform HL was created on laser-irradiated dentin surfaces regardless of laser irradiation protocol for all AS, while regular and uniform HL was observed in the control groups. ""Stretch mark""-like red lines were found within the HL as a result of resin infiltration into dentin microfissures, which were predominantly observed in 200 mJ/pulse groups regardless of AS. Poor resin infiltration into peritubular dentin was observed in most regions of adhesive interfaces created by all ASs on laser-irradiated dentin, resulting in thin resin tags with neither funnel-shaped morphology nor lateral resin projections. Conclusion: Laser irradiation of dentin surfaces at 120 or 200 mJ/pulse resulted in morphological changes in HL and resin tags for all ASs evaluated in the study. Lasers Surg. Med. 42:662-670, 2010. (C) 2010 Wiley-Liss, Inc.

Influence of irradiant energy on degree of conversion, polymerization rate and shrinkage stress in an experimental resin composite system

Objective. This study evaluated the degree of conversion (DC), maximum rate of cure (R(p)(max)), and polymerization stress (PS) developed by an experimental dental composite subjected to different irradiant energies (3,6,12, 24, or 48J/cm(2)) under constant irradiance (500 mw/cm(2)). Methods. DC and R(p)(max) were monitored for 10 min on the bottom surface of 2-mm thick disks and on 150-mu m thick films (representing the top of the specimen) using ATR-FTIR. PS was monitored for 10 min in 2-mm thick disks bonded to two glass rods (O = 5 mm) attached to a universal testing machine. One-way ANOVA/Tukey tests were used and differences in DC and R(p)(max) between top and bottom surfaces were examined using Student`s t-test. Statistical testing was performed at a pre-set alpha of 0.05. Results. For a given surface, DC showed differences among all groups, except at the top between 24 and 48 J/cm(2). R(p)(max) was similar among all groups at the same surface and statistically higher at the top surface. PS also showed significant differences among all groups. Data for 48 J/cm(2) were not obtained due to specimen failure at the glass/composite interface. Significance. Increases in irradiant exposure led to significant increases in DC and PS, but had no effect on R(p)(max) (c) 2008 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Degree of conversion and mechanical properties of a BisGMA : TEGDMA composite as a function of the applied radiant exposure

Objective: Verify the influence of radiant exposure (H) on composite degree of conversion (DC) and mechanical properties. Methods: Composite was photoactivated with 3, 6, 12, 24, or 48 J/cm(2). Properties were measured after 48-h dry storage at room temperature. DC was determined on the flat surfaces of 6 mm x 2 mm disk-shaped specimens using FTIR. Flexural strength (FS) and modulus (FM) were accessed by three-point bending. Knoop microhardness number (KHN) was measured on fragments of FS specimens. Data were analyzed by one-way ANOVA/Tukey test, Student`s t-test, and regression analysis. Results: DC/top between 6 and 12 J/cm(2) and between 24 and 48 J/cm(2) were not statistically different. No differences between DC/top and bottom were detected. DC/bottom, FM, and KHN/top showed significant differences among all H levels. FS did not vary between 12 and 24 J/cm(2) and between 24 and 48 J/cm(2). KHN/bottom at 3 and 6 J/cm(2) was similar. KHN between top and bottom was different up to 12 J/cm(2). Regression analyses having H as independent variable showed a plateau region above 24 J/cm(2). KHN increased exponentially (top) or linearly (bottom) with DC. FS and FM increased almost linearly with DC/bottom up to 55% conversion. Conclusions: DC and mechanical properties increased with radiant exposure. Variables leveled off at high H levels. (C) 2007 Wiley Periodicals, Inc.

Caracterização de isolados de Corynespora cassiicola e avaliação da sensibilidade in vitro a fungicidas

Tese (doutorado)—Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Fitopatologia, Programa de Pós-Graduação em Fitopatologia, 2015.