(18)F-FDG PET After 2 Cycles of ABVD Predicts Event-Free Survival in Early and Advanced Hodgkin Lymphoma

Our objective was to assess the prognostic value of (18)F-FDG PET after 2 cycles of chemotherapy using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in Hodgkin lymphoma (HL) patients overall and in subgroups of patients with early and advanced stages and with low and high risks according to the International Prognostic Score (IPS). Methods: One hundred fifteen patients with newly diagnosed HL were prospectively included in the study. All underwent standard ABVD therapy followed by consolidation radiotherapy in cases of bulky disease. After 2 cycles of ABVD, the patients were evaluated with PET (PET2). Prognostic analysis compared the 3-y event-free survival (EFS) rate to the PET2 results, clinical data, and IPS. Results: Of the 104 evaluated patients, 93 achieved complete remission after first-line therapy. During a median follow-up of 36 mo, relapse or disease progression was seen in 22 patients. Treatment failure was seen in 16 of the 30 PET2-positive patients and in only 6 of the 74 PET2-negative patients. PET2 was the only significant prognostic factor. The 3-y EFS was 53.4% for PET2-positive patients and 90.5% for PET2-negative ones (P < 0.001). When patients were categorized according to low or high IPS risk and according to early or advanced stage of disease, PET2 was also significantly associated with treatment outcome. Conclusion: PET2 is an accurate and independent predictor of EFS in HL. A negative interim (18)F-FDG PET result is highly predictive of treatment success in overall HL patients, as well as in subgroups with early or advanced-stage disease and with low or high IPS risk.

INCREASED SARCOLEMMAL PERMEABILITY AS AN EARLY EVENT IN EXPERIMENTAL SEPTIC CARDIOMYOPATHY: A POTENTIAL ROLE FOR OXIDATIVE DAMAGE TO LIPIDS AND PROTEINS

This study describes increased sarcolemmal permeability and myofilamentar damage that occur together with lipid peroxidation and protein nitration in the myocardium in severe sepsis induced by cecal ligation and puncture. Male C57BL/6 mice were submitted to moderate and severe septic injury and sham operation. Using light and laser confocal microscopy, diffuse foci of myocytolysis associated with focal disruption of the actin/myosin contractile apparatus could be seen in hearts with severe septic injury. The myocardial expressions of the sarcomeric proteins myosin and actin were downregulated by both severe and moderate injuries. The detection of albumin staining in the cytoplasm of myocytes to evaluate sarcolemmal permeability provided evidence of severe and mild injury of the plasma membrane in hearts with severe and moderate septic injury, respectively. The administration of a superoxide scavenger caused marked reduction of sarcolemmal permeability, indicating the involvement of free radicals in its genesis. On electron microscopy, these changes were seen to correspond to spread blocks of a few myocytes with fragmentation and dissolution of myofibrils, intracellular edema, and, occasionally, rupture of the sarcolemma. In addition, oxidative damage to lipids, using anti-4-hydroxynonenal, an indicator of oxidative stress and disruption of plasma membrane lipids, and to proteins, using antinitrotyrosine, a stable biomarker of peroxynitrite-mediated protein nitration, was demonstrated. These findings make plausible the hypothesis that increased sarcolemmal permeability might be a primary event in myocardial injury in severe sepsis possibly due to oxidative damage to lipids and proteins that could precede phenotypic changes that characterize a septic cardiomyopathy.

An event of stratospheric air intrusion and its associated secondary surface cyclogenesis over the South Atlantic Ocean

This work presents an analysis of a lowermost stratospheric air intrusion event over the coast of Brazil, which may have been responsible for a secondary surface cyclogenesis over the southwestern Atlantic Ocean. The surface cyclone initiated at 0600 UTC 17 April 1999 in a cold air mass in the rear of a cold front after a primary cyclone developed over the same region. The analysis of the secondary cyclone revealed the presence of lowermost stratospheric air intrusion characterized by anomalous potential vorticity (PV), dry air, and high concentration of ozone in atmospheric column. The system developed on the eastern side of an upper level core of PV anomaly, which induced a cyclonic wind circulation at lower levels and favored the onset of the secondary cyclone. In midlevels (500 hPa), the cutoff low development contributed to reduce the propagation speed of the wave pattern. This feature seemed to (1) allow the low-level cold/dry air to heat/moisten associated with sensible and latent fluxes transferred from the ocean to the atmosphere, which intensified a baroclinic zone parallel to the coast, and (2) contribute to the long duration of the system. The present analysis indicates that this secondary cyclone development could be the result of the coupling between the PV anomaly in the upper levels and low-level air-sea interaction.

Post-collisional lamprophyric event in Sierra Norte, Cordoba, Argentina: Mineralogical, geochemical and isotopic characteristics

Over 20 lamprophyre dykes, varying in width between a few centimeters and several meters, have been identified in central Sierra Norte - Eastern Pampean Ranges, Cordoba, Argentina. Their mineralogy and chemistry indicate that they are part of the calc-alkaline lamprophyres clan (CAL). They contain phenocrysts of magnesiohomblende +/- augite set in a groundmass of magnesiohornblende, calcic-plagioclase, alkali feldspar, and opaque minerals, which designate them as spessartite-type lamprophyres. Alteration products include chlorite, calcite and iron oxides after malfic phenocrysts, though some are partially replaced by actinolite. Feldspars are replaced by carbonate and clay minerals. The dykes are relatively primitive, and show restricted major element variation (SiO(2) 51.1-55.3 wt.%, Al(2)O(3) 12-16.6 wt.%, total alkalies 1.5-4.7 wt.%), high Mg# (55-77), high Cr contents (27-988 ppm) and moderate to high Ni contents (60-190 ppm). Lamprophyre LILE (e.g. Rb averages 110 ppm, Sr 211-387 ppm, Ba 203-452 ppm) are high relative to HFSE (e.g., Ta 0.2-1.6 ppm, Nb 4-11 ppm, Y 17-21 ppm), and are enriched in LREE (30-70 times chondrite). They are characterized by relatively high (208)Pb/(204)Pb (38.8-39.9), (207)Pb/(204)Pb(similar to 15.7), and (206)Pb/(204)Pb (18.7-20.1), combined with low (epsilon)epsilon(Nd) (-4.69 to -1.52) and a relative moderately high ((87)Sr/(86)Sr)(i) of 0.7055-0.7074. The Rb-Sr whole rock isochron indicates an Early Ordovician age of 485 +/- 25 Ma. The calculated T(DM) (1.7 Ga) suggests that these rocks appear to have originated from a reservoir that was created during a mantle metasomatism event related to the Pampean orogeny. The Sierra Norte lamprophyres show affinities with a subduction-related magma in an active continental margin. Their geochemical and isotopic features suggest a multicomponent source, composed of enriched mantle material variably contaminated by crustal components. The lamprophyric suite emplacement occurred at the dawning stage of the Pampean orogeny, in a regional post-collisional extensional setting developed in the Sierra Norte-Ambargasta batholith (SNAB) in Early Ordovician times. (C) 2008 Published by Elsevier Ltd.

Timing and structure of the 8.2 kyr BP event inferred from delta(18)O records of stalagmites from China, Oman, and Brazil

Oxygen isotope records of stalagmites from China and Oman reveal a weak summer monsoon event, with a double-plunging structure, that started 8.21 +/- 0.02 kyr B. P. An identical but antiphased pattern is also evident in two stalagmite records from eastern Brazil, indicating that the South American Summer Monsoon was intensified during the 8.2 kyr B. P. event. These records demonstrate that the event was of global extent and synchronous within dating errors of <50 years. In comparison with recent model simulations, it is plausible that the 8.2 kyr B. P. event can be tied in changes of the Atlantic Meridional Overturning Circulation triggered by a glacial lake draining event. This, in turn, affected North Atlantic climate and latitudinal position of the Intertropical Convergence Zone, resulting in the observed low-latitude monsoonal precipitation patterns.

Reproductive behavior, development and eye regression in the cave armored catfish, Ancistrus cryptophthalmus Reis, 1987 (Siluriformes: Loricariidae), breed in laboratory

The troglobitic armored catfish, Ancistrus cryptophthalmus (Loricariidae, Ancistrinae) is known from four caves in the São Domingos karst area, upper rio Tocantins basin, Central Brazil. These populations differ in general body shape and degree of reduction of eyes and of pigmentation. The small Passa Três population (around 1,000 individuals) presents the most reduced eyes, which are not externally visible in adults. A small group of Passa Três catfish, one male and three females, reproduced spontaneously thrice in laboratory, at the end of summertime in 2000, 2003 and 2004. Herein we describe the reproductive behavior during the 2003 event, as well as the early development of the 2003 and 2004 offsprings, with focus on body growth and ontogenetic regression of eyes. The parental care by the male, which includes defense of the rock shelter where the egg clutch is laid, cleaning and oxygenation of eggs, is typical of many loricariids. On the other hand, the slow development, including delayed eye degeneration, low body growth rates and high estimated longevity (15 years or more) are characteristic of precocial, or K-selected, life cycles. In the absence of comparable data for close epigean relatives (Ancistrus spp.), it is not possible to establish whether these features are an autapomorphic specialization of the troglobitic A. cryptophthalmus or a plesiomorphic trait already present in the epigean ancestor, possibly favoring the adoption of the life in the food-poor cave environment. We briefly discuss the current hypotheses on eye regression in troglobitic vertebrates.

Immune cells and oxidative stress in the endotoxin tolerance mouse model

Sepsis is a systemic inflammatory response that can lead to tissue damage and death. In order to increase our understanding of sepsis, experimental models are needed that produce relevant immune and inflammatory responses during a septic event. We describe a lipopolysaccharide tolerance mouse model to characterize the cellular and molecular alterations of immune cells during sepsis. The model presents a typical lipopolysaccharide tolerance pattern in which tolerance is related to decreased production and secretion of cytokines after a subsequent exposure to a lethal dose of lipopolysaccharide. The initial lipopolysaccharide exposure also altered the expression patterns of cytokines and was followed by an 8- and a 1.5-fold increase in the T helper 1 and 2 cell subpopulations. Behavioral data indicate a decrease in spontaneous activity and an increase in body temperature following exposure to lipopolysaccharide. In contrast, tolerant animals maintained production of reactive oxygen species and nitric oxide when terminally challenged by cecal ligation and puncture (CLP). Survival study after CLP showed protection in tolerant compared to naive animals. Spleen mass increased in tolerant animals followed by increases of B lymphocytes and subpopulation Th1 cells. An increase in the number of stem cells was found in spleen and bone marrow. We also showed that administration of spleen or bone marrow cells from tolerant to naive animals transfers the acquired resistance status. In conclusion, lipopolysaccharide tolerance is a natural reprogramming of the immune system that increases the number of immune cells, particularly T helper 1 cells, and does not reduce oxidative stress.

Thermal behavior and decomposition kinetics of rifampicin polymorphs under isothermal and non-isothermal conditions

The thermal behavior of two polymorphic forms of rifampicin was studied by DSC and TG/DTG. The thermoanalytical results clearly showed the differences between the two crystalline forms. Polymorph I was the most thermally stable form, the DSC curve showed no fusion for this species and the thermal decomposition process occurred around 245 ºC. The DSC curve of polymorph II showed two consecutive events, an endothermic event (Tpeak = 193.9 ºC) and one exothermic event (Tpeak = 209.4 ºC), due to a melting process followed by recrystallization, which was attributed to the conversion of form II to form I. Isothermal and non-isothermal thermogravimetric methods were used to determine the kinetic parameters of the thermal decomposition process. For non-isothermal experiments, the activation energy (Ea) was derived from the plot of Log β vs 1/T, yielding values for polymorph form I and II of 154 and 123 kJ mol-1, respectively. In the isothermal experiments, the Ea was obtained from the plot of lnt vs 1/T at a constant conversion level. The mean values found for form I and form II were 137 and 144 kJ mol-1, respectively.

Hydrodynamics of the Itapocu river and the Barra Velha lagoon estuarine system, SC, Brazil

A hydrodynamic characterization of the Itapocu river and Barra Velha lagoon estuarine system was carried out with the objective of evaluating how the current regime in this area is affected by astronomical and meteorological tides and the river discharge. Meteorological, water level and current velocity and direction data were gathered hourly during a twenty-day period, from 22-July until 10-August, 2004. Current meters were positioned at the inlet, at the entrance of the north and south lagoons and at the lower estuary of the river along with a tide gauge. The estuarine system showed distinct current behavior among the different sectors within the estuary, responding to the different forcings. The strongest currents were observed at the inlet while the weakest values were observed at the northern lagoon, a location that showed little dynamic. The general flow was ebb-dominated flux, in response to fluvial discharge, even during local wind water set-up event.

Nutritive value and physical characteristics of Xaraes palisadegrass as affected by grazing strategy

The aim of this study was to ascertain whether the defoliation frequency based on a fixed rest period would generate variable sward structural and physiological conditions at each subsequent grazing event. The relative importance of the physiological age was established in comparison with the chronological age in the determination of the forage nutritive value of Xaraes palisadegrass [Brachiaria brizantha (Hochst ex A. RICH.) STAPF. cv. Xaraes]. Two grazing frequencies were defined by light interception (LI) at initiation of grazing (95% LI - ""target grazing"" [TG] or 100% LI - ""delayed grazing"" [DG]) and one based on chronological time, grazing every 28 days (28-d). Forage produced under the TG schedule was mostly leaves (93%) with a higher concentration of crude protein (CP; 138 g/kg in the whole forage), a lower concentrations of neutral detergent fibre (NDF) in the stems (740 g/kg), and higher in vitro dry matter digestibility (IVDMD) of the leaves (690 g/kg), compared to the other treatments. Lower grazing frequency strategies (DG and 28-d) resulted in forage with higher proportions of stems (10 and 9%, respectively). Strategies based on light interception did not produce pre-graze forage with a uniform nutritive value, as the indicators varied across grazing cycles. The treatment based on fixed days of rest did not result in uniformity.

Beam-energy and system-size dependence of dynamical net charge fluctuations

We present measurements of net charge fluctuations in Au+Au collisions at s(NN)=19.6, 62.4, 130, and 200 GeV, Cu+Cu collisions at s(NN)=62.4 and 200 GeV, and p+p collisions at s=200 GeV using the dynamical net charge fluctuations measure nu(+-,dyn). We observe that the dynamical fluctuations are nonzero at all energies and exhibit a modest dependence on beam energy. A weak system size dependence is also observed. We examine the collision centrality dependence of the net charge fluctuations and find that dynamical net charge fluctuations violate 1/N(ch) scaling but display approximate 1/N(part) scaling. We also study the azimuthal and rapidity dependence of the net charge correlation strength and observe strong dependence on the azimuthal angular range and pseudorapidity widths integrated to measure the correlation.

First Description of a Cluster of Acute/Subacute Paracoccidioidomycosis Cases and Its Association with a Climatic Anomaly

Background: Identifying clusters of acute paracoccidioidomycosis cases could potentially help in identifying the environmental factors that influence the incidence of this mycosis. However, unlike other endemic mycoses, there are no published reports of clusters of paracoccidioidomycosis. Methodology/Principal Findings: A retrospective cluster detection test was applied to verify if an excess of acute form (AF) paracoccidioidomycosis cases in time and/or space occurred in Botucatu, an endemic area in Sao Paulo State. The scan-test SaTScan v7.0.3 was set to find clusters for the maximum temporal period of 1 year. The temporal test indicated a significant cluster in 1985 (P<0.005). This cluster comprised 10 cases, although 2.19 were expected for this year in this area. Age and clinical presentation of these cases were typical of AF paracccidioidomycosis. The space-time test confirmed the temporal cluster in 1985 and showed the localities where the risk was higher in that year. The cluster suggests that some particularities took place in the antecedent years in those localities. Analysis of climate variables showed that soil water storage was atypically high in 1982/83 (similar to 2.11/2.5 SD above mean), and the absolute air humidity in 1984, the year preceding the cluster, was much higher than normal (similar to 1.6 SD above mean), conditions that may have favored, respectively, antecedent fungal growth in the soil and conidia liberation in 1984, the probable year of exposure. These climatic anomalies in this area was due to the 1982/83 El Nino event, the strongest in the last 50 years. Conclusions/Significance: We describe the first cluster of AF paracoccidioidomycosis, which was potentially linked to a climatic anomaly caused by the 1982/83 El Nino Southern Oscillation. This finding is important because it may help to clarify the conditions that favor Paracoccidioides brasiliensis survival and growth in the environment and that enhance human exposure, thus allowing the development of preventive measures.

Blood Meal-Derived Heme Decreases ROS Levels in the Midgut of Aedes aegypti and Allows Proliferation of Intestinal Microbiota

The presence of bacteria in the midgut of mosquitoes antagonizes infectious agents, such as Dengue and Plasmodium, acting as a negative factor in the vectorial competence of the mosquito. Therefore, knowledge of the molecular mechanisms involved in the control of midgut microbiota could help in the development of new tools to reduce transmission. We hypothesized that toxic reactive oxygen species (ROS) generated by epithelial cells control bacterial growth in the midgut of Aedes aegypti, the vector of Yellow fever and Dengue viruses. We show that ROS are continuously present in the midgut of sugar-fed (SF) mosquitoes and a blood-meal immediately decreased ROS through a mechanism involving heme-mediated activation of PKC. This event occurred in parallel with an expansion of gut bacteria. Treatment of sugar-fed mosquitoes with increased concentrations of heme led to a dose dependent decrease in ROS levels and a consequent increase in midgut endogenous bacteria. In addition, gene silencing of dual oxidase (Duox) reduced ROS levels and also increased gut flora. Using a model of bacterial oral infection in the gut, we show that the absence of ROS resulted in decreased mosquito resistance to infection, increased midgut epithelial damage, transcriptional modulation of immune-related genes and mortality. As heme is a pro-oxidant molecule released in large amounts upon hemoglobin degradation, oxidative killing of bacteria in the gut would represent a burden to the insect, thereby creating an extra oxidative challenge to the mosquito. We propose that a controlled decrease in ROS levels in the midgut of Aedes aegypti is an adaptation to compensate for the ingestion of heme.

Association between intratumoral lymphatic microvessel density (LMVD) and clinicopathologic features in endometrial cancer: a retrospective cohort study

Background: Lymph node metastasis in endometrial cancer significantly decreases survival rate. Few data on the influence of intratumoral lymphatic microvessel density (LMVD) on survival in endometrial cancer are available. Our aim was to assess the intratumoral LMVD of endometrial carcinomas and to investigate its association with classical pathological factors, lymph node metastasis and survival. Methods: Fifty-seven patients with endometrial carcinoma diagnosed between 2000 and 2008 underwent complete surgical staging and evaluation of intratumoral LMVD and other histologic variables. Lymphatic microvessels were identified by immunohistochemical staining using monoclonal antibody against human podoplanin (clone D2-40) and evaluated by counting the number of immunostained lymphatic vessels in 10 hot spot areas at 400x magnification. The LMVD was expressed by the mean number of vessels in these 10 hot spot microscopic fields. We next investigated the association of LMVD with the clinicopathologic findings and prognosis. Results: The mean number of lymphatic vessels counted in all cases ranged between 0 and 4.7. The median value of mean LMVD was 0.5, and defined the cut-off for low and high LMVD. We identified low intratumoral LMVD in 27 (47.4%) patients and high LMVD in 30 (52.6%) patients. High intratumoral LMVD was associated with lesser miometrial and adnaexal infiltration, lesser cervical and peritoneal involvement, and fewer fatal cases. Although there was lower lymph node involvement among cases with high LMVD, the difference did not reach significance. No association was seen between LMVD and FIGO staging, histological type, or vascular invasion. On the other hand, low intratumoral LMVD was associated with poor outcome. Seventy-five percent of deaths occurred in patients with low intratumoral LMVD. Conclusion: Our results show association of high intratumoral LMVD with features related to more localized disease and better outcome. We discuss the role of lymphangiogenesis as an early event in the endometrial carcinogenesis.

Reciprocal Modulation of Cognitive and Emotional Aspects in Pianistic Performances

Background: High level piano performance requires complex integration of perceptual, motor, cognitive and emotive skills. Observations in psychology and neuroscience studies have suggested reciprocal inhibitory modulation of the cognition by emotion and emotion by cognition. However, it is still unclear how cognitive states may influence the pianistic performance. The aim of the present study is to verify the influence of cognitive and affective attention in the piano performances. Methods and Findings: Nine pianists were instructed to play the same piece of music, firstly focusing only on cognitive aspects of musical structure (cognitive performances), and secondly, paying attention solely on affective aspects (affective performances). Audio files from pianistic performances were examined using a computational model that retrieves nine specific musical features (descriptors) - loudness, articulation, brightness, harmonic complexity, event detection, key clarity, mode detection, pulse clarity and repetition. In addition, the number of volunteers' errors in the recording sessions was counted. Comments from pianists about their thoughts during performances were also evaluated. The analyses of audio files throughout musical descriptors indicated that the affective performances have more: agogics, legatos, pianos phrasing, and less perception of event density when compared to the cognitive ones. Error analysis demonstrated that volunteers misplayed more left hand notes in the cognitive performances than in the affective ones. Volunteers also played more wrong notes in affective than in cognitive performances. These results correspond to the volunteers' comments that in the affective performances, the cognitive aspects of piano execution are inhibited, whereas in the cognitive performances, the expressiveness is inhibited. Conclusions: Therefore, the present results indicate that attention to the emotional aspects of performance enhances expressiveness, but constrains cognitive and motor skills in the piano execution. In contrast, attention to the cognitive aspects may constrain the expressivity and automatism of piano performances.