Risk Factors for Adverse Prognosis and Death in American Visceral Leishmaniasis: A Meta-analysis

Background

In the current context of high fatality rates associated with American visceral leishmaniasis (VL), the appropriate use of prognostic factors to identify patients at higher risk of unfavorable outcomes represents a potential tool for clinical practice. This systematic review brings together information reported in studies conducted in Latin America, on the potential predictors of adverse prognosis (continued evolution of the initial clinical conditions of the patient despite the implementation of treatment, independent of the occurrence of death) and death from VL. The limitations of the existing knowledge, the advances achieved and the approaches to be used in future research are presented.

Methods/Principal Findings

The full texts of 14 studies conforming to the inclusion criteria were analyzed and their methodological quality examined by means of a tool developed in the light of current research tools. Information regarding prognostic variables was synthesized using meta-analysis. Variables were grouped according to the strength of evidence considering summary measures, patterns and heterogeneity of effect-sizes, and the results of multivariate analyses. The strongest predictors identified in this review were jaundice, thrombocytopenia, hemorrhage, HIV coinfection, diarrhea, age <5 and age >40–50 years, severe neutropenia, dyspnoea and bacterial infections. Edema and low hemoglobin concentration were also associated with unfavorable outcomes. The main limitation identified was the absence of validation procedures for the few prognostic models developed so far.

Conclusions/Significance

Integration of the results from different investigations conducted over the last 10 years enabled the identification of consistent prognostic variables that could be useful in recognizing and handling VL patients at higher risk of unfavorable outcomes. The development of externally validated prognostic models must be prioritized in future investigations.     

Meiotic self-pairing of the Psalidodon (Characiformes,Characidae) iso-B chromosome: A successful perpetuation mechanism

B chromosomes are non-essential additional genomic elements present in several animal and plant species. In fishes, species of the genus Psalidodon (Characiformes, Characidae) harbor great karyotype diversity, and multiple populations carry different types of non-essential B chromosomes. This study analyzed how the dispensable supernumerary B chromosome of Psalidodon paranae behaves during meiosis to overcome checkpoints and express its own meiosis-specific genes. We visualized the synaptonemal complexes of P. paranae individuals with zero, one, or two B chromosomes using immunodetection with anti-medaka SYCP3 antibody and fluorescence in situ hybridization with a (CA)₁₅ microsatellite probe. Our results showed that B chromosomes self-pair in cells containing only one B chromosome. In cells with two identical B chromosomes, these elements remain as separate synaptonemal complexes or close self-paired elements in the nucleus territory. Overall, we reveal that B chromosomes can escape meiotic silencing of unsynapsed chromatin through a self-pairing process, allowing expression of their own genes to facilitate regular meiosis resulting in fertile individuals. This behavior, also seen in other congeneric species, might be related to their maintenance throughout the evolutionary history of Psalidodon.     

Carbonate facies dominated by syndepositional cements: a key component of Middle Triassic platforms. The Marmolada case history (Dolomites, Italy)

Summary This article deals with the discussion of the role of the syndepositional cementation for the growth of the Middle Triassic pre-volcanic carbonate platforms of the Dolomites (Southern Alps, Northern Italy). The study is concentrated on the Marmolada Buildup, which escaped the facies destroying dolomitization which affected many surrounding platforms. The investigations took place within an almost isochronous uppermost Anisian palcogeographic transect, ranging from the platform-top to the margin and the upper slope. Methods used include geological mapping, sedimentological and paleontological studies, evaluation of the microfacies, as well as SEM and EDS epifluorescence analyses. The well bedded platform-top succession consists of intra-bioclast calcarenites and calcirudites, interbedded with subordinate boundstones, and organized in shallowing upward, meter scale depositional cycles, sometimes capped by subaerial surfaces. The platform margin belt is rich in boundstones and lacks a primary framework formed by organisms; metazoan skeletons form less then 5% of the rock volume. The outer margin and the uppermost slope are characterized by decimeter-scale boundstone blocks, coated and linked to each other by huge amounts of radiaxial fibrous calcite cements, arranged in concentric crusts. These cements (“evinospongiac”) represent the main component of the margin and upper slope facies. Epifluorescence analyses suggest the existence of abundant organic residual matter associated not only with the bioclasts and peloids, but also with the syndepositional cements. Organic matter likely played a significant role in carbonate cementation and was a key factor for the early lithification of the platform as well as for the sediment production. Minor element microanalyses reveal an uniform Mg content in different calcite types (2–4 Mole % MgCO₃), independently from the primary nature of the components. Late diagenetic sparry calcites exhibit similar Mg values but no iron. These data point to a homogenization of minor element distribution, probably associated with a slow but long-lasting semi-closed fluid circulation, possibly related with the Neogene uplifting of the Dolomite Mountains.     

Interaction of visual and olfactory cues in the aggregation behaviour of the haematophagous bug Triatoma infestans

We analysed how the assembling behaviour of Triatoma infestans is modulated by the convergence of chemical cues released by their faeces and the spectral quality of the light associated with refuges. Second-instar larvae were confronted with refuges associated with a visual stimulus (either blue, green or red lights having the same intensity, or darkness) and a chemical cue (presence or absence of faeces). In this context, faeces constitute a major attractant for bugs. In the absence of faeces, bugs always assembled in dark places. Green light was always rejected despite the presence of faeces, i.e. the assembling behaviour was controlled by a photonegative reaction to this light. In the presence of red light, orientation towards the chemical cue dominated over the bugs' photonegative reaction to this light. Such a light was avoided in the absence of faeces but not in their presence. Also, negative phototaxis to blue light could be counteracted by the presence of the chemical cue. Thus, a concrete interaction between visual and olfactory cues occurred in these experiments: the bugs' response changed depending on the specific combination of spectral light and faeces. Finally, bugs responded differentially to blue, red and green lights of the same intensity. They assembled preferentially on red, followed by blue and then by green. Thus, discrimination between lights of different spectral quality is possible, probably through an achromatic mechanism.     

Synthesis,conformation, and membrane modifying properties of the trikoningin KB lipopeptaibols: Effect of hydrophobicity and chirality in position 1

Summary We synthesized by solution-phase methods the naturally occurring, 10-amino acid residue lipopeptaibol antibiotics trikoningins KBI and KBII, and the [l-Iva¹] KB analogue, in which the amino acid in position 1 is different, with the aim at investigating the effect of hydrophobicity and chirality in that position. A solution conformational analysis, using FT-IR absorption and CD techniques, indicated that all of the three decapeptides are predominantly helical in a membrane-mimetic environment. Permeability measurements showed an increase of the activity from the [Aib¹] peptide to the more hydrophobic [Iva¹] peptides. Conversely, the effect of a change in chirality, obtained by replacingd-Iva¹ withl-Iva, turned out to be of minor significance.     

Low Plasma Leptin Concentration and Low Rates of Fat Oxidation in Weight‐Stable Post‐Obese Subjects

Objective: A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post‐obese adults (2 males and 6 females; 48.9 ± 12.2 years; body mass index [BMI]: 24.5 ± 1.0 kg/m²; body fat 33 ± 5%; mean ± SD) who lost 27.1 ± 21.3 kg (16 to 79 kg) and had maintained this weight loss for ≥2 months (2 to 9 months) to eight age‐ and BMI‐matched control never‐obese subjects (1 male and 7 females; 49.1 ± 5.2 years; BMI 24.4 ± 1.0 kg/m²; body fat 33 ± 7%). Research Methods and Procedures: Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10‐hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48‐hour period in free living conditions. Results: After adjustment for fat mass and fat‐free mass, post‐obese subjects had, compared with controls, similar levels of physical activity (4185 ± 205 vs. 4295 ± 204 counts) and similar RMR (1383 ± 268 vs. 1430 ± 104 kcal/day) but higher RQ (0.86 ± 0.04 vs. 0.81 ± 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat‐free mass, was lower in post‐obese than in control subjects (4.5 ± 2.1 vs. 11.6 ± 7.9 ng/mL, p < 0.05). Discussion: The low fat oxidation and low plasma leptin concentrations observed in post‐obese individuals may, in part, explain their propensity to relapse.     

Meiosis and the Neo- XY system of Dichroplus vittatus (Melanoplinae, Acrididae): a comparison between sexes

The origin of neo-XY sex systems in Acrididae is usually explained through an X-autosome centric fusion, and the behaviour of the neo-sex chromosomes has been solely studied in males. In this paper we analysed male and female Dichroplus vittatus. The karyotype comprises 2n = 20 chromosomes including 9 pairs of autosomes and a sex chromosome pair that includes a large metacentric neo-X and a small telocentric neo-Y. We compared the meiotic behaviour of the sex bivalent between both sexes. Mean cell autosomal chiasma frequency was low in both sexes and slightly but significantly higher in males than in females. Chiasma frequency of females increased significantly when the sex-bivalent was included. Chiasma distribution was basically distal in both sexes. Behaviour of the neo-XY pair is complex as a priori suggested by its structure, which was analysed in mitosis and meiosis of diploid and polyploid cells. During meiosis, orientation of the neo-XY is highly irregular; only 21% of the metaphase I spermatocytes show standard orientation. In the rest of cells, the alternate or simultaneous activity of an extra kinetochore in the distal end of the short arm (XL) of the neo-X, determined unusual MI orientations and a high frequency of non-disjunction and lagging of the sex-chromosomes. In females, the neo-XX bivalent had a more regular behaviour but showed 17% asynapsis in the XL arm which, in those cases orientated its distal ends towards opposite spindle poles suggesting, again, the activity of a second kinetochore. The dicentric nature and the unstable meiotic behaviour of the sex neo-chromosomes of D. vittatus suggest a recent origin of the sex determination mechanism, with presumable adaptive advantages which could compensate their potential negative heterosis. Our observations suggest that the origin of the neo-sex system was a tandem fusion of two original telocentric X-chromosomes followed by another tandem fusion with the small megameric bivalent and a further pericentric inversion of the neo-X. The remaining autosomal homolog resulted in the neo-Y chromosome. This revised version was published online in July 2006 with corrections to the Cover Date.     

Benthic community metabolism and trophic conditions of four South American lakes

Oxygen uptake rates of undisturbed sediment columns have been used as an integrative measure of the metabolic activities of benthic communities. Since the intensity of metabolic processes of profundal lake is dependent on the production of organic matter in the pelagic zone, oxygen uptake rates reflect the trophic condition of the whole lake. Four small lakes of central Chile, differing strongly in trophic conditions, provided a possibility to compare benthic oxygen uptake rates, under different oxygen conditions (Quiñenco, Grande, Chica and Lleulleu). Our objective was to establish the relationship between the oxygen uptake rates and bottom characteristics of lakes with different trophic conditions. At 8 mg O₂ l^-1 in the overlying water of the cores studied, the oxygen uptake rates of the sediment were: Quiñenco 51.2–56.0 mg O₂ m² h^-1 (eutrophic), Grande 41.2–46.4 mg O₂ m² h^-1 (mesotrophic), Chica 23.2–18.1 mg O₂ m² h^-1 (mesotrophic) and Lleulleu 11.7–16.0 mg O₂ m² h^-1 (oligotrophic). By exposing the sediments to different oxygen levels in the laboratory, it was found that benthic community metabolism decreased with oxygen concentrations. The slope of regression lines, relating oxygen uptake rates to oxygen concentrations, differed for the different sites investigated, closely related with the trophic conditions of the lakes. It was positively correlated with the organic matter content of the sediment of the cores (r ²= 0.78, p<0,05) and the nutrients of the bottom waters (total-P: r ²= 0.73, p<0,05; total-N: r ²= 0.73, p<0,05), and negatively with the redox potential of the sediments (r ²= 0.88, p<0,05).     

Opposing effects of ICOS on graft-versus-host disease mediated by CD4 and CD8 T cells

ICOS, a CD28 family member expressed on activated CD4(+) and CD8(+) T cells, plays important roles in T cell activation and effector function. Here we studied the role of ICOS in graft-vs-host disease (GVHD) mediated by CD4(+) or CD8(+) T cells in allogeneic bone marrow transplantation. In comparison of wild-type and ICOS-deficient T cells, we found that recipients of ICOS(-/-) CD4(+) T cells exhibited significantly less GVHD morbidity and delayed mortality. ICOS(-/-) CD4(+) T cells had no defect in expansion, but expressed significantly less Fas ligand and produced significantly lower levels of IFN-gamma and TNF-alpha. Thus, ICOS(-/-) CD4(+) T cells were impaired in effector functions that lead to GVHD. In contrast, recipients of ICOS(-/-) CD8(+) T cells exhibited significantly enhanced GVHD morbidity and accelerated mortality. In the absence of ICOS signaling, either using ICOS-deficient donors or ICOS ligand-deficient recipients, the levels of expansion and Tc1 cytokine production of CD8(+) T cells were significantly increased. The level of expansion was inversely correlated with the level of apoptosis, suggesting that increased ability of ICOS(-/-) CD8(+) T cells to induce GVHD resulted from the enhanced survival and expansion of those cells. Our findings indicate that ICOS has paradoxical effects on the regulation of alloreactive CD4(+) and CD8(+) T cells in GVHD.