A new species of Euprognatha Stimpson, 1871 (Crustacea, Brachyura, Inachoididae) from off coast of northeastern Brazil

A new species of Euprognatha Stimpson, 1871 from off coast of Brazil (Canopus Bank, 02º15.3'00"S - 38º16.0'00"W) is described and illustrated, namely Euprognatha limatula n. sp. The new species is compared to its congeners. Lectotypes are designated for E. acuta A. Milne-Edwards, 1880 and E. granulata Faxon, 1893. A key to the species of Euprognatha is provided.

Diversification and Species Boundaries of Rhinebothrium (Cestoda; Rhinebothriidea) in South American Freshwater Stingrays (Batoidea; Potamotrygonidae)

Background: Neotropical freshwater stingrays (Batoidea: Potamotrygonidae) host a diverse parasite fauna, including cestodes. Both cestodes and their stingray hosts are marine-derived, but the taxonomy of this host/parasite system is poorly understood. Methodology: Morphological and molecular (Cytochrome oxidase I) data were used to investigate diversity in freshwater lineages of the cestode genus Rhinebothrium Linton, 1890. Results were based on a phylogenetic hypothesis for 74 COI sequences and morphological analysis of over 400 specimens. Cestodes studied were obtained from 888 individual potamotrygonids, representing 14 recognized and 18 potentially undescribed species from most river systems of South America. Results: Morphological species boundaries were based mainly on microthrix characters observed with scanning electron microscopy, and were supported by COI data. Four species were recognized, including two redescribed (Rhinebothrium copianullum and R. paratrygoni), and two newly described (R. brooksi n. sp. and R. fulbrighti n. sp.). Rhinebothrium paranaensis Menoret & Ivanov, 2009 is considered a junior synonym of R. paratrygoni because the morphological features of the two species overlap substantially. The diagnosis of Rhinebothrium Linton, 1890 is emended to accommodate the presence of marginal longitudinal septa observed in R. copianullum and R. brooksi n. sp. Patterns of host specificity and distribution ranged from use of few host species in few river basins, to use of as many as eight host species in multiple river basins. Significance: The level of intra-specific morphological variation observed in features such as total length and number of proglottids is unparalleled among other elasmobranch cestodes. This is attributed to the large representation of host and biogeographical samples. It is unclear whether the intra-specific morphological variation observed is unique to this freshwater system. Nonetheless, caution is urged when using morphological discontinuities to delimit elasmobranch cestode species because the amount of variation encountered is highly dependent on sample size and/or biogeographical representation.

Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparum population divergence

Background: The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity in P. falciparum have begun to elucidate the demographic history of the species, as well as patterns of population structure and patterns of linkage disequilibrium within its genome. Such studies will be greatly enhanced by new genomic tools and recent large-scale efforts to map genomic variation. To that end, we have developed a high throughput single nucleotide polymorphism (SNP) genotyping platform for P. falciparum. Results: Using an Affymetrix 3,000 SNP assay array, we found roughly half the assays (1,638) yielded high quality, 100% accurate genotyping calls for both major and minor SNP alleles. Genotype data from 76 global isolates confirm significant genetic differentiation among continental populations and varying levels of SNP diversity and linkage disequilibrium according to geographic location and local epidemiological factors. We further discovered that nonsynonymous and silent (synonymous or noncoding) SNPs differ with respect to within-population diversity, interpopulation differentiation, and the degree to which allele frequencies are correlated between populations. Conclusions: The distinct population profile of nonsynonymous variants indicates that natural selection has a significant influence on genomic diversity in P. falciparum, and that many of these changes may reflect functional variants deserving of follow-up study. Our analysis demonstrates the potential for new high-throughput genotyping technologies to enhance studies of population structure, natural selection, and ultimately enable genome-wide association studies in P. falciparum to find genes underlying key phenotypic traits.

Comparison Between Perfadex and Locally Manufactured Low-Potassium Dextran Solution for Pulmonary Preservation in an Ex Vivo Isolated Lung Perfusion Model

Introduction. Lung tranplantation, a consolidated treatment for end-stage lung disease, utilizes preservation solutions, such as low potassium dextran (LPD), to mitigate ischemia reperfusion injury. We sought the local development of LPD solutions in an attempt to facilitate access and enhance usage. We also sought to evaluate the effectiveness of a locally manufactured LPD solution in a rat model of ex vivo lung perfusion. Methods. We randomized the following groups \?\adult of male Wistar rats (n = 25 each): Perfadex (LPD; Vitro life, Sweden); locally manufactured LPD-glucose (LPDnac) (Farmoterapica, Brazil), and normal saline solution (SAL) with 3 ischemic times (6, 12, and 24 hours). The harvested heart lung blocks were flushed with solution at 4 C. After storage, the blocks were connected to an IL-2 Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus) and reperfused with homologous blood for 60 minutes. Respiratory mechanics, pulmonary artery pressure, perfusate blood gas analysis, and lung weight were measured at 10-minute intervals. Comparisons between groups and among ischemic times were performed using analysis of variance with a 5% level of significance. Results. Lungs preserved for 24 hours were nonviable and therefore excluded from the analysis. Those preserved for 6 hours showed better ventilatory mechanics when compared with 12 hours. The oxygenation capacity was not different between lungs flushed with LPD or LPDnac, regardless of the ischemic time. SAL lungs showed higher PCO(2) values than the other solutions. Lung weight increased over time during perfusion; however, there were no significant differences among the tested solutions (LPD, P = .23; LPDnac, P = .41; SAL, P = .26). We concluded that the LPDnac solution results in gas exchange were comparable to the original LPD (Perfadex); however ventilatory mechanics and edema formation were better with LPD, particularly among lungs undergoing 6 hours of cold ischemia.

Challenges and Recommendations for Placebo Controls in Randomized Trials in Physical and Rehabilitation Medicine A Report of the International Placebo Symposium Working Group

Compared with other specialties, the field of physical and rehabilitation medicine has not received the deserved recognition from clinicians and researchers in the scientific community. One of the reasons is the lack of sound evidence to support the traditional physical and rehabilitation medicine treatments. The best way to change this disadvantage is through a well conducted clinical research, such as standard placebo- or sham-controlled randomized clinical trials. Therefore, having placebo groups in clinical trials is essential to improve the level of evidence-based practice in physical and rehabilitation medicine that ultimately translates to better clinical care. To address the challenges for the use of placebo in physical and rehabilitation medicine and randomized clinical trials and to create useful recommendations, we convened a working group during the inaugural International Symposium in Placebo (February 2009, in Sao Paulo, Brazil) in which the following topics were discussed: (1) current status of randomized clinical trials in physical and rehabilitation medicine, (2) challenges for the use of placebo in physical and rehabilitation medicine, (3) bioethics, (4) use of placebo in acupuncture trials and for the treatment of low-back pain, (5) mechanisms of placebo, and (6) insights from other specialties. The current article represents the consensus report from the working group.

A randomized, double-blind clinical trial on the efficacy of cortical direct current stimulation for the treatment of major depression

Preliminary findings suggest that transcranial direct current stimulation (tDCS) can have antidepressant effects. We sought to test this further in a parallel-group, double-blind clinical trial with 40 patients with major depression, medication-free randomized into three groups of treatment: anodal tDCS of the left dorsolateral prefrontal cortex (active group-`DLPFC`); anodal tDCS of the occipital cortex (active control group-`occipital`) and sham tDCS (placebo control group-`sham`). tDCS was applied for 10 sessions during a 2-wk period. Mood was evaluated by a blinded rater using the Hamilton Depression Rating Scale (HDRS) and Beck Depression Inventory (BDI). The treatment was well tolerated with minimal side-effects that were distributed equally across all treatment groups. We found significantly larger reductions in depression scores after DLPFC tDCS [HDRS reduction of 40.4 % (+/-25.8%)] compared to occipital [HDRS reduction of 21.3 % ( +/-12.9%)] and sham tDCS [HDRS reduction of 10.4 % (+/-36.6%)]. The beneficial effects of tDCS in the DLPFC group persisted for 1 month after the end of treatment. Our findings support further investigation on the effects of this novel potential therapeutic approach - tDCS - for the treatment of major depression.

Experimental Model of Isolated Lung Perfusion in Rats: First Brazilian Experience Using the IL-2 Isolated Perfused Rat or Guinea Pig Lung System

Introduction. Lung transplantation has become the mainstay therapy for patients with end-stage lung disease refractory to medical management. However, the number of patients listed for lung transplantation largely exceeds available donors. The study of lung preservation requires accurate, cost-effective small animal models. We have described a model of ex vivo rat lung perfusion using a commercially available system. Methods. Male Wistar rats weighing 250 g-300 g were anesthetized with intraperitoneal sodium thiopental (50 mg/kg body weight). The surgical technique included heart-lung block extraction, assembly, and preparation for perfusion and data collection. We used an IL-2 Isolated Perfused Rat or Guinea Pig Lung System (Harvard Apparatus, Holliston, Mass, United States; Hugo Sachs Elektronik, Alemanha). Results. Preliminary results included hemodynamic and pulmonary mechanics data gathered in the experiments. Conclusion. The isolated rat lung perfusion system is a reliable method to assess lung preservation.

Identification of a myeloid committed progenitor as the cancer-initiating cell in acute promyelocytic leukemia

Acute promyelocytic leukemia (APL) is characterized by a block in differentiation and accumulation of promyelocytes in the bone marrow and blood. The majority of APL patients harbor the t(15: 17) translocation leading to expression of the fusion protein promyelocytic-retinoic acid receptor alpha. Treatment with retinoic acid leads to degradation of promyelocytic-retinoic acid receptor alpha protein and disappearance of leukemic cells; however, 30% of APL patients relapse after treatment. One potential mechanism for relapse is the persistence of cancer ""stem"" cells in hematopoietic organs after treatment. Using a novel sorting strategy we developed to isolate murine myeloid cells at distinct stages of differentiation, we identified a population of committed myeloid cells (CD34(+), c-kit(+), Fc gamma RIII/II(+), Gr1(int)) that accumulates in the spleen and bone marrow in a murine model of APL. We observed that these cells are capable of efficiently generating leukemia in recipient mice, demonstrating that this population represents the APL cancer-initiating cell. These cells down-regulate the transcription factor CCAAT/enhancer binding protein alpha (C/EBP alpha) possibly through a methylation-dependent mechanism, indicating that C/EBP alpha deregulation contributes to transformation of APL cancer-initiating cells. Our findings provide further understanding of the biology of APL by demonstrating that a committed transformed progenitor can initiate and propagate the disease. (Blood. 2009; 114: 5415-5425)

TAC3/TACR3 Mutations Reveal Preferential Activation of Gonadotropin-Releasing Hormone Release by Neurokinin B in Neonatal Life Followed by Reversal in Adulthood

Context: Mutations in TAC3 and TACR3 (encoding neurokinin B and its receptor) have been identified in Turkish patients with idiopathic hypogonadotropic hypogonadism (IHH), but broader populations have not yet been tested and genotype-phenotype correlations have not been established. Objective: A broad cohort of normosmic IHH probands was screened for mutations in TAC3/TACR3 to evaluate the prevalence of such mutations and define the genotype/phenotype relationships. Design and Setting: The study consisted of sequencing of TAC3/TACR3, in vitro functional assays, and neuroendocrine phenotyping conducted in tertiary care centers worldwide. Patients or Other Participants: 345 probands, 18 family members, and 292 controls were studied. Intervention: Reproductive phenotypes throughout reproductive life and before and after therapy were examined. Main Outcome Measure: Rare sequence variants in TAC3/TACR3 were detected. Results: In TACR3, 19 probands harbored 13 distinct coding sequence rare nucleotide variants [three nonsense mutations, six nonsynonymous, four synonymous (one predicted to affect splicing)]. In TAC3, one homozygous single base pair deletion was identified, resulting in complete loss of the neurokinin B decapeptide. Phenotypic information was available on 16 males and seven females with coding sequence variants in TACR3/TAC3. Of the 16 males, 15 had microphallus; none of the females had spontaneous thelarche. Seven of the 16 males and five of the seven females were assessed after discontinuation of therapy; six of the seven males and four of the five females demonstrated evidence for reversibility of their hypogonadotropism. Conclusions: Mutations in the neurokinin B pathway are relatively common as causes of hypogonadism. Although the neurokinin B pathway appears essential during early sexual development, its importance in sustaining the integrity of the hypothalamic-pituitary-gonadal axis appears attenuated over time. (J Clin Endocrinol Metab 95: 2857-2867, 2010)