Is semantic verbal fluency impairment explained by executive function deficits in schizophrenia?

Objective: To investigate if verbal fluency impairment in schizophrenia reflects executive function deficits or results from degraded semantic store or inefficient search and retrieval strategies. Method: Two groups were compared: 141 individuals with schizophrenia and 119 healthy age and education-matched controls. Both groups performed semantic and phonetic verbal fluency tasks. Performance was evaluated using three scores, based on 1) number of words generated2) number of clustered/ related wordsand 3) switching score. A fourth performance score based on the number of clusters was also measured. Results: Individuals with schizophrenia produced fewer words than controls. After controlling for the total number of words produced, a difference was observed between the groups in the number of cluster-related words generated in the semantic task. In both groups, the number of words generated in the semantic task was higher than that generated in the phonemic task, although a significant group vs. fluency type interaction showed that subjects with schizophrenia had disproportionate semantic fluency impairment. Working memory was positively associated with increased production of words within clusters and inversely correlated with switching. Conclusion: Semantic fluency impairment may be attributed to an inability (resulting from reduced cognitive control) to distinguish target signal from competing noise and to maintain cues for production of memory probes.Fundacao de Amparo e Pesquisa do Estado de Sao Paulo (FAPESP)Univ Fed Sao Paulo, Dept Psiquiatria, Programa Esquizofrenia PROESQ, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psiquiatria, LINC, Sao Paulo, SP, BrazilCtr Univ FIEO UNIFIEO, Dept Psicol Educ, Ave Franz Voegeli 300,Bloco Prata,Sala 10, BR-06020190 Osasco, SP, BrazilBrown Univ, Dept Cognit & Linguist Sci, Providence, RI 02912 USAUniv Mackenzie, Programa Posgrad Disturbios Desenvolvimento, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psiquiatria, Programa Esquizofrenia PROESQ, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Psiquiatria, LINC, Sao Paulo, SP, BrazilFAPESP: 2011/50740-5FAPESP: 2007/58630-9Web of Scienc

Validation of low anterior resection syndrome score in Brazil with Portuguese

Purpose This study was performed to investigate the convergent validity, discriminative validity, and reliability of the Brazilian version of the low anterior resection syndrome (LARS) score in a population with low educational and socioeconomic levels. Methods The LARS score was translated into the Portuguese language by forward- and back-translation procedures. In total, 127 patients from a public hospital in Brazil completed the questionnaires. The convergent validity was tested by comparing the LARS score with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core Module 30 (QLQ-C30) and with patients’ self-reported quality of life. For the discriminative validity, we tested the ability of the score to differentiate among subgroups of patients regarding neoadjuvant radiotherapy, type of surgery, and tumor distance from the anal verge. The test-retest reliability was investigated in a subgroup of 36 patients who responded to the survey twice in 2 weeks. Results The LARS score demonstrated a strong correlation with 5 of 6 items from the EORTC QLQ-C30 (P<0.05) and good concordance with patients’ self-reported quality of life (95.3%), confirming the convergent validity. The score was able to discriminate between subgroups of patients with different clinical characteristics related to LARS (P<0.001). The agreement between the test and retest showed that 86.1% of the patients remained in the same LARS category, and there was no significant difference between the LARS score numerical values (P=0.80), indicating good reliability overall. Conclusion The Brazilian version of the LARS score is a valid and reliable instrument to assess postoperative bowel function in a population with low educational and socioeconomic levels

Plasmodium vivax gametocytes in the bone marrow of an acute malaria patient and changes in the erythroid miRNA profile

Plasmodium vivax is the most widely distributed human malaria parasite and responsible for large amounts of disease and burden [1]. The presence of P. vivax in the bone marrow was first noticed in the late 19th century [2], and examinations of sternal bone marrow aspirates were performed as an accessory to examinations of peripheral blood in malaria, including P. vivax [3]. Since then, little progress has been made in studying P. vivax infections in this tissue. One report explored accumulation of dyserythropoietic cells in anaemic infected patients [4]. In addition, two case studies reported P. vivax infections after autologous bone marrow transplantation [5][6], and a third one documented an accidental P. vivax infection due to bone marrow transplantation between a malaria-infected donor and a malaria-free receptor [7]. In Brazil, one patient with persistent thrombocytopaenia and an enlarged spleen was diagnosed with chronic P. vivax malaria after the finding of schizonts in the bone marrow aspirate [8]. In all these reports and case studies, however, parasite loads and life stages found in the bone marrow were not investigated, and no molecular tools were available to rule out mixed infections or to characterize specific parasite stages

Energy Metabolism in H460 Lung Cancer Cells: Effects of Histone Deacetylase Inhibitors

BACKGROUND: Tumor cells are characterized by accelerated growth usually accompanied by up-regulated pathways that ultimately increase the rate of ATP production. These cells can suffer metabolic reprogramming, resulting in distinct bioenergetic phenotypes, generally enhancing glycolysis channeled to lactate production. In the present work we showed metabolic reprogramming by means of inhibitors of histone deacetylase (HDACis), sodium butyrate and trichostatin. This treatment was able to shift energy metabolism by activating mitochondrial systems such as the respiratory chain and oxidative phosphorylation that were largely repressed in the untreated controls. METHODOLOGY/PRINCIPAL FINDINGS: Various cellular and biochemical parameters were evaluated in lung cancer H460 cells treated with the histone deacetylase inhibitors (HDACis), sodium butyrate (NaB) and trichostatin A (TSA). NaB and TSA reduced glycolytic flux, assayed by lactate release by H460 cells in a concentration dependent manner. NaB inhibited the expression of glucose transporter type 1 (GLUT 1), but substantially increased mitochondria bound hexokinase (HK) activity. NaB induced increase in HK activity was associated to isoform HK I and was accompanied by 1.5 fold increase in HK I mRNA expression and cognate protein biosynthesis. Lactate dehydrogenase (LDH) and pyruvate kinase (PYK) activities were unchanged by HDACis suggesting that the increase in the HK activity was not coupled to glycolytic flux. High resolution respirometry of H460 cells revealed NaB-dependent increased rates of oxygen consumption coupled to ATP synthesis. Metabolomic analysis showed that NaB altered the glycolytic metabolite profile of intact H460 cells. Concomitantly we detected an activation of the pentose phosphate pathway (PPP). The high O(2) consumption in NaB-treated cells was shown to be unrelated to mitochondrial biogenesis since citrate synthase (CS) activity and the amount of mitochondrial DNA remained unchanged. CONCLUSION: NaB and TSA induced an increase in mitochondrial function and oxidative metabolism in H460 lung tumor cells concomitant with a less proliferative cellular phenotype

HisAK70: Progress towards a vaccine against different forms of leishmaniosis

Background: Leishmania major and Leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL), respectively. The leishmanioses represent the second-largest parasitic killer in the world after malaria. Recently, we succeeded in generating a plasmid DNA (pCMV-HISA70m2A) and demonstrated that immunized mice were protected against L. major challenge. The efficacy of the DNA-vaccine was further enhanced by the inclusion of KMP-11 antigen into the antibiotic-free plasmid pVAX1-asd. Methods: Here, we describe the use of a HisAK70 DNA-vaccine encoding seven Leishmania genes (H2A, H2B, H3, H4, A2, KMP11 and HSP70) for vaccination of mice to assess the induction of a resistant phenotype against VL and CL. Results: HisAK70 was successful in vaccinated mice, resulting in a high amount of efficient sterile hepatic granulomas associated with a hepatic parasite burden fully resolved in the VL model; and resulting in 100 % inhibition of parasite visceralization in the CL model. Conclusions: The results suggest that immunization with the HisAK70 DNA-vaccine may provide a rapid, suitable, and efficient vaccination strategy to confer cross-protective immunity against VL and CL.This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (AGL2010-17394 and AGL2013-44100R) and PLATESA (P2013/ABI-2906) from the Comunidad de Madrid (Spain).Peer Reviewe