Intravitreal ranibizumab for myopic choroidal neovascularization: 12-month results

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intravitreal ranibizumab after 12 months in the treatment of choroidal neovascularization secondary to pathologic myopia. METHODS: This was a prospective, multicenter, consecutive, nonrandomized, interventional case series. The study included 34 eyes of 32 patients with choroidal neovascularization secondary to pathologic myopia; 13 eyes had previous photodynamic therapy, and 21 eyes had no previous treatment. The patients were followed for > or = 12 months. Best-corrected visual acuity, optical coherence tomography, and the presence of metamorphopsia were assessed monthly. RESULTS: Mean visual acuity improved 8 letters from baseline to 12-month follow-up, and the difference was statistically significant (P or = 3 lines, 44% improved > or = 2 lines, 65% improved > or = 1 line, and 79% improved > or = 0 lines. Central retinal thickness decreased significantly from baseline to the 12-month follow-up (P < 0.01). A mean of 3.6 treatments were performed during the 12-month follow-up, and no systemic or ocular side effects were registered during that time. CONCLUSION: One-year results of intravitreal ranibizumab for myopic choroidal neovascularization are very promising. Additional prospective studies are necessary to better determine long-term efficacy and safety

Changes in intracellular ion activities induced by adrenaline in human and rat skeletal muscle

To study the stimulating effect of adrenaline (ADR) on active Na+/K+ transport we used double-barrelled ion-sensitive micro-electrodes to measure the activities of extracellular K+ (aKe) and intracellular Na+ (aNai) in isolated preparations of rat soleus muscle, normal human intercostal muscle and one case of hyperkalemic periodic paralysis (h.p.p.). In these preparations bath-application of ADR (10−6 M) resulted in a membrane hyperpolarization and transient decreasesaKe andaNai which could be blocked by ouabain (3×10−4 M). In the h.p.p. muslce a continuous rise ofaNai induced by elevation ofaKe to 5.2 mM could be stopped by ADR. In addition, the intracellular K+ activity (aKi), the free intracellular Ca2+ concentration (pCai) and intracellular pH (pHi) were monitored in rat soleus muscle. During ADRaKi increased, pHi remained constant and intracellular Ca2+ apparently decreased. In conclusion, our data show that ADR primarily stimulates the Na+/K+ pump in mammalian skeletal muscle. This stimulating action is not impaired in the h.p.p. muscle

Environmental drivers of distribution and reef development of the Mediterranean coral Cladocora caespitosa

Cladocora caespitosa is the only Mediterranean scleractinian similar to tropical reef-building corals. While this species is part of the recent fossil history of the Mediterranean Sea, it is currently considered endangered due to its decline during the last decades. Environmental factors affecting the distribution and persistence of extensive bank reefs of this endemic species across its whole geographic range are poorly understood. In this study, we examined the environmental response of C. caespitosa and its main types of assemblages using ecological niche modeling and ordination analysis. We also predicted other suitable areas for the occurrence of the species and assessed the conservation effectiveness of Mediterranean marine protected areas (MPAs) for this coral. We found that phosphate concentration and wave height were factors affecting both the occurrence of this versatile species and the distribution of its extensive bioconstructions in the Mediterranean Sea. A set of factors (diffuse attenuation coefficient, calcite and nitrate concentrations, mean wave height, sea surface temperature, and shape of the coast) likely act as environmental barriers preventing the species from expansion to the Atlantic Ocean and the Black Sea. Uncertainties in our large-scale statistical results and departures from previous physiological and ecological studies are also discussed under an integrative perspective. This study reveals that Mediterranean MPAs encompass eight of the ten banks and 16 of the 21 beds of C. caespitosa. Preservation of water clarity by avoiding phosphate discharges may improve the protection of this emblematic species.Spanish Ministry of Economy and Competitiveness [CTM2014-57949-R]info:eu-repo/semantics/publishedVersio

Improved xylose and arabinose utilization by an industrial recombinant Saccharomyces cerevisiae strain using evolutionary engineering

<p>Abstract</p> <p>Background</p> <p>Cost-effective fermentation of lignocellulosic hydrolysate to ethanol by <it>Saccharomyces cerevisiae </it>requires efficient mixed sugar utilization. Notably, the rate and yield of xylose and arabinose co-fermentation to ethanol must be enhanced.</p> <p>Results</p> <p>Evolutionary engineering was used to improve the simultaneous conversion of xylose and arabinose to ethanol in a recombinant industrial <it>Saccharomyces cerevisiae </it>strain carrying the heterologous genes for xylose and arabinose utilization pathways integrated in the genome. The evolved strain TMB3130 displayed an increased consumption rate of xylose and arabinose under aerobic and anaerobic conditions. Improved anaerobic ethanol production was achieved at the expense of xylitol and glycerol but arabinose was almost stoichiometrically converted to arabitol. Further characterization of the strain indicated that the selection pressure during prolonged continuous culture in xylose and arabinose medium resulted in the improved transport of xylose and arabinose as well as increased levels of the enzymes from the introduced fungal xylose pathway. No mutation was found in any of the genes from the pentose converting pathways.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first report that characterizes the molecular mechanisms for improved mixed-pentose utilization obtained by evolutionary engineering of a recombinant <it>S. cerevisiae </it>strain. Increased transport of pentoses and increased activities of xylose converting enzymes contributed to the improved phenotype.</p

Validation of the Chinese version of the "Mood Disorder Questionnaire" for screening bipolar disorder among patients with a current depressive episode

<p>Abstract</p> <p>Background</p> <p>The Mood Disorder Questionnaire (MDQ) is a well-recognized screening tool for bipolar disorder, but its Chinese version needs further validation. This study aims to measure the accuracy of the Chinese version of the MDQ as a screening instrument for bipolar disorder (BPD) in a group of patients with a current major depressive episode.</p> <p>Methods</p> <p>142 consecutive patients with an initial DSM-IV-TR diagnosis of a major depressive episode were screened for BPD using the Chinese translation of the MDQ and followed up for one year. The final diagnosis, determined by a special committee consisting of three trained senior psychiatrists, was used as a 'gold standard' and ROC was plotted to evaluate the performance of the MDQ. The optimal cut-off was chosen by maximizing the Younden's index.</p> <p>Results</p> <p>Of the 142 patients, 122 (85.9%) finished the one year follow-up. On the basis of a semi-structured clinical interview 48.4% (59/122) received a diagnosis of unipolar depression (UPD), 36.9% (45/122) BPDII and 14.8% (18/122) BPDI. At the end of the one year follow-up,9 moved from UPD to BPD, 2 from BPDII to UPD, 1 from BPDII to BPDI, the overall rate of initial misdiagnosis was 16.4%. MDQ showed a good accuracy for BPD: the optimal cut-off was 4, with a sensitivity of 0.72 and a specificity of 0.73. When BPDII and BPDI were calculated independently, the optimal cut-off for BPDII was 4, with a sensitivity of 0.70 and a specificity of 0.73; while the optimal cut-off for BPDI was 5, with a sensitivity of 0.67 and a specificity of 0.86.</p> <p>Conclusions</p> <p>Our results show that the Chinese version of MDQ is a valid tool for screening BPD in a group of patients with current depressive episode on the Chinese mainland.</p

Reabilitação Cardíaca Após Síndrome Coronária Aguda. Deveremos Continuar a Reabilitar os Doentes de Baixo Risco? Experiência de um Centro

Introdução: A Reabilitação cardíaca (Rc) é um elemento fundamental na prevenção secundária após síndrome coronária aguda (ScA). A American Association of Cardiovascular and Pulmonary Rehabilitation (AAcPR)definiu critérios de estratificação de risco para os doentes elegíveis para programas de Rc. Contudo, tem sido questionada a integração de doentes de baixo risco em programas estruturados de treino de exercício. Objectivo: comparar o impacto da Rc nos doentes de baixo risco cardiovascular versus risco moderado/alto, segundo os critérios a AAcPR, de forma a avaliar o real benefício da Rc na capacidade de exercício nos doentes de baixo risco, quantificada por prova de esforço cardiorrespiratória (PecR). Métodos: Análise retrospetiva dos doentes submetidos a Rc após ScA e submetidos a PecR antes e após a integração num programa de treino de exercício supervisionado constituído por 36 sessões. Foram incluídos doentes desde janeiro de 2004 a dezembro de 2013, num centro Hospitalar Terciário. Os doentes foram divididos em dois grupos: grupo de risco cardiovascular baixo (GRB) e grupo de doentes com risco moderado a alto (GRMA) de acordo com os critérios da AAcPR. Os parâmetros avaliados na PecR foram: pico de consumo de oxigénio (pVO2), pVO2 em relação ao valor previsto para idade e género (%pVO2), declive da rampa do equivalente ventilatório de dióxido de carbono (Ve/VcO2slope), (Ve/VcO2slope)/pVO2 e potência circulatória de pico (PcP). Resultados: Foram incluídos em programa de Rc, pós ScA, 129 doentes, 86,0% do género masculino, com idade média de 56,3±9,8 anos. Setenta e nove doentes (61,3%) foram incluídos no grupo de baixo risco e 50 doentes (38,7%) no grupo de risco moderado a alto.Comparando os resultados da PecR basal verifica-se uma melhor capacidade funcional nos indivíduos de baixo risco (pVO2 26,7±7,0 versus 23,9±5,7 ml/kg/min; p=0,019). Esta diferença significativa desapareceu após a conclusão do programa de Rc, apresentando o GRB pVO2 final de 28,5±7,3ml/kg/min e o GRMA 27,0±7,0ml/kg/min (p=0,232). Ao confrontar os parâmetros da prova de esforço cardiorrespiratória prévios e após reabilitação cardíaca, verifica-se, em ambos os grupos, um aumento significativo da capacidade funcional expresso pelo aumento do pVO2, (Ve/VcO2slope)/pVO2, PcP e duração da prova. No entanto, apenas no grupo de baixo risco se evidencia uma diminuição signi-ficativa do Ve/VcO2 slope (26,7±6,2 versus 25,7±5,3; p=0,029). A amplitude da melhoria de pVO2 foi menos marcada no GRB (1,8±6,5 ml/kg/min versus 3,1±5,0 ml/kg/min; p=0.133). Um incremento no pVO2 superior a 10% em relação ao valor inicial foi atingido em 41,8% dos doentes no GRB e 58,0% dos doentes no GRMA (p=0,072). Conclusão: independentemente do grau de risco cardiovascular inicial, existe benefício na capacidade funcional de exercício após programa de Rc com 36 sessões de treino de exercício, objetivamente quantificado pelos parâmetros da PecR. No entanto, esta melhoria é mais acentuada nos indivíduos de risco moderado a alto comparativamente aos indivíduos de baixo risco. Atendendo à limitação de recursos, deverá ser privilegiada a inclusão de indivíduos de moderado e alto risco, não subvalorizando, no entanto, o benefício também alcançado pelos indivíduos de baixo risco cardiovascular

Synthesis, antitubercular activity and mechanism of resistance of highly effective thiacetazone analogues

Defining the pharmacological target(s) of currently used drugs and developing new analogues with greater potency are both important aspects of the search for agents that are effective against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Thiacetazone (TAC) is an anti-tubercular drug that was formerly used in conjunction with isoniazid, but removed from the antitubercular chemotherapeutic arsenal due to toxic side effects. However, several recent studies have linked the mechanisms of action of TAC to mycolic acid metabolism and TAC-derived analogues have shown increased potency against M. tuberculosis. To obtain new insights into the molecular mechanisms of TAC resistance, we isolated and analyzed 10 mutants of M. tuberculosis that were highly resistant to TAC. One strain was found to be mutated in the methyltransferase MmaA4 at Gly101, consistent with its lack of oxygenated mycolic acids. All remaining strains harbored missense mutations in either HadA (at Cys61) or HadC (at Val85, Lys157 or Thr123), which are components of the bhydroxyacyl-ACP dehydratase complex that participates in the mycolic acid elongation step. Separately, a library of 31 new TAC analogues was synthesized and evaluated against M. tuberculosis. Two of these compounds, 15 and 16, exhibited minimal inhibitory concentrations 10-fold lower than the parental molecule, and inhibited mycolic acid biosynthesis in a dose-dependent manner. Moreover, overexpression of HadAB HadBC or HadABC in M. tuberculosis led to high level resistance to these compounds, demonstrating that their mode of action is similar to that of TAC. In summary, this study uncovered new mutations associated with TAC resistance and also demonstrated that simple structural optimization of the TAC scaffold was possible and may lead to a new generation of TAC-derived drug candidates for the potential treatment of tuberculosis as mycolic acid inhibitors