Visual Performance of Tecnis ZM900 Diffractive Multifocal IOL after 2500 Implants: A 3-Year Followup

Purpose. To evaluate visual performance for near, intermediate, and distant vision; complaints of photic phenomena, and patient satisfaction with the new diffractive multifocal IOL used in eyes which underwent phacoemulsification. Methods. Two thousand and five hundred consecutive eyes undergoing Tecnis ZM900 multifocal IOL implantation were included in this retrospective analysis. The minimum followup of 3 months was required after the surgery. Patients were assessed for uncorrected near visual acuity (UNVA) at a fixed distance (33 cm), uncorrected intermediate visual acuity (UIVA) at 60 cm, and uncorrected distance visual acuity (UDVA). Using a subjective questionnaire, patients satisfaction, their independence from using glasses, and the perception of glare and halo phenomena were also evaluated at the last follow-up. Results. Two thousand and five hundred eyes of 1558 patients underwent cataract surgery and Tecnis ZM900 multifocal IOL implantation. Four hundred and eighty seven patients (31.3%) were men, and 1071 (68.7%) were women. The mean age of the patients was 66.17 years. A UDVA of 20/30 or better was achieved by 85% of eyes. A UNVA of J1 was achieved by 93.7% of eyes and that of J2 or better was achieved by 98%. A UIVA of J4 or better was achieved by 65% and J5 or better was achived by more than 82.8% of the eyes in the study. Glare and halos were reported as severe by only 6.1% and 2.12% of patients, respectively. Ninety seven percent reported complete spectacle independence and 88% stated that they are totally satisfied with their quality of vision and would choose to have the same lens implanted again after the first implant. Five percent of the eyes in the study needed a second procedure (enhancement) to achieve a better visual result. No patient underwent lens exchange. Conclusion. Excellent near, intermediate, and distant vision was observed in patients implanted with the Tecnis ZM900 diffractive multifocal IOL. Spectacle independence and a minimum occurrence of photic phenomena make this IOL an excellent option in patients with cataract

Zika Virus Disrupts Molecular Fingerprinting Of Human Neurospheres

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.7Brazilian Development Bank (BNDES)Funding Authority for Studies and Projects (FINEP)National Council of Scientific and Technological Development (CNPq)Foundation for Research Support in the State of Rio de Janeiro (FAPERJ)Sao Paulo Research Foundation (FAPESP) [14/21035-0, 14/14881-1, 13/08711-3, 14/10068-4]Coordination for the Improvement of Higher Education Personnel (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

NAADP-sensitive two-pore channels are present and functional in gastric smooth muscle cells

Nicotinic acid adenine dinucleotide phosphate (NAADP) has been identified as an important modulator of Ca2+ release from the endo-lysosomal system in a variety of cells by a new and ubiquitous class of endo-lysosomal ion channels known as the two-pore channels (TPCs). However, the role of TPCs in NAADP action in smooth muscle is not known. in the present work, we investigated the effects of NAADP in gastric smooth muscle cells and its ability to release Ca2+ by TPCs. We show that Ca2+ signals mediated by NAADP were inhibited by disrupting Ca2+ handling by either acidic organelles (using bafilomycin A1) or the Endoplasmic Reticulum (using thapsigargin, ryanodine or 2-APB). Transcripts for endogenous TPC1 and TPC2 were readily detected and recombinant TPCs localized to the endosomes and/or lysosomes. Overexpression of wild-type TPCs but not pore mutants enhanced NAADP-mediated cytosolic Ca2+ signals. Desensitizing the NAADP pathway inhibited Ca2+-responses to extracellular stimulation with carbachol but not ATP. Taken together, these results indicate that NAADP likely induces Ca2+ release from the endolysosomal system through TPCs which is subsequently amplified via the ER in an agonist-specific manner. Thus, we suggest a second messenger role for NAADP in smooth muscle cells. (C) 2014 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Biotechnology and Biological Sciences Research CouncilFed Univ São Paulo UNIFESP, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Interdisciplinary Ctr Gene Therapy, BR-04044020 São Paulo, BrazilUniv Oxford, Dept Pharmacol, Oxford OX1 3QT, EnglandUCL, Dept Cell & Dev Biol, London, EnglandFed Univ São Paulo UNIFESP, Dept Pharmacol, São Paulo, BrazilUniversidade Federal de São Paulo, Interdisciplinary Ctr Gene Therapy, BR-04044020 São Paulo, BrazilFAPESP: 2008/11.515-3CNPq: 482030/2010-0CAPES: BB/G013721/1Web of Scienc

Zika virus disrupts molecular fingerprinting of human neurospheres

Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFINANCIADORA DE ESTUDOS E PROJETOS - FINEPFUNDAÇÃO CARLOS CHAGAS FILHO DE AMPARO À PESQUISA DO ESTADO DO RIO DE JANEIRO - FAPERJFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPsem informaçãosem informaçãosem informaçãosem informação14/21035-0; 14/14881-1; 13/08711-3; 14/10068-

Zika virus disrupts molecular fingerprinting of human neurospheres

Submitted by Sandra Infurna ([email protected]) on 2018-04-03T16:26:16Z No. of bitstreams: 1 anamariab_filippis_etal_IOC_2017.pdf: 1347352 bytes, checksum: b3a68b2d8ea28413682153a717faa4c4 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2018-04-03T16:44:04Z (GMT) No. of bitstreams: 1 anamariab_filippis_etal_IOC_2017.pdf: 1347352 bytes, checksum: b3a68b2d8ea28413682153a717faa4c4 (MD5)Made available in DSpace on 2018-04-03T16:44:04Z (GMT). No. of bitstreams: 1 anamariab_filippis_etal_IOC_2017.pdf: 1347352 bytes, checksum: b3a68b2d8ea28413682153a717faa4c4 (MD5) Previous issue date: 2017Instituto D´Or de Pesquisa e Educação. Rio de Janeiro, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Rio de Janeiro, RJ, Brasil.Instituto D´Or de Pesquisa e Educação. Rio de Janeiro, Brasil / Universidade de Campinas. Departamento de Bioquímica e Biologia Tecidual. Campinas, SP, Brasil.Instituto Evandro Chagas. Centro de Inovação Tecnológica. Belém, PA, BrasilInstituto D´Or de Pesquisa e Educação. Rio de Janeiro, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biologia. Rio de Janeiro, RJ, BrasilInstituto D´Or de Pesquisa e Educação. Rio de Janeiro, Brasil.Instituto D´Or de Pesquisa e Educação. Rio de Janeiro, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biologia. Rio de Janeiro, RJ, BrasilUniversidade de Campinas. Departamento de Bioquímica e Biologia Tecidual. Campinas, SP, Brasil.Instituto D´Or de Pesquisa e Educação. Rio de Janeiro, Brasil.Fundação Oswaldo Cruz Fiocruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Instituto D´Or de Pesquisa e Educação. Rio de Janeiro, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biologia. Rio de Janeiro, RJ, BrasilUniversidade Federal do Pará. Belém, PA, Brasil.Fundação Oswaldo Cruz Fiocruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Instituto Evandro Chagas. Centro de Inovação Tecnológica. Belém, PA, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Biologia. Rio de Janeiro, RJ, BrasilUniversidade de Campinas. Departamento de Bioquímica e Biologia Tecidual. Campinas, SP, Brasil.Instituto D´Or de Pesquisa e Educação. Rio de Janeiro, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biológicas. Rio de Janeiro, RJ, Brasil.Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it

Comparative genomics uncovers the evolutionary history, demography, and molecular adaptations of South American canids

The remarkable radiation of South American (SA) canids produced 10 extant species distributed across diverse habitats, including disparate forms such as the short-legged, hypercarnivorous bush dog and the long-legged, largely frugivorous maned wolf. Despite considerable research spanning nearly two centuries, many aspects of their evolutionary history remain unknown. Here, we analyzed 31 whole genomes encompassing all extant SA canid species to assess phylogenetic relationships, interspecific hybridization, historical demography, current genetic diversity, and the molecular bases of adaptations in the bush dog and maned wolf. We found that SA canids originated from a single ancestor that colonized South America 3.9 to 3.5 Mya, followed by diversification east of the Andes and then a single colonization event and radiation of Lycalopex species west of the Andes. We detected extensive historical gene flow between recently diverged lineages and observed distinct patterns of genomic diversity and demographic history in SA canids, likely induced by past climatic cycles compounded by human-induced population declines. Genome-wide scans of selection showed that disparate limb proportions in the bush dog and maned wolf may derive from mutations in genes regulating chondrocyte proliferation and enlargement. Further, frugivory in the maned wolf may have been enabled by variants in genes associated with energy intake from short-chain fatty acids. In contrast, unique genetic variants detected in the bush dog may underlie interdigital webbing and dental adaptations for hypercarnivory. Our analyses shed light on the evolution of a unique carnivoran radiation and how it was shaped by South American topography and climate change