Vision Screening in Children Aged 6 Months to 5 Years: Evidence Report and Systematic Review for the US Preventive Services Task Force

Importance: Preschool vision screening could allow detection and treatment of vision abnormalities during a critical developmental stage, preserving function and quality of life. Objective: To review the evidence on screening for and treatment of amblyopia, its risk factors, and refractive error in children aged 6 months to 5 years to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, CINAHL, and trial registries through June 2016; references; and experts, with surveillance of the literature through June 7, 2017. Study Selection: English-language randomized clinical trials (RCTs) or prospective cohort studies that evaluated screening, studies evaluating test accuracy, RCTs of treatment vs inactive controls, and cohort studies or case-control studies assessing harms. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Studies were not quantitatively pooled because of clinical and methodological heterogeneity. Main Outcomes and Measures: Visual acuity, amblyopia, school performance, functioning, quality of life, test accuracy, testability, and harms. Results: Forty studies were included (N = 34 709); 34 evaluated test accuracy. No RCTs compared screening with no screening, and no studies evaluated school performance, function, or quality of life. Studies directly assessing earlier or more intensive screening were limited by high attrition. Positive likelihood ratios were between 5 and 10 for amblyopia risk factors or nonamblyogenic refractive error in most studies of test accuracy and were greater than 10 in most studies evaluating combinations of clinical tests. Inability to cooperate may limit use of some tests in children younger than 3 years. Studies with low prevalence (75%). Among children with amblyopia risk factors (eg, strabismus or anisometropia), patching improved visual acuity of the amblyopic eye by a mean of less than 1 line on a standard chart after 5 to 12 weeks for children pretreated with glasses (2 RCTs, 240 participants); more children treated with patching than with no patching experienced improvement of at least 2 lines (45% vs 21%; P = .003; 1 RCT, 180 participants). Patching plus glasses improved visual acuity by about 1 line after 1 year (0.11 logMAR [95% CI, 0.05-0.17]) for children not pretreated with glasses (1 RCT, 177 participants). Glasses alone improved visual acuity by less than 1 line after 1 year (0.08 logMAR [95% CI, 0.02-0.15], 1 RCT, 177 participants). Conclusions and Relevance: Studies directly evaluating the effectiveness of screening were limited and do not establish whether vision screening in preschool children is better than no screening. Indirect evidence supports the utility of multiple screening tests for identifying preschool children at higher risk for vision problems and the effectiveness of some treatments for improving visual acuity outcomes

FLORISTIC AND STRUCTURAL CHANGES IN AN OMBROPHYLLOUS MIXED FOREST BETWEEN THE YEARS 1979 AND 2000

Com o objetivo de estudar as altera\ue7\uf5es flor\uedsticas e estruturais ocorridas em uma Floresta Ombr\uf3fila Mista, localizada na Esta\ue7\ue3o Experimental da UFPR (S\ue3o Jo\ue3o do Triunfo-PR), nove parcelas de 1 ha cada, avaliadas inicialmente em 1979, foram remedidas em 2000. Em 1979, todos os indiv\uedduos arb\uf3reos com DAP igual ou superior a 20 cm foram identificados e etiquetados e tiveram as suas alturas total e comercial e o di\ue2metro medidos. Em 2000, usando os mesmos crit\ue9rios de inclus\ue3o, os indiv\uedduos que n\ue3o haviam sido computados em 1979 foram considerados como ingressos e os n\ue3o-encontrados como mortos. Em 1979, foram encontradas 2.133 indiv\uedduos, 51 esp\ue9cies e 29 fam\uedlias. No levantamento realizado em 2000, foram encontradas 2.202 indiv\uedduos, 55 esp\ue9cies e 31 fam\uedlias. As fam\uedlias Araucariaceae, Aquifoliaceae, Lauraceae, Sapindaceae, Myrtaceae e Canellaceae foram as mais expressivas em termos de quantidade de indiv\uedduos em ambos os levantamentos. Embora nas duas ocasi\uf5es, houvesse mais que cinquenta esp\ue9cies, apenas sete esp\ue9cies ( Araucaria angustifolia , Ilex dumosa , Matayba elaeagnoides , Ocotea porous , Capsicodendron dinisii , Nectandra grandiflora and Campomanesia xanthocarpa ) representavam 80,4% dos indiv\uedduos em 1979 e, no ano 2000, as mesmas sete esp\ue9cies acrescidas de Ocotea corymbosa responderam por 80,9% do n\ufamero total de indiv\uedduos. Hovenia dulcis (uva-do-jap\ue3o), esp\ue9cie ex\uf3tica, pelo n\ufamero de indiv\uedduos adultos e de regenera\ue7\ue3o, passou a configurar como uma invasora importante do ecossistema. Todos os indicadores estruturais analisados mostraram que a comunidade amadureceu no per\uedodo estudado e que Araucaria angustifolia acentuou sua domin\ue2ncia. Houve um aumento sens\uedvel no grau de ocupa\ue7\ue3o, indicado pela domin\ue2ncia absoluta que passou de 23,52 m2/ha, em 1979, para 28,53 m2/ha em 2000, ou seja, houve um aumento de 21,3%. Isso indica que essa comunidade est\ue1 em processo de desenvolvimento, ainda n\ue3o se encontrando completamente estocada. Ficou evidenciado tamb\ue9m que a domin\ue2ncia da arauc\ue1ria se acentuou no per\uedodo, sendo bem prov\ue1vel que tal domin\ue2ncia venha a aumentar ainda mais no futuro. Em rela\ue7\ue3o \ue0 diversidade, observou-se que os \uedndices que consideram tanto a quantidade de esp\ue9cies (riqueza) como a uniformidade da distribui\ue7\ue3o da densidade, ou seja, os \uedndices de Simpson, U e D de McIntosh, s\ue3o os que melhor representam as altera\ue7\uf5es ocorridas no per\uedodo.The floristic and structure alterations were studied in an Ombrophyllous Mixed Forest located in S\ue3o Jo\ue3o do Triunfo (Paran\ue1 State - Brazil). Nine plots of 1ha, first evaluated in 1979, were recovered and, measured in 2000. In 1979,all the trees with dbh3 20 cm were identified and tagged, and they had their commercial height and diameter measured. In 2000, based on the same criteria described before, the trees which had not been counted in 1979 were considered as ingrowth, and the missing ones were considered mortality. In 1979, 2133 individuals, 51 species and 29 families were found and in the 2000 survey, 2202 individuals, 55 species and 31 families ware journal. In both surveys, the families Araucariaceae, Aquifoliaceae, Lauraceae, Sapindaceae, Myrtaceae and Canellaceae were the most represented in terms of quantity of individuals. Although in both times more than 50 species were counted, in 1979 only 7 species ( Araucaria angustifolia , Ilex dumosa , Matayba elaeagnoides , Ocotea porous , Capsicodendron dinisii , Nectandra grandiflora and Campomanesia xanthocarpa ) represented 80.4% of the individuals and, in 2000, the same 7 species plus Ocotea corymbosa covered 80.9% of the total number of individuals. Hovenia dulcis, exotic specie, based on the number of adult and regeneration individuals, became to be seen as a threat to the autocnons species. All the structural indicators which were analyzed showed that the community has become more mature during the studied period and that the Araucaria angustifolia increased its dominance. There was a sensible increase of the occupancy grade, indicated by the absolutely dominance that changes from 23.52 m2/ha in 1979, to 28.53 m2/ha, in 2000, an increase of 21.3%. These results indicate that this community is still in development, and has not yet found its equilibrium. It also demonstrates that the Araucaria dominance increased in this period, suggesting that this profile can even increase future in the future. Regarding to the diversity, it was observed that the indices that consider, the amount of species (richness) and the homogeneity of the density distribution (the indexes of Simpson, U and D of McIntosh) are the ones that best represent the alterations of the period

Lessons learned from additional research analyses of unsolved clinical exome cases

BACKGROUND: Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery. METHODS: We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease. Pilot project data included 74 families, consisting mostly of parent-offspring trios. Analyses performed on a research basis employed both WES from additional family members and complementary bioinformatics approaches and protocols. RESULTS: Analysis of all possible modes of Mendelian inheritance, focusing on both single nucleotide variants (SNV) and copy number variant (CNV) alleles, yielded a likely contributory variant in 36% (27/74) of cases. If one includes candidate genes with variants identified within a single family, a potential contributory variant was identified in a total of ~51% (38/74) of cases enrolled in this pilot study. The molecular diagnosis was achieved in 30/63 trios (47.6%). Besides this, the analysis workflow yielded evidence for pathogenic variants in disease-associated genes in 4/6 singleton cases (66.6%), 1/1 multiplex family involving three affected siblings, and 3/4 (75%) quartet families. Both the analytical pipeline and the collaborative efforts between the diagnostic and research laboratories provided insights that allowed recent disease gene discoveries (PURA, TANGO2, EMC1, GNB5, ATAD3A, and MIPEP) and increased the number of novel genes, defined in this study as genes identified in more than one family (DHX30 and EBF3). CONCLUSION: An efficient genomics pipeline in which clinical sequencing in a diagnostic laboratory is followed by the detailed reanalysis of unsolved cases in a research environment, supplemented with WES data from additional family members, and subject to adjuvant bioinformatics analyses including relaxed variant filtering parameters in informatics pipelines, can enhance the molecular diagnostic yield and provide mechanistic insights into Mendelian disorders. Implementing these approaches requires collaborative clinical molecular diagnostic and research efforts

Modificações florístico-estruturais de um remanescente de Floresta Ombrófila Mista Montana no período entre 1979 e 2000.

The floristic and structure alterations were studied in an Ombrophyllous Mixed Forest located in São João do Triunfo (Paraná State - Brazil). Nine plots of 1ha, first evaluated in 1979, were recovered and, measured in 2000. In 1979, all the trees with dbh ³ 20 cm were identified and  tagged, and they had their commercial height and diameter measured. In 2000, based on the same criteria described before, the trees which had not been counted in 1979 were considered as ingrowth, and the missing ones were considered mortality. In 1979, 2133 individuals, 51 species and 29 families were found and in the 2000 survey, 2202 individuals, 55 species and 31 families ware journal. In both surveys, the families Araucariaceae, Aquifoliaceae, Lauraceae, Sapindaceae, Myrtaceae and Canellaceae were the most represented in terms of quantity of individuals. Although in both times more than 50 species were counted, in 1979 only 7 species (Araucaria angustifolia, Ilex dumosa, Matayba elaeagnoides, Ocotea porous, Capsicodendron dinisii, Nectandra grandiflora and Campomanesia xanthocarpa) represented 80.4% of the individuals and, in 2000, the same 7 species plus Ocotea corymbosa covered 80.9% of the total number of individuals. Hovenia dulcis, exotic specie, based on the number of adult and regeneration individuals, became to be seen as a threat to the autocnons species. All the structural indicators which were analyzed showed that the community has become more mature during the studied period and that the Araucaria angustifolia increased its dominance. There was a sensible increase of the occupancy grade, indicated by the absolutely dominance that changes from 23.52 m2/ha in 1979, to 28.53 m2/ha, in 2000, an increase of 21.3%. These results indicate that this community is still in development, and has not yet found its equilibrium. It also demonstrates that the Araucaria dominance increased in this period, suggesting that this profile can even increase future in the future. Regarding to the diversity, it was observed that the indices that consider, the amount of species (richness) and the homogeneity of the density distribution (the indexes of Simpson, U and D of McIntosh) are the ones that best represent the alterations of the period.Com o objetivo de estudar as alterações florísticas e estruturais ocorridas em uma Floresta Ombrófila Mista, localizada na Estação Experimental da UFPR (São João do Triunfo-PR), nove parcelas de 1 ha cada, avaliadas inicialmente em 1979, foram remedidas em 2000. Em 1979, todos os indivíduos arbóreos com DAP igual ou superior a 20 cm foram identificados e etiquetados e tiveram as suas alturas total e comercial e o diâmetro medidos. Em 2000, usando os mesmos critérios de inclusão, os indivíduos que não haviam sido computados em 1979 foram considerados como ingressos e os não-encontrados como mortos. Em 1979, foram encontradas 2.133 indivíduos, 51 espécies e 29 famílias. No levantamento realizado em 2000, foram encontradas 2.202 indivíduos, 55 espécies e 31 famílias. As famílias Araucariaceae, Aquifoliaceae, Lauraceae, Sapindaceae, Myrtaceae e Canellaceae foram as mais expressivas em termos de quantidade de indivíduos em ambos os levantamentos. Embora nas duas ocasiões, houvesse mais que cinquenta espécies, apenas sete espécies (Araucaria angustifolia, Ilex dumosa, Matayba elaeagnoides, Ocotea porosa, Capsicodendron dinisii, Nectandra grandiflora e Campomanesia xanthocarpa) representavam 80,4% dos indivíduos em 1979 e, no ano 2000, as mesmas sete espécies acrescidas de Ocotea corymbosa responderam por 80,9% do número total de indivíduos. Hovenia dulcis (uva-do-japão), espécie exótica, pelo número de indivíduos adultos e de regeneração, passou a configurar como uma invasora importante do ecossistema. Todos os indicadores estruturais analisados mostraram que a comunidade amadureceu no período estudado e que Araucaria angustifolia acentuou sua dominância. Houve um aumento sensível no grau de ocupação, indicado pela dominância absoluta que passou de 23,52 m2/ha, em 1979, para 28,53 m2/ha em 2000, ou seja, houve um aumento de 21,3%. Isso indica que essa comunidade está em processo de desenvolvimento, ainda não se encontrando completamente estocada. Ficou evidenciado também que a dominância da araucária se acentuou no período, sendo bem provável que tal dominância venha a aumentar ainda mais no futuro. Em relação à diversidade, observou-se que os índices que consideram tanto a quantidade de espécies (riqueza) como a uniformidade da distribuição da densidade, ou seja, os índices de Simpson, U e D de McIntosh, são os que melhor representam as alterações ocorridas no período

Modificações florístico-estruturais de um remanescente de Floresta Ombrófila Mista Montana no período entre 1979 e 2000.

<p>Com o objetivo de estudar as alterações florísticas e estruturais ocorridas em uma Floresta Ombrófila Mista, localizada na Estação Experimental da UFPR (São João do Triunfo-PR), nove parcelas de 1 ha cada, avaliadas inicialmente em 1979, foram remedidas em 2000. Em 1979, todos os indivíduos arbóreos com DAP igual ou superior a 20 cm foram identificados e etiquetados e tiveram as suas alturas total e comercial e o diâmetro medidos. Em 2000, usando os mesmos critérios de inclusão, os indivíduos que não haviam sido computados em 1979 foram considerados como ingressos e os não-encontrados como mortos. Em 1979, foram encontradas 2.133 indivíduos, 51 espécies e 29 famílias. No levantamento realizado em 2000, foram encontradas 2.202 indivíduos, 55 espécies e 31 famílias. As famílias Araucariaceae, Aquifoliaceae, Lauraceae, Sapindaceae, Myrtaceae e Canellaceae foram as mais expressivas em termos de quantidade de indivíduos em ambos os levantamentos. Embora nas duas ocasiões, houvesse mais que cinquenta espécies, apenas sete espécies (<em>Araucaria angustifolia, Ilex dumosa, Matayba elaeagnoides, Ocotea porosa, Capsicodendron dinisii, Nectandra grandiflora </em>e <em>Campomanesia xanthocarpa</em>) representavam 80,4% dos indivíduos em 1979 e, no ano 2000, as mesmas sete espécies acrescidas de <em>Ocotea corymbosa</em> responderam por 80,9% do número total de indivíduos. <em>Hovenia</em><em> dulcis</em> (uva-do-japão), espécie exótica, pelo número de indivíduos adultos e de regeneração, passou a configurar como uma invasora importante do ecossistema. Todos os indicadores estruturais analisados mostraram que a comunidade amadureceu no período estudado e que <em>Araucaria</em><em> angustifolia</em> acentuou sua dominância. Houve um aumento sensível no grau de ocupação, indicado pela dominância absoluta que passou de 23,52 m²/ha, em 1979, para 28,53 m²/ha em 2000, ou seja, houve um aumento de 21,3%. Isso indica que essa comunidade está em processo de desenvolvimento, ainda não se encontrando completamente estocada. Ficou evidenciado também que a dominância da araucária se acentuou no período, sendo bem provável que tal dominância venha a aumentar ainda mais no futuro. Em relação à diversidade, observou-se que os índices que consideram tanto a quantidade de espécies (riqueza) como a uniformidade da distribuição da densidade, ou seja, os índices de Simpson, <em>U</em> e <em>D</em> de McIntosh, são os que melhor representam as alterações ocorridas no período.</p

Repeated and Interrupted Resistance Exercise Induces the Desensitization and Re-Sensitization of mTOR-Related Signaling in Human Skeletal Muscle Fibers

The acute resistance exercise (RE)-induced phosphorylation of mTOR-related signaling proteins in skeletal muscle can be blunted after repeated RE. The time frame in which the phosphorylation (p) of mTORS2448, p70S6kT421/S424, and rpS6S235/236 will be reduced during an RE training period in humans and whether progressive (PR) loading can counteract such a decline has not been described. (1) To enclose the time frame in which pmTORS2448, prpS6S235/236, and pp70S6kT421/S424 are acutely reduced after RE occurs during repeated RE. (2) To test whether PR will prevent that reduction compared to constant loading (CO) and (3) whether 10 days without RE may re-increase blunted signaling. Fourteen healthy males (24 &plusmn; 2.8 yrs.; 1.83 &plusmn; 0.1 cm; 79.3 &plusmn; 8.5 kg) were subjected to RE with either PR (n = 8) or CO (n = 6) loading. Subjects performed RE thrice per week, conducting three sets with 10&ndash;12 repetitions on a leg press and leg extension machine. Muscle biopsies were collected at rest (T0), 45 min after the first (T1), seventh (T7), 13th (T13), and 14th (X-T14) RE session. No differences were found between PR and CO for any parameter. Thus, the groups were combined, and the results show the merged values. prpS6S235/236 and pp70s6kT421/S424 were increased at T1, but were already reduced at T7 and up to T13 compared to T1. Ten days without RE re-increased prpS6S235/236 and pp70S6kT421/S424 at X-T14 to a level comparable to that of T1. pmTORS2448 was increased from T1 to X-T14 and did not decline over the training period. Single-fiber immunohistochemistry revealed a reduction in prpS6S235/236 in type I fibers from T1 to T13 and a re-increase at X-T14, which was more augmented in type II fibers at T13 (p &lt; 0.05). The entity of myofibers revealed a high heterogeneity in the level of prpS6S235/236, possibly reflecting individual contraction-induced stress during RE. The type I and II myofiber diameter increased from T0 and T1 to T13 and X-T14 (p &lt; 0.05) prpS6S235/236 and pp70s6kT421/S424 reflect RE-induced states of desensitization and re-sensitization in dependency on frequent loading by RE, but also by its cessation