Ranibizumab versus Bevacizumab for Neovascular Age-related Macular Degeneration: Results from the GEFAL Noninferiority Randomized Trial.

OBJECTIVE: To evaluate the relative efficacy and safety profile of bevacizumab versus ranibizumab intravitreal injections for the treatment of neovascular age-related macular degeneration (AMD). DESIGN: Multicenter, prospective, noninferiority, double-masked, randomized clinical trial performed in 38 French ophthalmology centers. The noninferiority limit was 5 letters. PARTICIPANTS: Patients aged ≥50 years were eligible if they presented with subfoveal neovascular AMD, with best-corrected visual acuity (BVCA) in the study eye of between 20/32 and 20/320 measured on the Early Treatment of Diabetic Retinopathy Study chart and a lesion area of less than 12 optic disc areas (DA). METHODS: Patients were randomly assigned to intravitreal administration of bevacizumab (1.25 mg) or ranibizumab (0.50 mg). Hospital pharmacies were responsible for preparing, blinding, and dispensing treatments. Patients were followed for 1 year, with a loading dose of 3 monthly intravitreal injections, followed by an as-needed regimen (1 injection in case of active disease) for the remaining 9 months with monthly follow-up. MAIN OUTCOME MEASURES: Mean change in visual acuity at 1 year. RESULTS: Between June 2009 and November 2011, 501 patients were randomized. In the per protocol analysis, bevacizumab was noninferior to ranibizumab (bevacizumab minus ranibizumab +1.89 letters; 95% confidence interval [CI], -1.16 to +4.93, P < 0.0001). The intention-to-treat analysis was concordant. The mean number of injections was 6.8 in the bevacizumab group and 6.5 in the ranibizumab group (P = 0.39). Both drugs reduced the central subfield macular thickness, with a mean decrease of 95 μm for bevacizumab and 107 μm for ranibizumab (P = 0.27). There were no significant differences in the presence of subretinal or intraretinal fluid at final evaluation, dye leakage on angiogram, or change in choroidal neovascular area. The proportion of patients with serious adverse events was 12.6% in the bevacizumab group and 12.1% in the ranibizumab group (P = 0.88). The proportion of patients with serious systemic or ocular adverse events was similar in both groups. CONCLUSIONS: Bevacizumab was noninferior to ranibizumab for visual acuity at 1 year with similar safety profiles. Ranibizumab tended to have a better anatomic outcome. The results are similar to those of previous head-to-head studies. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Adenosquamous carcinoma of the head and neck: report of 20 cases and review of the literature.

PURPOSE: To assess the clinical profile and prognostic factors in patients with adenosquamous carcinoma (ASC) of the head and neck treated by surgery and/or radiation therapy with or without chemotherapy. METHODS: Data from 20 patients with stage I-II (n = 4), III (n = 5), or IVA (n = 11) head and neck ASC, treated between 1989 and 2010 were collected in a retrospective multicenter Rare Cancer Network study. Surgery was performed in 16 patients. Seventeen patients received combined modality treatment. RESULTS: After a median follow-up of 15.5 months, 12 patients recurred. The 3-year and median overall survival, disease-free survival (DFS), and loco-regional control were 52% and 39 months, 32% and 12 months, and 47% and 33 months respectively. In multivariate analysis, DFS was negatively influenced by the presence of extracapsular extension and advanced stage. CONCLUSION: Overall prognosis of locoregionally advanced ASC remains poor. However, early stage ASC patients managed with combined modality treatment may have prolonged DFS.

PPARγ Agonist-Induced Fluid Retention Depends on αENaC Expression in Connecting Tubules.

BACKGROUND/AIMS: Thiazolidinediones (TZDs, like rosiglitazone (RGZ)) are peroxisome proliferator-activated receptor γ (PPARγ) agonists used to treat type 2 diabetes. Clinical limitations include TZD-induced fluid retention and body weight (BW) increase, which are inhibited by amiloride, an epithelial-sodium channel (ENaC) blocker. RGZ-induced fluid retention is maintained in mice with αENaC knockdown in the collecting duct (CD). Since ENaC in the connecting tubule (CNT) rather than in CD appears to be critical for normal NaCl retention, we aimed to further explore the role of ENaC in CNT in RGZ-induced fluid retention. METHODS: Mice with conditional inactivation of αENaC in both CNT and CD were used (αENaC lox/lox AQP2-Cre; 'αENaC-CNT/CD-KO') and compared with littermate controls (αENaC lox/lox mice; 'WT'). BW was monitored and total body water (TBW) and extracellular fluid volume (ECF) were determined by bioelectrical impedance spectroscopy (BIS) before and after RGZ (320 mg/kg diet for 10 days). RESULTS: On regular NaCl diet, αENaC-CNT/CD-KO had normal BW, TBW, ECF, hematocrit, and plasma Na(+), K(+), and creatinine, associated with an increase in plasma aldosterone compared with WT. Challenging αENaC-CNT/CD-KO with a low NaCl diet unmasked impaired NaCl and K homeostasis, consistent with effective knockdown of αENaC. In WT, RGZ increased BW (+6.1%), TBW (+8.4%) and ECF (+10%), consistent with fluid retention. These changes were significantly attenuated in αENaC-CNT/CD-KO (+3.4, 1.3, and 4.3%). CONCLUSION: Together with the previous studies, the current results are consistent with a role of αENaC in CNT in RGZ-induced fluid retention, which dovetails with the physiological relevance of ENaC in this segment. © 2014 S. Karger AG, Basel.

Dinâmica físico-hídrica de uma toposseqüência de solos sob Savana Florestada (Cerradão) em Assis, SP

Este trabalho teve como objetivo a caracterização morfológica e físico-hídrica de uma toposseqüência de solos sob floresta nativa de uma parcela permanente de 320 x 320 m, instalada na Estação Ecológica de Assis (SP). A vegetação da parcela consiste em um remanescente de Savana Florestada (Cerradão) da zona limítrofe sul do grande domínio do Cerrado. O estudo da geometria bidimensional (horizontal e vertical) dos horizontes em uma toposseqüência possibilitou o detalhamento da morfologia do solo. Para estudar a dinâmica da água no ambiente de desenvolvimento das plantas nativas, foram obtidas curvas de retenção, análise granulométrica e medidas de condutividade hidráulica saturada no campo, utilizando o permeâmetro de Guelph. O monitoramento da umidade do solo in situ, utilizando o sensor WCR, e da distribuição de chuvas foi realizado no período de novembro de 2003 a novembro de 2004. Os solos foram classificados de montante a jusante em Latossolo Vermelho, Latossolo Vermelho-Amarelo, Latossolo Amarelo e Gleissolo Háplico. O alto teor de argila no horizonte de subsuperfície do Gleissolo, em contraste aos Latossolos com maior teor de areia, determina menor drenagem, maior retenção hídrica e baixa condutividade hidráulica nesta camada, não atingindo a saturação em nenhum momento do ano monitorado. O comportamento físico-hídrico dos solos é influenciado pelas condições do relevo, evidenciado pela transição lateral contínua de cor, textura e estrutura dos solos na toposseqüência, e pela pluviosidade. Em superfície, ocorre uma oscilação da umidade do solo intimamente ligada a eventos chuvosos. Em subsuperfície, este efeito é menos intenso, sendo deslocado no tempo. A disponibilidade de água em toda a toposseqüência é limitada na estação seca e também em parte da estação úmida, o que deve definir as características florísticas da formação florestal da parcela e determinar a distribuição espacial do mosaico vegetacional.

Atividade e especiação química na solução afetadas pela adição de fósforo em latossolo sob plantio direto em diferentes condições de acidez

No sistema plantio direto (SPD), ocorre acúmulo superficial de resíduos de culturas e de nutrientes, especialmente P e Ca, que contribuem para a inativação do Al3+ em solução. Assim, a presença desse elemento no solo não indica, necessariamente, que ocorre fitotoxidez, visto que ânions orgânicos e inorgânicos alteram a dinâmica do Al livre em solução, reduzindo sua atividade. Nestas condições, o conhecimento da atividade e da especiação iônica em solução pode ser útil para o entendimento da sua dinâmica no solo. No presente trabalho, determinaram-se a atividade e a especiação de íons na solução de um Latossolo, cultivado, há sete anos, no sistema plantio direto em diferentes condições de acidez provocadas pela adição anterior (1994) de doses de calcário. Feita a caracterização química do solo do experimento, amostras indeformadas foram coletadas em colunas de PVC rígido, onde se aplicaram, na superfície: 0, 40, 80, 160, 320, 640, 1.280 e 2.560 mg L-1 de P em solução, com posterior incubação, por 30 dias. Extraiu-se a solução do solo por centrifugação, determinando-se os atributos de acidez, os cátions e os ânions para estimar a atividade e especiação iônica em solução, utilizando o programa Visual Minteq A2. Com a aplicação das doses de P, houve decréscimo no teor de Al no solo e na sua atividade em solução. O aumento de P na solução não afetou, de forma direta, a inativação de Al, uma vez que não houve formação de fosfatos de Al. No entanto, os ânions orgânicos e inorgânicos, deslocados do complexo de troca pelo fosfato, foram efetivos na complexação do Al em solução.

Lack of the mitochondrial protein acylglycerol kinase causes Sengers syndrome.

Exome sequencing of an individual with congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis, all typical symptoms of Sengers syndrome, discovered two nonsense mutations in the gene encoding mitochondrial acylglycerol kinase (AGK). Mutation screening of AGK in further individuals with congenital cataracts and cardiomyopathy identified numerous loss-of-function mutations in an additional eight families, confirming the causal nature of AGK deficiency in Sengers syndrome. The loss of AGK led to a decrease of the adenine nucleotide translocator in the inner mitochondrial membrane in muscle, consistent with a role of AGK in driving the assembly of the translocator as a result of its effects on phospholipid metabolism in mitochondria.

Promoción de la lectura en las bibliotecas públicas de Cataluña: evaluación y resultados

Se presentan los resultados de una encuesta realizada en 2009 entre las 320 bibliotecas públicas de Cataluña sobre las prácticas de evaluación de las acciones de promoción de la lectura. Los resultados se basan tanto en los datos cuantitativos como en las opiniones y las valoraciones del personal directivo de las bibliotecas en torno a estas actividades.

Mutation hot spots in 5q31-linked corneal dystrophies.

Mutations in the BIGH3 gene on chromosome 5q31 cause four distinct autosomal dominant diseases of the human cornea: granular (Groenouw type I), Reis-Bücklers, lattice type I, and Avellino corneal dystrophies. All four diseases are characterized by both progressive accumulation of corneal deposits and eventual loss of vision. We have identified a specific recurrent missense mutation for each type of dystrophy, in 10 independently ascertained families. Genotype analysis with microsatellite markers surrounding the BIGH3 locus was performed in these 10 families and in 5 families reported previously. The affected haplotype could be determined in 10 of the 15 families and was different in each family. These data indicate that R555W, R124C, and R124H mutations occurred independently in several ethnic groups and that these mutations do not reflect a putative founder effect. Furthermore, this study confirms the specific importance of the R124 and R555 amino acids in the pathogenesis of autosomal dominant corneal dystrophies linked to 5q.