Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents

We have prepared a library of functionalized quinolines through the magnesiation of 7-chloroquinolines under mild conditions, employing both batch and continuous flow conditions. The preparation involved the generation of mixed lithium-magnesium intermediates, which were reacted with different electrophiles. Mixed lithium-zinc reagents allowed the synthesis of halogenated and arylated derivatives. Some of the synthesized 4-carbinol quinolines have shown interesting antiproliferative properties, their hydroxyl group being a suitable amino group bioisostere. We also report a two-step approach for optically active derivatives

Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

Background: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34.68 Early Treatment Diabetic Retinopathy Study letters (20/200.20/50 Snellen equivalent), and central retinal thickness (CRT) 65300 \u3bcm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was 6515-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Results: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n=261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had 6515-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 \u3bcm with DEX 0.7 versus -39.0 \u3bcm with sham(P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. Conclusions: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population

Consumo, degradabilidade ruminal e digestibilidade aparente de fenos de gramíneas do gênero Cynodon e rações concentradas utilizando indicadores internos Nutritional value of Cynodon grass hay. Intake, degradability and apparent digestibility by means of internal markers

Objetivou-se avaliar o consumo, a digestibilidade aparente dos nutrientes e a degradabilidade in situ da matéria seca (MS), proteína bruta (PB) e fibra em detergente neutro (FDN) dos fenos de capins-coastcross e Tifton 85 e de rações contendo quatro níveis de concentrado para animais na fase de recria. A produção fecal foi estimada usando-se as fibras em detergente neutro (FDNi) e em detergente ácido (FDAi) indigestíveis como indicadores internos, obtidos após 144 horas de incubação ruminal. Utilizaram-se cinco bovinos com oito meses de idade e 32 animais não-castrados na fase de recria, todos da raça Nelore, para as avaliações de consumo e digestibilidade. Utilizaram-se três bovinos fistulados no rúmen para estudar a degradação da MS, PB e FDN dos fenos. Os tempos de incubação foram 6, 12, 24, 48, 72, 96, 120 e 144 horas. Os consumos dos nutrientes do feno de capim-coastcross foram menores que os observados para o capim-Tifton 85. As determinações das digestibilidades do feno de capim-coastcross não diferiram entre indicadores, entretanto as do feno de capim-Tifton 85 foram maiores, quando se utilizou como indicador a FDAi. Na fase de recria, todos os coeficientes de digestibilidade foram menores, quando se utilizou a FDNi como indicador. Os fenos apresentaram taxas de degradação para MS, PB e FDN relativamente próximas. Concluiu-se que a FDAi estimou melhor a digestibilidade dos nutrientes.<br>It was aimed to evaluate intake, apparent digestibility and in situ degradability of dry matter (DM), crude protein (CP) and neutral detergent fiber (NDF) of coastcross and Tifton 85' bermudagrass hays, and of diets with four concentrate levels for growing animals. The fecal production was estimated by means of internal markers, indigestible neutral detergent fiber (NDFi) and acid detergent fiber (ADFi), obtained after 144 hours of ruminal incubation. It were used eight months old bovines and 32 non castrated animals in the growing phase, all Nellore, to evaluate intake and digestibility. Three-fistulated rumen bovines were used to study the disappearance of the dry matter (DM), crude protein (CP) and neutral detergent fiber (NDF) of the hays. The incubation times were 6, 12, 24, 48, 72, 96, 120 and 144 hours. The nutrient intakes of coastcross hay were smaller than Tifton 85 values. The DM, NDF and ADF apparent digestibility of the hays did not differ between markers, although the markers did not present statistical difference to estimate the coefficient of digestibility of coastcross hay, though for Tifton 85 nutrient apparent digestibility there was difference presenting larger value for ADFi. In the growing phase, all coefficients of digestibility were smaller when NDFi was used as marker. The degradation rate did not differ among the hays, inside of each studied entity (DM, CP, and NDF)

Erratum to: Measurement of exclusive Υ photoproduction from protons in pPb collisions at s NN = 5.02 TeV (The European Physical Journal C, (2019), 79, 3, (277), 10.1140/epjc/s10052-019-6774-8)

In this article the author name Luigi Calligaris was incorrectly written as A. Calligaris. The original article has been corrected. © CERN for the benefit of the CMS collaboration 2022