Efficacy and Safety of Emricasan in Liver Cirrhosis and/or Fibrosis

This study aimed to perform a meta-analysis to determine the efficacy and safety of emricasan. Nine databases were searched for clinical trials investigating the efficacy of emricasan treatment in patients with liver cirrhosis or fibrosis. A manual search was conducted to identify the missing trials. The quality of the included studies was assessed using the revised Cochrane risk of bias tool. Efficacy of emricasan treatment was defined as a positive change in apoptosis-related parameters from baseline to the last follow-up visit. Overall, emricasan treatment is more effective in patients with liver cirrhosis or fibrosis than placebo (standardized mean difference [SMD] [95% confidence intervals (CI)]=0.28 [0.14; 0.41]). No significant change in model for end-stage liver disease (MELD) score between the emricasan and placebo groups was noted (SMD [95% CI]=0.18 [-0.01; 0.36]; p=0.058). A 50 mg dose of emricasan had the highest efficacy rate compared to placebo (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012), followed by the 5 mg dosing regimen (SMD [95% CI]=0.28 [0.06; 0.50]; p=0.012). Treatment with emricasan resulted in significant reductions in ALT (mean difference (MD) [95% CI]=-5.89 [-10.59; -1.20]; p=0.014) and caspase3/7 levels (MD [95%CI]=-1215.93 [-1238.53; -1193.33]; p<0.001), respectively. No significant increase in the rate of overall adverse events was noted (OR [95% CI]=1.52 [0.97; 2.37]; p=0.069). Treatment with emricasan is more effective in improving liver function and apoptosis parameters compared to placebo, with a well-tolerated safety profile. However, due to the poor quality of the analyzed studies, the small number of trials and patients, and the short follow-up periods, more robust trials are still warranted

Existence of Monotone Positive Solution of Neutral Partial Difference Equation

AbstractThis paper is concerned with a class of neutral partial difference equations. The conditions for the existence of monotone eventually positive solutions are established which improve and extend some of the criteria existing in the literature. Comparison theorems are also derived. Results are obtained on the existence of a monotone eventually positive solution of dual equation

Case report: Single-session double-Ilizarov lengthening technique in the treatment of a child with congenital fibular deficiency

BackgroundCongenital fibular deficiency is a rare disease with a broad spectrum of deformities. Associated anomalies complicate the symptoms of patients and, consequently, individualized treatments that aim at normal function and acceptable appearance.Case presentationWe present a case of congenital femoral and fibular shortening in the right lower limb with foot anomaly at school age. The patient underwent limb lengthening procedure in a single session on the right femur and tibia at the same time using a double-Ilizarov frame. The functional and cosmetic of his right lower extremity achieved a good outcome. Complications were minimal except for the superficial infection. Treatment lasted for 9.2 months, allowing for returning the patient to functional activity as soon as possible.ConclusionA satisfactory result was obtained with limb lengthening in a single session using double Ilizarov external fixators in a school-aged patient with congenital fibular deficiency

Clinical assessment of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for endometrial cancer

OBJECTIVE: The aim of this study was to determine the efficacy of 252Californium neutron intracavitary brachytherapy using a two-channel Y applicator combined with external beam radiotherapy for the treatment of endometrial cancer. METHODS: Thirty-one patients with stage I-III endometrial cancer were recruited for this study. The stage I patients received only 252Californium neutron intracavitary brachytherapy with a two-channel applicator. The stage II and III patients received both 252Californium neutron intracavitary brachytherapy using a two-channel applicator and parallel-opposed whole pelvic radiotherapy. RESULTS: The five-year local control rate was 80.6% (25/31), the overall survival rate was 51.6% (16/31), and the disease-free survival rate was 54.8% (17/31). The incidence of serious late complications was 12.9% (4/31). CONCLUSIONS: 252Californium neutron intracavitary brachytherapy using a two-channel applicator combined with external beam radiotherapy was effective for treating endometrial cancer and the incidence of serious late complications related to this combination was within an acceptable range

Multiple Lines of Evidence from Mitochondrial Genomes Resolve Phylogenetic Relationships of Parasitic Wasps in Braconidae

The rapid increase in the number of mitochondrial genomes in public databases provides opportunities for insect phylogenetic studies; but it also provides challenges because of gene rearrangements and variable substitution rates among both lineages and sites. Typically, phylogenetic studies use mitochondrial sequence data but exclude other features of the mitochondrial genome from analyses. Here, we undertook large-scale sequencing of mitochondrial genomes from a worldwide collection of specimens belonging to Braconidae, one of the largest families of Metazoa. The strand-asymmetry of base composition in the mitochondrial genomes of braconids is reversed, providing evidence for monophyly of the Braconidae. We have reconstructed a backbone phylogeny of the major lineages of Braconidae from gene order of the mitochondrial genomes. Standard phylogenetic analyses of DNA sequences provided strong support for both Cyclostomes and Noncyclostomes. Four subfamily complexes, that is, helconoid, euphoroid, sigalphoid, and microgastroid, within the Noncyclostomes were reconstructed robustly, the first three of which formed a monophyletic group sister to the last one. Aphidiinae was recovered as a lineage sister to other groups of Cyclostomes, while the Ichneutinae was recovered as paraphyletic. Separate analyses of the subdivided groups showed congruent relationships, employing different matrices and methods, for the internal nodes of the Cyclostomes and the microgastroid complex of subfamilies. This research, using multiple lines of evidence from mitochondrial genomes, illustrates multiple uses of mitochondrial genomes for phylogenetic inference in Braconidae

Overexpression of the Tomato Pollen Receptor Kinase LePRK1 Rewires Pollen Tube Growth to a Blebbing Mode

The tubular growth of a pollen tube cell is crucial for the sexual reproduction of flowering plants. LePRK1 is a pollen-specific and plasma membrane–localized receptor-like kinase from tomato (Solanum lycopersicum). LePRK1 interacts with another receptor, LePRK2, and with KINASE PARTNER PROTEIN (KPP), a Rop guanine nucleotide exchange factor. Here, we show that pollen tubes overexpressing LePRK1 or a truncated LePRK1 lacking its extracellular domain (LePRK1ΔECD) have enlarged tips but also extend their leading edges by producing “blebs.” Coexpression of LePRK1 and tomato PLIM2a, an actin bundling protein that interacts with KPP in a Ca2+-responsive manner, suppressed these LePRK1 overexpression phenotypes, whereas pollen tubes coexpressing KPP, LePRK1, and PLIM2a resumed the blebbing growth mode. We conclude that overexpression of LePRK1 or LePRK1ΔECD rewires pollen tube growth to a blebbing mode, through KPP- and PLIM2a-mediated bundling of actin filaments from tip plasma membranes. Arabidopsis thaliana pollen tubes expressing LePRK1ΔECD also grew by blebbing. Our results exposed a hidden capability of the pollen tube cell: upon overexpression of a single membrane-localized molecule, LePRK1 or LePRK1ΔECD, it can switch to an alternative mechanism for extension of the leading edge that is analogous to the blebbing growth mode reported for Dictyostelium and for Drosophila melanogaster stem cells.Fil: Gui, Cai Ping. Chinese Academy of Sciences; República de ChinaFil: Dong, Xin. Chinese Academy of Sciences; República de ChinaFil: Liu, Hai Kuan. Chinese Academy of Sciences; República de ChinaFil: Huang, Wei Jie. Chinese Academy of Sciences; República de ChinaFil: Zhang, Dong. Chinese Academy of Sciences; República de ChinaFil: Wang, Shu Jie. Chinese Academy of Sciences; República de ChinaFil: Barberini, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; ArgentinaFil: Gao, Xiao Yan. Chinese Academy of Sciences; República de ChinaFil: Muschietti, Jorge Prometeo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; ArgentinaFil: McCormick, Sheila. University of California at Berkeley; Estados UnidosFil: Tang, Wei Hua. Chinese Academy of Sciences; República de China. University of California at Berkeley; Estados Unido

Effects of maternal enflurane exposure on NR2B expression in the hippocampus of their offspring

Este trabalho objetiva o estudo da patogênese de deficiência no aprendizado e memória de prole de ratos resultante da anestesia maternal por enflurano, por meio da expressão da subunidade 2B do receptor do ácidoN-metil-D-aspártico (NR2B) no hipocampo dos filhotes. Dividiram-se, aleatoriamente, 30 fêmeas de ratos Sprague-Dawley em três grupos: controle (grupo C), exposição ao enflurano por 4 h (grupo E1) e por 8 h (grupo E2). De oito a 10 dias após o início da gravidez, os ratos dos grupos E1 e E2 inalaram enflurano 1,7% em 2 L/min de oxigênio, por 4 h e 8 h, respectivamente. Ratos do grupo C inalaram apenas 2 L/min de oxigênio. O labirinto de água de Morris foi empregado para analisar as funções de aprendizado e memória da cria em 20 e 30 dias após o nascimento. Utilizaram-se ensaios de RT-PCR e de imuno-histoquímica para medir os níveis de mRNA e expressão da proteína do NR2B, respectivamente. Em comparação com os ratos controle do grupo C, aqueles dos grupos E1 e E2 exibiram latências de escape mais longas, menor número de travessias na plataforma e menos tempo gasto no quadrante alvo no teste de exploração espacial (P ; 0.05) in terms of mRNA levels and protein expression of NR2B. The cognitive function of the offspring is impaired when maternal rats are exposed to enflurane during early pregnancy. A possible mechanism of this effect is related to the down-regulation of NR2B expression

On the efficacy of anthracene isomers for triplet transmission from CdSe nanocrystals

The effect of isomeric substitutions on the transmitter for triplet energy transfer (TET) between nanocrystal (NC) donor and molecular acceptor is investigated. Each isomeric acceptor is expected to bind in a unique orientation with respect to the NC donor. We see that this orbital overlap drastically affects the transmission of triplets. Here, two functional groups, the carboxylic acid and dithiocarbamate, were varied between the 1-, 2- and 9-positions of the anthracene ring to give three ACA and three ADTC isomers. These six anthracene isomers served as transmitters for triplets between CdSe NC sensitizers and 9,10-diphenylanthracene annihilators for photon upconversion. The photon upconversion quantum yield (QY) is the highest for 9-ACA (12%), lowest for 9-ADTC (0.1%), around 3% for both 1-ACA and 1-ADTC, and about 1% for the 2-isomers. These trends in QYs are reflected in the rates of TET given by ultrafast transient absorption spectroscopy where a maximum of 3.8 × 107 s−1 for 9-ACA was measured. Molecular excited state energy levels were measured both in solution and polymer hosts to correlate structure to TET. This work confirms that anthracene excited states levels are very sensitive to molecular substitution, which in combination with orbital overlap, critically affect Dexter-based TET.Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicada