A Multi-epitope Vaccine Candidate Against Bolivian Hemorrhagic fever Caused by Machupo Virus.

Bolivian hemorrhagic fever (BHF) caused by Machupo virus (MACV) is a New World arenavirus having a reported mortality rate of 25-35%. The BHF starts with fever, followed by headache, and nausea which rapidly progresses to severe hemorrhagic phase within 7 days of disease onset. One of the key promoters for MACV viral entry into the cell followed by viral propagation is performed by the viral glycoprotein (GPC). GPC is post-transcriptionally cleaved into GP1, GP2 and a signal peptide. These proteins all take part in the viral infection in host body. Therefore, GPC protein is an ideal target for developing therapeutics against MACV infection. In this study, GPC protein was considered to design a multi-epitope, multivalent vaccine containing antigenic and immunogenic CTL and HTL epitopes. Different structural validations and physicochemical properties were analysed to validate the vaccine. Docking and molecular dynamics simulations were conducted to understand the interactions of the vaccine with various immune receptors. Finally, the vaccine was codon optimised in silico and along with which immune simulation studies was performed in order to evaluate the vaccine's effectiveness in triggering an efficacious immune response against MACV.

Pomalidomide-Based Regimens for Treatment of Relapsed and Relapsed/Refractory Multiple Myeloma: Systematic Review and Meta-analysis of Phase 2 and 3 Clinical Trials.

INTRODUCTION: Pomalidomide (Pom) has demonstrated synergistic antiproliferative activity in combination regimens as a result of its distinct anticancer, antiangiogenic, and immunomodulatory effects. This review aimed to compare outcome measures of different Pom regimens for relapsed/refractory multiple myeloma. METHODS: A comprehensive literature search identified a total of 1374 studies. Thirty-five studies assessing 4623 subjects met the inclusion criteria: phase 2/3 trial, ≥ 2 prior lines of therapy, and clearly documented efficacy outcomes like overall response rate (ORR), overall survival, and progression-free survival. Statistical analyses for meta-analysis was performed by CMA version 3 and Cochrane Q statistics (P < .05 considered significant, I2 index for heterogeneity). A random effects model was used if there was significant heterogeneity (P ≥ .05 over I2 ≥ 50%). RESULTS: Pooled analysis showed ORR 47.1% across all Pom-based (2- and 3-drug) regimens. Stratified analysis for efficacy outcomes (pooled ORR [%] and mean progression-free survival [months]) are reported. With doublet regimen, Pom with low-dose dexamethasone (LoDex) was the most common regimen (35.7%, 6.1 months), and overall survival was 14.37 months. With triplet regimens, pooled ORR was 61.9% (I2 = 87.3%). These included bortezomib + Pom + LoDex (83.5%, 15.7 months), carfilzomib-Pom + LoDex (77.1%, 15.3 months), Pom + LoDex-bendamustine (74.2%), Pom-dexamethasone-daratumumab (64.5%), Pom + LoDex-cyclophosphamide (59.4%, 9.5 months), and Pom + LoDex-doxorubicin (32%). Leading adverse events were myelosuppression, with mean incidences of grade 3 or higher neutropenia, anemia, and thrombocytopenia of 47.6%, 26.5%, and 20.8%, respectively. Mean incidence of grade 3 or higher nonhematologic adverse events were infections 29.1%, pneumonia 13.8%, and fatigue 10%. CONCLUSION: Three-drug Pom regimens yielded double the response rates compared to Pom + LoDex (pooled ORR, 61.9% vs. 35.7%), with bortezomib + Pom + LoDex and carfilzomib-Pom + LoDex demonstrating better outcomes than other regimens.

Fatty acid profile and effect of fish fermented silage on digestive enzymes in Labeo rohita / Perfil de ácidos graxos e efeito de peixe fermentado em silagem de enzimas digestivas em Labeo rohita

Due to inconsistency in demand and supply of fishmeal there is immense need of alternate protein sources. Present project was therefore designed to replace costly fishmeal (FM) with low-priced fermented fish silage (FFS) in fish feed. Fermented fish silage was prepared by fermentation process using Lacto bacillus bacteria and its fatty acid profile and effect on digestive system of Labeo rohita was investigated. Lipid contents were isolated by Soxhlet apparatus and recorded as 6.23 ± 1.23 g/100g of fermented fish silage (FFS). Fatty acid profile of extracted Lipids was determined by gas liquid chromatography (GLC), sufficient amount of unsaturated fatty acids were found with pattern mono unsaturated fatty acids (MUFA) > saturated fatty acids (SFA) >poly unsaturated fatty acids (PUFA). Three treatment diets containing 100% silage (T1), 75% silage (T2) and 50% silage (T3) were prepared by mixing it with soybean meal (SBM) and rice bran as co-ingredients while fermented fish silage was replaced by fishmeal in control diet (T0). The experiment was conducted in glass aquaria in triplicate. Fish growth parameters were recorded fortnightly while physicochemical parameters of water were recorded on daily basis. After completion of feeding trial, three fish were randomly dissected to excise out their intestines and determine activity for protease, amylase and lipase enzymes. Non-significant differences (P<0.05) were recorded in growth parameters and enzymatic activity among all diets except lipase enzyme. Deceptively, it can be concluded that FFS has reasonable concentration of nutrients and unsaturated fatty acids so it can successfully replace fishmeal in fish diets.

Devido à diferença na procura e na oferta de farinha de peixe há imensa necessidade de qualquer membro suplente da fonte de proteína. Tão presente projeto foi projetada para substituir a dispendiosa farinha de peixe (FM) com barato peixe fermentado de ensilagem (FFS) em alimentos para peixes. FFS foi preparado pelo processo de fermentação usando Lactobacillus bactérias e seu perfil de ácidos graxos e efeito sobre o sistema digestivo de Labeo rohita foi investigado. Conteúdo lipídico foram isoladas pelo aparelho de Soxhlet e registadas como 6,23 ± 1,23 g/100g de FFS. Perfil de ácidos graxos extraídos de lipídios foi determinada por cromatografia líquida de gás (GLC). Quantidade suficiente de ácidos graxos insaturados foram encontrados com padrão MUFA > SFA > AGPI. Tratamento de três dietas contendo silagem de 100% (T1), 75% silagem (T2) e 50% silagem (T3) foram preparados misturando com farinha de soja (SBM) e farelo de arroz como co ingredientes enquanto FFS foi substituído pela FM na dieta controle (T0). O experimento foi conduzido em aquários de vidro em triplicado. O Crescimento dos peixes foram anotados os parâmetros quinzenal enquanto parâmetros físico-químicos de água foram registradas diariamente. Após a conclusão do teste de alimentação, três peixes foram aleatoriamente dissecada a impostos especiais de consumo os seus intestinos e determinar a atividade de protease, enzimas amilase e lipase. As variações não significativas (P<0,05) foi registrada em parâmetros de crescimento e atividade enzimática entre as dietas exceto enzima lipase mostrou diferença significativa entre as dietas de tratamento. Aparentemente, é possível concluir que a concentração razoável de FFS tem nutrientes e ácidos graxos insaturados de modo que ela possa substituir com êxito a farinha de peixe na dieta de peixes.