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    Lonafarnib (Zokinvy™) is an orally active farnesyltransferase inhibitor developed by Eiger BioPharmaceuticals under license from Merck & Co. for the treatment of hepatitis D virus (HDV) infections, and progeria and progeroid laminopathies. The drug was originally discovered by Merck & Co as an investigational drug in oncology. In progeria, lonafarnib inhibits farnesyltransferase to prevent farnesylation and subsequent accumulation of progerin and progerin-like proteins in the nucleus and cellular cytoskeleton. In November 2020, lonafarnib received its first approval in the USA to reduce the risk of mortality in Hutchinson-Gilford Progeria Syndrome (HGPS) and for the treatment of processing-deficient progeroid laminopathies (with either heterozygous LMNA mutation with progerin-like protein accumulation, or homozygous or compound heterozygous ZMPSTE24 mutations) in patients ≥ 12 months of age with a body surface area (BSA) of ≥ 0.39 m2. Lonafarnib is under regulatory review in the European Union. Clinical development for the treatment of HDV infections is underway in multiple countries. This article summarizes the milestones in the development of lonafarnib leading to this first approval.Nowadays when conventional plastic is being looked as a menace, the possibility of it being replaced with polyhydroxyalkanoates (PHAs) which are biodegradable, environment friendly and biocompatible thermoplastics is not remote. PHAs are a fascinating group of biopolyesters stored within the cytoplasm of numerous bacterial cells as energy and carbon reserves. PHAs signify the best promising biological substitute to certain conventional petrochemical plastics which have wide range of applications in different industries such as biomedical sector, packaging, toners for printing, and adhesives for coating, etc. In the present study, PHAs producing bacterial strains were screened by Sudan black B staining and confirmed by Nile blue A staining. Out of forty bacterial strains showing positive results, six bacterial strains exhibited comparatively higher PHAs production. The highest PHAs producing bacterial strain was identified using 16s rRNA sequencing. Optimization of process parameters was performed by using one factor at a time (OFAT) approach. The isolated bacterium was able to synthesize PHAs when various agro-industrial wastes such as domestic kitchen waste, mixed fruit pulp, sugarcane molasses, and waste flour from bread factory were screened as a carbon substrate in the growth medium. The results showed accumulation of 44.5% PHAs of cell dry weight using domestic kitchen waste as carbon substrate. The characterization of biopolymers was performed using FTIR and XRD analysis. The commercial exploitation of results of this study may serve twin purposes of addressing the challenge of high production cost of PHAs being the major constraint in replacing petro-based plastics as well as address the problem of disposal of recurring domestic kitchen waste and other agro-industrial waste.Campylobacter spp. have been a predominant cause of bacterial foodborne gastroenteritis worldwide, causing substantial costs to public healthcare systems. This study aimed to assess the invasion and pro-inflammatory cytokine production capacity of Campylobacter coli strains isolated in Brazil. A total of 50 C. coli isolated from different sources in Brazil were analyzed for their capacity of invasion in Caco-2 and U-937 cell lines. The production of pro-inflammatory cytokines was quantitatively measured in response to C. coli. All the strains studied showed invasion percentage ≥ 40% in polarized Caco-2 cells. In U-937 cells assay, 35 of 50 C. coli strains studied showed invasion percentage ≥ 50%. A significant increase in IL-8 production by infected U-937 cells was observed for 17.5% of the C. coli isolates. The high percentages of invasion in Caco-2 and U-937 cells observed for all studied strains, plus the increased production of IL-8 by U-937 cells against some strains, highlighted the pathogenic potential of the C. coli studied and bring extremely relevant data since it has never been reported for strains isolated in Brazil and there are a few data for C. coli in the literature.Poultry litter is widely applied as agricultural fertilizer and can affect the soil microbiome through nutrient overload and antibiotic contamination. In this study, we assessed changes in soil bacterial diversity using high-throughput sequencing approaches. Four samples in triplicate were studied soils with short- and long-term fertilization by poultry litter (S1 = 10 months and S2 = 30 years, respectively), a soil inside a poultry shed (S3), and a forest soil used as control (S0). Samples S0, S1, and S2 revealed a relatively high richness, with confirmed operational taxonomic units (OTUs) in the three replicates of each sample ranging from 1243 to 1279, while richness in S3 was about three times lower (466). CID755673 PKD inhibitor The most abundant phyla were Proteobacteria, Bacteroidetes, and Actinobacteria. Acidobacteria, Planctomycetes, and Verrucomicrobia were also abundant but highly diminished in S3, while Firmicutes was less abundant in S0. Changes in bacterial communities were very evident at the genera level. The genera Gaiella, Rhodoplanes, Solirubacter, and Sphingomonas were predominant in S0 but strongly decreased in the other soils. Pedobacter and Devosia were the most abundant in S1 and were diminished in S2, while Herbiconiux, Brevundimonas, Proteiniphilum, and Petrimonas were abundant in S2. The most abundant genera in S3 were Deinococcus, Truepera, Rhodanobacter, and Castellaniella. A predictive analysis of the metabolic functions with Tax4Fun2 software suggested the potential presence of enzymes associated with antibiotic resistance as well as with denitrification pathways, indicating that the S3 soil is a potential source of nitrous oxide, a powerful greenhouse gas.The availability of pangenotypic direct-acting antivirals for treatment of hepatitis C (HCV) has provided an opportunity to simplify patient pathways. Recent clinical practice guidelines have recognised the need for simplification to ensure that elimination of HCV as a public health concern remains a priority. Despite the move towards simplified treatment algorithms, there remains some complexity in the recommendations for the management of genotype 3 patients with compensated cirrhosis. In an era where additional clinical trial data are not anticipated, clinical guidance should consider experience gained in real-world settings. Although more experience is required for some pangenotypic therapeutic options, on the basis of published real-world data, there is already sufficient evidence to consider a simplified approach for genotype 3 patients with compensated cirrhosis. The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need to minimise the need for complex patient pathways and clinical practice guidelines need to continue to evolve in order to ensure that patient outcomes remain optimised.

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