Background: Direct Acting Antivirals (DAAs) represent a large improvement in the treatment of chronic hepatitis C, resulting in <90% sustained virological response (SVR). There are no reports on the real-world DAA response for Mexico and few reports exist for Latin America. The aim of the study was to report SVR, and immediate benefits with the DAA treatments sofosbuvir, ledispavir, with/without ribavirin (SOF/LDV ± RBV) and ombitasvir, paritaprevir, ritonavir, dasabuvir with/without RBV (OBV/PTV/r/DSV ± RBV) in patients with viral genotype 1a or 1b, and who did not respond to previous peginterferon/ribavirin (PegIFNα2a+RBV) therapy.
Methods: A descriptive, ambispective, longitudinal study was conducted. A cohort of 261 adult patients received PegIFNα2a+RBV therapy before 2014; 167 (64%) did not respond, 83 of these were subsequently treated with SOF/LDV ± RBV or OBV/PTV/r/DSV ± RBV. Child-Pugh-Score (CPS), Fibrosis-4 (FIB-4), and AST to Platelet Ratio Index (APRI) were evaluated before and after treatment.
Results: SVR with PegIFNα2a+RBV was 36%, and 97.5% with DAAs. CPS, FIB-4 and APRI improved significantly after DAA treatment, mainly because of liver transaminase reduction.
Conclusions: DAA treatment showed excellent SVR rates in Mexican patients who had not responded to PegIFNα2a+RBV therapy. Improvement in CPS, FIB-4 and APRI without improvement in fibrosis was observed in cirrhotic and non-cirrhotic patients, as well as considerable reduction in liver transaminases, which suggests a reduction in hepatic necroinflammation.
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http://dx.doi.org/10.7717/peerj.12051 | DOI Listing |
Water Res
December 2024
Guangdong Key Laboratory of Environmental Pollution and Health, College of Environment and Climate, Jinan University, Guangzhou 511443, China. Electronic address:
Persulfate-based advanced oxidation processes (PS-AOPs) are considered as efficient techniques for the degradation of contaminants, whereas the effective activation methods for reactive oxygen species (ROS) generation play vital roles in PS-AOPs. However, the internal electric field mediated activation methods, like introducing chemicals and materials, are often restricted by their intrinsic properties. Conversely, the introduction of external fields can provide extra energy to remarkably enhance the PS activation performance from outside, acting as an additional impetus to promote the cleavage of OO bond and thus improve the generation efficiency of ROS.
View Article and Find Full Text PDFSci Rep
December 2024
Departamento de Astronomía, Universidad de Chile, Casilla 36-D, Santiago, Chile.
Multiple physiological traits correlates with lifespan, being unclear both the causal connection among them and with the process of ageing. In this paper, we show that six traits (such as metabolic rate, mass, heart rate, etc) acting at the system level, are all related to lifespan thru the existence of an approximately constant number of respiration cycles in a lifespan ([Formula: see text]), therefore, we find that those relationships are not independently related to ageing. In addition, we study if the approximately constant [Formula: see text] is possibly linked with the end-of-lifespan somatic mutation burden, another number recently found to be approximately constant (Cagan, Nature 604:517-524, 2022).
View Article and Find Full Text PDFNat Commun
December 2024
Architecture and Dynamics of Biological Macromolecules, Institut Pasteur, Université Paris Cité, CNRS UMR 3528, Paris, France.
Replication Protein A (RPA) plays a pivotal role in DNA replication by coating and protecting exposed single-stranded DNA, and acting as a molecular hub that recruits additional replication factors. We demonstrate that archaeal RPA hosts a winged-helix domain (WH) that interacts with two key actors of the replisome: the DNA primase (PriSL) and the replicative DNA polymerase (PolD). Using an integrative structural biology approach, combining nuclear magnetic resonance, X-ray crystallography and cryo-electron microscopy, we unveil how RPA interacts with PriSL and PolD through two distinct surfaces of the WH domain: an evolutionarily conserved interface and a novel binding site.
View Article and Find Full Text PDFHere we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.
View Article and Find Full Text PDFACS Infect Dis
December 2024
Chemistry and Biotechnology Science and Engineering Program, College of Science, The University of Alabama in Huntsville, Huntsville, Alabama 35899, United States.
New World alphaviruses, including Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV), are mosquito-transmitted viruses that cause disease in humans. These viruses are endemic to the western hemisphere, and disease in humans may lead to encephalitis and long-term neurological sequelae. There are currently no FDA-approved vaccines or antiviral therapeutics available for the prevention or treatment of diseases caused by these viruses.
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