Dactylogyrus extensus and Pseudomonas fluorescens are serious pathogens in Cyprinus carpio aquaculture causing severe impacts and substantial economic losses. During the early spring of 2021, abnormal mortalities were reported among farmed C. carpio. Moribund fish showed anorexia, respiratory distress, dermal ulcers, and septicemia. The water analysis revealed low dissolved oxygen (3.4 mg/L), and high un-ionized ammonia levels (0.65 mg/L). Seventy moribund C. carpio specimens were collected and subjected to parasitological and bacteriological examinations. The monogenetic trematode D. extensus was discovered in wet mounts from the gills of all the examined fish samples (100%). The identity of recovered parasites was confirmed by sequencing and alignment of the 28S rDNA gene. P. fluorescens was concurrently identified in the infested fish samples (58.5%) based on phenotypic characteristics using the API20 E. The identity of bacterial isolates was confirmed further by sequencing and alignment of 16S rRNA gene. The IL-1β and MHCII were upregulated in infested fish in tandem with the severity of infections. P. fluorescens isolates displayed high resistance to most of the tested antibiotics. The study is one of the earlier reports on D. extensus and P. fluorescens co-infections in farmed C. carpio and highlights the need of effective control programs to protect fish health and minimize losses.

OBJECTIVE: To evaluate the safety and efficacy of daclatasvir, an HCV NS5A inhibitor with pangenotypic activity, administered with peginterferon-alfa-2a/ribavirin.

DESIGN: In this Phase 2b double-blind, placebo-controlled study, treatment-naive adults with HCV genotype 1 (N=365) or 4 (N=30) infection were randomly assigned (2:2:1) to daclatasvir 20 mg or 60 mg, or placebo once daily plus weekly peginterferon-alfa-2a and twice-daily ribavirin. Daclatasvir recipients achieving protocol-defined response (PDR; HCV-RNA

INTRODUCTION: Globally, it is estimated that 290,000 patients infected with hepatitis C virus (HCV) died from hepatitis C consequences, including cirrhosis and hepatocellular carcinoma in 2019. Although daclatasvir (DCV), combined with sofosbuvir (SOF), is effective in HCV patients, the new pan-genotypic combinations are considered by many as more cost-effective and successful in eradicating HCV infection.

AREAS COVERED: This review discusses the safety, efficacy, and cost-effectiveness of DCV as an HCV treatment option based on real-world studies and pharmacoeconomic evaluations.

EXPERT OPINION: Real-life studies suggest that SOF/DCV has acceptable sustained virological response and can be used successfully to manage HCV. Nonetheless, the use of SOF/DCV is limited by the longer treatment duration in genotype (GT)-3 patients and the need for ribavirin (RBV) in treatment-experienced patients which increases the likelihood of adverse effects. DCV is likely to remain as a therapeutic option for the management of GT-1, GT-2, and GT-4 patients in resource limited settings, while GT-3 patients are more likely to benefit from RBV-free direct-acting antiviral combinations such as SOF/velpatasvir for 12 weeks or glecaprevir/pibrentasvir for 8 weeks. The introduction of generics for these new pan-genotypic drugs would likely eliminate the need for SOF/DCV in the near future.

BACKGROUND: The present work aimed at evaluation of the potential dynamic changes in hepatic fibrosis following treatment of chronic HCV using DAAs in patients coinfected with HIV.

PATIENTS AND METHODS: In total, 50 HCV/HIV coinfected patients [age; 34.68 ± 10.38 years, 82% men] were included. For all included patients, liver stiffness measured using transient elastography as well as serum liver fibrosis scores; [fibrosis-4 (FIB-4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were calculated at baseline and at 12 and 24-weeks following 12 weeks therapy of HCV with once daily sofosbuvir 400 mg plus daclatasvir 60 mg.

RESULTS: Most of the included patients (70%, n = 35) were on anti-retroviral therapy. SVR24 was achieved by 93.48% of the patients. There was significant serial improvement in baseline liver stiffness measurement (LSM), FIB-4 and APRI among responders; [LSM: baseline, 7.05 ± 4.84 kPa vs. 5.66 ± 2.63 kPa at SVR24, p < 0.001], [FIB-4: baseline, 1.24 ± 1.08 vs. 0.93 ± 0.64 at SVR24, p 0.001) and (APRI: baseline, 0.725 ± 0.66 vs. 0.36 ± 0.19at SVR24, p 0.001) respectively.

CONCLUSION: Treatment of HCV patients coinfected with HIV using DAAs is associated with a rapid significant regression in hepatic fibrosis, as evaluated by FibroScan, FIB-4, and APRI scores.

: The present work aimed at evaluation of the potential dynamic changes in hepatic fibrosis following treatment of chronic HCV using DAAs in patients coinfected with HIV. : In total, 50 HCV/HIV coinfected patients [age; 34.68 ± 10.38 years, 82% men] were included. For all included patients, liver stiffness measured using transient elastography as well as serum liver fibrosis scores; [fibrosis-4 (FIB-4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were calculated at baseline and at 12 and 24-weeks following 12 weeks therapy of HCV with once daily sofosbuvir 400 mg plus daclatasvir 60 mg. : Most of the included patients (70%, n = 35) were on anti-retroviral therapy. SVR24 was achieved by 93.48% of the patients. There was significant serial improvement in baseline liver stiffness measurement (LSM), FIB-4 and APRI among responders; [LSM: baseline, 7.05 ± 4.84 kPa vs. 5.66 ± 2.63 kPa at SVR24, p < 0.001], [FIB-4: baseline, 1.24 ± 1.08 vs. 0.93 ± 0.64 at SVR24, p 0.001) and (APRI: baseline, 0.725 ± 0.66 vs. 0.36 ± 0.19at SVR24, p 0.001) respectively. : Treatment of HCV patients coinfected with HIV using DAAs is associated with a rapid significant regression in hepatic fibrosis, as evaluated by FibroScan, FIB-4, and APRI scores.

The discovery of >60 monogenic causes of nephrotic syndrome (NS) has revealed a central role for the actin regulators RhoA/Rac1/Cdc42 and their effectors, including the formin INF2. By whole-exome sequencing (WES), we here discovered bi-allelic variants in the formin DAAM2 in four unrelated families with steroid-resistant NS. We show that DAAM2 localizes to the cytoplasm in podocytes and in kidney sections. Further, the variants impair DAAM2-dependent actin remodeling processes: wild-type DAAM2 cDNA, but not cDNA representing missense variants found in individuals with NS, rescued reduced podocyte migration rate (PMR) and restored reduced filopodia formation in shRNA-induced DAAM2-knockdown podocytes. Filopodia restoration was also induced by the formin-activating molecule IMM-01. DAAM2 also co-localizes and co-immunoprecipitates with INF2, which is intriguing since variants in both formins cause NS. Using in vitro bulk and TIRF microscopy assays, we find that DAAM2 variants alter actin assembly activities of the formin. In a Xenopus daam2-CRISPR knockout model, we demonstrate actin dysregulation in vivo and glomerular maldevelopment that is rescued by WT-DAAM2 mRNA. We conclude that DAAM2 variants are a likely cause of monogenic human SRNS due to actin dysregulation in podocytes. Further, we provide evidence that DAAM2-associated SRNS may be amenable to treatment using actin regulating compounds.

A multi-core processor is an Integrated Circuit (IC) which two or more processors have been attached inside a single package for enhanced performance, reduced power consumption, and more efficient simultaneous processing of multiple tasks. [n fact, the chip power consumption is limited by cooling system level capacity. The air cooling limitation is already reached in 2006. The CPU reaches the maximum operational temperature after certain time due to maximum CPU utilization, thus the CPU utilization is reduced to the safe utilization in order not to exceed the power limit, and this phenomenon is called CPU thermal throttling. The cores thermal problem is managed by adding temperature constraints through a threshold temperature (maximum temperature). This problem is related to the power consumption management that is a function of the operating frequency of each core where damaging one core means damaging the whole chip. The current software solutions of thermal management problems are not effective as they are slow and don' t take into the consideration the mutual heat transfer between the cores i.e. the correlation. Therefore, a hardware solution is proposed in this paper that takes into consideration the mutual heat transfer between the cores. This solution is built using the three dimensional fuzzy logic controller. The obtained results prove that the 3-D fuzzy logic controller is able to process the multicore CPU correlation information to improve the thermal management response and reduce the air cooling limitation effect. The controller is implemented using FPGAs technology where different architectures are explored according to the given constraints.

This study aimed to illustrate the use of D-optimal mixture design (DOMD) for optimization of an enhancer containing Dapsone niosomal formula for acne topical treatment. Mixture components (MixCs) studied were: Span 20, Cholesterol, and Cremophor RH. Different responses were measured. Optimized formula (OF) was selected to minimize particle size and maximize absolute zeta potential and entrapment efficiency. Optimized formula gel (OF-gel) was prepared and characterized. OF-gel in vivo skin penetration using confocal laser scanning microscopy and activity against in acne mouse model were studied. Based on DOMD results analysis, adequate models were derived. Piepel and contour plots were plotted accordingly to explain how alteration in MixCs L-pseudo values affected studied responses and regions for different responses' values. The OF had suitable predicted responses which were in good correlation with the actually measured ones. The OF-gel showed suitable characterization and in vivo skin penetration up to the dermis layer. In vivo acne mouse-model showed that OF-gel-treated group (OF-gel-T-gp) had significantly better recovery (healing) criteria than untreated (UT-gp) and Aknemycin-treated (A-T-gp) groups. This was evident in significantly higher reduction of inflammation percent observed in OF-gel-T-gp than both UT-gp and A-T-gp. Better healing in OF-gel-T-gp compared with other groups was also verified by histopathological examination. Moreover, OF-gel-T-gp and A-T-gp bacterial loads were non-significantly different from each other but significantly lower than UT-gp. Thus, DOMD was an adequate statistical tool for optimization of an appropriate enhancer containing Dapsone niosomal formula that proved to be promising for topical treatment of acne.