Hepatitis C Virus Infection Treatment: Recent Advances and New Paradigms in the Treatment Strategies

The advancement in hepatitis C virus (HCV) therapeutics has been profoundly enhanced by an improved understanding of viral life cycle in host cells, development of novel direct-acting antivirals (DAAs), and exploring other emerging treatment paradigms on the horizon. The approvals of first-, second-, and next-wave direct-acting antivirals highlight the swift pace of progress in the successful development of an expanding variety of therapeutic regimens for use in patients with chronic hepatitis C virus infection. Triple or quadruple therapies based on a combination of different direct-acting antivirals with or without pegylated interferon (IFN) and ribavirin (RBV) have raised the hopes to improve the current treatment strategies for other difficult-to-treat individuals. The development of more efficacious, well-tolerated, and cost-effective interferons with a low frequency of adverse events and short treatment durations is also in the pipeline. An experimental protective vaccine against hepatitis C virus demonstrated promise in preliminary human safety trials, and a larger phase II clinical trials are under consideration to further determine the efficacy of the vaccine. This pragmatic book chapter discusses the current state of knowledge in hepatitis C virus therapeutics and provides a conceptual framework of emerging and investigational treatment strategies directed against this silent epidemic

Genetics of drought tolerance at seedling and maturity stages in Zea mays L.

Shortage of irrigation water at critical growth stages of maize is limiting its production worldwide. Breeding drought-tolerant cultivars is one possible solution while identification of potential genotypes is crucial for genetic improvement. To assess genetic variation for seedling-stage drought tolerance, we tested 40 inbred lines in a completely randomized design under glasshouse conditions. From these, two contrasting inbred lines were used to develop six basic generations (P1, P2, F1, F2, BC1F1, BC2F2). These populations were then evaluated in a triplicated factorial randomized complete block design under non-stressed and drought-stressed conditions. For statistical analyses, a nested block design was employed to ignore the replication effects. Significant differences (p≤0.01) were recorded among the genotypes for investigated seedling-traits. Absolute values of fresh root length, fresh root weight, and dry root weight lead to select two genotypes, one tolerant (WFTMS) and one susceptible (Q66). Estimates of heritability, genetic advance, and genotypic correlation coefficients were higher and significant for most of the seedling-traits. Generation variance analysis revealed additive gene action. Narrow-sense heritability [F2 ≥ 65; F∞ ≥ 79] revealed the same results. Generation mean analysis signified additive genetic effects in the inheritance of cob girth, non-additive for plant height, grains per ear row and grain yield per plant, and environmental for ear leaf area, cob length, grain rows per ear, biomass per plant, and 100-grain weight under drought-stressed conditions. For conferring drought-tolerance in maize, breeders can adopt the recombinant breeding strategy to pyramid the desirable genes

Survival Analysis of Dialysis Patients Under Parametric and Non-Parametric Approaches

Dialysis is a recommended way of treatment for end stage kidney diseases and it provides a life saving procedure. Transplantation can also be useful source but it is restricted by financial limitations especially in developing countries like Pakistan. Censoring is an important part of the survival data which causes insensitivity to the usual procedures of analysis. A little work has been done in literature regarding the estimated survival time of dialysis patients in Pakistan. So, this study has estimated the median survival time of male/females patients separately by parametric and non-parametric approaches. Moreover, comparison of survival time to patients (50 years) was also compared. Frequently, in modeling the survival data, most of the time we have no prior information about the theoretical distribution of survival time is available, that’s why, and non-parametric methods are commonly used. The significance of this study is the fitting of probability distribution of real life time data of dialysis patients which is not done before. It is very laborious job to fit an appropriate distribution of the data. We find that the probability distribution of our real life time data is weibull distribution. Finding suggested that the Kaplan-Meier method and weibull model based on Anderson-Darling test provided a very close estimate of the survival function in both genders and age groups. On the average survival time in males is relatively high but not statistically different from females

Recent Advances in Angiogenesis Assessment Methods and their Clinical Applications

Angiogenesis, a natural phenomenon of developing new blood vessels, is an integral part of normal developmental processes as well as numerous pathological states in humans. The angiogenic assays are reliable predictors of certain pathologies in particular tumor growth, metastasis, inflammation, wound healing, tissue regeneration, ischemia, cardiovascular, and ocular diseases. The angiogenic inducer and inhibitor studies rely on both in vivo and in vitro angiogenesis methods, and various animal models are also standardized to assess qualitative and quantitative angiogenesis. Analogously, the discovery and development of anti-angiogenic agents are also based on the choice of suitable angiogenic assays and potential drug targeted sites within the angiogenic process. Similarly, the selection of cell types and compatible experimental conditions resembling the angiogenic disease being studied are also potential challenging tasks in recent angiogenesis studies. The imaging analysis systems for data acquisition from in vivo, in vitro, and in ova angiogenesis assay to preclinic, and clinical research also requires novel but easy-to-use tools and well-established protocols. The proposition of this pragmatic book chapter overviews the recent advances in angiogenesis assessment methods and discusses their applications in numerous disease pathogenesis

Balancing science and public policy in Pakistan\u27s COVID-19 response

Background: Coronavirus disease 2019 (COVID-19) has affected the world in an unprecedented manner and South Asian countries were among the first to experience imported cases. Pakistan\u27s response to COVID-19 has been under scrutiny for its granularity, reach and impact.Aims: to evaluate objectively the chronology and depth of the response to COVID-19 in Pakistan.Methods: We evaluated available national and subnational epidemiological and burden information on COVID-19 cases and deaths in Pakistan, including projection models available to the Government at an early stage of the pandemic.Results: Pakistan, with a population of 215 million and considerable geographic diversity, experienced case introduction from pilgrims returning from the Islamic Republic of Iran, followed by widespread community transmission. The National Command and Operations Centre, established through civilian and military partnership, was critical in fast tracking logistics, information gathering, real-time reporting and smart lockdowns, coupled with a massive cash support programme targeting the poorest sections of society. Cases peaked in June 2020 but the health system was able to cope with the excess workload. Since then, although testing rates remain low (\u3e 300 000 cases confirmed to date), case fatality rates have stabilized, and with 6300 deaths, Pakistan seems to have flattened the COVID-19 curve.Conclusion: Despite notable successes in controlling the pandemic, several weaknesses remain and there are risks of rebound as the economy and educational systems reopen. There is continued need for strong technical and programmatic oversight, linked to civic society engagement and working with religious scholars to ensure nonpharmacological intervention compliance

Balancing science and public policy in Pakistan\u27s COVID-19 response

Background: Coronavirus disease 2019 (COVID-19) has affected the world in an unprecedented manner and South Asian countries were among the first to experience imported cases. Pakistan\u27s response to COVID-19 has been under scrutiny for its granularity, reach and impact.Aims: to evaluate objectively the chronology and depth of the response to COVID-19 in Pakistan.Methods: We evaluated available national and subnational epidemiological and burden information on COVID-19 cases and deaths in Pakistan, including projection models available to the Government at an early stage of the pandemic.Results: Pakistan, with a population of 215 million and considerable geographic diversity, experienced case introduction from pilgrims returning from the Islamic Republic of Iran, followed by widespread community transmission. The National Command and Operations Centre, established through civilian and military partnership, was critical in fast tracking logistics, information gathering, real-time reporting and smart lockdowns, coupled with a massive cash support programme targeting the poorest sections of society. Cases peaked in June 2020 but the health system was able to cope with the excess workload. Since then, although testing rates remain low (\u3e 300 000 cases confirmed to date), case fatality rates have stabilized, and with 6300 deaths, Pakistan seems to have flattened the COVID-19 curve.Conclusion: Despite notable successes in controlling the pandemic, several weaknesses remain and there are risks of rebound as the economy and educational systems reopen. There is continued need for strong technical and programmatic oversight, linked to civic society engagement and working with religious scholars to ensure nonpharmacological intervention compliance

Effect of Salinity Stress on Physiological Changes in Winter and Spring Wheat

Salinity is a leading threat to crop growth throughout the world. Salt stress induces altered physiological processes and several inhibitory effects on the growth of cereals, including wheat (Triticum aestivum L.). In this study, we determined the effects of salinity on five spring and five winter wheat genotypes seedlings. We evaluated the salt stress on root and shoot growth attributes, i.e., root length (RL), shoot length (SL), the relative growth rate of root length (RGR-RL), and shoot length (RGR-SL). The ionic content of the leaves was also measured. Physiological traits were also assessed, including stomatal conductance (gs), chlorophyll content index (CCI), and light-adapted leaf chlorophyll fluorescence, i.e., the quantum yield of photosystem II (Fv′/Fm′) and instantaneous chlorophyll fluorescence (Ft). Physiological and growth performance under salt stress (0, 100, and 200 mol/L) were explored at the seedling stage. The analysis showed that spring wheat accumulated low Na+ and high K+ in leaf blades compared with winter wheat. Among the genotypes, Sakha 8, S-24, W4909, and W4910 performed better and had improved physiological attributes (gs, Fv′/Fm′, and Ft) and seedling growth traits (RL, SL, RGR-SL, and RGR-RL), which were strongly linked with proper Na+ and K+ discrimination in leaves and the CCI in leaves. The identified genotypes could represent valuable resources for genetic improvement programs to provide a greater understanding of plant tolerance to salt stress.Salinity is a leading threat to crop growth throughout the world. Salt stress induces altered physiological processes and several inhibitory effects on the growth of cereals, including wheat (Triticum aestivum L.). In this study, we determined the effects of salinity on five spring and five winter wheat genotypes seedlings. We evaluated the salt stress on root and shoot growth attributes, i.e., root length (RL), shoot length (SL), the relative growth rate of root length (RGR-RL), and shoot length (RGR-SL). The ionic content of the leaves was also measured. Physiological traits were also assessed, including stomatal conductance (gs), chlorophyll content index (CCI), and light-adapted leaf chlorophyll fluorescence, i.e., the quantum yield of photosystem II (Fv′ /Fm′ ) and instantaneous chlorophyll fluorescence (Ft). Physiological and growth performance under salt stress (0, 100, and 200 mol/L) were explored at the seedling stage. The analysis showed that spring wheat accumulated low Na+ and high K+ in leaf blades compared with winter wheat. Among the genotypes, Sakha 8, S-24, W4909, and W4910 performed better and had improved physiological attributes (gs, Fv′ /Fm′, and Ft) and seedling growth traits (RL, SL, RGR-SL, and RGR-RL), which were strongly linked with proper Na+ and K+ discrimination in leaves and the CCI in leaves. The identified genotypes could represent valuable resources for genetic improvement programs to provide a greater understanding of plant tolerance to salt stress

Numerical modelling of coastal structure using SPH-based DualSPHysics model

Coastal structures are implemented along the coasts as measures to counter coastal erosion and the detrimental effects caused by sea waves. In order to maximize the efficiency of these structures, sea conditions during extreme events should be taken into consideration as to avoid the occurrence of wave overtopping, erosion and thus leading to structure failure. This study with the objective to identify the force exerted on several coastal structures and overtopping occurrence under a variety of wave conditions will be compared with the numerical results done by Dang et al., (2021). This study, however, focuses on three different structures; the vertical wall, the trapezoidal wall and the stepped wall, and is simulated using DesignSPHysics, a new addition to the open-source code named DualSPHysics. A simulation with no coastal structure is also presented in this study. The cases take damping systems into account, particularly active wave absorption system. Furthermore, overtopping simulations were conducted as to assess the various structures under the chosen wave conditions. Results signifies that, the stepped wall has the least overtopping occurrence in comparison to the other structures. The simulation presented in this study well replicates that of the study done by Dang et al., (2021)

Colorization and Automated Segmentation of Human T2 MR Brain Images for Characterization of Soft Tissues

Characterization of tissues like brain by using magnetic resonance (MR) images and colorization of the gray scale image has been reported in the literature, along with the advantages and drawbacks. Here, we present two independent methods; (i) a novel colorization method to underscore the variability in brain MR images, indicative of the underlying physical density of bio tissue, (ii) a segmentation method (both hard and soft segmentation) to characterize gray brain MR images. The segmented images are then transformed into color using the above-mentioned colorization method, yielding promising results for manual tracing. Our color transformation incorporates the voxel classification by matching the luminance of voxels of the source MR image and provided color image by measuring the distance between them. The segmentation method is based on single-phase clustering for 2D and 3D image segmentation with a new auto centroid selection method, which divides the image into three distinct regions (gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) using prior anatomical knowledge). Results have been successfully validated on human T2-weighted (T2) brain MR images. The proposed method can be potentially applied to gray-scale images from other imaging modalities, in bringing out additional diagnostic tissue information contained in the colorized image processing approach as described