MCN portfolio: An efficient portfolio prediction and selection model using multiserial cascaded network with hybrid meta-heuristic optimization algorithm.

Generally, financial investments are necessary for portfolio management. However, the prediction of a portfolio becomes complicated in several processing techniques which may cause certain issues while predicting the portfolio. Moreover, the error analysis needs to be validated with efficient performance measures. To solve the problems of portfolio optimization, a new portfolio prediction framework is developed. Initially, a dataset is collected from the standard database which is accumulated with various companies' portfolios. For forecasting the benefits of companies, a Multi-serial Cascaded Network (MCNet) is employed which constitutes of Autoencoder, 1D Convolutional Neural Network (1DCNN), and Recurrent Neural Network (RNN) is utilized. The prediction output for the different companies is stored using the developed MCNet model for further use. After predicting the benefits, the best company with the highest profit is selected by Integration of Artificial Rabbit and Hummingbird Algorithm (IARHA). The major contribution of our work is to increase the accuracy of prediction and to choose the optimal portfolio. The implementation is conducted in Python platform. The result analysis shows that the developed model achieves 0.89% and 0.56% regarding RMSE and MAE measures. Throughout the analysis, the experimentation of the developed model shows enriched performance.

Primary Care Utilization, Preventative Screening, and Control of Metabolic Syndrome in Metabolic Dysfunction-Associated Steatohepatitis Liver Transplant Recipients.

OBJECTIVES: Patients with pre-transplant metabolic dysfunction-associated steatohepatitis (MASH) are at high risk of metabolic syndrome (MetS) after liver transplant. While many patients are co-managed by a transplant team, most preventative screening and MetS management may occur in the primary care setting. We aimed to evaluate primary care utilization by MASH liver transplant recipients as well as MetS screening and control. METHODS: We conducted a retrospective chart review that included adults who underwent liver transplant for MASH or cryptogenic cirrhosis at a single institution from January 2010 to December 2016, had available primary care data, and at least 36-months of follow-up post-transplant. Measures included primary care utilization, adherence to screening guidelines, and control of MetS. We used Fischer's exact test to explore the association of primary care utilization with screening and control. RESULTS: A total of 37 patients met inclusion criteria with 366 visits reviewed. The median time to first visit was 68 days post-transplant and patients had a median of 9 total visits. Few patients met screening guidelines for diabetes (8.1%) or hyperlipidemia (10.8%). The percentage of patients with control of obesity, hypertension, diabetes, and hyperlipidemia decreased over the 36-month follow-up period. Primary care utilization was not associated with adherence to screening recommendations for diabetes (P = .141) or hyperlipidemia (P = .103). Higher primary care utilization was not associated with control of hypertension (P = .107), diabetes (P = .871), or hyperlipidemia (P = .999). CONCLUSION: More research is needed to investigate barriers to screening and management of MetS conditions in this high-risk patient population in the primary care setting as well as to optimize post-transplant care coordination.

Implementation of a Hepatocellular Carcinoma Surveillance Program in a Community-Based Integrated Health System in Patients With Hepatitis C Cirrhosis.

INTRODUCTION: Underutilization of hepatocellular cancer (HCC) surveillance has been reported, although data evaluating interventions to improve surveillance are sparse. We assessed the effect of a population-based HCC surveillance program on HCC surveillance utilization and outcomes. METHODS: In this retrospective cohort study, we assessed preinclusion and postinclusion HCC surveillance patterns among 597 patients with hepatitis C virus cirrhosis enrolled in a program at an integrated health system between 2013 and 2020. Adequate surveillance was defined as at least 5 surveillance studies within 36 months pre-enrollment and postenrollment; a secondary outcome was proportion of time covered by surveillance over 36 months. Tumor size, stage, and receipt of curative therapy were compared between HCC detected on the first imaging examination (prevalent HCC) and surveillance-detected HCC (incident HCC). We performed Kaplan-Meier analysis and multivariable competing risk analysis to characterize the association between surveillance and mortality. RESULTS: The surveillance program significantly improved surveillance completion (77.6% vs 5.0%, P < 0.001) and proportion time covered (80.9% vs 15.8%, P < 0.001). Compared with prevalent HCC, surveillance-detected cases were more likely unifocal (77.8% vs 44.8%, P < 0.001), early-stage (85.2% vs 44.8%, P < 0.001), with smaller maximum diameter (median 2.3 vs 3.2 cm), and more likely to undergo curative therapy (92.5% vs 72.4% P = 0.010). Survival was improved compared with prevalent cases hazard ratio (HR) 0.23 (0.11-0.51) after adjusting for age and Model for End Stage Liver Disease score. DISCUSSION: Implementation of a population-based program resulted in significant improvement in HCC surveillance use and clinical outcomes among patients with hepatitis C virus cirrhosis. These findings may inform similar interventions by other healthcare systems.

Application of Shape Memory and Self-Healable Polymers/Composites in the Biomedical Field: A Review.

Shape memory-assisted self-healing polymers have drawn attention over the past few years owing to their interdisciplinary and wide range of applications. Self-healing and shape memory are two approaches used to improve the applicability of polymers in the biomedical field. Combining both these approaches in a polymer composite opens new possibilities for its use in biomedical applications, such as the "close then heal" concept, which uses the shape memory capabilities of polymers to bring injured sections together to promote autonomous healing. This review focuses on using shape memory-assisted self-healing approaches along with their respective affecting factors for biomedical applications such as tissue engineering, drug delivery, biomaterial-inks, and 4D printed scaffolds, soft actuators, wearable electronics, etc. In addition, quantification of self-healing and shape memory efficiency is also discussed. The challenges and prospects of these polymers for biomedical applications have been summarized.

AFP-L3 and DCP are superior to AFP in predicting waitlist dropout in HCC patients: Results of a prospective study.

In patients with HCC awaiting liver transplantation (LT), there is a need to identify biomarkers that are superior to AFP in predicting prognosis. AFP-L3 and des-gamma-carboxyprothrombin (DCP) play a role in HCC detection, but their ability to predict waitlist dropout is unknown. In this prospective single-center study commenced in July 2017, 267 HCC patients had all 3 biomarkers obtained at LT listing. Among them, 96.2% received local-regional therapy, and 18.8% had an initial tumor stage beyond Milan criteria requiring tumor downstaging. At listing, median AFP was 7.0 ng/mL (IQR 3.4-21.5), median AFP-L3 was 7.1% (IQR 0.5-12.5), and median DCP was 1.0 ng/mL (IQR 0.2-3.8). After a median follow-up of 19.3 months, 63 (23.6%) experienced waitlist dropout, while 145 (54.3%) received LT, and 59 (22.1%) were still awaiting LT. Using Cox proportional hazards analysis, AFP-L3≥35% and DCP≥7.5 ng/mL were associated with increased waitlist dropout, whereas AFP at all tested cutoffs, including ≥20,≥ 100, and≥250 ng/mL was not. In a multivariable model, AFP-L3≥35% (HR 2.25, p =0.04) and DCP≥7.5 ng/mL (HR 2.20, p =0.02) remained associated with waitlist dropout as did time from HCC diagnosis to listing ≥ 1 year and increasing MELD-Na score. Kaplan-Meier probability of waitlist dropout within 2 years was 21.8% in those with AFP-L3<35% and DCP<7.5 ng/mL, 59.9% with either AFP-L3 or DCP elevated, and 100% for those with both elevated ( p <0.001). In this prospective study, listing AFP-L3% and DCP were superior to AFP in predicting waitlist dropout with the combination of AFP-L3≥35% and DCP≥7.5 ng/mL associated with a 100% risk of waitlist dropout, thus clearly adding prognostic value to AFP alone.

Models to Predict Development or Recurence of Hepatocellular Carcinoma (HCC) in Patients with Advanced Hepatic Fibrosis.

PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the United States (U.S.).1 The purpose of this review is to highlight published models that predict development of HCC and estimate risk of HCC recurrence after treatments. RECENT FINDINGS: There have been several models created for both de novo HCC and HCC recurrence, with the more recent models using a combination of age, sex, decompensation, and laboratory values (platelet count, albumin, bilirubin), and liver disease etiology to predict both 5 and 10-year HCC incidence. For chronic hepatitis C, sustained virologic response has been a useful component of understanding HCC risk reduction. BMI and diabetes have been utilized in non-alcoholic fatty liver disease (NAFLD) models to predict HCC risk. For HCC recurrence after treatment (for both surgical resection and liver transplant), tumor size and number, vascular invasion, alpha-fetoprotein (AFP) and neutrophil to lymphocyte ratio (NLR) are all components of HCC recurrence risk models. Although numerous HCC risk prediction models have been established over the last several years, challenges remain including how to best incorporate these models into clinical practice, improve surveillance for NAFLD-HCC development, and determine timing and duration of post-resection recurrence surveillance.

Microstructural, electrical and biological activity in [Formula: see text] ceramic composites designed for tissue engineering applications.

The article investigates electrically active ceramic composite of [Formula: see text] (HAP) and [Formula: see text] (BST) for biomedical applications. The study is a systematic blend of the materials science aspect of composites with a special focus on the dielectric and biological properties and their relationships. The article emphasized primarily extracting the dielectric constant ([Formula: see text] of the specimens (that lay in the range of 3-65) and related them to microstructural properties like the grain size and at.% of BST. A broad outlook on the importance of [Formula: see text] in determining the suitability of bioceramics for clinical applications is presented. Bioactivity analysis of the specimens led to probing the surface charges (that were negative), and it was found crucial to the growth of dense apatite layers. Furthermore, the cytocompatibility of the specimens displayed cell viability above 100% for Day 1, which increased substantially for Day 3. To reveal other biological properties of the composites, protein adsorption studies using bovine serum albumin (BSA) and fetal bovine serum (FBS) was carried out. Electrostatic interactions govern the adsorption, and the mathematical dependence on surface charges is linear. The protein adsorption is also linearly correlated with the [Formula: see text], intrinsic to the biomaterials. We delve deeper into protein-biomaterials interactions by considering the evolution of the secondary structure of BSA adsorbed into the specimens. Based on the investigations, 20 at.% HAP-80 at.% BST (20H-80B) was established as a suitable composite comprising the desired features of HAP and BST. Such explorations of electrical and biological properties are interesting for modulating the behavior of bioceramic composites. The results project the suitability of 20H-80B for designing electrically active smart scaffolds for the proposed biomedical applications and are expected to incite further clinical trials.

Cancer in People with and without Hepatitis C Virus Infection: Comparison of Risk Before and After Introduction of Direct-Acting Antivirals.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a leading cause of liver cancer. The association of HCV infection with extrahepatic cancers, and the impact of direct-acting antiviral (DAA) treatment on these cancers, is less well known. METHODS: We conducted a cohort study in a healthcare delivery system. Using electronic health record data from 2007 to 2017, we determined cancer incidence, overall and by type, in people with HCV infection and by DAA treatment status. All analyses included comparisons with a reference population of people without HCV infection. Covariate-adjusted Poisson models were used to estimate incidence rate ratios. RESULTS: 2,451 people with HCV and 173,548 people without HCV were diagnosed with at least one type of cancer. Compared with people without HCV, those with HCV were at higher risk for liver cancer [adjusted incidence rate ratio (aIRR) = 31.4, 95% confidence interval (CI) = 28.9-34.0], hematologic cancer (aIRR = 1.3, 95% CI = 1.1-1.5), lung cancer (aIRR = 1.3, 95% CI = 1.2-1.5), pancreatic cancer (aIRR = 2.0, 95% CI = 1.6-2.5), oral/oropharynx cancer (aIRR = 1.4, 95% CI = 1.1-1.8), and anal cancer (aIRR = 1.6, 95% CI = 1.1-2.4). Compared with people without HCV, the aIRR for liver cancer was 31.9 (95% CI = 27.9-36.4) among DAA-untreated and 21.2 (95% CI = 16.8-26.6) among DAA-treated, and the aIRR for hematologic cancer was 1.5 (95% CI = 1.1-2.0) among DAA-untreated and 0.6 (95% CI = 0.3-1.2) among DAA-treated. CONCLUSIONS: People with HCV infection were at increased risk of liver cancer, hematologic cancer, and some other extrahepatic cancers. DAA treatment was associated with reduced risk of liver cancers and hematologic cancers. IMPACT: DAA treatment is important for reducing cancer incidence among people with HCV infection.

Performance study of a sterilization box using a combination of heat and ultraviolet light irradiation for the prevention of COVID-19.

SARS-CoV-2 virus and other pathogenic microbes are transmitted to the environment through contacting surfaces, which need to be sterilized for the prevention of COVID-19 and related diseases. In this study, a prototype of a cost-effective sterilization box is developed to disinfect small items. The box utilizes ultra violet (UV) radiation with heat. For performance assessment, two studies were performed. First, IgG (glycoprotein, a model protein similar to that of spike glycoprotein of SARS-COV-2) was incubated under UV and heat sterilization. An incubation with UV at 70 °C for 15 min was found to be effective in unfolding and aggregation of the protein. At optimized condition, the hydrodynamic size of the protein increased to ~171 nm from ~5 nm of the native protein. Similarly, the OD280 values also increased from 0.17 to 0.78 indicating the exposure of more aromatic moieties and unfolding of the protein. The unfolding and aggregation of the protein were further confirmed by the intrinsic fluorescence measurement and FTIR studies, showing a 70% increase in the ß-sheets and a 22% decrease in the α-helixes of the protein. The designed box was effective in damaging the protein's native structure indicating the effective inactivation of the SARS-COV-2. Furthermore, the incubation at 70 °C for 15 min inside the chamber resulted in 100% antibacterial efficacy for the clinically relevant E.coli bacteria as well as for bacteria collected from daily use items. It is the first detailed performance study on the efficacy of using UV irradiation and heat together for disinfection from virus and bacteria.

Yttrium iron garnet for hyperthermia applications: Synthesis, characterization and in-vitro analysis.

Exclusive magnetocaloric properties of orthoferrites offer advantages for their application in the magnetic hyperthermia as well as imaging applications. In the present study, the effect of yttrium concentration on the magnetic characteristics of the iron oxide based nanomaterials was analyzed to assess their potential for the hyperthermia applications. The Sol-gel method was used to synthesize the Yttrium Iron Garnet (YIG) based nanoparticles, using different molar ratios of Fe and Y precursors, followed by the calcination at 900, 1000 and 1100 °C. XRD analysis determined the formation of the pure phase of yttrium iron garnet Y3Fe5O12 (YIG) at 0.5 molar ratio of yttrium at all the calcination temperatures and pure phase of yttrium iron perovskite YFeO3 (YIP) for 1 molar ratio of yttrium at 1000 and 1100 °C. The mean particle size was observed in the range of 100 to 400 nm. The magnetic characterization studies showed the highest saturation magnetization for the sample containing 0.5 molar ratio of the yttrium calcinated at 1000 °C. The magnetization values were linearly related to the contents of YIG phases in the synthesized samples. Induction heating of YIG resulted in the hyperthermia temperature (42 to 44 °C) in 13 min with the SAR values 114.65 W/g at 1 mg/ml. The prepared samples showed no in-vitro toxic effects on the MG63 cells (>90% cell viability). In addition, in-vitro treatment at hyperthermia temperature for 15 min reduced cell viability of cancer cells (A549) to 55%, while no toxic effect was observed on MG 63 cells. The present study postulates Yttrium Iron Garnet as an effective therapeutic agent for hyperthermia cancer treatment.

Chain-End Modifications and Sequence Arrangements of Antimicrobial Peptoids for Mediating Activity and Nano-Assembly.

Poly(N-substituted glycine) "peptoids" are an interesting class of peptidomimics that can resist proteolysis and mimic naturally found antimicrobial peptides (AMPs), which exhibit wide spectrum activity against bacteria. This work investigates the possibility of modifying peptoid AMP mimics (AMPMs) with aliphatic lipid "tails" to generate "lipopeptoids" that can assemble into micellar nanostructures, and evaluates their antimicrobial activities. Two families of AMPMs with different distributions of hydrophobic and cationic residues were employed-one with a uniform repeating amphiphilicity, the other with a surfactant-like head-to-tail amphiphilicity. To further evaluate the interplay between self-assembly and activity, the lipopeptoids were variously modified at the AMPM chain ends with a diethylene glycol (EG2) and/or a cationic group (Nlys-Nlys dipeptoid) to adjust amphiphilicity and chain flexibility. Self-assembly was investigated by critical aggregation concentration (CAC) fluorescence assays and dynamic light scattering (DLS). The structure of a key species was also verified by small-angle X-ray scattering (SAXS) and cryo-electron microscopy (cryo-EM). To screen for antibacterial properties, we measured the minimum inhibitory concentrations (MIC) against S. aureus, E. coli, and P. aeruginosa. We found that certain combinations of lipid tail and AMPM sequences exhibit increased antibacterial activity (i.e., decreased MICs). Perhaps counter-intuitively, we were particularly interested in increased MICs in combination with low CACs. Concealing antimicrobial interactions due to packing of AMPMs in nano-assemblies could pave the way to AMPMs that may be "inert" even if unintentionally released and prevent microbes from gaining resistance to the lipopeptoids. Overall, incorporation of EG2 significantly improved lipopeptoids packing while the hydrophobic tail length was found to have a major influence over the MIC. One particular sequence, which we named C15-EG2-(kss)4, exhibited a very low CAC of 34 µM (0.0075 wt.%) and a significantly increased MIC above values for the unmodified AMPM. With the sequence design trends uncovered from this study, future work will focus on discovering more species such as C15-EG2-(kss)4 and on investigating release mechanisms and the potency of the released lipopeptoids.

Life Expectancy of Insured People With and Without Hepatitis C Virus Infection, 2007-2017.

Among 25 291 and 4 921 830 people with and without hepatitis C, life expectancy at age 20 increased 1.8 years and 0.3 years from the interferon to interferon-free era, respectively. Increases were highest for racial and/or ethnic minority groups with hepatitis C.

Prevalence of Spontaneous Clearance of Hepatitis C Virus Infection Doubled From 1998 to 2017.

Strategic planning for hepatitis C virus (HCV) screening and treatment requires up-to-date information on the prevalence of HCV spontaneous clearance. Published estimates of HCV spontaneous clearance range from 15% to 60%.1-3 We conducted an observational study over 20 years to evaluate trends in the prevalence of HCV spontaneous clearance. Our goals were to estimate the proportion of HCV-antibody-positive patients who were viremic, and to identify factors associated with viremia, thus facilitating prediction of the number of patients needing treatment.

Hepatitis C treatment uptake and response among human immunodeficiency virus/hepatitis C virus-coinfected patients in a large integrated healthcare system.

U.S. guidelines recommend that patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) be prioritized for HCV treatment with direct-acting antiviral agents (DAAs), but the high cost of DAAs may contribute to disparities in treatment uptake and outcomes. We evaluated DAA initiation and effectiveness in HIV/HCV-coinfected patients in a U.S.-based healthcare system during October 2014-December 2017. Of 462 HIV/HCV-coinfected patients, 276 initiated DAAs (70% cumulative proportion treated over three years). Lower likelihood of DAA initiation was observed among patients with Medicare (government-sponsored insurance) versus commercial insurance (adjusted rate ratio [aRR] = 0.62, 95% CI = 0.46-0.84), patients with drug abuse diagnoses (aRR = 0.72, 95% CI = 0.54-0.97), patients with CD4 cell count <200 cells/µl versus ≥500 (aRR = 0.45, 95% CI = 0.23-0.91), and patients without prior HCV treatment (aRR = 0.68, 95% CI = 0.48-0.97). There were no significant differences in DAA initiation by age, gender, race/ethnicity, socioeconomic status, HIV transmission risk, alcohol use, smoking, fibrosis level, HIV RNA levels, antiretroviral therapy use, hepatitis B infection, or number of outpatient visits. Ninety-five percent of patients achieved sustained virologic response (SVR). We found little evidence of sociodemographic disparities in DAA initiation among HIV/HCV-coinfected patients, and SVR rates were high. Efforts are needed to increase DAA uptake among coinfected Medicare enrollees, patients with drug abuse diagnoses, patients with low CD4 cell count, and patients receiving first-time HCV treatment.

Synthesis, characterization and in vitro analysis of α-Fe2O3-GdFeO3 biphasic materials as therapeutic agent for magnetic hyperthermia applications.

The use of gadolinium orthoferrite for biomedical application like as contrast agents for magnetic resonance imaging (MRI) has been found to be very promising due to its fascinating properties. The present study focuses on the determination of the effect of the gadolinium concentration in the formation biphasic α-Fe2O3-GdFeO3 for hyperthermia applications. An in-situ sol-gel technique was adopted for the synthesis of biphasic orthoferrites with four different gadolinium concentrations. The XRD analysis confirmed the formation of gadolinium orthoferrites after heat treatment at 1000 °C, 1100 °C, and 1200 °C. The presence of α-Fe2O3 in trace amounts was observed in the materials with low gadolinium concentrations. VSM (Vibrating-sample magnetometer) analysis was performed to ensure the magnetic properties of the materials, which were found to be weakly ferromagnetic. The biocompatibility of the materials was investigated through MTT assay and no cytotoxic effect was observed. The assessment of heating ability of the materials was performed under an alternating magnetic field using an induction heating instrument and all the samples showed temperature rise in the range of hyperthermia temperature with a maximum temperature of 55.71 °C in 6 min. The heating experiments at 44 °C in the absence of samples established the vulnerability of cancer cells as compared to normal cells.

Disparities in Initiation of Direct-Acting Antiviral Agents for Hepatitis C Virus Infection in an Insured Population.

OBJECTIVES: The cost of direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV) infection may contribute to treatment disparities. However, few data exist on factors associated with DAA initiation. METHODS: We conducted a retrospective cohort study of HCV-infected Kaiser Permanente Northern California members aged ≥18 during October 2014 to December 2016, using Poisson regression models to evaluate demographic, behavioral, and clinical factors associated with DAA initiation. RESULTS: Of 14 790 HCV-infected patients aged ≥18 (median age, 60; interquartile range, 53-64), 6148 (42%) initiated DAAs. DAA initiation was less likely among patients who were non-Hispanic black (adjusted rate ratio [aRR] = 0.7; 95% confidence interval [CI], 0.7-0.8), Hispanic (aRR = 0.8; 95% CI, 0.7-0.9), and of other minority races/ethnicities (aRR = 0.9; 95% CI, 0.8-1.0) than among non-Hispanic white people and among those with lowest compared with highest neighborhood deprivation index (ie, a marker of socioeconomic status) (aRR = 0.8; 95% CI, 0.7-0.8). Having maximum annual out-of-pocket health care costs >$3000 compared with ≤$3000 (aRR = 0.9; 95% CI, 0.8-0.9) and having Medicare (aRR = 0.8; 95% CI, 0.8-0.9) or Medicaid (aRR = 0.7; 95% CI, 0.6-0.8) compared with private health insurance were associated with a lower likelihood of DAA initiation. Behavioral factors (eg, drug abuse diagnoses, alcohol use, and smoking) were also significantly associated with a lower likelihood of DAA initiation (all P < .001). Clinical factors associated with a higher likelihood of DAA initiation were advanced liver fibrosis, HCV genotype 1, previous HCV treatment (all P < .001), and HIV infection ( P = .007). CONCLUSIONS: Racial/ethnic and socioeconomic disparities exist in DAA initiation. Substance use may also influence patient or provider decision making about DAA initiation. Strategies are needed to ensure equitable access to DAAs, even in insured populations.

Recent advances in conventional and contemporary methods for remediation of heavy metal-contaminated soils.

Remediation of heavy metal-contaminated soils has been drawing our attention toward it for quite some time now and a need for developing new methods toward reclamation has come up as the need of the hour. Conventional methods of heavy metal-contaminated soil remediation have been in use for decades and have shown great results, but they have their own setbacks. The chemical and physical techniques when used singularly generally generate by-products (toxic sludge or pollutants) and are not cost-effective, while the biological process is very slow and time-consuming. Hence to overcome them, an amalgamation of two or more techniques is being used. In view of the facts, new methods of biosorption, nanoremediation as well as microbial fuel cell techniques have been developed, which utilize the metabolic activities of microorganisms for bioremediation purpose. These are cost-effective and efficient methods of remediation, which are now becoming an integral part of all environmental and bioresource technology. In this contribution, we have highlighted various augmentations in physical, chemical, and biological methods for the remediation of heavy metal-contaminated soils, weighing up their pros and cons. Further, we have discussed the amalgamation of the above techniques such as physiochemical and physiobiological methods with recent literature for the removal of heavy metals from the contaminated soils. These combinations have showed synergetic effects with a many fold increase in removal efficiency of heavy metals along with economic feasibility.

No Difference in Effectiveness of 8 vs 12 Weeks of Ledipasvir and Sofosbuvir for Treatment of Hepatitis C in Black Patients.

BACKGROUND & AIMS: Treatment with the combination of ledipasvir and sofosbuvir for 12 weeks has been approved by the Food and Drug Administration for patients with genotype 1 hepatitis C virus (HCV) infection; some patients can be treated with an 8-week course. Guidelines recommend a 12-week treatment course for black patients, but studies have not compared the effectiveness of 8 vs 12 weeks in black patients who are otherwise eligible for an 8-week treatment regimen. METHODS: We conducted an observational study of Kaiser Permanente Northern California members with HCV genotype 1 infection who were eligible for 8 weeks of treatment with ledipasvir and sofosbuvir (treatment-naïve, no cirrhosis, no HIV infection, level of HCV RNA <6 million IU/mL) and were treated for 8 or 12 weeks from October 2014 through December 2016. We used χ2 analyses to compare sustained virologic response 12 weeks after the end of treatment (SVR12) among patients treated for 8 vs 12 weeks, and adjusted Poisson models to identify factors associated with receipt of 12 weeks of therapy among patients eligible for 8 weeks. RESULTS: Of 2653 patients eligible for 8 weeks of treatment with ledipasvir and sofosbuvir, 1958 (73.8%) received 8 weeks of treatment and 695 (26.2%) received 12 weeks; the proportions of patients with SVR12 were 96.3% and 96.3%, respectively (P = .94). Among 435 black patients eligible for the 8-week treatment regimen, there was no difference in the proportions who achieved an SVR12 following 8 vs 12 weeks' treatment (95.6% vs 95.8%; P = .90). Male sex, higher transient elastography or FIB-4 scores, higher INR and level of bilirubin, lower level of albumin, obesity, diabetes, and ≥15 alcohol drinks consumed/week were independently associated with receiving 12 weeks of treatment among patients eligible for the 8-week treatment regimen, but were not associated with reduced SVR12 after 8 weeks of treatment. CONCLUSION: In an observational study of patients who received ledipasvir and sofosbuvir treatment for HCV genotype 1 infection, we found that contrary to guidelines, 8-week and 12-week treatment regimens do not result in statistically significant differences in SVR12 in black patients. Patient characteristics were associated with receipt of 12-week regimens among patients eligible for 8 weeks, but were not associated with reduced SVR12 after 8 weeks. Shorter treatment courses might therefore be more widely used without compromising treatment effectiveness.

Surface Functionalization of Ti6Al4V via Self-assembled Monolayers for Improved Protein Adsorption and Fibroblast Adhesion.

Although metallic biomaterials find numerous biomedical applications, their inherent low bioactivity and poor osteointegration had been a great challenge for decades. Surface modification via silanization can serve as an attractive method for improving the aforementioned properties of such substrates. However, its effect on protein adsorption/conformation and subsequent cell adhesion and spreading has rarely been investigated. This work reports the in-depth study of the effect of Ti6Al4V surface functionalization on protein adsorption and cell behavior. We prepared self-assembled monolayers (SAMs) of five different surfaces (amine, octyl, mixed [1:1 ratio of amine:octyl], hybrid, and COOH). Synthesized surfaces were characterized by Fourier transform infrared-attenuated total reflection (FTIR-ATR) spectroscopy, contact angle goniometry, profilometry, and field emission scanning electron microscopy (FESEM). Quantification of adsorbed mass of bovine serum albumin (BSA) and fibronectin (FN) was determined on different surfaces along with secondary structure analysis. The adsorbed amount of BSA was found to increase with an increase in surface hydrophobicity with the maximum adsorption on the octyl surface while the reverse trend was detected for FN adsorption, having the maximum adsorbed mass on the COOH surface. The α-helix content of adsorbed BSA increased on amine and COOH surfaces while it decreased for other surfaces. Whereas increasing ß-turn content of the adsorbed FN with the increase in the surface hydrophobicity was observed. In FN, RGD loops are located in the ß-turn and consequently the increase in Δ adhered cells (%) was predominantly increased with the increasing Δ ß-turn content (%). We found hybrid surfaces to be the most promising surface modifier due to maximum cell adhesion (%) and proliferation, larger nuclei area, and the least cell circularity. Bacterial density increased with the increasing hydrophobicity and was found maximum for the amine surface (θ = 63 ± 1°) which further decreased with the increasing hydrophobicity. Overall, modified surfaces (in particular hybrid surface) showed better protein adsorption and cell adhesion properties as compared to unmodified Ti6Al4V and can be potentially used for tissue engineering applications.