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Chronic hepatitis C virus (HCV) is common in the Department of Corrections (DOC). Telemedicine is an effective way to treat HCV. The goal of this report was to demonstrate high SVR rate in DOC patients using telemedicine irrespective of the HCV genotype (GT) and DAAs used. Demographic, clinical and laboratory data were prospectively collected. A total of 870 DOC patients were evaluated and completed HCV therapy June 2015-December 2019 with SVR data were included. The mean age was 50 years, 90% were male, 63% were Caucasian, the majority (79%) had GT 1, 92% were treatment naive, and 80% had advanced fibrosis (FIB-4 ≥ 3.25 and/or transient elastography ≥ 9.5 kPa). The overall SVR was 97% and was similar among all DAAs irrespective of age, sex, race, HIV status, fibrosis level, GT, ribavirin use, prior treatment experience or DAA duration. We conclude that HCV treatment in the DOC through telemedicine is achievable and highly effective with overall SVR 97%, irrespective of the underlying GT or DAA regimen used and can eliminate HCV in this microenvironment and reduce the overall burden of HCV.

Liver biopsy and hepatic venous pressure gradient (HVPG), the gold standard for assessing advanced fibrosis (AF) and clinically significant portal hypertension (CSPH), are invasive, costly, and time-consuming.We investigated if the combination of fibrosis index based on 4 factors (FIB-4) and liver stiffness measure (LSM) can identify AF and more importantly, CSPH.Patients with chronic liver disease referred for transjugular liver biopsy were analyzed retrospectively. FIB-4 and LSM were compared with liver histology for diagnosing AF. FIB-4, LSM, and platelet count were compared with HVPG for diagnosing CSPH. Optimal cutoffs for predicting CSPH were determined by grid search. A composite log-odds to predict CSPH was derived from logistic regression using LSM, FIB-4, and gender. Internal bootstrap validation and external validation were performed.A total of 142 patients were included in the derivation; 42.3% had AF, and 11.3% had CSPH using the current gold standards. The area under the receiver operating characteristic curve (AUROC) for LSM, FIB-4, and their combination to predict AF were 0.7550, 0.7049, and 0.7768, respectively. LSM, FIB-4, and platelet count predicted CSPH with AUROC 0.6818, 0.7532, and 0.7240, respectively. LSM plus FIB-4 showed the best performance in predicting CSPH with AUROC 0.8155. Based on LSM, FIB-4, and gender, a novel model-the Portal Hypertension Assessment Tool (PHAT)-was developed to predict CSPH. PHAT score ≥-2.76 predicted CSPH with sensitivity 94%, specificity 67%, positive predictive value 27%, negative predictive value 99%, and accuracy 70%. In internal and external validation, AUROCs for the model were 0.8293 and 0.7899, respectively.A model consisting of FIB-4, LSM, and gender can identify CSPH among patients with chronic liver disease.

The design and implementation of a 16-Bit hack CPU, a modular processor, is presented in this paper. The paper is intended to showcase the process involved in building a complex circuit capable of performing real-world computations, from the most basic component used for digital data representation that is the CMOS. The design methodology used is a bottom-up approach, this starts with the construction of basic gates and moving up to major components like the program counter, ALU, etc. and ends with the complete construction of the CPU using the previously built components in a modular manner. This paper aims to give the reader a complete understanding of the functioning of a simple computer in a digital electronics abstract. This paper will also give an idea about the data flow in a CPU triggered by a CPU. An idea regarding the way a low-level programming language controls this data flow can also be understood. This CPU design is easily implementable on an FPGA and is hence a great tool to teach students about the basics of Computer Architecture and Digital System Design. The CPU reads instructions from the ROM and performs operations using the A register, D register, or the RAM units based on the instruction type. There are mainly two types of instructions, instructions and C instructions. The A instructions have the sole purpose of storing values into the A register while the C instruction can perform multiple operations.

Chronic hepatitis C virus (HCV) is widely prevalent in the Virginia Department of Corrections (DOC). However, sustained virologic response (SVR) with all oral direct-acting antiviral (DAA) therapy is unknown. HCV treatment was provided through telemedicine following guidelines of the American Association for the Study of Liver Diseases and Infectious Diseases Society of America. SVR12 in the DOC was compared in two control groups: privately insured and indigent patients receiving care in HCV treatment clinics by the same providers during the same time period. Of 220 DOC patients, 180 were started on therapy (158 genotype [GT] 1, 15 GT2, and 10 GT3). SVR12 data on GT1 patients who received ledipasvir/sofosbuvir with or without ribavirin (RBV) were 96%, similar to our indigent (95%) and private clinic (93%) patients despite differences in age, gender, treatment experience, FIB-4, and use of RBV. Multiple logistic regression of GT1 patients identified lower FIB-4 ( p = .008) and treatment clinic ( p = .01) as independent predictors of SVR12. HCV treatment in the DOC by telemedicine with DAA is not only feasible but has a very high SVR12 similar to published trials.

alphaA-crystallin is abundant in the lens of the eye and acts as a molecular chaperone by preventing aggregation of denaturing proteins. We previously found that chemical modification of the guanidino group of selected arginine residues by a metabolic alpha-dicarbonyl compound, methylglyoxal (MGO), makes human alphaA-crystallin a better chaperone. Here, we examined how the introduction of additional guanidino groups and modification by MGO influence the structure and chaperone function of alphaA-crystallin. alphaA-crystallin lysine residues were converted to homoarginine by guanidination with o-methylisourea (OMIU) and then modified with MGO. LC-ESI-mass spectrometry identified homoargpyrimidine and homohydroimidazolone adducts after OMIU and MGO treatment. Treatment with 0.25 M OMIU abolished most of the chaperone function. However, subsequent treatment with 1.0 mM MGO not only restored the chaperone function but increased it by approximately 40% and approximately 60% beyond that of unmodified alphaA-crystallin, as measured with citrate synthase and insulin aggregation assays, respectively. OMIU treatment reduced the surface hydrophobicity but after MGO treatment, it was approximately 39% higher than control. FRET analysis revealed that alphaA-crystallin subunit exchange rate was markedly retarded by OMIU modification, but was enhanced after MGO modification. These results indicate a pattern of loss and gain of chaperone function within the same protein that is associated with introduction of guanidino groups and their neutralization. These findings support our hypothesis that positively charged guanidino group on arginine residues keeps the chaperone function of alphaA-crystallin in check and that a metabolic alpha-dicarbonyl compound neutralizes this charge to restore and enhance chaperone function.

Increases in brain cyclooxygenase-2 (COX2) are associated with the central inflammatory response and with delayed neuronal death, events that cause secondary insults after traumatic brain injury. A growing literature supports the benefit of COX2-specific inhibitors in treating brain injuries.DFU [5,5-dimethyl-3(3-fluorophenyl)-4(4-methylsulfonyl)phenyl-2(5)H)-furanone] is a third-generation, highly specific COX2 enzyme inhibitor. DFU treatments (1 or 10 mg/kg intraperitoneally, twice daily for 3 d) were initiated either before or after traumatic brain injury in a lateral cortical contusion rat model.DFU treatments initiated 10 minutes before injury or up to 6 hours after injury enhanced functional recovery at 3 days compared with vehicle-treated controls. Significant improvements in neurological reflexes and memory were observed. DFU initiated 10 minutes before injury improved histopathology and altered eicosanoid profiles in the brain. DFU 1 mg/kg reduced the rise in prostaglandin E2 in the brain at 24 hours after injury. DFU 10 mg/kg attenuated injury-induced COX2 immunoreactivity in the cortex (24 and 72 h) and hippocampus (6 and 72 h). This treatment also decreased the total number of activated caspase-3-immunoreactive cells in the injured cortex and hippocampus, significantly reducing the number of activated caspase-3-immunoreactive neurons at 72 hours after injury. DFU 1 mg/kg amplified potentially anti-inflammatory epoxyeicosatrienoic acid levels by more than fourfold in the injured brain. DFU 10 mg/kg protected the levels of 2-arachidonoyl glycerol, a neuroprotective endocannabinoid, in the injured brain.These improvements, particularly when treatment began up to 6 hours after injury, suggest exciting neuroprotective potential for COX2 inhibitors in the treatment of traumatic brain injury and support the consideration of Phase I/II clinical trials.