The glucosylamine oxidation pathway of vitamin C recycling.

The proposed glucosylamine oxidation pathway (GOP) is a two-step, intraerythrocyte, thermodynamically favorable nonenzymatic reaction that first binds glucose to the N-terminal valine of beta globin (βVal1) to form a closed-chain glucosylamine that can spontaneously reduce oxidized vitamin C to its antioxidant form. This review summarizes analytical, biochemical and clinical research supporting the existence of the GOP and the surprising hypothesis that βVal1 glucosylamine is a reducing agent that works cooperatively with reduced glutathione to dynamically regulate vitamin C recycling during naturally occurring periods of transiently or chronically elevated blood glucose and oxidant production. Rationale for the existence of the GOP is presented from the perspective of the hemoglobin glycation index, a clinically practical biomarker of risk for chronic vascular disease that we propose is mechanistically explained by person-to-person variation in GOP activity.

Hip Fracture Repair by the Post-Call Surgeon: A Multicenter Retrospective Review.

Introduction: The purpose of this study was to evaluate surgeons' ability to perform or supervise a standard operation with agreed-upon radiologic parameters after being on call.

Methods: We reviewed a consecutive series of patients with intertrochanteric hip fractures treated with a fixed angle device at 9 centers and compared corrected tip-apex distance and reduction quality for post-call surgeons versus those who were not. Subgroup analyses included surgeons who operated the night before versus not and attending-only versus resident involved cases.

The Prolonged Terminal Phase of Human Life Induces Survival Response in the Skin Transcriptome.

Human death marks the end of organismal life under conditions such that the components of the human body continue to be alive. Such postmortem cellular survival depends on the nature (Hardy scale of slow-fast death) of human death. Slow and expected death typically results from terminal illnesses and includes a prolonged terminal phase of life.

The Antioxidant Activity and Induction of Apoptotic Cell Death by and sp. Honey Jelly in ORL115 and ORL188 Cells.

Background: Head and neck cancer patients usually need nutritional support due to difficulties in swallowing and chewing. Therefore, this study aimed to formulate and sp. honey jelly (MTJ) as a convenient functional food.

Acute Intermittent Porphyria as a Rare Challenging Neuro-Metabolic Disease; a Case Report.

Porphyria is a challenging metabolic disease due to its heterogeneous presentation symptoms and its difficult diagnosis. Many affected individuals can complain of recurrent neuro-visceral attacks per year, some of which may be persistent and life-threatening, which is confusing if there is no established diagnosis. Although the motor manifestations, autonomic changes and seizure are highly suggestive, the diagnosis is often overlooked and needs confirmatory genetic testing.

Georgia state spinal muscular atrophy newborn screening experience: Screening assay performance and early clinical outcomes.

The purpose of this study is to provide the results of the newborn screening (NBS) program for Spinal Muscular Atrophy (SMA) in the state of Georgia to determine disease incidence, time to diagnosis and treatment, and early outcomes. NBS for SMA was performed using real time PCR assays from February 2019 through February 2020 in a pilot phase of screening. This method continued as part of our official state panel, and here we describe the pilot period as well as the first year of standard screening through February 2021.

Apache Spark and Deep Learning Models for High-Performance Network Intrusion Detection Using CSE-CIC-IDS2018.

Keeping computers secure is becoming challenging as networks grow and new network-based technologies emerge. Cybercriminals' attack surface expands with the release of new internet-enabled products. As many cyberattacks affect businesses' confidentiality, availability, and integrity, network intrusion detection systems (NIDS) show an essential role.

The Impact of Nutritional Status on the Outcome of Transcatheter Aortic Valve Implantation.

Background: The present study aims to evaluate how nutritional status may affect transcatheter aortic valve implantation (TAVI) outcomes.

Materials And Methods: This is a retrospective study of 383 TAVI patients. In-hospital, 1-month, and 12-month survival was evaluated.

Reducing Narcotic Usage With 0.5% Bupivacaine Periarticular Injections in Total Knee Arthroplasty.

Background: Periarticular injections (PAIs) and adductor canal blocks (ACBs) are widely accepted pain management strategies for total knee arthroplasty (TKA); however, the optimal anesthetic concentration to provide adequate pain relief while avoiding toxicity remains controversial. The purpose of this study is to evaluate the efficacy of different anesthetic concentrations for PAI alone and in combination with ACB.

Methods: This retrospective cohort study of patients undergoing primary TKAs between January 2019 and November 2020 included 3 groups: 0.

Advancing therapies for viral infections using mechanistic computational models of the dynamic interplay between the virus and host immune response.

The COVID-19 pandemic has highlighted a need for improved frameworks for drug discovery, repurposing, clinical trial design and therapy optimization and personalization. Mechanistic computational models can play an important role in developing these frameworks. We discuss how mechanistic models, which consider viral entry, replication in target cells, viral spread in the body, immune response, and the complex factors involved in tissue and organ damage and recovery, can clarify the mechanisms of humoral and cellular immune responses to the virus, viral distribution and replication in tissues, the origins of pathogenesis and patient-to-patient heterogeneity in responses.

The effect of endurance training on non-alcoholic fatty liver disease in mice.

Chronic endurance exercise is a therapeutic strategy in the treatment of non-alcoholic fatty liver disease (NAFLD). Metabolic, cardiorespiratory, and endocrine pathways targeted by chronic endurance exercise have been identified; however, the specific cellular and molecular pathways modified by exercise in the steatotic liver remain unresolved. In this study, we show hepatic gene expression, and the structure, characteristics, and clinical differences between sedentary and exercised mice, by an endurance exercise model with wheels with a controlled velocity that allows for the quantification of a human-relevant endurance "dosage," after exposure to regular and high-fat diet.

The Relationship of Mitral Annulus Shape at CT to Mitral Regurgitation after Transcatheter Aortic Valve Replacement.

Background There are conflicting results over the improvement rate and predictors of mitral regurgitation in patients undergoing transcatheter aortic valve replacement (TAVR). Purpose To define the cause, degree of improvement, and improvement predictors of moderate to severe mitral regurgitation in patients undergoing TAVR by using a simplified D-shaped mitral annulus model derived from multisection CT (MSCT). Materials and Methods This retrospective cohort study included 528 consecutive patients who underwent TAVR between April 2012 and October 2019.

A Novel Approach to Improve Newborn Screening for Congenital Hypothyroidism by Integrating Covariate-Adjusted Results of Different Tests into CLIR Customized Interpretive Tools.

Newborn screening for congenital hypothyroidism remains challenging decades after broad implementation worldwide. Testing protocols are not uniform in terms of targets (TSH and/or T4) and protocols (parallel vs. sequential testing; one or two specimen collection times), and specificity (with or without collection of a second specimen) is overall poor.

Differences in Hospital Costs among Octogenarians and Nonagenarians Following Primary Total Joint Arthroplasty.

The proportion of patients over the age of 90 years continues to grow, and the anticipated demand for total joint arthroplasty (TJA) in this population is expected to rise concomitantly. As the country shifts to alternative reimbursement models, data regarding hospital expenses is needed for accurate risk-adjusted stratification. The aim of this study was to compare total in-hospital costs following primary TJA in octogenarians and nonagenarians, and to determine the primary drivers of cost.

Run for your life: an integrated virtual tissue platform for incorporating exercise oncology into immunotherapy.

The purpose of this paper is to introduce a novel in silico platform for simulating early-stage solid tumor growth and anti-tumor immune response. We present the model, test the sensitivity and robustness of its parameters, and calibrate it with clinical data from exercise oncology experiments which offer a natural biological backdrop for modulation of anti-tumor immune response. We then perform two virtual experiments with the model that demonstrate its usefulness in guiding pre-clinical and clinical studies of immunotherapy.

Newborn Screening for X-Linked Adrenoleukodystrophy in Georgia: Experiences from a Pilot Study Screening of 51,081 Newborns.

We screened 51,081 newborns for X-linked adrenoleukodystrophy (ALD) using a two-tiered strategy quantifying very long chain lysophosphatadylcholines (LPC). Our testing strategy used flow injection tandem mass spectrometry for the first-tier analysis of LPCs, and second-tier quantification of C26:0 LPC using liquid chromatography tandem mass spectrometry. There were 364 specimens considered abnormal using our first-tier algorithm that relied on the four LPC measurements and post-analytical tools.

Post-Analytical Tools for the Triage of Newborn Screening Results in Follow-up Can Reduce Confirmatory Testing and Guide Performance Improvement.

Georgia uses post-analytical tools through Collaborative Laboratory Integrated Reports (CLIR) to triage abnormal newborn screening (NBS) results for follow-up. Condition specific tools are used to assign each case a risk level, which is used to guide follow-up recommendations. Follow-up recommendations include assessment by the child's primary care provider as well as testing, either a repeat NBS or confirmatory testing.

Effect of endurance exercise training on liver gene expression in male and female mice.

Chronic endurance exercise is a therapeutic strategy in the treatment of many chronic diseases in humans, including the prevention and treatment of metabolic diseases such as diabetes mellitus. Metabolic, cardiorespiratory, and endocrine pathways targeted by chronic endurance exercise have been identified. In the liver, however, the cellular and molecular pathways that are modified by exercise and have preventive or therapeutic relevance to metabolic disease need to be elucidated.

Incidence, Predictors, and Outcome of Paravalvular Leak after Transcatheter Aortic Valve Implantation.

Background: Paravalvular leak (PVL) is common after transcatheter aortic valve implantation (TAVI) and has been linked with worse survival. This study aimed to investigate the determinants and outcome of PVL after TAVI and determine the role of aortic valve calcification (AVC) distribution in predicting PVL.

Methods And Results: This was a retrospective cohort study of 270 consecutive patients who underwent TAVI.

Formulation, Characterization and Biological Activity Screening of Sodium Alginate-Gum Arabic Nanoparticles Loaded with Curcumin.

The approach of drug delivery systems emphasizes the use of nanoparticles as a vehicle, offering the optional property of delivering drugs as a single dose rather than in multiple doses. The current study aims to improve antioxidant and drug release properties of curcumin loaded gum Arabic-sodium alginate nanoparticles (Cur/ALG-GANPs). The Cur/ALG-GANPs were prepared using the ionotropic gelation technique and further subjected to physico-chemical characterization using attenuated total reflectance-Fourier transform infrared (ATR-FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), size distribution, and transmission electron microscopy (TEM).

Two-Tiered Newborn Screening with Post-Analytical Tools for Pompe Disease and Mucopolysaccharidosis Type I Results in Performance Improvement and Future Direction.

We conducted a pilot newborn screening (NBS) study for Pompe disease (PD) and mucopolysaccharidosis type I (MPS I) in the multiethnic population of Georgia. We screened 59,332 infants using a two-tier strategy of flow injection tandem mass spectrometry (FIA-MSMS) enzyme assays. The first tier of testing was a 2-plex assay measuring PD and MPS I enzyme activity, followed by a second-tier test with additional enzymes to improve specificity.

A new aerobic fitness score based on lactate sensing during submaximal exercise.

Given the known clinical utility of cardiorespiratory fitness, measurement of physiological responses to submaximal exercise may be a feasible approach well suited for diagnostic and prognostic purposes in non-athletes and the chronically ill. Lactate levels and watt output during a short submaximal exercise and a subsequent relaxation period yield an aerobic score that is consistent with cardiorespiratory fitness grades in non-athletes and that may be used as a marker in such approaches. In this study, 28 females (23 ± 3 years) were submitted to a 15 min submaximal recumbent bike session, and their capillary and saliva lactate concentrations were recorded and plotted against time.

Increased parental anxiety and a benign clinical course: Infants identified with short-chain acyl-CoA dehydrogenase deficiency and isobutyryl-CoA dehydrogenase deficiency through newborn screening in Georgia.

The long-term consequences and need for therapy in children with short-chain acyl-CoA dehydrogenase deficiency (SCADD) or isobutyryl-CoA dehydrogenase deficiency (IBDD) identified via newborn screening (NBS) remains controversial. Initial clinical descriptions were severe; however, while most cases identified through NBS have remained asymptomatic, clinical concerns have been raised in these populations. It is not clear whether these children are asymptomatic because of the success of NBS, or because the normal clinical course of these disorders is relatively benign.