Neutralizing antibodies to interferon alfa arising during peginterferon therapy of chronic hepatitis B in children and adults: Results from the HBRN Trials.

Background Aims: Pegylated interferon-α (PegIFNα) is of limited utility during immunotolerant or immune active phases of chronic hepatitis B infection but is being explored as part of new cure regimens. Low/absent levels of IFNα found in some patients receiving treatment are associated with limited/no virological responses. The study aimed to determine if sera from participants inhibit IFNα activity and/or contain therapy-induced anti-IFNα antibodies.

Turning anecdotal irradiation-induced anti-cancer immune responses into reproducible in situ cancer vaccines via disulfiram/copper-mediated enhanced immunogenic cell death of breast cancer cells.

Irradiation (IR) induces immunogenic cell death (ICD) in tumors, but it rarely leads to the abscopal effect (AE). However, combining IR with immune checkpoint inhibitors has shown anecdotal success in inducing AEs. In this study, we aimed to enhance the IR-induced immune response and generate reproducible AEs using the anti-alcoholism drug disulfiram (DSF) and copper complex (DSF/Cu) via induction of tumor ICD.

The role of extracorporeal membrane oxygenation in COVID-19.

An extracorporeal membrane oxygenation (ECMO) program is an important component in the management of patients with COVID-19, but it is imperative to implement a system that is well-supported by the institution and staffed with well-trained clinicians to both optimize patient outcomes and to keep providers safe. There are many unknowns related to COVID-19, and one of the most challenging aspects for clinicians is the lack of predictive knowledge as to why some patients fail medical therapy and require advanced support such as ECMO. These factors can create challenges during a time of resource scarcity and interruptions in the supply chain.

Longitudinal impact of temporary mechanical circulatory support on durable ventricular assist device outcomes: An IMACS registry propensity matched analysis.

Background: Patients with advanced heart failure and cardiogenic shock (CS) often require temporary circulatory support (TCS) as a bridge to durable ventricular assist devices (dVADs). We aim to characterize longitudinal outcomes of patients with and without CS.

Methods: Between 2013 and 2017, 13,813 adult patients classified as Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profiles 1 to 3 with continuous flow left ventricular assist devices or biventricular assist devices were registered into the International Society for Heart and Lung Transplantation Registry for Mechanically Assisted Circulatory Support.

Surviving and Thriving-Shifting the Public Health Response to HIV-Exposed Uninfected Children: Report of the 3rd HIV-Exposed Uninfected Child Workshop.

Great gains were achieved with the introduction of the United Nations' Millennium Development Goals, including improved child survival. Transition to the Sustainable Development Goals (SDGs) focused on surviving, thriving, and transforming, representing an important shift to a broader public health goal, the achievement of which holds the promise of longer-term individual and societal benefits. A similar shift is needed with respect to outcomes for infants born to women living with HIV (WLHIV).

Enhanced Laws textures: A potential MRI surrogate marker of hepatic fibrosis in a murine model.

Purpose: To compare enhanced Laws textures derived from parametric proton density (PD) maps to other MRI surrogate markers (T, PD, apparent diffusion coefficient (ADC)) in assessing degrees of liver fibrosis in an ex vivo murine model of hepatic fibrosis imaged using 11.7T MRI.

Methods: This animal study was IACUC approved.

Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16.

Transmission of HIV across mucosal barriers accounts for the majority of HIV infections worldwide. Thus, efforts aimed at enhancing protective immunity at these sites are a top priority, including increasing virus-specific antibodies (Abs) and antiviral activity at mucosal sites. Mucin proteins, including the largest cell-associated mucin, mucin 16 (MUC16), help form mucus to provide a physical barrier to incoming pathogens.

A new look at informed consent for cancer clinical trials.

Informed consent is fundamental to the conduct of clinical trials. Prospective participants need to be adequately informed and given the opportunity to ask questions and consult with relatives or friends without feeling pressured or rushed.

Defining the high-risk patient for carotid endarterectomy: an analysis of the prospective National Surgical Quality Improvement Program database.

Background: Carotid endarterectomy (CEA) is the gold standard for the treatment of carotid stenosis, but carotid angioplasty and stenting has been advocated in high-risk patients. The definition of such a population has been elusive, particularly because the data are largely retrospective. Our study examined results for CEA in the National Surgical Quality Improvement Program database (both Veterans Affairs and private sector).

Targeted photodynamic therapy of established soft-tissue infections in mice.

The worldwide rise in antibiotic resistance necessitates the development of novel antimicrobial strategies. Although many workers have used photodynamic therapy (PDT) to kill bacteria in vitro, the use of this approach has seldom been reported in vivo in animal models of infection. We have previously described the first use of PDT to treat excisional wound infections by Gram-(-) bacteria in living mice.

Bringing good teaching cases "to life": a simulator-based medical education service.

Realistic medical simulation has expanded worldwide over the last decade. Such technology is playing an increasing role in medical education not merely because simulator sessions are enjoyable, but because they can provide an enhanced environment for experiential learning and reflective thought. High-fidelity patient simulators allow students of all levels to "practice" medicine without risk, providing a natural framework for the integration of basic and clinical science in a safe environment.

Autophagy regulates the processing of amino terminal huntingtin fragments.

The N-terminus of mutant huntingtin (htt) has a polyglutamine expansion and forms neuronal aggregates in the brain of Huntington's disease (HD) patients. Htt expression in vitro activates autophagy, but it is unclear whether autophagic/lysosomal pathways process htt, especially N-terminal htt fragments. We explored the role of autophagy in htt processing in three cell lines, clonal striatal cells, PC12 cells and rodent embryonic cells lacking cathepsin D.

Multiple, diverse senile plaque-associated proteins are ligands of an apolipoprotein E receptor, the alpha 2-macroglobulin receptor/low-density-lipoprotein receptor-related protein.

Both apolipoprotein E and its receptor, the low-density-lipoprotein receptor-related protein (LRP), are associated with senile plaques in Alzheimer's disease. We examined the relationship of other LRP-related molecules to senile plaques. LRP is a multifunctional receptor that binds and rapidly internalizes at least seven ligands: apolipoprotein E, activated alpha 2-macroglobulin, tissue and urokinase-type plasminogen activators, plasminogen activator inhibitor-1, lipoprotein lipase, and lactoferrin.

HIV-1 drug resistance. Molecular pathogenesis and laboratory monitoring.

Molecular and clinical aspects of HIV-1 pathogenesis are described, including the turnover of the HIV-1 population in vivo, the clinical significance of resistance to HIV-1 reverse transcriptase (RT) inhibitors, and the inter-relationship between virus replication and RT inhibitor resistance. The molecular genetics of RT inhibitor resistance, including interactive effects of different RT mutations and the implications of those effects for combination chemotherapy, are summarized. Structural studies of RT and the biochemical bases of drug resistance are discussed.

Chest CT in patients with scleroderma: prevalence of asymptomatic esophageal dilatation and mediastinal lymphadenopathy.

Objective: The high-resolution CT findings of chronic diffuse interstitial lung disease associated with scleroderma have been reported previously. This study determined the prevalence of esophageal dilatation and mediastinal adenopathy on high-resolution CT scans in patients with this disease.

Materials And Methods: We retrospectively reviewed the high-resolution CT scans of 25 patients with scleroderma who had diffuse interstitial lung disease.

The evolution of photochemotherapy with psoralens and UVA (PUVA): 2000 BC to 1992 AD.

The therapeutic uses of naturally occurring psoralens in modern-day medicine (8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 4,5',8-trimethylpsoralen, and a few other synthetic psoralens) have evolved through five stages of development. (1) In the historical period (2000 BC to 1930 AD), the pigment-stimulating properties of naturally occurring plants containing psoralens were described anecdotally. (2) The second period (1930-1960) dealing with the chemistry of psoralens involved extraction, identification of their structure, synthesis, and the relationship between chemical structure and their photoreactivity and pigment-stimulating properties.

The histology of the radiolucent line.

The radiographic and histological features of radiolucent areas at the cement-bone interface were correlated in 15 specimens retrieved at post-mortem from patients who had undergone cemented total hip arthroplasty, two weeks to 15 years prior to death. All but one of the components were securely fixed, as demonstrated by direct measurements of micromotion. Extensive radiolucencies were present in all but one case.

Generation and possible significance of trypsinogen activation peptides in experimental acute pancreatitis in the rat.

Trypsinogen activation peptides (TAP) were quantified by radioimmunoassay in blood, urine, and peritoneal exudate of rats with experimental pancreatitis. Forty-four animals were studied, comprising a control group and four different induction techniques (cerulein, cerulein plus either 2- or 10-min intraductal glycodeoxycholic acid [GDOC] infusion, and cerulein plus intraductal GDOC with enterokinase [EK]). Significantly higher TAP concentrations were found at 6 h (or at death) in plasma and ascites of all pancreatitis groups compared with controls.

Incorporation of marine lipids into mitochondrial membranes increases susceptibility to damage by calcium and reactive oxygen species: evidence for enhanced activation of phospholipase A2 in mitochondria enriched with n-3 fatty acids.

Experiments were designed to evaluate the susceptibility of mitochondrial membranes enriched with n-3 fatty acids to damage by Ca2+ and reactive oxygen species. Fatty acid content and respiratory function were assessed in renal cortical mitochondria isolated from fish-oil- and beef-tallow-fed rats. Dietary fish oils were readily incorporated into mitochondrial membranes.