A virtual scalable model of the Hepatic Lobule for acetaminophen hepatotoxicity prediction.

Addressing drug-induced liver injury is crucial in drug development, often causing Phase III trial failures and market withdrawals. Traditional animal models fail to predict human liver toxicity accurately. Virtual twins of human organs present a promising solution.

The emerging challenge of endocarditis after transcatheter aortic valve implantation: time for innovative treatment approaches.

SUMMARYInfective endocarditis (IE) is a life-threatening infection that has nearly doubled in prevalence over the last two decades due to the increase in implantable cardiac devices. Transcatheter aortic valve implantation (TAVI) is currently one of the most common cardiac procedures. TAVI usage continues to exponentially rise, inevitability increasing TAVI-IE.

Exploring Potential Mechanisms Accounting for Iron Accumulation in the Central Nervous System of Patients with Alzheimer's Disease.

Elevated levels of iron occur in both cortical and subcortical regions of the CNS in patients with Alzheimer's disease. This accumulation is present early in the disease process as well as in more advanced stages. The factors potentially accounting for this increase are numerous, including: (1) Cells increase their uptake of iron and reduce their export of iron, as iron becomes sequestered (trapped within the lysosome, bound to amyloid β or tau, etc.

Examining the Role of a Functional Deficiency of Iron in Lysosomal Storage Disorders with Translational Relevance to Alzheimer's Disease.

The recently presented Azalea Hypothesis for Alzheimer's disease asserts that iron becomes sequestered, leading to a functional iron deficiency that contributes to neurodegeneration. Iron sequestration can occur by iron being bound to protein aggregates, such as amyloid β and tau, iron-rich structures not undergoing recycling (e.g.

The Azalea Hypothesis of Alzheimer Disease: A Functional Iron Deficiency Promotes Neurodegeneration.

Chlorosis in azaleas is characterized by an interveinal yellowing of leaves that is typically caused by a deficiency of iron. This condition is usually due to the inability of cells to properly acquire iron as a consequence of unfavorable conditions, such as an elevated pH, rather than insufficient iron levels. The causes and effects of chlorosis were found to have similarities with those pertaining to a recently presented hypothesis that describes a pathogenic process in Alzheimer disease.

Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer's Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration.

The involvement of iron in the pathogenesis of Alzheimer's disease (AD) may be multifaceted. Besides potentially inducing oxidative damage, the bioavailability of iron may be limited within the central nervous system, creating a functionally iron-deficient state. By comparing staining results from baseline and modified iron histochemical protocols, iron was found to be more tightly bound within cortical sections from patients with high levels of AD pathology compared to subjects with a diagnosis of something other than AD.

Substrate Reduction Therapy for Krabbe Disease: Exploring the Repurposing of the Antibiotic D-Cycloserine.

Krabbe disease is a lysosomal storage disease that is caused by a deficiency in galactosylceramidase. Infantile onset disease is the most common presentation, which includes progressive neurological deterioration with corresponding demyelination, development of globoid cells, astrocyte gliosis, etc. Hemopoietic stem cell transplantation (HSCT) is a disease modifying therapy, but this intervention is insufficient with many patients still experiencing developmental delays and progressive deterioration.

A Simplified Method for the Histochemical Detection of Iron in Paraffin Sections: Intracellular Iron Deposits in Central Nervous System Tissue.

Although all cells contain iron, most histochemical methods fail to reveal the presence of iron within many cells of the central nervous system (CNS), particularly neurons. Previously, a sensitive method was developed that limited the extraction of iron in paraffin sections, and this method revealed staining within neurons. However, the staining was often too robust making it difficult to discern discrete intracellular structures.

An Engineered Galactosylceramidase Construct Improves AAV Gene Therapy for Krabbe Disease in Twitcher Mice.

Krabbe disease is an inherited neurodegenerative disease caused by mutations in the gene. In the infantile form, patients die before 3 years of age. Systemic adeno-associated virus serotype 9 (AAV9) gene therapy was recently shown to reverse the disease course in human patients in another lethal infantile neurodegenerative disease.

Lower Eyelid Blepharoplasty: Does the Literature Support the Longevity of this Procedure?

Background: Lower eyelid blepharoplasty has continued to evolve with ongoing debate regarding optimal techniques. Despite large case series publishing excellent results and minimal complications, the true longevity of these procedures remains unclear.

Objectives: The aim of this study was to determine how thoroughly the aesthetic surgery literature assesses the longevity of lower blepharoplasty.

Safety and efficacy of anti-PD-L1 therapy in the woodchuck model of HBV infection.

Immune clearance of Hepatitis B virus (HBV) is characterized by broad and robust antiviral T cell responses, while virus-specific T cells in chronic hepatitis B (CHB) are rare and exhibit immune exhaustion that includes programmed-death-1 (PD-1) expression on virus-specific T cells. Thus, an immunotherapy able to expand and activate virus-specific T cells may have therapeutic benefit for CHB patients. Like HBV-infected patients, woodchucks infected with woodchuck hepatitis virus (WHV) can have increased hepatic expression of PD-1-ligand-1 (PD-L1), increased PD-1 on CD8+ T cells, and a limited number of virus-specific T cells with substantial individual variation in these parameters.

Public Interest in Breast Augmentation: Analysis and Implications of Google Trends Data.

Introduction: Breast augmentation is the most common aesthetic surgery performed in the United States (US) annually. Analysis of Google Trends (GT) data may give plastic surgeons useful information regarding worldwide, national, and regional interest for breast augmentation and other commonly performed aesthetic surgeries.

Methods: Data were collected using GT for breast augmentation and associated search terms from January 2004 to May 2017.

Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis.

Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth: insufficient energy production mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, .

Selective Serotonin Reuptake Inhibitor-Induced Hyponatremia and the Plastic Surgery Patient.

Unlabelled: Cosmetic plastic surgery procedures continue to increase in frequency, and a greater number of them now occur outside of an acute-care hospital setting. In addition, antidepressant use is also rising, with a greater number of patients taking selective serotonin reuptake inhibitors to aid in a variety of mood and anxiety disorders. Americans spend more than $86 billion each year on antidepressants, as 34 million people in the United States are taking at least one of these medications.

Intersections of pathways involving biotin and iron relative to therapeutic mechanisms for progressive multiple sclerosis.

While there are a variety of therapies for relapsing remitting multiple sclerosis (MS), there is a lack of treatments for progressive MS. An early study indicated that high dose biotin therapy has beneficial effects in approximately 12-15% of patients with progressive MS. The mechanisms behind the putative improvements seen with biotin therapy are not well understood, but have been postulated to include: 1) improving mitochondrial function which is impaired in MS, 2) increasing synthesis of lipids and cholesterol to facilitate remyelination, and 3) affecting gene expression.

Piloting electronic medical record-based early detection of inpatient deterioration in community hospitals.

Patients who deteriorate in the hospital outside the intensive care unit (ICU) have higher mortality and morbidity than those admitted directly to the ICU. As more hospitals deploy comprehensive inpatient electronic medical records (EMRs), attempts to support rapid response teams with automated early detection systems are becoming more frequent. We aimed to describe some of the technical and operational challenges involved in the deployment of an early detection system.

Enhanced Histochemical Detection of Iron in Paraffin Sections of Mouse Central Nervous System Tissue: Application in the APP/PS1 Mouse Model of Alzheimer's Disease.

Histochemical methods of detecting iron in the rodent brain result mainly in the labeling of oligodendrocytes, but as all cells utilize iron, this observation suggests that much of the iron in the central nervous system goes undetected. Paraffin embedding of tissue is a standard procedure that is used to prepare sections for microscopic analysis. In the present study, we questioned whether we could modify the iron histochemical procedure to enable a greater detection of iron in paraffin sections.

Substrate reduction therapy for Krabbe's disease.

Krabbe's disease (KD) is a lysosomal storage disorder in which galactosylceramide, a major glycosphingolipid of myelin, and psychosine (galactose-sphingosine) cannot be adequately metabolized because of a deficiency in galactosylceramidase. Substrate reduction therapy (SRT) has been tested in preclinical studies. The premise of SRT is to reduce the synthesis of substrates that are not adequately digested so that the substrate burden is lowered, resulting in less accumulation of unmetabolized material.

Albumin and multiple sclerosis.

Leakage of the blood-brain barrier (BBB) is a common pathological feature in multiple sclerosis (MS). Following a breach of the BBB, albumin, the most abundant protein in plasma, gains access to CNS tissue where it is exposed to an inflammatory milieu and tissue damage, e.g.

Current Thoughts on Fat Grafting: Using the Evidence to Determine Fact or Fiction.

Background: Autologous fat grafting is an increasingly popular procedure used for facial rejuvenation and body contouring. The purpose of this article is to perform an evidence-based review to determine fact from fiction for the hot topics in autologous fat grafting.

Methods: A comprehensive literature search was performed.

The habenula and iron metabolism in cerebral mouse models of multiple sclerosis.

Iron accumulates in the CNS of patients with multiple sclerosis, but our understanding of the mechanism accounting for this accumulation is unclear. Mouse models of cerebral experimental autoimmune encephalomyelitis (EAE) in C57BL/6 and SJL mice were used together with a histochemical stain for iron and immunohistochemical stains for transferrin receptor, synaptophysin, iron regulatory protein 1 (IRP1) and/or IRP2 to investigate the role of disease activity on CNS iron metabolism. The expression of transferrin receptor, but not IRP1 or IRP2, increased in the medial habenula, which is adjacent to the third ventricle, in response to both types of cerebral EAE.

Aspirin and multiple sclerosis.

Aspirin is widely used to lessen the risks of cardiovascular events. Some studies suggest that patients with multiple sclerosis have an increased risk for some cardiovascular events, for example, venous thromboembolism and perhaps ischemic strokes, raising the possibility that aspirin could lessen these increased risks in this population or subgroups (patients with limited mobility and/or antiphospholipid antibodies). However, aspirin causes a small increased risk of hemorrhagic stroke, which is a concern as it could potentially worsen a compromised blood-brain barrier.

High Reproducibility of ELISPOT Counts from Nine Different Laboratories.

The primary goal of immune monitoring with ELISPOT is to measure the number of T cells, specific for any antigen, accurately and reproducibly between different laboratories. In ELISPOT assays, antigen-specific T cells secrete cytokines, forming spots of different sizes on a membrane with variable background intensities. Due to the subjective nature of judging maximal and minimal spot sizes, different investigators come up with different numbers.

Plastic Surgery Mortality: An 11-Year, Single-Institution Experience.

Background: Systematic reporting of mortality data is lacking in many surgical fields including plastic surgery. Current plastic surgery literature is largely limited to adverse events associated with specific procedures. Without mortality data, it is unclear how the recent growth of patient safety initiatives can rationally impact outcomes.