Renal Dysfunction After Heart Transplant.

Background: Moderate or severe renal dysfunction (MSRD) is a frequent complication after heart transplantation. Strategies to delay progression and improve outcomes, such as renoprotective medications and timely referral to nephrology, remain important in providing care to heart transplant recipients with MSRD.

Research Question: What are chronic renal dysfunction's prevalence, risk factors, and optimal clinical management strategies in heart transplant recipients?

Design: This single-center, cross-sectional study examined patients who received a heart transplant from January 1, 2000, to June 30, 2011, and followed until December 31, 2011.

Alzheimer's Disease and COVID-19 Pathogenic Overlap: Implications for Drug Repurposing.

As COVID-19 continues, a safe, cost-effective treatment strategy demands continued inquiry. Chronic neuroinflammatory disorders may appear to be of little relevance in this regard; often indolent and progressive disorders characterized by neuroinflammation (such as Alzheimer's disease (AD)) are fundamentally dissimilar in etiology and symptomology to COVID-19's rapid infectivity and pathology. However, the two disorders share extensive pathognomonic features, including at membrane, cytoplasmic, and extracellular levels, culminating in analogous immunogenic destruction of their respective organ parenchyma.

Cancer and Alzheimer's Inverse Correlation: an Immunogenetic Analysis.

Numerous studies have demonstrated an inverse link between cancer and Alzheimer's disease (AD), with data suggesting that people with Alzheimer's have a decreased risk of cancer and vice versa. Although other studies have investigated mechanisms to explain this relationship, the connection between these two diseases remains largely unexplained. Processes seen in cancer, such as decreased apoptosis and increased cell proliferation, seem to be reversed in AD.

Alzheimer's disease as an autoimmune disorder of innate immunity endogenously modulated by tryptophan metabolites.

Introduction: Alzheimer's disease (AD) is characterized by neurotoxic immuno-inflammation concomitant with cytotoxic oligomerization of amyloid beta (Aβ) and tau, culminating in concurrent, interdependent immunopathic and proteopathic pathogeneses.

Methods: We performed a comprehensive series of in silico, in vitro, and in vivo studies explicitly evaluating the atomistic-molecular mechanisms of cytokine-mediated and Aβ-mediated neurotoxicities in AD.  Next, 471 new chemical entities were designed and synthesized to probe the pathways identified by these molecular mechanism studies and to provide prototypic starting points in the development of small-molecule therapeutics for AD.

Ferulic acid amide derivatives with varying inhibition of amyloid-β oligomerization and fibrillization.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized, in part, by the misfolding, oligomerization and fibrillization of amyloid-β (Aβ). Evidence suggests that the mechanisms underpinning Aβ oligomerization and subsequent fibrillization are distinct, and may therefore require equally distinct therapeutic approaches. Prior studies have suggested that amide derivatives of ferulic acid, a natural polyphenol, may combat multiple AD pathologies, though its impact on Aβ aggregation is controversial.

Evaluation of a professional development course on research methods for healthcare professionals.

Healthcare is constantly evolving and thus requires lifelong learning. Evidence-based learning has been shown to lead to better patient outcomes, yet many healthcare professionals report gaps in their research abilities. We sought to evaluate the efficacy of a professional development program in addressing identified gaps.

Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide.

The novel coronavirus SARS-CoV-2 has become a global health concern. The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response. The latter may lead to excessive release of pro-inflammatory cytokines, IL-6 and IL-8, as well as TNF-α ultimately culminating in hypercytokinemia ("cytokine storm").

Misfolded proteins as a therapeutic target in Alzheimer's disease.

For decades, Alzheimer's Disease (AD) was defined as a disorder of protein misfolding and aggregation. In particular, the extracellular peptide fragment: amyloid-β (Aβ), and the intracellular microtubule-associated protein: tau, were thought to initiate a neurodegenerative cascade which culminated in AD's progressive loss of memory and executive function. As such, both proteins became the focus of intense scrutiny, and served as the principal pathogenic target for hundreds of clinical trials.

Inhibition of Pantothenate Synthetase by Analogs of β-Alanine Precursor Ineffective as an Antibacterial Strategy.

Background: Pantothenate, the fundamental precursor to coenzyme A, is required for optimal growth and virulence of microbial pathogens. It is synthesized by the enzyme-catalyzed condensation of β-alanine and pantoate, which has shown susceptibility to inhibition by analogs of its molecular constituents. Accordingly, analogs of β-alanine are gaining inquiry as potential antimicrobial chemotherapeutics.

Nutrients in Alzheimer's Disease: The Interaction of Diet, Drugs and Disease.

In recent decades, clinical trials in Alzheimer's disease (AD) have failed at an unprecedented rate. The etiology of AD has since come under renewed scrutiny, both to elucidate the underlying pathologies and to identify novel therapeutic strategies. Here, diet has emerged as a potential causative/protective agent.

The hidden variables problem in Alzheimer's disease clinical trial design.

As the leading cause of dementia worldwide, Alzheimer's disease has garnered intense academic and clinical interest. Yet, trials in search of a disease-modifying therapy have failed overwhelmingly. We suggest that, in part, this may be attributable to the influence of disruptive variables inherent to the framework of a clinical trial.

Phenylpropanoids and Alzheimer's disease: A potential therapeutic platform.

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by progressive dementia, neuroinflammation and the accumulation of intracellular neurofibrillary tangles and extracellular plaques. The etiology of AD is unclear, but is generally attributed to four leading hypotheses: (i) abnormal folding and aggregation of amyloid-β (Aβ)/tau proteins (ii) activation of the innate immune system, (iii) mitochondrial dysfunction, and (iv) oxidative stress. To date, therapeutic strategies have largely focused on Aβ-centric targets; however, the repeated failure of clinical trials and the continued lack of a disease-modifying therapy demand novel, multifaceted approaches.