Medical student misconceptions in cardiovascular physiology.

Students find cardiovascular physiology challenging. Misunderstandings can be due to the nature of the subject, the way it is taught, and prior knowledge, which impede learning of new concepts. Some misunderstood concepts can be corrected with teaching (i.

Atypical presentation of acute rheumatic fever (ARF) in a 25-year-old woman in the Caribbean: a challenging diagnosis.

A 25-year-old woman presented a challenging diagnosis of acute rheumatic fever (ARF). Initial symptoms included dry cough and three minor Jones criteria (unabating fever (38.4°C, 0d), elevated acute phase reactants (C-reactive protein, 13d) and joint pain (monoarthralgia) in her neck (0d)).

Using lectures to identify student misconceptions: a study on the paradoxical effects of hyperkalemia on vascular smooth muscle.

Medical students have difficulty understanding the mechanisms underlying hyperkalemia-mediated local control of blood flow. Such control mechanisms are crucial in the brain, kidney, and skeletal muscle vasculature. We aimed to identify medical students' misconceptions via assessment of students' in-class knowledge and, subsequently, improve future teaching of this concept.

Effect of a small-group, active learning, tutorial-based, in-course enrichment program on student performance in medical physiology.

Physiology is one of the major foundational sciences for the medical curriculum. This discipline has proven challenging for students to master due to ineffective content acquisition and retention. Preliminary data obtained from a survey completed by "low-performance" students (those maintaining a grade average below the passing mark of 70%) at Morehouse School of Medicine reported that students lacked the ability to adequately recognize and extract important physiological concepts to successfully navigate multiple-choice assessments.

Protein misfolding and aggregation in neurodegenerative diseases: a review of pathogeneses, novel detection strategies, and potential therapeutics.

Protein folding is a complex, multisystem process characterized by heavy molecular and cellular footprints. Chaperone machinery enables proper protein folding and stable conformation. Other pathways concomitant with the protein folding process include transcription, translation, post-translational modifications, degradation through the ubiquitin-proteasome system, and autophagy.

Evaluation of Metabolic and Synaptic Dysfunction Hypotheses of Alzheimer's Disease (AD): A Meta-Analysis of CSF Markers.

Background: Alzheimer's disease (AD) is currently incurable and a majority of investigational drugs have failed clinical trials. One explanation for this failure may be the invalidity of hypotheses focusing on amyloid to explain AD pathogenesis. Recently, hypotheses which are centered on synaptic and metabolic dysfunction are increasingly implicated in AD.

Amyloid Plaque-Associated Oxidative Degradation of Uniformly Radiolabeled Arachidonic Acid.

Oxidative stress is a frequently observed feature of Alzheimer's disease, but its pathological significance is not understood. To explore the relationship between oxidative stress and amyloid plaques, uniformly radiolabeled arachidonate was introduced into transgenic mouse models of Alzheimer's disease via intracerebroventricular injection. Uniform labeling with carbon-14 is used here for the first time, and made possible meaningful quantification of arachidonate oxidative degradation products.

Small molecules and Alzheimer's disease: misfolding, metabolism and imaging.

Small molecule interactions with amyloid proteins have had a huge impact in Alzheimer's disease (AD), especially in three specific areas: amyloid folding, metabolism and brain imaging. Amyloid plaque amelioration or prevention have, until recently, driven drug development, and only a few drugs have been advanced for use in AD. Amyloid proteins undergo misfolding and oligomerization via intermediates, eventually forming protease resistant amyloid fibrils.

Islet amyloid polypeptide (IAPP): a second amyloid in Alzheimer's disease.

Amyloid formation is the pathological hallmark of type 2 diabetes (T2D) and Alzheimer's disease (AD). These diseases are marked by extracellular amyloid deposits of islet amyloid polypeptide (IAPP) in the pancreas and amyloid β (Aβ) in the brain. Since IAPP may enter the brain and disparate amyloids can cross-seed each other to augment amyloid formation, we hypothesized that pancreatic derived IAPP may enter the brain to augment misfolding of Aβ in AD.

Adenosine triphosphate (ATP) reduces amyloid-β protein misfolding in vitro.

Alzheimer's disease (AD) is a devastating disease of aging that initiates decades prior to clinical manifestation and represents an impending epidemic. Two early features of AD are metabolic dysfunction and changes in amyloid-β protein (Aβ) levels. Since levels of ATP decrease over the course of the disease and Aβ is an early biomarker of AD, we sought to uncover novel linkages between the two.

Ruthenium red colorimetric and birefringent staining of amyloid-β aggregates in vitro and in Tg2576 mice.

Alzheimer's disease (AD) is a devastating neurodegenerative disease most notably characterized by the misfolding of amyloid-β (Aβ) into fibrils and its accumulation into plaques. In this Article, we utilize the affinity of Aβ fibrils to bind metal cations and subsequently imprint their chirality to bound molecules to develop novel imaging compounds for staining Aβ aggregates. Here, we investigate the cationic dye ruthenium red (ammoniated ruthenium oxychloride) that binds calcium-binding proteins, as a labeling agent for Aβ deposits.

Probing and trapping a sensitive conformation: amyloid-β fibrils, oligomers, and dimers.

Alzheimer's disease (AD) is a devastating neurodegenerative disease with pathological misfolding of amyloid-β protein (Aβ). The recent interest in Aβ misfolding intermediates necessitates development of novel detection methods and ability to trap these intermediates. We speculated that two regions of Aβ may allow for detection of specific Aβ species: the N-terminal and 22-35, both likely important in oligomer interaction and formation.

Amyloid-β metabolite sensing: biochemical linking of glycation modification and misfolding.

Glycation is the reaction of a reducing sugar with proteins and lipids, resulting in myriads of glycation products, protein modifications, cross-linking, and oxidative stress. Glycation reactions are also elevated during metabolic dysfunction such as in Alzheimer's disease (AD) and Down's syndrome. These reactions increase the misfolding of the proteins such as tau and amyloid-β (Aβ), and colocalize with amyloid plaques in AD.

Amyloids as Sensors and Protectors (ASAP) hypothesis.

This paper propounds the Amyloids as Sensors and Protectors (ASAP) hypothesis. In this novel hypothesis, we provide evidence that amyloids are capable of sensing dysfunction, and after misfolding, initiate protective cellular responses. Amyloid proteins are initially protective, but chronic stress and overstimulation of the amyloid sensor leads to pathology.

Vascular and metabolic dysfunction in Alzheimer's disease: a review.

Alzheimer's disease (AD) is thought to start years or decades prior to clinical diagnosis. Overt pathology such as protein misfolding and plaque formation occur at later stages, and factors other than amyloid misfolding contribute to the initiation of the disease. Vascular and metabolic dysfunctions are excellent candidates, as they are well-known features of AD that precede pathology or clinical dementia.

Oxidative stress and cell membranes in the pathogenesis of Alzheimer's disease.

Amyloid β proteins and oxidative stress are believed to have central roles in the development of Alzheimer's disease. Lipid membranes are among the most vulnerable cellular components to oxidative stress, and membranes in susceptible regions of the brain are compositionally distinct from those in other tissues. This review considers the evidence that membranes are either a source of neurotoxic lipid oxidation products or the target of pathogenic processes involving amyloid β proteins that cause permeability changes or ion channel formation.

Hydralazine modifies Aβ fibril formation and prevents modification by lipids in vitro.

Lipid oxidative damage and amyloid β (Aβ) misfolding contribute to Alzheimer's disease (AD) pathology. Thus, the prevention of oxidative damage and Aβ misfolding are attractive targets for drug discovery. At present, no AD drugs approved by the Food and Drug Administration (FDA) prevent or halt disease progression.

Lipid oxidation and modification of amyloid-β (Aβ) in vitro and in vivo.

Oxidative damage and amyloid-β (Aβ) protein misfolding are prominent features of Alzheimer's disease (AD). In vitro studies indicated a direct linkage between these two features, where lipid oxidation products augmented Aβ misfolding. We tested this linkage further, mimicking specific conditions present in amyloid plaques.

TNFalpha-dependent hepatic steatosis and liver degeneration caused by mutation of zebrafish S-adenosylhomocysteine hydrolase.

Hepatic steatosis and liver degeneration are prominent features of the zebrafish ducttrip (dtp) mutant phenotype. Positional cloning identified a causative mutation in the gene encoding S-adenosylhomocysteine hydrolase (Ahcy). Reduced Ahcy activity in dtp mutants led to elevated levels of S-adenosylhomocysteine (SAH) and, to a lesser degree, of its metabolic precursor S-adenosylmethionine (SAM).

Promotion of amyloid beta protein misfolding and fibrillogenesis by a lipid oxidation product.

Oxidatively damaged lipid membranes are known to promote the aggregation of amyloid beta proteins and fibril formation. Oxidative damage typically produces 4-hydroxy-2-nonenal when lipid membranes contain omega-6 polyunsaturated fatty acyl chains, and this compound is known to modify the three His residues in Abeta proteins by Michael addition. In this report, the ability of 4-hydroxy-2-nonenal to reproduce the previously observed amyloidogenic effects of oxidative lipid damage on amyloid beta proteins is demonstrated and the mechanism by which it exerts these effects is examined.

A mechanistic link between oxidative stress and membrane mediated amyloidogenesis revealed by infrared spectroscopy.

The fully developed lesion of Alzheimer's disease is a dense plaque composed of fibrillar amyloid beta-proteins (Abeta) with a characteristic and well-ordered beta-sheet secondary structure. Because the incipient lesion most likely develops when these proteins are first induced to form beta-sheet structure, it is important to understand factors that induced Abeta to adopt this conformation. In this review, we describe the application of polarized attenuated total internal reflection infrared FT-IR spectroscopy for characterizing the conformation, orientation, and rate of accumulation of Abeta on lipid membranes.

Mass spectrometric analysis demonstrates that BODIPY 581/591 C11 overestimates and inhibits oxidative lipid damage.

BODIPY C11 is being used with increasing frequency to quantify lipid oxidation; however, it is not known whether signals from the dye yield accurate information. To determine the quantitative accuracy of signals from this dye we utilized a triple-quadrupole mass spectroscopy method to measure concentrations of 1-stearoyl-2-arachidonyl-sn-glycero-3-phosphocholine (SAPC) as it underwent oxidative damage, and compared these results to fluorescence signals from the dye. Results indicate that BODIPY C11 was significantly more sensitive to oxidative damage than SAPC lipid.

Membrane-mediated amyloidogenesis and the promotion of oxidative lipid damage by amyloid beta proteins.

Evidence of oxidative stress and the accumulation of fibrillar amyloid beta proteins (Abeta) in senile plaques throughout the cerebral cortex are consistent features in the pathology of Alzheimer disease. To define a mechanistic link between these two processes, various aspects of the relationship between oxidative lipid membrane damage and amyloidogenesis were characterized by chemical and physical techniques. Earlier studies of this relationship demonstrated that oxidatively damaged synthetic lipid membranes promoted amyloidogenesis.

Beta-synuclein modulates alpha-synuclein neurotoxicity by reducing alpha-synuclein protein expression.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by fibrillar aggregates of alpha-synuclein in characteristic inclusions known as "Lewy bodies". As mutations altering alpha-synuclein structure or increasing alpha-synuclein expression level can cause familial forms of PD or related Lewy body disorders, alpha-synuclein is believed to play a central role in the process of neuron toxicity, degeneration and death in "synucleinopathies". beta-synuclein is closely related to alpha-synuclein and has been shown to inhibit alpha-synuclein aggregation and ameliorate alpha-synuclein neurotoxicity.