A dynamic model for the evolution of protein structure

Protein domains are three-dimensional arrangements of atomic structure that are recurrent in the proteomes of organisms. Since the three-dimensional structure of a protein determines its function, it is the fold, much more than the underlying protein sequence and underlying chemistry, that is evolutionarily conserved. We are interested in probing the history of life with these domain structures and glimpsing qualitative changes over time by studying a dynamic model of protein evolution. Using standard phylogenetic methods and a census of protein domain structure in hundreds of genomes, we have reconstructed phylogenetic trees of protein domains, defined using the Structural Classification of Proteins (SCOP), where the nodes are folds or fold superfamilies (FSFs), the character vector for each node is a list of abundances of said fold or FSF across a range of species that spans all three superkingdoms of life, and the character states are linearly polarized by abundance; higher abundance within and among species equates to older structures and determines tree structure. Here we explore at what rate fold or FSF variants and new folds or FSFs appear in evolution. We also explore what collective model of proteome evolution explains such rates. Briefly, what are the dynamics of change? A set of birth-death differential equations was selected to capture the change of interest, with one set for folds and another for FSFs. The models assume that at any given moment there are a certain number of different folds or FSFs, with various abundances, and as each fold or FSF diversifies there are slight changes in the folds or FSFs, producing fold or FSF variants. Eventually as the variants continue to diversify and change as well, a new fold or FSF is born. Thus, there are two rate parameters in each model: the growth rate of fold or FSF variants and the rate of appearance of new folds or FSFs. The model governs the rate change of the average total abundance of a fold or FSF with time. It is fit to the tree so only those fold or FSF transitions actually present in the tree are assumed possible in the equations. It assumes a global perspective: the total abundance of a fold or FSF is that of the fold or FSF across all species, not within one organism. This perspective is used to properly discount terms of horizontal transfer in a birth-death model since such a transfer contributes no new folds or FSFs to the net abundance across all organisms. Our model determines 1) that there is a tight connection between the history of folds and FSFs, 2) that the corresponding transition probabilities to new variants of a fold experienced a sharp increase just as the transition probabilities to new folds experienced a steep decline and 3) that this simultaneous sharp increase and decline is explainable by and consistent with the combinatorial explosion of structural domains, referring to the period of high combination and rearrangement of domains and distribution of these new combinations in novel lineages, and the rise of organismal diversification. Our simulations suggest a picture of the past in which exploration of protein structure space proceeds much like that of a budding field of knowledge: first, coarse grain discoveries are made, followed by fine-grain elaboration of each once the coarse-grain discoveries have been exhausted

Selective Serotonin-Norepinephrine Reuptake Inhibitors-Induced Takotsubo Cardiomyopathy

CONTEXT: Takotsubo translates to octopus pot in Japanese. Takotsubo cardiomyopathy (TTC) is characterized by a transient regional systolic dysfunction of the left ventricle. Catecholamine excess is the one most studied and favored theories explaining the pathophysiology of TTC. CASE REPORT: We present the case of a 52-year-old Hispanic female admitted for venlafaxine-induced TTC with a review literature on all the cases of Serotonin-norepinephrine reuptake inhibitors (SNRI)-associated TTC published so far. CONCLUSION: SNRI inhibit the reuptake of catecholamines into the presynaptic neuron, resulting in a net gain in the concentration of epinephrine and serotonin in the neuronal synapses and causing iatrogenic catecholamine excess, ultimately leading to TTC

Takotsubo Syndrome in African American vs. Non-African American Women

Objectives: Takotsubo syndrome (TTS) is a reversible cause of heart failure rarely described in African-American patients. This study aimed to compare and contrast the clinical characteristics of TTS in African-American (AA) and non-African-American (NAA) patients.Methods: We retrospectively reviewed the charts of eight patients (four AA and four NAA) diagnosed with TTS, between June 2006 and August 2008, in four different teaching hospitals: St Michael’s Medical Center, St Joseph’s Medical Center, Trinitas hospital and St Louis’ University Hospital. We compared the patients with regard to presenting symptoms, precipitating stressors, electrocardiographic findings, troponin levels, ejection fraction and in-hospital course.Results: All patients were females (mean age 64 for AA and 67 for NAA). All patients experienced chest pain and had elevated troponin levels. Two AA and three NAA patients had associated shortness of breath and one NAA had syncope. All AA and three NAA had T-wave inversions. Three NAA and one AA had ST segment elevation. Three patients in both groups developed prolongation of the QT interval. Coronary angiograms did not reveal any significant obstructive coronary artery disease. Three patients, all NAA, needed hemodynamic support during their hospital stay but none died.Conclusion: AA and NAA women with TTS have similar presenting symptoms but may differ in the electrocardiographic findings and in-hospital course of the disease. [West J Emerg Med. 2011;12(2):218-223.

Delayed Spontaneous Recanalization of Chronic Total Occlusion of Left Anterior Descending Artery after Attempted but Failed Revascularization During Percutaneous Coronary Intervention

Chronic total occlusion (CTO) of coronary artery remains the Achilles heel of the interventional cardiologist and is present in a significant proportion of referrals for coronary artery bypass graft surgery (CABG); however, with the development and standardization of modern CTO recanalization techniques, it has been able to achieve excellent success while coping with lesions of increasing complexity. Nevertheless, failure to recanalize despite the development of new techniques still remains one of the challenges in the field of interventional cardiology. Spontaneous recanalization has been described in nonocclusive coronary artery dissections in detail; none has addressed the possibility of spontaneous recanalization after failed percutaneous coronary intervention (PCI). We report a case of spontaneous but delayed recanalization of CTO of left anterior descending artery 3 years after attempted but failed revascularization during PCI

Value of Neutrophil to Lymphocyte Ratio as a Predictor of Mortality in Patients Undergoing Aortic Valve Replacement

Background: Neutrophil to lymphocyte ratio (NLR) has been studied as a measure of inflammation and as a prognosticating factor in various medical conditions including neoplastic, inflammatory and cardiovascular. The prognostic role of NLR in predicting mortality in patients with aortic stenosis undergoing surgical aortic valve replacement (AVR) has not been studied. The aim of our study is to explore the utility of NLR as a predictor of both, short and long-term mortality, in patients undergoing surgical AVR. Methods: Consecutive patients with aortic stenosis admitted for AVR to our institution were evaluated for study inclusion. Of the 335 patients admitted from January 2007 to September 2011, 234 met study inclusion criteria. Patients were divided into two groups depending on their initial preoperative NLR level with a cutoff value of 3. Three-year vital status was accessed with electronic medical records and Social Security Death Index. Survival analysis, stratified by NLR, was used to evaluate the predictive value of preoperative NLR levels. Results: Patients with NLR \u3e/=3, when compared to those with NLR /=3 had 4.77 fold increase in 3-year mortality (1.48-15.32, P=0.0090). Conclusions: NLR is an independent predictor of short-term and long-term mortality in patients with aortic stenosis undergoing AVR surgery, especially those with NLR \u3e/=3. We strongly suggest the use of NLR as a tool to risk stratify patients with aortic stenosis undergoing AVR surgery

Diagnostic Yield of Echocardiography in Syncope Patients with Normal ECG

Aim. This study aimed to assess the role of echocardiography as a diagnostic tool in evaluating syncope patients with normal versus abnormal electrocardiogram. Methods. We conducted a retrospective study of 468 patients who were admitted with syncope in 2011 at St. Joseph’s Regional Medical Center, Paterson, NJ. Hospital records and patient charts, including initial emergency room history and physical, were carefully reviewed. Patients were separated into normal versus abnormal electrocardiogram groups and then further divided as normal versus abnormal echocardiogram groups. Causes of syncope were extrapolated after reviewing all test results and records of consultations. Results. Three hundred twelve of the total patients (68.6%) had normal ECG. Two-thirds of those patients had echocardiograms; 11 patients (5.7%) had abnormal echo results. Of the aforementioned patients, three patients had previous documented history of severe aortic stenosis on prior echocardiograms. The remaining eight had abnormal but nondiagnostic echocardiographic findings. Echocardiography was done in 93 of 147 patients with abnormal ECG (63.2%). Echo was abnormal in 27 patients (29%), and the findings were diagnostic in 6.5% patients. Conclusions. This study demonstrates that echocardiogram was not helpful in establishing a diagnosis of syncope in patients with normal ECG and normal physical examination

A Giant Left Atrial Myxoma

Atrial myxomas are the most common primary cardiac tumors. Patients with left atrial myxomas generally present with mechanical obstruction of blood flow, systemic embolization, and constitutional symptoms. We present a case of an unusually large left atrial myxoma discovered incidentally in a patient with longstanding dyspnea being managed as bronchial asthma

Fragmented QRS and ejection fraction in heart failure patients admitted to the hospital

Fragmented QRS (FQRS) in 12 lead ECG was recently correlated with various outcomes in ischemic and non-ischemic heart disease. We studied the relationship between FQRS and ejection fraction (EF) in heart failure patients with QRS < 120 ms. Medical records and echocardiograms of 339 patients admitted with CHF were reviewed. ECGs were read twice by a reader blinded to all data. 70 patients with wide QRS were excluded, 63 patients had FQRS and 206 patients did not have FQRS. FQRS group were more likely to be black (OR = 2.17, p = 0.0093), and diabetic (OR = 1.79, p = 0.0451). ROC curve analysis revealed a significant relationship between EF and FQRS (p = 0.002). At EF of 48%, OR for FQRS was 4.36 (95% CI: 2.1–9.05, p < .0001). Adjustment for race and diabetes did not change the OR, or confidence intervals (Adjusted OR for race: 4.08 (95% CI: 1.06–15.67, p = 0.04), for diabetes: 4.13 (95% CI: 1.46–11.69, p = 0.008)). There was a significant difference in EF between patients with FQRS involving ≥ 2 ECG areas and non-FQRS group (p < 0.05), but not between patients with ≥ 2 vs. one area, or 1 area vs. non-FQRS. In heart failure patients with QRS < 120 ms, FQRS was observed more frequently in persons of black race and in diabetics and was associated with lower EF. This was mainly seen in patients with FQRS involving ≥ 2 ECG areas

Skin rash, eosinophilia, and renal impairment in a patient recently started on allopurinol

Allopurinol is a hypoxanthine analog which inhibits xanthine oxidase, it is a widely used medication for the treatment of hyperuricemia and gout. Allopurinol-induced drug-induced rash with eosinophilia and systemic symptoms syndrome is an infrequent, life-threatening adverse reaction of allopurinol therapy that is remarkable for the higher mortality rate with the use of allopurinol than with the use of another agent. We present a case of a 62-year-old male with a history of chronic kidney disease stage 3, hypertension and gout who developed skin rash, eosinophilia, and renal impairment 2 weeks after he was started on allopurinol therapy for gout. Allopurinol was stopped, and the patient was started on steroids. This case emphasizes that although allopurinol is commonly used the drug for the treatment of gout. However, it can be associated with serious life-threatening complications. Therefore, care should be taken when prescribing allopurinol, and it should be prescribed only for the appropriate indications