Heyde's Syndrome - An Enigma.

Heyde's syndrome (HS) is described as the association between recurrent bleeding from angiodysplasia of the gastrointestinal tract and aortic stenosis. Aortic valve replacement has been reported to stop the bleeding. In unfit patients, the options available are interventional or conservative management. We hereby report an elderly obese patient with severe comorbidity with complicated HS involving a narrow aortic root. She underwent left ventricular outlet myomectomy and aortic root replacement to promote better forward flow and prevent restenosis and recurrence of symptoms. She was discharged home symptom-free despite being on coumadin anticoagulants.

Multiple Migrated Superior Vena Cava Stents With Cardiac Injury - A Stepwise Open Cardiotomy Strategy to Mitigate Potential Fatality.

Iatrogenic injuries with migrated interventional stents can sometimes be life-threatening. The interventional retrieval management is generally the treatment of choice, as surgical procedures carry a high mortality risk with only a few cases reported. We report a patient with two stents migrated into the right atrium from superior vena cava resulting in cardiac perforation. She was successfully treated using pericardiocentesis followed by surgical intervention with rapid post-operative resolution of symptoms. The technique presented here substantiates the steps for a safe and effective removal of these multiple displaced stents with minimal postprocedural complications.

Absent pericardium and lung hypoplasia in a child with severe mitral regurgitation.

An 8-year-old girl with severe mitral regurgitation presented with symptoms of heart failure. Clinical investigations did not raise suspicion of an absent left pericardium. Congenital defects of the pericardium are rare and frequently associated with other cardiac lesions. We describe a case of severe mitral regurgitation in a child in whom an absent left-sided pericardium with hypoplasia of left lung was found incidentally during surgery to repair the mitral valve. We believe such associations with other heart diseases is usually circumstantial but can influence the perioperative morbidity, length of hospital stay, and even alter the surgical management.

A phased Vanilla planifolia genome enables genetic improvement of flavour and production.

The global supply of vanilla extract is primarily sourced from the cured beans of the tropical orchid species Vanilla planifolia. Vanilla plants were collected from Mesoamerica, clonally propagated and globally distributed as part of the early spice trade. Today, the global food and beverage industry depends on descendants of these original plants that have not generally benefited from genetic improvement. As a result, vanilla growers and processors struggle to meet global demand for vanilla extract and are challenged by inefficient and unsustainable production practices. Here, we report a chromosome-scale, phased V. planifolia genome, which reveals sequence variants for genes that may impact the vanillin pathway and therefore influence bean quality. Resequencing of related vanilla species, including the minor commercial species Vanilla × tahitensis, identified genes that could impact productivity and post-harvest losses through pod dehiscence, flower anatomy and disease resistance. The vanilla genome reported in this study may enable accelerated breeding of vanilla to improve high-value traits.

Cardiac Arrest with Multi-vessel Coronary Artery Disease and Successful Treatment After Long Conventional Cardiopulmonary Resuscitation: How Long Is Too Long?

Coronary artery disease (CAD) is the most common killer disease, responsible for about one-third of all deaths at ages above 35. The majority of all survivors of out-of-hospital cardiac arrests present to the emergency department (ED) with an initial shockable rhythm (ventricular fibrillation or pulse-less ventricular tachycardia), which is a predictor of survival. Odds for survival are less for non-shockable rhythm and favorable neurologic outcomes decrease as the length of cardiopulmonary resuscitation (CPR) increases. The median time-to-return of spontaneous circulation among those with favorable neurological outcomes is less than 10 minutes. On the other hand, a large review of more than 64,000 patients with in-hospital cardiac arrests showed that patients with longer median resuscitation times had a greater chance of the return of spontaneous circulation and survival to discharge. We described a case of prolonged resuscitation lasting almost three hours of CPR followed by successful percutaneous intervention with a favorable neurologic outcome.

Factor VII deficiency: do all need replacement for cardiac surgery?

In cardiac surgery, supplementation with recombinant factor VIIa is the treatment of choice for patients with factor VII deficiency, but overzealous administration can be associated with thromboembolic side-effects. A 53-year-old man with factor VII activity 15.2%, international normalized ratio 2.9, and acute thrombotic critical coronary anatomy, underwent coronary artery bypass surgery and a thoracotomy with decortication 5 months later. He was managed successfully without recombinant factor VIIa supplementation. This case demonstrates that current bedside and laboratory tests such as thromboelastography, prothrombin time or international normalized ratio, and factor VII activity may not predict replacement therapy in these patients.

Management issues during postinfarction ventricular septal defect and role of perioperative optimization: A case series.

The development of a myocardial infarction ventricular septal rupture is a rare fatal complication, and the surgical repair is the treatment of choice. In most of the scenarios, the operation will be done as an emergency procedure that carries high mortality. Prognosis of these patients depends on prompt echocardiographic diagnosis and the proactive medical and surgical therapy. More recently, various options have been put forward including the timing for surgery, percutaneous closure devices, and the improved outcome with initial stabilization with medical treatment including mechanical support. In this retrospective case series, we are presenting the management of these patients who presented us in different clinical scenarios and trying to identify the risks for the poor outcome and to formulate a strategy to improve the outcome.

Is baseline cerebral oximetry a better predictor than carotid scan for postoperative delirium in cardiac surgery?

Guidelines recommend screening patients for carotid-artery stenosis, but unfortunately, measurement of baseline cerebral oximetry levels is still not a routine practice prior to cardiac surgery. We report a 41-year-old woman who presented with a normal carotid scan and unexpectedly low baseline cerebral oximetry levels. She had delayed postoperative recovery and discharge from hospital following her coronary-artery bypass surgery. This case report reiterates the prognostic significance of cerebral oximetry in the preoperative checkup and the association of low intraoperative values to postoperative cerebral impairment. It can also be identified as a comparatively better tool for preventing cognitive disturbances after cardiac surgery.

Cerebral oxygenation monitoring in patients with bilateral carotid stenosis undergoing urgent cardiac surgery: Observational case series.

BACKGROUND: Patients with significant bilateral carotid artery stenosis requiring urgent cardiac surgery have an increased risk of stroke and death. The optimal management strategy remains inconclusive, and the available evidence does not support the superiority of one strategy over another. MATERIALS AND METHODS: A number of noninvasive strategies have been developed for minimizing perioperative stroke including continuous real-time monitoring of cerebral oxygenation with near-infrared spectroscopy (NIRS). The number of patients presenting with this combination (bilateral significant carotid stenosis requiring urgent cardiac surgery) in any single institution will be small and hence there is a lack of large randomized studies. RESULTS: This case series describes our early experience with NIRS in a select group of patients with significant bilateral carotid stenosis undergoing urgent cardiac surgery (n = 8). In contrast to other studies, this series is a single surgeon, single center study, where the entire surgery (both distal ends and proximal ends) was performed during single aortic clamp technique, which effectively removes several confounding variables. NIRS monitoring led to the early recognition of decreased cerebral oxygenation, and corrective steps (increased cardiopulmonary bypass flow, increased pCO 2 , etc.,) were taken. CONCLUSION: The study shows good clinical outcome with the use of NIRS. This is our "work in progress," and we aim to conduct a larger study.

Severe antiphospholipid syndrome and cardiac surgery: Perioperative management.

Antiphospholipid syndrome is an antiphospholipid antibody-mediated prothrombotic state leading to arterial and venous thrombosis. This condition alters routine in-vitro coagulation tests, making results unreliable. Antiphospholipid syndrome patients requiring cardiac surgery with cardiopulmonary bypass present a unique challenge in perioperative anticoagulation management. We describe 3 patients with antiphospholipid syndrome who had successful heart valve surgery at our institution. We have devised an institutional protocol for antiphospholipid syndrome patients, and all 3 patients were managed according to this protocol. An algorithm-based approach is recommended because it improves team work, optimizes treatment, and improves patient outcome.

Cellular localization and characterization of cytosolic binding partners for Gla domain-containing proteins PRRG4 and PRRG2.

The genes encoding a family of proteins termed proline-rich γ-carboxyglutamic acid (PRRG) proteins were identified and characterized more than a decade ago, but their functions remain unknown. These novel membrane proteins have an extracellular γ-carboxyglutamic acid (Gla) protein domain and cytosolic WW binding motifs. We screened WW domain arrays for cytosolic binding partners for PRRG4 and identified novel protein-protein interactions for the protein. We also uncovered a new WW binding motif in PRRG4 that is essential for these newly found protein-protein interactions. Several of the PRRG-interacting proteins we identified are essential for a variety of physiologic processes. Our findings indicate possible novel and previously unidentified functions for PRRG proteins.

In vivo genome editing restores haemostasis in a mouse model of haemophilia.

Editing of the human genome to correct disease-causing mutations is a promising approach for the treatment of genetic disorders. Genome editing improves on simple gene-replacement strategies by effecting in situ correction of a mutant gene, thus restoring normal gene function under the control of endogenous regulatory elements and reducing risks associated with random insertion into the genome. Gene-specific targeting has historically been limited to mouse embryonic stem cells. The development of zinc finger nucleases (ZFNs) has permitted efficient genome editing in transformed and primary cells that were previously thought to be intractable to such genetic manipulation. In vitro, ZFNs have been shown to promote efficient genome editing via homology-directed repair by inducing a site-specific double-strand break (DSB) at a target locus, but it is unclear whether ZFNs can induce DSBs and stimulate genome editing at a clinically meaningful level in vivo. Here we show that ZFNs are able to induce DSBs efficiently when delivered directly to mouse liver and that, when co-delivered with an appropriately designed gene-targeting vector, they can stimulate gene replacement through both homology-directed and homology-independent targeted gene insertion at the ZFN-specified locus. The level of gene targeting achieved was sufficient to correct the prolonged clotting times in a mouse model of haemophilia B, and remained persistent after induced liver regeneration. Thus, ZFN-driven gene correction can be achieved in vivo, raising the possibility of genome editing as a viable strategy for the treatment of genetic disease.

Enhanced delivery and expression of a nanoencapsulated DNA vaccine vector for respiratory syncytial virus.

This study evaluated the efficiency of chitosan-encapsulated DNA-based respiratory syncytial virus (RSV) vaccine. Antigenic regions of RSV F, M2, and G genes were cloned into the human cytomegalovirus promoter-based constitutive expression vector, resulting in a DNA vaccine vector named DR-FM2G. This vector was used to formulate DNA-chitosan nanoparticles (DCNPs) using a complex coacervation process that yielded an encapsulation efficiency of 94.7%. The DCNP sizes ranged from 80 to 150 nm with uniform size distribution and spherical shape. DNA release was between 50% and 60% when DCNPs were incubated with similar gastrointestinal fluid (pH 2), whereas 21% to 25% of DNA was released from DCNPs in 30 minutes at pH 10. Differential scanning calorimetry showed DCNPs to be more stable than naked DNA or chitosan, offering protection from DNA degradation by nucleases. DCNPs were not toxic to cells when used at concentrations < or =400 microg/mL. Immunohistochemical and real-time polymerase chain reaction results showed a higher level of RSV protein expression in mouse tissues given when DCNPs were injected intravenously as compared with naked DNA. FROM THE CLINICAL EDITOR: This study evaluated the efficiency of chitosan-encapsulated DNA-based respiratory syncytial virus (RSV) vaccine, showing a higher level of RSV protein expression in mouse tissues given when DCNPs were injected intravenously as compared with naked DNA.

DNA recombination activity in soybean mitochondria.

Mitochondrial genomes in higher plants are much larger and more complex as compared to animal mitochondrial genomes. There is growing evidence that plant mitochondrial genomes exist predominantly as a collection of linear and highly branched DNA molecules and replicate by a recombination-dependent mechanism. However, biochemical evidence of mitochondrial DNA (mtDNA) recombination activity in plants has previously been lacking. We provide the first report of strand-invasion activity in plant mitochondria. Similar to bacterial RecA, this activity from soybean is dependent on the presence of ATP and Mg(2+). Western blot analysis using an antibody against the Arabidopsis mitochondrial RecA protein shows cross-reaction with a soybean protein of about 44 kDa, indicating conservation of this protein in at least these two plant species. mtDNA structure was analyzed by electron microscopy of total soybean mtDNA and molecules recovered after field-inversion gel electrophoresis (FIGE). While most molecules were found to be linear, some molecules contained highly branched DNA structures and a small but reproducible proportion consisted of circular molecules (many with tails) similar to recombination intermediates. The presence of recombination intermediates in plant mitochondria preparations is further supported by analysis of mtDNA molecules by 2-D agarose gel electrophoresis, which indicated the presence of complex recombination structures along with a considerable amount of single-stranded DNA. These data collectively provide convincing evidence for the occurrence of homologous DNA recombination in plant mitochondria.

Investigation of the role of the histidine-aspartate pair in the human exonuclease III-like abasic endonuclease, Ape1.

Hydrogen bonded histidine-aspartate (His-Asp) pairs are critical constituents in several key enzymatic reactions. To date, the role that these pairs play in catalysis is best understood in serine and trypsin-like proteases, where structural and biochemical NMR studies have revealed important pK(a) values and hydrogen bonding patterns within the catalytic pocket. However, the role of the His-Asp pair in metal-assisted catalysis is less clear. Here, we apply liquid-state NMR to investigate the role of a critical histidine residue of apurinic endonuclease 1 (Ape1), a human DNA repair enzyme that cleaves adjacent to abasic sites in DNA using one or more divalent cations and an active-site His-Asp pair. The results of these studies suggest that the Ape1 His-Asp pair does not function as either a general base catalyst or a metal ligand. Rather, the pair likely stabilizes the pentavalent transition state necessary for phospho-transfer.