Unveiling the nongenomic actions of thyroid hormones in adult mammalian brain: The legacy of Mary B. Dratman.

A comprehensive review was conducted to compile the contributions of Mary B. Dratman and studies by other researchers in the field of nongenomic actions of thyroid hormones in adult mammalian brain. Dratman and her collaborators authored roughly half of the papers in this area. It has been almost fifty years since Dratman introduced the novel concept of thyroid hormones as neurotransmitters for the first time. The characterization of unique brain-region specific accumulation of thyroid hormones within the nerve terminals in adult mammals was a remarkable contribution by Dratman. It suggested a neurotransmitter- or neuromodulator-like role of thyroid hormone and/or its derivative, 3-iodothyronamine within adrenergic systems in adult mammalian brain. Several studies by other researchers using synaptosomes as a model system, have contributed to the concept of direct nongenomic actions of thyroid hormones at synaptic regions by establishing that thyroid hormones or their derivatives can bind to synaptosomal membranes, alter membrane functions including enzymatic activities and ion transport, elicit Ca2+/NO-dependent signaling pathways and induce substrate-protein phosphorylation. Such findings can help to explain the physiological and pathophysiological roles of thyroid hormone in psychobehavioral control in adult mammalian brain. However, the exact mode of nongenomic actions of thyroid hormones at nerve terminals in adult mammalian brain awaits further study.

Nongenomic roles of thyroid hormones and their derivatives in adult brain: are these compounds putative neurotransmitters?

We review the evidence regarding the nongenomic (or non-canonical) actions of thyroid hormones (thyronines) and their derivatives (including thyronamines and thyroacetic acids) in the adult brain. The paper seeks to evaluate these compounds for consideration as candidate neurotransmitters. Neurotransmitters are defined by their (a) presence in the neural tissue, (b) release from neural tissue or cell, (c) binding to high-affinity and saturable recognition sites, (d) triggering of a specific effector mechanism and (e) inactivation mechanism. Thyronines and thyronamines are concentrated in brain tissue and show distinctive patterns of distribution within the brain. Nerve terminals accumulate a large amount of thyroid hormones in mature brain, suggesting a synaptic function. However, surprisingly little is known about the potential release of thyroid hormones at synapses. There are specific binding sites for thyroid hormones in nerve-terminal fractions (synaptosomes). A notable cell-membrane binding site for thyroid hormones is integrin αvß3. Furthermore, thyronines bind specifically to other defined neurotransmitter receptors, including GABAergic, catecholaminergic, glutamatergic, serotonergic and cholinergic systems. Here, the thyronines tend to bind to sites other than the primary sites and have allosteric effects. Thyronamines also bind to specific membrane receptors, including the trace amine associated receptors (TAARs), especially TAAR1. The thyronines and thyronamines activate specific effector mechanisms that are short in latency and often occur in subcellular fractions lacking nuclei, suggesting nongenomic actions. Some of the effector mechanisms for thyronines include effects on protein phosphorylation, Na+/K+ ATPase, and behavioral measures such as sleep regulation and measures of memory retention. Thyronamines promptly regulate body temperature. Lastly, there are numerous inactivation mechanisms for the hormones, including decarboxylation, deiodination, oxidative deamination, glucuronidation, sulfation and acetylation. Therefore, at the current state of the research field, thyroid hormones and their derivatives satisfy most, but not all, of the criteria for definition as neurotransmitters.

Self-perceived evidence-based practice competencies: a survey of faculty and students at a chiropractic institution.

OBJECTIVE: To assess the self-perceived importance, skills, and utilization of evidence-based practice (EBP) among faculty and students at a chiropractic institution without a structured EBP program. The survey also evaluated EBP satisfaction among students and EBP implementation barriers/facilitators among the faculty. METHODS: In this cross-sectional study, a set of organized questionnaires to assess the importance of EBP and self-perceived skills, utilization, barriers, and facilitators for faculty members, and student satisfaction was administered to the students and faculty of a chiropractic institution in February-March 2016. Descriptive statistics were used to evaluate responses. RESULTS: A total of 417 (60.1%) students and 27 (60.0%) faculty members completed the survey. Faculty members' and students' EBP importance values were similar (8.4 and 8.3 out of 10, respectively), but faculty members self-reported their EBP skills (7.3/10) at a higher level than the student self-reported skill level (6.1/10). For utilization, students reported a higher utilization of EBP than that reported by the responding faculty members. Perceived student satisfaction on the quality and content of research-related experiences decreased from the first year to the third (final) year. CONCLUSION: This study found variance in the self-perceived EBP skills, utilization, barriers, and facilitators and that these skills are lagging at our doctor of chiropractic program, which does not have a structured EBP program. Faculty members and students identified the importance for EBP. Similar observations have been found at other chiropractic institutions prior to their implementation of a systematic EBP program. Those developing an EBP curriculum might use these findings to better design, implement, and assess a structured program.

Training the novice to become cardiac surgeon: does the "early learning curve" training compromise surgical outcomes?

OBJECTIVE: It is unclear whether novice trainees can be taught safely to perform adult cardiac surgery without any impact on early or late outcomes. METHODS: All patients (n = 1305) data were obtained from an externally validated, mandatory institutional database (2003-2010). 'Novice' is defined as a trainee who required substantial assistance or supervision to perform part or whole of the specified procedure (Intercollegiate Surgical Curriculum Programme UK, Competency Level ≤2). Outcome measures were in-hospital mortality, composite score of in-hospital mortality-morbidities, mid-term survival and revascularisation rate after CABG. Follow-up up to 7 years (median 3.2 years) was determined. RESULTS: Some 39 % (n = 510) of the cases involved novice (28 %-part, 11 %-whole procedure), 12 % (n = 157) competent trainees and 49 % (n = 638) consultant. Median EuroSCORE was higher in consultant group (p < 0.001). Without risk adjustment, composite outcome score and mid-term mortality were higher in consultant group (p = 0.03). With adjustment using EuroSCORE and propensity scores, EuroSCORE was significantly predictive of in-hospital mortality [odd ratio (OR) 1.38, 95 %CI 1.20-1.57, p < 0.001], composite outcome (OR 1.26, 95 %CI 1.15-1.37, p < 0.001) and mid-term mortality (HR 1.24, 95 %CI 1.18-1.31, p < 0.001) but not the operator categories. Further analysis of subcohort undergoing first-time, isolated CABG (n = 1070) showed that EuroSCORE remained predictive of adjusted in-hospital mortality (OR 1.39, 95 %CI 1.13-1.71, p = 0.002), composite outcome (OR 1.33, 95 %CI 1.19-1.49, p < 0.001) and mid-term mortality (HR 1.22, 95 %CI 1.10-1.35, p < 0.001). The operator categories were not associated with adjusted outcome measures including revascularisation rate after CABG. CONCLUSION: Supervised training in adult cardiac surgery can be achieved safely at the early learning curve phase without compromising both early and mid-term clinical outcomes.

Mechanisms of L-triiodothyronine-induced inhibition of synaptosomal na(+)-k(+)-ATPase activity in young adult rat brain cerebral cortex.

The role of thyroid hormones (TH) in the normal functioning of adult mammalian brain is unclear. Our studies have identified synaptosomal Na(+)-K(+)-ATPase as a TH-responsive physiological parameter in adult rat cerebral cortex. L-triiodothyronine (T3) and L-thyroxine (T4) both inhibited Na(+)-K(+)-ATPase activity (but not Mg(2+)-ATPase activity) in similar dose-dependent fashions, while other metabolites of TH were less effective. Although both T3 and the ß -adrenergic agonist isoproterenol inhibited Na(+)-K(+)-ATPase activity in cerebrocortical synaptosomes in similar ways, the ß -adrenergic receptor blocker propranolol did not counteract the effect of T3. Instead, propranolol further inhibited Na(+)-K(+)-ATPase activity in a dose-dependent manner, suggesting that the effect of T3 on synaptosomal Na(+)-K(+)-ATPase activity was independent of ß -adrenergic receptor activation. The effect of T3 on synaptosomal Na(+)-K(+)-ATPase activity was inhibited by the α2-adrenergic agonist clonidine and by glutamate. Notably, both clonidine and glutamate activate Gi-proteins of the membrane second messenger system, suggesting a potential mechanism for the inhibition of the effects of TH. In this paper, we provide support for a nongenomic mechanism of action of TH in a neuronal membrane-related energy-linked process for signal transduction in the adult condition.

Acute Right Coronary Ostial Stenosis during Aortic Valve Replacement.

We report a rare case of acute right coronary artery stenosis developing in a patient undergoing aortic valve replacement. We present a case report with a brief overview of the literature relating to coronary artery occlusion associated with cardiac valve surgery - the theories and treatments are discussed. A 85 year-old female was admitted under the care of the cardiothoracic team with signs and symptoms of heart failure. Investigations, including cardiac echocardiography and coronary angiography, indicated a critical aortic valve stenosis. Intraoperative right ventricular failure ensued post aortic valve replacement. Subsequent investigations revealed an acute occlusion of the proximal right coronary artery with resultant absence of distal flow supplying the right ventricle. An immediate right coronary artery bypass procedure was performed with resolution of the right ventricular failure. Subsequent weaning off cardiopulmonary bypass was uneventful and the patient continued to make excellent recovery in the postoperative phase. To our knowledge this is one of the few documented cases of intraoperative acute coronary artery occlusion developing during valve surgery. However, surgeons should be aware of the potential for acute occlusion so that early recognition and rapid intervention can be instituted.

Fracture-dislocation of humeral head with intrathoracic displacement.

Intrathoracic displacement of fractured head of the humerus is a very rare injury. We describe a case of such injury in a 48-old-year lady who presented after a simple fall. She required chest drainage and a thoracotomy to remove the head of the humerus. She subsequently had shoulder hemiarthroplasty with a good outcome.

Comprehensive preassessment form for adult cardiac surgery.

Comprehensive evaluation of our patients before putting them under "the knife" can never be overemphasized. It is our duty to care for the patients. Detailed history-taking, clinical examination, and investigations are mandatory prior to surgery. For many years, we have striven to make our method thorough and safe for all patients. We propose here a simple, comprehensive preassessment form that is easily applicable in any unit.

Non-genomic effect of L-triiodothyronine on calmodulin-dependent synaptosomal protein phosphorylation in adult rat cerebral cortex.

The present study was undertaken to examine calmodulin-dependent effect of thyroid hormones (THs) on synaptosomal protein phosphorylation in mature rat brain. Effect of L-triiodothyronine (L-T3) on in vitro protein phosphorylation was measured in a hypotonic lysate of synaptosomes prepared from adult male rat cerebral cortex, incubated in presence and absence of calcium ion (Ca2+) and calmodulin. L-T3 significantly enhanced incorporation of 32P into synaptosomal proteins as compared to basal level of phosphorylation in the presence of Ca2+ and calmodulin. Under these conditions, increase in protein phosphorylation was 47, 74 and 52% for 10 nM, 100 nM and 1 microM L-T3, respectively. Chelation of Ca2+ using ethylene glycol-bis (2-aminoethylether)-N, N, N', N'-tetraacetic acid (EGTA) inhibited the effects of Ca2+/calmodulin on TH-stimulated protein phosphorylation levels. This study suggests that a high proportion of L-T3-stimulated protein phosphorylation involves Ca2+/calmodulin-dependent pathways in adult rat cerebrocortical synaptosomes.

Atrial myxomas: a single unit's experience in the modern era.

BACKGROUND: Although an atrial myxoma is the commonest cardiac tumor, it is still relatively rare, with an annual incidence of approximately 0.5 per million. In our unit, which performs 1000 major cardiac procedures per year, this equates to approximately 3 patients annually. We therefore sought to evaluate our experience of managing this type of tumor over the last 5 years. METHODS: A retrospective review was performed of prospectively collected data from the departmental database. We analyzed consecutive patients who were operated upon between 2002 and 2007. Three patients with a papillary fibroelastoma on histological examination were excluded from this study. RESULTS: We have performed excision of atrial myxoma in 18 patients. Twelve patients (66%) were female; the median age was 64 years (range, 35-80 years), and the median logistic euroSCORE was 5.22% (range, 1.51-27.82%). Fifteen patients (83%) were deemed urgent, 2 elective, and 1 emergency. Sixteen tumors (89%) were left sided. Symptoms attributable to the tumor were found in 16 of the 18 patients (embolic, n = 9; chest pain, n = 3; palpitations, n = 2; incidental finding, n = 2, others n = 4), and the mean time from diagnosis to operation was 3 days (range, 0-22 months). The median cardiopulmonary bypass time was 87 minutes (range, 28-228 minutes), with the median aortic cross clamp time being 61 minutes (16-175 minutes).The approaches used were transeptal via right atriotomy (n = 8), biatrial/Dubost (n = 4), left atrial (n = 4), and right atrial (n = 2); the interatrial septum was involved in 14 patients. The resultant defect was closed using a pericardial (n = 8) or prosthetic patch (n = 5) or directly sutured (n = 5). Concomitant procedures were performed in 8 patients (coronary artery bypass graft [CABG], n = 4; mitral valve replacement [MVR], n = 2; valve + grafts, n = 2). All tumors were completely excised.Postoperatively there were no deaths within 30 days of the procedure. Indeed, only 2 patients have died at 4 and 25 months postoperatively, respectively, both of unrelated causes. Median intensive therapy unit (ITU) stay was 2 days (range, 1-9 days), and median hospital stay was 10 days (range, 5-20 days). A permanent pacemaker was required in only 1 patient, and median blood loss was 340 mL (range, 140-1760 mL). Atrial fibrillation was the commonest complication affecting 6/18 patients (33%). CONCLUSIONS: Excision of atrial myxoma can be performed using a variety of intraoperative approaches and closure techniques, all with acceptable postoperative morbidity and low mortality rates. To date, no recurrences have been found at median 2-year follow-up.

Conduits for coronary artery bypass surgery: the quest for second best.

Coronary artery bypass grafting is one of the most outstanding surgical achievements of the 20th century. Over its 50-year history patient outcomes have become excellent owing to technical refinements, myocardial protection, the use of antiplatelet and anticholesterol drugs, and the continued search for better conduits. The performance of conduits used for bypass remains the most important prognostic factor, with the left internal mammary artery being the conduit of choice due to its excellent patency rates. There is, however, uncertainty with regards which conduit is second best. The recent resurgence of the radial artery has led to an increase in its use as surgeons lean towards total arterial revascularization but there is emerging evidence that the performance of the long saphenous vein graft is improving. Furthermore, bilateral internal mammary artery grafting is preferred in some centres as an alternative approach to total arterial revascularization, with multiple reports of superior long-term event-free outcome with its use. This extensive review of current literature reveals an absence of clear consensus as to what mix of conduits provides the best long-term outcomes. The quest for second best continues. Arterial conduits appear to be superior when grafted to tight stenosis but veins remain popular with surgeons. More supportive evidence from the concluding Arterial Revascularization trial and the Radial Artery Patency and Clinical Outcomes trial should guide future practice.

'Scoop and run' strategy for a resuscitative sternotomy following unstable penetrating chest injury.

The optimal management strategy of an unstable penetrating thoracic trauma remains a debate. It is unclear whether a 'stay and treat' or 'scoop and run' to the nearest operating theatre with cardiothoracic expertise is the best strategy. We describe a successful outcome of a young patient with injuries to the left internal mammary artery, upper lobe and main pulmonary artery following a stab injury to his left chest. He was transferred to the nearest cardiac centre for emergency sternotomy. Thoracotomy is the classical surgical approach in emergency setting but sternotomy allows adequate exposure to repair any cardiac injury, institution of cardiopulmonary bypass, and careful inspection of the mediastinal structures to prevent any late complications including pulmonary artery pseudoaneurysm. An immediate transfer, where possible, to the nearest trauma centre with cardiothoracic expertise for 'resuscitative' sternotomy is advocated in penetrating thoracic injury for optimal outcome. An emergency room thoracotomy should be reserved to those in the extremis.

The risk of fatal re-expansion pulmonary oedema in poor left ventricular reserve.

Re-expansion pulmonary oedema (REPO) is an uncommon complication which may be encountered following drainage of pneumothorax, pleural effusion or haemopneumothorax. Treatment is usually supportive and some patients may require positive pressure ventilation. We provide a novel description of the mechanism of a fatal REPO in a patient with a small and non-compliant left ventricle (LV). We urge for an extreme caution when performing thoracocentesis in patients with poor LV reserve.

Simple technique of talc delivery for video-assisted talc pleurodesis.

It has been proven that talc is the sclerosant of choice for pleurodesis, especially for malignant effusions. Uniform talc deposition on the visceral pleura is often difficult, resulting in clump deposition with the use of an atomizer or bladder syringe delivery apparatus. We have devised a simple sterile apparatus that allows the operator to retain full control over the talc delivery rate and coat the lung uniformly under direct vision using a pressurized system.

Successful angiographic embolisation of bleeding into the chest wall after chest drain insertion.

Peripheral arterial injuries after blunt or penetrating trauma commonly follow injuries to adjacent soft tissue and bone. The traditional approach to these injuries is by open exploration, with identification and ligation of the bleeding vessel. We describe the case of a type II respiratory failure patient who had an enormous pectoral muscle haematoma following chest drain insertion, in whom the bleeding was only controlled by angiographic embolisation following failure of surgical exploration.