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.

A single group trial (before - after) on impact of physiotherapeutic intervention package on relief from low back pain of pregnant women.

Introduction: More than half of the women have low back pain (LBP) at some point during pregnancy; the intensity of back pain increases as the pregnancy progresses. Such changes increase their risk for musculoskeletal disorders and fall injuries. Aim and Objective: Our study's objective was to estimate the prevalence of LBP in antenatal and postnatal cases of pregnancy in PGIMER, Chandigarh and to ascertain impact of a training intervention on incidence and severity of LBP in the study subjects. Methodology: A single group trial (before and after) on impact of physiotherapeutic intervention package on relief from LBP in pregnant women in between 20 and 35 years of age group were selected. The study duration was one year. The numeric pain rating scale was taken for measuring pain intensity at different levels. Where 0 indicates no pain, 1-3 indicates mild pain (which may be nagging, annoying, and interfering little with activities of daily livings (ADLs)), 4-6 indicates moderate pain (interferes significant with ADLs), and 7-10 indicates severe pain (Disabling, unable to perform ADLs). As per available time, it was decided to include at least 30 subjects in the study. Results: Initially 45 patients were enrolled. Of those, 30 patients were suffering from backache, that is, 67% of the total and 33% did not have any backache. There were no backaches reported in the first trimester, five cases were in the second trimester, and 18 cases were in the third trimester. Of 30 patients, 11 were less than 25 years of age and remaining 19 patients were in the age group of 26-35 years.

Postural deviation in pregnancy: A significant debilitating balance problem which can be rectified by physiotherapeutic intervention.

Objective: The purpose of this study was to evaluate the effect of physiotherapeutic intervention to improve the deviated balance of pregnant women. Method: A total of 174 subjects were included in the study out of which 62 had postural deviation. They were divided into three groups, two intervention groups and one control group. The target population consisted of women in the antenatal stage, randomly selected from Obstetrics and Gynecology OPD, PGIMER, Chandigarh. The study was conducted over a period of 3 years (2014-2017). They were advised exercises, postural correction, regular walking, and hot water fomentation. Six follow-ups were taken into consideration throughout the pregnancy and postnatal stage. Result: The impact of the intervention package on both ante-natal and postnatal women with balance problems showed significant improvement. Conclusion: Postural deviations, pain, heaviness in the lower limb, incontinence, breathlessness, etc., are common complaints during and after pregnancy. The problem starts early in pregnancy and increased over time and may persist throughout life if treatment does not start early in the pregnancy. This intervention can be practiced in primary care setting after giving proper training to the health care workers by experienced physiotherapists.

Ecological safety with multifunctional applications of biogenic mono and bimetallic (Au-Ag) alloy nanoparticles.

Recently, the design and biosynthesis of metallic nanoparticles (NPs) have drawn immense interest, but their very specific function and secondary toxic effects are major concern towards commercial application of NPs. That's why environment-friendly (nontoxic) NPs having multiple functions are extremely important. Herein, we report the mechanism of biosynthesis of mono and bimetallic (Au-Ag) alloy NPs and study their multifunctional (antioxidant, antifungal and catalytic) activity and ecotoxicological property. AgNPs exhibit phytotoxicity (at 100 µg/ml) on morphological characteristics of Lentil (during germination), while alloy and AuNPs are non-toxic (up to 100 µg/ml). In-vitro antioxidant response using DPPH methods reveals that alloy NPs (IC50 = 55.8 µg/ml) possesses better antioxidant activity compared to the monometallic NPs (IC50 = 73.6-82.6 µg/ml). In addition, alloy NPs displayed appreciable antifungal efficacy against a plant pathogenic fungus Gloeosporium musarum by structural damage to hyphae and conidia of the fungus. The catalytic performance of NPs for degradation of chlorpyriphos (CP) pesticide reveals that alloy NPs is more efficient in terms of rate constant (k = 0.405 d-1) and half-life (T50 = 1.71 d) compared to the monometallic counterparts (k = 0.115-0.178 d-1; T50 = 3.89-6.04 d). Degradation products of CP (3,5,6-trichloropyridinol and diethyl thiophosphate) are confirmed using mass spectrometry and based on that a degradation pathway has been suggested. Thus, these sustainable and ecological safe biogenic (Au-Ag) alloy NPs promise multiple applications as an antioxidant in the pharmaceutical sector, as a fungicide for disease control in agriculture, as a catalyst for remediation of toxic pollutants and in other pertinent areas.

Impact of two intervention packages on the health and fitness of ante - and post-natal women attending in a teaching hospital.

INTRODUCTION: Pregnancy brings about many changes in mothers' body which continue even after the baby is born. After a vaginal delivery, taking good care of the mother is an essential part of postpartum care and to maintain overall fitness. OBJECTIVE: The purpose of this research was to evaluate the effect of a physiotherapeutic intervention to improve the maternity fitness of Indian women. METHODOLOGY: It was a three-group RCT (randomized controlled trial). The target population consisted of women in ante and postnatal stage, 50 participants (58 were included in the end) in each group, randomly selected from Obstetrics and Gynecology OPD of a tertiary care hospital in North India. The study was carried out in the department of PRM (Physiotherapy). A total of 174 participants was included in the study and was divided into three groups, two intervention groups, and one control group. The target population consisted of women in ante and postnatal stage, randomly selected from ANC (Antenatal clinic) and PNC (Post-natal clinic). The study was conducted over a period of 4 years (2014-2018). They were advised to do exercise, postural correction, regular walking, and electrotherapy modalities and six follow-ups throughout their pregnancy. Outcome measures like (Visual Analogue Scale = VAS): Low and upper back pain relief (n = 158), Leg cramps (n = 41), Coccyx pain (n = 36), Sacro-iliac joint pain (n = 26) was considered. RESULTS: The impact of the intervention package on both ante-natal and post-natal women with fitness-related health problems showed significant improvement. CONCLUSION: Pain, leg cramp and heaviness in the lower limb, coccyx pain, etc., during pregnancy are common complaints that start early in pregnancy and may persist throughout life if treatment does not start early in the pregnancy.

Effect of superoxide dismutase, catalase, and glutathione reductase supplementation on cryopreservation of Black Bengal buck semen.

The present experiment was carried out with the objectives to study the effects of antioxidants superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH) on cryopreservation of Black Bengal buck semen. Semen ejaculates (n = 60) were collected from eight bucks by artificial vagina method and diluted with Tris citrate egg yolk glycerol extender. To study the effect of antioxidants, SOD was added @ 0, 100, and 150 IU/ml; CAT was added @ 0, 200, and 400 IU/ml while GSH was added @ 0, 1, and 2 mM of diluted semen. Semen samples were equilibrated and vapor frozen in liquid nitrogen. Semen samples were evaluated after 48 h of storage for post thaw in vitro characters such as motility, viability, functional membrane integrity, and acrosome integrity. Semen extenders supplemented with SOD @ 100 and 150 IU/ml and GSH @ 1 and 2 mM had a higher (p < 0.01) number of motile cells, viable cells, HOST reacted cells, and acrosome intact cells than their respective controls. Further, semen extenders added with catalase @ 200 and 400 IU/ml had more (p < 0.05) number of viable, HOST reacted cells and significantly higher (p < 0.01) acrosome intact sperm cells than its control group. It can be concluded that supplementation of antioxidants SOD, GSH, and CAT had a beneficial effect on cryopreservation of Black Bengal buck semen.

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.

Miracle still happens: a rare case of self-inflicted penetrating injury of ear.

Though foreign bodies of ear are quite commonly encountered in our day-to-day practice, self-inflicted penetrating injury of ear is not common. One such case of selfinflicted penetrating injury of ear with giant sized nail is presented here. In this patient the nail had traversed the whole thickness of skull and the pointed end of the nail could be traced at opposite temporal area. Extraction of the nail was posed with great difficulties as it was deeply impacted inside the dense bone of skull base. Miraculously, post-operative morbidity was very minimal in this case both in terms of intracranial tissue damage and hearing impairment.

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.

The short saphenous vein: a viable alternative conduit for coronary artery bypass grafts harvested using a novel technical approach.

A multitude of vascular conduits are available to the Cardiac Surgeon performing Coronary Artery Bypass Graft operations. The Internal Mammary Artery, Radial Artery (RA), and the Long Saphenous Vein (LSV) have proven to be excellent conduits, especially in the current era of statin usage. However, previous stripping or varicosities of the LSV and calcification of the RA, coupled with the need for multiple vessel grafting, requires an alternative candidate. We describe a novel harvesting technique for bilateral simultaneous Short Saphenous Vein harvest and propose this, often forgotten vein, as a viable alternative conduit.

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.

Sternotomy following minimally invasive thoracoscopic procedures: a word of caution.

An increasing number of patients with previous minimally invasive thoracic procedures for anterior mediastinal tumors are now requiring cardiac surgery. This paper highlights the potential damage that can occur when standard sternal splitting techniques are used in these patients.

Role of intragastric balloon in cardiac surgery: an adjunct to preoperative optimization for morbid obesity.

Obesity is associated with a high risk of developing intraoperative and postoperative complications in patients undergoing cardiac surgery. Morbid obesity is a relatively common cause for delay in surgery, whereas the patients are optimized to a near normal body mass index. We evaluate the role of intragastric balloon in this group of patients. We present the case of a 68-year-old man who had successful treatment of his obesity prior to undergoing a successful triple bypass using an intragastric balloon. We draw the conclusion that intragastric balloon is a simple, safe procedure for preoperative optimization in patients with morbid obesity prior to cardiac surgery.

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.