Δευτέρα 9 Οκτωβρίου 2017

Calcium and electrical dynamics in lymphatic endothelium

Abstract

Subsequent to a rise in intracellular Ca2+ ([Ca2+]i), hyperpolarization of the endothelium coordinates vascular smooth muscle relaxation along resistance arteries during blood flow control. In the lymphatic vasculature, collecting vessels generate rapid contractions coordinated along lymphangions to propel lymph, but the underlying signalling pathways are unknown. We tested the hypothesis that lymphatic endothelial cells (LECs) exhibit Ca2+ and electrical signalling properties that facilitate lymph propulsion. To study electrical and intracellular Ca2+ signalling dynamics in lymphatic endothelium, we excised collecting lymphatic vessels from the popliteal fossa of mice and removed their muscle cells to isolate intact LEC tubes (LECTs). Intracellular recording revealed a resting membrane potential of ∼−70 mV. Acetylcholine (ACh) increased [Ca2+]i with a time course similar to that observed in endothelium of resistance arteries (i.e. rapid initial peak with a sustained "plateau"). In striking contrast to the endothelium-derived hyperpolarization (EDH) characteristic of arteries, LECs depolarized (>15 mV) to either ACh or TRPV4 channel activation. This depolarization was facilitated by the absence of Ca2+-activated K+ channels (KCa) as confirmed with PCR, persisted in the absence of extracellular Ca2+, was abolished by LaCl3 and was attenuated ∼70% in LECTs from Trpv4−/− mice. Computational modelling of ion fluxes in LECs indicated that omitting K+ channels supports our experimental results. These findings reveal novel signalling events in LECs, which are devoid of the KCa activity abundant in arterial endothelium. Absence of EDH with effective depolarization of LECs may promote the rapid conduction of contraction waves along lymphatic muscle during lymph propulsion.

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Radiation, radionuclides and bacteria: An in-perspective review

Publication date: December 2017
Source:Journal of Environmental Radioactivity, Volume 180
Author(s): Arpit Shukla, Paritosh Parmar, Meenu Saraf
There has been a significant surge in consumption of radionuclides for various academic and commercial purposes. Correspondingly, there has been a considerable amount of generation of radioactive waste. Bacteria and archaea, being earliest inhabitants on earth serve as model microorganisms on earth. These microbes have consistently proven their mettle by surviving extreme environments, even extreme ionizing radiations. Their ability to accept and undergo stable genetic mutations have led to development of recombinant mutants that are been exploited for remediation of various pollutants such as; heavy metals, hydrocarbons and even radioactive waste (radwaste). Thus, microbes have repeatedly presented themselves to be prime candidates suitable for remediation of radwaste. It is interesting to study the behind-the-scenes interactions these microbes possess when observed in presence of radionuclides. The emphasis is on the indigenous bacteria isolated from radionuclide containing environments as well as the five fundamental interaction mechanisms that have been studied extensively, namely; bioaccumulation, biotransformation, biosorption, biosolubilisation and bioprecipitation. Application of microbes exhibiting such mechanisms in remediation of radioactive waste depends largely on the individual capability of the species. Challenges pertaining to its potential bioremediation activity is also been briefly discussed. This review provides an insight into the various mechanisms bacteria uses to tolerate, survive and carry out processes that could potentially lead the eco-friendly approach for removal of radionuclides.

Graphical abstract

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Disclosing hidden information in the electroencephalogram using advanced signal analytical techniques

Abstract

Recording of brain activity with the aid of the electroencephalogram (EEG) can be regarded as one of the gold standards in the diagnosis of epilepsy, a neurological disorder characterized by recurrent periods of hypersynchronous activity, visible as sharp spike- or polyspike-wave complexes in the recording traces of the EEG.

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Architecture and Distribution of Introns in Core Genes of Four Fusarium Species

Removal of introns from transcribed RNA represents a crucial step during the production of mRNA in eukaryotes. Available whole-genome sequences and expressed sequence tags (ESTs) has increased our knowledge of this process and revealed various commonalities among eukaryotes. However, certain aspects of intron structure and diversity are taxon-specific, which can complicate the accuracy of in silico gene prediction methods. Using core genes, we evaluated the distribution and architecture of Fusarium circinatum spliceosomal introns and linked these characteristics to the accuracy of the predicted gene models of the genome of this fungus. We also evaluated intron distribution and architecture in F. verticillioides, F. oxysporum and F. graminearum and made comparisons with F. circinatum. Results indicated that F. circinatum and the three other Fusarium species have canonical 5 and 3 splice sites, but with subtle differences that are apparently not shared with those of other fungal genera. The polypyrimidine tract of Fusarium introns was also found to be highly divergent among species and genes. Furthermore, the conserved Adenosine nucleoside required during the first step of splicing is contained within unique branch site motifs in certain Fusarium introns. Data generated here show that introns of F. circinatum as well as F. verticillioides, F. oxysporum and F. graminearum are characterized by a number of unique features such as the CTHAH and ACCAT motifs of the branch site.  Incorporation of such information into genome annotation software will undoubtedly improve the accuracy of gene prediction methods used for Fusarium species and related fungi.



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Performance of Pediatric Rehabilitation Medicine Candidates on the Subspecialty Board Certification Examination from 2003-2015

Pediatric Rehabilitation Medicine (PRM) physicians enter the field via several pathways. It is unknown if different training pathways impact performance on the American Board of Physical Medicine and Rehabilitation (ABPMR) PRM Examination and Maintenance of Certification (MOC) Examination.

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Using principal trabecular orientation to differentiate joint loading orientation in the 3rd metacarpal heads of humans and chimpanzees

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Publication date: December 2017
Source:Journal of Human Evolution, Volume 113
Author(s): Meir M. Barak, Emma Sherratt, Daniel E. Lieberman
If Wolff's law is valid, then quantifying the three-dimensional architecture of trabecular bone, specifically 3D principal trabecular orientation (3D-PTO), can reveal joint loading direction among different taxa. This study measured the architecture of trabecular bone in the 3rd metacarpal head of humans and chimpanzees, and then tested their association with expected joint loading direction. We postulate that since chimpanzees, unlike humans, directly load their metacarpal bones during knuckle-walking, trabecular structure in the dorsal aspect of the 3rd metacarpal head will be significantly more organized and robust in chimpanzees. To test this hypothesis, we micro-CT scanned the 3rd metacarpal from 11 chimpanzees and 12 humans. Three 6 mm volumes of interest (VOI; palmar, center and dorsal) were selected and trabecular bone properties and 3D-PTO were measured. The results revealed many similarities between humans and chimpanzees: in both taxa the dorsal VOI demonstrated the lowest bone volume fraction (BV/TV), the most rod-like trabecular structure, the fewest and thinnest trabeculae, and low organization of the trabecular architecture (degree of anisotropy). Nevertheless, 3D-PTO in the dorsal VOI differed significantly between humans and chimpanzees. While 3D-PTO in humans was clustered together and aligned nearly along the bone long axis, in chimpanzees 3D-PTO was divided into two distinct groups and aligned with an angle toward either the medial or lateral orientations. Our results suggest that loading effects on trabecular bone properties such as BV/TV might be partially constrained by genetic factors. On the other hand, 3D-PTO is continually affected by active loading (i.e., modeling) and thus may serve as a useful tool to infer differences in joint loading directions.



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Atrial myxomas causing severe left and right ventricular dysfunction

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Aanchal Dixit, Prabhat Tewari, Rashmi Soori, Surendra Kumar Agarwal

Annals of Cardiac Anaesthesia 2017 20(4):450-452

Myxomas are the most common cardiac tumors, accounting for about 50% of benign primary cardiac tumors, with the majority located in the left atrium, and 80% of which originate in the interatrial septum. We report two cases with severe cachexia, neurological sequelae, and severe biventricle dysfunction secondary to atrial myxomas with marked early improvement after tumor excision.

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Think beyond right bundle branch block in atrial septal defect

AnnCardAnaesth_2017_20_4_475_216253_f1.j

Monish S Raut, Arvind Verma, Arun Maheshwari, Ganesh Shivnani

Annals of Cardiac Anaesthesia 2017 20(4):475-476



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Congenital syndromes affecting heart and airway alike

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Rajinder Singh Rawat

Annals of Cardiac Anaesthesia 2017 20(4):393-394



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The use of intravenous hydroxocobalamin as a rescue in methylene blue-resistant vasoplegic syndrome in cardiac surgery

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Yi Cai, Anwar Mack, Beth L Ladlie, Archer Kilbourne Martin

Annals of Cardiac Anaesthesia 2017 20(4):462-464

Vasoplegic syndrome is a well-recognized complication during cardiopulmonary bypass (CPB) and is associated with increased morbidity and mortality, especially when refractory to conventional vasoconstrictor therapy. This is the first reported case of vasoplegia on CPB unresponsive to methylene blue whereas responsive to hydroxocobalamin, which indicates that the effect of hydroxocobalamin outside of the nitric oxide system is significant or that the two drugs have a synergistic effect in one or multiple mechanisms.

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Low-dose intravenous ketamine for postcardiac surgery pain: Effect on opioid consumption and the incidence of chronic pain

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Jennifer Cogan, Geneviève Lalumière, Grisell Vargas-Schaffer, Alain Deschamps, Zeynep Yegin

Annals of Cardiac Anaesthesia 2017 20(4):395-398

Background: Recent meta-analyses have concluded that low-dose intravenous ketamine infusions (LDKIs) during the postoperative period may help to decrease acute and chronic postoperative pain after major surgery. Aims: This study aims to evaluate the level of pain at least 3 months after surgery for patients treated with a postoperative LDKI versus patients who were not treated with a postoperative LDKI. Methods: Administrative and Ethics Board approval were obtained for this study. We performed a retrospective chart review for all patients receiving LDKI, and equal number of age-, sex-, and surgery-matched patients who did not receive LDKI. Low-dose ketamine was prepared using 100 mg of ketamine in 100 ml of normal saline and run between 50 and 200 mcg/kg/h. Results: We reviewed 115 patients with LDKI and 115 without LDKI. The average age was 63.1 years, 73% of the patients were men and sex was evenly distributed between LDKI and non-LDKI. The average duration of the ketamine infusions was 26.8 h with the average dose being 169.9 mg. At an average of 9 months after surgery, 42% of the ketamine group and 38% of the nonketamine group stated that they had had pain on discharge. Of these patients, 30% of the ketamine group and 26% of the nonketamine group still had pain at the time of the phone call. Women in both groups had more acute and chronic pain than men. Conclusion: These results show that LDKI does not promote a decrease in long-term postoperative pain.

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An uncommon intraoperative implantable cardiac device complication and subsequent troubleshooting

AnnCardAnaesth_2017_20_4_483_216265_f1.j

Rekha Suthar, Omar Viswanath, S Howard Wittels, Gerald P Rosen

Annals of Cardiac Anaesthesia 2017 20(4):483-484



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An innovative technique to improve safety of volatile anesthetics suction from the cardiopulmonary bypass circuit

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Francesco De Simone, Luigi Cassarà, Salvatore Sardo, Elena Scarparo, Omar Saleh, Caetano Nigro Neto, Alberto Zangrillo, Giovanni Landoni

Annals of Cardiac Anaesthesia 2017 20(4):399-402

Context: Myocardial injury during cardiac surgery on cardiopulmonary bypass (CPB) is a major determinant of morbidity and mortality. Preclinical and clinical evidence of dose- and time-related cardioprotective effects of volatile anesthetic drugs exist and their use during the whole surgery duration could improve perioperative cardiac protection. Even if administering volatile agents during CPB are relatively easy, technical problems, such as waste gas scavenging, may prevent safe and manageable administration of halogenated vapors during CPB. Aims: The aim of this study is to improve the safe administration of volatile anesthesia during CPB. Settings and Design: Tertiary teaching hospital. Subjects and Methods: We describe an original device that collects and disposes of any volatile anesthetic vapors present in the exit stream of the oxygenator, hence preventing its dispersal into the operating theatre environment and adaptively regulates pressure of oxygenator chamber in the CPB circuit. Results: We have so far applied a prototype of this device in more than 1300 adult cardiac surgery patients who received volatile anesthetics during the CPB phase. Conclusions: Widespread implementation of scavenging system like the one we designed may facilitate the perfusionist and the anesthesiologist in delivering these cardioprotective drugs with beneficial impact on patients' outcome without compromising on safety.

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Lutembacher syndrome: Dilemma of doing a tricuspid annuloplasty

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AV Varsha, Gladdy George, Raj Sahajanandan

Annals of Cardiac Anaesthesia 2017 20(4):456-458

We discuss the case of a 24-year-old woman with Lutembacher syndrome and severe tricuspid regurgitation (TR) who underwent surgical closure of atrial septal defect and mitral valve replacement without tricuspid annuloplasty despite a severe TR and a large tricuspid annulus on preoperative echo. The pathophysiology of Lutembacher syndrome is discussed below. The utility of perioperative echocardiography in assessing the annular diameter, tenting area and coaptation depth and thus providing insights into the functioning of the tricuspid valve will also be emphasized.

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Relationship between perioperative left atrial appendage doppler velocity estimates and new-onset atrial fibrillation in patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass

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Kunal Sarin, Sandeep Chauhan, Akshay K Bisoi, Poonam Malhotra Kapoor, Parag Gharde, Arindam Choudhury

Annals of Cardiac Anaesthesia 2017 20(4):403-407

Background: Literature search reveals that postoperative atrial fibrillation (POAF) occurs in 15%–40% of coronary artery bypass graft (CABG) patients. Although several risk models exist for predicting the development of POAF, few have studied left atrial appendage (LAA) velocity. We hypothesize that an association between LAA velocity and development of POAF exists. Design and Methods: Single institution university hospital prospective observational clinical study performed between May 2016 and November 2016 in 96 adult patients undergoing CABG surgery utilizing cardiopulmonary bypass (CPB). Transesophageal echocardiography was performed perioperatively to measure LAA velocity and left atrial (LA) size after anesthetic induction, post-CPB and during the postoperative period before extubation. Student's t-test was used for inter-group comparisons. Data are expressed as mean ± (standard deviation). The value of P < 0.05 was considered statistically significant. Results: A total of 95 patients (69 males and 26 females) completed the study and were included in the final analysis. Of these, 21 (22%) (15 males and 5 females) developed POAF. The patient group which developed POAF was compared with the group that did not develop POAF. On comparing mean age of patients in each group (59 years in patients with no POAF and 63.71 years in patients with POAF, P = 0.04). LA volume indexed in POAF group (34.13 ml/m2) compared with that in group with no POAF (34.82 ml/m2) resulted in P = 0.04. Mean LAA velocities (pre-CPB, post-CPB, postoperative Intensive Care Unit) in group with no POAF were 41.06, 56.33, and 60.44 cm/s, respectively, whereas in the other group with POAF the values were 39.68, 55.04, and 58.09 cm/s, respectively. No statistical significance was noted (P > 0.05). Comparison of comorbidities also did not yield any significant results (P > 0.05). Conclusions: Decreasing LAA velocity does not appear to independently predict the development of POAF in patients undergoing CABG surgery with the use of CPB. There is, however, a positive correlation of POAF with age and LA volume.

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Perioperative management of a patient with glanzmann's thrombasthenia for mitral valve repair under cardiopulmonary bypass

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Parimala Prasanna Simha, Prasanna Simha Mohan Rao, Deepak Arakalgud, Rakesh Rajashekharappa, Manjunath Narasimhaih

Annals of Cardiac Anaesthesia 2017 20(4):468-471

A 30-year-old male patient presented with Glanzmann's thrombasthenia and mitral valve prolapse. He was in acute decompensated congestive heart failure due to severe mitral and tricuspid regurgitation. After his cardiac failure had been stabilized, the patient was subjected to mitral and tricuspid valve repair. His transfusion requirements were guided by thrombelastography and his bleeding disorder was managed by infusing single donor plasmapheresed platelet transfusions in the perioperative period. The patient underwent surgery uneventfully.

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Comparison of the renoprotective effect of dexmedetomidine and dopamine in high-risk renal patients undergoing cardiac surgery: A double-blind randomized study

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Rabie Soliman, Mohamed Hussien

Annals of Cardiac Anaesthesia 2017 20(4):408-415

Objective: The purpose of the current study was to compare the renoprotective effects of continuous infusion of dexmedetomidine and dopamine in high-risk renal patients undergoing cardiac surgery. Design: A double-blind randomized study. Setting: Cardiac Centers. Patients: One hundred and fifty patients with baseline serum creatinine level ≥1.4 mg/dl were scheduled for cardiac surgery with cardiopulmonary bypass. Intervention: The patients were classified into two groups (each = 75): Group Dex – the patients received a continuous infusion of dexmedetomidine 0.4 μg/kg/h without loading dose during the procedure and the first 24 postoperative hours and Group Dopa – the patients received a continuous infusion of dopamine 3 μg/kg/min during the procedure and the first 24 postoperative hours. Measurements: The monitors included serum creatinine, creatinine clearance, blood urea nitrogen, and urine output. Main Results: The creatinine levels and blood urea nitrogen decreased at days 1, 2, 3, 4, and 5 in Dex group and increased in patients of Dopa group (P < 0.05). The creatinine clearance increased at days 1, 2, 3, 4, and 5 in Dex group and decreased in patients of Dopa group (P < 0.05). The amount of urine output was too much higher in the Dex group than the Dopa group (P < 0.05). Conclusions: The continuous infusion of dexmedetomidine during cardiac surgery has a renoprotective effect and decreased the deterioration in the renal function in high-risk renal patients compared to the continuous infusion of dopamine.

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Bifid epiglottis: What perioperative physician should know about it?

AnnCardAnaesth_2017_20_4_479_216264_f1.j

Rupesh Yadav, Sohan Lal Solanki, Jeson R Doctor

Annals of Cardiac Anaesthesia 2017 20(4):479-480



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Does bilevel positive airway pressure improve outcome of acute respiratory failure after open-heart surgery?

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Ahmed Said Elgebaly

Annals of Cardiac Anaesthesia 2017 20(4):416-421

Background: Respiratory failure is of concern in the postoperative period after cardiac surgeries. Invasive ventilation (intermittent positive pressure ventilation [IPPV]) carries the risks and complications of intubation and mechanical ventilation (MV). Aims: Noninvasive positive pressure ventilation (NIPPV) is an alternative method and as effective as IPPV in treating insufficiency of respiration with less complications and minimal effects on respiratory and hemodynamic parameters next to open-heart surgery. Design: This is a prospective, randomized and controlled study. Materials and Methods: Forty-four patients scheduled for cardiac surgery were divided into two equal groups: Group I (IPPV) and Group II (NIPPV). Heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), oxygen saturation (SpO2), arterial blood gas, weaning time, reintubation, tracheotomy rate, MV time, postoperative hospital stay, and ventilator-associated pneumonia during the period of hospital stay were recorded. Results: There was statistically significant difference in HR between groups with higher in Group I at 30 and 60 min and at 12 and 24 h. According to MAP, it started to increase significantly at hypoxemia, 15 min, 30 min, 4 h, 12 h, and at 24 h which was higher in Group I also. RR, PaO2, and PaCO2showed significant higher in Group II at 15, 30, and 60 min and 4 h. According to pH, there was a significant difference between groups at 15, 30, and 60 min and at 4, 12, and 24 h postoperatively. SpO2showed higher significant values in Group I at 15 and 30 min and at 12 h postoperatively. Duration of postoperative supportive ventilation was higher in Group I than that of Group II with statistically significant difference. Complications were statistically insignificant between Group I and Group II. Conclusion: Our study showed superiority of invasive over noninvasive mode of ventilator support. However, NIPPV (bilevel positive airway pressure) was proved to be a safe method.

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Atmospheric pollution in cardiac operating rooms

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Mukul Chandra Kapoor

Annals of Cardiac Anaesthesia 2017 20(4):391-392



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Comparison of dexmedetomidine and ketamine versus propofol and ketamine for procedural sedation in children undergoing minor cardiac procedures in cardiac catheterization laboratory

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Vidya Sagar Joshi, Sandeep S Kollu, Ram Murti Sharma

Annals of Cardiac Anaesthesia 2017 20(4):422-426

Background: The ideal anaesthetic technique for management of paediatric patients scheduled to undergo cardiac catheterisation is still not standardised. Aim: To compare the effects of ketamine-propofol and ketamine-dexmedetomidine combinations on hemodynamic parameters and recovery time in paediatric patients undergoing minor procedures and cardiac catheterisation under sedation for various congenital heart diseases. Material and Methods: 60 children of either sex undergoing cardiac catheterisation were randomly assigned into two groups Dexmedetomidine-ketamine group (DK) and Propofol-ketamine (PK) of 30 patients each. All patients were premedicated with glycopyrrolate and midazolam (0.05mg/kg) intravenously 5-10 min before anaesthetic induction. Group 'DK'received dexmedetomidineiv infusion 1 μg/kg over 10 min + ketamine1mg/kg bolus, followed by iv infusion of dexmedetomidine 0.5μg/kg/hr and of ketamine1 mg/kg/hr. Group 'PK' received propofol 1mg/kg and ketamine 1mg/kg/hr for induction followed by iv infusion of propofol 100 μg/kg/hr and ketamine 1 mg/kg/hr for maintenance. Haemodynamic parameters and recovery time was recorded postoperatively. Statistical Analysis: Independent sample t test was used to compare the statistical significance of continuous variables of both the groups.Chi square test was used for numerical data like gender.Fischer exact test was applied for non parametric data like ketamine consumption. Results: We observed that heart rate in dexmedetomidine (DK) group was significantly lower during the initial 25 mins after induction compared to the propofol (PK) group. Recovery was prolonged in the DK group compared to the PK group (40.88 vs. 22.28 min). Even ketamine boluses consumption was higher in DK group. Conclusion: Use of dexmedetomidine-ketamine combination is a safe alternative, without any hemodynamic orrespiratory effects during the cardiac catheterization procedure but with some delayed recovery.

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Rhabdomyolysis and compartment syndrome in a bodybuilder undergoing minimally invasive cardiac surgery

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Sebastian John Baxter, Madhusudan Rao Puchakayala, Vinayak N Bapat

Annals of Cardiac Anaesthesia 2017 20(4):453-455

Rhabdomyolysis is the result of skeletal muscle tissue injury and is characterized by elevated creatine kinase levels, muscle pain, and myoglobinuria. It is caused by crush injuries, hyperthermia, drugs, toxins, and abnormal metabolic states. This is often difficult to diagnose perioperatively and can result in renal failure and compartment syndrome if not promptly treated. We report a rare case of inadvertent rhabdomyolysis and compartment syndrome in a bodybuilder undergoing minimally invasive cardiac surgery. The presentation, differential diagnoses, and management are discussed. Hyperkalemia may be the first presenting sign. Early recognition and management are essential to prevent life-threatening complications.

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Evaluation of the effect of metformin and insulin in hyperglycemia treatment after coronary artery bypass surgery in nondiabetic patients

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Kamran Ghods, Hossein Davari, Abbasali Ebrahimian

Annals of Cardiac Anaesthesia 2017 20(4):427-431

Introduction: Insulin therapy is the most commonly used treatment for controlling hyperglycemia after coronary artery bypass surgery in both diabetic and nondiabetic patients. Metformin has been indicated for critically ill patients as an alternate for the treatment of hyperglycemia. This study evaluated the effect of metformin and insulin in hyperglycemia treatment after coronary artery bypass surgery in nondiabetic patients. Settings and Design: This study was a clinical trial comprising nondiabetic patients who had undergone coronary artery bypass surgery. Patients were randomly divided into the insulin group and the metformin group. Methods: Patients in the insulin group received continuous infusion of insulin while those in the metformin group received 500 mg metformin tablets twice daily. All the patients were followed up for 3 days after stabilization of blood glucose levels. Statistical Analysis: Data were analyzed using Chi-square test and Mann–Whitney U-test. Results: This study included a total of 56 patients. During the study period, the mean blood glucose levels decreased from 225.24 to 112.36 mg/dl (↓112.88 mg/dl) in the insulin group and from 221.80 to 121.92 mg/dl in the metformin group (↓99.88 mg/dl). There was no significant difference in the blood glucose levels of the patients between the two groups at any measurement times (P > 0.05). Conclusion: Using 500 mg metformin twice daily is similar to using insulin in nondiabetic patients undergoing coronary artery bypass graft. Therefore, the use of metformin can be considered as a treatment strategy for controlling hyperglycemia in this group of patients.

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Two episodes of cardiac tamponade in the same patient from removing pacing wires and a pericardial drain: A case report

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Rekha Suthar, Osman Nawazish Salaria, Carolina De La Cuesta, Omar Viswanath

Annals of Cardiac Anaesthesia 2017 20(4):459-461

A patient presented for an elective transcatheter aortic valve replacement with temporary transvenous pacing (TVP) wires placement per protocol. On postoperative day 1, the patient remained stable, so the wires were subsequently removed, after which the patient acutely decompensated, with transthoracic echocardiography revealing pericardial effusion. Emergent pericardiocentesis was performed, and a pericardial drain was placed. Three days later, the drain was removed; again, the patient acutely decompensated, requiring another emergent pericardiocentesis. Despite the relatively benign nature of TVP wires and pericardial drains, the possibility of cardiac tamponade should be kept in mind as a potential complication when they are being removed.

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Ischemic mitral regurgitation

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Praveen Kerala Varma, Neethu Krishna, Reshmi Liza Jose, Ashish Narayan Madkaiker

Annals of Cardiac Anaesthesia 2017 20(4):432-439

Ischemic mitral regurgitation (IMR) is a frequent complication of left ventricular (LV) global or regional pathological remodeling due to chronic coronary artery disease. It is not a valve disease but represents the valvular consequences of increased tethering forces and reduced closing forces. IMR is defined as mitral regurgitation caused by chronic changes of LV structure and function due to ischemic heart disease and it worsens the prognosis. In this review, we discuss on etiology, pathophysiology, and mechanisms of IMR, its classification, evaluation, and therapeutic corrective methods of IMR.

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A case report of combined radical pericardiectomy and beating heart coronary artery bypass grafting in a patient with tubercular chronic constrictive pericarditis with coronary artery disease

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Gauranga Majumdar, Surendra Kumar Agarwal, Shantanu Pande, Bipin Chandra, Prabhat Tewari

Annals of Cardiac Anaesthesia 2017 20(4):465-467

We here report a successful midterm outcome following combined off-pump radical pericardiectomy and coronary artery bypass surgery (CABG) in a 65-year-old male patient who was suffering from chronic constrictive calcified tubercular pericarditis with coronary artery disease. Simultaneous off-pump CABG and radical pericardiectomy for nonsurgical constrictive pericarditis is reported very rarely in English literature.

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Systematic evaluation of commercial pharmacogenetic testing in psychiatry: a focus on CYP2D6 and CYP2C19 allele coverage and results reporting

imageObjective: The aim of this study was to systematically assess commercial pharmacogenetic tests relevant to prescribing in psychiatry, with specific attention on CYP2D6 and CYP2C19 star allele coverage as well as compliance with consensus recommendations for pharmacogenetic test result reporting. Materials and methods: The CYP2D6 and CY2C19 star (*) allele contents of 20 pharmacogenetic test panels were compared and their test results reports were evaluated on the basis of consensus reporting recommendations published by The Centers for Disease Control and Prevention as well as the Clinical Pharmacogenetics Implementation Consortium. Results: Most test panels included the major CYP2D6 (*2, *4, *5, *10, *17) and CYP2C19 (*2, *3, *17) alleles, but no two test panels contained the same combination of CYP2D6 and CYP2C19 alleles. Of the 20 pharmacogenetic reports that we evaluated, none fulfilled all the recommendations and no recommendation was fulfilled by all tests. Conclusion: Consensus has yet to be reached on which CYP2D6 and CYP2C19 star alleles to include on pharmacogenetic testing panels and pharmacogenetic results reporting could be considerably improved. Collaboration between test manufacturers and end-users is required to narrow the gap between the availability and integration of these pharmacogenetic-based decision-support tools into routine practice.

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High plasma concentrations of dolutegravir in patients with ABCG2 genetic variants

imageThe ATP-binding cassette transporters B1 (ABCB1) and G2 (ABCG2) are both expressed in the intestine and known as efflux transporters of drugs. Dolutegravir was identified recently as a substrate of both ABCB1 and ABCG2. This study aimed to determine the relations between single-nucleotide polymorphisms of ABCB1 and ABCG2 genes and plasma dolutegravir concentrations. Plasma samples were obtained from 42 HIV-1-infected patients treated with dolutegravir-containing regimens 0.5–4 h after dolutegravir dosing. Plasma dolutegravir concentrations were measured by liquid chromatography–mass spectrometry. Genomic DNA was isolated from peripheral blood mononuclear cells. Genotyping of allelic variants of ABCB1 1236 C>T (rs1128503), 2677 G>T/A (rs2032582), 3435 C>T (rs1045642), 4036 A>G (rs3842), and ABCG2 421 C>A (rs2231142) was performed using the TaqMan drug metabolism assays. None of the genotypes in ABCB1 1236 C>T, 2677 G>T/A, 3435 C>T, and 4036 A>G correlated with plasma dolutegravir concentration. In contrast, the mean peak plasma concentration of dolutegravir was significantly higher in the genotypes of ABCG2 421 AA (5002 ng/ml, n=3) compared with the genotypes of ABCG2 421 CC (2569 ng/ml, n=22) and ABCG2 421 CA (2479 ng/ml, n=17) (P=0.0005). The speculated peak level of plasma dolutegravir concentration was significantly higher in ABCG2 genetic variant holders, probably, at least in part, because of low expression levels of efflux transporters in the intestines associated with these genetic variants.

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The genotypes and methylation of MAO genes as factors behind smoking behavior

imageObjective: Smoking dependence is the main cause for tobacco-related illnesses. The addiction-causing substance in tobacco, nicotine, acts through the dopamine pathway in the brain, causing several pleasurable experiences through cigarette smoking. Thus, both genetic and epigenetic factors related to dopamine metabolism may play an important role in influencing an individual's smoking behavior. Materials and methods: We studied the 1460 C/T variation and the variable number tandem repeat polymorphism in the MAOA gene and A/G variation in intron 13 in the MAOB gene together with four DNA methylation sites in both of these genes in relation to several smoking-related phenotypes in a study population of 1230 Whites of Russian origin. Results: The genotypes studied were found to be associated with smoking status in women; the MAOB G variant allele was more prevalent in female smokers than nonsmokers [odds ratio (OR): 2.16, 95% confidence interval (CI): 1.08–4.33], whereas a reverse relation was observed for the MAOA 1460 T-variant allele (OR: 0.44, 95% CI: 0.21–0.91) and variable number tandem repeat low-activity alleles (OR: 0.49, 95% CI: 0.24–0.98). Moreover, the mean methylation values of the CpG sites studied in the MAOA gene were related to smoking behavior in women. Similarly, several methylation patterns in the MAOB gene were associated with a smoking history, with each CpG site showing a remarkable sex dependence. Conclusion: Smoking behavior seems to be related to the genetic and epigenetic profile of MAO genes, with considerable individual and sex-related differences.

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Functional assessment of genetic variants located in the promoter of SHP1 (NR0B2)

imageSmall heterodimer partner 1 (SHP1, NR0B2) is a member of the superfamily of nuclear receptors (NRs). Even if this orphan receptor, unlike other NRs, lacks the DNA-binding domain, it is capable of regulating transcription by repressing the activity of other NRs by direct protein–protein interaction. Accordingly, SHP1 is part of negative feedback loops of the transcriptional regulation of genes involved in drug metabolism and various metabolic pathways including bile acid and glucose homeostasis. Although it is known that several interacting partners of SHP1 also modulate its expression, there is little information about genetic variability of this regulatory mechanism. Our study aimed to identify genetic variants in the NR0B2 promoter region and to determine their impact on NR0B2 transcription. For this, DNA samples originating from 119 participants of the population-based cohort Study of Health in Pomerania were analyzed by Sanger sequencing revealing four genetic variants: NR0B2:c.−594T>C (rs71636795), NR0B2:c.−414G>C (newly identified), NR0B2:c.−423C>T (rs78182695), and NR0B2:c.−224delCTGA (rs145613139) localized in the 5′ untranslated region of NR0B2. The impact of these variants on transactivation of the NR0B2 promoter by NRs known to be regulators of SHP1 expression (hepatocyte nuclear factor 4α, liver receptor homolog-1, and farnesoid X receptor) was assessed in a cell-based reporter gene assay, showing that transactivation by hepatocyte nuclear factor 4α and liver receptor homolog-1 was significantly decreased in the presence of the genetic variant NR0B2:c.−594T>C, even though this effect was cell specific. However, SHP1 mRNA expression in a small collection of human kidney samples was not affected by these genetic variants.

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Comprehensive assessment of cytochromes P450 and transporter genetics with endoxifen concentration during tamoxifen treatment

imageObjectives: Tamoxifen bioactivation to endoxifen is mediated primarily by CYP2D6; however, considerable variability remains unexplained. Our aim was to perform a comprehensive assessment of the effect of genetic variation in tamoxifen-relevant enzymes and transporters on steady-state endoxifen concentrations. Patients and methods: Comprehensive genotyping of CYP enzymes and transporters was performed using the iPLEX ADME PGx Pro Panel in 302 tamoxifen-treated breast cancer patients. Predicted activity phenotype for 19 enzymes and transporters were analyzed for univariate association with endoxifen concentration, and then adjusted for CYP2D6 and clinical covariates. Results: In univariate analysis, higher activity of CYP2C8 (regression β=0.22, P=0.020) and CYP2C9 (β=0.20, P=0.04), lower body weight (β=−0.014, P

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PharmGKB summary: very important pharmacogene information for ABCG2

imageNo abstract available

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Exploring Provider Use of a Digital Implementation Support System for School Mental Health: A Pilot Study

Abstract

This pilot study explored provider use of an online system, Centervention, to support the delivery of empirically supported school-based mental health interventions (ESIs); and associations between components of this system [resources, training, technical assistance (TA), feedback loops], implementation indicators, and student outcomes. Multilevel modeling data were collected from 39 providers implementing ESIs with 758 students. Training, TA, and progress monitoring predicted ESI adherence, and perceived value of resources and TA influenced student responsiveness. Greater adherence was predictive of better socio-emotional outcomes. Interviews with 15 providers illuminated how they used these four Centervention support strategies. Implications for digital implementation support research are discussed.



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Impact of the New Mental Health Services on Rates of Suicide and Hospitalisations by Attempted Suicide, Psychiatric Problems, and Alcohol Problems in Brazil

Abstract

A sizeable proportion of all suicides have mental health issues in the background. The association between access to mental health care in the community and decreased suicide rates is inconsistent in the literature. Brazil undertook a major psychiatric reform strengthening psychiatric community-based care. To evaluate the impact of the new Brazilian community mental health care units (CAPS-Psychosocial-Community-Centres) on municipal rates of suicide, and hospitalisations by attempted suicide, psychiatric and alcohol problems. We performed robust multivariable negative binomial regression models with fixed effect for panel data from all 5507 Brazilian municipalities. Suicide and hospitalization rates were calculated by sex and standardised by age for each municipality and year from 2008 to 2012. The main variable of interest was municipal CAPS coverage. CAPS municipal coverage was associated with lower suicide rates but this was not statistically significant (RR: 0.981; 95% CI 0.952–1.011). However, increased CAPS coverage was associated with lower hospitalizations for attempted suicide (RR: 0.887; 95% CI 0.841–0.935), psychiatric (RR: 0.841; 95% CI 0.821–0.862), and alcohol problems (RR: 0.882; 95% CI 0.860–0.904). Our results suggest that access to community mental health services seems to reduce hospitalisations due to attempted suicide, psychiatric and alcohol problems but not suicidal rates. Therefore, increased investments in community mental health services in low-middle-income countries might decrease costs associated with potentially avoidable hospitalizations.



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Frequency sensitivity in Northern saw-whet owls ( Aegolius acadicus )

Abstract

Northern saw-whet owls (Aegolius acadicus) are known for their unique asymmetrical ear structure and ability to localize prey acoustically, yet few attempts have been made to explore the auditory capabilities of this species. In this study, we evoked auditory brainstem responses (ABRs) with tonebursts to assess three main hypotheses regarding the evolution of auditory sensitivity: sender-receiver matching, ecological constraints, and phylogenetic/morphological constraints. We found that ABR amplitude increased with increasing stimulus level, which is consistent with results in other avian species. ABR amplitudes, latencies, and thresholds indicate that the hearing range of Northern saw-whet owls extends from 0.7 to 8.6 kHz, with an extended frequency range of best sensitivity between 1.6 and 7.1 kHz. Sensitivity fell off rapidly above and below these frequencies. The average audiogram was structurally similar to those found in other species of owls, suggesting that phylogeny or morphology may be constraining the frequency range of auditory sensitivity. However, ABR thresholds were 10–25 dB lower than those of Eastern screech-owls (Megascops asio), with thresholds below 0 dB SPL in some individuals. The lowest thresholds were at frequencies not found in the vocalizations of Northern saw-whet owls, suggesting ecological constraints rather than conspecific vocalizations are driving absolute sensitivity.



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Prenatal hypoxia and placental oxidative stress: linkages to developmental origins of cardiovascular disease

Intrauterine growth restriction (IUGR, a pregnancy complication where the fetus does not reach its genetic growth potential) is a leading cause of fetal morbidity and mortality with a significant impact on population health. IUGR is associated with gestational hypoxia; which can lead to placental oxidative stress and fetal programming of cardiovascular disease. Mitochondria are a major source of placental oxidative stress and may provide a therapeutic target to mitigate the detrimental effects of placental oxidative stress on pregnancy outcomes. A nanoparticle-mediated delivery of a mitochondrial antioxidant to the placenta is a potential novel approach that may avoid unwanted off-target effects on the developing offspring.



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Long-term effects of a renin inhibitor versus a thiazide diuretic on arterial stiffness and left ventricular diastolic function in elderly hypertensive patients

Arterial stiffness and cardiac function are important predictors of cardiovascular events in patients with hypertension, even with adequate blood pressure (BP) control. We evaluated whether a direct renin inhibitor, aliskiren, reduces arterial stiffness and modulates left ventricular function compared with a diuretic, hydrochlorothiazide, in elderly hypertensive patients. Twenty-one hypertensive patients [67 ± 14 (SD) yr] were randomly assigned to receive 6-mo aliskiren (n = 11) or hydrochlorothiazide (n = 10)-based therapy. We assessed β-stiffness of the local arteries, arterial elastance (Ea), and echocardiographic variables, including early (E) and late (A) mitral inflow velocity, deceleration time of E, early (E') and late (A') diastolic mitral annular velocity, and left ventricular end-systolic elastance (Ees) before and after treatment. BP decreased similarly (P < 0.001) after both therapies. β-Stiffness of the carotid artery decreased after aliskiren but increased after hydrochlorothiazide treatment (aliskiren: 6.42 ± 2.34 pre vs. 5.07 ± 1.29 post; hydrochlorothiazide: 5.05 ± 1.78 vs. 7.25 ± 2.68, P = 0.001 for interaction). β-Stiffness of the femoral and radial arteries were not different after either treatment. Different from aliskiren, E decreased (73 ± 16 vs. 67 ± 14 cm/s, P = 0.026), and the deceleration time was prolonged (218 ± 40 vs. 236 ± 35 ms, P = 0.032) after hydrochlorothiazide therapy, whereas the E/A, and E' remained unchanged after both treatments. Ea and Ees decreased after aliskiren therapy (both P < 0.05), whereas the Ea/Ees (ventricular-arterial coupling) was maintained after both treatments. Thus, aliskiren decreased the stiffness of carotid artery and left ventricular end-systolic elastance with maintenance of ventricular-arterial coupling without any effects on diastolic filling, while hydrochlorothiazide increased carotid arterial stiffness and slowed early diastolic filling in elderly hypertensive patients.



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High-protein diet improves sensitivity to cholecystokinin and shifts the cecal microbiome without altering brain inflammation in diet-induced obesity in rats

High-protein diet (HPD) curtails obesity and/or fat mass, but it is unknown whether it reverses neuroinflammation or alters glucose levels, CCK sensitivity, and gut microbiome in rats fed a Western diet (WD)-induced obesity (DIO). Male rats fed a WD (high fat and sugar) for 12 wk were switched to a HPD for 6 wk. Body composition, food intake, meal pattern, sensitivity to intraperitoneal CCK-8S, blood glucose, brain signaling, and cecal microbiota were assessed. When compared with a normal diet, WD increased body weight (9.3%) and fat mass (73.4%). CCK-8S (1.8 or 5.2 nmol/kg) did not alter food intake and meal pattern in DIO rats. Switching to a HPD for 6 wk reduced fat mass (15.7%) with a nonsignificantly reduced body weight gain, normalized blood glucose, and decreased feeding after CCK-8S. DIO rats on the WD or switched to a HPD showed comparable microbial diversity. However, in HPD versus WD rats, there was enrichment of 114 operational taxonomic units (OTUs) and depletion of 188 OTUs. Of those, Akkermansia muciniphila (enriched on a HPD), an unclassified Clostridiales, a member of the RF39 order, and a Phascolarctobacterium were significantly associated with fat mass. The WD increased cytokine expression in the hypothalamus and dorsal medulla that was unchanged by switching to HPD. These data indicate that HPD reduces body fat and restores glucose homeostasis and CCK sensitivity, while not modifying brain inflammation. In addition, expansion of cecal Akkermansia muciniphila correlated to fat mass loss may represent a potential peripheral mechanism of HPD beneficial effects.



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Bradykinin does not acutely sensitize the reflex pressor response during hindlimb skeletal muscle stretch in decerebrate rats

Hindlimb skeletal muscle stretch (i.e., selective activation of the muscle mechanoreflex) in decerebrate rats evokes reflex increases in blood pressure and sympathetic nerve activity. Bradykinin has been found to sensitize mechanogated channels through a bradykinin B2 receptor-dependent mechanism. Moreover, bradykinin B2 receptor expression on sensory neurons is increased following chronic femoral artery ligation in the rat (a model of simulated peripheral artery disease). We tested the hypothesis that injection of bradykinin into the arterial supply of a hindlimb in decerebrate, unanesthetized rats would acutely augment (i.e., sensitize) the increase in blood pressure and renal sympathetic nerve activity during hindlimb muscle stretch to a greater extent in rats with a ligated femoral artery than in rats with a freely perfused femoral artery. The pressor response during static hindlimb muscle stretch was compared before and after hindlimb arterial injection of 0.5 µg of bradykinin. Injection of bradykinin increased blood pressure to a greater extent in "ligated" (n = 10) than "freely perfused" (n = 10) rats. The increase in blood pressure during hindlimb muscle stretch, however, was not different before vs. after bradykinin injection in freely perfused (14 ± 2 and 15 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.62) or ligated (15 ± 3 and 14 ± 2 mmHg for pre- and post-bradykinin, respectively, P = 0.80) rats. Likewise, the increase in renal sympathetic nerve activity during stretch was not different before vs. after bradykinin injection in either group of rats. We conclude that bradykinin did not acutely sensitize the pressor response during hindlimb skeletal muscle stretch in freely perfused or ligated decerebrate rats.



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Respiratory muscle endurance training reduces the O2 cost of cycling and perceived exertion in obese adolescents

In obesity, the increased O2 cost of breathing negatively affects the O2 cost of exercise and exercise tolerance. The purpose of the study was to determine whether, in obese adolescents, the addition of respiratory muscle endurance training (RMET) (isocapnic hyperpnea) to a standard body mass reduction program decreases the O2 cost of exercise and perceived exertion. Nine male obese adolescents [16.0 ± 1.4 yr (x ± SD), body mass 114.4 ± 22.3 kg] underwent 3 wk of RMET (5 days/week) in addition to a standard body mass reduction program. Eight age- and sex-matched obese adolescents underwent only the standard program (CTRL). Before and after interventions, patients performed on a cycle ergometer: incremental exercise; 12-min exercises at a constant work rate (CWR) of 65% and 120% at the gas exchange threshold (GET) determined before the intervention. Breath-by-breath pulmonary ventilation (Ve) and O2 uptake (Vo2), heart rate (HR), and ratings of perceived exertion for dyspnea/respiratory discomfort (RPER) and leg effort (RPEL) were determined. Body mass decreased (by ~3.0 kg) after both RMET (P = 0.003) and CTRL (P = 0.002). Peak Vo2 was not affected by both interventions. Peak work rate was slightly, but significantly (P = 0.04), greater after RMET but not after CTRL. During CWR < GET, no changes were observed after both interventions. During CWR > GET, the O2 cost of cycling at the end of exercise (P = 0.02), the slope of Vo2 vs. time (3–12 min) (P = 0.01), RPER (P = 0.01), and RPEL (P = 0.01) decreased following RMET, but not following CTRL. HR decreased after both RMET (P = 0.02) and CTRL (P = 0.03), whereas Ve did not change. In obese adolescents RMET, superimposed on a standard body mass reduction program, lowered the O2 cost of cycling and perceived exertion during constant heavy-intensity exercise.



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Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse

Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT1AR) most widely expressed in adult neurons. Activation of the AT1R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT1R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT1AR-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT1AR promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT1AR-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT1AR-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT1AR-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT1AR-GFP neurons and TH-GFP neurons showed similar AT1AR-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT1AR-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing.



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Renal denervation attenuates hypertension but not salt sensitivity in ETB receptor-deficient rats

Hypertension is a prevalent pathology that increases risk for numerous cardiovascular diseases. Because the etiology of hypertension varies across patients, specific and effective therapeutic approaches are needed. The role of renal sympathetic nerves is established in numerous forms of hypertension, but their contribution to salt sensitivity and interaction with factors such as endothelin-1 are poorly understood. Rats deficient of functional ETB receptors (ETB-def) on all tissues except sympathetic nerves are hypertensive and exhibit salt-sensitive increases in blood pressure. We hypothesized that renal sympathetic nerves contribute to hypertension and salt sensitivity in ETB-def rats. The hypothesis was tested through bilateral renal sympathetic nerve denervation and measuring blood pressure during normal salt (0.49% NaCl) and high-salt (4.0% NaCl) diets. Denervation reduced mean arterial pressure in ETB-def rats compared with sham-operated controls by 12 ± 3 (SE) mmHg; however, denervation did not affect the increase in blood pressure after 2 wk of high-salt diet (+19 ± 3 vs. +16 ± 3 mmHg relative to normal salt diet; denervated vs. sham, respectively). Denervation reduced cardiac sympathetic-to-parasympathetic tone [low frequency-high frequency (LF/HF)] during normal salt diet and vasomotor LF/HF tone during high-salt diet in ETB-def rats. We conclude that the renal sympathetic nerves contribute to the hypertension but not to salt sensitivity of ETB-def rats.



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Detection of maltodextrin and its discrimination from sucrose are independent of the T1R2 + T1R3 heterodimer

Maltodextrins, such as Maltrin and Polycose, are glucose polymer mixtures of varying chain lengths that are palatable to rodents. Although glucose and other sugars activate the T1R2 + T1R3 "sweet" taste receptor, recent evidence from T1R2- or T1R3-knockout (KO) mice suggests that maltodextrins, despite their glucose polymer composition, activate a separate receptor mechanism to generate a taste percept qualitatively distinguishable from that of sweeteners. However, explicit discrimination of maltodextrins from prototypical sweeteners has not yet been psychophysically tested in any murine model. Therefore, mice lacking T1R2 + T1R3 and wild-type controls were tested in a two-response taste discrimination task to determine whether maltodextrins are 1) detectable when both receptor subunits are absent and 2) perceptually distinct from that of sucrose irrespective of viscosity, intensity, and hedonics. Most KO mice displayed similar Polycose sensitivity as controls. However, some KO mice were only sensitive to the higher Polycose concentrations, implicating potential allelic variation in the putative polysaccharide receptor or downstream pathways unmasked by the absence of T1R2 + T1R3. Varied Maltrin and sucrose concentrations of approximately matched viscosities were then presented to render the oral somatosensory features, intensity, and hedonic value of the solutions irrelevant. Although both genotypes competently discriminated Maltrin from sucrose, performance was apparently driven by the different orosensory percepts of the two stimuli in control mice and the presence of a Maltrin but not sucrose orosensory cue in KO mice. These data support the proposed presence of an orosensory receptor mechanism that gives rise to a qualitatively distinguishable sensation from that of sucrose.



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Acute effects of angiotensin-converting enzyme inhibition versus angiotensin II receptor blockade on cardiac sympathetic activity in patients with heart failure

The beneficial effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (ANG II) receptor antagonists in patients with heart failure secondary to reduced ejection fraction (HFrEF) are felt to result from prevention of the adverse effects of ANG II on systemic afterload and renal homeostasis. However, ANG II can activate the sympathetic nervous system, and part of the beneficial effects of ACE inhibitors and ANG II antagonists may result from their ability to inhibit such activation. We examined the acute effects of the ACE inhibitor captopril (25 mg, n = 9) and the ANG II receptor antagonist losartan (50 mg, n = 10) on hemodynamics as well as total body and cardiac norepinephrine spillover in patients with chronic HFrEF. Hemodynamic and neurochemical measurements were made at baseline and at 1, 2, and 4 h after oral dosing. Administration of both drugs caused significant reductions in systemic arterial, cardiac filling, and pulmonary artery pressures (P < 0.05 vs. baseline). There was no significant difference in the magnitude of those hemodynamic effects. Plasma concentrations of ANG II were significantly decreased by captopril and increased by losartan (P < 0.05 vs. baseline for both). Total body sympathetic activity increased in response to both captopril and losartan (P < 0.05 vs. baseline for both); however, there was no change in cardiac sympathetic activity in response to either drug. The results of the present study do not support the hypothesis that the acute inhibition of the renin-angiotensin system has sympathoinhibitory effects in patients with chronic HFrEF.



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Spot urine protein measurements in normotensive pregnancies, pregnancies with isolated proteinuria and preeclampsia

We performed a prospective, longitudinal study of pregnant women presenting to their first obstetrics visits to characterize the changes in spot urine protein-to-creatinine (UPCR) and albumin-to-creatinine ratios (UACR) in normotensive pregnancies, as well as identify clinical characteristics associated with isolated proteinuria and preeclampsia. We measured spot urinary albumin, protein, and creatinine at the first prenatal visit, end of the second trimester, and at delivery. In the normotensive pregnancies (n = 142), we found that from the beginning of pregnancy to delivery, UACR increased by a median [interquartile range (IQR)] of 14.7 mg/g Cr (3.74–51.8) and UPCR by 60 mg/g Cr (30–130) (P < 0.001 for both changes). Isolated proteinuria (defined as UPCR > 300 mg/g Cr in the absence of hypertension) was identified in 19/142 (13.4%) normotensive pregnancies. Increases in systolic and diastolic blood pressure from early pregnancy to delivery and increases in UACR from early to midpregnancy were associated with isolated proteinuria at delivery. Twelve women developed preeclampsia. Nulliparity, early, and midpregnancy diastolic blood pressures were strongly associated with the development of preeclampsia, but early changes in UACR were not. In conclusion, women who develop isolated proteinuria at delivery have a larger increase in blood pressure than women without proteinuria and have a "microalbuminuric" phase earlier in gestation, unlike women who develop preeclampsia. These findings suggest a different mechanism of urine protein excretion in women with isolated proteinuria as compared with women with preeclampsia, where proteinuria has a more abrupt onset.



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Automated full-range pressure-volume curves in mice and rats

Pressure-volume (PV) curves constructed over the entire lung volume range can reliably detect functional changes in mouse models of lung diseases. In the present study, we constructed full-range PV curves in healthy and elastase-treated mice using either a classic manually operated technique or an automated approach using a computer-controlled piston ventilator [flexiVent FX; Scientific Respiratory Equipment (SCIREQ), Montreal, Quebec, Canada]. On the day of the experiment, subjects were anesthetized, tracheotomized, and mechanically ventilated. Following an initial respiratory mechanics scan and degassing of the lungs with 100% O2, full-range PV curves were constructed using either the classic or the automated technique. In control mice, superimposable curves were obtained, and statistical equivalence was attained between the two methodologies. In the elastase-treated ones, where significant changes in respiratory mechanics and lung volumes were expected, very small differences were observed between the two techniques, and the criteria for statistical equivalence were met in two out of four parameters assessed. The automated technique was adapted to rats and used to estimate the functional residual capacity (FRC) by volume subtraction. This novel approach generated FRC estimates consistent with the literature, with added accuracy relative to the existing method in diseased subjects. In conclusion, the automated technique generated full-range PV curves that were equivalent or very close to those obtained with the classic method under physiological or severe pathological conditions. The automation facilitated some technical aspects of the procedure, eased its use across species, and helped derive a more accurate estimate of FRC in preclinical models of respiratory disease.

NEW & NOTEWORTHY Partial and full-range pressure-volume (PV) curves are frequently used to characterize lung disease models. Whereas automated techniques exist to construct partial PV curves, a manually operated approach is classically employed to build the full-range ones. In this study, the full-range PV curve technique was automated using a computer-controlled piston ventilator. The automation simplified the technique, facilitated its extension to other species, and inspired a novel way of estimating the functional residual capacity in laboratory rodents.



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In vivo assessment of regional mechanics post-myocardial infarction: A focus on the road ahead

Cardiovascular disease, particularly the occurrence of myocardial infarction (MI), remains a leading cause of morbidity and mortality (Go et al., Circulation 127: e6–e245, 2013; Go et al. Circulation 129: e28–e292, 2014). There is growing recognition that a key factor for post-MI outcomes is adverse remodeling and changes in the regional structure, composition, and mechanical properties of the MI region itself. However, in vivo assessment of regional mechanics post-MI can be confounded by the species, temporal aspects of MI healing, as well as size, location, and extent of infarction across myocardial wall. Moreover, MI regional mechanics have been assessed over varying phases of the cardiac cycle, and thus, uniform conclusions regarding the material properties of the MI region can be difficult. This review assesses past studies that have performed in vivo measures of MI mechanics and attempts to provide coalescence on key points from these studies, as well as offer potential recommendations for unifying approaches in terms of regional post-MI mechanics. A uniform approach to biophysical measures of import will allow comparisons across studies, as well as provide a basis for potential therapeutic markers.



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Changes in brachial artery endothelial function and resting diameter with moderate-intensity continuous but not sprint interval training in sedentary men

Moderate-intensity continuous training (MICT) improves peripheral artery function in healthy adults, a phenomenon that reverses as continued training induces structural remodeling. Sprint interval training (SIT) elicits physiological adaptations similar to MICT, despite a lower exercise volume and time commitment; however, its effect on peripheral artery function and structure is largely unexplored. We compared peripheral artery responses to 12 wk of MICT and SIT in sedentary, healthy men (age = 27 ± 8 yr). Participants performed MICT (45 min of cycling at 70% peak heart rate; n = 10) or SIT (3 x 20-s "all out" cycling sprints with 2 min of recovery; n = 9), and responses were compared with a nontraining control group (CTL, n = 6). Allometrically scaled brachial flow-mediated dilation (FMD) increased 2.2% after 6 wk of MICT and returned to baseline levels by 12 wk, but did not change in SIT or CTL (group x time interaction, P = 0.04). Brachial artery diameter increased after 6 and 12 wk (main effect, P = 0.03), with the largest increases observed in MICT. Neither training protocol affected popliteal relative FMD and diameter, or central and lower limb arterial stiffness (carotid distensibility, central and leg pulse wave velocity) (P > 0.05 for all). Whereas earlier and more frequent measurements are needed to establish the potential presence and time course of arterial responses to low-volume SIT, our findings suggest that MICT was superior to the intense, but brief and intermittent SIT stimulus at inducing brachial artery responses in healthy men.

NEW & NOTEWORTHY We compared the effects of 12 wk of moderate-intensity continuous training (MICT) and sprint interval training (SIT) on peripheral artery endothelial function and diameter, and central and lower limb stiffness in sedentary, healthy men. Whereas neither training program affected the popliteal artery or stiffness indexes, we observed changes in brachial artery function and diameter with MICT but not SIT. Brachial artery responses to SIT may follow a different time course or may not occur at all.



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Automated quality control of forced oscillation measurements: respiratory artifact detection with advanced feature extraction

The forced oscillation technique (FOT) can provide unique and clinically relevant lung function information with little cooperation with subjects. However, FOT has higher variability than spirometry, possibly because strategies for quality control and reducing artifacts in FOT measurements have yet to be standardized or validated. Many quality control procedures rely on either simple statistical filters or subjective evaluation by a human operator. In this study, we propose an automated artifact removal approach based on the resistance against flow profile, applied to complete breaths. We report results obtained from data recorded from children and adults, with and without asthma. Our proposed method has 76% agreement with a human operator for the adult data set and 79% for the pediatric data set. Furthermore, we assessed the variability of respiratory resistance measured by FOT using within-session variation (wCV) and between-session variation (bCV). In the asthmatic adults test data set, our method was again similar to that of the manual operator for wCV (6.5 vs. 6.9%) and significantly improved bCV (8.2 vs. 8.9%). Our combined automated breath removal approach based on advanced feature extraction offers better or equivalent quality control of FOT measurements compared with an expert operator and computationally more intensive methods in terms of accuracy and reducing intrasubject variability.

NEW & NOTEWORTHY The forced oscillation technique (FOT) is gaining wider acceptance for clinical testing; however, strategies for quality control are still highly variable and require a high level of subjectivity. We propose an automated, complete breath approach for removal of respiratory artifacts from FOT measurements, using feature extraction and an interquartile range filter. Our approach offers better or equivalent performance compared with an expert operator, in terms of accuracy and reducing intrasubject variability.



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Rat supraspinatus tendon responds acutely and chronically to exercise

The objective of this study was to identify acute responses and chronic adaptations of supraspinatus tendon to noninjurious exercise. We hypothesized that chronic exercise (EX) increases tendon mechanical properties, and a single exercise bout increases matrix metalloproteinase (MMP) activity acutely. Rats were divided into acute or chronic EX or cage activity groups. Animals in acute EX groups were euthanized, 3, 12, 24, 48, or 72 h upon completion of a single bout of exercise (10 m/min, 1 h) on a flat treadmill. Animals in chronic EX groups walked on a flat treadmill for 3 days or 1, 2, or 8 wk. Tendon histology, MMP activity, and mechanics were measured. A single bout of exercise trended toward reducing tendon mechanical properties, but 2 or 8 wk of chronic EX increased tendon mechanics. Cell density was not affected. Cells became rounder with chronic EX. All tendons were highly organized. MMP activity decreased after a single bout of exercise and returned to baseline by 72 h. MMP activity decreased after 8 wk of chronic EX. Decreased MMP activity may indicate an anabolic instead of catabolic response in contrast to injury. Results suggest that mild, acute decreases in MMP activity and tendon mechanics following a single exercise bout lead to enhanced tendon mechanical adaptations with repeated exercise bouts. This study defines acute and chronic changes of MMP activity, mechanical properties, and histology of the rat supraspinatus tendon in response to beneficial exercise and proposes a mechanism by which acute responses translate to chronic adaptations.

NEW & NOTEWORTHY The line between beneficial exercise and overuse has not been elucidated. This study defines the acute and chronic temporal response to exercise of supraspinatus tendon in an in vivo model. We found that decreased matrix metalloproteinase activity and tendon mechanics after a single bout of exercise are followed by beneficial chronic adaptations of the tendon with repeated bouts. How the acute responses to exercise lead to chronic adaptations may distinguish beneficial exercise from overuse.



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The effects of RSR13 on microvascular PO2 kinetics and muscle contractile performance in the rat arterial ligation model of peripheral arterial disease

Exercise intolerance and claudication are symptomatic of peripheral arterial disease. There is a close relationship between muscle O2 delivery, microvascular oxygen partial pressure (PmvO2), and contractile performance. We therefore hypothesized that a reduction of hemoglobin-oxygen affinity via RSR13 would maintain a higher PmvO2 and enhance blood-muscle O2 transport and contractile function. In male Wistar rats (12 wk of age), we created hindlimb ischemia via right-side iliac artery ligation (AL). The contralateral (left) muscle served as control (CONT). Seven days after AL, phosphorescence-quenching techniques were used to measure PmvO2 at rest and during contractions (electrical stimulation; 1 Hz, 300 s) in tibialis anterior muscle (TA) under saline (n = 10) or RSR13 (n = 10) conditions. RSR13 at rest increased TA PmvO2 in CONT (13.9 ± 1.6 to 19.3 ± 1.9 Torr, P < 0.05) and AL (9.0 ± 0.5 to 9.9 ± 0.7 Torr, P < 0.05). Furthermore, RSR13 extended maintenance of the initial TA force (i.e., improved contractile performance) such that force was not decreased significantly until contraction 240 vs. 150 in CONT and 80 vs. 20 in AL. This improved muscle endurance with RSR13 was accompanied by a greater PmvO2 (PmvO2 decrease from baseline) (CONT, 7.4 ± 1.0 to 11.2 ± 1.3; AL, 6.9 ± 0.5 to 8.6 ± 0.6 Torr, both P < 0.05). Whereas RSR13 did not alter the kinetics profile of PmvO2 (i.e., mean response time) substantially during contractions, muscle force was elevated, and the ratio of muscle force to PmvO2 increased. In conclusion, reduction of hemoglobin-oxygen affinity via RSR13 in AL increased PmvO2 and improved muscle contractile performance most likely via enhanced blood-muscle O2 diffusion.

NEW & NOTEWORTHY This is the first investigation to examine the effect of RSR13 (erythrocyte allosteric effector) on skeletal muscle microvascular oxygen partial pressure kinetics and contractile function using an arterial ligation model of peripheral arterial disease in experimental animals. The present results provide strong support for the concept that reducing hemoglobin-O2 affinity via RSR13 improved tibialis anterior muscle contractile performance most likely via enhanced blood-muscle O2 diffusion.



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Maximal rate of heart rate increase correlates with fatigue/recovery status in female cyclists

Abstract

Purpose

Being able to identify how an athlete is responding to training would be useful to optimise adaptation and performance. The maximal rate of heart rate increase (rHRI), a marker of heart rate acceleration has been shown to correlate with performance changes in response to changes in training load in male athletes; however, it has not been established if it also correlates with performance changes in female athletes.

Methods

rHRI and cycling performance were assessed in six female cyclists following 7 days of light training (LT), 14 days of heavy training (HT) and a 10 day taper period. rHRI was the first derivative maximum of a sigmoidal curve fit to R-R data recorded during 5 min of cycling at 100 W. Cycling performance was assessed as work done (kJ) during time-trials of 5 (5TT) and 60 (60TT) min duration.

Results

5TT was possibly decreased at HT (ES ± 90% confidence interval = − 0.16 ± 0.25; p = 0.60), while, 5TT and 60TT very likely to almost certainly increased from HT to taper (ES = 0.71 ± 0.24; p = 0.007 and ES = 0.42 ± 0.19; p = 0.02, respectively). Large within-subject correlations were found between rHRI, and 5TT (r = 0.65 ± 0.37; p = 0.02) and 60TT (r = 0.70 ± 0.31; p = 0.008).

Conclusions

rHRI during the transition from rest to light exercise correlates with training induced-changes in exercise performance in females, suggesting that rHRI may be a useful monitoring tool for female athletes.



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Intraoperative oliguria predicts acute kidney injury after major abdominal surgery

Abstract
Background
The threshold of intraoperative urine output below which the risk of acute kidney injury (AKI) increases is unclear. The aim of this retrospective cohort study was to investigate the relationship between intraoperative urine output during major abdominal surgery and the development of postoperative AKI and to identify an optimal threshold for predicting the differential risk of AKI.
Methods
Perioperative data were collected retrospectively on 3560 patients undergoing major abdominal surgery (liver, colorectal, gastric, pancreatic, or oesophageal resection) at Kyoto University Hospital. We evaluated the relationship between intraoperative urine output and the development of postoperative AKI as defined by recent guidelines. Logistic regression analysis was performed to adjust for patient and operative variables, and the minimum P-value approach was used to determine the threshold of intraoperative urine output that independently altered the risk of AKI.
Results
The overall incidence of AKI in the study population was 6.3%. Using the minimum P-value approach, a threshold of 0.3 ml kg−1 h−1 was identified, below which there was an increased risk of AKI (adjusted odds ratio, 2.65; 95% confidence interval, 1.77–3.97; P<0.001). The addition of oliguria <0.3 ml kg−1 h−1 to a model with conventional risk factors significantly improved risk stratification for AKI (net reclassification improvement, 0.159; 95% confidence interval, 0.049–0.270; P=0.005).
Conclusions
Among patients undergoing major abdominal surgery, intraoperative oliguria <0.3 ml kg−1 h−1 was significantly associated with increased risk of postoperative AKI.

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Response to Ciuculete et al



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Issue Information - Editorial Board



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Response to Leusink et al



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Response to Lefebvre et al

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Congenital scoliosis (CS) is a common vertebral malformation with incidence of up to 1 of 1000 births worldwide. Recently, TBX6 has been reported as the first disease gene for CS: about 10% of CS patients are compound heterozygotes of rare null mutations and a common haplotype composed by 3 SNPs in TBX6. Lefebvre et al in this journal reported that 2 patients with spondylocostal dysostosis (SCD), a rare skeletal dysplasia affecting spine and ribs also have TBX6 mutations: 1 carried the microdeletion and a rare missense variant, and another 2 rare missense variants. We investigated the pathogenicity of the 3 missense variants in SCD by a luciferase assay. The results were negative for the proposal of Lefebvre et al. We consider these 2 SCD patients are more probably compound heterozygotes of null mutations and a common risk haplotype just as CS patients with TBX6 mutations.



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