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Background: ChatGPT has demonstrated notable capabilities and has gained popularity in various medical tasks, including patient education. This study evaluates the content and readability of ChatGPT's responses to parents' questions about congenital anomalies., Methods: Information on four congenital anomalies (congenital diaphragmatic hernia, esophageal atresia and tracheoesophageal fistula, anorectal malformation, and gastroschisis) was assessed. Seven questions frequently asked by parents were posed for each anomaly, and responses generated by GPT-4 were compared to online information sheets from three top pediatric medical centers. Two senior pediatric surgeons, blinded to the source, evaluated the answers based on accuracy, comprehensiveness, and conciseness. Reading time and readability of the answers were also assessed., Results: ChatGPT answered all 28 questions, while online information sheets varied in completeness. ChatGPT's responses were rated significantly higher regarding full accuracy, comprehensiveness, and conciseness compared to the online information sheets (p < 0.00001, <0.00001, 0.0002, respectively). Despite having longer reading times and more challenging to read, ChatGPT's responses were more precise and detailed., Conclusions: ChatGPT outperforms online information sheets in providing accurate, comprehensive, and concise answers about congenital anomalies. This positions ChatGPT as a beneficial supplementary resource in pediatric healthcare. Future research should explore real-world applications and usability among parents., Level of Evidence: Level III., Competing Interests: Conflict of interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Planarians are well-known model organisms for regeneration and developmental biology research due to their remarkable regenerative capacity. Here, we aim to advocate for the use of planaria as a valuable model for neurobiology, as well. Planarians have most of the major qualities of more developed organisms, including a primal brain. These traits combined with their exceptional regeneration capabilities, allow neurobiological experiments not possible in any other model organism, as we demonstrate by electrophysiological recording from planaria with two heads that control a shared body. To facilitate planarian neuroscience research, we developed an extracellular multi-unit recording procedure for the planarians fragile brain (Dugesia japonica). We created a semi-intact preparation restrained with fine dissection pins, enabling hours of reliable recording, via a suction electrode. Here, we demonstrate the feasibility and potential of planarian neurophysiological research by characterizing the neuronal activity during simple learning processes and responses to various stimuli. In addition, we examined the use of linalool as anesthetic agent to allows recordings from an intact, large worm and for fine electrophysiological approaches such as intracellular recording. The demonstrated ability for neurophysiological measurements, along with the inherent advantages of planarians, promotes this exceptional model organism for neuroscience research., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Achieving complex behavior in soft-bodied animals is a hard task, because their body morphology is not constrained by a fixed number of jointed elements, as in skeletal animals, and thus the control system has to deal with practically an infinite number of control variables (degrees of freedom). Almost 30 years of research on Octopus vulgaris motor control has revealed that octopuses efficiently control their body with strategies that emerged during the adaptive coevolution of their nervous system and body morphology. In this minireview, we highlight principles of embodied organization that were revealed by studying octopus motor control, and that are used as inspiration for soft robotics. We describe the evolved solutions to the problem, implemented from the lowest level, the muscular system, to the network organization in higher motor control centers of the octopus brain. We show how the higher motor control centers, where the sensory-motor interface lies, can control and coordinate limbs with large degrees of freedom without using body-part maps to represent sensory and motor information, as they do in vertebrates. We demonstrate how this unique control mechanism, which allows efficient control of the body in a large variety of behaviors, is embodied within the animal's body morphology., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

COVID-19 affects the respiratory parenchyma and may potentially contribute to the tendency of myasthenia gravis (MG) patients to develop respiratory failure. It is, therefore, important to study the safety of vaccines against SARS-CoV-2 and to assess the risk of COVID-19 in MG patients. The safety of the three-dose BNT162b2 mRNA vaccine and outcomes of COVID-19 during the alpha, delta, and omicron waves were studied in MG patients as well as the rate of exacerbations and safety for a period of up to 6 weeks from each vaccine dose and patient morbidity and mortality during COVID-19 compared to the general population. 430 vaccine doses were administered across 150 patients. Thirteen patients (8.7%) complained of exacerbation within 6 weeks of each vaccine dose. Both MG onset rate and exacerbation rate were similar to previous years. MG exacerbation rate among fifteen patients who had COVID-19 was significantly higher (40%) compared to the rate following vaccination. During the alpha and delta waves, COVID-19 mortality and severe disease were significantly higher (26.7%) compared to the general population (0.96%). All of them were unvaccinated and had generalized MG. During the omicron wave, all the MG patients who contracted COVID-19 were vaccinated and had mild disease. We concluded that COVID-19 is hazardous for generalized MG patients, while the vaccination did not raise the risk for either exacerbation or new onset of MG and was associated with a reduced risk for severe COVID-19. Hence, it is recommended for generalized MG patients to get vaccinated., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: The highly contagious COVID-19 has created unprecedented challenges in providing care to patients with resectable non-small cell lung carcinoma (NSCLC). Surgical management now needs to consider the risks of malignant disease progression by delaying surgery, and those of COVID-19 transmission to patients and operating room staff. The goal of our study was to describe our experience in providing both emergent and elective surgical procedures for patients with NSCLC during the COVID-19 pandemic in Israel, and to present our point of view regarding the safety of performing lung cancer surgery., Methods: This observational cross-sectional study included all consecutive patients with NSCLC who operated at Tel Aviv Medical Center, a large university-affiliated hospital, from February 2020 through December 2020, during the COVID-19 pandemic in Israel. The patients' demographics, COVID-19 preoperative screening results, type and side of surgery, pathology results, morbidity and mortality rates, postoperative complications, including pulmonary complications management, and hospital stay were evaluated., Results: Included in the study were 113 patients, 68 males (60.2%) and 45 females (39.8%), with a median age of 68.2 years (range, 41-89). Of these 113 patients, 83 (73.5%) underwent video-assisted thoracic surgeries (VATS), and 30 (26.5%) underwent thoracotomies. Fifty-five patients (48.7%) were preoperatively screened for COVID-19 and received negative results. Fifty-six postoperative complications were reported in 35 patients (30.9%). A prolonged air leak was detected in 11 patients (9.7%), atrial fibrillation in 11 patients (9.7%), empyema in 5 patients (4.4%), pneumonia in 9 patients (7.9%) and lobar atelectasis in 7 patients (6.2%). Three patients (2.7%) with postoperative pulmonary complications required mechanical ventilation, and two of them (1.6%) underwent tracheostomy. Two patients (1.6%) were postoperatively diagnosed as positive for COVID-19., Conclusions: Our data demonstrate the feasibility and efficacy of implementing precautionary strategies to ensure the safety of lung cancer patients undergoing pulmonary resection during the COVID-19 pandemic. The strategy was equally effective in protecting the surgical staff and healthcare providers, and we recommend performing lung cancer surgery during the pandemic era.

Objective: The optimal surgical approach for critically ill patients with complex coronary disease remains uncertain. We compared outcomes of bilateral internal thoracic artery (BITA) versus single ITA (SITA) revascularization in critical patients., Methods: We evaluated 394 consecutive critical patients with multi-vessel disease who underwent CABG during 1996-2001. Outcomes measured were early mortality, strokes, myocardial-infarctions, sternal infections, revisions for bleeding, and late survival. The critical preoperative state was acknowledged concisely by one or more of the following: preoperative ventricular tachycardia/fibrillation, aborted sudden cardiac death, or the need for mechanical ventilation or for preoperative insertion of intra-aortic-balloon counter-pulsation., Results: During the study period, 193 of our patients who underwent SITA and 201 who underwent BITA were in critical condition. The SITA group was older (mean 68.0 vs. 63.3 years, p = 0.001) and higher proportions were females (28.5% vs. 18.9% p = 0.025), after recent-MI (69.9% vs. 57.2% p = 0.009) and with left-main disease (38.3% vs. 49.3% p = .029); the median logistic EuroSCORE was higher (0.2898 vs. 0.1597, p<0.001). No statistically significant differences were observed between the SITA and BITA groups in 30-day mortality; and in rates of early CVA, MI and sternal infections (13.0% vs. 8.5%, p = 0.148; 4.1% vs. 6.0%, p = 0.49; 6.7% vs. 4.5%, p = 0.32 and 2.1% vs. 2.5%, p>0.99, respectively). Long-term survival (median follow-up of 15 years, interquartile-range: 13.57-15) was better in the BITA group (median 14.39 vs. 9.31± 0.9 years, p = 0.001). Propensity-score matching (132 matched pairs) also yielded similar early outcomes and improved long-term survival (median follow-up of 15 years, interquartile-range: 13.56-15) for the BITA group (median 12.49±1.71 vs. 7.63±0.99 years, p = 0.002). In multivariable analysis, BITA revascularization was found to be a predictor for improved survival (hazard-ratio of 0.419, 95%CI 0.23-0.76, p = 0.004)., Conclusions: This study demonstrated long-term survival benefit for BITA revascularization in patients in a critical pre-operative state who presented for surgical revascularization., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Review octopus ocular anatomy and describe the histopathologic findings in three octopuses diagnosed with phakitis and retinitis., Animals: Two common octopuses (Octopus vulgaris) and one giant Pacific octopus (Enteroctopus dofleini) with a history of ophthalmic disease., Methods: A literature search was performed for the ocular anatomy section. Both eyes from all three octopuses, and two control eyes, were submitted for histopathologic evaluation. Hematoxylin and eosin stain was used for standard histopathologic evaluation; GMS stain was used to screen for fungi, gram stain for bacteria; and Fite's acid fast stain for acid fast bacteria., Results: Anatomically, the anterior chamber of the octopus has direct contact with ambient water due to an opening in the dorsal aspect of a pseudocornea. The octopus lens is divided into anterior and posterior segments. The anterior half is exposed to the environment through the opening into the anterior chamber. Neither part of the lens has a lens capsule. The retina is everted, unlike the inverted vertebrate retina, and consists of just two layers. Histopathology revealed inflammatory phakitis and retinitis of varying severity in all six eyes of the study animals. No intraocular infectious organisms were recognized but one common octopus eye had clusters of coccidian parasites, identified as Aggregata sp., in extraocular tissues and blood vessels., Conclusion: We describe inflammatory phakitis and retinitis in two species of octopuses. The underlying cause for the severe intraocular response may be direct intraocular infection, water quality, an ocular manifestation of a systemic disease, or natural senescence., (© 2021 American College of Veterinary Ophthalmologists.)

Controlling the octopus's flexible hyper-redundant body is a challenging task. It is assumed that the octopus has poor proprioception which has driven the development of unique mechanisms for efficient body control. Here we report on such a mechanism: a phototactic response of extraocular photoreception. Extraocular photoreception has been observed in many and diverse species. Previous research on cephalopods revealed that increased illumination on their skin evokes chromatophore expansion. Recently, the mechanism was investigated and has been termed 'light-activated chromatophore expansion' (LACE). In this work we show that in response to illumination, the arm tip reacts in a reflex-like manner, folding in and moving away from the light beam. We performed a set of behavioral experiments and surgical manipulations to elucidate and characterize this phototactic response. We found that in contrast to the local activation and control of LACE, the phototactic response is mediated by the brain, although it is expressed in a reflex-like pattern. Our research results and observations led us to propose that the phototaxis is a means for protecting the arms in an instinctive manner from potential daytime predators such as fish and crabs, that could identify the worm-like tips as food. Indeed, observations of the octopuses revealed that their arm tips are folded in during the daytime, whereas at night they are extended. Thus, the phototactic response might compensate for the octopus's poor proprioception by keeping their arms folded in illuminated areas, without the need to be aware of their state., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Coronary artery bypass grafting (CABG) is the standard of care for the treatment of complex coronary artery disease. However, the optimal surgical treatment for patients with reduced left ventricular function with low ejection fraction (EF) is inconclusive. In our center, left-sided coronary grafting with bilateral internal thoracic artery (BITA) is generally the preferred method for surgical revascularization, also for patients with low EF. We compared early and long-term outcomes between BITA grafting and single internal thoracic artery (SITA) grafting in patients with low EF.We evaluated short- and long-term outcomes of all patients who underwent surgical revascularization in our center during 1996 to 2011, according to EF ≥30% and <30%. Univariate and multivariate analyses were performed. In addition, patients who underwent BITA and SITA grafting were matched using propensity score matching.In total, 5337 patients with multivessel disease underwent surgical revascularization during the study period. Of them, 394 had low EF. Among these, 188 underwent SITA revascularization and 206 BITA grafting. Those who underwent SITA were more likely to have comorbidities such as chronic obstructive pulmonary disease, diabetes, congestive heart failure, chronic renal failure, and a critical preoperative condition including preoperative intra-aortic balloon pump insertion.Statistically significant differences were not observed between the SITA and BITA groups in 30-day mortality (8.5% vs 6.8%, P = .55), sternal wound infection (2.7% vs 1.0%, P = .27), stroke (3.7% vs 6.3%, P = .24), and perioperative myocardial infarction (5.9% vs 2.9%, P = .15). Long-term survival (median follow up of 14 years, interquartile range, 11.2-18.9) was also similar between the groups. Propensity score matching (129 matched pairs) yielded similar early and long-term outcomes for the groups.This study did not demonstrate any clinical benefit for BITA compared with SITA revascularization in individuals with low EF.

Cells with contractile functions are present in almost all metazoans, and so are the related processes of muscle homeostasis and regeneration. Regeneration itself is a complex process unevenly spread across metazoans that ranges from full-body regeneration to partial reconstruction of damaged organs or body tissues, including muscles. The cellular and molecular mechanisms involved in regenerative processes can be homologous, co-opted, and/or evolved independently. By comparing the mechanisms of muscle homeostasis and regeneration throughout the diversity of animal body-plans and life cycles, it is possible to identify conserved and divergent cellular and molecular mechanisms underlying muscle plasticity. In this review we aim at providing an overview of muscle regeneration studies in metazoans, highlighting the major regenerative strategies and molecular pathways involved. By gathering these findings, we wish to advocate a comparative and evolutionary approach to prompt a wider use of "non-canonical" animal models for molecular and even pharmacological studies in the field of muscle regeneration.

Objective: We compared early and long-term outcomes between bilateral internal thoracic artery (BITA) grafting and single internal thoracic artery (SITA) grafting in patients with LM disease., Methods: We evaluated the outcomes of all patients with LM disease who underwent revascularization in our center during 1996-2011. Variables that were adjusted for in a multivariate analysis and in propensity matching included age, sex, comorbid diseases, repeat operation, the number of diseased vessels, other conduits used, the use of sequential grafting, the number of grafts constructed, and the operative era (1996-2000 vs. 2001-2011)., Results: In total, 949 patients with LM disease underwent BITA grafting and 564 underwent SITA grafting during the study period. SITA patients were more often female and more likely to have comorbidities such as chronic obstructive pulmonary disease, ejection fraction <30%, recent myocardial infarction, diabetes, congestive heart failure, chronic renal failure, and peripheral vascular disease, and to have undergone an emergency operation. We found no statistically significant difference between the SITA and BITA groups in 30-day mortality (4.8% vs. 3.3%, P = 0.136), sternal wound infection (2.0% vs. 2.4%, P = 0.548), and stroke (3.2% vs. 4.4%, P = 0.234). BITA patients had improved long-term survival (70.1% vs. 52.0% p<0.001), median follow-up of 15 years. In multivariate analysis, after propensity score matching (477 matched pairs), this finding was not statistically significant (P = 0.135)., Conclusion: This study did not demonstrate a clear benefit of BITA grafts among patients with LM disease.

Objectives: The use of bilateral internal thoracic artery graft for myocardial revascularization has improved the long-term survival and decreased the rate of repeat interventions in patients. A key technical factor for complete arterial revascularization is sufficient length of the internal thoracic artery (ITA) graft. The purpose of this study was to compare early and long-term outcomes of 'standard composite' grafting and 'reverse composite' grafting. In the former, the left ITA (LITA) is connected to the left anterior descending artery, and the right ITA is connected end-to-side to the LITA for revascularization of the left circumflex artery. In 'reverse composite' grafting, the LITA is connected to the left circumflex artery, and the right ITA is connected end-to-side to the LITA, for revascularization of the left anterior descending artery., Methods: We compared the outcomes of 1365 patients who underwent coronary artery bypass grafting in Tel-Aviv Sourasky Medical Centre, using bilateral ITA as standard composite versus 'reverse composite' grafts, between January 1996 and December 2011. A propensity score matching analysis compared 132 pairs of patients who underwent bilateral ITA by the 2 modes., Results: Twelve hundred and thirty patients underwent standard 'composite' grafts and 135 underwent 'reverse composite' grafts. Early mortality and early adverse effects did not differ significantly between the groups. After matching, the difference in late mortality between the groups was not statistically significant., Conclusions: This study suggests that revascularization of the left anterior descending with the right ITA, arising from an in situ LITA, is safe and provides early outcomes and long-term survival that are not significantly different from those of the standard composite grafting technique. However, there was evidence of better survival in the standard composite group., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Although bilateral internal thoracic artery (BITA) grafting is associated with improved survival, many surgeons are reluctant to use this technique due to its greater complexity and the potentially increased risk of sternal infection. This observational study examined if BITA grafting provides improved outcomes compared with single internal thoracic artery (SITA) grafting in patients with multivessel coronary disease., Methods: Patients in our institution who underwent BITA grafting during 1996-2011 were compared to those who underwent SITA grafting during the same period. To adjust for differences in demographic and clinical characteristics, patients were matched by propensity score. The Cox model was used to identify predictors of decreased survival and the Kaplan-Meier analysis was performed, both for the entire cohort and for the matched cohort., Results: SITA patients were older than BITA patients, included more females, and were more likely to have chronic obstructive lung disease, an ejection fraction <30%, diabetes, renal insufficiency, peripheral vascular disease and emergency and repeat operations. Three-vessel and left main diseases were more common among BITA patients, and operative mortality was reduced (2.1% vs 3.6% for SITA, P = 0.002). Sternal infection and stroke rates were similar for the groups. Ten-year Kaplan-Meier survival of BITA patients was better (71.2% vs 56.8%, respectively, P < 0.001). BITA grafting was found to be a predictor of better survival in the analysis of the matched cohort (P < 0.001)., Conclusions: Our results support the routine use of BITA grafting in patients who undergo myocardial revascularization., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

The muscular-hydrostat configuration of octopus arms allows high manoeuvrability together with the efficient motor performance necessary for its multitasking abilities. To control this flexible and hyper-redundant system the octopus has evolved unique strategies at the various levels of its brain-to-body organization. We focus here on the arm neuromuscular junction (NMJ) and excitation-contraction (E-C) properties of the arm muscle cells. We show that muscle cells are cholinergically innervated at single eye-shaped locations where acetylcholine receptors (AChR) are concentrated, resembling the vertebrate neuromuscular endplates. Na + and K + contribute nearly equally to the ACh-activated synaptic current mediating membrane depolarization, thereby activating voltage-dependent L-type Ca 2+ channels. We show that cell contraction can be mediated directly by the inward Ca 2+ current and also indirectly by calcium-induced calcium release (CICR) from internal stores. Indeed, caffeine-induced cell contraction and immunohistochemical staining revealed the presence and close association of dihydropyridine (DHPR) and ryanodine (RyR) receptor complexes, which probably mediate the CICR. We suggest that the dynamics of octopus arm contraction can be controlled in two ways; motoneurons with large synaptic inputs activate vigorous contraction via activation of the two routs of Ca 2+ induced contraction, while motoneurons with lower-amplitude inputs may regulate a graded contraction through frequency-dependent summation of EPSP trains that recruit the CICR. Our results thus suggest that these motoneuronal pools are likely to be involved in the activation of different E-C coupling modes, thus enabling a dynamics of muscles activation appropriate for various tasks such as stiffening versus motion generation.

Objectives: Bilateral internal thoracic artery (BITA) grafting is associated with improved survival, but this technique is reluctantly used in women due to an increased risk of sternal wound infection. The aim of this study was to compare the long-term survival of women who underwent BITA grafting and single internal thoracic artery (SITA) grafting., Methods: We performed a retrospective analysis of 556 consecutive female BITA patients and 685 female SITA patients., Results: SITA patients were older and more likely to have comorbidities (diabetes mellitus, chronic lung disease, chronic renal failure, peripheral vascular disease and cerebral vascular disease). Operative mortality showed a trend towards a benefit for BITA (2.9% vs 5.0% for SITA, P = 0.06). The sternal wound infection rates were similar (3.4% vs 2.9%, P = 0.6); however, the occurrence of stroke was significantly lower in the SITA group (3.4% vs 1.2%, P = 0.007). The median survival of the BITA group was significantly better {13.8 years [95% confidence interval (CI) 12.8-14.9] vs 10.3 years [95% CI 9.6-11.1], P = 0.001}. After propensity score matching (491 pairs), the assignment to BITA was not associated with increased early mortality or complication rates, and the choice of BITA grafting was associated with better survival [14.5 years (95% CI 13.3-15.6) vs 11.8 years (95% CI 10.7-12.9)]. Only the choice of conduits was associated with increased late mortality (multivariable analysis, hazard ratio 1.28, 95% CI 1.024-1.591; P = 0.03)., Conclusions: The low early mortality and complication rate, and the long-term survival benefit of BITA compared to SITA grafting, support the use of BITA grafting in women., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Identification of the biological features of autism is essential for designing an efficient treatment and for prevention of the disorder. Though the subject of extensive research, the neurophysiological features of autism remain unclear. One of the proposed biological causes of autism is malfunction of the pineal gland and deficiency of its principal hormone, melatonin. The main function of melatonin is to link and synchronize the body's homeostasis processes to the circadian and seasonal rhythms, and to regulate the sleep-wake cycle. Therefore, pineal dysfunction has been implicated based on the common observation of low melatonin levels and sleep disorders associated with autism. In this perspective, we highlight several recent findings that support the hypothesis of pineal gland/melatonin involvement in autism. Another common symptom of autism is abnormal neuroplasticity, such as cortical overgrowth and dendritic spine dysgenesis. Here, we synthesize recent information and speculate on the possibility that this abnormal neuroplasticity is caused by hyperactivity of endogenous N,N-dimethyltryptamine (DMT). The pineal gland was proposed as the source of DMT in the brain and therefore, our assumption is that besides melatonin deficiency, pineal dysfunction might also play a part in the development of autism through abnormal metabolism of DMT. We hope that this manuscript will encourage future research of the DMT hypothesis and reexamination of several observations that were previously attributed to other factors, to see if they could be related to pineal gland/melatonin malfunction. Such research could contribute to the development of autism treatment by exogenous melatonin and monitored light exposure.

Background: The use of two bilateral internal thoracic artery grafting (BITA) was shown to lead to survival benefit. However, operators are reluctant to use BITA with peripheral vascular disease (PVD) because of concerns of increased rates of sternal wound infection and lack of studies supporting survival benefit compared with single internal thoracic artery (SITA) grafting. The aim of this study is to compare outcome BITA grafting versus of SITA and vein grafts in PVD patients., Patients and Methods: Six hundred and twenty-one PVD patients who underwent BITA between 1996 and 2011 were compared with 372 patients who underwent SITA., Results: SITA patients were older and more likely more likely to have comorbidities (female, insulin-dependent diabetes, chronic obstructive lung disease, congestive heart failure, previous coronary artery bypass grafting, renal insufficiency, cerebrovascular disease, and emergency operation). Operative mortality (5.1 vs. 4.5%, in the SITA and BITA, respectively, P=0.758), rate of sternal wound infection (5.1 vs. 3.9%, P=0.421), and strokes (4.8 vs. 7.4%, P=0.141) were not significantly different between groups. BITA patients did not have significantly better 10-year survival (52.6 vs. 45.9%, P=0.087) and after propensity score matching (302 well-matched pairs), BITA was not associated with improved survival (hazard ratio: 0.902; 95% confidence interval: 0.742-1.283; P=0.784) (Cox model)., Conclusion: The routine use of BITA versus SITA in PVD patients does not improve long-term survival. Selective use of BITA in lower risk patients might unmask the benefits of BITA.

[This corrects the article DOI: 10.1371/journal.pone.0201227.].

Objectives: Bilateral internal thoracic artery (ITA) grafting is associated with improved survival. However, potential survival benefit of using two ITA`s in patients with chronic lung disease (CLD) is questionable due to their increased risk of sternal wound infection (SWI) compared to operations incorporating single ITA (SITA). The purpose of this study is to compare early and long-term outcome of bilateral internal thoracic artery (BITA) grafting to that of grafting with single internal thoracic grafts and vein grafts or radial artery (SITA) in CLD patients with multi-vessels coronary disease., Methods: One hundred and forty eight CLD patients who underwent BITA between 1996 and 2011 were compared with 239 who underwent SITA at the same period., Results: SITA patients were more often female, more likely to have insulin treated diabetes (DM), DM with end organ damage, neurologic dysfunction and unstable angina. Despite of the difference in preoperative characteristics, early mortality (5.4% vs. 5.4%, in the SITA and BITA respectively, p = 0 < .999) and occurrences of SWI (6.3% vs 9.5%, p = 0.320) and strokes (3.8% vs 5.4%,p = 0.611) were not significantly different between groups. BITA patients did not have better Kaplan-Meier 10 year survival (52.8% vs. 42.6%, p = 0.088) and after matching, BITA and SITA had similar adjusted survival (HR 0.983[95%CI 0.755-1.280] p = 0.901) (cox model)., Conclusion: Our study results suggest that in patients with CLD, the choice of BITA grafting technique did not provide survival benefit compared to SITA with other conduits., Competing Interests: The authors have declared that no competing interests exist.

Background: Bilateral internal thoracic artery grafting (BITA) is associated with improved survival. However, surgeons do not commonly use BITA in patients after myocardial infarction (MI) because survival is good with single internal thoracic artery grafting (SITA). We aimed to compare the outcomes of BITA with those of SITA and other approaches in patients with multivessel disease after recent MI., Methods and Results: In total, 938 patients with recent MI (<3 months) who underwent BITA between 1996 and 2011 were compared with 682 who underwent SITA. SITA patients were older and more likely to have comorbidities (diabetes mellitus, chronic obstructive pulmonary disease, chronic renal failure, peripheral vascular disease), to be female, and to have had a previous MI. Acute MI and 3-vessel disease were more prevalent in the BITA group. Operative mortality of BITA patients was lower (3.0% versus 5.8%, P =0.01), and sternal infections and strokes were similar. Median follow-up was 15.21 years (range: 0-21.25 years). Survival of BITA patients was better (70.3% versus 52.5%, P <0.001). Propensity score matching was used to account for differences in preoperative characteristics between groups. Overall, 551 matched pairs had similar preoperative characteristics. BITA was a predictor of better survival in the matched groups (hazard ratio: 0.679; P =0.002; Cox model). Adjusted survival of emergency BITA and SITA patients was similar (hazard ratio: 0.883; P =0.447); however, in the nonemergency group, BITA was a predictor of better survival (hazard ratio: 0.790; P =0.009; Cox model)., Conclusions: This study suggests that survival is better with BITA compared with SITA in nonemergency cases after recent MI, with proper patient selection., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: The potential survival benefit of bilateral internal thoracic artery (BITA) grafting in patients undergoing off-pump coronary artery bypass graft surgery (OPCABG) is controversial owing to the technical complexity of these operations. Our objective was to compare the outcome of patients undergoing OPCABG with BITA to the outcome of patients undergoing OPCABG with a single internal thoracic artery (SITA) and saphenous vein grafts or radial artery., Methods: Five hundred and thirty-five consecutive patients who underwent OPCABG BITA at our institute between 2000 and 2008 were compared with 422 patients who underwent OPCABG with SITA. Propensity score matching was used to account for differences between groups in preoperative characteristics., Results: Being female (20.9% versus 36.0%, p < 0.001), having diabetes mellitus (36.6% versus 55.7%, p > 0.001), recent myocardial infarction (23.6% versus 33.2%, p > 0.001), aged 70 years or more (41.1% versus 49.8%, p = 0.001), peripheral vascular disease (26.1% versus 46.7%, p > 0.001), and chronic renal failure (7.9% versus 15.9%, p > 0.001) were less frequent in the BITA group than in the SITA group, respectively. The European System for Cardiac Operative Risk Evaluation score was significantly higher for the SITA group (7.62, versus 5.46 for BITA group, p = 0.001), whereas operative mortality (1.7% BITA versus 2.6% SITA) and sternal wound infections (1.7% BITA versus 2.1% SITA) were similar. The mean follow-up was 11.6 ± 3.5 years. The BITA patients' 10-year survival (Kaplan-Meier) was better (72.2% versus 55.1% for SITA, p > 0.001). However, after propensity matching, survival for BITA and SITA were similar., Conclusions: This large cohort study suggests that long-term outcomes for patients undergoing OPCABG are not better with BITA grafting., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: The composite T-graft with radial artery (RA) attached end-to-side to the left internal thoracic artery (ITA) provides arterial myocardial revascularization without the increased risk of deep sternal wound infection associated with harvesting 2 ITAs. However, many surgeons are reluctant to use RA in patients with peripheral vascular disease (PVD) due to concerns regarding the quality of the conduit in this subset of patients. The purpose of this study is to compare early- and long-term outcomes of arterial grafting with bilateral ITAs (BITA) to that of single ITA and RA in patients with PVD., Methods: Between 1999 and 2010, 619 consecutive patients with PVD (500 BITAs and 119 single ITA and RA) underwent myocardial revascularization in our institution., Results: Occurrence of following risk factors as female sex, age 70+, diabetes, unstable angina, emergency operation, cerebrovascular disease and chronic obstructive pulmonary disease was higher in the RA-ITA group. The RA-ITA group also had a higher logistic EuroSCORE (22.1 vs 13.3). Operative mortality and occurrence of deep sternal wound infection of the two groups was similar (4.2% vs 5.0% and 2.5% vs 4.0% for the radial and bilateral ITA, respectively). Median follow-up was 9.75 years. Unadjusted Kaplan-Meier 10-year survival of the two groups was similar (44.1% vs 49.6%, P  = 0.7). After propensity score matching (100 pairs), assignment to BITA was not associated with better adjusted survival (hazard ratio 0.593, 95% confidence interval 0.265-1.327, P  = 0.20, Cox model)., Conclusions: In patients with PVD, complete arterial revascularization with left ITA and RA can be justified with regards to survival., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aim: To assess the impact of left ventricular (LV) filling parameters on outcomes following trans-catheter aortic valve replacement (TAVR)., Methods and Results: A total of 526 TAVR patients were compared with 300 patients with severe aortic stenosis (AS) treated conservatively. Clinical variables were collected along with echocardiographic data at baseline, 1 month, and 6 months after study entry. End points included all-cause mortality and the combination of death and heart failure admission. LV filling parameters associated with mortality included reduced A wave velocity (P = 0.005) and shorter deceleration time (DT) (P = 0.0005). DT was superior to all other parameters (P = 0.05) apart from patients with atrial fibrillation in whom E/e' was better. Short DT (<160 ms) was associated with lower survival than long DT (≥220 ms; P = 0.002) or intermediate DT (P = 0.05), even after adjustment for age, gender, stroke volume index (SVI), and co-morbidities. However, patients with short baseline DT exhibited greater improvement in DT, E/A, and systolic pulmonary pressure at follow-up than patients with baseline DT ≥160 ms (P < 0.05 for all time x group interactions). Most importantly, among patients with short DT, TAVR was associated with better survival than conservative treatment (46 ± 7 vs. 28 ± 12% at 3 years, P = 0.05), even after adjustment for age, gender, and SVI (P = 0.05)., Conclusion: Short DT is an independent predictor of adverse outcome following TAVR. Nevertheless, LV filling parameters improve in most patients post TAVR, and TAVR is associated with improved survival compared with conservative therapy, even in patients with evidence of elevated LV filling. Thus, evidence of elevated LV filling should not be viewed as a contraindication for TAVR., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background: Bilateral internal thoracic artery (BITA) grafting in patients with diabetes mellitus is controversial because of a higher risk for sternal infection. The purpose of this study is to compare the outcome of BITA grafting to that of single ITA (SITA) grafting in patients with diabetes., Methods: Between 1996 and 2010, 964 diabetic patients with multivessel disease who underwent primary coronary artery bypass graft surgery with BITA were compared with 564 patients who underwent coronary artery bypass graft surgery with SITA and saphenous vein grafts., Results: The SITA patients were older, more often female, more likely to have chronic obstructive pulmonary disease, ejection fraction 30% or less, insulin-dependent diabetes, recent myocardial infarction, renal insufficiency, peripheral vascular disease, and emergency operation. The BITA patients more often underwent coronary artery bypass graft surgery with three or more grafts. The two groups had similar operative mortality, 2.6% BITA versus 3.0% SITA, and sternal infection, 3.1% versus 3.9%, respectively. The mean follow-up was 12.2 ± 4.3 years. Unadjusted Kaplan-Meier 10-year survival of the BITA group was better than that of the SITA group (65.3% ± 3.1% versus 55.5% ± 4.5%, respectively; p = 0.004), After propensity score matching (490 well-matched pairs), Kaplan-Meier 10-year survival was not significantly different between the matched groups; however, the Cox-adjusted survival of the BITA patients was better (hazard ratio 0.729, 95% confidence interval: 0.551 to 0.964, p = 0.027)., Conclusions: The findings of this large cohort study suggest that the long-term outcome of patients with diabetes and multivessel disease who undergo BITA grafting is better than that of diabetic patients who undergo coronary artery bypass graft surgery with SITA and saphenous vein grafts., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Bilateral internal mammary artery (BIMA) grafting is associated with improved survival. However, many surgeons are reluctant to use this technique, owing to the potentially increased risk of sternal infection. The composite T-graft with radial artery (RA) attached end-to-side to the left internal mammary artery (IMA) provides complete arterial revascularization without increased risk of sternal infection. The purpose of this study is to compare outcomes of these 2 strategies., Methods: Patients who underwent BIMA grafting using the composite T-graft technique, between 1996 and 2010 (n = 1329), were compared with 389 patients who underwent composite grafting with a single IMA + RA during the same time period., Results: Patients undergoing single IMA grafting were older, more often women, and more likely to have diabetes, peripheral vascular disease, and COPD, and to need an emergency operation. Congestive heart failure, left main disease, and recent myocardial infarction were more prevalent with bilateral grafting. Propensity-score matching was used to account for differences between groups in preoperative patient characteristics. The 268 matched pairs had similar characteristics. The median follow-up time was 14.19 (95% confidence interval 13.43-14.95) years. Operative mortality and Kaplan-Meier 10-year survival of the 2 matched groups were similar (3.4% vs 3.7%, and 61.6% vs 64%, for the groups treated with BIMA and single IMA, respectively). Cox-adjusted survival was similar (P = .514). Age, chronic renal failure, and performance of <3 bypass grafts were independent predictors of decreased survival., Conclusions: This study suggests that long-term outcomes of arterial revascularization with a composite T-graft constructed using left IMA and RA are not inferior to outcomes after BIMA grafting., (Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Aims: To evaluate the prognostic role of pulmonary venous flow parameters and their role in patients with preserved ejection fraction (EF)., Methods and Results: Pulmonary venous flow parameters were measured in 365 patients in sinus rhythm, without significant mitral disease, and EF >50% (age 64.9 ± 19; 52% female) by a single sonographer. Survival, time to re-admission for heart failure, and to a combined cardiac end point (cardiac death, heart failure, and atrial fibrillation) were retrospectively analysed and correlated to echo parameters. Systolic (S) and diastolic (D) pulmonary vein flow were obtainable in 73% of patients and Ar in 65%. The lower peak S/D ratio and higher ΔAr-A time were associated with higher rate of heart failure readmission (P = 0.03 for both). The S/D integral ratio was the best pulmonary vein flow predictor of heart failure readmissions (P = 0.0009), better than the peak S/D ratio, or ΔA-Ar time (P < 0.01 for both), and independently predicted worse outcome even when adjusted for diastolic grading (using recent guidelines), left ventricle mass index, E/e', and left atrial volume index (P < 0.05 for all). The addition S/D ratio to diastolic grading recognized patients with pseudo-normal filling pattern and S/D ratio >1 with similar clinical outcomes to grade I (P > 0.5), but worse clinical outcomes than in the pseudo-normal patients with lower S/D ratio (P < 0.01)., Conclusions: PVFP are obtainable in most patients, add prognostic information on top of routine diastolic parameters, and define an early stage of diastolic dysfunction resembling the pseudo-normal pattern in which S/D ratio is >1, and outcome is excellent., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Objectives: The purpose of this study was to assess individual mechanisms of effort intolerance in patients with heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), or normal cardiac function using combined echocardiography and cardiopulmonary stress testing., Background: Combined stress echocardiography and cardiopulmonary tests visualize cardiac chambers in 4 well-defined activity levels (rest, unloaded, anaerobic threshold, and peak), allowing noninvasive assessment of cardiac function, hemodynamics, and arterial venous oxygen content difference (AVo(2)Diff) during all stages., Methods: Left ventricular volumes, stroke volume (SV), S', E/e', oxygen consumption (Vo(2)), and AVo(2)Diff were measured in all effort stages using ramp semirecumbent cycle prolonged (≥8 min) exercise in 45 consecutive subjects evaluated for effort intolerance (14 normal cardiac function, 16 HFpEF, and 15 HFrEF patients; age 56.5 ± 16 years; 73% male)., Results: In HFpEF and HFrEF, the changes in Vo2 were attenuated (between group p = 0.003; group by time interaction p < 0.0001), as well as peak heart rate (p = 0.0001; p = 0.0001) and SV (p = 0.006; p = 0.0001). End-diastolic volume to E/e' ratio (measure of compliance) was superior in HFrEF and normal patients at baseline but worsened in HFpEF and HFrEF at peak exercise (8.3 ± 4 vs. 11.6 ± 5 vs. 19.1 ± 8; p = 0.004; p = 0.01). Functional mitral regurgitation worsened even during the unloaded stage, mostly in patients with HFrEF, but also in several patients with HFpEF. In multivariable analysis, heart rate response (p = 0.007), and AVo(2)Diff (p < 0.0001) were the most significant independent predictors of effort capacity; SV was not., Conclusions: Combined tests are feasible and allow noninvasive evaluation of effort intolerance. In HFpEF and HFrEF patients, exercise intolerance is predominantly due to chronotropic incompetence and peripheral factors. Combined stress echocardiography and cardiopulmonary tests may have potential for clinical management and selection of patients for trials., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To use cardiovascular data from computerized tomographic (CT) pulmonary angiography for facilitating the identification of pulmonary hypertension (PH) in patients without acute pulmonary embolism., Materials and Methods: The institutional human research committee approved this retrospective study; informed consent was waived. Patients without pulmonary embolism who underwent CT pulmonary angiography and echocardiography within 24 hours of each other between December 2008 and October 2012 were retrospectively identified. The diameters of the pulmonary artery, aorta, and right and left ventricles and the severity of reflux of contrast material were assessed. The volumes of each cardiac compartment were calculated. Doppler echocardiography served as a reference standard for PH. A prediction model for PH was built by using backward logistic regression and was presented on a nomogram. The prediction model was evaluated with 10-fold cross-validation, and a test group of patients was studied between November 2012 and June 2014., Results: The final study group included 182 patients, of whom 98 (54%) were given a diagnosis of PH on the basis echocardiographic results. Age of 67 years or older (odds ratio [OR] = 4.46), reflux grade of 3 or higher (OR = 2.63), right atrial volume of greater than or equal to 106 cm(3) (OR = 3.59), pulmonary artery diameter greater than or equal to 28 mm (OR = 2.52) and pulmonary artery diameter to aorta diameter ratio of greater than or equal to 0.86 (OR = 2.17) were independently associated with PH. The logistic model showed good discrimination ability (area under the curve = 0.844, discrimination slope = 0.359). Tenfold cross-validation showed 85.7% sensitivity, 60.7% specificity, 71.3% positive predictive value, and 76.1% negative predictive value for identification of PH, while the test group showed similar results (84.1%, 60.5%, 71.2%, and 76.7%, respectively)., Conclusion: Cardiovascular data derived from CT pulmonary angiography are associated with PH, and a nomogram can be created that may facilitate identification of PH after exclusion of acute pulmonary embolism., ((©) RSNA, 2015 Online supplemental material is available for this article.)

Objectives: Bilateral internal thoracic artery grafting in elderly patients is controversial. We compared the outcome of bilateral internal thoracic artery grafting with that of single internal thoracic artery and saphenous vein and radial artery conduits in these patients., Methods: Patients aged 70 years or more who underwent bilateral internal thoracic artery grafting between 1996 and 2008 (n = 1045) were compared with patients who underwent coronary artery bypass grafting with a single internal thoracic artery + saphenous vein graft (n = 582) or a single internal thoracic artery + radial artery (n = 249)., Results: Prevalence of female gender, diabetes, emergency operation, and chronic obstructive pulmonary disease was lower in the bilateral internal thoracic artery grafting group compared with the internal thoracic artery + radial artery and internal thoracic artery + saphenous vein graft groups, whereas congestive heart failure and recent myocardial infarction were more prevalent in the bilateral internal thoracic artery grafting group. Operative mortality and sternal wound infections were not significantly different between groups. The mean follow-up was 8.17 ± 4.45 years. Ten-year survival (Kaplan-Meier) in the internal thoracic artery + saphenous vein graft group was significantly lower than in the bilateral internal thoracic artery grafting and internal thoracic artery + radial artery groups (P < .001). Assignment to the saphenous vein graft group was also associated with decreased adjusted survival (P < .001) compared with the bilateral internal thoracic artery and internal thoracic artery + radial artery groups., Conclusions: This study supports the use of arterial grafts in elderly patients undergoing coronary artery bypass grafting., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: New therapeutic approaches to improve cardiac contractility without severe risk would improve the management of acute heart failure. Increasing systolic sodium influx can increase cardiac contractility, but most sodium channel activators have proarrhythmic effects that limit their clinical use. Here, we report the cardiac effects of a novel positive inotropic peptide isolated from the toxin of the Black Judean scorpion that activates neuronal tetrodotoxin-sensitive sodium channels., Methods and Results: All venoms and peptides were isolated from Black Judean Scorpions (Buthotus Hottentotta) caught in the Judean Desert. The full scorpion venom increased left ventricular function in sedated mice in vivo, prolonged ventricular repolarization, and provoked ventricular arrhythmias. An inotropic peptide (BjIP) isolated from the full venom by chromatography increased cardiac contractility but did neither provoke ventricular arrhythmias nor prolong cardiac repolarization. BjIP increased intracellular calcium in ventricular cardiomyocytes and prolonged inactivation of the cardiac sodium current. Low concentrations of tetrodotoxin (200 nmol/L) abolished the effect of BjIP on calcium transients and sodium current. BjIP did not alter the function of Nav1.5, but selectively activated the brain-type sodium channels Nav1.6 or Nav1.3 in cellular electrophysiological recordings obtained from rodent thalamic slices. Nav1.3 (SCN3A) mRNA was detected in human and mouse heart tissue., Conclusions: Our pilot experiments suggest that selective activation of tetrodotoxin-sensitive neuronal sodium channels can safely increase cardiac contractility. As such, the peptide described here may become a lead compound for a new class of positive inotropic agents., (© 2014 American Heart Association, Inc.)

Objective: Numerous anomalies or postprocedural stricture of the venous system prevent optimal endovascular implantation of a pacing lead in more than 10% of patient indicated for permanent pacing or cardiac resynchronization therapy. The purpose of this report was to summarize our experience and immediate postoperative results of thoracoscopic lead implantation as a lesser invasive solution to an unsuccessful endovascular lead insertion., Methods: From January 2008 to April 2013, 11 epicardial leads were introduced thoracoscopically at our center as a rescue treatment after failed endovascular attempts. Patients were ventilated using a double-lumen endotracheal tube. A 5-mm 30-degree lance thoracoscope was used with either 2 or 3 additional working ports. A screw-in pacing lead (Medtronic Model 5071 Pacing lead, Minneapolis, MN USA) was inserted into the left ventricular epicardium. After the lead placement and assessment for threshold less than 1 V, the lead was brought to the chest wall and tunneled to the pacemaker generator pocket. At the end of the procedure, a small, flexible 14F thoracic drain, was left inside the pleural cavity for the next 24 hours., Results: There were no mortality or any major surgical complications among these patients. All patients responded to the epicardial lead implantation in terms of appropriate pacing and conductivity. No clinical failure was observed, and no patient required a repeat procedure., Conclusions: Thoracoscopic lead insertion is safe and easy to perform. We believe it should be offered as the first choice after failed endovascular pacing lead implantation.

Objective: Most studies describing the outcome of coronary artery bypass grafting patients supported preoperatively with an intra-aortic balloon pump (IABP) have reported early results. The purpose of our study was to evaluate the early and long-term results., Methods: Of 2658 isolated coronary artery bypass grafting procedures performed from 1996 to 2001, 215 were supported preoperatively with an IABP. The indications for IABP insertion were cardiogenic shock in 18 (8.4%), acute evolving myocardial infarction in 38 (17.7%), clinical instability in 84 (39.1%), and critical coronary lesions in 75 (34.9%)., Results: Operative mortality was 12.6%. The mortality of the cardiogenic shock patients was greater (22.2%; P=.174). Logistic regression analysis showed patient age (odds ratio, 1.057; 95% confidence interval, 1.010-1.108) and cardiopulmonary bypass (CPB) time (odds ratio, 1.020; 95% confidence interval, 1.008-1.031) were associated with increased operative mortality. An increased number of bypass grafts had a protective effect (odds ratio, 0.241; 95% confidence interval, 0.113-0.515). The actual early mortality was lower than the logistic EuroSCORE calculated mortality (12.6% vs 32.8%, P<.0001). The mean follow-up was 8±4 years. The Kaplan-Meier 10-year survival was 49%. The Cox adjusted overall (early and late) survival and major adverse cardiac events-free survival of the different IABP subgroups was similar. Cox analyses showed peripheral vascular disease, off-pump coronary artery bypass surgery, age, CPB time, female gender, and fewer bypass grafts were associated with decreased survival., Conclusions: In patients supported preoperatively with an IABP, better early and long-term results were strongly related to younger age, a shorter CPB time, and a greater number of bypass grafts. Avoiding the use of CPB (off pump) in these emergency cases is not recommended., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

AdE-1, a cardiotonic peptide recently isolated from the sea anemone Aiptasia diaphana, contains 44 amino acids and has a molecular mass of 4907 Da. It was previously found to resemble other sea anemone type 1 and 2 Na+ channel toxins, enhancing contractions of rat cardiomyocytes and slowing their twitch relaxation; however, it did not induce spontaneous twitches. AdE-1 increased the duration of the cardiomyocyte action potential and decreased its amplitude and its time-to-peak in a concentration-dependent manner, without affecting its threshold and cell resting potential. Nor did it generate the early and delayed after-depolarizations characteristic of sea anemone Na+ channel toxins. To further understand its mechanism of action we investigated the effect of AdE-1 on the major ion currents of rat cardiomyocytes. In the present study we show that AdE-1 markedly slowed inactivation of the Na+ current, enhancing and prolonging the current influx with no effect on current activation, possibly through direct interaction with the site 3 receptor of the Na+ channel. No significant effect of AdE-1 on the Ca2+ current was observed, but, unexpectedly, AdE-1 significantly increased the amplitude of the transient component of the K+ current, shifting the current threshold to more negative membrane potentials. This effect on the K+ current has not been found in any other sea anemone toxin and may explain the exclusive reduction in action potential amplitude and the absence of the action potential disorders found with other toxins, such as early and delayed after-depolarizations.

Controlling movements of flexible arms is a challenging task for the octopus because of the virtually infinite number of degrees of freedom (DOFs) [1, 2]. Octopuses simplify this control by using stereotypical motion patterns that reduce the DOFs, in the control space, to a workable few [2]. These movements are triggered by the brain and are generated by motor programs embedded in the peripheral neuromuscular system of the arm [3-5]. The hundreds of suckers along each arm have a tendency to stick to almost any object they contact [6-9]. The existence of this reflex could pose significant problems with unplanned interactions between the arms if not appropriately managed. This problem is likely to be accentuated because it is accepted that octopuses are "not aware of their arms" [10-14]. Here we report of a self-recognition mechanism that has a novel role in motor control, restraining the arms from interfering with each other. We show that the suckers of amputated arms never attach to octopus skin because a chemical in the skin inhibits the attachment reflex of the suckers. The peripheral mechanism appears to be overridden by central control because, in contrast to amputated arms, behaving octopuses sometime grab amputated arms. Surprisingly, octopuses seem to identify their own amputated arms, as they treat arms of other octopuses like food more often than their own. This self-recognition mechanism is a novel peripheral component in the embodied organization of the adaptive interactions between the octopus's brain, body, and environment [15, 16]., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure (CRF). Defective nitric oxide (NO) generation due to decreased endothelial nitric oxide synthase (eNOS) activity is a crucial parameter characterizing ECD. Decreased activity of cationic amino acid transporter-1 (CAT-1), the selective arginine transporter of eNOS, has been shown to inhibit eNOS in uremia. Recently, we failed to demonstrate a decrease in glomerular arginine transport in uremic female rats (Schwartz IF, Grupper A, Soetendorp H, Hillel O, Laron I, Chernichovski T, Ingbir M, Shtabski A, Weinstein T, Chernin G, Shashar M, Hershkoviz R, Schwartz D. Am J Physiol Renal Physiol 303: F396-F404, 2012). The current experiments were designed to determine whether sexual dimorphism which characterizes glomerular arginine transport system in uremia involves the systemic vasculature as well and to assess the effect of L-arginine in such conditions. Contractile and vasodilatory responses, ultrastructural changes, and measures of the L-arginine-NO system were performed in thoracic aortas of female rats subjected to 5/6 nephrectomy. The contractile response to KCl was significantly reduced, and acetylcholine-induced vasodilation was significantly impaired in aortas from CRF dames compared with healthy rats. Both of these findings were prevented by the administration of arginine in the drinking water. The decrease in both cGMP generation, a measure of eNOS activity, and aortic eNOS and phosphorylated eNOS abundance observed in CRF rats was completely abolished by l-arginine, while arginine transport and CAT-1 protein were unchanged in all experimental groups. Arginine decreased both serum levels of advanced glycation end products and the asymmetrical dimethylarginine/arginine ratio and restored the endothelial ultrastructure in CRF rats. In conclusion. arginine administration has a profound beneficial effect on ECD, independently of cellular arginine uptake, in CRF female rats.

Background: Stentless aortic bioprostheses were designed to provide improved hemodynamic performance and potentially better survival., Objectives: To report the outcomes of patients after aortic valve replacement with the Freestyle stentless bioprosthesis at the Tel Aviv Medical Center followed for < or = 15 years., Methods and Results: Between 1997 and 2011, 268 patients underwent primary aortic valve replacement with a Freestyle bioprosthesis, 211 (79%) of them in the sub-coronary position. Mean age, Charlson comorbidity index and Euro-score were 71.0 +/- 9.2 years, 4.2 +/- 1.5 and 10.2 +/- 11 respectively, and 156 (58%) were male. Peak and mean trans-aortic gradient decreased significantly (75.0 +/- 29.1 vs. 22.8 +/- 9.6 mmHg, P < 0.0001; and 43.4 +/- 17.2 vs. 12.1 +/- 5.4 mmHg, P < 0.0001 respectively) during 3 months of follow-up. Mean overall follow-up was 4.9 +/- 3.1 years and was complete in all patients. In-hospital mortality was 4.1% (n=11) but differed significantly between the first 100 patients operated before 2006 and the last 168 patients operated after January 2006 (8 vs. 3 patients, 8.0% vs. 1.8%, P = 0.01). Overall, 5 and 10 year survival rates were 85 +/- 2.5% and 57.2 +/- 5.7%, respectively. Five year survival was markedly improved in patients operated after January 2006 compared to those operated in the early years of the experience (92.3 +/- 2.3% vs. 76.0 +/- 4.4%, P = 0.0009). All the 21 octogenarians operated after January 2006 survived surgery, with excellent 5 year survival (85.1 +/- 7.9%). Six patients required reoperation during follow-up: structural valve deterioration in five and endocarditis in one., Conclusions: Aortic valve replacement with the Freestyle bioprosthesis provides good long-term hemodynamic and clinical outcomes, even in octogenarians. Valve calcification is the major (and rare) mode of valve deterioration leading to reoperation in these patients.

Background: Increased perioperative fluid administration is an independent risk factor for lung injury after pulmonary resection. In clinical practice, fluid therapy is heavily guided by urinary output; however, diuretic response to plasma volume expansion has been reported to be blunted during anesthesia and surgery. We therefore hypothesized that in patients undergoing video-assisted thoracoscopic surgery, different regimens of intraoperative fluid management would not affect urinary output as would be expected in the nonsurgical scenario. Moreover, a restrictive perioperative fluid approach, as indicated in these operations, will not harm renal function., Methods: One hundred two patients undergoing video-assisted thoracoscopic surgery were randomly allocated to receive intraoperatively either high (8 mL/[kg · h]; n = 51) or low (2 mL/[kg · h]; n = 51) amounts of Ringer's lactate solution. The primary end point was intraoperative urinary output. Secondary end points included postoperative creatinine serum levels and postoperative complication rate., Results: Demographic and surgical data were comparable between groups. Regardless of the intraoperatively fluids administered (mean ± SD, 2131 ± 850 vs 1035 ± 652 mL in high and low groups, respectively; P < .0001), urinary output was similar (median 300 mL). Perioperative creatinine serum levels decreased significantly postoperatively and were not significantly different among the groups., Conclusions: In patients undergoing video-assisted thoracoscopic surgery, intraoperative urinary output and postoperative renal function are not affected by administration of fluids in the range of 2 to 8 mL/(kg · h). The clinical practice of administering fluids to enhance diuresis in the perioperative period should therefore be abandoned., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Although bilateral internal thoracic artery grafting is associated with improved survival, the use of this technique in the elderly is controversial because of their increased surgical risk and shorter life expectancy. The purpose of this study was to evaluate the effect of age on outcome of patients undergoing bilateral internal thoracic artery grafting., Methods and Results: Between 1996 and 2001, 1714 consecutive patients underwent skeletonized bilateral internal thoracic artery grafting, of whom 748 were ≤65 years of age, 688 were between 65 and 75 years of age, and 278 were ≥75 years of age. Operative mortality of the 3 age groups (1.2%, 4.1%, and 5.8%, respectively) was lower than the logistic EuroSCORE predicted mortality (3.9%, 6.5%, and 9.3%, respectively; P<0.001). There were no significant differences among the groups in occurrence of sternal infection (1.3%, 2.6%, and 1.4%, respectively; P=0.171). Mean follow-up was 11.5 years. Kaplan-Meier 10-year survival for patients ≤65, 65 to 75, and >75 years of age was 85%, 65%, and 40%, respectively (P<0.001). These rates were better than the corresponding predicted Charlson Comorbidity Index survival rates (68%, 37%, and 20%, respectively; P<0.001 for all age groups), approaching survival of the sex- and age-matched general population (90%, 70%, and 41%, respectively). Age ≤65 years (hazard ratio, 0.232; 95% confidence interval, 0.188-0.288) and age 65 to 75 years (hazard ratio, 0.499; 95% confidence interval, 0.414-0.602) were independent predictors of improved survival (Cox model)., Conclusions: Bilateral internal thoracic artery grafting should be considered in patients >65 years of age because of the significant survival benefit obtained with this surgical technique with no additional risk of sternal wound infection related to age.

Heart failure is one of the most prevalent causes of death in the western world. Sea anemone contains a myriad of short peptide neurotoxins affecting many pharmacological targets, several of which possess cardiotonic activity. In the present study we describe the isolation and characterization of AdE-1 (ion channel modifier), a novel cardiotonic peptide from the sea anemone Aiptasia diaphana, which differs from other cnidarian toxins. Although AdE-1 has the same cysteine residue arrangement as sea anemone type 1 and 2 Na(+) channel toxins, its sequence contains many substitutions in conserved and essential sites and its overall homology to other toxins identified to date is low (<36%). Physiologically, AdE-1 increases the amplitude of cardiomyocyte contraction and slows the late phase of the twitch relaxation velocity with no induction of spontaneous twitching. It increases action potential duration of cardiomyocytes with no effect on its threshold and on the cell's resting potential. Similar to other sea anemone Na(+) channel toxins such as Av2 (Anemonia viridis toxin II), AdE-1 markedly inhibits Na(+) current inactivation with no significant effect on current activation, suggesting a similar mechanism of action. However, its effects on twitch relaxation velocity, action potential amplitude and on the time to peak suggest that this novel toxin affects cardiomyocyte function via a more complex mechanism. Additionally, Av2's characteristic delayed and early after-depolarizations were not observed. Despite its structural differences, AdE-1 physiologic effectiveness is comparable with Av2 with a similar ED(50) value to blowfly larvae. This finding raises questions regarding the extent of the universality of structure-function in sea anemone Na(+) channel toxins.

Objective: Thymectomy for thymoma has traditionally been performed through midsternotomy that provides excellent exposure for a complete and safe resection. Minimally invasive alternatives have not been extensively evaluated for this disease process because data regarding the long-term oncologic effectiveness of these techniques remain to be established. Furthermore, video-assisted surgery as a unilateral approach may compromise the extension of the resection and could cause irreversible damage to the phrenic nerve of the opposite side. We evaluated the clinical feasibility and safety of a bilateral concomitant video-assisted approach with contralateral surveillance camera in patients undergoing thymectomy for thymoma., Methods: Four patients (3 females, 1 male) with thymoma causing myasthenia gravis (MG) were operated thoracoscopically at our institute under general anesthesia with double-lumen endotracheal intubation. The patients were placed in a supine position, and a 5-mm 30-degree lens thoracoscope was introduced into the left pleural space. Two other 10-mm working channels were applied. En bloc thymectomy was then performed, including mediastinal and pericardial fat pads, other tissue, and pleura from the level of the thoracic inlet to the diaphragm. A second 5-mm thoracoscope was inserted into the right hemithorax, and it was kept inside during the entire procedure to allow lateral surveillance of the extension and safety of the resection. Carbon dioxide insufflation and valved ports were used., Results: The duration of the operation was 90 ± 72 minutes. Complete resection was achieved in all patients without any nerve injury. There were no perioperative adverse events. Gradual remission from extremity and ocular weakness was achieved after recovery., Conclusions: The ultimate surgical goal of thymectomy is to completely remove the gland and anterior mediastinal tissue without nerve injury. Bilateral concomitant video-assisted thoracic thymectomy with a contralateral surveillance camera was found feasible and safe. Given the capability of our technique to perform a complete and extensive thymectomy associated with less invasiveness and beneficial effects, there seems to be a role for minimally invasive thymectomy in the treatment of thymoma.

Combined heat acclimation (AC) and exercise training (EX) enhance exercise performance in the heat while meeting thermoregulatory demands. We tested the hypothesis that different stress-specific adaptations evoked by each stressor individually trigger similar cardiac alterations, but when combined, overriding/trade-off interactions take place. We used echocardiography, isolated cardiomyocyte imaging and cDNA microarray techniques to assay in situ cardiac performance, excitation-contraction (EC) coupling features, and transcriptional programs associated with cardiac contractility. Rat groups studied were controls (sedentary 24°C); AC (sedentary, 34°C, 1 mo); normothermic EX (treadmill at 24°C, 1 mo); and heat-acclimated, exercise-trained (EXAC; treadmill at 34°C, 1 mo). Prolonged heat exposure decreased heart rate and contractile velocity and increased end ventricular diastolic diameter. Compared with controls, AC/EXAC cardiomyocytes demonstrated lower l-type Ca(2+) current (I(CaL)) amplitude, higher Ca(2+) transient (Ca(2+)T), and a greater Ca(2+)T-to-I(CaL) ratio; EX alone enhanced I(CaL) and Ca(2+)T, whereas aerobic training in general induced cardiac hypertrophy and action potential elongation in EX/EXAC animals. At the genomic level, the transcriptome profile indicated that the interaction between AC and EX yields an EXAC-specific molecular program. Genes affected by chronic heat were linked with the EC coupling cascade, whereas aerobic training upregulated genes involved with Ca(2+) turnover via an adrenergic/metabolic-driven positive inotropic response. In the EXAC cardiac phenotype, the impact of chronic heat overrides that of EX on EC coupling components and heart rate, whereas EX regulates cardiac morphometry. We suggest that concerted adjustments induced by AC and EX lead to enhanced metabolic and mechanical performance of the EXAC heart.

Objective: : Percutaneous radiofrequency ablation (RFA) is among the best options in the treatment of primary liver malignancy and metastases because it is a highly effective and minimally invasive alternative to resection in small, nonresectable tumors or in poor surgical candidates and is associated with low morbidity and mortality. We evaluated the clinical feasibility and safety of thoracoscopic, ultrasound (US)-guided RFA of subdiaphragmatic liver malignancies in advanced cirrhotic patients awaiting transplantation., Methods: : Two patients (one female and one male) with end-stage cirrhosis who developed hepatocellular carcinoma were treated thoracoscopically by US-guided RFA. An endoscopic US probe was inserted into the right pleural space through a 10-mm working channel. An RF-operating needle applicator was inserted through a second 10-mm working port after identification of the lesion, penetrating the diaphragm toward the lesion. The procedure duration, applied energy, and generator output were recorded during the intervention. The treatment result and procedure-related complications were analyzed., Results: : The procedure duration was 74 and 92 minutes, respectively. A mean energy deposition of 353 joules resulted in a mean coagulation volume of 115 cm. Tumor ablation was achieved as determined by the postinterventional lack of contrast enhancement in the target region at the follow-up computed tomographic scans performed after 4 months., Conclusions: : RFA offers definite possibilities in the management of small-sized tumors. Thoracoscopic, US-guided transdiaphragmatic RFA has proven to be clinically feasible and safe and can be an effective modality for treating subdiaphragmatic liver lesions. Its minimally invasive nature is the most important advantage compared with surgical resection, especially for patients with high operative risk.

Ketamine was recently shown to attenuate postoperative pain when used in combination with morphine in patients who had undergone general and orthopedic surgery. We assessed its effects in 46 patients undergoing minimally invasive direct coronary artery bypass, off-pump coronary artery bypass, or thoracotomy and correlated them with patient and family satisfaction. Patient-controlled analgesia (PCA) was available for 72 hours. One group received 2mg/bolus morphine randomly and double-blindly (group MO), and another group received 1mg morphine plus 5mg ketamine/bolus (group MK), both using IV-PCA. The patients' pain and satisfaction rates were assessed three times daily during hospitalization using a visual analog scale. Their families' satisfaction was assessed as well. Although the 3-day mean amount of morphine used by the MK patients was approximately 60% of that used by the MO patients, their levels of pain and satisfaction were better than those of the MO group. There was an inverted and statistically significant correlation between the patients' level of satisfaction on the second postoperative day (POD) and the satisfaction of their families on POD 2, 3, and 7 and the POD 3 patients' pain assessment in the MK group but not in the MO group. There were no differences in hemodynamic, respiratory, side effects, or complication rates between the groups. The conclusion is that the effects of adding a small ketamine dose to half of the standard morphine dose via IV-PCA after thoracotomy was superior to the standard morphine dose in terms of the patients' self-reported pain score and satisfaction, as well as the family satisfaction rate.

Patients who received clopidogrel prior to coronary bypass surgery are at increased risk for bleeding that must be balanced with risk of ongoing ischemia if coronary artery bypass grafting is delayed. This study aimed to evaluate the impact of clopidogrel on mortality and major bleeding in patients undergoing urgent coronary bypass surgery. We reviewed 451 consecutive patients who underwent urgent isolated coronary bypass surgery; 262 had not received clopidogrel, whereas 189 received clopidogrel < or = 5 days preoperative. The primary endpoint was in-hospital death, massive transfusion or massive blood loss. Patient characteristics were almost similar between groups. There was no difference in in-hospital death or massive bleeding indices between groups (clopidogrel: 7% vs. no clopidogrel: 6%, P = 0.9). No difference was observed even after adjusting for the date of stopping clopidogrel preoperatively. Multivariate regression analysis showed that clopidogrel or the duration it was stopped preoperatively, did not predict adverse outcomes. Significant independent predictors included preoperative renal dysfunction, hemoglobin level and peripheral vascular disease. clopidogrel, or the time it was stopped prior to surgery, was not a risk factor for in-hospital death, massive bleeding, or other poor early outcomes in patients undergoing urgent coronary artery bypass surgery., (2010 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Thoracotomy is associated with severe pain. We hypothesized that the concomitant use of a subanesthetic dose of ketamine plus a two-third-standard morphine dose might provide more effective analgesia with fewer side effects than a standard morphine dose for early pain control., Methods: We conducted a 6-month randomized, double-blind study in patients undergoing thoracotomy for minimally invasive direct coronary artery bypass or for lung tumor resection. After extubation, when objectively awake (>or= 5/10 visual analogue scale [VAS]) and complaining of pain (>or= 5/10 VAS), patients were connected to patient-controlled IV analgesia delivering 1.5 mg of morphine plus saline solution (MO) or 1.0 mg of morphine plus a 5-mg ketamine bolus (MK), with a 7-min lockout time. Rescue IM diclofenac, 75 mg, was available. Follow-up lasted 4 h., Results: Forty-one patients completed the study. MO patients (n = 20) used 6.8 +/- 1.9 mg/h (mean +/- SD) and 5.5 +/- 3.6 mg/h of morphine during the first and second hours, respectively; MK patients (n = 21) used 3.7 +/- 1.2 mg/h and 2.8 +/- 2.3 mg/h, respectively (p < 0.01). The 4-h activation rate of the device was double in the MO patients than in the MK patients (66 +/- 54 vs 28 +/- 20, p < 0.001). The maximal self-rated pain score was 5.6 +/- 1.0 for the MO group vs 3.7 +/- 0.7 for the MK group (p < 0.01). Four MO patients vs one MK patient required diclofenac; 6 MO patients but no MK patients had oxygen saturation by pulse oximetry < 94% on a fraction of inspired oxygen of 0.4 (p < 0.01); two MO patients required reintubation. Paco(2) was higher in the MO group (40 +/- 6 mm Hg vs 33 +/- 5 mm Hg, p < 0.05). Heart rate, BP, and incidence of nausea/vomiting were similar; no ketamine-related hallucinations were detected., Conclusions: Subanesthetic ketamine combined with a 35%-lower morphine dose provided equivalent pain control compared to the standard morphine dose alone, with fewer adverse side effects and a 45% reduction in morphine consumption., Trial Registration: ClinicalTrials.gov Identifier: NCT00625911.

Objective: A higher prevalence of stroke appears to exist among women aged 45 to 54 years compared with same-aged men. In addition, compared with their male counterparts, women have a threefold risk of delay in hospital arrival time. Inadequate knowledge of stroke symptomology may account for this disparity in hospital arrival time. We assessed current knowledge of stroke symptoms among US women in midlife and examined the relationship between symptom knowledge and race, income, education, deferring medical care, having a primary care provider, and health insurance status., Methods: This was a cross-sectional study analyzing 2003-2005 Behavioral Risk Factor Surveillance Survey data. From the 7 stroke symptom knowledge questions asked on the survey, a Stroke Knowledge Score was computed for each respondent. Multivariate data analysis techniques were used., Results: Multivariate analysis revealed that US women aged 45 to 54 years with low stroke knowledge scores were: more likely to be Hispanic (OR = 4.44, CI = 4.37-4.51) or African-American (OR = 2.55, CI = 2.52-2.58); have less than a high school education (OR = 2.67, CI = 2.63-2.71); have an annual household income <$35,000 (OR = 2.00, CI = 1.98-2.02); have a primary care provider (OR = 1.78, CI = 1.75-1.81); have deferred medical care because of cost (OR = 1.35, CI = 1.33,1.36); and are less likely to have health insurance (OR = 0.70, CI = 0.67- 0.71)., Conclusions: Disparities in stroke symptom knowledge exist along racial/ethnic and socioeconomic lines. Nevertheless, mid-life women have high levels of knowledge about the symptoms of stroke, hence strategies aimed at encouraging women to act promptly when experiencing symptoms could yield more benefit in reducing delays in stroke treatment than educational programs.

Background: Tumor necrosis factor alpha (TNF-alpha) is a key cytokine in the pathogenesis of ischemia-reperfusion injury (I/R) that also possesses negative inotropic and direct cardiotoxic effects. We investigated whether myocardial ischemia and/or reperfusion is the trigger for TNF-alpha synthesis and whether TNF-alpha release is time dependent., Methods: Isolated rat hearts undergoing 30 min of coronary perfusion with modified Krebs-Henseleit solution followed by cardioplegic arrest for 60 min of global cardioplegic normothermic ischemia (GCI) and 30 min of reperfusion using a modified Langendorff model. Myocardial TNF-mRNA expression and TNF-alpha protein levels in effluent from the coronary sinus were measured at baseline and then after 15, 30, and 60 min of GCI and after 10 and 30 min of reperfusion., Results: GCI induced myocardial TNF-alpha mRNA expression and elevation protein TNF-alpha levels in a time-dependent manner after 30 min of ischemia from 78+/-17 pg/ml to 915+/-287 pg/ml after 60 min (p<0.0015). Reperfusion did not cause time-dependent increase of TNF-alpha synthesis and release but was accompanied by progressive decrease of left ventricular (LV) function. There was a correlation between TNF-alpha protein levels and depression of LV function immediately after GCI but not with TNF-alpha protein levels at 30 min of reperfusion., Conclusion: This study demonstrated that myocardial ischemia rather than reperfusion is the main trigger for time-dependent TNF-alpha synthesis. Depression of LV function during reperfusion correlated significantly only with TNF-alpha levels at the end of GCI.

Background: Thoracotomy is associated with severe pain. Large doses of morphine can depress respiratory drive and compromise hemodynamic stability. Ketamine reduces hyperalgesia, prevents opioid tolerance and resistance and lowers morphine consumption. At sub-anesthetic (< or = 500 microg/kg) doses, ketamine rarely produces undesirable hemodynamic alterations. We hypothesized that by combining a sub-anesthetic dose of ketamine with morphine, we could effectively control pain with less morphine and minimize drowsiness, while maintaining safe hemodynamic and respiratory parameters., Methods: Sequential patients undergoing anterolateral thoracotomy for MIDCAB, lung tumor resection, or median sternotomy for OPCAB were randomized to one of the two intravenous patient-controlled analgesia (IV-PCA) protocols. MO-only patients received 1.5 mg MO bolus, and MK patients received 1.0 mg MO+5 mg ketamine/bolus, both with a 7 min lockout time. IV-PCA was initiated when the patient was sufficiently awake (> or = 5/10 VAS) and rated pain > or = 5/10 on a 0-10 VAS. Rescue intramuscular diclofenac 75 mg was available. Follow-up of respiratory, hemodynamic and pain statuses lasted 72 h., Results: Fifty-eight patients completed the 6-month study. Heart rate and blood pressures were identically stable in both groups. Respiratory rate and pulse oximetry were higher (P < 0.05) in the MK than in the MO group. MO patients (n = 28) used twice (2.0 +/-2.3 mg/patient/h) the amount of morphine compared to MK patients (n = 30, 1.0 +/- 1.4 mg/patient/h, P < 0.05). Thirty-six hours after starting PCA, 10 MO patients still required IV-PCA compared to 5 MK patients (P < 0.05). Diclofenac was used 70% more in MO than in MK patients. MO patients suffered more postoperative nausea and vomiting. No patients had hallucinations., Conclusions: The concomitant use of sub-anesthetic ketamine plus two-thirds the standard MO dose following thoracotomy, MIDCAB or OPCAB resulted in lower pain scores, reduced MO consumption and shorter postoperative IV-PCA dependence. These advantages were associated with cardiovascular stability and even better respiratory parameters.

Venomous organisms are usually resistant to their own venoms, and utilize mechanical behavioral means to resolve intra-specific conflicts, such as those occurring over territory, mates or social status. The present study deals with a venom apparatus, which has been specifically designed for conspecific aggression, by the aid of a unique pharmacology. Actinarian sea anemones such as Actinia equina utilize vesicular organs termed acrorhagi in order to deter conspecific territorial competitors. The territorial aggression was shown to be performed by the aid of acrorhagial cnidocysts, which inflict localized tissue necroses on the body of the approaching-threatening anemone. In view of the fact that sea anemones were shown to resist mechanical injuries and their own cytolytic, necrosis-inducing pore-forming substances-the above acrorhagial injuries are ambiguous. Using an electrical device to collect acrorhagial cnidocyst-derived venom, we have shown that the venom is devoid of paralytic-neurotoxic activity, contains heat denaturable hemolytic polypeptides of a low molecular weight and is capable of inducing intracellular formation of reactive oxygen species (ROS) upon medium application to various cultured cells. The ROS formation phenomenon provides a reasonable pharmacological solution to the, above-mentioned, paradoxical conspecific self-intoxication by triggering a preexisting global endogenous mechanism of oxygen toxicity common to aerobic organisms.