Neurosurgical Anesthesiology

A Prospective Randomized Trial Comparing Topical Intranasal Lidocaine and Levobupivacaine in Patients Undergoing Endoscopic Binostril Transnasal Transsphenoidal Resection of Pituitary Tumors Introduction: Local anesthetic intranasal packing is used in transnasal surgery to reduce hemodynamic fluctuations. We hypothesized that the long acting local anesthetic levobupivacaine would provide superior hemodynamic stability and postoperative analgesia compared with lidocaine in endoscopic transnasal transsphenoidal (TNTS) surgery. Materials and Methods: In this prospective, randomized, double-blind trial, 48 patients undergoing TNTS surgery were allocated to the 2 groups to receive preoperative intranasal packing with 15 mL of 1.5% lidocaine or 0.5% levobupivacaine each mixed with 60 mg ephedrine. Heart rate and mean arterial blood pressure were recorded immediately before induction of anesthesia, at various time points throughout surgery, and at tracheal extubation. Bleeding in the surgical field, time to extubation, and postoperative pain were also assessed. Results: There was no significant difference in heart rate between the lidocaine and levobupivacaine groups at any point. Mean arterial pressure was also similar between the 2 groups during surgery, whereas at extubation blood pressure was lower in the lidocaine compared with levobupivacaine group (85±10 vs. 96±16 mm Hg; P=0.0010). There were no differences between the 2 groups in the other outcome variables. Conclusions: Preoperative intranasal packing with 1.5% lidocaine or 0.5% levobupivacaine provide similar hemodynamic stability throughout TNTS. Lidocaine packing may be more advantageous for hemodynamic stability during extubation. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Georgene Singh, MD, DM. E-mail: georgenesingh@gmail.com. Received January 10, 2018 Accepted May 9, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Patient-specific ICP Epidemiologic Thresholds in Adult Traumatic Brain Injury: A CENTER-TBI Validation Study Background: Patient-specific epidemiologic intracranial pressure (ICP) thresholds in adult traumatic brain injury (TBI) have emerged, using the relationship between pressure reactivity index (PRx) and ICP, displaying stronger association with outcome over existing guideline thresholds. The goal of this study was to explore this relationship in a multi-center cohort in order to confirm the previous finding. Methods: Using the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit cohort, we derived individualized epidemiologic ICP thresholds for each patient using the relationship between PRx and ICP. Mean hourly dose of ICP was calculated for every patient for the following thresholds: 20, 22 mm Hg and the patient's individual ICP threshold. Univariate logistic regression models were created comparing mean hourly dose of ICP above thresholds to dichotomized outcome at 6 to 12 months, based on Glasgow Outcome Score—Extended (GOSE) (alive/dead—GOSE≥2/GOSE=1; favorable/unfavorable—GOSE 5 to 8/GOSE 1 to 4, respectively). Results: Individual thresholds were identified in 65.3% of patients (n=128), in keeping with previous results (23.0±11.8 mm Hg [interquartile range: 14.9 to 29.8 mm Hg]). Mean hourly dose of ICP above individual threshold provides superior discrimination (area under the receiver operating curve [AUC]=0.678, P=0.029) over mean hourly dose above 20 mm Hg (AUC=0.509, P=0.03) or above 22 mm Hg (AUC=0.492, P=0.035) on univariate analysis for alive/dead outcome at 6 to 12 months. The AUC for mean hourly dose above individual threshold trends to higher values for favorable/unfavorable outcome, but fails to reach statistical significance (AUC=0.610, P=0.060). This was maintained when controlling for baseline admission characteristics. Conclusions: Mean hourly dose of ICP above individual epidemiologic ICP threshold has stronger associations with mortality compared with the dose above Brain Trauma Foundation defined thresholds of 20 or 22 mm Hg, confirming prior findings. Further studies on patient-specific epidemiologic ICP thresholds are required. P.S. and M.C. are joint senior authors. The CENTER-TBI High Resolution Sub-Study Participants and Investigators: Anke Audny (Department of Physical Medicine and Rehabilitation, University Hospital Northern Norway), Beer Ronny (Department of Neurology, Neurological Intensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria), Bellander Bo-Michael (Department of Neurosurgery & Anesthesia & Intensive Care Medicine, Karolinska University Hospital, Stockholm, Sweden), Buki Andras (Department of Neurosurgery, University of Pecs and MTA-PTE Clinical Neuroscience MR Research Group and Janos Szentagothai Research Centre, University of Pecs, Hungarian Brain Research Program, Pecs, Hungary), Chevallard Giorgio (NeuroIntensive Care, Niguarda Hospital, Milan, Italy), Chieregato Arturo (NeuroIntensive Care, Niguarda Hospital, Milan, Italy), Citerio Giuseppe (NeuroIntensive Care Unit, Department of Anesthesia & Intensive Care, ASST di Monza, Monza, Italy, School of Medicine and Surgery, Università Milano Bicocca, Milano, Italy), Czeiter Endre (Department of Neurosurgery, University of Pecs and MTA-PTE Clinical Neuroscience MR Research Group and Janos Szentagothai Research Centre, University of Pecs, Hungarian Brain Research Program [Grant No. KTIA 13 NAP-A-II/8], Pecs, Hungary), Depreitere Bart (Department of Neurosurgery, University Hospitals Leuven, Leuven, Belgium), Eapen George✠ (Death), Frisvold Shirin (Department of Anesthesiology and Intensive care, University Hospital Northern Norway, Tromso, Norway), Helbok Raimund (Department of Neurology, Neurological Intensive Care Unit, Medical University of Innsbruck, Innsbruck, Austria), Jankowski Stefan (Neurointensive Care, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK), Kondziella Daniel (Departments of Neurology, Clinical Neurophysiology and Neuroanesthesiology, Region Hovedstaden Rigshospitalet, Copenhagen, Denmark), Koskinen Lars-Owe (Department of Clinical Neuroscience, Neurosurgery, Umea University Hospital, Umea, Sweden), Meyfroidt Geert (Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium), Moeller Kirsten (Department Neuroanesthesiology, Region Hovedstaden Rigshospitalet, Copenhagen, Denmark), Nelson David (Department of Neurosurgery & Anesthesia & Intensive Care Medicine, Karolinska University Hospital, Stockholm, Sweden), Piippo-Karjalainen Anna (Helsinki University Central Hospital, Helsinki, Finland), Radoi Andreea (Department of Neurosurgery, Vall d'Hebron University Hospital, Barcelona, Spain), Ragauskas Arminas (Department of Neurosurgery, Kaunas University of technology and Vilnius University, Vilnius, Lithuania), Raj Rahul (Helsinki University Central Hospital, Helsinki, Finland), Rhodes Jonathan (Department of Anaesthesia, Critical Care & Pain Medicine NHS Lothian & University of Edinburg, Edinburgh, UK), Rocka Saulius (Department of Neurosurgery, Kaunas University of technology and Vilnius University, Vilnius, Lithuania), Rossaint Rolf (Department of Anaesthesiology, University Hospital of Aachen, Aachen, Germany), Sahuquillo Juan (Department of Neurosurgery, Vall d'Hebron University Hospital, Barcelona, Spain), Sakowitz Oliver (Klinik für Neurochirurgie, Klinikum Ludwigsburg, Ludwigsburg, Germany, Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany), Stevanovic Ana (Department of Anaesthesiology, University Hospital of Aachen, Aachen, Germany), Sundström Nina (Department of Radiation Sciences, Biomedical Engineering, Umea University Hospital, Umea, Sweden), Takala Riikka (Perioperative Services, Intensive Care Medicine, and Pain Management, Turku University Central Hospital and University of Turku, Turku, Finland), Tamosuitis Tomas (Neuro-intensive Care Unit, Kaunas University of Health Sciences, Kaunas, Lithuania), Tenovuo Olli (Rehabilitation and Brain Trauma, Turku University Central Hospital and University of Turku, Turku, Finland), Vajkoczy Peter (Neurologie, Neurochirurgie und Psychiatrie, Charité—Universitätsmedizin Berlin, Berlin, Germany), Vargiolu Alessia (NeuroIntensive Care Unit, Department of Anesthesia & Intensive Care, ASST di Monza, Monza, Italy), Vilcinis Rimantas (Department of Neurosurgery, Kaunas University of Health Sciences, Kaunas, Lithuania), Wolf Stefan (Interdisciplinary Neuro Intensive Care Unit, Charité—Universitätsmedizin Berlin, Berlin, Germany), Younsi Alexander (Department of Neurosurgery, University Hospital Heidelberg, Heidelberg, Germany). Data used in preparation of this manuscript were obtained in the context of CENTER-TBI, a large collaborative project with the support of the European Union 7th Framework program (EC grant 602150). Additional funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind and from Integra LifeSciences Corporation. D.K.M. was also supported by funding from the National Institute for Health Research (NIHR, UK) through a Senior Investigator award and the Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust. The study also received additional support from the NIHR Clinical Research network. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care, UK. F.A.Z. is supported by the University of Manitoba Thorlakson Chair for Surgical Research Establishment Grant, University of Manitoba VPRI Research Investment Fund (RIF), Winnipeg Health Sciences Centre (HSC) Foundation, and the University of Manitoba Rudy Falk Clinician-Scientist Professorship. P.S. and M.C. receive part of licensing fees for the software ICM+ (Cambridge Enterprise Ltd, UK) used for data collection and analysis in this study. The remaining authors have no conflicts of interest to disclose. Address correspondence to: Frederick A. Zeiler, BSc, MD, PhD, FRCSC (Neurosurgery), E-mail: umzeiler@myumanitoba.ca. Received January 14, 2019 Accepted April 25, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Journal Club No abstract available

Real-Time Monitoring of Cerebral Blood Flow and Cerebral Oxygenation During Rapid Ventricular Pacing in Neurovascular Surgery: A Pilot Study Background: Rapid ventricular pacing (RVP) can be used to produce short periods of flow arrest during dissection or rupture of a cerebral aneurysm but carries the risk of inducing cerebral ischemia. This study evaluates the intraoperative effect of RVP on local cerebral blood flow (CBF) and cerebral oxygenation during neurovascular surgery. Materials and Methods: Five patients undergoing elective cerebrovascular surgery were included in a single-center prospective study. RVP was applied in pacing periods of 40 seconds with 30% and 100% FiO2. Regional cerebral oxygenation was monitored using a Foresight near-infrared spectroscopy sensor. A Clark-type electrode and a thermal diffusion microprobe located in the white matter were used to monitor brain tissue pO2 and CBF, respectively. Results: CBF response to RVP closely followed the blood pressure pattern and resulted in a low-flow state. Unlike CBF, brain tissue pO2 and regional cerebral oxygenation showed a delayed response to RVP, decreasing beyond the pacing period and slowly recovering after RVP cessation. We found a correlation between brain tissue pO2 and regional cerebral oxygenation. Increasing the inspired oxygen concentration had a positive impact on absolute regional cerebral oxygenation and brain tissue pO2 values, but the pattern resulting from applying RVP remained unaltered. Conclusions: RVP reduces CBF and cerebral oxygenation. Brain tissue pO2 and regional cerebral oxygenation are correlated but unlike CBF respond to RVP in a delayed manner. Further research is required to evaluate the impact of longer RVP bursts on brain oxygenation. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Vera Saldien, MD. E-mail: vera.saldien@uza.be. Received January 29, 2019 Accepted May 1, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Effective Cerebral Perfusion Pressure: Does the Estimation Method Make a Difference? Introduction: The effective cerebral perfusion pressure (CPPe), zero-flow pressure (ZFP), and resistance area product (RAP) are important determinants of cerebral blood flow. ZFP and RAP are usually estimated by linear regression analysis of pressure-velocity relationships of the middle cerebral artery. The aim of this study was to validate 4 other estimation methods against the standard linear regression method. Methods: In a previous study, electroencephalography, arterial blood pressure, and middle cerebral artery flow velocity were measured in patients during internal cardioverter defibrillator implantation procedures to determine the electroencephalography frequency ranges that represent ischemic changes during periods of circulatory arrest. In this secondary analysis, arterial blood pressure and middle cerebral artery flow velocity were used to estimate CPPe, ZFP, and RAP by 4 different methods—the 3-point intercept calculation (LR3, systolic/mean/diastolic) and methods described by Czosnyka (systolic/diastolic), Belford (mean/diastolic), and Schmidt (systolic/diastolic)—and compare them with the reference linear regression method. CPPe was calculated as the difference between mean arterial pressure and ZFP. The primary endpoint was the difference, correlation, and agreement of these differently estimated CPPe measurements. Results: In total, 174 measurements in 35 patients were collected under steady-state conditions before the first circulatory arrest phase during internal cardioverter defibrillator testing. CPPe, ZFP, and RAP measurements based on the 3-point intercept and Czosnyka calculation methods showed small mean differences, good agreement, low percentage errors, and excellent correlation when compared with the reference method. Agreement and correlation were moderate for the Belford method and unsatisfactory for the Schmidt method. Conclusions: CPPe, ZFP, and RAP measurements based on 2 alternative calculation methods are comparable to the linear regression reference method. The primary analysis was supported by The Netherlands Heart Foundation (grant no. 93.149) (Visser et al, 2001). In the secondary analysis, support was provided solely from institutional and/or departmental sources. Work is attributed to: Erasmus MC, Rotterdam, NL. The authors acknowledge that the enclosed manuscript is part of a larger series of prospective studies about cerebral circulation and cerebral metabolism in the perioperative setting. In 56 patients during internal cardioverter defibrillator (ICD) device testing under general anesthesia, we determined 4 main EEG frequency ranges that represent ischemic changes during short periods of circulatory arrest. These former results have been published (Visser et al, 2001). Medical Ethical Research Committee Utrecht. Trial: Cerebral effects of repeated periods of circulatory arrest by induced ventricular fibrillation during ICD implantation (Cerebrale effecten van herhaalde perioden van circulatiestilstand door geïnduceerd kamerfibrilleren tijdens ICD implantatie), Nr.:92/59. The trial was planned and done before CONSORT 2010. Dutch laws did not require international registration of this type of clinical trial at that time. The Netherlands Trial register does not accept closed studies (www.trialregister.nl). A registration at "clinical trials" was not possible, too (www.clinicaltrials.gov). Here, the completion date of our study was before December 26, 2007, which is an exclusion criterion following the FDAAA 801 note (https://clinicaltrials.gov/ct2/manage-recs/fdaaa). The authors have no conflicts of interest to disclose. Address correspondence to: Frank Grüne, MD, E-mail: f.grune@erasmusmc.nl. Received March 31, 2018 Accepted April 18, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Optimizing Design for the Way Clinicians Use Critical Event Cognitive Aids No abstract available

The Effect of Depth of Anesthesia on Hemodynamic Changes Induced by Therapeutic Compression of the Trigeminal Ganglion Background: Percutaneous compression of the trigeminal ganglion (PCTG) has been used to treat trigeminal neuralgia since 1983. A PCTG-related trigeminocardiac reflex (TCR) can induce dramatic hemodynamic disturbances. This study investigates the effects of depth of propofol anesthesia on hemodynamic changes during PCTG. Materials and Methods: A total of 120 patients who underwent PTCG for trigeminal neuralgia were randomly assigned to control group-intravenous saline pretreatment before PCTG puncture and anesthesia targeted to bispectral index (BIS) 40 to 60 throughout, and study group-intravenous propofol 1 to 2 mg/kg pretreatment to deepen anesthesia to BIS<40 before PCTG. Mean arterial pressure, heart rate (HR), cardiac output, system vascular resistance, and BIS were measured at 9 time points during the procedure, and the incidence of the TCR was observed at T5 and T6. Results: BIS was lower in the study group compared with the control after pretreatment with propofol or saline, respectively. Compared with the control group, mean arterial pressure was lower in the study group at several points during the procedure, but there was no difference in HR between the 2 groups at any point. Cardiac output was higher and system vascular resistance lower in the study compared with the control group. In the control group, 42 (70.0%) and 52 (86.7%) of patients developed a TCR at the 2 points, and 37 (67.1%) and 45 (75.0%) in the study group. There was no difference in the incidence of TCR between the 2 groups. Conclusion: Increasing the depth of propofol anesthesia partially attenuated PTCG-related elevation of blood pressure but did not modify the abrupt reduction in HR. This work was funded by the Liaoning Natural Science Foundation of China (no. 20170540524) and the National Nature Science Foundation of China (no. 81671311 and no. 81870838), the Key Research and Development Program of Liaoning Province (no. 2018225004), and the Outstanding Scientific Fund of Shengjing Hospital (no. 201708). Supported by the Department of Anaesthesiology, Second Department of Neurosurgery, People's Hospital of China Medical University (Liaoning Provincial People's Hospital), and the Department of Anaesthesiology, Shengjing Hospital of China Medical University, P.R. China. C.-M.W.: wrote the manuscript. Z.-Y.G. and Q.-C.W.: were responsible for data statistics. All operations were performed by Y.M. J.Z., and P.Z. intensively supervised the work and substantially helped in the writing process. All authors read and approved the final manuscript. The authors have no conflicts of interest to disclose. Address correspondence to: Ping Zhao, MD, E-mail: zhaopingdoctor@yeah.net. Received January 9, 2019 Accepted April 10, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Defining a Taxonomy of Intracranial Hypertension: Is ICP More Than Just a Number? Intracranial pressure (ICP) monitoring and control is a cornerstone of neuroanesthesia and neurocritical care. However, because elevated ICP can be due to multiple pathophysiological processes, its interpretation is not straightforward. We propose a formal taxonomy of intracranial hypertension, which defines ICP elevations into 3 major pathophysiological subsets: increased cerebral blood volume, masses and edema, and hydrocephalus. (1) Increased cerebral blood volume increases ICP and arises secondary to arterial or venous hypervolemia. Arterial hypervolemia is produced by autoregulated or dysregulated vasodilation, both of which are importantly and disparately affected by systemic blood pressure. Dysregulated vasodilation tends to be worsened by arterial hypertension. In contrast, autoregulated vasodilation contributes to intracranial hypertension during decreases in cerebral perfusion pressure that occur within the normal range of cerebral autoregulation. Venous hypervolemia is produced by Starling resistor outflow obstruction, venous occlusion, and very high extracranial venous pressure. Starling resistor outflow obstruction tends to arise when cerebrospinal fluid pressure causes venous compression to thus increase tissue pressure and worsen tissue edema (and ICP elevation), producing a positive feedback ICP cycle. (2) Masses and edema are conditions that increase brain tissue volume and ICP, causing both vascular compression and decrease in cerebral perfusion pressure leading to oligemia. Brain edema is either vasogenic or cytotoxic, each with disparate causes and often linked to cerebral blood flow or blood volume abnormalities. Masses may arise from hematoma or neoplasia. (3) Hydrocephalus can also increase ICP, and is either communicating or noncommunicating. Further research is warranted to ascertain whether ICP therapy should be tailored to these physiological subsets of intracranial hypertension. Supported by Department of Health and Human Services, National Institutes of Health, and National Institute of Neurological Disorders and Stroke, 1R01NS082309-01A1. W.A.K.: funded by 1R01NS082309-01A1. Legal consultant; multiple legal and health care entities. Royalty payments Oxford University Press and Elsevier. Honoraria NIH study sections. Editorial Board Neurocritical Care. Editorial Board J Neurosurg Anesth. Coauthor on provisional patent number 17-8261/103241.000816 Trustees of the University of Pennsylvania. R.B.: funded by 1R01NS082309-01A1. Coauthor on provisional patent number 17-8261/103241.000816 Trustees of the University of Pennsylvania. The remaining authors have no conflicts of interest to disclose. Address correspondence to: W. Andrew Kofke, MD, MBA. E-mail: kofkea@uphs.upenn.edu. Received November 26, 2018 Accepted April 14, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Subanesthetic Dose of Ketamine Improved CFA-induced Inflammatory Pain and Depression-like Behaviors Via Caveolin-1 in Mice Background: Ketamine, a commonly used nonbarbiturate anesthetic drug, possesses antidepressant properties at subanesthetic doses; however, the underlying mechanisms remain unclear. Materials and Methods: The analgesic and antidepressant effects of ketamine were explored using a complete Freund adjuvant (CFA)-induced peripheral inflammatory pain model in vivo. Mice were first divided into sham or CFA injection group randomly, and were observed for mechanical hyperalgesia, depression-like behavior, and mRNA expression of caveolin-1. Then ketamine was administered in CFA-treated mice at day 7. Results: The behavioral testing results revealed mechanical hyperalgesia and depression in mice from days 7 to 21 after CFA injection. Ketamine reversed depression-like behaviors induced by CFA injection. It also restored the brain-regional expression levels of caveolin-1 in CFA-treated mice. In addition, caveolin-1 mRNA and protein expression were increased in the prefrontal cortex and nucleus accumbens of CFA-treated mice. However, ketamine reversed the increase in caveolin-1 expression in the ipsilateral and contralateral prefrontal cortex and nucleus accumbens, supporting the distinct roles of specific brain regions in the regulation of pain and depression-like behaviors. Conclusions: In CFA-treated mice that exhibited pain behavior and depression-like behavior, ketamine reversed depression-like behavior. The prefrontal cortex and nucleus accumbens are the important brain regions in this regulation network. Despite these findings, other molecules and their mechanisms in the signal pathway, as well as other regions of the brain in the pain matrix, require further exploration. J.L. and R.H. contributed equally to this work. J.W. and Q.Z. are co-first authors. This work was funded by the Beijing Municipal Administration of Hospitals' Ascent Plan (code number DFL20180502) and Clinical Medicine Development of Special Funding Support (code number ZYLX201708). R.H. is a member of the Editorial Board of the Journal of Neurosurgical Anethesiology. The authors have no conflicts of interest to disclose. Address correspondence to: Ruquan Han, MD, PhD. E-mail: ruquan.han@ccmu.edu.cn. Received November 21, 2018 Accepted April 8, 2019 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved

Remifentanil Patient-controlled Analgesia in Awake Craniotomy: An Introduction of an Innovative Technique No abstract available

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Medicine & Science in Sports & Exercise

Exercise Intensity Matters in Chronic Nonspecific Low Back Pain Rehabilitation Introduction Exercise therapy (ET) is advocated as a treatment for chronic nonspecific low back pain (CNSLBP). However, therapy effect sizes remain low. In other chronic disorders, training at higher intensity has resulted in greater improvements on both general health related and disease specific outcomes compared to lower intensity ET. Possibly, high intensity training also improves effect sizes in CNSLBP. Objective To compare the effects of a high intensity ET program with a similar moderate intensity ET program on disability, pain, function, exercise capacity, and abdominal/back muscle strength in persons with CNSLBP. Methods In a randomized controlled trial, persons with CNSLBP performed a 12-week ET program (24 sessions, 1.5hours/session, 2x/week) at high (HIT) or moderate intensity (MIT). Questionnaires to assess disability (Modified Oswestry Index (MODI)), pain intensity (Numeric Pain Rating Scale (NPRS)), and function (Patient Specific Functioning Scale (PSFS)), a cardiopulmonary exercise test to assess exercise capacity (VO2max, cycling time), and a maximum isometric muscle strength test to assess abdominal/back muscle strength (maximum muscle torque) were administered at baseline and after the training program. Results Thirty-eight participants (HIT: n=19, MIT: n=19) were included (mean age: 44.1y, SD=9.8, 12 males). Groups did not differ at baseline. Between group differences (p<0.01) in favor of HIT were found for MODI, VO2max, and cycling time. Within group improvements (p<0.01) were found in both groups on MODI (HIT:-64%, MIT:-33%), NPRS (HIT:-56%, MIT:-39%), PSFS (HIT:+37%, MIT:+39%), VO2max (HIT:+14, MIT:+4%), cycling time (HIT:+18%, MIT:+13%), and back muscle strength (HIT:+10%, MIT:+14%). Conclusion HIT proved to be a feasible, well tolerated, and effective therapy modality in CNSLBP. Moreover, it shows greater improvements on disability and exercise capacity than a similar ET performed at moderate intensity. Corresponding author: Jonas Verbrugghe, Hasselt University, Faculty of Rehabilitation Sciences, REVAL, Gebouw A, Agoralaan 5, 3590, Diepenbeek, Belgium, Tel: +003211269239, jonas.verbrugghe@uhasselt.be This project is funded by the UHasselt research fund BOF New initiatives (project number R-5211). This funding source had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results. The authors would like to thank all the persons with CNSLBP that participated in this study. Conflict of Interest. The authors report no conflict of interest. Accepted for Publication: 24 June 2019 © 2019 American College of Sports Medicine

Lower Trapezius Weakness and Shoulder Complex Biomechanics during the Tennis Serve PURPOSE This study aimed to assess the effect of lower trapezius (LT) weakness on humeral and scapular kinematics and shoulder muscle activity during the tennis serve. METHODS Fifteen competitive male tennis players (age: 23.8 ± 3.4 years; height: 182.8 ± 6.7 cm; mass: 76.6 ± 8.7 kg; tennis experience: 15.6 ± 4.9 years) performed two tennis serves before and after selective fatigue of the LT (25-min electric muscle stimulation). During each tennis serve, racket, humeral and scapular kinematics and the activity of 13 shoulder muscles were recorded using an optoelectronic system synchronized with indwelling and surface electromyography. The serve was split into five phases, i.e., early and late cocking, acceleration, early and late follow-through. RESULTS Selective fatigue led to a 22.5 ± 10.4% strength decrease but did not alter maximum racket speed and humerothoracic joint kinematics. However, increased scapular upward rotation was observed in the acceleration (p=0.02) and early follow-through (p=0.01) phases. Decreased muscular activity was observed during the early cocking phase for the LT (p=0.01), during the acceleration phase for the LT (p=0.01), anterior deltoid (p=0.03), pectoralis major (p=0.04) and subscapularis (p=0.03), and during the early follow-through phase for the anterior deltoid (p=0.03) and LT (p=0.04). CONCLUSION LT weakness altered neither serve velocity nor humerothoracic joint kinematics, but impaired scapulothoracic kinematics and anterior shoulder muscle activation. Such alterations may reduce the subacromial space and jeopardize humeral head stability. These findings shed new light on the consequences of LT weakness, highlighting the importance of monitoring and strengthening this muscle in overhead athletes. Corresponding author: Isabelle Rogowski, UCB Lyon 1 – UFRSTAPS, 27-29, bd du 11 novembre 1918, 69622 Villeurbanne Cedex France, E-mail: isabelle.rogowski@univ-lyon1.fr This study was supported by Auvergne-Rhône-Alpes with the explora'doc program and by Mitacs with the globalink program. Conflict of interest. The authors declare no conflict of interest. Accepted for Publication: 21 June 2019 © 2019 American College of Sports Medicine

Reduced Active Muscle Stiffness after Intermittent Submaximal Isometric Contractions Purpose Whether muscle stiffness is influenced by fatigue remains unclear. Classical methods used to assess muscle stiffness provide a global measure at the joint level. As fatigue may selectively affect specific muscles, a joint-level approach may not be sensitive enough to detect potential changes in muscle stiffness. Taking advantage of ultrasound shear wave elastography, this study aimed to determine the influence of a fatiguing protocol involving intermittent submaximal isometric contractions on muscle shear modulus (an index of stiffness). Methods Shear modulus was measured on either the vastus lateralis (VL; n=9) or the abductor digiti minimi (ADM; n=10) before and after 15-mins of intermittent submaximal isometric contractions at 60% of maximal voluntary contraction (MVC; 4 s ON, 4 s OFF). An index of active muscle stiffness was estimated PRE and POST-fatigue as the slope of the linear regression established between shear modulus and absolute joint force up to 60% MVC. Results After the fatiguing exercise, MVC was significantly decreased by 22 ± 7 % and 32 ± 15 % for knee extension and little finger abduction, respectively (p<0.001). When compared to PRE-fatigue, the index of active muscle stiffness was 12 ± 15 % lower for the VL (p < 0.031) and 44 ± 19 % lower for the ADM (p < 0.001) POST-fatigue. Conclusion Although the present results cannot clearly determine the involved mechanisms, they demonstrate a decreased active muscle stiffness after a fatiguing task involving intermittent submaximal isometric contractions. Further studies should now determine whether this change in stiffness affects performance and risk of injury. CORRESPONDING AUTHOR: Thomas LAPOLE, Laboratoire Interuniversitaire de Biologie de la Motricité, Bâtiment IRMIS, 10 rue de la Marandière, 42270 Saint Priest en Jarez, thomas.lapole@univ-st-etienne.fr The authors declare they have no conflict of interest. The authors did not receive any funding for this study. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. Accepted for Publication: 21 June 2019 © 2019 American College of Sports Medicine

High-Intensity Interval Training is Feasible in Women at High Risk for Breast Cancer Purpose This trial aimed to demonstrate feasibility of high-intensity interval training (HIIT) in post-menopausal, overweight/obese women at high-risk of invasive breast cancer, and explore HIIT on changes in cardiorespiratory fitness (CRF), body weight, and body mass index (BMI) compared to moderate-intensity continuous training (MICT) and usual care (UC). Methods Forty-four women were randomized to HIIT, MICT or UC for a 12-week, thrice weekly, supervised exercise intervention. HIIT included a 5-minute warm-up at 50-70% peak heart rate (HR), four cycles of four minutes at 90-100% peak HR followed by three minutes at 50-70% peak HR. MICT consisted of 41 minutes at 60-70% peak HR. Feasibility was assessed by consent, adherence, compliance and retention rates. CRF, body weight and BMI were measured at baseline and end-of-study. Repeated measures linear mixed models were used to assess within- and between-group differences. Results Average age was 63.9±8.8 years. BMI was 30.9±5.7 kg/m2. Participants completed 90% and 89% of HIIT and MICT workouts respectively, with 100% compliance to the exercise prescriptions. No serious adverse events were reported. Compared to MICT and UC, HIIT exhibited improvements in change in treadmill time (101 seconds greater than MICT, and 125 seconds greater than UC, respectively, p<0.001). Compared to UC, HIIT exhibited improvement in changes in absolute and relative VO2peak (a 0.15 increase in L/min, p=0.005; and 2.3 increase in ml/kg/min, p=0.004). There were no significant differences between groups for body weight or BMI (p>0.05). Conclusions HIIT is feasible, safe, and appears to promote greater improvements in CRF compared to MICT and UC in women at high risk for breast cancer. Correspondence: Susan C Gilchrist, MD; The University of Texas MD Anderson Cancer Center, 1155 Pressler Street, Unit 1360, Houston TX 77230-1439; Phone: 713-745-6251; Fax: 713-794-4403; sgilchrist@mdanderson.org The authors thank the NCI R25 Cancer Prevention Research Training Program (CA057730, PI: Shine Chang PhD), the MD Anderson Cancer Center/Energy Balance Assessment Supplemental Funding (PI: Susan Gilchrist MD), and the MD Anderson Cancer Center, Center for Energy Balance in Cancer Prevention and Survivorship. The authors declare that they have no conflicts of interest to disclose. The results of the present study do not constitute endorsement by the ACSM, and are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Accepted for publication: 10 May 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. © 2019 American College of Sports Medicine

Data-informed Intervention Improves Football Technique and Reduces Head Impacts Introduction Although sport participation is a key contributor to the physical and mental health of children and youth, exposure to sub-concussive head impacts in football has raised concerns about safety for athletes. Purpose To demonstrate the efficacy of incorporating targeted football drills into a team's practice routine with the goal of improving players' technique, and reduce exposure to sub-concussive head impacts. Methods Seventy high-school football players (age=16.4±1.1years) were tested PRE-season using a sport-specific functional assessment. Results from the testing were used to inform the design of a pre-practice intervention aimed at improving tackling and blocking techniques, while reducing exposure to head impacts. The assessment included drills which evaluated the players' ability to safely tackle, and block, while simulating game-like situations. Testing was repeated at MID-season (internal control) without an intervention, and again at POST-season (experimental), following introduction of the pre-practice intervention between these timepoints, administered twice weekly. All testing sessions were recorded, and subsequently reviewed by trained graders based on selected criteria defined by football coaches. A subset of nineteen participants wore in-helmet accelerometers to assess the effectiveness of the intervention in decreasing head impacts during practice. Results Significant improvements in blocking and tackling techniques were observed following the introduction of the intervention (P<0.0001). Participating athletes also showed better techniques when evaluated in new game-like situations, post-season, providing evidence for proper acquisition and generalizability of these safer habits. Finally, frequency of head impacts (>15g) per practice was significantly reduced by ~30% after one month of training. Conclusion Our results suggest that data-informed methods can be used to improve coaching practices, and promote safer play, which can have a positive public health impact moving forward. Corresponding author: Douglas J. Cook, Department of Surgery, Queen's University, Room 232, 18 Stuart St. Kingston, ON K7L 3N6. Phone: 613-549-6666 ext. 3696. Fax: 613-548-1346. dj.cook@queensu.ca Results from this study are presented clearly, honestly and without fabrication, falsification, or inappropriate data manipulation. Results of the present study do not constitute endorsement by the American College of Sports Medicine. The authors declare no conflict of interest. Funding from the Southeastern Ontario Academic Medical Organization (SEAMO) helped making this project possible. Accepted for publication: 7 May 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. © 2019 American College of Sports Medicine

Motor Strategies Learned during Pain Are Sustained upon Pain-free Re-exposure to Task Introduction Pain affects movement planning and execution, and may interfere with the ability to learn new motor skills. Variations among previous studies suggest task-specific effects of pain on the initial acquisition and subsequent retention of motor strategies. Methods The present study assessed how acute pain in the anterior deltoid muscle affects movement accuracy of fast arm-reaching movements during force field perturbations, and upon immediate pain-free repetition of the same task. Results Despite having slower initial rate of improvement, individuals who experienced pain during training achieved the same final performance as pain-free controls. However, pain altered the strategy of muscle activation adopted to perform the task, which involved less activity of the shoulder and arm muscles. Strikingly, motor strategies developed during the first exposure to the force field were retained upon re-exposure to the same perturbation, after resolution of pain. Conclusion Although reduced muscle activation may be interpreted as metabolically efficient, it reduces joint stability and can have negative consequences for joint integrity. These results demonstrate that alternative motor strategies developed in the presence of pain can be maintained when training is resumed after resolution of pain. This effect could have deleterious consequences if it applies when learning motor skills in sports training and rehabilitation. Corresponding author: Dr Paul W. Hodges, School of Health and Rehabilitation Sciences, The University of Queenslandm, Brisbane QLD 4072, Australia, Phone: +61 7 3365 2008, E-mail: p.hodges@uq.edu.au Disclosures and Acknowledgements This study was funded by a Program Grant (APP1091302), a Senior Principal Research Fellowship (APP1102905) from the National Health and Medical Research Council (NHMRC) of Australia, and a Future Fellowship grant to TC (FT120100391). The authors have no conflicts of interest to declare. All the authors are properly listed, and all have contributed substantially to the manuscript. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and statement that results of the present study do not constitute endorsement by ACSM. Accepted for Publication: 29 May 2019 © 2019 American College of Sports Medicine

Cytokine and Sclerostin Response to High-Intensity Interval Running versus Cycling Purpose This study examined whether the exercise-induced changes in inflammatory cytokines differ between impact and no-impact high intensity interval exercise, and whether they are associated with post-exercise changes in sclerostin. Methods Thirty-eight females (n=19, 22.6±2.7 years) and males (n=19, 22.3±2.4 years) performed two high-intensity interval exercise trials in random order (cross-over design): running on a treadmill and cycling on a cycle ergometer. Trials consisted of eight repetitions of 1 min running or cycling at ≥90% maximal heart rate, separated by 1 min passive recovery intervals. Blood was collected pre-exercise, and 5 min, 1h, 24h and 48h post-exercise, and was analyzed for serum levels of interleukins (IL-1β, IL-6, IL-10), tumor necrosis factor alpha (TNF-α) and sclerostin. Results Inflammatory cytokines significantly increased over time in both sexes with some differences between trials. Specifically, IL-1β significantly increased from pre- to 5 min after both trials (23%, p<0.05), IL-6 increased 1h following both trials (39%, p<0.05), IL-10 was elevated 5 min after running (20%, p<0.05) and 1h after both running and cycling (41% and 64%, respectively, p<0.05), and TNF-α increased 5 min after running (10%, p<0.05). Sclerostin increased 5 min following both trials, with a greater increase in males than in females (62 vs 32 pg/ml in running, p=0.018; 63 vs 30 pg/ml in cycling, p=0.004). In addition, sclerostin was significantly correlated with the corresponding changes in inflammatory cytokines and 34% of the variance in its post-exercise gain score (Δ) was explained by sex and the corresponding gain scores in TNF-α, which was the strongest predictor. Conclusion A single bout of either impact or no-impact high-intensity exercise induces changes in inflammatory cytokines, which are associated with the post-exercise increase in sclerostin. Corresponding author: Panagiota Klentrou Department of Kinesiology Faculty of Applied Health Sciences Brock University 1812 Sir Isaac Brock Way St. Catharines, ON, L2S 3A1, Canada E-mail: nklentrou@brocku.ca This study was funded by a National Science Engineer Research Council of Canada (NSERC) grant to P. Klentrou (grant # 2015-04424). R. Kouvelioti holds an Ontario Trillium Scholarship. N. Kurgan holds an NSERC Doctoral Scholarship. W. Wards holds a Canada Research Chair in Bone and Muscle Development. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by ACSM. Conflicts of interest: The authors have no conflict of interest to declare. Accepted for publication: 14 June 2019. © 2019 American College of Sports Medicine

Extended Sleep Maintains Endurance Performance better than Normal or Restricted Sleep Purpose The cumulative influence of sleep time on endurance performance remains unclear. This study examined effects of three consecutive nights of both sleep extension and restriction on endurance cycling performance. Methods Endurance cyclists/triathletes (n=9) completed a counterbalanced crossover experiment with three conditions; sleep restriction (SR), normal sleep (NS), and sleep extension (SE). Each condition comprised seven days/nights of data collection (-2, -1, D1, D2, D3, D4, +1). Sleep was monitored using actigraphy throughout. Participants completed testing sessions on days D1-D4 that included an endurance time-trial (TT), mood, and psychomotor vigilance assessment. Perceived exertion (RPE) was monitored throughout each TT. Participants slept habitually prior to D1, however, time in bed was reduced by 30% (SR), remained normal (NS), or extended by 30% (SE) on nights D1, D2, and D3. Data were analysed using Generalised Estimating Equations. Results On nights D1, D2, and D3, total sleep time was longer (P<0.001) in the SE condition (8.6±1.0; 8.3±0.6; 8.2±0.6h, respectively), and shorter (P<0.001) in the SR condition (4.7±0.8; 4.8±0.8; 4.9±0.4h) compared with NS (7.1±0.8; 6.5±1.0; 6.9±0.7h). Compared with NS, TT performance was slower (P<0.02) on D3 of SR (58.8±2.5 vs 60.4±3.7min) and faster (P<0.02) on D4 of SE (58.7±3.4 vs 56.8±3.1min). RPE was not different between or within conditions. Compared with NS, mood disturbance was higher-, and psychomotor vigilance impaired, following SR. Compared with NS, psychomotor vigilance improved following SE. Conclusion Sleep extension for three nights led to better maintenance of endurance performance compared with normal and restricted sleep. Sleep restriction impaired performance. Cumulative sleep time affects performance by altering the perceived exertion of a given exercise intensity. Endurance athletes should sleep >8 hours per night to optimise performance. Corresponding author: Spencer S. H. Roberts, PhD Candidate School of Exercise and Nutrition Sciences, Deakin University. 221 Burwood Hwy, Burwood, Victoria, Australia, 3125 Email: rspen@deakin.edu.au The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. Results do not constitute endorsement by the American College of Sports Medicine. Spencer Roberts, Wei-Peng Teo, Brad Aisbett, and Stuart Warmington declare they have no conflict of interest. The authors acknowledge the School of Exercise and Nutrition Sciences at Deakin University for funding the study. Accepted for publication: 9 June 2019. © 2019 American College of Sports Medicine

Methodological Recommendations for Menstrual Cycle Research in Sports and Exercise Introduction The aim of this review is to provide methodological recommendations for menstrual cycle research in exercise science and sports medicine based on a review of recent literature. Research in this area is growing, but often reports conflicting results and it is proposed that some of this may be explained by methodological issues. Methods This review examined the menstrual cycle verification methodologies used in recent literature on exercise performance over the menstrual cycle identified through a literature search of PubMed and SportDiscus from 2008 until 2018. Results Potential changes over the menstrual cycle are likely related to hormone fluctuations, however, only 44% of the selected studies measured the actual concentrations of the female steroid hormones estrogen and progesterone. It was shown that the likely inclusion of participants with anovulatory or luteal phase deficient cycles in combination with small participant numbers has impacted results in recent menstrual cycle research and consequently our understanding of this area. Conclusion To improve the quality of future menstrual cycle research it is recommended that a combination of three methods is used to verify menstrual cycle phase: the calendar-based counting method combined with urinary luteinizing hormone surge testing and the measurement of serum estrogen and progesterone concentrations at the time of testing. A strict luteal phase verification limit of >16 nmol·L-1 for progesterone should be set. It is also recommended that future research focusses on the inclusion of the late follicular estrogen peak. It is envisaged that these methodological recommendations will assist in clarifying some of the disagreement around the effects of the menstrual cycle on exercise performance and other aspects of exercise science and sports medicine. Corresponding author: Xanne Janse de Jonge Exercise & Sport Science Faculty of Science The University of Newcastle, Australia Central Coast Campus PO Box 127 Ourimbah NSW 2258 Australia E: X.Jansedejonge@newcastle.edu.au ORCID 0000-0003-3657-5298 Xanne Janse de Jonge, Belinda Thompson and Ahreum Han declare that they have no conflicts of interest relevant to the content of this review. The results of the present study do not constitute endorsement by ACSM. The results of this review are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. No funding was received for this review. Accepted for publication: 22 May 2019. © 2019 American College of Sports Medicine

Estimated Cardiorespiratory Fitness and Risk of Atrial Fibrillation: The HUNT Study Purpose To investigate the association between estimated cardiorespiratory fitness (eCRF) and risk of atrial fibrillation (AF), and examine how long-term changes in eCRF affects the AF risk. Methods This prospective cohort study includes data of 39 844 men and women from the HUNT2 (August 15, 1995 - June 18, 1997) and the HUNT3 study (October 3, 2006 – June 25, 2008). The follow-up period was from HUNT3 until AF diagnosis or November 30, 2015. AF diagnoses were retrieved from hospital registers and validated by medical doctors. A non-exercise test based on age, waist circumference, resting heart rate and self-reported physical activity was used to estimate CRF. Cox regression was performed to assess the association between eCRF and AF. Results The mean age was 50.6 ± 14.6 years for men and 50.2 ± 15.2 years for women. Mean follow-up time was 8.1 years. 1 057 cases of AF were documented. For men, the highest risk reduction of AF was 31% in the 4th quintile of eCRF when compared to the 1st quintile (HR, 0.69; 95% CI, 0.53-0.89). For women, the highest risk reduction was 47% in the 5th quintile when compared to the 1st quintile (HR, 0.53; 95% CI, 0.38-0.74). One metabolic equivalent increase in eCRF over a 10-year period was associated with 7% lower risk of AF (HR, 0.93; 95% CI, 0.86-1.00) Participants with improved eCRF had 44% lower AF risk compared to those with decreased eCRF (HR, 0.56; 95% CI, 0.36-0.87). Conclusion eCRF was inversely associated with AF, and participants with improved eCRF over a 10-year period had less risk of AF. These findings support the hypothesis that fitness may prevent AF. Correspondence and reprints to: Lars E. Garnvik, Department of Circulation and Medical Imaging, NTNU, Medisinsk Teknisk Forskningssenter, Post box 8905, 7491 Trondheim, Norway. E-mail: lars.e.garnvik@ntnu.no This work was supported by grants from the The Liaison Committee for education, research and innovation in Central Norway. The results of the study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation, and statement that results of the present study do not constitute endorsement by ACSM. The Nord-Trøndelag Health Study (The HUNT Study) is a collaboration between HUNT Research Centre, (Faculty of Medicine and Health Sciences, NTNU, Norwegian University of Science and Technology), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health. We would like to thank all the participants and technicians of the HUNT study for their contributions. Conflict of interest: None declared. Accepted for publication: 14 June 2019. © 2019 American College of Sports Medicine

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Acta Biomaterialia

In Vivo Characterization of the Deformation of the Human Optic Nerve Head Using Optical Coherence Tomography and Digital Volume Correlation Publication date: Available online 3 July 2019 Source: Acta Biomaterialia Author(s): Dan E. Midgett, Harry A. Quigley, Thao. D. Nguyen Abstract We developed a method to measure the 3-dimensional (3D) strain field in the optic nerve head (ONH) in vivo between two intraocular pressures (IOP). Radial optical coherence tomography (OCT) scans were taken of the ONH of 5 eyes from 5 glaucoma patients before and after IOP-lowering surgery and from 5 eyes from 3 glaucoma suspect patients before and after raising IOP by wearing tight-fitting swimming goggles. Scans taken at higher and lower IOP were compared using a custom digital volume correlation (DVC) algorithm to calculate strains in the anterior lamina cribrosa (ALC), retina, and choroid. Changes in anterior lamina depth (ALD) relative to Bruch's membrane were also analyzed. Average displacement error was estimated to be subpixel and strain errors were smaller than 0.37%. Suturelysis decreased IOP by 9 - 20 mmHg and decreased compressive anterior-posterior strain Ezz in the ALC by 0.76% (p=0.002,n=5). Goggle-wearing increased IOP by 3-4 mmHg and produced compressive Ezz in the ALC (-0.32%,p=0.001,n=5). Greater IOP decrease was associated with greater ALD change (p=0.047,n=10) and greater strains in the ALC (Ezz:p=0.002,n=10). A deepening of ALD was associated with lower IOP and greater ALC strains (p⩽0.045,n=10). A DVC-based method to measure strains from OCT images caused by IOP changes as small as 2.3 mmHg provides preliminary evidence that ALD is shallower and ALC strains are less compressive at higher IOP and that ALD change is associated with ALC strains. Statement of Significance Glaucoma causes vision loss through progressive damage of the retinal ganglion axons at the lamina cribrosa, a connective tissue structure in the optic nerve head that supports the axons as they pass through the eye wall. It is hypothesized that strains caused by intraocular pressure (IOP) may initiate this damage, but few studies have measured the strain response to pressure of the optic nerve head in patients. We present a method to measure the 3D displacement and strain field in the optic nerve head caused by IOP alteration in glaucoma patients using clinically available images. We used this method to measure strain within the optic nerve head from IOP changes caused by glaucoma surgery and wearing tight-fitting swimming goggles. Graphical abstract

3-D Printed Ti-6Al-4V Scaffolds for Supporting Osteoblast and Restricting Bacterial Functions Without Using Drugs: Predictive Equations and Experiments Publication date: Available online 3 July 2019 Source: Acta Biomaterialia Author(s): Nicole J. Bassous, Christopher L. Jones, Thomas J. Webster Abstract Conditions resulting from musculoskeletal deficiencies (MSDs) are wide-ranging and retain the likelihood for restricting motion or producing pain, especially in the lower back, neck, and upper limbs. Engineered scaffold devices are being produced to replace antiquated modalities that suffer from structural and mechanical deficiencies in the treatment of MSDs. Here, as-fabricated Ti-6Al-4V-based HiveTM interbody fusion scaffolds, commercialized by HD Lifesciences LLC, were assayed for their osteogenicity and antibacterial potential using a series of characterization and in vitro tests, as well as by quantitative analyses. A topographical assessment of the HiveTM meshes indicated that the elementally pure substrates are microscopically porous and rough, in addition to displaying structural heterogeneity. Roughness estimations and static contact angle measurements recommended the use of the as-fabricated Ti-6Al-4V substrates for supporting cellular attachment, especially, due to the improved surface roughness and wettability values of these scaffolds relative to the unembellished Ti-6Al-4V surfaces. Quantitative correlations relating the surface properties of roughness and energy were applied to predict cellular behaviors. Cell growth suppositions were experimentally corroborated. Critical in vitro data indicated the competencies of HiveTM scaffolds for promoting the adhesion and proliferation of human fetal osteoblasts (hFOBs); accumulating substantial calcium buildups from metabolizing hFOBs; and restricting the attachment of bacterial biofilms. The model system that investigated the pre-adsorption of casein proteins along HiveTM test substrates additionally furthered the notion that bacterial attachment may be restricted, with short-scale adhesion dynamics serving as the theoretical basis for this hypothesis. Statement of Significance Sintered Ti-6Al-4V spinal fusion devices (HiveTM) manufactured and marketed by HD Lifesciences LLC were assessed for their biocompatibility and antibacterial performance. A mixed methods approach was employed, whereby quantitative measures were used to predict the ability for HiveTM substrates to adsorb specialized proteins and to restrict bacterial surface colonization. In vitro tests that evaluated bone cell and bacterial adhesion, calcium deposition, and protein adsorption supported quantitative predictions. The data herein presented demonstrate the following: (1) surface energy is an important predictor of implant-cell interactions, (2) strong correlations exist between surface energy and surface roughness, (3) mathematical models can be used to improve implant devices, and (4) porous, rough, 3D-printed materials perform well in terms of biocompatibility and antimicrobial efficacy. Graphical abstract

Concanavalin A-targeted mesoporous silica nanoparticles for infection treatment Publication date: Available online 3 July 2019 Source: Acta Biomaterialia Author(s): Marina Martínez-Carmona, Isabel Izquierdo-Barba, Montserrat Colilla, María Vallet-Regí Abstract The ability of bacteria to form biofilms hinders any conventional treatment for chronic infections and has serious socio-economic implications. For this purpose, a nanocarrier capable of overcoming the barrier of the mucopolysaccharide matrix of the biofilm and releasing its loaded-antibiotic within this matrix would be desirable. Herein, we developed a new nanosystem based on levofloxacin (LEVO)-loaded mesoporous silica nanoparticles (MSNs) decorated with the lectin concanavalin A (ConA). The presence of ConA promotes the internalization of this nanosystem into the biofilm matrix, which increases the antimicrobial efficacy of the antibiotic hosted within the mesopores. This nanodevice is envisioned as a promising alternative to conventional treatments for infection by improving the antimicrobial efficacy and reducing side effects. Statement of Significance The present study is focused on finding an adequate therapeutic solution for the treatment of bone infection using nanocarriers that are capable of overcoming the biofilm barrier by increasing the therapeutic efficacy of the loaded antibiotic. For this purpose, we present a nanoantibiotic that increases the effectiveness of levofloxacin to destroy the biofilm formed by the model bacterium E. coli.. This work opens new lines of research in the treatment of chronic infections based on nanomedicines. Graphical abstract

Corrigendum to "Functional quantum dot-siRNA nanoplexes to regulate chondrogenic differentiation of mesenchymal stem cells" [Acta Biomater. 46 (2016) 165–176] Publication date: Available online 2 July 2019 Source: Acta Biomaterialia Author(s): Yang Wu, Bo Zhou, Fuben Xu, Xiaoyong Wang, Gang Liu, Li Zheng, Jinmin Zhao, Xingdong Zhang

Plasma deposited poly-oxazoline nanotextured surfaces dictate osteoimmunomodulation towards ameliorative osteogenesis Publication date: Available online 2 July 2019 Source: Acta Biomaterialia Author(s): Zetao Chen, Rahul Madathiparambil Visalakshan, Jia Guo, Fei Wei, Linjun Zhang, Lingling Chen, Zhengmei Lin, Krasimir Vasilev, Yin Xiao Abstract Developing "osteoimmune-smart" bone substitute materials have become the forefront of research in bone regeneration. Biocompatible polymer coatings are applied widely to improve the bioactivity of bone substitute materials. In this context, polyoxazolines (Pox) have attracted substantial attention recently due to properties such as biocompatibility, stability, and low biofouling. In view of these useful properties, it is interesting to explore the capacity of Pox as an osteoimmunomodulatory agent to generate a favorable osteoimmune environment for osteogenesis. We applied a technique called plasma polymerization and succeeded in preparing Pox-like coatings (Ppox) and engineered their nanotopography at the nanoscale. We found that Ppox switched macrophages towards M2 extreme, thus inhibiting the release of inflammatory cytokines. The underlying mechanism may be related to the suppression of TLR pathway. The generated osteoimmune environment improved osteogenesis while inhibited osteoclastogenesis. This may be related to the release of osteogenic factors, especially Wnt10b from macrophages. The addition of nanotopography (16nm, 38nm, 68nm) can tune the Ppox-mediated inhibition on inflammation and osteoclastic activities, while no significant effects were observed within the tested nano sizes on the Ppox-mediated osteogenesis. These results collectively suggest that Ppox can be useful as an effective osteoiumunomodulatory agent to endow bone substitute materials with favourable osteoimmunomodulatory property. Statement of significance In this study, we succeeded in preparing plasma deposited Pox-like nano-coatings (Ppox) via plasma polymerization and found that Ppox nanotopographies are useful osteoimmunomodulatory tools. Their osteoimmunodolatory effects and underlying mechanisms are unveiled. It is the first investigation into the feasibility of applying poly-oxazoline as an osteoimmunomodulatory agent. This expand the application of poly-oxazoline into the forefront in bone regeneration area for the development of advanced "osteoimmune-smart" bone substitute materials. Graphical abstract

A Bioink Blend for Rotary 3D Bioprinting Tissue Engineered Small-Diameter Vascular Constructs Publication date: Available online 2 July 2019 Source: Acta Biomaterialia Author(s): Sebastian Freeman, Rafael Ramos, Paul Alexis Chando, Luxi Zhou, Kyle Reeser, Sha Jin, Pranav Soman, Kaiming Ye Abstract 3D bioprinted vascular constructs have gained increased interest due to their significant potential for creating customizable alternatives to autologous vessel grafts. In this study, we developed a new approach for biofabricating fibrin-based vascular constructs using a novel rotary 3D bioprinter developed in our lab. We formulated a new bioink by incorporating fibrinogen with gelatin to achieve a desired shear-thinning property for rotary bioprinting. The blending of heat-treated gelatin with fibrinogen turned unprintable fibrinogen into a printable biomaterial for vessel bioprinting by leveraging the favorable rheological properties of gelatin. We discovered that the heat-treatment of gelatin remarkably affects the rheological properties of a gelatin-fibrinogen blended bioink, which in turn influences the printability of the ink. Further characterizations revealed that not only concentration of the gelatin but the heat treatment also affects cell viability during printing. Notably, the density of cells included in the bioinks also influenced printability and tissue volumetric changes of the printed vessel constructs during cultures. We observed increased collagen deposition and construct mechanical strength during two months of the cultures. The burst pressure of the vessel constructs reached 1,110 mmHg, which is about 52% of the value of the human saphenous vein. An analysis of the tensile mechanical properties of the printed vessel constructs unveiled an increase in both the circumferential and axial elastic moduli during cultures. This study highlights important considerations for bioink formulation when bioprinting vessel constructs. Statement of Significance There has been an increased demand for small-diameter tissue-engineered vascular grafts. Vascular 3D bioprinting holds the potential to create equivalent vascular grafts but with the ability to tailor them to meet patient's needs. Here, we presented a new and innovative 3D rotary bioprinter and a new bioink formulation for printing vascular constructs using fibrinogen, a favorable biomaterial for vascular tissue engineering. The bioink was formulated by blending fibrinogen with a more printable biomaterial, gelatin. The systematic characterization of the effects of heat treatment and gelatin concentration as well as bioink cell concentration on the printability of the bioink offers new insight into the development of printable biomaterials for tissue biofabrication. Graphical abstract

Mechanical behavior of ctenoid scales: Joint-like structures control the deformability of the scales in the flatfish Solea solea (Pleuronectiformes) Publication date: 1 July 2019 Source: Acta Biomaterialia, Volume 92 Author(s): Marlene Spinner, Clemens F. Schaber, Shao-Min Chen, Marco Geiger, Stanislav N. Gorb, Hamed Rajabi Abstract Ctenoid scales protect the fish body against predators and other environmental impacts. At the same time, they allow for sufficient degree of flexibility to perform species-specific locomotion. The scales of the flatfish Solea solea were chosen to study the specific mechanical behavior and material properties of the ctenoid scales. Using scanning electron microscopy and micro-computed tomography, three-dimensional asymmetric structures of the stacked mineralized ctenial spines in the posterior field, which is a part of the scales exposed to the environment, were examined in detail. Nanoindentations on the surface of the ctenial spines indicated that the elastic modulus and hardness of these mineralized structures are about 14 GPa and 0.4 GPa, respectively. The spines appeared to be connected to each other by means of joint-like structures containing soft tissues. Bending tests showed that the ctenoid scales have two functional zones: a stiff supporting main body and an anisotropically deformable posterior field. While the stiff plate-like main body provides support for the whole scale, the deformable joint-like structures in the ctenial spines increase the deformability of the posterior field in downward bending. During upward bending, however, the spines prevent complete folding of the posterior field by an interlocking effect. Statement of significance In contrast to the continuously mineralized cycloid scales, ctenoid scales combine two conflicting properties: They are hard to protect the body of fish against predators and other environmental impacts, yet flexible enough to allow for sufficient degree of body bendability for locomotion. To understand the structural background underlying this specific biomechanical feature, here we investigated the scales of the flatfish Solea solea. For the first time, we demonstrated the presence of joint-like structures within the scales, which increase scale deformability during downward bending, but prevent scale deformation during upward bending by interlocking. Our results shed lights on the material-structure-function relationships in ctenoid scales, as well as on their functional adaptations to the specific environment. Graphical abstract

Synchrotron tomography of intervertebral disc deformation quantified by digital volume correlation reveals microstructural influence on strain patterns Publication date: 1 July 2019 Source: Acta Biomaterialia, Volume 92 Author(s): C.M. Disney, A. Eckersley, J.C. McConnell, H. Geng, A.J. Bodey, J.A. Hoyland, P.D. Lee, M.J. Sherratt, B.K. Bay Abstract The intervertebral disc (IVD) has a complex and multiscale extracellular matrix structure which provides unique mechanical properties to withstand physiological loading. Low back pain has been linked to degeneration of the disc but reparative treatments are not currently available. Characterising the disc's 3D microstructure and its response in a physiologically relevant loading environment is required to improve understanding of degeneration and to develop new reparative treatments. In this study, techniques for imaging the native IVD, measuring internal deformation and mapping volumetric strain were applied to an in situ compressed ex vivo rat lumbar spine segment. Synchrotron X-ray micro-tomography (synchrotron CT) was used to resolve IVD structures at microscale resolution. These image data enabled 3D quantification of collagen bundle orientation and measurement of local displacement in the annulus fibrosus between sequential scans using digital volume correlation (DVC). The volumetric strain mapped from synchrotron CT provided a detailed insight into the micromechanics of native IVD tissue. The DVC findings showed that there was no slipping at lamella boundaries, and local strain patterns were of a similar distribution to the previously reported elastic network with some heterogeneous areas and maximum strain direction aligned with bundle orientation, suggesting bundle stretching and sliding. This method has the potential to bridge the gap between measures of macro-mechanical properties and the local 3D micro-mechanical environment experienced by cells. This is the first evaluation of strain at the micro scale level in the intact IVD and provides a quantitative framework for future IVD degeneration mechanics studies and testing of tissue engineered IVD replacements. Statement of Significance Synchrotron in-line phase contrast X-ray tomography provided the first visualisation of native intact intervertebral disc microstructural deformation in 3D. For two annulus fibrosus volumes of interest, collagen bundle orientation was quantified and local displacement mapped as strain. Direct evidence of microstructural influence on strain patterns could be seen such as no slipping at lamellae boundaries and maximum strain direction aligned with collagen bundle orientation. Although disc elastic structures were not directly observed, the strain patterns had a similar distribution to the previously reported elastic network. This study presents technical advances and is a basis for future X-ray microscopy, structural quantification and digital volume correlation strain analysis of soft tissue. Graphical abstract

Investigating the passive mechanical behaviour of skeletal muscle fibres: Micromechanical experiments and Bayesian hierarchical modelling Publication date: 1 July 2019 Source: Acta Biomaterialia, Volume 92 Author(s): Markus Böl, Rahul Iyer, Johannes Dittmann, Mayra Garcés-Schröder, Andreas Dietzel Abstract Characterisation of the skeletal muscle's passive properties is a challenging task since its structure is dominated by a highly complex and hierarchical arrangement of fibrous components at different scales. The present work focuses on the micromechanical characterisation of skeletal muscle fibres, which consist of myofibrils, by realising three different deformation states, namely, axial tension, axial compression, and transversal compression. To the best of the authors' knowledge, the present study provides a novel comprehensive data set representing of different deformation states. These data allow for a better understanding of muscle fibre load transfer mechanisms and can be used for meaningful modelling approaches. As the present study shows, axial tension and compression experiments reveal a strong tension-compression asymmetry at fibre level. In comparison to the tissue level, this asymmetric behaviour is more pronounced at the fibre scale, elucidating the load transfer mechanism in muscle tissue and aiding in the development of future modelling strategies. Further, a Bayesian hierarchical modelling approach was used to consider the experimental fluctuations in a parameter identification scheme, leading to more comprehensive parameter distributions that reflect the entire observed experimental uncertainty. Statement of Significance This article examines for the first time the mechanical properties of skeletal muscle fibres under axial tension, axial compression, and transversal compression, leading to a highly comprehensive data set. Moreover, a Bayesian hierarchical modelling concept is presented to identify model parameters in a broad way. The results of the deformation states allow a new and comprehensive understanding of muscle fibres' load transfer mechanisms; one example is the effect of tension-compression asymmetry. On the one hand, the results of this study contribute to the understanding of muscle mechanics and thus to the muscle's functional understanding during daily activity. On the other hand, they are relevant in the fields of skeletal muscle multiscale, constitutive modelling. Graphical abstract

Nonlinear elasticity of the lung extracellular microenvironment is regulated by macroscale tissue strain Publication date: 1 July 2019 Source: Acta Biomaterialia, Volume 92 Author(s): Ignasi Jorba, Gabriel Beltrán, Bryan Falcones, Béla Suki, Ramon Farré, José Manuel García-Aznar, Daniel Navajas Abstract The extracellular matrix (ECM) of the lung provides physical support and key mechanical signals to pulmonary cells. Although lung ECM is continuously subjected to different stretch levels, detailed mechanics of the ECM at the scale of the cell is poorly understood. Here, we developed a new polydimethylsiloxane (PDMS) chip to probe nonlinear mechanics of tissue samples with atomic force microscopy (AFM). Using this chip, we performed AFM measurements in decellularized rat lung slices at controlled stretch levels. The AFM revealed highly nonlinear ECM elasticity with the microscale stiffness increasing with tissue strain. To correlate micro- and macroscale ECM mechanics, we also assessed macromechanics of decellularized rat lung strips under uniaxial tensile testing. The lung strips exhibited exponential macromechanical behavior but with stiffness values one order of magnitude lower than at the microscale. To interpret the relationship between micro- and macromechanical properties, we carried out a finite element (FE) analysis which revealed that the stiffness of the alveolar cell microenvironment is regulated by the global strain of the lung scaffold. The FE modeling also indicates that the scale dependence of stiffness is mainly due to the porous architecture of the lung parenchyma. We conclude that changes in tissue strain during breathing result in marked changes in the ECM stiffness sensed by alveolar cells providing tissue-specific mechanical signals to the cells. Statement of Significance The micromechanical properties of the extracellular matrix (ECM) are a major determinant of cell behavior. The ECM is exposed to mechanical stretching in the lung and other organs during physiological function. Therefore, a thorough knowledge of the nonlinear micromechanical properties of the ECM at the length scale that cells probe is required to advance our understanding of cell-matrix interplay. We designed a novel PDMS chip to perform atomic force microscopy measurements of ECM micromechanics on decellularized rat lung slices at different macroscopic strain levels. For the first time, our results reveal that the microscale stiffness of lung ECM markedly increases with macroscopic tissue strain. Therefore, changes in tissue strain during breathing result in variations in ECM stiffness providing tissue-specific mechanical signals to lung cells. Graphical abstract

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Tropical Biomedicine

Pam3CSK4 enhances adaptive immune responses to recombinant Mycobacterium bovis bacille Calmette-Guérin expressing Plasmodium falciparum C-terminus merozoite surface protein-1 Mohamed H Abdikarim, Muhammad A Abbas, Munirah N Zakaria, Robaiza Zakaria, Rapeah Suppian Asian Pacific Journal of Tropical Biomedicine 2019 9(7):271-277 Objective: To determine the effects of toll-like receptor 2 (TLR-2) agonist, Pam3CSK4, on cellular and humoral immune response against recombinant Mycobacterium bovis bacille Calmette-Guérin (rBCG) expressing the C-terminus of merozoite surface protein-1 of Plasmodium falciparum. Methods: Six groups of mice (n=6 per group) received intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of Pam3CSK4. Enzyme- linked immunosorbent assay was carried out to measure serum total IgG, IgG1, IgG2a, and IgG2b production. Spleens were also harvested and splenocytes were co-cultured with rBCG antigen for in vitro determination of IL-4 and IFN- γ via enzyme-linked immunosorbent assay. Results: The production of total IgG and the isotype IgG1, IgG2a and IgG2b was significantly higher in rBCG-immunised mice than in the BCG and PBS-T80-immunised mice, and Pam3CSK4 further enhanced their productions. A similar pattern was also observed in IFN- γ production. Moreover, there was no significant difference in IL-4 production in all groups either in the presence or absence of Pam3CSK4. Conclusions: We present evidence of the adjuvant effects of TLR-2 agonist in enhancing the production of total IgG, IgG1, IgG2a, IgG2b, as well as IFN- γ in response to rBCG. However, the presence or absence of Pam3CSK4 had no effect on IL-4 production.

Cynodon dactylon extract ameliorates cognitive functions and cerebellar oxidative stress in whole body irradiated mice Roopesh Poojary, Nayanatara Arun Kumar, Reshma Kumarchandra, NA Vinodini, K Bhagyalakshmi, Ganesh Sanjeev Asian Pacific Journal of Tropical Biomedicine 2019 9(7):278-283 Objective: To explore the effect of hydroalcoholic extract of Cynodon dactylon on the whole body radiation-induced oxidative status of the cerebellum and cognitive impairments in mice. Methods: Swiss albino mice were randomly divided into the control group, radiation control group, low dose and high dose Cynodon dactylon extract treated groups and pre-treated with Cynodon dactylon extract before irradiation. Cynodon dactylon extract was administered for 7 d daily in low dose (0.25 g/kg) and high dose (1 g/kg). On day 7, mice were irradiated with a sublethal dose of 5 Gy gamma rays. Motor coordination was assessed by elevated rotarod test and spatial memory was studied by water maze test. Subsequently, biochemical markers (glutathione, lipid peroxidation and nitric oxide levels) in the cerebellum were evaluated. Results: The gamma irradiated group showed significant impairment in motor coordination and spatial memory compared to normal mice. Mice treated by Cynodon dactylon extract prior to gamma radiation showed good improvement in both paradigms compared to the radiation control group. Moreover, glutathione level was increased, while lipid peroxidation and nitric oxide levels were significantly reduced in mice receiving low dose and high dose of Cynodon dactylon extract compared to the radiation control group. Conclusions: The present study suggests the neuroprotective role of Cynodon dactylon against radiation-induced cognitive impairment and oxidative stress on the cerebellum of mice.

Galangin ameliorates changes of membrane–bound enzymes in rats with streptozotocin–induced hyperglycemia Amal A Aloud, Chinnadurai Veeramani, Chandramohan Govindasamy, Mohammed A Alsaif, Khalid S Al-Numair Asian Pacific Journal of Tropical Biomedicine 2019 9(7):284-290 Objective: To assess the protective effect of galangin on membrane bound enzymes in rats with streptozotocin-induced diabetes. Methods: A single low dose of streptozotocin was injected to adult male albino rats to induce hyperglycemia. Galangin (8 mg/kg) or glibenclamide 600 μg/kg as a standard drug was given orally once daily for 45 days by gavage. Membrane-bound adenosine triphosphatases were determined including total ATPase, sodium-potassium-ATPase, calcium-ATPase and magnesium-ATPase in erythrocytes and tissues (kidney, liver, and heart). Results: The levels of total ATPases, sodium-potassium-ATPase, calcium-ATPase and magnesium-ATPase in erythrocytes and tissues were significantly altered in diabetic rats as compared to that in normal rats. After 45 days of treatment with galangin or glibenclamide, the levels of these enzymes were similar to that of normal control rats. Conclusions: Oral administration of galangin or glibenclamide can improve activities of these membrane-bound ATPases towards normal levels. Mechanism of galangin needs to be further explored in future.

Thai pigmented rice bran extracts inhibit production of superoxide, nitric oxide radicals and inducible nitric oxide synthase in cellular models Kedsara Junmarkho, Pintusorn Hansakul Asian Pacific Journal of Tropical Biomedicine 2019 9(7):291-298 Objective: To study the inhibitory effect of rice bran extracts of Thai black Kam Muang and red Hawm Dawk Mali Deang on oxidative stress factors including superoxide (O2•-), nitric oxide (NO•), and inducible nitric oxide synthase (iNOS). Methods: Bran extracts (40% ethanol) of Kam Muang and Hawm Dawk Mali Deang were obtained and evaluated for in vitro 2-2’-azino-di-(3-ethylbenzthiazoline sulfonate) (ABTS) and NO• scavenging activity. Their inhibitory effects on cellular O2•- and NO• were measured in phorbol 12-myristate 13-acetate-stimulated neutrophil-like HL-60 cells and lipopolysaccharide- stimulated RAW264.7 macrophages, respectively, and their viability was monitored using the MTT assay. The effect on iNOS expression was also assessed by the Western blotting assay. Total contents of phenolics, flavonoids, and subtypes were also determined. Results: Hawm Dawk Mali Deang exhibited about 3.5-fold greater cellular O2•- inhibitory activity than Kam Muang [EC50 values of (23.57±4.54) and (81.98±1.45) μg/mL, respectively] in phorbol 12-myristate 13-acetate-stimulated HL-60 cells. Hawm Dawk Mali Deang exhibited about 2-fold higher in vitro ABTS•+ and NO• scavenging activity than Kam Muang, but it exerted cellular NO• inhibitory activity of only about 26% (undetermined EC50 value) in lipopolysaccharide-stimulated RAW264.7 cells. Conversely, Kam Muang exerted potent cellular NO• inhibitory activity [EC50 value: (281.13±59.18) μg/mL] and dose-dependently decreased iNOS levels. No cytotoxicity of both extracts was detected in both cell types. As for corresponding contents, Hawm Dawk Mali Deang contained higher contents of phenolics and flavonoids than Kam Muang. Moreover, Kam Muang and Hawm Dawk Mali Deang had a high content of total anthocyanins [(14.73±0.52) mg C3GE/g of extract] and total proanthocyanidins [(115.13±1.47) mg CE/g of extract], respectively. Conclusions: Based on these data, bran extracts of Thai black Kam Muang and red rice Hawm Dawk Mali Deang can help lower oxidative stress and inflammation attributed partly to O2•- and NO•.

Cytotoxic, apoptotic and cell migration inhibitory effects of atranorin on SPC212 mesothelioma cells Erhan Sahin, Sinem Dabagoglu Psav, Ilker Avan, Mehmet Candan, Varol Sahinturk, Ayse Tansu Koparal Asian Pacific Journal of Tropical Biomedicine 2019 9(7):299-306 Objective: To investigate the effects of atranorin, a lichen secondary metabolite, on SPC212 malignant mesothelioma cells in vitro. Methods: SPC212 malignant mesothelioma cell line was used. 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide assay was used to evaluate cytotoxic effects of atranorin and cisplatin at 24, 48 and 72 h. Hematoxylin-eosin staining and 4’,6-diamidino-2-phenylindole, dihydrochloride staining were used for determining cell and nucleus morphology, respectively. Wound healing assay was used for investigating cell migration. The xCELLigence real-time cell analysis system was used for determining cell proliferation. Results: Atranorin at 5-450 μΜ decreased cell viability at 24, 48 and 72 h. IC50 values of atranorin were 300.94, 292.6 and 278.02 μM at 24, 48 and 72 h, respectively; meanwhile, the IC50 values of cisplatin were 128.00, 34.37 and 17.05 μM at 24, 48 and 72 h, respectively. Furthermore, atranorin disrupted cell and nuclear morphology with increasing concentrations. Atranorin significantly reduced cell migration by 38%, 37% and 35% at 300, 250 and 200 μM, respectively (P<0.000). Atranorin at 160-450 μM decreased cell proliferation at 72 h (P<0.000). Conclusions: Atranorin has cytotoxic, antiproliferative, apoptotic and cell migration inhibitory effects on SPC212 malignant mesothelioma cancer cells.

Antimicrobial, cytotoxicity, anticancer and antioxidant activities of Jatropha zeyheri Sond. roots (Euphorbiaceae) NI Mongalo, OS Soyingbe, TJ Makhafola Asian Pacific Journal of Tropical Biomedicine 2019 9(7):307-314 Objective: To evaluate the antimicrobial, antioxidant, cytotoxicity and anticancer activity of fractions from Jatropha zeyheri roots and to explore the phytochemical profile of the most biologically active fraction. Methods: Fractions from Jatropha zeyheri ethyl acetate extract were investigated for antimicrobial activity against a plethora of pathogenic microorganisms of different origins. The cytotoxicity studies of fractions were evaluated in vitro using tetrazolium-based calorimetric assay against human dermal fibroblast, colon adenocarcinoma (Caco-2), breast cancer (MCF-7) and lung cancer (A547) cell lines. The anti-oxidant activity of fractions was determined in vitro against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2’-azino-bis-(3-ethylbenzothiazoline- 6-sulfonic acid) diammonium salt (ABTS) and chelation of iron (Fe2+). Gas chromatography mass spectrometry analysis was performed to detect phytochemical constituents in fraction with potent biological activity. Results: Fraction 2 of Jatropha zeyheri roots exhibited the lowest minimum inhibitory concentration of 40 μg/mL against Klebsiella pneumoniae and 80 μg/mL against Candida albicans, Staphylococcus aureus and Mycoplasma hominis. The fractions revealed some varying degrees of cytotoxicity against human dermal fibroblasts yielding LC50 values ranging from 28.96 to 166.52 μg/mL. Fraction 3 exhibited the highest selectivity index value of 2.08 against Klebsiella pneumoniae. Moreover, fraction 2 selectively inhibited the growth of Caco-2 with LC50 of 8.83 μg/mL, compared to other cancerous cell lines. Fraction 2 of Jatropha zeyheri further exhibited IC50 of 19.66, 22.63 and 1.82 μg/mL against DPPH, ABTS and Fe2+, respectively. Gas chromatography mass spectrometry analysis revealed the presence of cyclotetracosane (10.08%), 9-hexacosene (9.40%), hexadecanoic acid (3.90%), (Z)-9-octadecenamide (3.63%), octacosane (2.27%), 11-n-decylheneicosane (2.23%), ethyl vallesiachotamate (2.17%), heneicosanoic acid (2.10%), and octadecanoic acid (2.08%) in fraction 2 of Jatropha zeyheri. Conclusions: These identified compounds, particularly cyclotetracosane (hydrocarbon), may well explain the biological activity of fraction 2 of Jatropha zeyheri, which possesses higher biological activity than other fractions. These compounds can be further investigated for use in treating various bacterial and fungal opportunistic infections associated with HIV-AIDS and related cancers.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Endoscopic Surgery

Superior outcomes (but at higher costs) of non‐operative management with interval appendectomy over immediate surgery in appendicitis with abscess: Results from a large adult population cohort Asian Journal of Endoscopic Surgery, EarlyView.

Laparoscopic surgery for an esophageal duplication cyst using a near‐infrared indocyanine green fluorescence system: A case report Asian Journal of Endoscopic Surgery, EarlyView.

Single‐port laparoscopic colectomy in elderly patients with colon cancer: A propensity score‐matched comparison with younger patients Asian Journal of Endoscopic Surgery, EarlyView.

Idiopathic mesenteric phlebosclerosis treated with laparoscopic subtotal colectomy: A case report Asian Journal of Endoscopic Surgery, EarlyView.

A minimally invasive abdominal and left thoracic approach as a palliative treatment for adenocarcinoma of the esophagogastric junction with severe stenosis: A case report Asian Journal of Endoscopic Surgery, EarlyView.

The usefulness of intraoperative X‐ray fluoroscopy in avoiding urethral injury during transanal total mesorectal excision Asian Journal of Endoscopic Surgery, EarlyView.

Laparoscopic decision‐making concerning the repair area for traumatic abdominal wall pseudohernia: A case report Asian Journal of Endoscopic Surgery, EarlyView.

Laparoscopic repair of an irreducible femoral hernia containing an epiploic appendage of the sigmoid colon Asian Journal of Endoscopic Surgery, EarlyView.

Hemi‐double stapling technique performed with a transorally inserted anvil for esophagojejunostomy in the surgical treatment of gastric cancer Asian Journal of Endoscopic Surgery, EarlyView.

Transfascial suture fixation technique in laparoscopic repair of inguinal hernia Asian Journal of Endoscopic Surgery, EarlyView.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com