Τετάρτη, 20 Ιουνίου 2018

Neural basis of trigeminal chemo- and thermonociception in brown treesnakes, Boiga irregularis (Squamata: Colubridae)


To elucidate the nociceptive system of the brown treesnake, Boiga irregularis, we exposed isolated brown treesnake trigeminal neurons to thermal and chemical stimulation. We measured responses as changes in intracellular calcium using ratiometric fluorescent calcium imaging. Responses to aversive thermal and chemical identified several classes of putative nociceptors. Compounds that were aversive excited many trigeminal neurons, putative chemonociceptors. Identification as nociceptors was further supported by lack of activation by compounds that were not aversive. Brown treesnake neurons had thermal thresholds ranging from 32 to 49 °C. The distribution was discontinuous, with a population of thresholds from 32 to 45 °C and a population with thresholds > 48 °C. Thermal stimulation of 48 °C has been shown to be strongly aversive to brown treesnakes, is lethal, and suggests the presence of thermonociceptors. Thermal sensitivity of brown treesnake trigeminal neurons greatly overlaps with chemical sensitivity; only 1.1% of neurons were sensitive to only thermal stimulation. 50% of brown treesnake trigeminal neurons tested with both > 48 °C and cinnamaldehyde responded to both stimuli, identifying putative polymodal nociceptors. Although a previous study found brown treesnakes insensitive to capsicum extract containing capsaicin, brown treesnake trigeminal neurons responded to capsaicin. These findings are of evolutionary interest as well as providing potential insights into managing this significant pest species.

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Clinical Significance of Incidental Pituitary TC-99m MIBI Uptake on Parathyroid Spect and Factors Affecting Uptake Intensity

Cancer Biotherapy and Radiopharmaceuticals, Ahead of Print.

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Toward a Better Understanding of the Fused Deposition Modeling Process: Comparison with Injection Molding

3D Printing and Additive Manufacturing, Ahead of Print.

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A Normalized Trace Geometry Modeling Method with Bulge-Free Analysis for Direct Ink Writing Process Planning

3D Printing and Additive Manufacturing, Ahead of Print.

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Fission Yeast CENP-C (Cnp3) Plays a Role in Restricting the Site of CENP-A Accumulation

The centromere is a chromosomal locus where a microtubule attachment site, termed kinetochore, is assembled in mitosis. In most eukaryotes, with the exception of holocentric species, each chromosome contains a single distinct centromere. A chromosome with an additional centromere undergoes successive rounds of anaphase bridge formation and breakage, or triggers a cell cycle arrest imposed by DNA damage and replication checkpoints. We report here a study in Schizosaccharomyces pombe to characterize a mutant (cnp3-1) in a gene encoding a homolog of mammalian centromere-specific protein, CENP-C. At the restrictive temperature 36 °C, the Cnp3-1 mutant protein loses its localization at the centromere. In the cnp3-1 mutant, the level of the Cnp1 (a homolog of a centromere-specific histone CENP-A) also decreases at the centromere. Interestingly, the cnp3-1 mutant is prone to promiscuous accumulation of Cnp1 at non-centromeric regions, when Cnp1 is present in excess. Unlike the wild type protein, Cnp3-1 mutant protein is found at the sites of promiscuous accumulation of Cnp1, suggesting that Cnp3-1 may stabilize or promote accumulation of Cnp1 at non-centromeric regions. From these results, we infer the role of Cnp3 in restricting the site of accumulation of Cnp1 and thus to prevent formation of de novo centromeres.

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Angiotensin II and tumor necrosis factor-α stimulate the growth, migration and invasion of BEL-7402 cells via down-regulation of GRK2 expression

To investigate the effects of angiotensin II (Ang II) and tumor necrosis factor-α (TNF-α) on the biological characteristics of hepatocellular carcinoma (HCC) cells and the associated changes in G protein-coupled receptor kinase 2 (GRK2) expression.

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Thrombopoietin receptor agonists and risk of portal vein thrombosis in Patients with Liver disease and Thrombocytopenia: a meta-analysis

Treatment of thrombocytopenia with thrombopoietin receptor agonists (TPORAs) seems to be associated with portal vein thrombosis (PVT) in patients with chronic liver disease (CLD). We performed a meta-analysis of the trials carried out in this clinical setting to assess if such association is detectable.

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Influence of body weight unloading on human gait characteristics: a systematic review

Body weight support (BWS) systems have shown promise as rehabilitation tools for neurologically impaired individuals. This paper reviews the experiment-based research on BWS systems with the aim: (1) To invest...

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Central neuropathic pain in paraplegia alters movement related potentials

Publication date: August 2018
Source:Clinical Neurophysiology, Volume 129, Issue 8
Author(s): Aleksandra Vučković, Mohammed Jarjees, Muhammad Abul Hasan, Makoto Miyakoshi, Matthew Fraser
ObjectivesSpinal Cord Injured (SCI) persons with and without Central Neuropathic Pain (CNP) show different oscillatory brain activities during imagination of movement. This study investigates whether they also show differences in movement related cortical potentials (MRCP).MethodsSCI paraplegic patients with no CNP (n = 8), with CNP in their lower limbs (n = 8), and healthy control subjects (n = 10) took part in the study. EEG clustering involved independent component analysis, equivalent current dipole fitting, and Measure Projection to define cortical domains that have functional modularity during the motor imagery task.ResultsThree domains were identified: limbic system, sensory-motor cortex and visual cortex. The MRCP difference between the groups of SCI with and without CNP was reflected in a domain located in the limbic system, while the difference between SCI patients and control subjects was in the sensorimotor domain. Differences in MRCP morphology between patients and healthy controls were visible for both paralysed and non paralysed limbs.ConclusionSCI but not CNP affects the movement preparation, and both SCI and CNP affect sensory processes.SignificanceRehabilitation strategies of SCI patients based on MRCP should take into account the presence of CNP.

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Issue Information

Psychophysiology, Volume 55, Issue 7, July 2018.

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Effects of endurance exercise training on inflammatory circulating progenitor cell content in lean and obese adults

The Journal of Physiology, EarlyView.

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A Conversation with Swiss Product Designer, Christophe Guberan

3D Printing and Additive Manufacturing, Volume 5, Issue 2, Page 87-89, June 2018.

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Development of 3D-Printed Embedded Temperature Sensor for Both Terrestrial and Aquatic Environmental Monitoring Robots

3D Printing and Additive Manufacturing, Volume 5, Issue 2, Page 160-169, June 2018.

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3D-Printed Reusable Cell Culture Chamber with Integrated Electrodes for Electrical Stimulation and Parallel Microscopic Evaluation

3D Printing and Additive Manufacturing, Volume 5, Issue 2, Page 115-125, June 2018.

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Bidimensional Acculturation and Psychological Distress in Pakistani Immigrant Women in Norway: A Cross-Sectional Study


Immigrants from South Asia have higher risks of mental health problems . Low levels of acculturation and self-efficacy may be risk factors for depression and psychological distress in immigrants. 355 Pakistani immigrant women in Oslo, filled out a questionnaire concerning demographic variables, self-efficacy, and psychological distress. A bidimensional acculturation variable was constructed. A stepwise logistic regression model was used to investigate the importance of the level of acculturation and self-efficacy on psychological distress. Low levels of acculturation were reported. Integrated participants reported significantly less psychological distress on the depression score and total score than separated and marginalized participants. The model showed that assimilated or marginalized participants had a fourth and three times higher risk of high levels of distress compared with integrated participants. The possibility to be bicultural seems important in order to ensure mental health and national policies should promote an integrative and multiculturalism approach.

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Understanding the Gap: Perceived Health Literacy Levels Among Spanish-Speaking Immigrants in Miami-Dade County, 2016


Health literacy levels among immigrant populations in Miami-Dade County have yet to be examined. This study investigates perceived health literacy ability and measured health literacy scores among Miami-Dade County immigrants. Methods: Patients seen in the Refugee Health Assessment Program and Family Planning Program completed a health literacy assessment in November 2016. Participants were immigrants from Spanish-speaking countries who reported living in the U.S. for ≤ 10 years. Logistic regression models were used to determine predictors of agreement. 283 patients responded. No characteristics were significant predictors of agreement; However, we found lower agreement among participants that were 18–24 years old (49%), received medical information from the internet/television (46%), and had lived in the U.S. for only 6–12 months (49%). Our findings suggest that immigrant patients may have limited understanding of their health literacy abilities. Clinicians need to take health literacy levels into account when interacting with patients.

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Temperature modulates photoperiodic seasonal responses in the subtropical tree sparrow, Passer montanus


We studied the effects of temperature on the photoperiodic regulation of seasonal reproduction and related events in the subtropical tree sparrow at Shillong, India. In the first experiment, one group of birds was maintained in an outdoor open aviary receiving natural photoperiod and temperature conditions, while the other group was exposed to natural photoperiod and constant temperature of 17 ± 2 °C in an outdoor closed aviary for 12 months. Although both sexes achieved peak gonadal growth at the same time (May) under the two conditions, gonadal regression and feathers molt were delayed under the temperature controlled condition. In the second experiment, the groups of birds were exposed to three different temperatures (17, 25 and 30 °C) under both long (LD-14L:10D) and short (SD-9L:15D) day lengths for 7 months. Birds showed relatively small but significant gonadal growth, darkening of bill color and feathers molt only at 30 °C under SD. However, they behaved as though they were under natural conditions and exhibited the above responses significantly at all temperatures under LD. There was delayed gonadal regression at the lower temperature (17 °C), while feathers molt delayed with increasing temperature (25, 30 °C) under LD. These results clearly indicate that temperature modulates photoperiodic seasonal responses in the tree sparrow.

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What makes us human?

What makes us human?

What makes us human?, Published online: 20 June 2018; doi:10.1038/s41576-018-0029-7

A publication in Science reports the sequencing, assembly and comparative analysis of new and improved great ape genomes and provides a stepping stone for the identification of genetic variation specific to humans.

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Understanding Health-related Quality of Life in Caregivers of Civilians and Service Members/Veterans with Traumatic Brain Injury: Establishing the Reliability and Validity of PROMIS Mental Health Measures

Publication date: Available online 19 June 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Noelle E. Carlozzi, Robin Hanks, Rael T. Lange, Tracey A. Brickell D.Psych, Phillip A. Ianni, Jennifer A. Miner, Louis M. French Psy.D., Michael A. Kallen, Angelle M. Sander
ObjectiveTo provide important reliability and validity data to support the use of the PROMIS Mental Health measures in caregivers of civilians or service members/veterans with traumatic brain injury (TBI).DesignPatient-reported outcomes surveys administered through an electronic data collection platform.SettingThree TBI Model Systems rehabilitation hospitals, an academic medical center, and a military medical treatment facility.Participants560 caregivers of individuals with a documented TBI (344 civilians and 216 military)InterventionNot ApplicableMain Outcome MeasuresPROMIS Anxiety, Depression, and Anger Item BanksResultsInternal consistency for all of the PROMIS Mental Health item banks was very good (all α > .86) and three-week test retest reliability was good to adequate (ranged from .65 to .85). Convergent validity and discriminant validity of the PROMIS measures was also supported. Caregivers of individuals that were low functioning had worse emotional HRQOL (as measured by the three PROMIS measures) than caregivers of high functioning individuals, supporting known groups validity. Finally, levels of distress, as measured by the PROMIS measures, were elevated for those caring for low-functioning individuals in both samples (rates ranged from 26.2% to 43.6% for caregivers of low-functioning individuals).ConclusionsResults support the reliability and validity of the PROMIS Anxiety, Depression, and Anger item banks in caregivers of civilians and service members/veterans with TBI. Ultimately, these measures can be used to provide a standardized assessment of HRQOL as it relates to mental health in these caregivers.

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Understanding health-related quality of life in caregivers of civilians and service members/veterans with traumatic brain injury: Establishing the reliability and validity of PROMIS Fatigue and Sleep Disturbance item banks

Publication date: Available online 20 June 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Noelle E. Carlozzi, Phillip A. Ianni, David S. Tulsky, Tracey A. Brickell, Rael T. Lange, Louis M. French, David Cella, Michael A. Kallen, Jennifer A. Miner, Anna L. Kratz
ObjectiveTo examine the reliability and validity of Patient Reported Outcomes Measurement Information System (PROMIS) measures of sleep disturbance and fatigue in TBI caregivers and to determine the severity of fatigue and sleep disturbance in these caregivers.DesignCross-sectional survey data collected through an online data capture platform.SettingFour rehabilitation hospitals and Walter Reed National Military Medical Center.ParticipantsCaregivers (N=560) of civilians (n=344) and service member/veterans (n=216) with TBI.InterventionNot ApplicableMain Outcome MeasuresPROMIS sleep and fatigue measures administered as both computerized adaptive tests (CATs) and 4-item short forms (SFs).ResultsFor both samples, floor and ceiling effects for the PROMIS measures were low (<11%), internal consistency was very good (all alphas ≥0.80), and test-retest reliability was acceptable (all r≥0.70 except for the fatigue CAT in the service member/veteran sample r=0.63). Convergent validity was supported by moderate correlations between the PROMIS and related measures. Discriminant validity was supported by low correlations between PROMIS measures and measures of dissimilar constructs. PROMIS scores indicated significantly worse sleep and fatigue for those caring for someone with high levels versus low levels of impairment.ConclusionsFindings support the reliability and validity of the PROMIS CAT and SF measures of sleep disturbance and fatigue in caregivers of civilians and service members/veterans with TBI.

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What makes us human?

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Curvature of the left main bronchus caused by postural change from supine to left lateral position


This study was designed to examine deviation of the bronchus by postural change from supine to lateral position during spontaneous respiration. Fifteen healthy volunteers [13 men and 2 women, mean age: 34 years (range 26–42)] participated. Chest radiograms (anterior–posterior) were acquired in the order of supine, left lateral, and right lateral position. The bilateral bronchus angles and secondary carina angles were measured in the acquired images, and the angles were compared between the supine and lateral positions to evaluate deviation of the bronchus in the lateral position. The left secondary carina angle in the supine position was 61.3° ± 4.0° and it significantly increased to 65.5° ± 6.0° in the left lateral position (P = 0.001), but no significant difference was noted in the left bronchus angle between the supine and left lateral positions (P = 0.158). The curvature of left main bronchus, which we defined more than 5° increase in secondary carina angle, was observed in a half of the male participants during left lateral position. We should be aware of these anatomical changes due to the surgical posture as a possible cause for ventilation failure during one-lung ventilation.

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Relationship-focused vs. Structural Activities in Medical Home Measurement in Pediatrics


Objectives The Family-Centered Medical Home (FCMH) has become a model of effective and efficient primary care. However, efforts to measure the FCMH may ignore its complexity. We sought to determine whether U.S. primary care pediatricians view structure-focused and relationship-focused practice activities of the FCMH as distinct constructs and how these constructs are associated with practice functions. Methods We analyzed data from the 2012 American Academy of Pediatrics Periodic Survey of Fellows #79 (n = 572) addressing opinions and practice activities related to the FCMH. Through a modified Delphi expert process, we selected items believed to be primarily structure-focused and items that were relationship-focused. Confirmatory factor analysis was used to test whether these constructs were distinct. Separate structural equation models assessed whether structure-focused and relationship-focused activities predicted three broader survey items: (1) interest in FCMH; (2) application for FCMH recognition; and (3) whether a team meets to discuss FCMH improvements. Results The initial two-factor model did not fit well, but improved with movement of two items from the structure to the relationship-focused group. The two factors correlated at r = 0.70. Respondents with increased relationship-focused activities had statistically higher odds of having medium/high interest in FCMH, and having a team meet to discuss FCMH improvements. Respondents with increased structure-focused activities also had higher odds of having team meetings to discuss FCMH improvements, but lower odds of applying for FCMH recognition. Conclusions for Practice The FCMH is multi-dimensional, with relationship- and structure-focused activities differentially linked to pediatrician reports of broader FCMH functions.

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The Effectiveness of Resisted Sled Training (RST) for Sprint Performance: A Systematic Review and Meta-analysis



Sprinting is key in the development and final results of competitions in a range of sport disciplines, both individual (e.g., athletics) and team sports. Resisted sled training (RST) might provide an effective training method to improve sprinting, in both the acceleration and the maximum-velocity phases. However, substantial discrepancies exist in the literature regarding the influence of training status and sled load prescription in relation to the specific components of sprint performance to be developed and the phase of sprint.


Our objectives were to review the state of the current literature on intervention studies that have analyzed the effects of RST on sprint performance in both the acceleration and the maximum-velocity phases in healthy athletes and to establish which RST load characteristics produce the largest improvements in sprint performance.


We performed a literature search in PubMed, SPORTDiscus, and Web of Science up to and including 9 January 2018. Peer-reviewed studies were included if they met all the following eligibility criteria: (1) published in a scientific journal; (2) original experimental and longitudinal study; (3) participants were at least recreationally active and towed or pulled the sled while running at maximum intensity; (4) RST was one of the main training methods used; (5) studies identified the load of the sled, distance covered, and sprint time and/or sprint velocity for both baseline and post-training results; (6) sprint performance was measured using timing gates, radar gun, or stopwatch; (7) published in the English language; and (8) had a quality assessment score > 6 points.


A total of 2376 articles were found. After filtering procedures, only 13 studies were included in this meta-analysis. In the included studies, 32 RST groups and 15 control groups were analyzed for sprint time in the different phases and full sprint. Significant improvements were found between baseline and post-training in sprint performance in the acceleration phase (effect size [ES] 0.61; p = 0.0001; standardized mean difference [SMD] 0.57; 95% confidence interval [CI] − 0.85 to − 0.28) and full sprint (ES 0.36; p = 0.009; SMD 0.38; 95% CI − 0.67 to − 0.10). However, non-significant improvements were observed between pre- and post-test in sprint time in the maximum-velocity phase (ES 0.27; p = 0.25; SMD 0.18; 95% CI − 0.49 to 0.13). Furthermore, studies that included a control group found a non-significant improvement in participants in the RST group compared with the control group, independent of the analyzed phase.


RST is an effective method to improve sprint performance, specifically in the early acceleration phase. However, it cannot be said that this method is more effective than the same training without overload. The effect of RST is greatest in recreationally active or trained men who practice team sports such as football or rugby. Moreover, the intensity (load) is not a determinant of sprint performance improvement, but the recommended volume is > 160 m per session, and approximately 2680 m per week, with a training frequency of two to three times per week, for at least 6 weeks. Finally, rigid surfaces appear to enhance the effect of RST on sprint performance.

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Ultrasound-Guided Infraclavicular Brachial Plexus Block: Prospective Randomized Comparison of the Lateral Sagittal and Costoclavicular Approach

Background and Objectives It has recently been proposed that an infraclavicular brachial plexus block (BPB) at the costoclavicular (CC) space may overcome some of the limitations of the lateral sagittal (LS) approach. In this study, we hypothesized that the CC approach will produce faster onset of sensory blockade of the 4 major terminal nerves of the brachial plexus than the LS approach. Methods Forty patients undergoing elective upper extremity surgery under a BPB were randomized to receive either the LS (Gp-LS, n = 20) or CC approach (Gp-CC, n = 20) for infraclavicular BPB. Twenty-five milliliters of 0.5% ropivacaine was used for the BPB in both study groups. Sensory-motor blockade of the ipsilateral median, radial, ulnar, and musculocutaneous nerves was assessed by a blinded observer at regular intervals for 45 minutes after the block. Sensory block was assessed using a verbal rating scale (0–100) and motor block using a 3-point qualitative scale (0–2). Onset of sensory (primary outcome variable) and motor blockade was defined as the time it took to achieve a sensory verbal rating scale of 30 or less and motor grade of 1 or less, respectively. Time to readiness for surgery was defined as the time it took to achieve a sensory score of 30 or less and motor grade of 1 or less in all the 4 nerves tested. Results The overall sensory onset time (median [interquartile range]) was significantly faster (P = 0.004) in Gp-CC (10 [10–26.25] minutes) than in Gp-LS (20 [15–30] minutes). The overall sensory score was significantly lower in Gp-CC than in Gp-LS at 5 (P

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Lack of Association Between Levels and Length of Intraoperative Controlled Hypotension and Acute Kidney Injury in Total Hip Arthroplasty Patients Receiving Neuraxial Anesthesia

Background and Objectives Previous research suggests that increased duration and lower levels of intraoperative hypotension (IOH) are associated with postoperative acute kidney injury (AKI). However, this association has not been evaluated in the context of intraoperative controlled hypotension (IOCH), a practice that has been linked in the past to improved outcomes with respect to blood loss and transfusion needs. This study aimed to investigate whether IOCH is associated with postoperative AKI among total hip arthroplasty patients at an institution where this technique is commonly practiced. Methods We performed a retrospective cohort study of 2431 unilateral total hip arthroplasty patients who received IOCH under neuraxial anesthesia as well as invasive arterial monitoring between March 2016 and January 2017. Multiple logistic regression was used to compute the adjusted odds ratios of postoperative AKI, adjusting for covariates including duration of intraoperative mean arterial pressure of less than 60 mm Hg. Sensitivity analyses also considered the effects of IOH defined at mean arterial pressure of less than 55 and less than 65 mm Hg. Results Acute kidney injury occurred in 45 (1.85%) of the 2431 patients in this cohort. Longer duration of hypotension was not associated with increased odds of postoperative AKI. Preexisting differences, such as compromised renal function, best predicted increased odds of AKI. Conclusions In this study, AKI was rare. We found a lack of association between IOH and postoperative AKI in a setting where neuraxial anesthesia–facilitated IOCH is routinely practiced. Therefore, it seems prudent for future research and clinical guidelines to consider the distinction between inadvertent and controlled hypotension. Accepted for publication February 11, 2018. Address correspondence to: Stavros G. Memtsoudis, MD, PhD, FCCP, Department of Anesthesiology, Hospital for Special Surgery, 535 E 70th St, New York, NY 10021 (e-mail: memtsoudiss@hss.edu). This study was internally funded by the Department of Anesthesiology, Hospital for Special Surgery, New York, NY. J.T.Y. is coinvestigator on a project about intravenous acetaminophen for postoperative analgesia funded by Mallinckrodt and performs editorial board activity for Anesthesia & Analgesia and Regional Anesthesia and Pain Medicine. S.G.M. is a director on the boards of the American Society of Regional Anesthesia and Pain Medicine and the Society of Anesthesia and Sleep Medicine. He is a one-time consultant for Sandoz Inc. and the holder of US Patent US-2017-0361063, Multicatheter Infusion System. He is the owner of SGM Consulting, LLC and co-owner of FC Monmouth, LLC. None of the above relations influenced the conduct of the present study. S.M.W. declares no conflict of interest. Author Contributions: S.M.W. helped design the study, analyze the data, and write the manuscript. J.T.Y. helped design the study, analyze the data, and write the manuscript. S.G.M. helped design the study, analyze the data, and write the manuscript. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.rapm.org). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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A Cadaver Study Investigating Structures Encountered by the Needle During a Retroclavicular Approach to Infraclavicular Brachial Plexus Block

Background and Objectives Retroclavicular block is designed to overcome the negative aspects of the commonly utilized ultrasound-guided parasagittal approach to the infraclavicular block. However, this approach necessitates the needle traversing an area posterior to the clavicle inaccessible to ultrasound wave conduction. This study sought to document the structures vulnerable to needle injury during a retroclavicular block. Methods A Tuohy needle was inserted using a retroclavicular approach to the infraclavicular block in 3 lightly embalmed cadavers followed by a catheter insertion 4 cm beyond the needle tip. The process was repeated on the contralateral side. With the needle and catheter in position, the cadavers were dissected and photographed. Results In 4 of the 6 dissections, the needle was directly touching the suprascapular nerve deep to the clavicle. In the remaining 2 dissections, the suprascapular nerve was within 2 cm of the needle. In 1 dissection, the suprascapular vein was indented, behind the clavicle. The trapezius was the only muscle layer traversed by the needle in all dissections. In 3 of the 6 dissections, the catheter penetrated the posterior cord. In the remaining 3, the catheter threaded along the neurovascular bundle. Conclusions The suprascapular nerve is consistently in the path of the block needle posterior to the clavicle. This raises the possibility of risk of injury to the suprascapular nerve when using this approach to the brachial plexus. Vascular injury is also possible deep to the clavicle, and because of the noncompressible location, caution is advised in patients with disordered coagulation. Accepted for publication March 10, 2018. S.F.S. is now with the Department of Anesthesiology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Address correspondence to: Vishal Uppal, DA, EDRA, FRCA, Department of Anesthesia, Perioperative Medicine and Pain Management, Dalhousie University, Nova Scotia Health Authority and IWK Health Centre, Halifax, Nova Scotia, Canada B3H 2Y9 (e-mail: v.uppal@dal.ca). No external funds were obtained for the study. Internal departmental funds were used. V.U. has been a principal investigator for a Recro Pharma (Devault, PA)–funded clinical trial involving intravenous meloxicam in Halifax, Nova Scotia, Canada. This conflict does not directly or indirectly affect the conduct or reporting of this study. The authors declare no conflict of interest. Author contributions: Study design/planning: all authors; study conduct: S.F.S., V.U., R.S.; writing of the paper: S.F.S., V.U; revision of the manuscript: all authors. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.rapm.org). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Ketamine for Refractory Headache: A Retrospective Analysis

Background and Objectives The burden of chronic headache disorders in the United States is substantial. Some patients are treatment refractory. Ketamine, an N-methyl-D-aspartate antagonist, provides potent analgesia in subanesthetic doses in chronic pain, and limited data suggest it may alleviate headache in some patients. Methods We performed a retrospective study of 61 patients admitted over 3 years for 5 days of intravenous therapy that included continuous ketamine to determine responder rate and patient and ketamine infusion characteristics. Pain ratings at 2 follow-up visits were recorded. An immediate responder was a patient with decrease of 2 points or greater in the numerical rating scale (0–10) from start to final pain in the hospital. Sustained response at office visits 1 and 2 was determined based on maintaining the 2-point improvement at those visits. Patients were assessed daily for pain and adverse events (AEs). Results Forty-eight (77%) of the 61 patients were immediate responders. There were no differences regarding demographics, opioid use, or fibromyalgia between immediate responders and nonresponders. Maximum improvement occurred 4.56 days (mean) into treatment. Sustained response occurred in 40% of patients at visit 1 (mean, 38.1 days) and 39% of patients at visit 2 (mean, 101.3 days). The mean maximum ketamine rate was 65.2 ± 2.8 mg/h (0.76 mg/kg per hour). Ketamine rates did not differ between groups. Adverse events occurred equally in responders and nonresponders and were mild. Conclusions Ketamine was associated with short-term analgesia in many refractory headache patients with tolerable adverse events. A prospective study is warranted to confirm this and elucidate responder characteristics. Accepted for publication March 25, 2018. Address correspondence to: Eric S. Schwenk, MD, Department of Anesthesiology, Sidney Kimmel Medical College at Thomas Jefferson University, Suite 8130, Gibbon Bldg, 111 South 11th St, Philadelphia, PA 19107 (e-mail: Eric.Schwenk@jefferson.edu). E.S.S. has received consulting fees from Avenue Therapeutics. C.G.L. has received honoraria from Cefaly Technology. S.D.S. receives, or has received, honoraria from Alder Biopharmaceuticals; Allergan, Inc; Amgen; Avanir Pharmaceuticals, Inc; Curelator, Inc; Dr Reddy's Laboratories; eNeura Inc; electroCore Medical, LLC; Lilly USA, LLC; Medscape, LLC; NINDS; Supernus Pharmaceuticals, Inc; Teva Pharmaceuticals; Theranica; and Trigemina, Inc. W.Y. has received consulting fees from Allergan; he is on the advisory board for Amgen, Avanir, Cipla, Alder, Eli Lilly, and Supernus. He has received research support from Allergan, Amgen, Autonomic Technologies, Colucis, Cumberland, Dr Reddy's Laboratories, Eli Lilly, Novartis, PCORI, Scion, Teva, and Zosano. Eugene Viscusi has served as a consultant for AcelRx, Medicines Company, Mallinkrodt, Trevena, Cara Pharmaceuticals, Salix, AstraZeneca, and Merck. His institution has received research grants in the past from AcelRx, Adolor, Progenics, and Pacira. He has been a paid lecturer for AcelRx, Merck, Salix, and Mallinkrodt. None of these companies were involved in any aspect of the development of this manuscript. A.C.D., A.R., M.C.T., and M.G.H. declare no conflict of interest. Institutional affiliation of manuscript: Department of Anesthesiology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA. Source of funding: Departmental funding. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.rapm.org). Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Hypertonic Sodium Chloride Preinjectate Increases In Vivo Radiofrequency Ablation Size: Histological and Magnetic Resonance Imaging Findings

Background and Objectives Emphasis has been placed on methods to enlarge monopolar radiofrequency (RF) lesion size for pain management. Ex vivo research has suggested that fluid modulation may be an effective method to enlarge lesion zone. To date, these findings have not been confirmed in vivo. The purpose of this study was to determine the effect of hypertonic saline on in vivo lesion size through both histological and magnetic resonance imaging (MRI) analysis. A secondary purpose was to validate in vivo characterization of RF lesions using contrast-enhanced MRI. Methods Monopolar RF was performed in an in vivo porcine model in 3 groups: (1) without fluid preinjection, (2) with preinjection of 1% lidocaine, or (3) with preinjection of 1% lidocaine and 8% sodium chloride. Following lesioning, MRI processing with gadolinium-enhanced, T1-weighted imaging and histological analysis was performed. Results The addition of 8% sodium chloride significantly increased the size of RF lesion in comparison to the addition of 1% lidocaine alone and to the absence of fluid injection, as assessed by histological and MRI analysis. Three distinct histological lesion zones were identified. In comparison to the no-fluid group, the addition of hypertonic saline significantly altered the shape and histological composition of the lesion. There was a significant correlation of lesion volume as assessed by MRI and by histology measurements. Peak power and total energy delivery also correlated with lesion size. Conclusions This study validates the ability of hypertonic saline to increase in vivo RF lesion size. With further refinement, MRI may be a viable method to assess RF lesion size. Accepted for publication March 28, 2018. Address correspondence to: David A. Provenzano, MD, Pain Diagnostics and Interventional Care, 301 Ohio River Blvd, Suite 203, Edgeworth Medical Commons, Sewickley, PA 15143 (e-mail: davidprovenzano@hotmail.com). This study was supported by Medtronic. This study was conducted at the Medtronic Physiological Research Laboratory. Medtronic PLC provided funding for animal acquisition and supplies. No monetary compensation was provided to any of the investigators for their participation in this nonclinical research. This work was presented in part at the American Academy of Pain Medicine 33th Annual Meeting, Orlando, FL, April 2017; and the American Society of Regional Anesthesia and Pain Medicine 15th Annual Meeting, San Diego, CA, November 2016. D.A.P. is a consultant for Bioness, Boston Scientific, Halyard, Medtronic, Nevro, Sollis, and Abbott. He receives research support from Medtronic and Abbott. D.A.P. received no funding or reimbursement for his work on this project. J.T.W. is an employee of Medtronic. E.R.C. is an employee of Boston Scientific. Cosman Medical is a wholly owned subsidiary of Boston Scientific. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Is a Retrolaminar Approach to the Thoracic Paravertebral Space Possible?: A Human Cadaveric Study

Background and Objectives The retrolaminar block (RB) is used for truncal analgesia, but its mechanism of neural blockade remains obscure. We sought to learn the pattern of local anesthetic spread after thoracic RB using cadaveric models. Methods In 8 fresh cadavers, an ultrasound-guided T4 RB was performed with 20 mL of methylene blue 1% and bupivacaine 0.5%. For comparison, an RB at T9 in 1 cadaver and a T4 thoracic paravertebral block in another cadaver were performed. Subsequently, posterior and anterior thoracic dissections were performed to examination where the dye spread. Results After T4 RB, dye was noted to spread in the ipsilateral retrolaminar plane (all 8 cadavers, median cephalad spread 3.5 cm, caudad spread 10.7 cm, lateral spread 2.5 cm), the contralateral retrolaminar plane (6 cadavers), the paravertebral space (5 cadavers, median of 3 segments, T3–T5), the intercostal space (5 cadavers, median of 3.5 cm laterally), the T4 epidural space (6 cadavers), and the intervertebral foramina (4 cadavers, median of 2 segments, T4–T5). After T9 retrolaminar injection, dye was noted in the ipsilateral retrolaminar plane (5.5 cm cephalad, 13.5 cm caudad, and 2.5 cm lateral), the contralateral retrolaminar plane, and the epidural space. Dye after T4 traditional paravertebral block spread to T1–T6 paravertebral space with 15-cm lateral spread. Conclusions Injectate spread to the paravertebral space, epidural space, intercostal space, and intervertebral foramina is possible in the RB but is quite variable. In comparison to the thoracic paravertebral block, injectate spread within the paravertebral space is more limited. Accepted for publication April 23, 2018. Address correspondence to: A. Sassan Sabouri, MD, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit St, GRJ 446, Boston, MA 02114 (e-mail: asabouri@mgh.harvard.edu). This work is attributed to the Department of Anesthesiology, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA. This study was supported by DACCPM Clinical Pilot Grant (no. 1200-218309). Primary results of this study were presented at the 41st American Society of Regional Anesthesia Annual Regional Anesthesia and Acute Pain Medicine Meeting, New Orleans, LA, as a poster presentation on April 2, 2016, and final results were presented as a poster at the Department of Anesthesia, Critical Care and Pain Medicine Research Day, Massachusetts General Hospital, Boston, MA, on October 18, 2017. The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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Lipid Emulsion Pretreatment Decreased the Maximum Total and Free Plasma Concentration of Levobupivacaine for Femoral and Sciatic Nerve Block in Below-Knee Fracture Surgery

Background and Objectives Although intravenous lipid emulsion has been proved a powerful antidote for local anesthetic toxicity, there are few pharmacokinetic data on using lipid infusion as a pretreatment for other clinical applications. We assessed the influence of lipid pretreatment on the pharmacodynamics and pharmacokinetics of levobupivacaine. Methods Altogether, 12 patients undergoing below-knee surgery for a fracture were randomly assigned to 2 groups (6 patients per group): pretreatment with 1.5 mL/kg lipid infusion (lipid group) or saline infusion (control subjects) followed by complete femoral and sciatic nerve block with 0.375% levobupivacaine (2.5 mg/kg). Total and free (non–protein bound) plasma levobupivacaine concentrations and triglycerides in the lipid group were determined. Results Results were given as means ± SD. Total and free maximum plasma levobupivacaine concentrations were lower in the lipid group than in control subjects (865 ± 98 vs 1145 ± 177 μg/L and 56.8 ± 7.5 vs 78.2 ± 13.7 μg/L, respectively; P

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