UW Neurological Surgery Recent PubMed Publications

Economic evaluation in the National Drug Abuse Treatment Clinical Trials Network: Past, present, and future.

J Subst Abuse Treat. 2020 Mar;112S:18-27

Authors: Jalali A, Ryan DA, McCollister KE, Marsch LA, Schackman BR, Murphy SM

Abstract
Economic evaluations provide evidence that informs stakeholders on how to efficiently allocate real and financial healthcare resources. The purpose of this study was to review and discuss the integration of economic evaluations into the National Drug Abuse Treatment Clinical Trials Network (CTN) since its inception, as well as expectations for the future of this relationship. A systematic review was performed on published and planned CTN economic evaluations in the CTN dissemination library and PubMed. The well-established Drummond checklist was used to evaluate the comprehensiveness and methodological rigor of published articles. One hundred thirty-eight ancillary, follow-up, or original protocols were reviewed, and 78 potentially relevant published articles were identified. A total number of 14 protocols included an economic evaluation. Of these, 6 protocols were completed, 2 were reported as active, and 6 were reported as in-development at the time of this review. Of the 78 published articles, 9 met the inclusion criteria. As gauged by the Drummond checklist, the quality of CTN published economic evaluations were found to improve over time, and recent published articles were identified as guides to cutting-edge economic research. As the CTN continues to grow and mature, it is imperative that high-quality economic evaluations are incorporated alongside trials in order to maximize the public health impact of the CTN.

PMID: 32220406 [PubMed - in process]

Percutaneous cervical cordotomy for cancer-related pain: national data.

BMJ Support Palliat Care. 2020 Mar 27;:

Authors: Poolman M, Makin M, Briggs J, Scofield K, Campkin N, Williams M, Sharma ML, Laird B, Mayland CR, INPIC Group

Abstract
OBJECTIVES: Percutaneous cervical cordotomy (PCC) is an interventional ablative procedure in the armamentarium for cancer pain treatment, but there is limited evidence to support its use. This study aimed to assess the effectiveness and safety of PCC.
METHODS: Analysis was undertaken of the first national (UK) prospective data repository of adult patients with cancer undergoing PCC for pain treatment. The relationship between pain and other outcomes before and after PCC was examined using appropriate statistical methods.
RESULTS: Data on 159 patients' PCCs (performed from 1 January 2012 to 6 June 2017 in three centres) were assessed: median (IQR) age was 66 (58-71) years, 47 (30%) were female. Mesothelioma was the most common primary malignancy (57%). The median (IQR) time from cancer diagnosis to PCC assessment was 13.3 (6.2-23.2) months; PCC to follow-up was 9 (8-25) days; and survival after PCC was 1.3 (0.6-2.8) months. The mean (SD) for 'average pain' using a numerical rating scale was 6 (2) before PCC and 2 (2) at follow-up, and for 'worst pain' 9 (1) and 3 (3), respectively. The median (IQR) reduction in strong opioid dose at follow-up was 50% (34-50). With the exception of 'activity', all health-related quality of life scores (5-level version of EuroQol-5 Dimension) either improved or were stable after PCC. Six patients (4%) had PCC-related adverse events.
CONCLUSIONS: PCC is an effective treatment for cancer pain; however, findings in this study suggest PCC referrals tended to be late in patients' disease trajectories. Further study into earlier treatment and seeking international consensus on PCC outcomes will further enhance opportunities to improve patient care.

PMID: 32220943 [PubMed - as supplied by publisher]

Bilateral Squamosal Suture Craniosynostosis Presenting with Abducens Nerve Palsy and Severe Papilledema.

World Neurosurg. 2020 06;138:344-348

Authors: Cho DY, Evans KN, Weed MC, Lee A, Susarla SM

Abstract
BACKGROUND: Patients with single-suture or minor suture craniosynostosis are typically asymptomatic at early presentation; intervention is aimed at reducing the risk of elevated intracranial pressure and associated developmental sequelae. Patients may be symptomatic in cases of major multisuture syndromic synostoses or delayed diagnosis. Clinical presentation in this context may include headaches, papilledema, cognitive delay, or behavioral issues. Cranial nerve palsies are atypical symptoms of intracranial hypertension in this patient population.
CASE DESCRIPTION: An 11-month-old, otherwise healthy girl presented with bilateral severe papilledema and left abducens nerve palsy owing to nonsyndromic near-complete bilateral squamosal suture synostosis with associated incomplete sagittal and right lambdoid synostoses. The patient underwent urgent open cranial expansion, with resolution of her papilledema and improvement in eye position and motility.
CONCLUSIONS: Cranial nerve palsies may be presenting symptoms of intracranial hypertension in patients with craniosynostosis. Multidisciplinary evaluation and treatment is paramount for appropriate management.

PMID: 32217173 [PubMed - indexed for MEDLINE]

Incorporation of transradial approach in neuroendovascular procedures: defining benchmarks for rates of complications and conversion to femoral access.

J Neurointerv Surg. 2020 Nov;12(11):1122-1126

Authors: Almallouhi E, Al Kasab S, Sattur MG, Lena J, Jabbour PM, Sweid A, Chalouhi N, Gooch MR, Starke RM, Peterson EC, Yavagal DR, Chen SH, Li Y, Gross BA, Tonetti DA, Zussman BM, Stone JG, Jadhav AP, Jankowitz BT, Young CC, Lim DH, Levitt MR, Osbun JW, Spiotta AM

Abstract
BACKGROUND: The transradial approach (TRA) has gained increasing popularity for neuroendovascular procedures. However, the experience with TRA in neuroangiography is still in early stages in most centers, and the safety and feasibility of this approach have not been well established. The purpose of this study is to report the safety and feasibility of TRA for neuroendovascular procedures.
METHODS: We reviewed charts from six institutions in the USA to include consecutive patients who underwent diagnostic or interventional neuroendovascular procedures through TRA from July 2018 to July 2019. Collected data included baseline characteristics, procedural variables, complications, and whether there was a crossover to transfemoral access.
RESULTS: A total of 2203 patients were included in the study (age 56.1±15.2, 60.8% women). Of these, 1697 (77%) patients underwent diagnostic procedures and 506 (23%) underwent interventional procedures. Successfully completed procedures included aneurysm coiling (n=97), flow diversion (n=89), stent-assisted coiling (n=57), balloon-assisted coiling (n=19), and stroke thrombectomy (n=76). Crossover to femoral access was required in 114 (5.2%). There were no major complications related to the radial access site. Minor complications related to access site were seen in 14 (0.6%) patients.
CONCLUSION: In this early stage of transforming to the 'radial-first' approach for neuroendovascular procedures, TRA was safe with low complication rates for both diagnostic and interventional procedures. A wide range of procedures were completed successfully using TRA.

PMID: 32217626 [PubMed - indexed for MEDLINE]

Cytotoxic Effects of Zoom® Whitening Product in Human Fibroblasts.

Materials (Basel). 2020 Mar 25;13(7):

Authors: Marto CM, Laranjo M, Paula A, Coelho AS, Abrantes AM, Casalta-Lopes J, Gonçalves AC, Sarmento-Ribeiro AB, Ferreira MM, Cabrita A, Botelho MF, Carrilho E

Abstract
Tooth whitening procedures are increasing; however, side effects can occur, such as damage to pulp cells, by the whitening products. This study aims to assess the cellular effects promoted by a whitening product, namely, the oxidative stress fostered by the active agent hydrogen peroxide, with and without photoactivation. Additionally, if cellular recovery occurred, we intended to determine the time point where cells recover from the tooth whitening induced damage. Human fibroblasts were exposed to hydrogen peroxide, Zoom®, Zoom® + irradiation, and irradiation alone. The following analysis was performed: metabolic activity evaluation by the MTT assay; cell viability, mitochondrial membrane potential, peroxides production, superoxide radical production, and reduced glutathione expression by flow cytometry. We determined the IC50 value for all groups, and a dose-dependent cytotoxic effect was verified. At the times analyzed, hydrogen peroxide groups showed no metabolic activity recovery while a cell recovery was observed after 24 h (Zoom®) and 48 h (Zoom® + irradiation). Cell death was seen in hydrogen peroxide and Zoom® + irradiation groups, mainly by apoptosis, and the irradiation had a cytotoxic effect per se. This in vitro study supports that whitening products with moderate hydrogen peroxide (HP) concentration have a temporary effect on cells, allowing a cellular recovery.

PMID: 32218276 [PubMed - as supplied by publisher]

Aberrant cell migration contributes to defective airway epithelial repair in childhood wheeze.

JCI Insight. 2020 Mar 24;:

Authors: Iosifidis T, Sutanto EN, Buckley A, Coleman LA, Gill EE, Lee AH, Ling KM, Hillas J, Looi K, Garratt LW, Martinovich KM, Shaw NC, Montgomery ST, Kicic-Starcevich E, Karpievitch YV, Le Souef P, Laing IA, Vijayasekaran S, Lannigan FJ, Rigby PJ, Hancock RE, Knight D, Stick SM, Kicic A, Waerp OBO, AusREC OBO

Abstract
Abnormal wound repair has been observed in the airway epithelium of patients with chronic respiratory diseases including asthma. Therapies focusing on repairing vulnerable airways, particularly in early life, present an extremely novel treatment strategy. We report defective lower airway epithelial cell repair to strongly associate with common pre-school and school-aged wheezing phenotypes, characterised by aberrant migration patterns and reduced α5β1 integrin expression. Next generation sequencing identified the PI3K/Akt pathway as the top upstream transcriptional regulator of α5β1 integrin, where Akt activation enhanced repair and α5β1 integrin expression in primary cultures from children with wheeze. Conversely, inhibition of PI3K/Akt signaling in primary cultures from children without wheeze reduced α5β1 expression and attenuated repair. Importantly, the FDA-approved drug celecoxib, and its non-COX2-inhibiting analogue dimethyl-celecoxib, stimulated the PI3K/Akt-integrin α5β1 axis and restored airway epithelial repair in cells from children with wheeze. When compared with published clinical datasets the identified transcriptomic signature was also associated with viral-induced wheeze exacerbations highlighting the clinical potential of such therapy. Collectively, these results identify airway epithelial restitution via targeting the PI3K/Akt-integrin axis as a novel therapeutic avenue for childhood wheeze and asthma. We propose that the next step in the therapeutic development process should be a proof-of-concept clinical trial since relevant animal models to test the crucial underlying premise are unavailable.

PMID: 32208383 [PubMed - as supplied by publisher]

Extrusion-Based Bioprinting: Current Standards and Relevancy for Human-Sized Tissue Fabrication.

Methods Mol Biol. 2020;2140:65-92

Authors: Willson K, Ke D, Kengla C, Atala A, Murphy SV

Abstract
The field of bioengineering has long pursued the goal of fabricating large-scale tissue constructs for use both in vitro and in vivo. Recent technological advances have indicated that bioprinting will be a key technique in manufacturing these specimens. This chapter aims to provide an overview of what has been achieved to date through the use of microextrusion bioprinters and what major challenges still impede progress. Microextrusion printer configurations will be addressed along with critical design characteristics including nozzle specifications and bioink modifications. Significant challenges within the field with regard to achieving long-term cell viability and vascularization, and current research that shows promise in mitigating these challenges in the near future are discussed. While microextrusion is a broad field with many applications, this chapter aims to provide an overview of the field with a focus on its applications toward human-sized tissue constructs.

PMID: 32207106 [PubMed - in process]

Enhanced transient striatal dopamine release and reuptake in Lphn3 KO rats.

ACS Chem Neurosci. 2020 Mar 23;:

Authors: Regan SL, Cryan MT, Williams MT, Vorhees CV, Ross AE

Abstract
Latrophilin-3 (LPHN3) is an adhesion G protein coupled receptor involved in regulating neuroplasticity. Variants of LPHN3 are associated with increased risk of attention-deficit hyperactivity disorder. Data from mouse, zebrafish, Drosophila, and rat show that disruption of LPHN3 results in hyperactivity and in the Sprague-Dawley Lphn3 knock-out rat exhibit deficits in learning and memory and changes in dopamine (DA) markers in the neostriatum. To determine the effects of Lphn3 deletion on DA neurotransmission, we compared the concentration, duration, and frequency of DA transients in KO and wildtype rats using fast-scan cyclic voltammetry in brain slices. Lphn3 KO rats showed higher release of DA and the duration and inter-event time were markedly decreased compared with wildtype rats. The data demonstrate that LPHN3 plays a heretofore unrecognized role in DA signaling and may represent a new target for small molecule regulation of DA neurotransmission with translational implications.

PMID: 32203648 [PubMed - as supplied by publisher]

MetaBridge: An Integrative Multi-Omics Tool for Metabolite-Enzyme Mapping.

Curr Protoc Bioinformatics. 2020 Jun;70(1):e98

Authors: Blimkie T, Lee AH, Hancock REW

Abstract
MetaBridge is a web-based tool designed to facilitate the integration of metabolomics with other "omics" data types such as transcriptomics and proteomics. It uses data from the MetaCyc metabolic pathway database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to map metabolite compounds to directly interacting upstream or downstream enzymes in enzymatic reactions and metabolic pathways. The resulting list of enzymes can then be integrated with transcriptomics or proteomics data via protein-protein interaction networks to perform integrative multi-omics analyses. MetaBridge was developed to be intuitive and easy to use, requiring little to no prior computational experience. The protocols described here detail all steps involved in the use of MetaBridge, from preparing input data and performing metabolite mapping to utilizing the results to build a protein-protein interaction network. © 2020 by John Wiley & Sons, Inc. Basic Protocol 1: Mapping metabolite data using MetaCyc identifiers Basic Protocol 2: Mapping metabolite data using KEGG identifiers Support Protocol 1: Converting compound names to HMDB IDs Support Protocol 2: Submitting mapped genes produced by MetaBridge for protein-protein interaction (PPI) network construction.

PMID: 32199034 [PubMed - as supplied by publisher]

Inflammation in Heart Failure: JACC State-of-the-Art Review.

J Am Coll Cardiol. 2020 03 24;75(11):1324-1340

Authors: Murphy SP, Kakkar R, McCarthy CP, Januzzi JL

Abstract
It has long been observed that heart failure (HF) is associated with measures of systemic inflammation. In recent years, there have been significant advancements in our understanding of how inflammation contributes to the pathogenesis and progression of HF. However, although numerous studies have validated the association between measures of inflammation and HF severity and prognosis, clinical trials of anti-inflammatory therapies have proven mostly unsuccessful. On this backdrop emerges the yet unmet goal of targeting precise phenotypes within the syndrome of HF; if such precise definitions can be realized, and with better understanding of the roles played by specific inflammatory mediators, the expectation is that targeted anti-inflammatory therapies may improve prognosis in patients whose HF is driven by inflammatory pathobiology. Here, the authors describe mechanistic links between inflammation and HF, discuss traditional and novel inflammatory biomarkers, and summarize the latest evidence from clinical trials of anti-inflammatory therapies.

PMID: 32192660 [PubMed - indexed for MEDLINE]

Slow release oral morphine versus methadone for opioid use disorder in the fentanyl era (pRESTO): Protocol for a non-inferiority randomized clinical trial.

Contemp Clin Trials. 2020 Mar 16;:105993

Authors: Socias ME, Wood E, Dong H, Brar R, Bach P, Murphy SM, Fairbairn N

Abstract
BACKGROUND: North America is facing an unprecedented public health crisis of opioid-related morbidity and mortality, increasingly as a result of the introduction of illicitly manufactured fentanyl into the street drug market. Although the treatment of opioid use disorder (OUD) is a key element in the response to the opioid overdose epidemic, currently available pharmacotherapies (e.g., methadone, buprenorphine) may not be acceptable to or effective in all patients. Available evidence suggests that slow-release oral morphine (SROM) has similar efficacy rates as methadone with respect to promoting abstinence, and with improvements in a number of patient-reported outcomes among persons using heroin. However, little is known about the relative effectiveness and acceptability of SROM compared to methadone in the context of fentanyl use. This study aims to address this research gap.
METHODS: pRESTO is a 24-week, open-label, two arm, non-inferiority, randomized controlled trial comparing SROM versus methadone for the treatment of OUD. Participants will be 298 clinically stable, non-pregnant adults with OUD, recruited from outpatient clinics in Vancouver, Canada, where the majority of the illicit opioids are contaminated with fentanyl. The primary outcome is suppression of illicit opioid use, measured by bi-weekly urine drug screens. Secondary outcomes include: treatment retention, medication safety, overdose events, treatment satisfaction, psychological functioning, changes in drug-related problems, changes in quality of life, opioid cravings, other substance use, and cost-effectiveness.
DISCUSSION: pRESTO will be among the first studies to evaluate treatment options for individuals primarily using synthetic street opioids, providing important evidence to guide treatment strategies for this population.

PMID: 32194251 [PubMed - as supplied by publisher]

Repeated Application of Transcranial Diagnostic Ultrasound Towards the Visual Cortex Induced Illusory Visual Percepts in Healthy Participants.

Front Hum Neurosci. 2020;14:66

Authors: Schimek N, Burke-Conte Z, Abernethy J, Schimek M, Burke-Conte C, Bobola M, Stocco A, Mourad PD

Abstract
Transcranial magnetic stimulation (TMS) of the visual cortex can induce phosphenes as participants look at a visual target. So can non-diagnostic ultrasound (nDU), delivered in a transcranial fashion, while participants have closed their eyes during stimulation. Here, we sought to determine if DU, aimed at the visual cortex, could alter the perception of a visual target. We applied a randomized series of actual or sham DU, transcranially and towards the visual cortex of healthy participants while they stared at a visual target (a white crosshair on a light-blue background), with the ultrasound device placed where TMS elicited phosphenes. These participants observed percepts seven out of ten times, which consisted of extra or extensions of lines relative to the original crosshair, and additional colors, an average of 53.7 ± 2.6% of the time over the course of the experiment. Seven out of ten different participants exposed to sham-only DU observed comparable percepts, but only an average of 36.3 ± 1.9% of the time, a statistically significant difference (p < 0.00001). Moreover, on average, participants exposed to a combination of sham and actual ultrasound reported a net increase of 47.9 percentage points in the likelihood that they would report a percept by the end of the experiment. Our results are consistent with the hypothesis that a random combination of sham-only and actual DU, applied directly over the visual cortex of participants, increased the likelihood that they would observe visual effects, but not the type of effects, with that likelihood increasing over the course of the experiment. From this, we conclude that repeated exposures by DU may make the visual cortex more responsive to stimulation of their visual cortex by the visual target itself. Future studies should identify the biophysical mechanism(s) and neural pathways by which DU, in our hands and others, can generate its observed effects on brain function. These observations, consistent with other's observation of effects of DU stimulation of the human motor cortex and amygdala, as well as the FDA approved nature of DU, may lead to increased use of DU as a means of altering brain function.

PMID: 32194387 [PubMed]

CCAP regulates feeding behavior via the NPF pathway in Drosophila adults.

Proc Natl Acad Sci U S A. 2020 03 31;117(13):7401-7408

Authors: Williams MJ, Akram M, Barkauskaite D, Patil S, Kotsidou E, Kheder S, Vitale G, Filaferro M, Blemings SW, Maestri G, Hazim N, Vergoni AV, Schiöth HB

Abstract
The intake of macronutrients is crucial for the fitness of any animal and is mainly regulated by peripheral signals to the brain. How the brain receives and translates these peripheral signals or how these interactions lead to changes in feeding behavior is not well-understood. We discovered that 2 crustacean cardioactive peptide (CCAP)-expressing neurons in Drosophila adults regulate feeding behavior and metabolism. Notably, loss of CCAP, or knocking down the CCAP receptor (CCAP-R) in 2 dorsal median neurons, inhibits the release of neuropeptide F (NPF), which regulates feeding behavior. Furthermore, under starvation conditions, flies normally have an increased sensitivity to sugar; however, loss of CCAP, or CCAP-R in 2 dorsal median NPF neurons, inhibited sugar sensitivity in satiated and starved flies. Separate from its regulation of NPF signaling, the CCAP peptide also regulates triglyceride levels. Additionally, genetic and optogenetic studies demonstrate that CCAP signaling is necessary and sufficient to stimulate a reflexive feeding behavior, the proboscis extension reflex (PER), elicited when external food cues are interpreted as palatable. Dopaminergic signaling was also sufficient to induce a PER. On the other hand, although necessary, NPF neurons were not able to induce a PER. These data illustrate that the CCAP peptide is a central regulator of feeding behavior and metabolism in adult flies, and that NPF neurons have an important regulatory role within this system.

PMID: 32179671 [PubMed - indexed for MEDLINE]

In defense of the AAN position on lawful physician-hastened death.

Neurology. 2020 04 14;94(15):641-643

Authors: Russell JA, Epstein LG, Bonnie RJ, Conwit R, Graf WD, Kirschen M, Kurek JA, Larriviere DG, Pascuzzi RM, Rizzo M, Sattin JA, Simmons Z, Taylor L, Williams MA, Ethics, Law, and Humanities Committee (a joint committee of the AAN, ANA, and CNS)

PMID: 32179699 [PubMed - indexed for MEDLINE]

Metabolic and evolutionary responses of Clostridium thermocellum to genetic interventions aimed at improving ethanol production.

Biotechnol Biofuels. 2020;13:40

Authors: Holwerda EK, Olson DG, Ruppertsberger NM, Stevenson DM, Murphy SJL, Maloney MI, Lanahan AA, Amador-Noguez D, Lynd LR

Abstract
Background: Engineering efforts targeted at increasing ethanol by modifying the central fermentative metabolism of Clostridium thermocellum have been variably successful. Here, we aim to understand this variation by a multifaceted approach including genomic and transcriptomic analysis combined with chemostat cultivation and high solids cellulose fermentation. Three strain lineages comprising 16 strains total were examined. Two strain lineages in which genes involved in pathways leading to organic acids and/or sporulation had been knocked out resulted in four end-strains after adaptive laboratory evolution (ALE). A third strain lineage recapitulated mutations involving adhE that occurred spontaneously in some of the engineered strains.
Results: Contrary to lactate dehydrogenase, deleting phosphotransacetylase (pta, acetate) negatively affected steady-state biomass concentration and caused increased extracellular levels of free amino acids and pyruvate, while no increase in ethanol was detected. Adaptive laboratory evolution (ALE) improved growth and shifted elevated levels of amino acids and pyruvate towards ethanol, but not for all strain lineages. Three out of four end-strains produced ethanol at higher yield, and one did not. The occurrence of a mutation in the adhE gene, expanding its nicotinamide-cofactor compatibility, enabled two end-strains to produce more ethanol. A disruption in the hfsB hydrogenase is likely the reason why a third end-strain was able to make more ethanol. RNAseq analysis showed that the distribution of fermentation products was generally not regulated at the transcript level. At 120 g/L cellulose loadings, deletions of spo0A, ldh and pta and adaptive evolution did not negatively influence cellulose solubilization and utilization capabilities. Strains with a disruption in hfsB or a mutation in adhE produced more ethanol, isobutanol and 2,3-butanediol under these conditions and the highest isobutanol and ethanol titers reached were 5.1 and 29.9 g/L, respectively.
Conclusions: Modifications in the organic acid fermentative pathways in Clostridium thermocellum caused an increase in extracellular pyruvate and free amino acids. Adaptive laboratory evolution led to improved growth, and an increase in ethanol yield and production due a mutation in adhE or a disruption in hfsB. Strains with deletions in ldh and pta pathways and subjected to ALE demonstrated undiminished cellulolytic capabilities when cultured on high cellulose loadings.

PMID: 32175007 [PubMed]

Single pedicle advancement flap for treatment of feline stenotic nares: technique and results in five cases.

J Feline Med Surg. 2020 Mar 16;:1098612X20910539

Authors: Berns CN, Schmiedt CW, Dickerson VM, Murphy SM

Abstract
OBJECTIVES: Brachycephalic obstructive airway syndrome (BOAS) is a common cause of upper airway obstruction in dogs, but is appreciated less commonly in cats. Of the components of BOAS, stenotic nares appear to play a major role in cats. However, the axial deviation of the alar wing, a common cause of nasal obstruction in dogs, is typically not present. We report a series of brachycephalic cats with a ventral nasal obstruction resulting from redundant skin along the floor of the nares. In these cats, surgical techniques developed for dogs were felt to be suboptimal. Our aim is to describe a novel surgical procedure designed specifically to surgically correct stenotic nares in cats with an obstructive fold of skin ventral to the nostril.
METHODS: Five brachycephalic cats presenting for clinical signs of stenotic nares underwent surgical repair. In each case, a resection of the skin fold followed by a bilateral single pedicle advancement flap technique was performed. Postoperative outcomes were obtained by contacting owners by telephone.
RESULTS: All cats had positive outcomes, resulting in immediate reduction of the nasal fold and opening of the nares. Owners noted resolution of stertor and no episodes of respiratory distress. No surgical complications were reported.
CONCLUSIONS AND RELEVANCE: In brachycephalic cats, the ventral skin fold may be a significant contributor to stenotic nares, unlike dogs. Resection of the skin fold, followed by bilateral single pedicle advancement flaps is a novel technique and appeared to be successful for treating stenotic nares in this series of brachycephalic cats.

PMID: 32175790 [PubMed - as supplied by publisher]

Another version of the truth.

J Neurointerv Surg. 2020 04;12(4):335-336

Authors: Levitt M

PMID: 32161165 [PubMed - indexed for MEDLINE]

Presynaptic calcium channels: specialized control of synaptic neurotransmitter release.

Nat Rev Neurosci. 2020 04;21(4):213-229

Authors: Dolphin AC, Lee A

Abstract
Chemical synapses are heterogeneous junctions formed between neurons that are specialized for the conversion of electrical impulses into the exocytotic release of neurotransmitters. Voltage-gated Ca2+ channels play a pivotal role in this process as they are the major conduits for the Ca2+ ions that trigger the fusion of neurotransmitter-containing vesicles with the presynaptic membrane. Alterations in the intrinsic function of these channels and their positioning within the active zone can profoundly alter the timing and strength of synaptic output. Advances in optical and electron microscopic imaging, structural biology and molecular techniques have facilitated recent breakthroughs in our understanding of the properties of voltage-gated Ca2+ channels that support their presynaptic functions. Here we examine the nature of these channels, how they are trafficked to and anchored within presynaptic boutons, and the mechanisms that allow them to function optimally in shaping the flow of information through neural circuits.

PMID: 32161339 [PubMed - indexed for MEDLINE]

Telephone-delivered cognitive behavioral therapy for veterans with chronic pain following traumatic brain injury: Rationale and study protocol for a randomized controlled trial study.

Contemp Clin Trials. 2019 01;76:112-119

Authors: Hoffman JM, Ehde DM, Dikmen S, Dillworth T, Gertz K, Kincaid C, Lucas S, Temkin N, Sawyer K, Williams R

Abstract
BACKGROUND AND OBJECTIVES: Chronic pain is a highly prevalent and potentially disabling condition in Veterans who have had a traumatic brain injury (TBI) and access to non-pharmacological pain treatments such as cognitive behavioral therapy is limited and variable. The purpose of this randomized controlled trial (RCT) is to evaluate the efficacy of a telephone-delivered cognitive behavioral therapy (T-CBT) for pain in Veterans with a history of TBI.
METHODS: Veterans with a history of TBI and chronic pain of at least six months duration (N = 160) will be randomized to either T-CBT or a telephone-delivered pain psychoeducational active control condition (T-Ed). The eight-week T-CBT intervention builds on other efficacious CBT interventions for chronic pain in the general population but is novel in that it is conducted via telephone and adapted for Veterans with a history of TBI. Outcome variables will be collected pre, mid-, and post-treatment, and 6 months following randomization (follow-up).
PROJECTED OUTCOMES: In addition to evaluating the effects of the interventions on pain intensity (primary outcome), this study will determine their effects on pain interference, sleep, depression, and life satisfaction. We will also examine potential moderators of treatment outcomes such as cognition, PTSD, and alcohol and drug use. This non-pharmacologic one-on-one therapeutic intervention has the potential to reduce pain and pain-related dysfunction, improve access to care, and reduce barriers associated with geography, finances, and stigma, without the negative effects on physical and cognitive performance and potential for addiction as seen with some pharmacologic treatments for pain. This trial is registered at ClinicalTrials.gov, protocol NCT01768650.

PMID: 30553077 [PubMed - indexed for MEDLINE]

Diurnal variation in autonomic regulation among patients with genotyped Rett syndrome.

J Med Genet. 2020 Mar 10;:

Authors: Carroll MS, Ramirez JM, Weese-Mayer DE

Abstract
BACKGROUND: Rett syndrome is a severe neurological disorder with a range of disabling autonomic and respiratory symptoms and resulting predominantly from variants in the methyl-CpG binding protein 2 gene on the long arm of the X-chromosome. As basic research begins to suggest potential treatments, sensitive measures of the dynamic phenotype are needed to evaluate the results of these research efforts. Here we test the hypothesis that the physiological fingerprint of Rett syndrome in a naturalistic environment differs from that of controls, and differs among genotypes within Rett syndrome.
METHODS: A comprehensive array of heart rate variability, cardiorespiratory coupling and cardiac repolarisation measures were evaluated from an existing database of overnight and daytime inhome ambulatory recordings in 47 cases and matched controls.
RESULTS: Differences between girls with Rett syndrome and matched controls were apparent in a range of autonomic measures, and suggest a shift towards sympathetic activation and/or parasympathetic inactivation. Daily temporal trends analysed in the context of circadian rhythms reveal alterations in amplitude and phase of diurnal patterns of autonomic balance. Further analysis by genotype class confirms a graded presentation of the Rett syndrome phenotype such that patients with early truncating mutations were most different from controls, while late truncating and missense mutations were least different from controls.
CONCLUSIONS: Comprehensive autonomic measures from extensive inhome physiological measurements can detect subtle variations in the phenotype of girls with Rett syndrome, suggesting these techniques are suitable for guiding novel therapies.

PMID: 32156713 [PubMed - as supplied by publisher]