UW Neurological Surgery Recent PubMed Publications

Characterization of Motor and Non-Motor Behavioral Alterations in the Dj-1 (PARK7) Knockout Rat.

J Mol Neurosci. 2019 Oct;69(2):298-311

Authors: Kyser TL, Dourson AJ, McGuire JL, Hemmerle AM, Williams MT, Seroogy KB

Abstract
Parkinson's disease is a neurodegenerative disorder that encompasses a constellation of motor and non-motor symptoms. The etiology of the disease is still poorly understood because of complex interactions between environmental and genetic risk factors. Using animal models to assess these risk factors may lead to a better understanding of disease manifestation. In this study, we assessed the Dj-1 knockout (KO) genetic rat model in a battery of motor and non-motor behaviors. We tested the Dj-1 KO rat, as well as age-matched wild-type (WT) control rats, in several sensorimotor tests at 2, 4, 7, and 13 months of age. The Dj-1-deficient rats were found to rear and groom less, and to have a shorter stride length than their WT counterparts, but to take more forelimb and hindlimb steps. In non-motor behavioral tasks, performed at several different ages, we evaluated the following: olfactory function, anxiety-like behavior, short-term memory, anhedonia, and stress coping behavior. Non-motor testing was conducted as early as 4.5 months and as late as 17 months of age. We found that Dj-1 KO animals displayed deficits in short-term spatial memory as early as 4.5 months of age during place preference testing, as well as impaired coping strategies in the forced swim test, which are consistent with a parkinsonian-like phenotype. In some instances, effects of chronic stress were evaluated in the Dj-1-deficient rats, as an initial test of an environmental challenge combined with a genetic disposition for PD. Although some of the results were mixed with differential effects across several of the behaviors, the combination of the changes we observed indicates that the Dj-1 KO rat may be a promising model for the assessment of the prodromal stage of Parkinson's disease, but further evaluation is necessary.

PMID: 31250274 [PubMed - indexed for MEDLINE]

Advocacy in pediatric neurosurgery: results from a 2017 survey of the American Society of Pediatric Neurosurgeons.

J Neurosurg Pediatr. 2019 Jun 28;:1-5

Authors: LoPresti M, Lam S, Orrico K, Browd SR, Ellenbogen RG, Martin J

Abstract
OBJECTIVE: Pediatric neurosurgeons are unswerving advocates for public health-related issues in children, with most providers participating in local, regional, national, or international efforts. Collective advocacy efforts by organized pediatric neurosurgeons have not been undertaken to date.
METHODS: A 10-item survey was administered to members of the American Society of Pediatric Neurosurgeons (ASPN) in order to evaluate attitudes and opinions regarding the development of a formal advocacy effort by the organization.
RESULTS: Seventy-nine of 178 registered members of the ASPN (44.38%) participated in the survey. Participants were 82.61% male, with age, stage of career, and practice type varied. Although there was unequivocal support for participation in organized advocacy, respondents were divided on methods and topics for advocacy. In this survey, the ASPN membership prioritized public health and clinical issues over economic issues that affected children.
CONCLUSIONS: Most respondents favored the drafting of position statements on key issues and partnerships with larger organizations to pursue an advocacy agenda. The survey provides data regarding pediatric neurosurgeons' attitudes that may assist with the design of a successful advocacy program.

PMID: 31252384 [PubMed - as supplied by publisher]

Acellular Dermal Matrix as a Definitive Reconstructive Option for Management of a Large Myelomeningocele Defect in the Setting of Severe Lumbar Kyphosis.

World Neurosurg. 2019 Sep;129:363-366

Authors: Susarla SM, Hauptman J, Ettinger R, Sittler B, Ellenbogen RG

Abstract
BACKGROUND: Severe kyphosis is infrequently seen in neonates with myelomeningoceles. Spinal skeletal dysmorphology complicates repair, as local tissue may be insufficient to cover the dural repair. Although neonatal kyphectomy has been proposed as a potential solution to this problem, it carries significant potential risks that may not be acceptable to families.
CASE DESCRIPTION: A neonate presented with a large myelomeningocele defect with associated severe lumbar kyphosis. Kyphectomy was both declined by the family owing to the potential surgical risks and deemed not appropriate by the surgeons based on the challenging anatomic considerations. Soft tissue closure was not possible with local tissue rearrangement. Acellular dermal matrix was used as a definitive soft tissue coverage option, with complete epithelialization noted at 8 weeks postoperatively.
CONCLUSIONS: Acellular dermal matrix is a potentially useful adjunct for definitive reconstruction of complex neonatal soft tissue defects where local tissue is not available.

PMID: 31247357 [PubMed - indexed for MEDLINE]

Clinical outcomes and cost-effectiveness analysis for the treatment of basilar tip aneurysms.

J Neurointerv Surg. 2019 Dec;11(12):1210-1215

Authors: Abecassis IJ, Sen R, Kelly CM, Levy S, Barber J, Ghodke B, Levitt M, Kim LJ, Sekhar LN

Abstract
BACKGROUND: Endovascular treatment of basilar tip aneurysms is less invasive than microsurgical clipping, but requires closer follow-up.
OBJECTIVE: To characterize the additional costs associated with endovascular treatment of basilar tip aneurysms rather than microsurgical clipping.
MATERIALS AND METHODS: We obtained clinical records and billing information for 141 basilar tip aneurysms treated with clip ligation (n=48) or endovascular embolization (n=93). Costs included direct and indirect costs associated with index hospitalization, as well as re-treatments, follow-up visits, imaging studies, rehabilitation, and disability. Effectiveness of treatment was quantified by converting functional outcomes (modified Rankin Scale (mRS) score) into quality-adjusted life-years (QALYs). Cost-effectiveness was performed using cost/QALY ratios.
RESULTS: Average index hospitalization costs were significantly higher for patients with unruptured aneurysms treated with clip ligation ($71 400 ± $47 100) compared with coil embolization ($33 500 ± $22 600), balloon-assisted coiling ($26 200 ± $11 600), and stent-assisted coiling ($38 500 ± $20 900). Multivariate predictors for higher index hospitalization cost included vasospasm requiring endovascular intervention, placement of a ventriculoperitoneal shunt, longer length of stay, larger aneurysm neck and width, higher Hunt-Hess grade, and treatment-associated complications. At 1 year, endovascular treatment was associated with lower cost/QALY than clip ligation in unruptured aneurysms ($52 000/QALY vs $137 000/QALY, respectively, p=0.006), but comparable rates in ruptured aneurysms ($193 000/QALY vs $233 000/QALY, p=0.277). Multivariate predictors for higher cost/QALY included worse mRS score at discharge, procedural complications, and larger aneurysm width.
CONCLUSIONS: Coil embolization of basilar tip aneurysms is associated with a lower cost/QALY. This effect is sustained during follow-up. Clinical condition at discharge is the most significant predictor of overall cost/QALY at 1 year.

PMID: 31239332 [PubMed - indexed for MEDLINE]

Sex Differences in Patient Characteristics, Treatment Strategies, and Outcomes for Type 2 Myocardial Infarction.

J Am Coll Cardiol. 2019 06 25;73(24):3230-3232

Authors: McCarthy CP, Murphy S, Cohen JA, Rehman S, Jones-O'Connor M, Olshan DS, Singh A, Vaduganathan M, Januzzi JL, Wasfy JH

PMID: 31221266 [PubMed - indexed for MEDLINE]

Effects of interleukin-6 receptor blockade on allergen-induced airway responses in mild asthmatics.

Clin Transl Immunology. 2019;8(6):e1044

Authors: Revez JA, Bain LM, Watson RM, Towers M, Collins T, Killian KJ, O'Byrne PM, Gauvreau GM, Upham JW, Ferreira MA

Abstract
Background: Interleukin (IL)-6 signalling has been implicated in allergic asthma by animal, genetic association and clinical studies. In this study, we tested the hypothesis that tocilizumab (TCZ), a human monoclonal antibody that blocks IL-6 signalling, can prevent the development of allergen-induced bronchoconstriction in humans.
Methods: We performed a randomised, double-blind, placebo-controlled study, with eligible participants completing two allergen inhalation challenge tests, conducted before and after treatment with a single dose of TCZ or placebo. The primary efficacy endpoint was the magnitude of the late asthmatic response recorded between 3 and 7 after allergen challenge. The secondary efficacy endpoint was the early asthmatic response, measured 20 min to 2 h after allergen challenge.
Results: A total of 66 patients enrolled between September 2014 and August 2017, when the trial was stopped for futility based on results from an interim analysis. Eleven patients fulfilled all eligibility criteria assessed at baseline and were subsequently randomised to the TCZ (n = 6) or placebo (n = 5) groups. Both the primary and secondary efficacy endpoints were not significantly different between the two groups. Five patients reported adverse events (AEs), three in the TCZ group (11 AEs) and two in the placebo group (four AEs). Only one AE was TCZ-related (mild neutropenia), and there were no serious AEs. Significant treatment effects were observed for serum levels of C-reactive protein, IL-6 and soluble IL-6R levels.
Conclusion: In a small proof-of-concept clinical trial, we found no evidence that a single dose of tocilizumab was able to prevent allergen-induced bronchoconstriction. (Trial registered in the Australian New Zealand Clinical Trials Registry, number ACTRN12614000123640).

PMID: 31223480 [PubMed]

Bow Hunter's Syndrome: Complete Microsurgical Decompression of Vertebral Artery by Far Lateral Retrocondylar Approach: 3-Dimensional Operative Video.

Oper Neurosurg (Hagerstown). 2019 Jun 21;:

Authors: Zeeshan Q, Hernandez JPC, Sekhar LN

Abstract
This 50-yr-old man had a 15-yr history of presyncopal episodes that were precipitated by turning his head to the right, and had worsened recently. Cerebral angiogram demonstrated complete cessation of anterograde flow in left vertebral artery (VA) at the level of the C1 sulcus arteriosus while turning head to right, indicating dynamic compression at the C1 level.  Patient underwent left extreme lateral retrocondylar approach, partial C1 laminectomy and opening of the C1 foramen with complete microsurgical decompression of the VA. After skin incision, meticulous muscle dissection was performed and superior and inferior oblique muscles were disconnected from the tubercle of C1. The VA was exposed, and three areas of constriction were visible, first at the atlanto-occipital membrane laterally; second, located more medially as the artery curved around the occipital condyle to enter the posterior fossa; and third, located anterior to C2 nerve root. The artery was dissected from all the surrounding tissues, preserving the C2 nerve root, and the Cl foramen was opened completely. The Cl lamina was also partially resected and grooved to allow free placement of the VA. The VA was also decompressed near the C2 foramen. Postoperative computed tomography angiogram of the head and neck showed complete decompression of VA. The patient had no episodes of presyncope or dizziness while turning head to right and his mRs was 0 at 8 mo follow up.  This 3D video shows the technical nuances of decompression of V3 segment of VA in bow hunters's syndrome.  Informed consent was obtained from the patient prior to the surgery that included videotaping of the procedure and its distribution for educational purposes. All relevant patient identifiers have also been removed from the video and accompanying radiology slides.

PMID: 31225628 [PubMed - as supplied by publisher]

Just the tonic! Legume biorefining for alcohol has the potential to reduce Europe's protein deficit and mitigate climate change.

Environ Int. 2019 09;130:104870

Authors: Lienhardt T, Black K, Saget S, Costa MP, Chadwick D, Rees RM, Williams M, Spillane C, Iannetta PM, Walker G, Styles D

Abstract
Industrialised agriculture is heavily reliant upon synthetic nitrogen fertilisers and imported protein feeds, posing environmental and food security challenges. Increasing the cultivation of leguminous crops that biologically fix nitrogen and provide high protein feed and food could help to address these challenges. We report on the innovative use of an important leguminous crop, pea (Pisum sativum L.), as a source of starch for alcohol (gin) production, yielding protein-rich animal feed as a co-product. We undertook life cycle assessment (LCA) to compare the environmental footprint of 1 L of packaged gin produced from either 1.43 kg of wheat grain or 2.42 kg of peas via fermentation and distillation into neutral spirit. Allocated environmental footprints for pea-gin were smaller than for wheat-gin across 12 of 14 environmental impact categories considered. Global warming, resource depletion, human toxicity, acidification and terrestrial eutrophication footprints were, respectively, 12%, 15%, 15%, 48% and 68% smaller, but direct land occupation was 112% greater, for pea-gin versus wheat-gin. Expansion of LCA boundaries indicated that co-products arising from the production of 1 L of wheat- or pea-gin could substitute up to 0.33 or 0.66 kg soybean animal feed, respectively, mitigating considerable greenhouse gas emissions associated with land clearing, cultivation, processing and transport of such feed. For pea-gin, this mitigation effect exceeds emissions from gin production and packaging, so that each L of bottled pea gin avoids 2.2 kg CO2 eq. There is great potential to scale the use of legume starches in production of alcoholic beverages and biofuels, reducing dependence on Latin American soybean associated with deforestation and offering considerable global mitigation potential in terms of climate change and nutrient leakage - estimated at circa 439 Tg CO2 eq. and 8.45 Tg N eq. annually.

PMID: 31226560 [PubMed - indexed for MEDLINE]

Infection-induced endothelial amyloids impair memory.

FASEB J. 2019 09;33(9):10300-10314

Authors: Balczon R, Pittet JF, Wagener BM, Moser SA, Voth S, Vorhees CV, Williams MT, Bridges JP, Alvarez DF, Koloteva A, Xu Y, Zha XM, Audia JP, Stevens T, Lin MT

Abstract
Patients with nosocomial pneumonia exhibit elevated levels of neurotoxic amyloid and tau proteins in the cerebrospinal fluid (CSF). In vitro studies indicate that pulmonary endothelium infected with clinical isolates of either Pseudomonas aeruginosa, Klebsiella pneumoniae, or Staphylococcus aureus produces and releases cytotoxic amyloid and tau proteins. However, the effects of the pulmonary endothelium-derived amyloid and tau proteins on brain function have not been elucidated. Here, we show that P. aeruginosa infection elicits accumulation of detergent insoluble tau protein in the mouse brain and inhibits synaptic plasticity. Mice receiving endothelium-derived amyloid and tau proteins via intracerebroventricular injection exhibit a learning and memory deficit in object recognition, fear conditioning, and Morris water maze studies. We compared endothelial supernatants obtained after the endothelia were infected with P. aeruginosa possessing an intact [P. aeruginosa isolated from patient 103 (PA103) supernatant] or defective [mutant strain of P. aeruginosa lacking a functional type 3 secretion system needle tip complex (ΔPcrV) supernatant] type 3 secretion system. Whereas the PA103 supernatant impaired working memory, the ΔPcrV supernatant had no effect. Immunodepleting amyloid or tau proteins from the PA103 supernatant with the A11 or T22 antibodies, respectively, overtly rescued working memory. Recordings from hippocampal slices treated with endothelial supernatants or CSF from patients with or without nosocomial pneumonia indicated that endothelium-derived neurotoxins disrupted the postsynaptic synaptic response. Taken together, these results establish a plausible mechanism for the neurologic sequelae consequent to nosocomial bacterial pneumonia.-Balczon, R., Pittet, J.-F., Wagener, B. M., Moser, S. A., Voth, S., Vorhees, C. V., Williams, M. T., Bridges, J. P., Alvarez, D. F., Koloteva, A., Xu, Y., Zha, X.-M., Audia, J. P., Stevens, T., Lin, M. T. Infection-induced endothelial amyloids impair memory.

PMID: 31211919 [PubMed - indexed for MEDLINE]

Integration of screening, assessment, and treatment for cannabis and other drug use disorders in primary care: An evaluation in three pilot sites.

Drug Alcohol Depend. 2019 08 01;201:134-141

Authors: Richards JE, Bobb JF, Lee AK, Lapham GT, Williams EC, Glass JE, Ludman EJ, Achtmeyer C, Caldeiro RM, Oliver M, Bradley KA

Abstract
BACKGROUND: This pilot study evaluated whether use of evidence-based implementation strategies to integrate care for cannabis and other drug use into primary care (PC) as part of Behavioral Health Integration (BHI) increased diagnosis and treatment of substance use disorders (SUDs).
METHODS: Patients who visited the three pilot PC sites were eligible. Implementation strategies included practice coaching, electronic health record decision support, and performance feedback (3/2015-4/2016). BHI introduced annual screening for past-year cannabis and other drug use, a Symptom Checklist for DSM-5 SUDs, and shared decision-making about treatment options. Main analyses tested whether the proportions of PC patients diagnosed with, and treated for, new cannabis or other drug use disorders (CUDs and DUDs, respectively), differed significantly pre- and post-implementation.
RESULTS: Of 39,599 eligible patients, 57% and 59% were screened for cannabis and other drug use, respectively. Among PC patients reporting daily cannabis use (2%) or any drug use (1%), 51% and 37%, respectively, completed an SUD Symptom Checklist. The proportion of PC patients with newly diagnosed CUD increased significantly post-implementation (5 v 17 per 10,000 patients, p < 0.0001), but not other DUDs (10 vs 13 per 10,000, p = 0.24). The proportion treated for newly diagnosed CUDs did not increase post-implementation (1 vs 1 per 10,000, p = 0.80), but did for those treated for newly diagnosed other DUDs (1 vs 3 per 10,000, p = 0.038).
CONCLUSIONS: A pilot implementation of BHI to increase routine screening and assessment for SUDs was associated with increased new CUD diagnoses and a small increase in treatment of new other DUDs.

PMID: 31212213 [PubMed - indexed for MEDLINE]

Learning and Memory Effects of Neonatal Methamphetamine Exposure in Sprague-Dawley Rats: Test of the Role of Dopamine Receptors D1 in Mediating the Long-Term Effects.

Dev Neurosci. 2019;41(1-2):44-55

Authors: Jablonski SA, Williams MT, Vorhees CV

Abstract
Methamphetamine (MA) abuse is a worldwide issue that produces health and cognitive effects in the user. MA is abused by some women who then become pregnant and expose their developing child to the drug. Preclinical rodent models demonstrate cognitive deficits following developmental MA exposure, an effect observed in children exposed to MA in utero. To determine if the dopamine receptor D1 (DRD1) is involved in the learning and memory deficits following MA exposure, male Sprague-Dawley rats were treated 4 times daily at 2 h intervals with 0 (saline) or 10 mg/kg of MA from postnatal day (P)6-15, 30 min after 0.5, 1.0, or 2.0 mg/kg SCH23390. Cincinnati water maze testing began on P30, and the high dose of SCH23390 blocked the learning deficits induced by MA with no effect from the lower doses. Morris water maze (MWM) learning deficits following MA were not protected by SCH23390, although there was a non-dose dependent effect in the acquisition phase. Locomotor deficits induced by MA were reversed by all doses of SCH23390. There were no effects of MA on criterion to trial passive avoidance. Taken together, these data show that behaviors that are dependent on the striatum are better protected with the DRD1 antagonist during MA treatment than the hippocampally mediated spatial learning in the MWM. This suggests that multiple mechanisms exist for the deficits induced by neonatal MA administration.

PMID: 31212274 [PubMed - indexed for MEDLINE]

Enhanced Perioperative Care for Major Spine Surgery.

Spine (Phila Pa 1976). 2019 Jul 01;44(13):959-966

Authors: Dagal A, Bellabarba C, Bransford R, Zhang F, Chesnut RM, O'Keefe GE, Wright DR, Dellit TH, Painter I, Souter MJ

Abstract
STUDY DESIGN: The enhanced perioperative care (EPOC) program is an institutional quality improvement initiative. We used a historically controlled study design to evaluate patients who underwent major spine surgery before and after the implementation of the EPOC program.
OBJECTIVE: To determine whether multidisciplinary EPOC program was associated with an improvement in clinical and financial outcomes for elective adult major spine surgery patients.
SUMMARY OF BACKGROUND DATA: The enhanced recovery after surgery (ERAS) programs successfully implemented in hip and knee replacement surgeries, and improved clinical outcomes and patient satisfaction.
METHODS: We compared 183 subjects in traditional care (TRDC) group to 267 intervention period (EPOC) in a single academic quaternary spine surgery referral center. One hundred eight subjects in no pathway (NOPW) care group was also examined to exclude if the observed changes between the EPOC and TRDC groups might be due to concurrent changes in practice or population over the same time period. Our primary outcome variables were hospital and intensive care unit lengths of stay and the secondary outcomes were postoperative complications, 30-day hospital readmission and cost.
RESULTS: In this highly complex patient population, we observed a reduction in mean hospital length of stay (HLOS) between TRDC versus EPOC groups (8.2 vs. 6.1 d, standard deviation [SD] = 6.3 vs. 3.6, P < 0.001) and intensive care unit length of stay (ILOS) (3.1 vs. 1.9 d, SD = 4.7 vs. 1.4, P = 0.01). The number (rate) of postoperative intensive care unit (ICU) admissions was higher for the TRDC n = 109 (60%) than the EPOC n = 129 (48%) (P = 0.02). There was no difference in postoperative complications and 30-day hospital readmissions. The EPOC spine program was associated with significant average cost reduction-$62,429 to $53,355 (P < 0.00).
CONCLUSION: The EPOC program has made a clinically relevant contribution to institutional efforts to improve patient outcomes and value. We observed a reduction in HLOS, ILOS, costs, and variability.
LEVEL OF EVIDENCE: 3.

PMID: 31205177 [PubMed - indexed for MEDLINE]

Brain Bypass Surgery for Complex Middle Cerebral Artery Aneurysms: Evolving Techniques, Results, and Lessons Learned.

World Neurosurg. 2019 Oct;130:e272-e293

Authors: Natarajan SK, Zeeshan Q, Ghodke BV, Sekhar LN

Abstract
OBJECTIVE: To analyze a consecutive series of patients with middle cerebral artery (MCA) aneurysms who needed an adjunctive cerebral revascularization procedure to achieve aneurysm occlusion with preservation of flow through all MCA branches.
METHODS: A total of 42 patients with 43 MCA aneurysms underwent 52 bypass procedures over 13 years. The location of the aneurysm were M1 trunk, M1 bifurcation, M2 and beyond. The bypasses performed included intracranial bypasses (resection with end to end anastomosis, end to side implantation, side to side anastomosis, and short interposition graft), extraintracranial bypasses (superficial temporal to middle cerebral artery anastomosis, and radial artery bypass graft, or saphenous vein graft), double bypasses, Y-grafts, and combined techniques.
RESULTS: Forty-two of 43 aneurysms (98%) had patent bypasses at long-term follow-up. All 43 aneurysms were completely occluded at last follow-up. Six patients (14%) developed strokes related to the surgical treatment. At last follow-up, 36 patients had a modified Rankin score of 0-2, 5 patients had modified Rankin score 3-5, and 1 died. In this series, 31 (73.8%) patients improved, 8 (19%) patients had same functional status, and 3 (7.2%) patients deteriorated, including 1 patient who expired due to sepsis. The mean clinical follow-up duration was 39.3 months (0.4-124 months) and the mean radiological follow-up was 37 months (0.4-134 months).
CONCLUSIONS: Cerebral revascularization is an important adjunct for treating MCA aneurysms and can be done safely. The article provides the insights we gained by rising through the learning curve.

PMID: 31207370 [PubMed - indexed for MEDLINE]

Keeping carbon dioxide in check.

Elife. 2017 05 17;6:

Authors: Garcia AJ, Ramirez JM

Abstract
The response of the brainstem to increased levels of carbon dioxide in the blood is coordinated with the response of the cardiovascular system.

PMID: 28513432 [PubMed - indexed for MEDLINE]

Physiotherapists implicitly evaluate bending and lifting with a round back as dangerous.

Musculoskelet Sci Pract. 2019 02;39:107-114

Authors: Caneiro JP, O'Sullivan P, Smith A, Ovrebekk IR, Tozer L, Williams M, Teng MLW, Lipp OV

Abstract
BACKGROUND: Beliefs can be assessed using explicit measures (e.g. questionnaires) that rely on information of which the person is 'aware' and willing to disclose. Conversely, implicit measures evaluate beliefs using computer-based tasks that allow reduced time for introspection thus reflecting 'automatic' associations. Thus far, physiotherapists' beliefs about back posture and safety have not been evaluated with implicit measures.
OBJECTIVES: (1) Evaluate implicit associations between bending lifting back posture (straight-back vs round-back) and safety (safe vs danger); (2) Explore correlations between implicit and explicit measures of beliefs towards vulnerability of the back.
DESIGN: Exploratory cross-sectional quantitative study.
METHODS: 47 musculoskeletal physiotherapists completed explicit measures of fear of movement (TSK-HC), back beliefs (BackPAQDanger) and beliefs related to bending and lifting back posture and safety (BSB). An Implicit Association Test (IAT) was used to assess implicit associations between (i) images of people bending/lifting with a 'round-back' or with a 'straight-back' posture, and (ii) words representing 'safety' and 'danger'. A one-sample t-test assessed the degree and direction of the sample's IAT score. Cohen's d provided an effect size of the estimated bias. Correlation between IAT and each explicit measure was assessed using Pearson's coefficient.
RESULTS: The sample displayed an implicit association between 'round-back' and 'danger' (μ = 0.213, 95% CI [0.075-0.350], p = .003), with an effect size magnitude of 0.45. There were fair to moderate correlations between IAT and BSB (r = 0.320, 95% CI [0.036-0.556], p = .029) and, IAT and BackPAQDanger (r = 0.413, 95%CI [0.143-0.626], p = .004).
CONCLUSIONS: Physiotherapists displayed an implicit bias towards bending and lifting with a round-back as dangerous.

PMID: 30553986 [PubMed - indexed for MEDLINE]

Knockout of latrophilin-3 in Sprague-Dawley rats causes hyperactivity, hyper-reactivity, under-response to amphetamine, and disrupted dopamine markers.

Neurobiol Dis. 2019 10;130:104494

Authors: Regan SL, Hufgard JR, Pitzer EM, Sugimoto C, Hu YC, Williams MT, Vorhees CV

Abstract
Attention deficit hyperactivity disorder is a pervasive developmental disorder characterized by inattention, impulsivity, and hyperactivity and is 75-90% heritable. Latrophilin-3 (LPHN3; or ADGRL(3)) is associated with a subtype of ADHD, but how it translates to symptoms is unknown. LPHN3 is a synaptic adhesion G protein coupled receptor that binds to fibronectin leucine rich transmembrane protein 3 and teneurin-3 (FLRT3 and TEN-3). We created a null mutation of Lphn3 (KO) in Sprague-Dawley rats using CRISPR/Cas9 to delete exon-3. The KO rats had no effects on reproduction or survival but reduced growth. KO females showed catch-up weight gain whereas KO males did not. We tested WT and KO littermates for home-cage activity, anxiety-like behavior, acoustic startle response, and activity after amphetamine challenge. Expression of Lphn3-related genes, monoamines, and receptors were determined. Lphn3 KO rats showed persistent hyperactivity, increased acoustic startle, reduced activity in response to amphetamine relative to baseline, and female-specific reduced anxiety-like behavior. Expression of Lphn1, Lphn2, and Flrt3 by qPCR and their protein products by western-blot analysis showed no compensatory upregulation. Striatal tyrosine hydroxylase, aromatic L-amino acid decarboxylase (AADC), and the dopamine transporter were increased and dopamine D1 receptor (DRD1) and dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) decreased with no changes in DRD2, DRD4, vesicular monoamine transporter-2, N-methyl-d-aspartate (NMDA)-NR1, -NR2A, or -NR2B. LPHN3 is expressed in many brain regions but its function is largely unknown. Data from human, mouse, zebrafish, Drosophila and our new Lphn3 KO rat data collectively show that its disruption is significantly correlated with hyperactivity and associated striatal changes in dopamine markers.

PMID: 31176715 [PubMed - indexed for MEDLINE]

Synthetic Calcium Phosphate Ceramics as a Potential Treatment for Bisphosphonate-Related Osteonecrosis of the Jaw.

Materials (Basel). 2019 Jun 06;12(11):

Authors: Paulo S, Laranjo M, Abrantes AM, Casalta-Lopes J, Santos K, Gonçalves AC, Paula AB, Marto CM, Sarmento-Ribeiro AB, Carrilho E, Serra A, Botelho MF, Ferreira MM

Abstract
(1) Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is one of the most often seen side effects in patients treated with nitrogen-containing bisphosphonates (BPs), a post-surgical non-healing wound condition. Since calcium phosphate (CP) compounds are able to adsorb zoledronate (ZOL) when used as a drug delivery vehicle, we aimed to verify if these ceramics might have a potential protective effect for soft tissues surrounding surgical osseous wounds. (2) Methods: The chemical reaction between ZOL and CP compounds was evaluated through ultraviolet-visible spectroscopy and elemental analysis. A primary culture of human gingival fibroblasts (HGF) was established as a model to evaluate the cytotoxicity of the association of ZOL (5-500 μM) and of ZOL/biphasic calcium phosphates (BCP). Metabolic activity, cell viability, types of cell death, the cell cycle through, and the migration ability of human gingival fibroblasts were evaluated. (3) Results: ZOL was adsorbed by biphasic calcium phosphate compounds in an aqueous solution. The HGF were sensitive to ZOL toxicity; nevertheless, ZOL/BCP showed a significant protective effect regarding metabolic activity, cell viability, and cell migration. (4) Conclusions: BCP interaction with ZOL reduces or abolishes its toxicity in HGF. This finding represents a potential solution for BRONJ in the case of patients undergoing therapy with ZOL.

PMID: 31174333 [PubMed]

Carotid Plaque Inflammation Imaged by 18F-Fluorodeoxyglucose Positron Emission Tomography and Risk of Early Recurrent Stroke.

Stroke. 2019 07;50(7):1766-1773

Authors: Kelly PJ, Camps-Renom P, Giannotti N, Martí-Fàbregas J, Murphy S, McNulty J, Barry M, Barry P, Calvet D, Coutts SB, Cronin S, Delgado-Mederos R, Dolan E, Fernández-León A, Foley S, Harbison J, Horgan G, Kavanagh E, Marnane M, McDonnell C, O'Donohoe M, Sharma V, Walsh C, Williams D, O'Connell M

Abstract
Background and Purpose- Plaque inflammation contributes to stroke and coronary events. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) identifies plaque inflammation-related metabolism. Almost no prospective data exist on the relationship of carotid 18F-FDG uptake and early recurrent stroke. Methods- We did a multicenter prospective cohort study BIOVASC (Biomarkers/Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease) of patients with carotid stenosis and recent stroke/transient ischemic attack with 90-day follow-up. On coregistered carotid 18F-FDG PET/computed tomography angiography, 18F-FDG uptake was expressed as maximum standardized uptake value (SUVmax) in the axial single hottest slice. We then conducted a systematic review of similar studies and pooled unpublished individual-patient data with 2 highly similar independent studies (Dublin and Barcelona). We analyzed the association of SUVmax with all recurrent nonprocedural stroke (before and after PET) and with recurrent stroke after PET only. Results- In BIOVASC (n=109, 14 recurrent strokes), after adjustment (for age, sex, stenosis severity, antiplatelets, statins, diabetes mellitus, hypertension, and smoking), the hazard ratio for recurrent stroke per 1 g/mL SUVmax was 2.2 (CI, 1.1-4.5; P=0.025). Findings were consistent in the independent Dublin (n=52, hazard ratio, 2.2; CI, 1.1-4.3) and Barcelona studies (n=35, hazard ratio, 2.8; CI, 0.98-5.5). In the pooled cohort (n=196), 37 recurrent strokes occurred (29 before and 8 after PET). Plaque SUVmax was higher in patients with all recurrence ( P<0.0001) and post-PET recurrence ( P=0.009). The fully adjusted hazard ratio of any recurrent stroke was 2.19 (CI, 1.41-3.39; P<0.001) and for post-PET recurrent stroke was 4.57 (CI, 1.5-13.96; P=0.008). Recurrent stroke risk increased across SUVmax quartiles (log-rank P=0.003). The area under receiver operating curve for all recurrence was 0.70 (CI, 0.59-0.78) and for post-PET recurrence was 0.80 (CI, 0.64-0.96). Conclusions- Plaque inflammation-related 18F-FDG uptake independently predicted future recurrent stroke post-PET. Although further studies are needed, 18F-FDG PET may improve patient selection for carotid revascularization and suggest that anti-inflammatory agents may have benefit for poststroke vascular prevention.

PMID: 31167623 [PubMed - indexed for MEDLINE]

Identifying Pseudomonas syringae Type III Secreted Effector Function via a Yeast Genomic Screen.

G3 (Bethesda). 2019 02 07;9(2):535-547

Authors: Lee AH, Bastedo DP, Youn JY, Lo T, Middleton MA, Kireeva I, Lee JY, Sharifpoor S, Baryshnikova A, Zhang J, Wang PW, Peisajovich SG, Constanzo M, Andrews BJ, Boone CM, Desveaux D, Guttman DS

Abstract
Gram-negative bacterial pathogens inject type III secreted effectors (T3SEs) directly into host cells to promote pathogen fitness by manipulating host cellular processes. Despite their crucial role in promoting virulence, relatively few T3SEs have well-characterized enzymatic activities or host targets. This is in part due to functional redundancy within pathogen T3SE repertoires as well as the promiscuity of individual T3SEs that can have multiple host targets. To overcome these challenges, we generated and characterized a collection of yeast strains stably expressing 75 T3SE constructs from the plant pathogen Pseudomonas syringae This collection is devised to facilitate heterologous genetic screens in yeast, a non-host organism, to identify T3SEs that target conserved eukaryotic processes. Among 75 T3SEs tested, we identified 16 that inhibited yeast growth on rich media and eight that inhibited growth on stress-inducing media. We utilized Pathogenic Genetic Array (PGA) screens to identify potential host targets of P. syringae T3SEs. We focused on the acetyltransferase, HopZ1a, which interacts with plant tubulin and alters microtubule networks. To uncover putative HopZ1a host targets, we identified yeast genes with genetic interaction profiles most similar (i.e., congruent) to the PGA profile of HopZ1a and performed a functional enrichment analysis of these HopZ1a-congruent genes. We compared the congruence analyses above to previously described HopZ physical interaction datasets and identified kinesins as potential HopZ1a targets. Finally, we demonstrated that HopZ1a can target kinesins by acetylating the plant kinesins HINKEL and MKRP1, illustrating the utility of our T3SE-expressing yeast library to characterize T3SE functions.

PMID: 30573466 [PubMed - indexed for MEDLINE]

IMPACT OF RETINAL ISCHEMIA ON FUNCTIONAL AND ANATOMICAL OUTCOMES AFTER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY IN PATIENTS WITH RETINAL VEIN OCCLUSION.

Retina. 2019 May 30;:

Authors: Khayat M, Wright DM, Yeong J, Xu D, Donley C, Lakshmipathy GR, Low MK, White N, Williams M, Lois N

Abstract
PURPOSE: To compare the impact of the classification of retinal vein occlusion (RVO) into ischemic or nonischemic forms on outcomes after anti-vascular endothelial growth factor therapy.
METHODS: Retrospective review of consecutive patients with RVO evaluated at the Belfast Health and Social Care Trust between July 1, 2014, and December 31, 2015. Outcomes, including gain of ≥10 and ≥15 letters at 12 months, mean change in best-corrected visual acuity from baseline to 12 months, resolution of macular edema at 12 months, and development of neovascular complications and epiretinal membrane after anti-vascular endothelial growth factor therapy, were compared between ischemic and nonischemic eyes using regression models.
RESULTS: One hundred and seventeen eyes (115 patients), 58 with central RVO and 59 with branch RVO, were included. A greater proportion of eyes with ischemic branch RVO gained ≥10 and ≥15 letters at 12 months than those with nonischemic branch RVO (P = 0.005 and P = 0.016, respectively). No statistically significant differences in visual outcomes were observed between ischemic and nonischemic central RVO. Retinal vein occlusion classification was not associated with anatomical outcomes after treatment.
CONCLUSION: Findings support the use of anti-vascular endothelial growth factors in ischemic and nonischemic forms of RVO.

PMID: 31157714 [PubMed - as supplied by publisher]