UW Neurological Surgery Recent PubMed Publications

Synthesis and Evaluation of Baylis-Hillman Reaction Derived Imidazole and Triazole Cinnamates as Antifungal Agents.

Int J Med Chem. 2018;2018:5758076

Authors: Nelson GL, Williams MJ, Jonnalagadda S, Alam MA, Mereddy G, Johnson JL, Jonnalagadda SK

Abstract
Allylic acetates derived from Baylis-Hillman reaction undergo efficient nucleophilic isomerization with imidazoles and triazoles to provide imidazolylmethyl and triazolylmethyl cinnamates stereoselectively. Antifungal evaluation of these derivatives against Cryptococcus neoformans exhibits good minimum inhibitory concentration values. These compounds exhibit low toxicity in proliferating MCF-7 breast cancer cell line. Structure activity relationship studies indicate that halogenated aromatic derivatives provide better antifungal activity.

PMID: 30410798 [PubMed]

Comparative functional genomic screens of three yeast deletion collections reveal unexpected effects of genotype in response to diverse stress.

Open Biol. 2017 06;7(6):

Authors: Acton E, Lee AH, Zhao PJ, Flibotte S, Neira M, Sinha S, Chiang J, Flaherty P, Nislow C, Giaever G

Abstract
The Yeast Knockout (YKO) collection has provided a wealth of functional annotations from genome-wide screens. An unintended consequence is that 76% of gene annotations derive from one genotype. The nutritional auxotrophies in the YKO, in particular, have phenotypic consequences. To address this issue, 'prototrophic' versions of the YKO collection have been constructed, either by introducing a plasmid carrying wild-type copies of the auxotrophic markers (Plasmid-Borne, PBprot) or by backcrossing (Backcrossed, BCprot) to a wild-type strain. To systematically assess the impact of the auxotrophies, genome-wide fitness profiles of prototrophic and auxotrophic collections were compared across diverse drug and environmental conditions in 250 experiments. Our quantitative profiles uncovered broad impacts of genotype on phenotype for three deletion collections, and revealed genotypic and strain-construction-specific phenotypes. The PBprot collection exhibited fitness defects associated with plasmid maintenance, while BCprot fitness profiles were compromised due to strain loss from nutrient selection steps during strain construction. The repaired prototrophic versions of the YKO collection did not restore wild-type behaviour nor did they clarify gaps in gene annotation resulting from the auxotrophic background. To remove marker bias and expand the experimental scope of deletion libraries, construction of a bona fide prototrophic collection from a wild-type strain will be required.

PMID: 28592509 [PubMed - indexed for MEDLINE]

Simultaneous Quantification of Plasmodium Antigens and Host Factor C-Reactive Protein in Asymptomatic Individuals with Confirmed Malaria by Use of a Novel Multiplex Immunoassay.

J Clin Microbiol. 2019 01;57(1):

Authors: Jang IK, Tyler A, Lyman C, Kahn M, Kalnoky M, Rek JC, Arinaitwe E, Adrama H, Murphy M, Imwong M, Ling CL, Proux S, Haohankhunnatham W, Rist M, Seilie AM, Hanron A, Daza G, Chang M, Das S, Barney R, Rashid A, Landier J, Boyle DS, Murphy SC, McCarthy JS, Nosten F, Greenhouse B, Domingo GJ

Abstract
Malaria rapid diagnostic tests (RDTs) primarily detect Plasmodium falciparum antigen histidine-rich protein 2 (HRP2) and the malaria-conserved antigen lactate dehydrogenase (LDH) for P. vivax and other malaria species. The performance of RDTs and their utility is dependent on circulating antigen concentration distributions in infected individuals in a population in which malaria is endemic and on the limit of detection of the RDT for the antigens. A multiplexed immunoassay for the quantification of HRP2, P. vivax LDH, and all-malaria LDH (pan LDH) was developed to accurately measure circulating antigen concentration and antigen distribution in a population with endemic malaria. The assay also measures C-reactive protein (CRP) levels as an indicator of inflammation. Validation was conducted with clinical specimens from 397 asymptomatic donors from Myanmar and Uganda, confirmed by PCR for infection, and from participants in induced blood-stage malaria challenge studies. The assay lower limits of detection for HRP2, pan LDH, P. vivax LDH, and CRP were 0.2 pg/ml, 9.3 pg/ml, 1.5 pg/ml, and 26.6 ng/ml, respectively. At thresholds for HRP2, pan LDH, and P. vivax LDH of 2.3 pg/ml, 47.8 pg/ml, and 75.1 pg/ml, respectively, and a specificity ≥98.5%, the sensitivities for ultrasensitive PCR-confirmed infections were 93.4%, 84.9%, and 48.9%, respectively. Plasmodium LDH (pLDH) concentration, in contrast to that of HRP2, correlated closely with parasite density. CRP levels were moderately higher in P. falciparum infections with confirmed antigenemia versus those in clinical specimens with no antigen. The 4-plex array is a sensitive tool for quantifying diagnostic antigens in malaria infections and supporting the evaluation of new ultrasensitive RDTs.

PMID: 30404944 [PubMed - indexed for MEDLINE]

Microsurgical Clipping of a Ruptured Basilar Apex Aneurysm: 3-Dimensional Operative Video.

Oper Neurosurg (Hagerstown). 2018 Nov 08;:

Authors: Cheng CY, Qazi Z, Hallam DK, Ghodke BV, Sekhar LN

Abstract
A 59-yr-old woman presented with a sudden onset of headache with neck pain and stiffness, Hunt and Hess grade 2. Brain computed tomography (CT) showed subarachnoid hemorrhage, Fisher Grade 2. Intra-arterial digital subtraction angiography (IADSA) showed a basilar artery apex aneurysm, dome size 9 mm and neck 3 mm, leaning towards the right, and a dominant right artery of Percheron. Endovascular treatment and microsurgical clipping were both explained to the patient, but she decided to undergo microsurgery due to the durability of treatment.She underwent a right frontotemporal craniotomy and orbital osteotomy. We performed optic nerve decompression and intradural anterior clinoidectomy to enhance the exposure. Working through the carotid-oculomotor space, the posterior communicating artery was traced back to the posterior cerebral artery. The basilar artery was temporarily occluded for aneurysm dissection after burst suppression to protect the brain. The aneurysm was irregular, multilobulated, and projecting upward. The dominant thalamoperforate artery (artery of Percheron) was arising from the right P1, and densely adherent to the sac of the aneurysm. After dissection of the artery of Percheron away from the aneurysm, it was completely occluded by a side-curved titanium clip. The patient had right oculomotor nerve paresis and headache postoperatively, but at discharge 2 wk later the headache and paresis had completely resolved. The postoperative IADSA showed total occlusion of the aneurysm with patency of the artery of Percheron.This 3-dimensional video shows the technical nuances of microsurgical clipping of a ruptured basilar apex aneurysm and intraoperative dissection of the artery of Percheron.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: 30407554 [PubMed - as supplied by publisher]

Disseminated Tuberculosis Presenting as Chronic Orchiepididymitis in a Military Trainee: A Case Report and Review of the Literature.

Case Rep Infect Dis. 2018;2018:7316097

Authors: Williams MU, Burris A, Zingalis A, Lindholm DA, White BK

Abstract
Orchiepididymitis is a clinical diagnosis. The acute form secondary to sexually transmitted or enteric pathogens is well known to primary care providers. However, chronic orchiepididymitis may be secondary to genitourinary tuberculosis (TB), and physicians in countries with a low prevalence of TB might not consider it in their differential diagnosis. Indeed, cognitive errors, such as anchoring or availability bias, may contribute to a delayed diagnosis of genitourinary TB. We present a case of chronic orchiepididymitis as a result of disseminated TB in a Cameroonian male who was visiting the United States for military training. He experienced diagnostic delay and was ultimately diagnosed by orchiectomy. Early consideration of a diagnosis of TB for chronic or recurrent orchiepididymitis in a patient with epidemiologic risk factors is of utmost importance because delayed diagnosis could lead to organ loss.

PMID: 30402306 [PubMed]

ARB-1740, a RNA Interference Therapeutic for Chronic Hepatitis B Infection.

ACS Infect Dis. 2019 05 10;5(5):725-737

Authors: Thi EP, Dhillon AP, Ardzinski A, Bidirici-Ertekin L, Cobarrubias KD, Cuconati A, Kondratowicz AS, Kwak K, Li AHL, Miller A, Pasetka C, Pei L, Phelps JR, Snead NM, Wang X, Ye X, Sofia MJ, Lee ACH

Abstract
Current approved nucleoside analogue treatments for chronic hepatitis B virus (HBV) infection are effective at controlling viral titer but are not curative and have minimal impact on the production of viral proteins such as surface antigen (HBsAg), the HBV envelope protein believed to play a role in maintaining the immune tolerant state required for viral persistence. Novel agents are needed to effect HBV cure, and reduction of HBV antigenemia may potentiate activation of effective and long-lasting host immune control. ARB-1740 is a clinical stage RNA interference agent composed of three siRNAs delivered using lipid nanoparticle technology. In a number of cell and animal models of HBV, ARB-1740 caused HBV RNA reduction, leading to inhibition of multiple elements of the viral life cycle including HBsAg, HBeAg, and HBcAg viral proteins as well as replication marker HBV DNA. ARB-1740 demonstrated pan-genotypic activity in vitro and in vivo, targeting three distinct highly conserved regions of the HBV genome, and effectively inhibited replication of nucleoside analogue-resistant HBV variants. Combination of ARB-1740 with a capsid inhibitor and pegylated interferon-alpha led to greater liver HBsAg reduction which correlated with more robust induction of innate immune responses in a human chimeric mouse model of HBV. The preclinical profile of ARB-1740 demonstrates the promise of RNA interference and HBV antigen reduction in treatment strategies driving toward a cure for HBV.

PMID: 30403127 [PubMed - indexed for MEDLINE]

Acute Post-Traumatic Sleep May Define Vulnerability to a Second Traumatic Brain Injury in Mice.

J Neurotrauma. 2019 04 15;36(8):1318-1334

Authors: Rowe RK, Harrison JL, Morrison HW, Subbian V, Murphy SM, Lifshitz J

Abstract
Chronic neurological impairments can manifest from repetitive traumatic brain injury (rTBI), particularly when subsequent injuries occur before the initial injury completely heals. Herein, we apply post-traumatic sleep as a physiological biomarker of vulnerability, hypothesizing that a second TBI during post-traumatic sleep worsens neurological and histological outcomes compared to one TBI or a second TBI after post-traumatic sleep subsides. Mice received sham or diffuse TBI by midline fluid percussion injury; brain-injured mice received one TBI or rTBIs at 3- or 9-h intervals. Over 40 h post-injury, injured mice slept more than shams. Functional assessments indicated lower latencies on rotarod and increased Neurological Severity Scores for mice with rTBIs within 3 h. Anxiety-like behaviors in the open field task were increased for mice with rTBIs at 3 h. Based on pixel density of silver accumulation, neuropathology was greater at 28 days post-injury (DPI) in rTBI groups than sham and single TBI. Cortical microglia morphology was quantified and mice receiving rTBI were de-ramified at 14 DPI compared to shams and mice receiving a single TBI, suggesting robust microglial response in rTBI groups. Orexin-A-positive cells were sustained in the lateral hypothalamus with no loss detected, indicating that loss of wake-promoting neurons did not contribute to post-traumatic sleep. Thus, duration of post-traumatic sleep is a period of vulnerability that results in exacerbated injury from rTBI. Monitoring individual post-traumatic sleep is a potential clinical tool for personalized TBI management, where regular sleep patterns may inform rehabilitative strategies and return-to-activity guidelines.

PMID: 30398389 [PubMed - indexed for MEDLINE]

Endovascular Treatment of Acute Ischemic Stroke Under General Anesthesia: Predictors of Good Outcome.

J Neurosurg Anesthesiol. 2018 Jul;30(3):223-230

Authors: Athiraman U, Sultan-Qurraie A, Nair B, Tirschwell DL, Ghodke B, Havenon AD, Hallam DK, Kim LJ, Becker KJ, Sharma D

Abstract
BACKGROUND: The choice of anesthetic technique, general anesthesia (GA) versus Monitored Anesthesia Care, may impact the outcome of patients undergoing endovascular treatment of acute ischemic stroke (AIS). The aim of this study was to identify the factors associated with good discharge outcome in patients receiving GA for AIS.
MATERIALS AND METHODS: Electronic medical records of patients above 18 years old who underwent endovascular treatment of AIS under GA at a Comprehensive Stroke Center from 2010 to 2014 were reviewed. Good outcome was defined as discharge modified Rankin Score 0 to 2 and poor outcome as modified Rankin Score 3 to 6; logistic regression analysis was performed to examine the association between the clinical characteristics and the outcome.
RESULTS: In total, 88 patients (56 males), aged 63±15 years with median National Institute of Health Stroke Scale (NIHSS) score 16 (range, 4 to 38) were included. Nineteen (22%) patients had good outcome and 78 (88%) had systolic blood pressure below the guideline recommended 140 mm Hg under GA. After adjusting for age and NIHSS score, the independent predictors of good discharge outcomes were higher maximum end-tidal carbon dioxide (odds ratio [OR], 1.14; confidence interval [CI], 1.02-1.28; P=0.02) and extubation after endovascular treatment (OR, 26.31; CI, 4.80-144.12; P<0.0001). A secondary analysis was performed after excluding 25 patients emergently intubated in the Emergency Department for airway protection. In the logistic regression analysis controlling for age and NIHSS score, postprocedure extubation was still associated with higher odds of good outcomes (OR, 13.35; CI, 2.58-68.90; P=0.002).
CONCLUSIONS: These findings indicate the importance of ventilation management and extubation after endovascular intervention under GA in patients with AIS.

PMID: 28763432 [PubMed - indexed for MEDLINE]

h-Channels Contribute to Divergent Intrinsic Membrane Properties of Supragranular Pyramidal Neurons in Human versus Mouse Cerebral Cortex.

Neuron. 2018 12 05;100(5):1194-1208.e5

Authors: Kalmbach BE, Buchin A, Long B, Close J, Nandi A, Miller JA, Bakken TE, Hodge RD, Chong P, de Frates R, Dai K, Maltzer Z, Nicovich PR, Keene CD, Silbergeld DL, Gwinn RP, Cobbs C, Ko AL, Ojemann JG, Koch C, Anastassiou CA, Lein ES, Ting JT

Abstract
Gene expression studies suggest that differential ion channel expression contributes to differences in rodent versus human neuronal physiology. We tested whether h-channels more prominently contribute to the physiological properties of human compared to mouse supragranular pyramidal neurons. Single-cell/nucleus RNA sequencing revealed ubiquitous HCN1-subunit expression in excitatory neurons in human, but not mouse, supragranular layers. Using patch-clamp recordings, we found stronger h-channel-related membrane properties in supragranular pyramidal neurons in human temporal cortex, compared to mouse supragranular pyramidal neurons in temporal association area. The magnitude of these differences depended upon cortical depth and was largest in pyramidal neurons in deep L3. Additionally, pharmacologically blocking h-channels produced a larger change in membrane properties in human compared to mouse neurons. Finally, using biophysical modeling, we provide evidence that h-channels promote the transfer of theta frequencies from dendrite-to-soma in human L3 pyramidal neurons. Thus, h-channels contribute to between-species differences in a fundamental neuronal property.

PMID: 30392798 [PubMed - indexed for MEDLINE]

Effects of Acute Deltamethrin Exposure in Adult and Developing Sprague Dawley Rats on Acoustic Startle Response in Relation to Deltamethrin Brain and Plasma Concentrations.

Toxicol Sci. 2019 03 01;168(1):61-69

Authors: Williams MT, Gutierrez A, Vorhees CV

Abstract
Deltamethrin (DLM) is a commonly used pesticide that helps to control crop destruction, disease, and nuisance insects. In rodents DLM can produce choreoathetosis, salivation, and decreased acoustic startle responses (ASR). Herein, adult Sprague Dawley rats were assessed for ASR 2 h after DLM delivered in 5 ml/kg corn oil, however no decrease was observed. Therefore, a test-retest protocol was used to reduce variability, and the effects on ASR on postnatal day 15 (P15) and adult rats were assessed 2, 4, 6, and 8 h after DLM administration (0, 1, 2, or 4 mg/kg for P15 rats and 0, 2, 8, or 25 mg/kg for adults). In a separate set of rats identically treated, DLM levels were determined in blood and brain. DLM (8 or 25 mg/kg) in adult rats decreased ASR up to 4 h, whereas in P15 rats decreases were observed between 2 and 8 h. The adult 25 mg/kg group showed consistent signs of salivation and tremor, whereas in P15 rats salivation was observed in the 2 and 4 mg/kg groups and tremor was observed at all doses over the 8-h period. Mortality was observed in all P15 dose groups but not in adults. Dose-dependent increases of DLM in blood and brain regardless of age were observed. At approximately equivalent whole brain concentrations, effects were more pronounced in P15 rats than in adult rats. Comparable brain levels of DLM do not explain differences in ASR and tremor between the P15 and adult rats. These data indicate age-dependent differences in sensitivity to DLM.

PMID: 30395337 [PubMed - indexed for MEDLINE]

Stroke: Basic and Clinical.

Adv Neurobiol. 2017;15:281-293

Authors: Singh TP, Weinstein JR, Murphy SP

Abstract
Tissue plasminogen activator (tPA) was first approved in the USA 25 years ago for those who had experienced a recent occlusion (<3 h) of a cerebral vessel. Now, advances in clot retrieval (stentriever), in concert with tPA, heralds new optimism for ischemic stroke victims, but adds more pressure to identify therapies that will minimize hypoxic damage, protect compromised cells, and promote rehabilitation. In the past preclinical investigations have been poor at predicting potential clinical therapy, but they have contributed enormously to understanding post-stroke pathology. Current clinical trials ( www.strokecenter.org/trials ) anticipate a broad range of approaches: from hypothermia, to cell therapy, to neuroprotection.

PMID: 28674985 [PubMed - indexed for MEDLINE]

Microglia Induce PDGFRB Expression in Glioma Cells to Enhance Their Migratory Capacity.

iScience. 2018 Oct 16;9:71-83

Authors: Wallmann T, Zhang XM, Wallerius M, Bolin S, Joly AL, Sobocki C, Leiss L, Jiang Y, Bergh J, Holland EC, Enger PØ, Andersson J, Swartling FJ, Miletic H, Uhrbom L, Harris RA, Rolny C

Abstract
High-grade gliomas (HGGs) are the most aggressive and invasive primary brain tumors. The platelet-derived growth factor (PDGF) signaling pathway drives HGG progression, and enhanced expression of PDGF receptors (PDGFRs) is a well-established aberration in a subset of glioblastomas (GBMs). PDGFRA is expressed in glioma cells, whereas PDGFRB is mostly restricted to the glioma-associated stroma. Here we show that the spatial location of TAMMs correlates with the expansion of a subset of tumor cells that have acquired expression of PDGFRB in both mouse and human low-grade glioma and HCGs. Furthermore, M2-polarized microglia but not bone marrow (BM)-derived macrophages (BMDMs) induced PDGFRB expression in glioma cells and stimulated their migratory capacity. These findings illustrate a heterotypic cross-talk between microglia and glioma cells that may enhance the migratory and invasive capacity of the latter by inducing PDGFRB.

PMID: 30384135 [PubMed - as supplied by publisher]

Epigenetic and Transcriptome Profiling Identifies a Population of Visceral Adipose-Derived Progenitor Cells with the Potential to Differentiate into an Endocrine Pancreatic Lineage.

Cell Transplant. 2019 01;28(1):89-104

Authors: Williams MD, Joglekar MV, Satoor SN, Wong W, Keramidaris E, Rixon A, O'Connell P, Hawthorne WJ, Mitchell GM, Hardikar AA

Abstract
Type 1 diabetes (T1D) is characterized by the loss of insulin-producing β-cells in the pancreas. T1D can be treated using cadaveric islet transplantation, but this therapy is severely limited by a lack of pancreas donors. To develop an alternative cell source for transplantation therapy, we carried out the epigenetic characterization in nine different adult mouse tissues and identified visceral adipose-derived progenitors as a candidate cell population. Chromatin conformation, assessed using chromatin immunoprecipitation (ChIP) sequencing and validated by ChIP-polymerase chain reaction (PCR) at key endocrine pancreatic gene promoters, revealed similarities between visceral fat and endocrine pancreas. Multiple techniques involving quantitative PCR, in-situ PCR, confocal microscopy, and flow cytometry confirmed the presence of measurable (2-1000-fold over detectable limits) pancreatic gene transcripts and mesenchymal progenitor cell markers (CD73, CD90 and CD105; >98%) in visceral adipose tissue-derived mesenchymal cells (AMCs). The differentiation potential of AMCs was explored in transgenic reporter mice expressing green fluorescent protein (GFP) under the regulation of the Pdx1 (pancreatic and duodenal homeobox-1) gene promoter. GFP expression was measured as an index of Pdx1 promoter activity to optimize culture conditions for endocrine pancreatic differentiation. Differentiated AMCs demonstrated their capacity to induce pancreatic endocrine genes as evidenced by increased GFP expression and validated using TaqMan real-time PCR (at least 2-200-fold relative to undifferentiated AMCs). Human AMCs differentiated using optimized protocols continued to produce insulin following transplantation in NOD/SCID mice. Our studies provide a systematic analysis of potential islet progenitor populations using genome-wide profiling studies and characterize visceral adipose-derived cells for replacement therapy in diabetes.

PMID: 30376726 [PubMed - indexed for MEDLINE]

Effects of tumor grade and dexamethasone on myeloid cells in patients with glioma.

Oncoimmunology. 2018;7(11):e1507668

Authors: Moyes KW, Davis A, Hoglund V, Haberthur K, Lieberman NA, Kreuser SA, Deutsch GH, Franco S, Locke D, Carleton MO, Gilbertson DG, Simmons R, Winter C, Silber J, Gonzalez-Cuyar LF, Ellenbogen RG, Crane CA

Abstract
Efforts to reduce immunosuppression in the solid tumor microenvironment by blocking the recruitment or polarization of tumor associated macrophages (TAM), or myeloid derived suppressor cells (MDSCs), have gained momentum in recent years. Expanding our knowledge of the immune cell types, cytokines, or recruitment factors that are associated with high-grade disease, both within the tumor and in circulation, is critical to identifying novel targets for immunotherapy. Furthermore, a better understanding of how therapeutic regimens, such as Dexamethasone (Dex), chemotherapy, and radiation, impact these factors will facilitate the design of therapies that can be targeted to the appropriate populations and retain efficacy when administered in combination with standard of care regimens. Here we perform quantitative analysis of tissue microarrays made of samples taken from grades I-III astrocytoma and glioblastoma (GBM, grade IV astrocytoma) to evaluate infiltration of myeloid markers CD163, CD68, CD33, and S100A9. Serum, flow cytometric, and Nanostring analysis allowed us to further elucidate the impact of Dex treatment on systemic biomarkers, circulating cells, and functional markers within tumor tissue. We found that common myeloid markers were elevated in Dex-treated grade I astrocytoma and GBM compared to non-neoplastic brain tissue and grade II-III astrocytomas. Cell frequencies in these samples differed significantly from those in Dex-naïve patients in a pattern that depended on tumor grade. In contrast, observed changes in serum chemokines or circulating monocytes were independent of disease state and were due to Dex treatment alone. Furthermore, these changes seen in blood were often not reflected within the tumor tissue. Conclusions: Our findings highlight the importance of considering perioperative treatment as well as disease grade when assessing novel therapeutic targets or biomarkers of disease.

PMID: 30377570 [PubMed]

Is postoperative Doppler ultrasonography useful for the early detection of asymptomatic pseudoaneurysm and prevention of haemorrhagic complications after partial nephrectomy?

BJU Int. 2018 11;122 Suppl 5:15-21

Authors: Nouhaud FX, Williams M, Arnfield E, Perera ML, Cho J, Esler R, Coughlin G

Abstract
OBJECTIVE: To assess the clinical utility of systematic Doppler ultrasonography (DUS) after robot-assisted partial nephrectomy (PN) for the detection of renal artery pseudoaneurysm (PA) and to allow pre-emptive arterial embolization to reduce the postoperative bleeding risk.
MATERIALS AND METHODS: A retrospective study was conducted including all consecutive patients treated with robot-assisted PN for renal tumours between 2015 and 2017. Every patient underwent renal DUS in the early postoperative period. The presence of PA, arteriovenous malformation or collection on the DUS, as well as the incidence of haemorrhagic complications and need for transfusion/embolization were assessed.
RESULTS: Eighty-three patients were included, with a median (range) age of 58 (19-80) years. The median (range) follow-up was 5 (1-30) months. The mean (±sd) tumour size was 31 (±13.1) mm, the median (range) RENAL nephrometry score was 6 (4-11), and the mean (±sd) warm ischaemia time was 22 (±7) min. A haemostatic agent was used in 12 patients (14.5%). No patient encountered haemorrhagic complications postoperatively, and no patient required transfusion. The median (interquartile range) time to DUS postoperatively was 7 (6-8) days. DUS revealed one asymptomatic PA (1.2%), which was treated with pre-emptive embolization. This was the only patient who encountered a Clavien grade III complication, while 20 patients (24%) had a complication grade I/II.
CONCLUSIONS: No haemorrhagic complications occurred in the present study population, although one asymptomatic PA was found. It was diagnosed early with DUS, allowing pre-emptive management with embolization. These results suggest the potential clinical utility of early postoperative DUS in order to screen for PA to reduce the risk of post-PN haemorrhagic complications.

PMID: 30370984 [PubMed - indexed for MEDLINE]

The "Real" Number of Washington State Adolescents Using Marijuana, and Why: A Misclassification Analysis.

Subst Use Misuse. 2019;54(1):89-96

Authors: Murphy SM, Rosenman R

Abstract
BACKGROUND: Although causality is difficult to establish, the regular use of marijuana has been associated with many adverse physiological and sociological consequences. There is considerable concern regarding marijuana use among adolescents, as the likelihood of adverse consequences increases significantly for this age group. The most comprehensive data for identifying risk factors for adolescent marijuana use is typically self-report, which may be over- or under-reported for a variety of reasons, including stigmatization, peer-pressure, or fear of being discovered.
OBJECTIVES: To identify the prevalence of adolescent marijuana use in Washington State, and the associated risk and protective factors, while controlling for and estimating the extent of misreporting, and its determinants.
METHOD: Data came from the 2014 Washington State Healthy Youth Survey. We accounted for missingness using chained multivariate imputation equations, resulting in 33,320 complete observations. Our model was estimated using a maximum likelihood multiple regression designed to control for systematic misclassification in binary dependent variables.
RESULTS: Approximately 12% of Washington adolescents claimed to have used marijuana in the past 30 days. Our estimates indicate this figure is likely closer to 18%. Determinants of use included use of other substances, gender, age, and measures of deviant social influences, personality/attitude, school and family bonds, bullying, and acquisition ease. Determinants of misreporting included use of other substances, gender, parental education, and family bonds.
CONCLUSIONS: Failing to control for misreporting considerably underestimates the prevalence of marijuana use among adolescents. Our model allows us to better identify at-risk adolescents and inform focused prevention efforts.

PMID: 30362862 [PubMed - indexed for MEDLINE]

A cause of recurrent strokes: carotid webs detected by CT angiogram.

BJR Case Rep. 2018;4(1):20170066

Authors: Smyth H, Byrne D, Hayden D, Eoin K, Murphy S

Abstract
Carotid webs are an uncommon cause of recurrent ischaemic strokes. They are considered a form of fibromuscular dysplasia, possibly developmental in origin, with non-inflammatory and non-atherosclerotic features and a characteristic appearance on CT angiography. They have been described as a thin intraluminal filling defect along the posterior wall of the carotid bulb in oblique sagittal reformats and a septum on axial CT angiography. Here we summarize two cases of ischaemic strokes secondary to carotid webs with characteristic images. Detection and awareness of carotid webs and their imaging features among radiologists and physicians are important as it is associated with a high risk of recurrent cerebrovascular events.

PMID: 30363186 [PubMed]

Towards a non-invasive cardiac arrest monitor: An in vivo pilot study.

Resuscitation. 2019 01;134:76-80

Authors: Kucewicz JC, Salcido DD, Adedipe AA, Truong K, Nichol G, Mourad PD

Abstract
INTRODUCTION: Hemodynamic-guided cardiopulmonary resuscitation (HGCPR) achieves better outcomes than standard resuscitation. Currently, HGCPR requires an invasive procedure, infeasible during resuscitation. Non-invasive measures of blood flow could provide useful hemodynamic guidance to rescuers.
OBJECTIVE: We describe initial efforts to develop a device that detects, analyzes, and measures the velocity of carotid artery blood flow (CABF) towards the brain at pre-arrest baseline ('baseline') and during cardiopulmonary resuscitation, here tested in a swine model of cardiac arrest (CA). A key element of that device consists of non-imaging diagnostic ultrasound, due to its simplicity and small form factor, hence potential for deployment during HGCPR in a bandage placed on the neck.
METHODS: Sixteen mixed-breed domestic swine were sedated, anesthetized and paralyzed, followed by endotracheal intubation and mechanical ventilation. Cardiac arrest was induced with a 3-s 100 mA transthoracic shock or bolus of fentanyl, after which all animals received mechanical CPR. A non-imaging ultrasound probe was manually applied to the neck over the carotid artery to capture CABF during baseline, as verified with diagnostic ultrasound imaging, and during mechanical resuscitation.
RESULTS: We successfully collected CABF measurements at baseline in 14/16 swine and during attempted resuscitation with mechanical chest compression in 5/16 swine. Signal characteristics include peak blood flow both towards (90.4 +/-20.4 cm/s) and away from the brain (-44.2 +/-31.8 cm/s) during resuscitation, each larger than flow towards (41.7+/-14.8 cm/s) and away from brain (-3.0 +/-7.8 cm/s) during baseline.
CONCLUSION: Measurement of CABF before and during CPR in swine with a non-imaging ultrasound probe is feasible before CA and informative when achieved during CPR. For example, observations of reverse flow within the carotid artery during CPR merits further study for its prevalence and effect on resuscitation outcomes. Also, tissue motion represents a significant obstacle for CABF measurement during CPR. Additional work will determine the feasibility and utility of non-imaging ultrasound measurements of CABF during resuscitation.

PMID: 30365974 [PubMed - indexed for MEDLINE]

Reply: Corticosteroids compromise survival in glioblastoma in part through their elevation of blood glucose levels.

Brain. 2017 03 01;140(3):e17

Authors: Weller M, Holland EC, Hambardzumyan D

PMID: 28007996 [PubMed - indexed for MEDLINE]

Whole genome analysis of Yersinia ruckeri isolated over 27 years in Australia and New Zealand reveals geographical endemism over multiple lineages and recent evolution under host selection.

Microb Genom. 2016 11;2(11):e000095

Authors: Barnes AC, Delamare-Deboutteville J, Gudkovs N, Brosnahan C, Morrison R, Carson J

Abstract
Yersinia ruckeri is a salmonid pathogen with widespread distribution in cool-temperate waters including Australia and New Zealand, two isolated environments with recently developed salmonid farming industries. Phylogenetic comparison of 58 isolates from Australia, New Zealand, USA, Chile, Finland and China based on non-recombinant core genome SNPs revealed multiple deep-branching lineages, with a most recent common ancestor estimated at 18 500 years BP (12 355-24 757 95% HPD) and evidence of Australasian endemism. Evolution within the Tasmanian Atlantic salmon serotype O1b lineage has been slow, with 63 SNPs describing the variance over 27 years. Isolates from the prevailing lineage are poorly/non-motile compared to a lineage pre-vaccination, introduced in 1997, which is highly motile but has not been isolated since from epizootics. A non-motile phenotype has arisen independently in Tasmania compared to Europe and USA through a frameshift in fliI, encoding the ATPase of the flagella cluster. We report for the first time lipopolysaccharide O-antigen serotype O2 isolates in Tasmania. This phenotype results from deletion of the O-antigen cluster and consequent loss of high-molecular-weight O-antigen. This phenomenon has occurred independently on three occasions on three continents (Australasia, North America and Asia) as O2 isolates from the USA, China and Tasmania share the O-antigen deletion but occupy distant lineages. Despite the European and North American origins of the Australasian salmonid stocks, the lineages of Y. ruckeri in Australia and New Zealand are distinct from those of the northern hemisphere, suggesting they are pre-existing ancient strains that have emerged and evolved with the introduction of susceptible hosts following European colonization.

PMID: 28348835 [PubMed - indexed for MEDLINE]