Matt Wheatley - Academia.edu (original) (raw)

Papers by Matt Wheatley

(A) HERV-K(II) env transcript analysis of HIV−) an... more (A) HERV-K(II) env transcript analysis of HIV−) and HIV+ brains revealed high levels of HERV-K(II) env in cortex of HIV+ as compared to HIV− brains. (B) Immunohistochemical analyses of brain sections from HIV+ patients showed increased immunoreactivity of HERV-K(II) Env (arrow) protein in neurons as compared to the HIV− brain sections. HERV-K(II) Env protein expression co-localized in neurons expressing MAP-2 (insert: brown, MAP-2; blue, HERV-K Env). (C) In cerebral cortical specimens, HIV+ patients exhibited higher levels of HERV-K(II) Env detection than HIV− patients on immunoblotting of HERV-K(II) Env protein. (D) Quantitation of HERV-K(II) Env/β-actin band density on immunoblots (Original magnification: B-400X; insert, 200X). (Student t test, **p<0.01).</p

(A) Analyses of SK-N-SH cells transfected with the pHERV-Kenv plasmid... more (A) Analyses of SK-N-SH cells transfected with the pHERV-Kenv plasmid compared to the control (pGFP) showed that the efficiency of transfection was ∼20% (n = 3, with technical triplicates). (B) HERV-K(II) Env immunoreactivity was minimally detected in cells transfected with the control vector. pHERV-Kenv-transfected cells showed HERV-K(II) Env immunoreactivity at low (C) and high magnification (D). (E) Comparison of BDNF and NGF transcript levels in SKN-N-SH cells transfected with pGFP or pHERV-Kenv. (F) Exposure of pHERV-Kenv and control vector-transfected NG108 cells to staurosporine, HIV-1 Vpr or NMDA, showed that pHERV-Kenv-transfected cells were differentially protected depending on the neurotoxin. (Student t test, *p<0.05, ***p<0.001).</p

(A) Deep sequencing of the HIV− and HIV+ autopsied cerebral white mat... more (A) Deep sequencing of the HIV− and HIV+ autopsied cerebral white matter revealed a higher tag frequency of HERV-K in both clinical groups compared to other HERVs. (B) With the use of the DAVID bioinformatics resources, the predicted target genes were classified according to KEGG functional annotations to identify pathways that were actively regulated by HERV-K(II) env transcripts in brain tissue.</p

(A) Schematic of representation of C17.2 implantation site (marked by... more (A) Schematic of representation of C17.2 implantation site (marked by the •) in Vpr/RAG1−/− mice. (B) Western blot showing HERV-K(II) Env immunoreactivity in transfected cells. (C) TNF-α expression was suppressed in the brains of animals implanted with cells expressing HERV-K(II) env while (C) IL-6 was induced. Nissl staining showed similar striatal neuronal densities in animals implanted with cells transfected with either pGFP or pHERV-Kenv/pGFP (E, I). Immunohistochemistry revealed lower expression the microglia protein, Iba-1 (K) and higher expression levels astrocyte protein, GFAP (L) in HERV-K(II) env implanted brains compared to control vector (pGFP) implanted animals (F, G), respectively. Cleaved caspase-6 immunoreactvity was comparative reduced in striatum of animals receiving cells transfected with pHERV-Kenv/pGFP (M) but BDNF immunoreactivity was increased in the same animals (N) compared to controls (H, I). (O) At days 7 and 14, neurobehavioral deficits were greater in terms of ipsiversive rotations among the animals implanted with c17.2 cells transfected with the pGFP vector. (Original magnification: E–J, 400X) (Mann-Whitney test, *p<0.05).</p

Oligonucleotide primers used in Real-time RT PCR analyses.</p

The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques, 2016

Classical neurosurgical teaching suggests that corticosteroid administration reduces the diagnost... more Classical neurosurgical teaching suggests that corticosteroid administration reduces the diagnostic yield of stereotactic brain biopsy for primary central nervous system lymphoma (PCNSL). In a single-center series spanning 6 years, we reviewed 155 consecutive biopsy patients, 135 treated with prebiopsy corticosteroids. PCNSL was correctly diagnosed on initial biopsy in 15 of 16 steroid-treated patients; in the single nondiagnostic specimen, polymerase chain reaction reanalysis by an outside institution showed evidence of lymphoproliferative disease consistent with PCNSL. Our data challenge the notion that it is necessary to withhold corticosteroid therapy for cerebral edema in patients awaiting stereotactic biopsy for suspected PCNSL.

Critical Care Medicine

OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 ... more OBJECTIVES: Studies have suggested intrapulmonary shunts may contribute to hypoxemia in COVID-19 acute respiratory distress syndrome (ARDS) with worse associated outcomes. We evaluated the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia workup for shunt etiology and associations with mortality. DESIGN: Prospective, observational cohort study. SETTING: Four tertiary hospitals in Edmonton, Alberta, Canada. PATIENTS: Adult critically ill, mechanically ventilated, ICU patients admitted with COVID-19 or non-COVID (November 16, 2020, to September 1, 2021). INTERVENTIONS: Agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler ± transesophageal echocardiography assessed for R-L shunts presence. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were shunt frequency and association with hospital mortality. Logistic regression analysis was used for adjustment. The study enrolled 226 patients (182 COVI...

ImportanceStudies have suggested intra-pulmonary shunts may contribute to hypoxemia in COVID-19 A... more ImportanceStudies have suggested intra-pulmonary shunts may contribute to hypoxemia in COVID-19 ARDS and may be associated with worse outcomes.ObjectiveTo evaluate the presence of right-to-left (R-L) shunts in COVID-19 and non-COVID ARDS patients using a comprehensive hypoxemia work-up for shunt etiology and associations with mortality.Design, Setting, ParticipantsWe conducted a multi-centre (4 Canadian hospitals), prospective, observational cohort study of adult critically ill, mechanically ventilated, ICU patients admitted for ARDS from both COVID-19 or non-COVID (November 16, 2020-September 1, 2021).InterventionContrast-enhanced agitated-saline bubble studies with transthoracic echocardiography/transcranial Doppler (TTE/TCD) ± transesophageal echocardiography (TEE) assessed for the presence of R-L shunts.Main Outcomes and MeasuresPrimary outcomes were shunt incidence and association with hospital mortality. Logistic regression analysis was used to determine association of shunt p...

Epilepsia open, Sep 13, 2019

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

$Research paper thumbnail of A.06 Selective amygdalohippocampectomy in pediatric medically refractory temporal lobe epilepsy yields worse seizure outcomes$

Canadian Journal of Neurological Sciences, Jun 1, 2017

Suppl. 2-S10 cases each year. Conclusions: This is the largest case series of RTD to date. Early ... more Suppl. 2-S10 cases each year. Conclusions: This is the largest case series of RTD to date. Early recognition and prompt riboflavin treatment is essential for survival and optimal outcome. A.06 Selective amygdalohippocampectomy in pediatric medically refractory temporal lobe epilepsy yields worse seizure outcomes

$Research paper thumbnail of C.03: Progressive contralateral hippocampal atrophy following surgery for medically refractory temporal lobe epilepsy$

Canadian Journal of Neurological Sciences, Jun 1, 2016

variables on diagnosis of epilepsy. Diagnostic concordance between SSC nurses and epileptologists... more variables on diagnosis of epilepsy. Diagnostic concordance between SSC nurses and epileptologists was also assessed. Results: Predominant referral sources were emergency department physicians and general practitioners. Mean wait-time for fi rst assessment was significantly reduced by 70.5% employing the SSC model versus historical usual care. A diagnosis was established at fi rst-contact in 80.5% of cases while 16.0% of patients required a second visit. Eighty-two patients (41.0%) were diagnosed with epilepsy. The most common non-seizure diagnosis was syncope (24.0%). An abnormal EEG was found in 93.9% of patients diagnosed with epilepsy. Sixty-three patients were started on anti-epileptic drugs. In 18% of cases driving restrictions were initiated by the SSC. There was moderate correlation between SSC nurses and physicians (kappa=0.54; p<0.001) diagnoses. Conclusions: The SSC model reduces wait-times, streamlines assessments, and impacts clinical care decisions.

Journal of Neurosurgery, 2019

OBJECTIVEDiffusion tensor imaging (DTI) tractography is commonly used in neurosurgical practice b... more OBJECTIVEDiffusion tensor imaging (DTI) tractography is commonly used in neurosurgical practice but is largely limited to the preoperative setting. This is due primarily to image degradation caused by susceptibility artifact when conventional single-shot (SS) echo-planar imaging (EPI) DTI (SS-DTI) is acquired for open cranial, surgical position intraoperative DTI (iDTI). Readout-segmented (RS) EPI DTI (RS-DTI) has been reported to reduce such artifact but has not yet been evaluated in the intraoperative MRI (iMRI) environment. The authors evaluated the performance of RS versus SS EPI for DTI of the human brain in the iMRI setting.METHODSPre- and intraoperative 3-T 3D T1-weighted and 2D multislice RS-iDTI (called RESOLVE [readout segmentation of long variable echo-trains] on the Siemens platform) and SS-iDTI images were acquired in 22 adult patients undergoing intraaxial iMRI resections for suspected low-grade glioma (14; 64%), high-grade glioma (7; 32%), or focal cortical dysplasia....

$Research paper thumbnail of Seizure outcome in pediatric medically refractory temporal lobe epilepsy surgery: selective amygdalohippocampectomy versus anterior temporal lobectomy$

Journal of neurosurgery. Pediatrics, Jan 22, 2018

OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation... more OBJECTIVE The aim of this study was to investigate long-term seizure outcome, rate of reoperation, and postoperative neuropsychological performance following selective amygdalohippocampectomy (SelAH) or anterior temporal lobectomy (ATL) in pediatric patients with medically refractory temporal lobe epilepsy (TLE). METHODS The authors performed a retrospective review of cases of medically refractory pediatric TLE treated initially with either SelAH or ATL. Standardized pre- and postoperative evaluation included seizure charting, surface and long-term video-electroencephalography, 1.5-T MRI, and neuropsychological testing. RESULTS A total of 79 patients treated initially with SelAH (n = 18) or ATL (n = 61) were included in this study, with a mean follow-up of 5.3 ± 4 years (range 1-16 years). The patients' average age at initial surgery was 10.6 ± 5 years, with an average surgical delay of 5.7 ± 4 years between seizure onset and surgery. Seizure freedom (Engel I) following the init...

Epilepsy research, 2018

Characterize the evolution of microstructural changes in the contralateral, non-operated hippo... more 1) Characterize the evolution of microstructural changes in the contralateral, non-operated hippocampus-using longitudinal diffusion tensor imaging (DTI)-following surgery for temporal lobe epilepsy (TLE). 2) Characterize the downstream extra-hippocampal volumetric changes of the fornix and mammillary bodies after TLE surgery. 3) Examine the relationship between these measures and seizure/cognitive outcome. Serial structural and DTI brain MRI scans were collected in 25 TLE patients pre- and post-surgery (anterior temporal lobectomy, ATL - 13; selective amygdalohippocampectomy, SelAH - 12) and in 12 healthy controls. Contralateral hippocampal fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) were computed with manual hippocampal tracings as volumes of interest following co-registration to anatomical images. Fornix and mammillary body volumetry was performed by manual segmentation. After surgery, the non-resected hippocampus showed s...

Epilepsia, Jun 1, 2016

Rasmussen encephalitis tissue transfer program DISCLOSURE OF CONFLICT OF INTEREST Gary Mathern se... more Rasmussen encephalitis tissue transfer program DISCLOSURE OF CONFLICT OF INTEREST Gary Mathern serves on the Editorial Board and International League Against Epilepsy (ILAE) Executive Committee for Epilepsia. William D. Gaillard and Adam L. Hartman serve on the Editorial Board for Epilepsia. The remaining authors have no conflicts of interest. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Epilepsy Research, 2020

Neuropathological studies indicate that hippocampal sclerosis (HS) consists of three subtypes (IL... more Neuropathological studies indicate that hippocampal sclerosis (HS) consists of three subtypes (ILAE types 1-3 HS). However, HS subtypes currently can only be diagnosed by pathological analysis of hippocampal tissue resected during epilepsy surgery or at autopsy. In vivo diagnosis of HS subtypes holds potential to improve our understanding of these variants in the ipsilateral as well as contralateral hippocampus. In this study, we aimed to: i) evaluate the reliability of our histology-derived segmentation protocol when applied to in vivo MRI; and ii) characterize variability of HS subtypes along the hippocampal long axis in patients with epilepsy. Methods: Eleven subjects with unilateral HS were compared with ten healthy controls. We used 4.7 T MRI to acquire high resolution MR Images of the hippocampus in each subject. In vivo MRI-based diagnoses of HS subtypes were then determined in each patient by two methods: i) hippocampal subfield volumetry of the entire hippocampal body; and ii) subfield area analysis at multiple thin slices throughout the hippocampal body. Results: Hippocampal body subfield segmentation demonstrated excellent reliability and volumetry of the symptomatic hippocampus revealed abnormalities in all eleven patients. Six subjects demonstrated findings consistent with type 1 HS while five subjects had volumetry-defined atypical HS (two with type 2 HS & three with type 3 HS) in the symptomatic hippocampus, while five subjects were found to have type 3 HS in the contralateral hippocampus. Subfield area analyses demonstrated remarkable variability of HS subtypes along the hippocampal long axis, both ipsilateral and contralateral to the seizure focus. Significance: Our results provide preliminary evidence that determining HS Subtype using in vivo MRI may allow preoperative diagnosis of ILAE HS subtypes. Further studies are essential to determine the pathological correlates of these neuroimaging findings. The heterogeneity of abnormalities observed along the long axis of the hippocampus is consistent with previous autopsy studies and highlights the necessity of studying the entire hippocampus both ipsilateral and contralateral to the seizure focus in these future studies.

(A) Deep sequencing of the fetal and surgically resected (Surg) brain... more (A) Deep sequencing of the fetal and surgically resected (Surg) brain samples revealed that HERV-H exhibited the highest tag frequency and median number of tags followed by HERV-K. (B) When analyzing the HERV-K tags, LTR tags were most abundant, followed by gag-pol and then the env region tags (tags were normalized to respective gene lengths) (C) All host genes with transcript expression profiles correlated with HERV-K(II) env tag abundance (r2≥0.5) were analyzed using the DAVID tools <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097984#pone.0097984-DAVID1" target="_blank">[58]</a> for enriched gene ontology (GO) terms. Genes related to cell cycle functions and chromosomal organization were most strongly associated with HERV-K(II) env expression. With the use of DAVID bioinformatics resources <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0097984#pone.0097984-Dennis1" target="_blank">[59]</a>, the predicted target genes were classified according to KEGG functional annotations to identify pathways that were actively regulated by HERV-K(II) env transcripts in brain tissue. The most over-represented GO term belonged to the transcriptional regulation and chromosome organization followed by different stages of cell cycle pathway. (Mann Whitney t test, *p<0.05, **p<0.01).</p

(A) Individual cell lines displayed differential constitutive HERV-K(... more (A) Individual cell lines displayed differential constitutive HERV-K(II) env expression profiles. (B) Upon treatment of human fetal neurons, db-cAMP did not have any effects on HERV-K(II) env expression but EGF down-regulated HERV-K(II) expression. (C) U937 and (D) HFA showed decreased in HERV-K(II) env expression upon both db-cAMP and EGF exposure. (n = 4 replicates per group across two independent experiments).</p

(A) Transfection of the pHERV-Kenv plasmid into SK-N-SH cells showed ... more (A) Transfection of the pHERV-Kenv plasmid into SK-N-SH cells showed HERV-K(II) Env immunoreactivity at the predicted molecular weight on western blot. (B) Upon treatment with supernatants from SK-N-SH cells transfected with pHERV-Kenv plasmid, HFN showed increases in BDNF and NGF transcript abundance compared to the control vector transfected cells. (n = 3, with technical quadruplicates) (C) βIII-tubulin expression in HFN following 24-hour exposure to supernatants from HFA-transfected with the pHERV-Kenv or the control vector, showing an increase in βIII-tubulin immunoreactivity in cells exposed to HERV-K Env-transfected cells. (n = 2, with technical octuplicates) (Student t test, *p<0.05, **p<0.01).</p