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Introduction: Neurology wait times - from referral to consultation - continue to grow, leading to various adverse effects on patient outcomes. Key elements of virtual care can be leveraged to improve efficiency. This study examines the implementation of a novel virtual care model - Virtual Rapid Access Clinics - at the Neurology Centre of Toronto. The model employs a patient-centred care workflow, involving multidisciplinary staff and online administrative tools that are synthesized to expedite care and maintain quality., Methods: Virtual Rapid Access Clinic efficacy was studied by determining average wait times and patient throughput, calculated from anonymous data that was extracted from the clinic patient database (n  =  1542). Comparative analysis focused on new patient consultations during the 12-month periods prior to (pre-Virtual Rapid Access Clinic, n  =  456) and following (post-Virtual Rapid Access Clinic, n  =  1086) Virtual Rapid Access Clinic implementation., Results: After Virtual Rapid Access Clinic implementation, there was a mean 15-day wait time reduction, and a monthly average 52-patient increase in patient throughput. Wait time reductions and increased patient throughput were observed in all three Virtual Rapid Access Clinic sub-clinics - epilepsy, headache and concussion. Respectively, average wait times reduced significantly by 26.4 and 18.9 days and insignificantly by 1.1 days; monthly average patient throughputs increased by 235%, 95% and 161%., Discussion: These findings demonstrated that the Virtual Rapid Access Clinic model of care is effective at reducing patient wait times and increasing patient throughput. While the Virtual Rapid Access Clinic presents a feasible model both during and after pandemic restrictions, further research exploring its scalability in other care contexts, potential changes in care quality and efficiency outside of pandemic restrictions must be performed., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Setting: Task sharing can fill health workforce gaps, improve access to care, and enhance health equity by redistributing health services to providers with less training. We report learnings from a demonstration project designed to assess whether lay student vaccinators can support community immunizations., Intervention: Between July 2022 and February 2023, 27 undergraduate and graduate students were recruited from the University of Toronto Emergency First Responders organization and operated 11 immunization clinics under professional supervision. Medical directives, supported with online and in-person training, enabled lay providers to administer and document vaccinations when supervised by nurses, physicians, or pharmacists. Participants were invited to complete a voluntary online survey to comment on their experience., Outcomes: Lay providers administered 293 influenza and COVID-19 vaccines without adverse events. A total of 141 participants (122 patients, 17 lay vaccinators, 1 nurse, and 1 physician) responded to our survey. More than 80% of patients strongly agreed to feeling safe and comfortable with lay providers administering vaccines under supervision, had no concerns with lay vaccinators, and would attend another lay vaccinator clinic. Content and thematic analysis of open-text responses revealed predominantly positive experiences, with themes about excellent vaccinators, organized and efficient clinics, and the importance of training, communication, and access to regulated professionals. The responding providers expressed comfort working in collaborative immunization teams., Implications: Lay student providers can deliver vaccines safely under a medical directive while potentially improving patient experiences. Rather than redeploying scarce professionals, task sharing strategies could position trained lay vaccinators to support immunizations, improve access, and foster community engagement., (© 2024. The Author(s).)

The objective of this study was to evaluate the effects of supplementing monensin (19.8 g/Mg DM TMR; MON) and Saccharomyces cerevisiae CNCM I-1077 live-cell yeasts (Saccharomyces cerevisiae CNCM I-1077; 1 × 10 10 cfu/head per day; LCY) on lactation performance, feeding behavior, and total-tract nutrient digestibility of high-producing dairy cows. Sixty-four multiparous Holstein cows (3.2 ± 1.5 lactations; 97 ± 16 DIM, and 724 ± 68 kg of BW at covariate period initiation) and 32 gate feeders were enrolled in a study with a completely randomized design and a 2 × 2 factorial arrangement. Cows and gate feeders were randomly assigned to treatments (16 cows and 8 gate feeders per treatment). Cows were allowed 2 wk to acclimate to feeding gates followed by a 2-wk covariate period. During the acclimation and covariate periods, all cows were fed a diet containing MON and LCY. Following the covariate period, cows were enrolled in a 10-wk treatment period during which cows were randomly assigned to 1 of 4 treatments: (1) a combination of MON and LCY (MON-LCY), (2) MON-CON, (3) CON-LCY, or (4) neither MON nor LCY (CON-CON). Data were analyzed using a mixed model with week as a repeated measure and fixed effects of MON, LCY, week, and all their interactions. Cow (treatment) was included as a random effect. The average covariate period value of each variable was used as a covariate. Three-way interactions were observed for DMI and feed efficiency. Dry matter intake decreased from wk 4 to 5 and wk 8 to 10 in MON-LCY cows compared with CON-CON. No treatment differences were observed for actual or component-corrected milk yield or milk components, except for a tendency for LCY to decrease milk fat yield. Feed efficiency was greater for MON-LCY relative to CON-CON in 4 of 10 wk. Interactions between MON and LCY were observed for dry matter and organic matter digestibility, where both were lower for CON-CON than other treatments. Under the conditions of the present study, feeding dairy cows in a high feed bunk density a combination of MON and LCY can decrease intake and improve feed efficiency without affecting milk production or components. Additionally, monensin and live-cell yeasts may each improve total-tract digestibility based on improvements in DM and OM digestibility., (The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Functional seizures (FS), the most common subtype of functional neurological disorder (FND), cause serious neurological disability and significantly impact quality of life. Characterized by episodic disturbances of functioning that resemble epileptic seizures, FS coincide with multiple comorbidities and are treated poorly by existing approaches. Novel treatment approaches are sorely needed. Notably, mounting evidence supports the safety and efficacy of psychedelic-assisted therapy (PAT) for several psychiatric conditions, motivating investigations into whether this efficacy also extends to neurological disorders. Here, we synthesize past empirical findings and frameworks to construct a biopsychosocial mechanistic argument for the potential of PAT as a treatment for FS. In doing so, we highlight FS as a well-defined cohort to further understand the large-scale neural mechanisms underpinning PAT. Our synthesis is guided by a complexity science perspective which we contend can afford unique mechanistic insight into both FS and PAT, as well as help bridge these two domains. We also leverage this perspective to propose a novel analytic roadmap to identify markers of FS diagnostic specificity and treatment success. This endeavor continues the effort to bridge clinical neurology with psychedelic medicine and helps pave the way for a new field of psychedelic neurology., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: At the time of writing this manuscript, authors EL and AJ were employed by Numinus Wellness Inc. MG serves as Chief Research Officer of EntheoTech Bioscience. MB and EA are part-time consultants to Numinus Wellness Inc.

Psychedelic compounds have been utilized by humans for centuries for medicinal, religious, and tribal purposes. Clinical trial data starting from the early 2000s and continuing today indicates that psychedelics are a clinically efficacious treatment for a variety of neurological and psychiatric disorders. However, all clinical trials examining these substances have excluded any individual with a past or current history of seizures, leaving a large cohort of epilepsy and non-epilepsy chronic seizure disorder patients without anywhere to turn for psychedelic-assisted therapy. These exclusions were made despite any significant evidence that clinically supervised psychedelic use causes or exacerbates seizures in this population. To date, no clinical trial or preclinical seizure model has demonstrated that psychedelics induce seizures. This review highlights several cases of individuals experiencing seizures or seizure remission following psychedelic use, with the overall trend being that psychedelics are safe for use in a controlled, supervised clinical setting. We also suggest future research directions for this field., Competing Interests: Author FC was employed by Jamaican Medical Cannabis Corporation. Author ECL is employed by Numinus. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Freidel, Kreuder, Rabinovitch, Chen, Huang and Lewis.)

Psychedelic-assisted therapy (PAT) may treat various mental health conditions. Despite its promising therapeutic signal across mental health outcomes, less attention is paid on its potential to provide therapeutic benefits across complex medical situations within rehabilitation medicine. Persons with spinal cord injury (SCI) have a high prevalence of treatment-resistant mental health comorbidities that compound the extent of their physical disability. Reports from online discussion forums suggest that those living with SCI are using psychedelics, though the motivation for their use is unknown. These anecdotal reports describe a consistent phenomenon of neuromuscular and autonomic hypersensitivity to classical serotonergic psychedelics, such as psilocybin and lysergic acid diethylamide (LSD). Persons describe intense muscle spasms, sweating, and tremors, with an eventual return to baseline and no reports of worsening of their baseline neurological deficits. The discomfort experienced interferes with the subjective beneficial effects self-reported. This phenomenon has not been described previously in the academic literature. We aim to provide a descriptive review and explanatory theoretical framework hypothesizing this phenomenon as a peripherally dominant serotonin syndrome-like clinical picture-that should be considered as such when persons with SCI are exposed to classical psychedelics. Raising awareness of this syndrome may help our mechanistic understanding of serotonergic psychedelics and stimulate development of treatment protocols permitting persons with SCI to safely tolerate their adverse effects. As PAT transitions from research trials into accepted clinical and decriminalized use, efforts must be made from a harm reduction perspective to understand these adverse events, while also serving as an informed consent process aid if such therapeutic approaches are to be considered for use in persons living with SCI., Competing Interests: E.C.L. is the VP of Psychedelic Neurology at Numinus., (© Stephanie Karzon Abrams et al., 2023; Published by Mary Ann Liebert, Inc.)

The objective of this experiment was to evaluate the effect of microbial inoculation and storage length on the fermentation profile and nutrient composition of high-moisture corn (HMC) ensiled at 2 different dry matter (DM) concentrations. High-moisture corn was harvested when kernel DM concentrations were approaching 65% as-fed, and either left undried (HMC65; 67.6% DM) or dried at 40 °C to approximately 70% DM (HMC70; 71.0% DM), and then ensiled in quadruplicate vacuum pouches untreated (CON) or after one of the following inoculant treatments: 6.36 × 105 cfu of Lentilactobacillus buchneri DSM 12856, Lactiplantibacillus plantarum DSM 12836, and Pediococcus acidilactici DSM 16243 per g of HMC (LBLP); or 3.0 × 105 cfu of Lentilactobacillus buchneri DSM 12856, Lentilactobacillus diolivorans DSM 32074, and P. acidilactici DSM 16243 per g of HMC (LBLD). Vacuum pouches were allowed to ferment for 7, 14, 28, or 56 d. A three-way interaction was observed (P = 0.01) for the pH of HMC, where CON for HMC70 was greatest across storage lengths and HMC65 treatments generally had a lower pH than other treatments. Concentrations of total acids were greater (P = 0.001) in HMC65 than HMC70 and greater (P = 0.001) in HMC treated with LBLP and LBLD than CON. An interaction between DM concentration, microbial inoculation, and storage length was observed (P = 0.05) for concentrations of acetic acid. At 14 d, acetic acid concentrations were greater in HMC65 treated with LBLD than other treatments. Likewise, at 56 d, concentrations of acetic acid were greatest in HMC65 treated with LBLD, followed by HMC70 treated with LBLD. An interaction between DM concentration, microbial inoculation, and storage length was observed (P = 0.05) for 7-h starch disappearance (starchD). Across all DM concentration and inoculant treatment combinations, starchD increased with increasing storage length. StarchD was also generally greater for HMC65 treatments compared to HMC70, with small differences among inoculants. Results suggest that microbial inoculation can improve fermentation of HMC by increasing the production of antifungal acetic acid, but that DM concentration at ensiling remains a primary determinant of HMC fermentability., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study aimed to evaluate the effects of cutting height, heterofermentative microbial inoculants, and storage length on the fermentation profile and nutrient composition of whole-plant corn silage. The experiment was a completely randomized design with a 2 (cutting height) × 3 (microbial inoculation) × 5 (storage length) factorial arrangement of treatments. Corn forage was harvested at two cutting heights: either 25 cm (REG) or 65 cm (HI). Then, forage was inoculated with one of three microbial inoculants: (1) 300,000 CFU/g of fresh forage of Pediococcus acidilactici DSM 16243, Lentilactobacillus buchneri DSM 12856, and L. diolivorans DSM 32074 (LBLD; Bonsilage Speed inoculant, Provita Supplements Inc., Mendota Heights, MN), (2) 500,000 CFU/g of fresh forage of Lactiplantibacillus plantarum DSM 12837 and L. buchneri DSM 16774 (LPLB; Bonsilage Corn + WS inoculant, Provita Supplements Inc., Mendota Heights, MN), or (3) distilled water (CON). Last, forage was randomly assigned to ferment for 5, 7, 14, 28, or 56 d of storage in vacuum-sealed bags. Silage pH was affected by a three-way interaction ( P  = 0.01), where CON treatments decreased continually over time while LPLB and LBLD began to increase at later storage lengths. Acetic acid concentration was greater ( P  = 0.001) in LPLB and LBLD than CON silage after 56 d of storage. Silage treated with LBLD did not have detectable levels of propionic acid ( P  > 0.05), although 1-propanol concentration was greater ( P  = 0.001) in LBLD treatments after 56 d of storage. The concentrations of total acids and acetic acid were greater ( P  = 0.01 and P  = 0.001, respectively) for REG silage compared to HI. Additionally, HI silage had greater ( P  = 0.001 and P  = 0.001, respectively) concentrations of dry matter (DM) and starch, while neutral detergent fiber (aNDF) and lignin concentrations were lower ( P  = 0.001 and P  = 0.001, respectively) in HI silage compared to REG silage. Last, HI silage had a greater ( P  = 0.001) NDF digestibility than REG silage. The results of this study demonstrate that increasing cutting height can improve nutrient composition of whole-plant corn silage. Additionally, results demonstrate that heterofermentative microbial inoculants can be used to shift silage fermentation to the production of lactic and acetic acids., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Background: A small body of evidence suggests medical cannabis may facilitate wound healing, but the exact mechanism of this effect is unclear., Purpose: This case report describes a patient with a pressure injury (PI) who received cannabis oil treatment for pain management and sleep improvement., Methods: A 37-year-old woman with multiminicore disease, scoliosis, short-chain acyl-CoA dehydrogenase deficiency, and epilepsy presented to the Neurology Centre of Toronto with chronic pain and sleep disturbance, including difficulty initiating and maintaining sleep. She also had a 5-year history of a PI between her right iliac crest and right rib cage that had progressively worsened. The patient received a medical cannabis oil protocol that used a combination of cannabidiol and tetrahydrocannabinol., Results: Cannabis oil was effective in treating pain and sleep difficulties. Unexpectedly, during the first 2 weeks of treatment, the PI started to heal and was almost completely closed at the 2-month follow-up., Conclusion: Although it is unknown if the observed healing of this refractory PI was indirectly or directly related to the cannabidiol and tetrahydrocannabinol treatment, the potential relationships among pain, sleep disturbance, cannabis treatment, and healing should be explored.

This study aimed to assess the effects of a heterofermentative microbial inoculant and storage length on fermentation profile, aerobic stability, and nutrient composition in whole-plant sorghum silage (WPSS) from different varieties. Experiment 1, a completely randomized design with a 2 × 3 factorial treatment arrangement, evaluated microbial inoculation [CON (50 mL distilled water) or LBLD ( Lactobacillus plantarum DSM 21762, L. buchneri DSM 12856, and L. diolivorans DSM 32074; 300,000 CFU/g of fresh forage)] and storage length (14, 28, or 56 d) in forage WPSS. The LBLD silage had lower pH compared to CON, and greater concentrations of succinic acid, ethanol, 1,2-propanediol (1,2-PD), 1-propanol, 2,3-butanediol and total acids. After 56 d, lactic acid concentration was greater for CON, while acetic acid and aerobic stability were greater in LBLD silage. Experiment 2, a completely randomized design with a 2 × 3 factorial treatment arrangement, evaluated effects of microbial inoculation (same as experiment 1) and storage length (14, 28, or 56 d) in WPSS of three varieties [forage sorghum (Mojo Seed, OPAL, Hereford, TX), sorghum-sudangrass (Dyna-gro Seed, Fullgraze II, Loveland, CO, United States), or sweet sorghum (MAFES Foundation Seed Stocks, Dale, MS State, MS)]. The LBLD forage sorghum had greater acetic acid and 1,2-PD concentrations at 56 d and 28 d, respectively, but lower concentrations of propionic acid at 56 d and butyric acid at 14 and 28 d. Additionally, WSC concentration was greater for CON than LBLD at 28 d. Furthermore, CON sweet sorghum had greater lactic acid, propionic acid, and butyric acid concentrations. However, greater acetic acid and 1,2-PD were observed for LBLD sweet sorghum. The CON sweet sorghum had greater concentration of WSC and yeast counts. The CON sorghum sudangrass had greater lactic and butyric acid concentrations than LBLD at 14 d, but lower acetic acid and 1,2-PD concentrations at 56 d. Yeast counts were greater for CON than LBLD sorghum sudangrass silage. Overall, results indicate inoculation of WPSS with Lactobacillus plantarum DSM 21762, L. buchneri DSM 12856, and L. diolivorans DSM 32074 improves heterofermentative co-fermentation allowing the accumulation of acetic acid concentration and increasing antifungal capacities and aerobic stability of WPSS., Competing Interests: The authors declare that this study received partial funding from Provita Supplements Inc. (Mendota Heights, MN, United States). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication. The reviewer CA declared a shared affiliation with one of the authors, JG, to the handling editor at the time of the review., (Copyright © 2021 Diepersloot, Pupo, Ghizzi, Gusmão, Heinzen, McCary, Wallau and Ferraretto.)

Background and Purpose: Genetics and drug interactions contribute to large interindividual variation in human CYP2D6 activity. Here, we have characterized propranolol inhibition of human and mouse CYP2D using transgenic (TG) mice, which express both mouse CYP2D and human CYP2D6, and wild-type (WT) mice. Our purpose was to develop a method for in vivo manipulation of CYP2D6 enzyme activity which could be used to investigate the role of CYP2D6 in drug-induced behaviours., Experimental Approach: Dextromethorphan metabolism to dextrorphan was used to measure CYP2D activity and to characterize propranolol inhibition in vitro and in vivo. Effects of propranolol pretreatment (24 hr) on serum levels of the CYP2D6 substrate haloperidol and haloperidol-induced catalepsy were also studied., Key Results: Dextrorphan formation velocity in vitro was threefold higher in liver microsomes of TG compared to WT mice. Propranolol acted as a mechanism-based inhibitor (MBI), inactivating CYP2D in liver microsomes from TG and WT mice, and humans. Pretreatment (24 hr) of TG and WT mice with 20 mg·kg -1 intraperitoneal propranolol reduced dextrorphan formation in vivo and by liver microsomes in vitro. Serum haloperidol levels and catalepsy were increased., Conclusions and Implications: Propranolol was a potent MBI of dextrorphan formation in liver microsomes from TG and WT mice, and humans. The inhibition parameters in TG overlapped with those in WT mice and in humans. Inhibition of CYP2D with propranolol in vivo in TG and WT mice altered drug responses, allowing further investigation of variations in CYP2D6 on drug interactions and drug responses., (© 2019 The British Pharmacological Society.)

Migration from countries where female genital cutting (FGC) is practiced means women's healthcare providers need to meet this population's unique healthcare needs. We explored providers' FGC-related experience, knowledge of the cultural practice, prior training, attitudes towards medicalization, including reinfibulation, and clinical practice. An online, 53-question survey to a multidisciplinary sample of women's health providers in the US were recruited by email via professional organizations, medical departments, and the authors' professional networks. From a total of 508 usable surveys, nearly half of respondents did not receive formal FGC training, but a majority had cared for FGC-affected women in their practice. A 'know-do' gap existed with managing infibulated patients; and surgical defibulation procedures were not routinely offered. Most respondents (79%, n = 402) reported a desire for additional education. Women's healthcare providers in the US, regardless of disciplinary backgrounds, are inadequately prepared to meet the needs of FGC-affected women. To address these, FGC content needs to be embedded in educational and training curricula, and ongoing clinical mentorship made available.

Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The purpose of the present study was to examine the effects of electrode placements centered over and offset from the innervation zone (IZ) with different interelectrode distances (IED) on the time and frequency domain parameters of the electromyographic (EMG) signal during a fatiguing submaximal, isometric workout. 11 adults performed an isometric leg extension muscle action at 50% maximal voluntary isometric contraction (MVIC) to exhaustion. Electromyographic amplitude and frequency parameters were determined from electrode placements with different IED centered over, at proximal offset, at distal offset, and away from the IZ at 10, 50, and 100% of the time to exhaustion using an electrode array. There were greater absolute EMG amplitude and lower absolute EMG frequency for electrode placements over and offset from the IZ, but lower absolute EMG amplitude over than offset from the IZ regardless of IED at each time-point during the time to exhaustion. The absolute EMG frequency values were affected by the location relative to the IZ and IED of the electrode placements, and were greater for distal offset vs. proximal offset electrode placements at each time-point. Normalization of the EMG amplitude and EMG frequency values to MVIC eliminated differences due to IED and electrode placements during the fatiguing workout., (© Georg Thieme Verlag KG Stuttgart · New York.)

This study aimed to assess extent of knowledge and perceptions of TB within the growing Hispanic community of Utah County, Utah, and the need for focused community educational intervention within that demographic. A mixed-method approach was used and included a survey of 166 adult males and females, and two focus groups with Hispanic women. TB was better known for its ability to kill (92.8 %) than for being contagious (64.5 %); while most knew that TB mainly affects the lungs (77.7 %) and is spread through coughing (75.3 %). Few believed that overcrowded living conditions were a risk factor for TB (30.1 %). Many believed that TB could be cured with medicine (75.3 %). And 65.7 % reported they had been tested for TB, and 7 % had been told by a doctor they had TB. Focus group data showed while most had knowledge of major TB symptoms, some had key misperceptions about disease transmission, testing, TB vaccine, and various protective factors. Enhanced education and dissemination of information on TB, to include an emphasis on symptoms, testing, and treatment within this demographic is recommended. A culturally-appropriate intervention should utilize a participatory approach, to include the local health department in partnership with various Hispanic community-based organizations.

Repeated exposure to sub-anesthetic doses of ketamine in rats has been shown to induce cognitive deficits, as well as behavioral changes akin to the negative symptoms of schizophrenia, giving much face validity to the use of ketamine administration as a pharmacological model of schizophrenia. This study sought to further characterize the behavioral effects of two different ketamine pre-treatment regimens, focusing primarily on the effects of repeated ketamine administration on novelty processing, a capacity that is disrupted in schizophrenia. Rats received 5 or 14 intra-peritoneal injections of 30mg/kg ketamine or saline across 5 or 7days, respectively. They were then tested in an associative mismatch detection task to examine their ability to detect novel configurations of familiar audio-visual sequences. Furthermore, rats underwent a sequential novel object and novel object location exploration task. Subsequently, rats were also tested on the delayed matching to place T-maze task, sucrose preference task and locomotor tests involving administering a challenge dose of amphetamine (AMPH). The high-dose ketamine pre-treatment regimen elicited impairments in mismatch detection and working memory. In contrast, the low-dose ketamine pre-treatment regimen improved performance of novelty detection. In addition, low-dose ketamine pre-treated rats showed locomotor sensitization following an AMPH challenge, while the high-dose ketamine pre-treated rats showed an attenuated locomotor response to AMPH, compared to control rats. These findings demonstrate that different regimens of repeated ketamine administration induce alterations in novelty processing in opposite directions, and that differential neural adaptations occurring in the mesolimbic dopamine system may underlie these effects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To report the feasibility, safety, and clinical outcomes of an exploratory study of MR-guided Laser Interstitial Thermal Therapy (MRgLITT) as a minimally invasive surgical procedure for the ablation of epileptogenic foci in children with drug-resistant, lesional epilepsy., Methods: Retrospective chart review of all MRgLITT procedures at a single tertiary care center. All procedures were performed using a U.S. Food and Drug Administration (FDA)-cleared surgical laser ablation system (Visualase Thermal Therapy System). Predefined clinical and surgical variables were extracted from archived medical records., Results: Seventeen patients underwent 19 MRgLITT procedures from May 2011 to January 2014. Mean age at seizure onset was 7.1 years (range 0.1-14.8 years). Mean age at surgery was 15.3 years (range 5.9-20.6 years). Surgical substrates were mixed but mainly composed of focal cortical dysplasia (n = 11). Complications occurred in four patients. Average length of hospitalization postsurgery was 1.56 days. Mean follow-up was 16.1 months (n = 16; range 3.5-35.9 months). Engel class I outcome was achieved in seven patients (7/17; 41%), Engel class II in one (1/17; 6%), Engel class III in three (3/17; 18%), and Engel class IV in six (6/17; 35%). Three patients (3/8; 38%) with class I and II outcomes and five patients (5/9; 56%) with class III and IV outcomes had at least one prior resection. Fisher's exact test was not statistically significant for the association between Engel class outcome and previous resection (p = 0.64)., Significance: This study provides descriptive results regarding the use of MRgLITT in a mixed population of pediatric, lesional, drug-resistant epilepsy cases. The ability to classify case-specific outcomes and reduce technical complications is anticipated as experience develops. Further multicenter, prospective studies are required to delineate optimal candidates for MRgLITT, and larger cohorts are needed to more accurately define outcome and complication rates., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Objective: The natural history of succinic semialdehyde dehydrogenase (SSADH) deficiency in adulthood is unknown; we elucidate the clinical manifestations of the disease later in life., Methods: A 63-year-old man with long-standing intellectual disability was diagnosed with SSADH deficiency following hospitalization for progressive decline, escalating seizures, and prolonged periods of altered consciousness. We present a detailed review of his clinical course and reviewed our SSADH deficiency database adult cohort to derive natural history information., Results: Of 95 patients in the database for whom age at diagnosis is recorded, there are 40 individuals currently aged 18 years or older. Only 3 patients were diagnosed after age 18 years. Of 25 adults for whom data are available after age 18, 60% have a history of epilepsy. Predominant seizure types are generalized tonic-clonic, absence, and myoclonic. EEGs showed background slowing or generalized epileptiform discharges in two-thirds of adults for whom EEG data were collected. History of psychiatric symptoms was prominent, with frequent anxiety, sleep disturbances, and obsessive-compulsive disorder., Conclusions: We identified patients older than 18 years with SSADH deficiency in our database following identification and review of a patient diagnosed in the seventh decade of life. The illness had a progressive course with escalating seizures in the index case, with fatality at age 63. Diagnosis in adulthood is rare. Epilepsy is more common in the adult than the pediatric SSADH deficiency cohort; neuropsychiatric morbidity remains prominent., (© 2015 American Academy of Neurology.)

Objective: Headaches are a common problem in the pediatric population. In 2002, the American Academy of Neurology (AAN) developed guidelines on neuroimaging for patients presenting with headache. Our objective was to determine the frequency of computed tomographic (CT) scanning ordered by a range of medical practitioners for pediatric patients presenting with primary headache., Methods: A retrospective chart review was conducted at the Children's Hospital of Eastern Ontario (CHEO), a tertiary care centre in Ontario. One hundred fifty-one records of patients referred to the outpatient neurology clinic at CHEO with ''headache'' or ''migraine'' as the primary complaint from 2004 to 2009 were randomly selected. Ninety-nine patients with normal neurologic examinations were ultimately included., Results: Thirty-four patients (34%; 95% CI 25-45) had undergone CT scanning. None of the 34 CT scans (0%; 95% CI 0-10) showed significant findings, and none changed the headache diagnosis or management. Eleven (32%) of the CT scans were ordered by CHEO neurologists, 15 (44%) by community physicians, and 8 (24%) by CHEO emergency physicians., Conclusion: A high proportion of children presenting with primary headaches and a normal neurologic examination undergo CT scanning, despite well-established AAN guidelines regarding neuroimaging. Most of these CT scans do not appear to alter diagnosis and management. A variety of non-evidencebased factors may be encouraging physicians to overinvestigate this population and, as a result, increasing the risk of adverse events due to radiation exposure. Implementing initiatives at a site-based level that promote the use of established guidelines before performing CT scanning in this population may be beneficial.

Nitric oxide (NO) exerts vasodilatatory, antiplatelet, antioxidant, and antiproliferative effects. Endothelium-derived NO has been shown to be of crucial importance in cardiovascular protection, whereas evidence that NO is synthesized by platelets and regulates platelet function is still controversial. By using a sensitive and specific fluorescent probe, 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM), we visualized NO production in individual platelets undergoing adhesion on a collagen substrate under flow conditions. NO production, monitored in real time, was dependent on the shear rates applied, increasing with the raising of the shear rates. Furthermore, NO production increased in the presence of l-arginine (nitric-oxide synthase [NOS] substrate), and it decreased in the presence of L-NG-monomethyl arginine (L-NMMA) (NOS inhibitor) but not of D-NG-monomethyl arginine (D-NMMA) (L-NMMA-inactive enantiomer). Platelet deposition, measured with mepacrine-labeled platelets, was inversely related to NO production. A correlation was evident between Ca(++) elevation and NO production, suggesting that platelet NO formation is triggered by intracytoplasmic Ca(++) elevation. Simultaneous measurement of NO and Ca(++) indicated that NO production in individual platelets is preceded by Ca(++) elevations, with a lag phase of 33 ± 9.5 s. Our studies provide the first direct demonstration of platelet NO production triggered by the interaction with an activating surface under flow and suggest that intraplatelet Ca(++) elevation elicits the production of NO which, in turn, modulates thrombus size., (© 2015 by The American Society of Hematology.)