Neuropsychiatric symptoms and brain morphology in patients with mild cognitive impairment, cerebrovascular disease and Parkinson disease: A cross sectional and longitudinal study.

OBJECTIVES: Neuropsychiatric symptoms (NPS) increase risk of developing dementia and are linked to various neurodegenerative conditions, including mild cognitive impairment (MCI due to Alzheimer's disease [AD]), cerebrovascular disease (CVD), and Parkinson's disease (PD). We explored the structural neural correlates of NPS cross-sectionally and longitudinally across various neurodegenerative diagnoses. METHODS: The study included individuals with MCI due to AD, (n = 74), CVD (n = 143), and PD (n = 137) at baseline, and at 2-years follow-up (MCI due to AD, n = 37, CVD n = 103, and PD n = 84). We assessed the severity of NPS using the Neuropsychiatric Inventory Questionnaire. For brain structure we included cortical thickness and subcortical volume of predefined regions of interest associated with corticolimbic and frontal-executive circuits. RESULTS: Cross-sectional analysis revealed significant negative correlations between appetite with both circuits in the MCI and CVD groups, while apathy was associated with these circuits in both the MCI and PD groups. Longitudinally, changes in apathy scores in the MCI group were negatively linked to the changes of the frontal-executive circuit. In the CVD group, changes in agitation and nighttime behavior were negatively associated with the corticolimbic and frontal-executive circuits, respectively. In the PD group, changes in disinhibition and apathy were positively associated with the corticolimbic and frontal-executive circuits, respectively. CONCLUSIONS: The observed correlations suggest that underlying pathological changes in the brain may contribute to alterations in neural activity associated with MBI. Notably, the difference between cross-sectional and longitudinal results indicates the necessity of conducting longitudinal studies for reproducible findings and drawing robust inferences.

Evaluating the Current State of Epilepsy Care in the Province of Ontario.

There are numerous challenges pertaining to epilepsy care across Ontario, including Epilepsy Monitoring Unit (EMU) bed pressures, surgical access and community supports. We sampled the current clinical, community and operational state of Ontario epilepsy centres and community epilepsy agencies post COVID-19 pandemic. A 44-item survey was distributed to all 11 district and regional adult and paediatric Ontario epilepsy centres. Qualitative responses were collected from community epilepsy agencies. Results revealed ongoing gaps in epilepsy care across Ontario, with EMU bed pressures and labour shortages being limiting factors. A clinical network advising the Ontario Ministry of Health will improve access to epilepsy care.

Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

INTRODUCTION: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases. METHODS: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative. RESULTS: PVS was significantly associated with sEF (c = -0.125 ± 0.054, 95% bootstrap confidence interval [CI] [-0.2309, -0.0189], p = 0.021). This effect was mediated by both GFAP and WMH. DISCUSSION: In this unique clinical cohort of neurodegenerative diseases, we demonstrated that the effect of PVS on sEF was mediated by the presence of elevated plasma GFAP and white matter disease. These findings highlight the potential utility of imaging and plasma biomarkers in the current landscape of therapeutics targeting dementia. HIGHLIGHTS: Perivascular spaces (PVS) and white matter hyperintensities (WMH) are imaging markers of small vessel disease. Plasma glial fibrillary protein acidic protein (GFAP) is a biomarker of astroglial injury. PVS, WMH, and GFAP are relevant in executive dysfunction from neurodegeneration. PVS's effect on executive function was mediated by GFAP and white matter disease.

Association of plasma biomarkers with cognition, cognitive decline, and daily function across and within neurodegenerative diseases: Results from the Ontario Neurodegenerative Disease Research Initiative.

INTRODUCTION: We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS: Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p-tau)181 and amyloid beta (Aß)42/40 were measured using ultra-sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS: GFAP, NfL, and/or p-tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p-tau181 were highly predictive across diseases, p-tau181 was more specific to the AD/MCI cohort. Sparse associations were found in the FTD and CVD cohorts and for Aß42/40 . DISCUSSION: GFAP, NfL, and p-tau181 are valuable predictors of cognition and function across common neurodegenerative diseases, and may be useful in specialized clinics and clinical trials.

Neuropsychiatric Symptom Burden across Neurodegenerative Disorders and its Association with Function.

OBJECTIVE: Neuropsychiatric symptoms (NPS) are prevalent in neurodegenerative disorders, however, their frequency and impact on function across different disorders is not well understood. We compared the frequency and severity of NPS across Alzheimer's disease (AD) (either with mild cognitive impairment or dementia), Cerebrovascular disease (CVD), Parkinson's disease (PD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), and explored the association between NPS burden and function. METHODS: We obtained data from Ontario Neurodegenerative Disease Research Initiative (ONDRI) that included following cohorts: AD (N = 111), CVD (N = 148), PD (N = 136), FTD (N = 50) and ALS (N = 36). We compared the frequency and severity of individual NPS (assessed by the neuropsychiatric inventory questionnaire) across cohorts using generalized estimating equations and analysis of variance. Second, we assessed the relationship of NPS burden with instrumental (iADLs) and basic (ADLs) activities of living across cohorts using multivariate linear regression while adjusting for relevant demographic and clinical covariates. RESULTS: Frequency of NPS varied across cohorts (χ2(4) = 34.4, p < .001), with post-hoc tests showing that FTD had the greatest frequency as compared to all other cohorts. The FTD cohort also had the greatest severity of NPS (H(4) = 34.5, p < .001). Further, there were differences among cohorts in terms of the association between NPS burden and ADLs (F(4,461) = 3.1, p = 0.02). Post-hoc comparisons suggested that this finding was driven by the FTD group, however, the differences did not remain significant following Bonferroni correction. There were no differences among cohorts in terms of the association between NPS burden and IADLs. CONCLUSIONS: NPS frequency and severity are markedly greater in FTD as compared to other neurodegenerative diseases. Further, NPS burden appears to be associated differently with function across neurodegenerative disorders, highlighting the need for individualized clinical interventions.

Rare neurovascular genetic and imaging markers across neurodegenerative diseases.

INTRODUCTION: Cerebral small vessel disease (SVD) is common in patients with cognitive impairment and neurodegenerative diseases such as Alzheimer's and Parkinson's. This study investigated the burden of magnetic resonance imaging (MRI)-based markers of SVD in patients with neurodegenerative diseases as a function of rare genetic variant carrier status. METHODS: The Ontario Neurodegenerative Disease Research Initiative study included 520 participants, recruited from 14 tertiary care centers, diagnosed with various neurodegenerative diseases and determined the carrier status of rare non-synonymous variants in five genes (ABCC6, COL4A1/COL4A2, NOTCH3/HTRA1). RESULTS: NOTCH3/HTRA1 were found to significantly influence SVD neuroimaging outcomes; however, the mechanisms by which these variants contribute to disease progression or worsen clinical correlates are not yet understood. DISCUSSION: Further studies are needed to develop genetic and imaging neurovascular markers to enhance our understanding of their potential contribution to neurodegenerative diseases.

Characteristics of the Ontario Neurodegenerative Disease Research Initiative cohort.

INTRODUCTION: Understanding synergies between neurodegenerative and cerebrovascular pathologies that modify dementia presentation represents an important knowledge gap. METHODS: This multi-site, longitudinal, observational cohort study recruited participants across prevalent neurodegenerative diseases and cerebrovascular disease and assessed participants comprehensively across modalities. We describe univariate and multivariate baseline features of the cohort and summarize recruitment, data collection, and curation processes. RESULTS: We enrolled 520 participants across five neurodegenerative and cerebrovascular diseases. Median age was 69 years, median Montreal Cognitive Assessment score was 25, median independence in activities of daily living was 100% for basic and 93% for instrumental activities. Spousal study partners predominated; participants were often male, White, and more educated. Milder disease stages predominated, yet cohorts reflect clinical presentation. DISCUSSION: Data will be shared with the global scientific community. Within-disease and disease-agnostic approaches are expected to identify markers of severity, progression, and therapy targets. Sampling characteristics also provide guidance for future study design.

Placenta percreta in primigravida with unscarred uterus complicated by uterine rupture and sudden maternal and fetal death: an autopsy case report.

Placenta percreta is a rare, aggressive, and severe form of the placenta accreta spectrum. One of its most devastating effects is the sudden rupture of uterus. Uterine scarring is the leading risk factor for uterine rupture, although it can also happen, but rarely, in an unscarred uterus showing more severe repercussions. The present study reported a case of an Egyptian primigravida female, aged 29 years old, at 32 weeks of gestation who died suddenly due to uterine rupture complicating placenta percreta, the diagnosis of which was first settled during autopsy. There was no history of abdominal trauma. No medical history of significance was present. Autopsy denoted an intrauterine fetal death of 32 weeks gestational age. The fundus of the uterus had a laceration (rupture) of the uterine wall including the serosa and myometrium. The placenta has extensively infiltrated the fundus uterine wall and penetrated the myometrium and serosa. Histopathological examination of the ruptured site on the uterus confirms total invasion of the uterine wall by chorionic villi with the presence of hemorrhage and fibrin indicating placenta percreta. Uterine rupture due to placenta percreta may go unnoticed, especially when no associated high-risk factors exist. The current case depicts that placenta percreta is a rare but critical complication of pregnancy that may exist at any stage of pregnancy without any associated high-risk factors with unusual symptoms and leads to uterine rupture and sudden death.

Caregiving concerns and clinical characteristics across neurodegenerative and cerebrovascular disorders in the Ontario neurodegenerative disease research initiative.

OBJECTIVES: Caregiving burdens are a substantial concern in the clinical care of persons with neurodegenerative disorders. In the Ontario Neurodegenerative Disease Research Initiative, we used the Zarit's Burden Interview (ZBI) to examine: (1) the types of burdens captured by the ZBI in a cross-disorder sample of neurodegenerative conditions (2) whether there are categorical or disorder-specific effects on caregiving burdens, and (3) which demographic, clinical, and cognitive measures are related to burden(s) in neurodegenerative disorders? METHODS/DESIGN: N = 504 participants and their study partners (e.g., family, friends) across: Alzheimer's disease/mild cognitive impairment (AD/MCI; n = 120), Parkinson's disease (PD; n = 136), amyotrophic lateral sclerosis (ALS; n = 38), frontotemporal dementia (FTD; n = 53), and cerebrovascular disease (CVD; n = 157). Study partners provided information about themselves, and information about the clinical participants (e.g., activities of daily living (ADL)). We used Correspondence Analysis to identify types of caregiving concerns in the ZBI. We then identified relationships between those concerns and demographic and clinical measures, and a cognitive battery. RESULTS: We found three components in the ZBI. The first was "overall burden" and was (1) strongly related to increased neuropsychiatric symptoms (NPI severity r = 0.586, NPI distress r = 0.587) and decreased independence in ADL (instrumental ADLs r = -0.566, basic ADLs r = -0.43), (2) moderately related to cognition (MoCA r = -0.268), and (3) showed little-to-no differences between disorders. The second and third components together showed four types of caregiving concerns: current care of the person with the neurodegenerative disease, future care of the person with the neurodegenerative disease, personal concerns of study partners, and social concerns of study partners. CONCLUSIONS: Our results suggest that the experience of caregiving in neurodegenerative and cerebrovascular diseases is individualized and is not defined by diagnostic categories. Our findings highlight the importance of targeting ADL and neuropsychiatric symptoms with caregiver-personalized solutions.

Clinical course, viral etiology, and the diagnostic workup for patients with suspected myocarditis: a single-center prospective study.

BACKGROUND: Myocarditis is a highly heterogeneous disorder with a challenging diagnostic work-up. We aimed to focus on the possible diagnostic workup for this condition in settings where endomyocardial biopsy as a gold standard is not always feasible, detect the etiologic cardiotropic viruses in our locality, and follow the clinical course in patients admitted with clinically suspected myocarditis. METHODS: This is a prospective observational study. We recruited patients with clinically suspected myocarditis presenting at a university hospital from October 1st, 2020 until March 31st, 2021. All Patients had a diagnostic coronary angiography and were included only if they had a non-obstructive coronary artery disease. All patients also had cardiac magnetic resonance imaging (CMR) with contrast. Sera were obtained from all suspected patients for detection of antibodies against viruses using enzyme-linked immunosorbent assay, and viral genomes using polymerase chain reaction (PCR), and reverse transcription-PCR. Endomyocardial biopsy was done for patients with a typical CMR picture of myocarditis. RESULTS: Out of 2163 patients presenting to the hospital within the 6 months, only 51 met the inclusion criteria. Males represented 73%, with a mean age of 39 ± 16 years. CMR showed an ischemic pattern in 4 patients and thus they were excluded. We classified patients into two categories based on CMR results: group A (CMR-positive myocarditis), 12 patients (25.5%), and group B (CMR-negative myocarditis), 35 (74.5%) patients. On serological analysis, 66% of patients (n = 31/47) showed antibodies against the common cardiotropic viruses. Parvovirus B19 IgM in 22 patients (47%) and coxsackievirus IgM in 16 (34%) were the most observed etiologies. Regarding the outcome, 42.5% of patients recovered left ventricular ejection fraction and three patients died at 6 months' clinical follow-up. CONCLUSION: Patients with Clinically suspected myocarditis represented 2.2% of total hospital admissions in 6 months. CMR is only a good positive test for the diagnosis of acute myocarditis. Parvovirus B19 and coxsackievirus were the most common pathogens in our locality. TRIAL REGISTRATION: Clinical trial registration no., NCT04312490; first registration: 18/03/2020. First recruited case 01/10/2020. URL: https://register. CLINICALTRIALS: gov/prs/app/action/SelectProtocol?sid=S0009O3D&selectaction=Edit&uid=U0002DVP&ts=2&cx=9zdfin .

Lactating buffalos' productive performance, ruminal kinetics, nutrients digestibility and oxidative status as response to supplementing diets with alpinia galanga.

The current study investigated the effect of adding different doses of galangal rhizome powder (Alpinia galanga) to the diets of lactating buffaloes on milk production, composition and in vitro ruminal fermentation kinetics. Twenty buffaloes were divided into four groups: (T1) a control diet comprising of concentrates, corn silage and rice straw at 50: 35: 15 on a DM basis, (T2) a control diet plus 15 g of galangal/animal/day and (T3) a control diet plus 30 g of galangal/animal/day and (T4) a control diet plus 45 g of galangal/animal/day. Results showed that inclusion of galangal in diets decreased (p < 0.05) the concentrations of butyrate, ammonia-nitrogen, CO2, and total protozoa count as compared with T1. Acetate concentration was lower in T4 as compared with other groups (p < 0.05). While propionate concentration was lower (p < 0.05) in T2 as compared with T1. T3 and T4 lowered (p < 0.05) methane, CO2 productions, and protozoa count. T3 increased (p < 0.05) milk yield, energy corrected milk (ECM), yield of total solids, total protein, and solids not fat (SNF) than recorded for T1. While T4 recorded the lowest values (p < 0.05) of milk yield, ECM, total solids, fat, and total protein. The current results support the hypothesis that the inclusion of galangal in lactating buffaloes' diets at 30 g per animal daily improved feed intake and milk yield.

Impact of atrial septal defect device size on biventricular global and regional function: a two-dimensional strain echocardiographic study.

OBJECTIVE: In this study, we assessed the acute changes in biventricular longitudinal strain after atrial septal defect transcatheter closure and its relation to the device size. METHODS: Hundred atrial septal defect patients and 40 age-matched controls were included. Echocardiography and strain study were performed at baseline and 24 hours and 1 month after the intervention. The study group was divided into two subgroups; group 1: smaller devices were used (mean device size = 1.61 ± 0.05 cm, n = 74) and group 2: larger devices were used (mean device size = 2.95 ± 0.07 cm, n = 26). RESULTS: At baseline, there was a significant difference between the study group and controls as regards right ventricular global longitudinal strain with significant hyperkinetic apex (p = 0.033, p = 0.020, respectively). There was a significant immediate reduction in right ventricular global longitudinal strain (from -24.43 ± 0.49% to -21.62 ± 0.47%, p < 0.001), which showed insignificant improvement after 1-month follow-up. While only left ventricular global longitudinal strain increased after 1 month. Within 24 hours of device closure, all the basal- and mid-lateral segments strains and apical right ventricular strains showed a significant reduction. There was a significant negative correlation between the indexed large device size and an immediate change in the right ventricular global longitudinal strain (r = -0.425, p = 0.034). CONCLUSION: Significant right ventricular global longitudinal strain reduction starts as early as 24 hours after transcatheter closure, irrespective of the device size used. The rapid impact of closure was mainly on the biventricular basal and lateral segments and right ventricular apical ones, especially with the large sized atrial septal defect.

Grape seed alleviates lindane-induced oxidative stress and improves growth performance, caecal fermentation and antioxidant capacity in growing rabbits.

This study evaluated the protective effect of grape seed on performance, caecal characteristics, blood metabolites and liver antioxidant status in lindane-treated rabbits. Four-week-old New Zealand White rabbits (n = 96) with an initial body weight of 0.750 ± 0.23 g were randomly divided into four groups (n = 24). One group was the control received only corn oil orally, while group L were received lindane daily via gavage in corn oil (4 mg/kg BW; 1/50 LD50 for oral dose), group GS was treated with 50 g grape seed /kg diet, and group LGS treated with a combination of both L and GS for 98 days. Results revealed that final body weight (FBW), average daily gain (ADG), dry matter intake and feed efficiency (FE) were similar between GS and control groups, and achieved the highest FBW and ADG, and the best FE. Caecum pH of the L group increased, while the caecum pH of the GS group decreased sharply. There was a significant increase in the concentration of total VFA, acetic acid, propionic acid and NH3 -N in the GS group, but butyric acid level decreased. GS treatment resulted in a significant increase in the concentrations of total protein, albumin and AChE. GPx, GST, CAT and SOD activity decreased, but TBARS activity significantly increased in the group L, while GS caused a significant elevation of antioxidant activity in the liver. These results confirm that the antioxidant compounds present in grape seed can alleviate the oxidative stress caused by lindane-induced hepatotoxicity and could be a useful supplement to maintain health and improve performance in rabbits.

The effects of an initial depolarization pulse on dissolved phase hyperpolarized 129 Xe brain MRI.

PURPOSE: To evaluate the effect of an initial 90° depolarization RF pulse on the dissolved-phase hyperpolarized (HP) xenon-129 (129 Xe) brain imaging and to compare the SNR variability of HP 129 Xe images acquired without an initial depolarization RF pulse to those following the initial depolarization pulse. METHODS: Five cognitive normal healthy volunteers were imaged using a Philips Achieva 3.0T MRI scanner during a single breath-hold following inhalation of 1 L of HP 129 Xe. Each participant underwent six HP 129 Xe scans. Three scans were performed using conventional single-slice projection HP 129 Xe brain imaging, and the other three scans were performed using the HP 129 Xe time-of-flight imaging with an initial rectangular depolarization pulse. RESULTS: Although the utilization of an initial depolarization results in the reduction of the mean image SNR, the presence of an initial depolarization RF pulse reduces the SNR variability of the HP 129 Xe brain image by a factor of 2.26. The highest SNR variability was observed from the posterior brain region, where the anterior region possessed the lower level of signal variability. CONCLUSION: An initial 90° depolarization RF pulse, applied prior to the HP 129 Xe image acquisition, reduced the HP 129 Xe signal variability more than two times between the different breath-hold images.

Hyperpolarized 129 Xe multi-slice imaging of the human brain using a 3D gradient echo pulse sequence.

PURPOSE: To demonstrate the possibility of performing multi-slice in-vivo human brain MRI using hyperpolarized (HP) xenon-129 (129 Xe) in two different orientations and to calculate the signal-to-noise ratio (SNR). METHODS: Two healthy female participants were imaged during a single breath-hold of HP 129 Xe using a Philips Achieva 3.0T MRI scanner (Philips, Andover, MA). Each HP 129 Xe multi-slice brain image was acquired during separate HP 129 Xe breath-holds using 3D gradient echo (GRE) imaging. The acquisition started 10 s after the inhalation of 1 L of HP 129 Xe. Overall, four sagittal and three axial images were acquired (seven imaging sessions per participant). The SNR was calculated for each slice in both orientations. RESULTS: The first ever HP 129 Xe multi-slice images of the brain were acquired in axial and sagittal orientations. The HP 129 Xe signal distribution correlated well with the gray matter distribution. The highest SNR values were close in the axial and sagittal orientations (19.46 ± 3.25 and 18.76 ± 4.94, respectively). Additionally, anatomical features, such as the ventricles, were observed in both orientations. CONCLUSION: The possibility of using multi-slice HP 129 Xe human brain magnetic resonance imaging was demonstrated for the first time. HP 129 Xe multi-slice MRI can be implemented for brain imaging to improve current diagnostic methods.

Development of a simple dynamic algorithm for individualized hepatocellular carcinoma risk-based surveillance using pre- and post-treatment general evaluation score.

BACKGROUND AND AIMS: With the growing number of treated hepatitis C patients, the current 'one-size-fits-all' hepatocellular carcinoma (HCC) surveillance strategies for patients with advanced fibrosis represents a great burden on healthcare systems. An individualized HCC risk strategy incorporates the dynamic changes of HCC risk are lacking. METHODS: This single-centre observational study included 3075 patients, with advanced fibrosis (≥F3) who achieved SVR following DAAs at Egyptian Liver research institute and hospital (ELRIAH) with follow-up period (range 6-72 months). The performance of a recently developed General Evaluation Score (GES) HCC risk stratification score was calculated pre- and post-treatment using Harrell's c statistic. Times to HCC and cumulative incidences were calculated with Kaplan-Meier method and compared using log-rank (Mantel-Cox) test. RESULTS: Pre-treatment GES score stratified patients into low (60.4%), intermediate (23.4%), and (16.2%) high-risk score where 5-year cumulative incidences of HCC were 1.66%, 4.45% and 7.64%, respectively. Harrell's c statistic was 0.801. Post-treatment GES score stratified patients into low (57.4%), intermediate (30.7%) and (11.9%) high-risk score where 5-year cumulative incidences of HCC were 1.35%, 3.49% and 11.09% respectively. The cumulative HCC incidence increased significantly with higher scores (P < .001). Harrell's c statistic was 0.818. Using pre- and post-treatment GES score, GES algorithm was developed with higher predictive value. The cumulative HCC incidence increased significantly with higher scores (P < .001). Harrell's c statistic was 0.832. CONCLUSION: A dynamic algorithm incorporating both pre- and post-GES scores have better performance and predictive value compared with only pre-treatment assessments. The proposed algorithm would help to stratify those who need intensive or being excluded from screening.

Milk yield and composition, feed efficiency, haemato-biochemical parameters and antioxidant status of lactating ewes fed diet supplemented with prickly pear cactus peels.

Prickly pear cactus peels (Opuntia ficus-indica, PPCP) are a powerful source of antioxidant components and available as a by-product in arid regions in large quantities. The current work investigated the effect of dietary supplementation of PPCP on feed efficiency, milk yield and composition, haematology, serum biochemical constituents and antioxidant status of lactating Barki ewes. Fifteen multiparous female Barki sheep (2-3 years old, body weight post partum 46.9 ± 0.59 kg) were individually and randomly distributed into three groups (five ewes each). The first group was the control without PPCP supplementation; the second and third groups were fed for 60 d diets supplemented with dried PPCP powder at daily doses of 5 and 10 g/ewe, respectively. The results revealed a significant increase in total dry matter intake (p ≤ 0.001) and numerical rise in total milk yield (p = 0.054) with PPCP addition at 5 g/ewe compared with the control group. The serum lipid profile was significantly altered by PPCP supplementation. Serum urea nitrogen decreased (p ≤ 0.001) with PPCP treatment. Antioxidant enzyme activities, such as superoxide dismutase, catalase and glutathione peroxidase, were significantly increased (p ≤ 0.001) and the level of thiobarbituric acid-reactive substances was significantly decreased (p ≤ 0.001) with increasing PPCP supplementation levels in a dose-dependent manner. In conclusion, supplementation with 5 g PPCP improved total dry matter intake, serum lipid profiles and antioxidant status in Barki ewes during lactation.

Date press cake replaces corn grains in the diet of lactating Egyptian buffaloes and Barki rams.

High prices of corn grains due to their shortage in some regions force researcher to explore nonconventional alternatives. Therefore, the present study aimed to evaluate the effect of replacing corn grains at 25% (dry matter (DM) basis) with date press cake (DPC) without/with exogenous enzymes at 2 L/ton feed in diets of Barki sheep (24 rams divided as 6 rams/treatment) and Egyptian buffaloes (16 buffaloes divided as 4 buffalo/treatment). Each experiment was conducted under 4 treatments regime: control diet containing only corn grains, T1 diet where the control diet supplemented with exogenous enzyme, T2 diet where the control diet contained DPC on corn replacement (25% DM basis), and T3 diet where the control diet contained DPC on corn replacement (25% DM basis) along with exogenous enzyme supplement. The control diet contained concentrate feed mixture, corn silage, and rice straw at 50:40:10, respectively. Data on nutrient intake, digestibility, and nitrogen balance in sheep, as well as on blood parameters, milk production, and composition in buffaloes, were analyzed using the PROC GLM/MIXED procedure of SAS. The sheep under T2 and T3 treatments demonstrated greater digestibility of dry matter, organic matter, and neutral detergent fibers, along with improved nitrogen balance. The milk yield and its constituents were improved in the buffaloes under T3 treatment followed by those buffaloes under T2 and T1 treatments. This investigation could conclude that replacing corn grains with DPC at 25% (DM basis) in ruminant diets had beneficial effects on nutrients digestibility and milk yield along with its composition.

Implementation of Epilepsy Multigene Panel Testing in Ontario, Canada.

BACKGROUND: Epilepsy is a common neurological condition that shows a marked genetic predisposition. The advent of next-generation sequencing (NGS) has transformed clinical genetic testing by allowing the rapid screen for causative variants in multiple genes. There are currently no NGS-based multigene panel diagnostic tests available for epilepsy as a licensed clinical diagnostic test in Ontario, Canada. Eligible patient samples are sent out of country for testing by commercial laboratories, which incurs significant cost to the public healthcare system. OBJECTIVE: An expert Working Group of medical geneticists, pediatric neurologists/epileptologists, biochemical geneticists, and clinical molecular geneticists from Ontario was formed by the Laboratories and Genetics Branch of the Ontario Ministry of Health and Long-Term Care to develop a programmatic approach to implementing epilepsy panel testing as a provincial service. RESULTS: The Working Group made several recommendations for testing to support the clinical delivery of care in Ontario. First, an extension of community healthcare outcomes-based program should be incorporated to inform and educate ordering providers when requesting and interpreting a genetic panel test. Second, any gene panel testing must be "evidence-based" and takes into account varied clinical indications to reduce the chance of uncertain and secondary results. Finally, an ongoing evaluative process was recommended to ensure continued test improvement for the future. CONCLUSION: This epilepsy panel testing implementation plan will be a model for genetic care directed toward a specific set of conditions in the province and serve as a prototype for genetic testing for other genetically heterogeneous diseases.

Mise en œuvre d'un test diagnostique permettant en Ontario l'analyse d'un panel de plusieurs gènes liés à l'épilepsie.Contexte:L'épilepsie demeure un trouble neurologique fréquent dont la prédisposition génétique apparaît notable. L'émergence du séquençage de nouvelle génération (SNG) a aussi transformé les tests génétiques en permettant un dépistage rapide des variantes causales que l'on retrouve dans de nombreux gènes. À l'heure actuelle, il n'existe pas, pour l'épilepsie, de tests diagnostiques homologués qui permettent en Ontario l'analyse d'un panel de gènes en vertu du SNG. Les échantillons de patients admissibles sont alors envoyés à l'extérieur du Canada afin d'être analysés par des laboratoires commerciaux, ce qui pèse lourd dans les budgets des systèmes publics de santé. Objectif : Un groupe de travail formé d'experts (généticiens médicaux, neurologues pédiatriques et spécialistes en épileptologie, généticiens biochimiques et généticiens moléculaires cliniques) a été formé par le service des laboratoires et de la génétique des ministères de la Santé et des Soins de Longue durée de l'Ontario afin d'élaborer une démarche programmatique visant à mettre en œuvre des tests diagnostiques basés sur un panel de plusieurs gènes. Ces tests seraient ensuite reconnus à titre de service public. Résultats:En matière de dépistage, ce groupe de travail a ainsi émis plusieurs recommandations visant à accompagner la prestation clinique en Ontario. Tout d'abord, un programme s'inspirant du projet « ECHO ¼ (Extension of Community Healthcare Outcomes) devrait être ajouté dans le but de renseigner et de sensibiliser les prestataires de soins de santé qui demandent et qui interprètent ces tests basés sur un panel de plusieurs gènes. Ensuite, tout test de ce type doit reposer sur des preuves et tenir compte d'une panoplie d'indications cliniques afin de réduire les possibilités d'incertitude et de résultats secondaires. Enfin, il a été recommandé de procéder à un processus continu d'évaluation pour s'assurer que ces tests puissent être améliorés dans le futur. Conclusion:Ce plan de mise en œuvre de tests basés sur un panel de plusieurs gènes deviendra un modèle pour les soins destinés à un ensemble spécifique de problèmes de santé en Ontario. Outre l'épilepsie, il pourra servir comme prototype pour le dépistage d'autres maladies hétérogènes sur le plan génétique.

Methods for Improving Screening for Vascular Cognitive Impairment Using the Montreal Cognitive Assessment.

BACKGROUND: Vascular cognitive impairment (VCI) post-stroke is frequent but may go undetected, which highlights the need to better screen cognitive functioning following a stroke. AIM: We examined the clinical utility of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment against a gold-standard neuropsychological battery. METHODS: We assessed cognitive status with a comprehensive battery of neuropsychological tests in 161 individuals who were at least 3-months post-stroke. We used receiver operating characteristic (ROC) curves to identify two cut points for the MoCA to maximize sensitivity and specificity at a minimum 90% threshold. We examined the utility of the Symbol Digit Modalities Test, a processing speed measure, to determine whether this additional metric would improve classification relative to the MoCA total score alone. RESULTS: Using two cut points, 27% of participants scored ≤ 23 and were classified as high probability of cognitive impairment (sensitivity 92%), and 24% of participants scored ≥ 28 and were classified as low probability of cognitive impairment (specificity 91%). The remaining 48% of participants scored from 24 to 27 and were classified as indeterminate probability of cognitive impairment. The addition of a processing speed measure improved classification for the indeterminate group by correctly identifying 65% of these individuals, for an overall classification accuracy of 79%. CONCLUSIONS: The utility of the MoCA in detecting cognitive impairment post-stroke is improved when using a three-category approach. The addition of a processing speed measure provides a practical and efficient method to increase confidence in the determined outcome while minimally extending the screening routine for VCI.