Impacts of enzymes and probiotic in improving the utilization of sieved olive pulp meal in growing rabbit diets.

Objective: This research assesses the utilization of sieved olive pulp (SOP) in the diet of growing rabbits through the use of an exogenous enzyme or dry yeast as a pretreatment. Materials and Methods: One hundred sixty-eight male V-Line rabbits aged 5 weeks (weighing 550 ± 25 gm) were randomly divided into seven groups with eight replicates each as follows: the control group was fed a basal diet without supplementation; while the other six groups were fed basal diets containing 20% and 25% of SOP and supplemented with 0.1 gm/kg Econase (E), 0.5 gm/kg dry yeast (Y), and a combination of both. The experiment lasted for 8 weeks. Results: The results indicated that supplementation of E, Y, and EY into rabbit diets containing SOP improved live body weight, body weight gain, feed conversion ratio, and nutrient digestibility. A higher dressing percentage was observed in the groups fed a 20% and 25% SOP diet supplemented with EY (p < 0.05). The treated groups showed an increase in total protein, albumin, globulin, A/G ratio, total antioxidant capacity, superoxide dismutase, and glutathione peroxidase (p < 0.05), while there was a significant decrease in triglycerides, total cholesterol, and malondialdehyde levels (p < 0.05) compared to the control. Rabbit groups fed an SOP diet supplemented with E, Y, or EY demonstrated higher (p < 0.05) economic efficiency compared to the control. Conclusion: Supplementing the diet of rabbits containing SOP with exogenous enzymes and/or dry yeast enhances the nutritional value of SOP while improving rabbit performance, nutrient digestibility, and antioxidant status.

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.

Effects of Dietary Supplementations of Vitamin C, Organic Selenium, Betaine, and Pomegranate Peel on Alleviating the Effect of Heat Stress on Growing Rabbits.

The aim of this study was to investigate the biological activity and sustainable biorefinery development of vitamin C, organic selenium, betaine, and pomegranate peel on the performance, cecal fermentation, and antioxidant status of growing rabbits to alleviate the negative impacts of heat stress. A total of 105 male rabbits at 35 days old with an average weight of 752.55 ± 27.56 g were randomly assigned to five groups (21 rabbits in each). The experimental dietary groups included a control group fed a basal diet without additives (control group) and four treated groups, A, B, C, and D, fed a basal diet supplemented with either a 1000 mg vitamin C/kg diet, a 25 mg organic selenium/kg diet, a 1000 mg betaine/kg diet, or a 20 g pomegranate peel/kg diet, respectively. No negative group (not heat-stressed) was included in the trial. Rabbits given A, B, C, and D supplements showed a significant increase (p < 0.05) in growth performance, nutrient digestion, concentration of total volatile fatty acids (VFA), acetic, and propionic acids, and total bacterial count, and a significant decrease (p < 0.05) in NH3-N concentration, Enterococcus, coliforms, and E. coli counts in the cecum of rabbits. Total protein, albumin, globulin, superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and glutathione peroxidase (GPx) were significantly (p < 0.05) higher in groups supplemented with A, B, C, and D supplements compared to those in the control group. Total cholesterol, triglycerides, creatinine, urea, and malondialdehyde (MDA) were significantly (p < 0.05) lower in groups supplemented with A, B, C, and D supplements compared to those in the control group. In conclusion, the finding showed that the supplementation of vitamin C, organic selenium, betaine, and pomegranate peel played a significant role in alleviating heat stress and had a further beneficial impact on rabbit performance, cecal fermentation and microbiota, and antioxidant status. However, betaine supplementation had a superior positive effect on the nutritional and physiological profile of heat-stressed rabbits.

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.

The significance of PCSK-9's level and polymorphism in premature coronary artery disease: Relation to risk and severity.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a circulating protein that plays an important role in lipid metabolism and is linked to inflammation, which has implications for atherosclerosis and its severe cardiac effects. We studied the potential association of the PCSK-9 gene single nucleotide polymorphism (SNP), Oxidized low-density lipoprotein receptor 1- (OLR-1), and caspase-3 serum levels with the risk and severity of premature coronary artery disease (PCAD). The potential contribution of PCSK-9 serum level to the severity of PCAD patients was also assessed. METHOD: This case-control study included 120 PCAD patients (age < 45), and 60 age matched healthy controls. Serum PCSK-9 and caspase-3 levels and clinical characteristics were recorded. SYNTAX score was calculated to estimate the severity of the coronary artery lesions. The SNP rs2483205 of the PCSK-9 gene and the rs11053646 of the OLR-1gene were genotyped in all participants. RESULTS: Serum PCSK-9 levels were higher in PCAD patients and were significantly different among the three SYNTAX score groups (SS ≤ 12, 12 < SS ≤ 21.5, and SS > 21.5). The diagnostic cutoff values of PCSK-9 and caspase-3 levels for PCAD were > 3.2 ng/mL for both, yielding an area under the curve (AUC) of 0.98 and 0.92, sensitivity of 85 %, 98 %, and specificity of 99.5 %, 93 % for PCSK-9 and caspase-3, respectively. The genotypes TT + CT vs. CC of PCSK-9's rs2483205 SNP presented a higher risk for PCAD and higher SYNTAX scores. Furthermore, the rs11053646 SNP of OLR-1 presented the CG genotype as more risky and having higher SYNTAX scores. CONCLUSION: Circulating PCSK9 and caspase-3 concentrations were higher in PCAD patients and were associated with CAD severity. The SNPs of PCSK-9 (rs2483205) and OLR-1 (rs11053646) were associated with PCAD and its severity.

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.

Medicolegal study of Egyptian unnatural female deaths in the childbearing period during 2019-2020.

Violence against women is a global public health problem, especially in the childbearing period. However, it is considered as the least documented human rights violation worldwide which at its worst can result in femicide. This medico-legal study aims to explore the pattern of unnatural deaths among women in childbearing age group in the Egyptian community in recent years for early detection of women who are at risk and for establishment preventive measures. One hundred and one fifty of suspicious deaths of women in the reproductive age from 13 to 49 years were autopsied in Zeinhom Morgue (the Egyptian Forensic Medicine Authority) during 2019-2020. Demographic data, circumstances of death, causes and manner of death were defined and statistically analyzed. Unnatural death occurred during the 2nd -3rdh decades, 83.4 % were from urban residence, 40.4 % were single while 39.1 % of cases were married. In the majority of deaths, bodies were found at home. Regarding the manner of death, there were 38.4 % suicidal deaths and 38.4 % were homicidal death, while 19.2 % were accidental deaths. Sharp traumatic injuries were the most common pattern in homicidal cases mainly after domestic arguments by a spouse or relative while the most common suicidal and accidental pattern was jumping from height. The present study proved that violence against women resulting in unnatural deaths is very prevalent in Egypt with a rising rate in recent years. These findings could be useful for early identification of vulnerable women and for preventing woman deaths in the future.

Adherence to Quality Indicators for ST-Elevation Myocardial Infarction Management: An Egyptian Experience.

Coronary artery disease remains a significant health problem, especially in developing countries. Adherence to guideline-directed therapy improves the quality of care. In this study we assessed adherence to quality indicators (QIs) for ST-elevation myocardial infarction (STEMI) management in our center as an example from a developing country. Our study included 870 STEMI patients who were admitted to our center (Assiut University Heart Hospital, Egypt) and eligible for primary percutaneous coronary intervention during the period from January 2022 to December 2022. Fifteen QIs were studied. The results show that our center is closely adherent to STEMI management guidelines. However, the most important gaps were related to time delays. The mean of first medical contact (FMC) to electrocardiogram (ECG) time was 13.2 ± 16.1 minutes and arrival time to ECG time was 12.8 ± 3.9 minutes. The mean of FMC to device time for total patients was 61.2 ± 42.8 minutes. However, that for patients transferred from non-PCI capable center was 108.2 ± 63.5 minutes compared to patients presented directly to our center (mean arrival time to a device was around Mean 49.6 ± 22.5 minutes). This resulted in only 77% of patients having FMC to device time < 90 minutes. Regarding guideline-directed medical therapy, we are adherent by more than 90%. In-hospital mortality was 1.1%. So we conclued that many centers in developing countries are closely adherent to QIs of STEMI management. However, there are still some limitations including delays in transportation, a limited number of primary PCI centers, absence of a well-established network of communication between centers, and financial issues.

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.

Plasma brain natriuretic peptide, D-Dimer, and serum troponin-I as predictors for in-hospital death in patients with COVID-19.

The severe acute respiratory syndrome coronavirus 2, first appeared in Wuhan, China, in December 2019. Since then, a variety of strains of the virus were spread throughout the world, prompting the World Health Organization to declare a pandemic in March 2020. Additionally, Coronavirus disease 2019 (COVID-19) can cause a variety of symptoms, ranging from fatigue and fever to severe respiratory and cardiovascular complications. This study evaluated the role of brain natriuretic peptide (BNP), troponin-I and D-dimer as biomarkers for death prediction in hospitalized patients with COVID-19. The study included 90 patients with COVID -19 diagnosed with PCR-RNA testing. They were divided into survivors and non-survivors. Also, 20 apparently healthy individuals age and sex matched were included as a control group. Plasma BNP and serum troponin-I were measured by enzyme linked immune-sorbent assay (ELISA) technique. D-dimer was measured by a turbidimetric technique. Patients with COVID-19 had significantly elevated levels of serum Troponin-I and plasma BNP in comparison to controls (p < 0.0001, for both). D-dimer, troponin-I and BNP levels were significantly higher in the non-survivors group when compared to the survivors group. Troponin-1 can predict COVID-19 severity with sensitivity, specificity, and accuracy of 55.1%, 66.7%, and 57.8%, respectively at a cutoff value of 0.075 (ng /ml); and area under the receiver operating characteristic (AUC) curve of 0.670 (95% CI: 0.551 - 0.790, p=0.018). BNP can predict COVID-19 severity with sensitivity, specificity, and accuracy of 98.6%, 71.4%, 92.2%, respectively at a cutoff value of 16.02 (Pg /ml) and AUC of 0.872 (95% CI: 0.778 - 0.965, p < 0.001). Univariate and multivariate logistic regression analysis showed that only BNP level can significantly predict death among COVID-19 infected patients. In conclusion, plasma BNP and serum troponin-I could be used as prognostic biomarkers for determination of the severity of COVID-19 and BNP could predict mortality.

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.

Association of Dual-Task Gait Cost and White Matter Hyperintensity Burden Poststroke: Results From the ONDRI.

BACKGROUND: Acute change in gait speed while performing a mental task [dual-task gait cost (DTC)], and hyperintensity magnetic resonance imaging signals in white matter are both important disability predictors in older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC is associated with overall hyperintensity volume from specific major brain regions in poststroke. METHODS: This is a cohort study with a total of 123 older (69 ± 7 years of age) participants with history of stroke were included from the Ontario Neurodegenerative Disease Research Initiative. Participants were clinically assessed and had gait performance assessed under single- and dual-task conditions. Structural neuroimaging data were analyzed to measure both, white matter hyperintensity (WMH) and normal appearing volumes. Percentage of WMH volume in frontal, parietal, occipital, and temporal lobes as well as subcortical hyperintensities in basal ganglia + thalamus were the main outcomes. Multivariate models investigated associations between DTC and hyperintensity volumes, adjusted for age, sex, years of education, global cognition, vascular risk factors, APOE4 genotype, residual sensorimotor symptoms from previous stroke and brain volume. RESULTS: There was a significant positive global linear association between DTC and hyperintensity burden (adjusted Wilks' λ = .87, P = .01). Amongst all WMH volumes, hyperintensity burden from basal ganglia + thalamus provided the most significant contribution to the global association (adjusted ß = .008, η2 = .03; P = .04), independently of brain atrophy. CONCLUSIONS: In poststroke, increased DTC may be an indicator of larger white matter damages, specifically in subcortical regions, which can potentially affect the overall cognitive processing and decrease gait automaticity by increasing the cortical control over patients' locomotion.

White matter hyperintensities and smaller cortical thickness are associated with neuropsychiatric symptoms in neurodegenerative and cerebrovascular diseases.

BACKGROUND: Neuropsychiatric symptoms (NPS) are a core feature of most neurodegenerative and cerebrovascular diseases. White matter hyperintensities and brain atrophy have been implicated in NPS. We aimed to investigate the relative contribution of white matter hyperintensities and cortical thickness to NPS in participants across neurodegenerative and cerebrovascular diseases. METHODS: Five hundred thirteen participants with one of these conditions, i.e. Alzheimer's Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia, Parkinson's Disease, or Cerebrovascular Disease, were included in the study. NPS were assessed using the Neuropsychiatric Inventory - Questionnaire and grouped into hyperactivity, psychotic, affective, and apathy subsyndromes. White matter hyperintensities were quantified using a semi-automatic segmentation technique and FreeSurfer cortical thickness was used to measure regional grey matter loss. RESULTS: Although NPS were frequent across the five disease groups, participants with frontotemporal dementia had the highest frequency of hyperactivity, apathy, and affective subsyndromes compared to other groups, whilst psychotic subsyndrome was high in both frontotemporal dementia and Parkinson's disease. Results from univariate and multivariate results showed that various predictors were associated with neuropsychiatric subsyndromes, especially cortical thickness in the inferior frontal, cingulate, and insula regions, sex(female), global cognition, and basal ganglia-thalamus white matter hyperintensities. CONCLUSIONS: In participants with neurodegenerative and cerebrovascular diseases, our results suggest that smaller cortical thickness and white matter hyperintensity burden in several cortical-subcortical structures may contribute to the development of NPS. Further studies investigating the mechanisms that determine the progression of NPS in various neurodegenerative and cerebrovascular diseases are needed.

Men Are at Higher Risk of Screening Positive for Vascular Cognitive Impairment Compared to Women after Stroke and Transient Ischemic Attack.

While women have greater incidence of dementia, men have higher prevalence of vascular risk factors. This study examined sex differences in risk of screening positive for cognitive impairment after stroke. Ischemic stroke/TIA patients (N = 5969) participated in this prospective, multi-centered study, which screened for cognitive impairment using a validated brief screen. Men showed a higher risk of screening positive for cognitive impairment after adjusting for age, education, stroke severity, and vascular risk factors, suggesting that other factors may be contributing to increased risk among men (OR = 1.34, CI 95% [1.16, 1.55], p < 0.001). The effect of sex on cognitive impairment after stroke warrants further attention.

Language discordance as a marker of disparities in cerebrovascular risk and stroke outcomes: A multi-center Canadian study.

Background: Differences in ischemic stroke outcomes occur in those with limited English proficiency. These health disparities might arise when a patient's spoken language is discordant from the primary language utilized by the health system. Language concordance is an understudied concept. We examined whether language concordance is associated with differences in vascular risk or post-stroke functional outcomes, depression, obstructive sleep apnea and cognitive impairment. Methods: This was a multi-center observational cross-sectional cohort study. Patients with ischemic stroke/transient ischemic attack (TIA) were consecutively recruited across eight regional stroke centers in Ontario, Canada (2012 - 2018). Participants were language concordant (LC) if they spoke English as their native language, ESL if they used English as a second language, or language discordant (LD) if non-English speaking and requiring translation. Results: 8156 screened patients. 6,556 met inclusion criteria: 5067 LC, 1207 ESL and 282 LD. Compared to LC patients: (i) ESL had increased odds of diabetes (OR = 1.28, p = 0.002), dyslipidemia (OR = 1.20, p = 0.007), and hypertension (OR = 1.37, p<0.001) (ii) LD speaking patients had an increased odds of having dyslipidemia (OR = 1.35, p = 0.034), hypertension (OR = 1.37, p<0.001), and worse functional outcome (OR = 1.66, p<0.0001). ESL (OR = 1.88, p<0.0001) and LD (OR = 1.71, p<0.0001) patients were more likely to have lower cognitive scores. No associations were noted with obstructive sleep apnea (OSA) or depression. Conclusions: Measuring language concordance in stroke/TIA reveals differences in neurovascular risk and functional outcome among patients with limited proficiency in the primary language of their health system. Lower cognitive scores must be interpreted with caution as they may be influenced by translation and/or greater vascular risk. Language concordance is a simple, readily available marker to identify those at risk of worse functional outcome. Stroke systems and practitioners must now study why these differences exist and devise adaptive care models, treatments and education strategies to mitigate barriers influenced by language discordance.

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.

Silver nanoparticles induced testicular damage targeting NQO1 and APE1 dysregulation, apoptosis via Bax/Bcl-2 pathway, fibrosis via TGF-ß/α-SMA upregulation in rats.

In medicine, silver nanoparticles (AgNPs) are employed often. They do, however, have negative impacts, particularly on the reproductive organs. This research aimed to assess AgNP impact on the testis and the possible intracellular mechanisms to induce testicular deteriorations in rats at various concentrations and different time intervals. Sprague Dawley rats (n = 40) were allocated into four equal groups: the control one, and three other groups injected intra-peritoneally with AgNP solution 0.25, 0.5, and 1 mg/kg b.w. respectively for 15 and 30 days. Our findings revealed that AgNPs reduced body and testicular weights, estradiol (E2) and testosterone (T) hormone levels, and sperm parameters while elevating the nitric oxide and malondialdehyde levels with inhibition of reduced glutathione contents in testicular tissue. Interestingly, AgNPs significantly upregulated the testicular inducible nitric oxide synthase, B cell lymphoma 2 (Bcl-2)-associated X, transforming growth factor, and alpha-smooth muscle actin (α-SMA) expression levels. However, apurinic/apyrimidinic endo deoxyribonuclease 1 (APE1), NAD (P) H quinone dehydrogenase 1 (NQO1), and Bcl-2 expression levels were all downregulated indicating exhaustion of body antioxidant and repairing defense mechanisms in testicles in comparison with the control rats. Various histological alterations were also detected which dramatically increased in rats sacrificed after 30 days such as loss of the lining cells of seminiferous tubules with no spermatozoa and tubular irregularities associated with thickening of their basement membranes. Immunolabeling implicated in the apoptotic pathway revealed a negative expression of Bcl-2 and marked immunoreactivity for caspase-3 after 30 days of AgNP treatment in comparison to the control rats. To our knowledge, there have been no previous publications on the role of the α-SMA, APE1, and NQO1 genes in the molecular pathogenesis of AgNP testicular cytotoxicity following AgNP acute and chronic exposure.

Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke.

Background Cerebral small vessel disease is associated with higher ratios of soluble-epoxide hydrolase derived linoleic acid diols (12,13-dihydroxyoctadecenoic acid [DiHOME] and 9,10-DiHOME) to their parent epoxides (12(13)-epoxyoctadecenoic acid [EpOME] and 9(10)-EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra-high-performance liquid chromatography-mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13-DiHOME/12(13)-EpOME ratio (ß=0.251, P=0.023). The 12,13-DiHOME/12(13)-EpOME ratio was associated with more lacunes (ß=0.266, P=0.028) but not with large vessel stroke volumes. Ratios of 12,13-DiHOME/12(13)-EpOME and 9,10-DiHOME/9(10)-EpOME were associated with greater volumes of white matter hyperintensities (ß=0.364, P<0.001; ß=0.362, P<0.001) and white matter MRI-visible perivascular spaces (ß=0.302, P=0.011; ß=0.314, P=0.006). In small vessel stroke, the 12,13-DiHOME/12(13)-EpOME ratio was associated with higher white matter free water diffusion (ß=0.439, P=0.016), which was specific to the temporal lobe in exploratory regional analyses. The 9,10-DiHOME/9(10)-EpOME ratio was associated with temporal lobe atrophy (ß=-0.277, P=0.031). Conclusions Linoleic acid markers of cytochrome P450/soluble-epoxide hydrolase activity were associated with small versus large vessel stroke, with small vessel disease markers consistent with blood brain barrier and neurovascular-glial disruption, and temporal lobe atrophy. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration.

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.