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BACKGROUND: Plasma p-tau217 has emerged as the most promising blood-based marker (BBM) for the detection of Alzheimer Disease (AD) pathology, yet few studies have evaluated plasma p-tau217 performance in memory clinic settings. We examined the performance of plasma p-tau217 for the detection of AD using a high-sensitivity immunoassay in individuals undergoing diagnostic lumbar puncture (LP). METHODS: Paired plasma and cerebrospinal fluid (CSF) samples were analysed from the TIMC-BRAiN cohort. Amyloid (Aß) and Tau (T) pathology were classified based on established cut-offs for CSF Aß42 and CSF p-tau181 respectively. High-sensitivity electrochemiluminescence (ECL) immunoassays were performed on paired plasma/CSF samples for p-tau217, p-tau181, Glial Fibrillary Acidic Protein (GFAP), Neurofilament Light (NfL) and total tau (t-tau). Biomarker performance was evaluated using Receiver-Operating Curve (ROC) and Area-Under-the-Curve (AUC) analysis. RESULTS: Of 108 participants (age: 69 ± 6.5 years; 54.6% female) with paired samples obtained at time of LP, 64.8% (n = 70/108) had Aß pathology detected (35 with Mild Cognitive Impairment and 35 with mild dementia). Plasma p-tau217 was over three-fold higher in Aß + (12.4 pg/mL; 7.3-19.2 pg/mL) vs. Aß- participants (3.7 pg/mL; 2.8-4.1 pg/mL; Mann-Whitney U = 230, p < 0.001). Plasma p-tau217 exhibited excellent performance for the detection of Aß pathology (AUC: 0.91; 95% Confidence Interval [95% CI]: 0.86-0.97)-greater than for T pathology (AUC: 0.83; 95% CI: 0.75-0.90; z = 1.75, p = 0.04). Plasma p-tau217 outperformed plasma p-tau181 for the detection of Aß pathology (z = 3.24, p < 0.001). Of the other BBMs, only plasma GFAP significantly differed by Aß status which significantly correlated with plasma p-tau217 in Aß + (but not in Aß-) individuals. Application of a two-point threshold at 95% and 97.5% sensitivities & specificities may have enabled avoidance of LP in 58-68% of cases. CONCLUSIONS: Plasma p-tau217 measured using a high-sensitivity ECL immunoassay demonstrated excellent performance for detection of Aß pathology in a real-world memory clinic cohort. Moving forward, clinical use of plasma p-tau217 to detect AD pathology may substantially reduce need for confirmatory diagnostic testing for AD pathology with diagnostic LP in specialist memory services.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Proteínas tau , Humanos , Proteínas tau/sangue , Proteínas tau/líquido cefalorraquidiano , Feminino , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Masculino , Idoso , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/líquido cefalorraquidiano , Imunoensaio/métodos , Pessoa de Meia-Idade , Estudos de Coortes , Medições Luminescentes/métodosRESUMO
BACKGROUND: Penile fibropapilloma is a condition caused by bovine papilloma virus and is frequently encountered in young bulls. Penile fibropapillomatosis is thought to be spread through homosexual mounting behaviour. Fibropapillomas of the penis are painful, often bleed and can impede normal intromission. Treatment may range from allowing time for slow, spontaneous regression to surgical resection but recurrence following surgery is reported by some authors. CASE PRESENTATION: Thirty one bulls that were presented to University College Dublin Veterinary Hospital from March 2017 to March 2023 for surgical resection of penile fibropapillomas were included in this retrospective case series. Twenty-seven of the 31 bulls (87%) were under two years of age. The majority (42%) of bulls presented were Hereford, but Angus, Charolais, Holstein-Friesian and Limousin breeds were also seen. Following examination and diagnosis of penile fibropapilloma, regional anaesthesia (xylazine-procaine epidural and internal pudendal nerve block) and standing surgical intervention (resection and cautery) was performed in each case. Phone call follow-up was performed by one author (EET) in all 31 cases and 2 cases out of the 28 that were contactable showed post-surgical recurrence of penile fibropapillomatosis (i.e., 7.1% recurrence rate). CONCLUSION: This case series summarises the history and presenting findings of 31 bovine penile fibropapilloma cases and describes a regional anaesthetic and standing surgical approach for successful case management.
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BACKGROUND: Headache represents a significant proportion of disability globally in general practice, neurology outpatient settings, and emergency departments. There is scant literature regarding the impact of headache on healthcare services in Ireland. AIMS: We aimed to investigate headache burden across the emergency department, inpatient stays, and neurology outpatient department referrals in an Irish University teaching hospital. METHODS: We prospectively collected data regarding emergency department presentations, inpatient neurology consultations, and neurology outpatient referrals for patients with headache between 13th January and 8th March 2020. Data were analyzed using descriptive statistics. RESULTS: There were 180 emergency department attendances, 50 inpatient consultations, and 76 outpatient referrals with headache. Neurological examinations were often incomplete; neuroimaging was commonly employed. Migraine was the most frequent headache diagnosis at discharge in the emergency department and among inpatients after neurology review. Diagnostic uncertainty was identified-33% of patients left the emergency department with no diagnosis, and "unknown/unspecified headache" was recorded on 49% of outpatient referrals and 30% of inpatient consult requests. Medication overuse headache coexisted with migraine in nine patients in the inpatient group. Prophylaxis had been trialed in 56% of patients with migraine referred to outpatients. CONCLUSIONS: Primary headache disorders have a large impact on hospital services. Diagnostic uncertainty is common; neuroimaging is relied upon. Appropriate care pathways, education, and resource allocation should be prioritized.
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Transtornos da Cefaleia , Transtornos de Enxaqueca , Neurologia , Humanos , Pacientes Ambulatoriais , Pacientes Internados , Universidades , Cefaleia , Serviço Hospitalar de Emergência , Hospitais de Ensino , Encaminhamento e ConsultaRESUMO
Anti-Müllerian hormone (AMH) is secreted by granulosa cells of healthy, growing follicles and is positively correlated with the ovarian reserve. Maternal and environmental factors, such as nutrition, disease, parity and endocrine disruptors, are thought to have a profound impact on ovarian reserve development during early foetal life. For genetic progress, it can be advantageous to breed dairy replacements from heifers to expedite the generation interval; however, there is some evidence that nulliparous animals produce female offspring with smaller ovarian reserves compared with multiparous animals. The objective of this prospective, observational study was to determine whether maternal growth in the pre-conception and early gestational period of nulliparous dairy heifers is associated with pre-weaning AMH concentrations in their female offspring. Our hypothesis was that excessive growth in this period would negatively impact AMH concentrations. Seasonal, pasture-based dairy heifer calves (n = 156) born from nulliparous dams, from six Irish farms, were blood sampled at an average of 60 days of age in spring 2022 and tested for AMH. Mixed-effects linear regression models were constructed with Box-Cox transformed AMH concentration as the dependent variable. The independent variables tested included maternal average daily gain (ADG) from pre-breeding examination (PBE) to pregnancy diagnosis (PD) between 30 and 60 days in calf (DIC), ADG from PBE to PD over 60 DIC and ADG between the two PDs. Calf breed and age at sampling were forced into the models, and the farm was treated as a random effect in all models. We found that as ADG increased from the pre-breeding period to their first PD visit, the AMH concentration in their offspring reduced. However, ADG explained only a small amount of the variation in AMH concentrations (marginal R2 = 0.041). In conclusion, the results of our study suggest that excessive growth prior to conception and in early gestation of nulliparous heifers could impact the ovarian reserve of their female offspring, and may imply that farmers should avoid excessive growth in the immediate pre-breeding and early gestational periods.
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Hormônio Antimülleriano , Hormônios Peptídicos , Gravidez , Bovinos , Animais , Feminino , Estudos Prospectivos , Fertilização , Paridade , PartoRESUMO
INTRODUCTION: Alzheimer's disease and other dementias affect >50 million individuals globally and are characterised by broad clinical and biological heterogeneity. Cohort and biobank studies have played a critical role in advancing the understanding of disease pathophysiology and in identifying novel diagnostic and treatment approaches. However, further discovery and validation cohorts are required to clarify the real-world utility of new biomarkers, facilitate research into the development of novel therapies and advance our understanding of the clinical heterogeneity and pathobiology of neurodegenerative diseases. METHODS AND ANALYSIS: The Tallaght University Hospital Institute for Memory and Cognition Biobank for Research in Ageing and Neurodegeneration (TIMC-BRAiN) will recruit 1000 individuals over 5 years. Participants, who are undergoing diagnostic workup in the TIMC Memory Assessment and Support Service (TIMC-MASS), will opt to donate clinical data and biological samples to a biobank. All participants will complete a detailed clinical, neuropsychological and dementia severity assessment (including Addenbrooke's Cognitive Assessment, Repeatable Battery for Assessment of Neuropsychological Status, Clinical Dementia Rating Scale). Participants undergoing venepuncture/lumbar puncture as part of the clinical workup will be offered the opportunity to donate additional blood (serum/plasma/whole blood) and cerebrospinal fluid samples for longitudinal storage in the TIMC-BRAiN biobank. Participants are followed at 18-month intervals for repeat clinical and cognitive assessments. Anonymised clinical data and biological samples will be stored securely in a central repository and used to facilitate future studies concerned with advancing the diagnosis and treatment of neurodegenerative diseases. ETHICS AND DISSEMINATION: Ethical approval has been granted by the St. James's Hospital/Tallaght University Hospital Joint Research Ethics Committee (Project ID: 2159), which operates in compliance with the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 and ICH Good Clinical Practice Guidelines. Findings using TIMC-BRAiN will be published in a timely and open-access fashion.
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Doença de Alzheimer , Disfunção Cognitiva , Doenças Neurodegenerativas , Humanos , Bancos de Espécimes Biológicos , Doença de Alzheimer/diagnóstico , Envelhecimento , Cognição , Doenças Neurodegenerativas/diagnóstico , Hospitais , Disfunção Cognitiva/diagnósticoRESUMO
Heifers that conceive early in the breeding season are key to the maintenance of a compact calving pattern in seasonal dairy herds. The purpose of this prospective observational study was to determine whether a single pre-breeding examination is useful in predicting future reproductive and calving performance in dairy heifers. This evaluation was based on a matrix of easily measurable variables which could be applied to seasonal, pasture-based dairy heifers. The matrix variables were; body weight (≥55% mature body weight at mating start date), body condition score (≥3.5), and the presence of a corpus luteum. Seasonal, pasture-based dairy heifers (n = 572) on six commercial dairy farms were examined at an average of 28 days prior to the breeding season. At this examination, they were classified as READY (meeting all three of the above criteria), INTERMEDIATE (meeting one or two of the above criteria) or PROBLEM (meeting none of the above criteria) based on the matrix and then exposed to a routine artificial insemination (AI) breeding period followed by bull breeding depending on individual farm management. Subsequent pregnancy status was determined by transrectal ultrasonography initially at 30-60 days in calf (DIC), and confirmed at over 60 DIC. After the breeding season, 519 (96%) of heifers were determined to be pregnant, of which 345 (64%) became pregnant within the first three weeks of the breeding season. Farmers collected calving data; including calving difficulty score, from the heifers the following spring. A logistic regression model was used to analyse the association between the matrix categories and the following outcomes: reproductive (21 day submission rate, 1st AI conception rate, 3 wk and 6 wk in calf rate) and calving (assistance and dystocia). Heifers classified as PROBLEM had significantly lower odds of conceiving to the first AI serve and of becoming pregnant within the first three and six weeks of the breeding season (P ≤ 0.05). In conclusion, the proposed matrix could be practically useful for classifying heifers prior to the breeding season.
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Inseminação Artificial , Reprodução , Animais , Bovinos , Feminino , Masculino , Gravidez , Peso Corporal , Fertilização , Inseminação Artificial/veterinária , Estações do AnoRESUMO
High submission rates and pregnancies per AI are essential to ensure compact calving is achieved in seasonal calving pasture-based systems. Estrus detection inaccuracy (EDI) is one area that negatively impacts pregnancies per AI as it increases the inseminations per pregnancy with little probability of conception, while also having the potential to disrupt established pregnancies. The aims of this cross-sectional study were to provide cow-level estimates of EDI prevalence and determine cow-level risk factors for EDI in seasonal calving pasture-based systems. A total of 1071 milk samples were obtained from 984 cows on 19 farms in spring 2018 and analyzed by radioimmunoassay to determine the progesterone concentration at the time of artificial insemination. Based on a validation study on a subset of cows, an inaccurate estrus detection was described as a concentration of progesterone in foremilk of ≥3 ng/ml which corresponded to a composite milk progesterone value of 5 ng/ml. To investigate selected risk factors for EDI, we conducted statistical analyses using two multivariate logistic regression models, stratifying by insemination number (first versus repeat). The overall prevalence of EDI was 4.7% with a prevalence of 3.3% of EDI at first insemination and 14.1% at repeat insemination. Absence of a mounting abrasion (Adjusted odds ratio (AOR) = 3.0) was a significant risk factor for EDI on first insemination while abnormal preceding repeat interval (AOR = 9.5), the absence of an observed standing estrus (AOR = 12.5) and the absence of a mounting abrasion (AOR = 4.1) were significant risk factors for EDI on repeat insemination. The results indicate that cow-level estimated prevalence of EDI in a selection of pasture-based herds was low at first insemination but higher for repeat insemination. It confirms that certain cow-level risk factors existed for EDI, thus providing preliminary evidence for potential future investigation into the targeted use of on-farm progesterone assays in pasture-based herds.
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Detecção do Estro , Inseminação Artificial , Animais , Bovinos , Estudos Transversais , Feminino , Inseminação Artificial/veterinária , Lactação , Leite , Gravidez , Prevalência , Progesterona , Fatores de Risco , Estações do AnoRESUMO
The first aim of this study was to evaluate the relationship between the concentrations of plasma insulin-like growth factor-I (IGF-I) in the transition period and the incidence of clinical endometritis postpartum. The second aim was to evaluate the relationship between the concentration of plasma IGF-I in the transition period and the estrous synchrony response and pregnancy rate to a controlled internal drug release (CIDR) protocol. A total of 402 dairy cows, 250 multiparous and 152 primiparous, were enrolled. A blood sample was taken from all cows 2 and 1 wk precalving and wk 1, 3, 4, and 5 postcalving for subsequent analysis of IGF-I. Vaginal discharge score as a measurement of uterine health was recorded in wk 3, 4, and 5 postcalving. Estrous cycles of all cows were synchronized on ≥37 d in milk (mean = 59; range 37-93) using an 8-d CIDR protocol. All cows were scanned at 32 to 35 d after insemination to confirm pregnancy. Data were analyzed using Proc Mixed and Proc Logistic models in SAS (version 9.3; SAS Institute Inc., Cary, NC). Plasma IGF-I concentrations were significantly greater in the primiparous cows than in the multiparous cows, both before and after calving, and were therefore analyzed separately. In multiparous cows plasma IGF-I concentrations postcalving were significantly lower among cows with uterine infection than in those without infection, and multiparous cows with a plasma IGF-I concentration less than 40 ng/mL 1 wk after calving were 3 times more likely to suffer from a uterine infection 4 to 5 weeks postcalving (odds ratio 2.8; 95% confidence interval 1.0-7.6). Plasma IGF-I concentrations were significantly greater after calving in the 121 primiparous cows that exhibited estrus post-CIDR protocol (mean 125 ng/mL) than in the 25 primiparous cows that did not respond (mean 95 ng/mL). Multiparous cows with greater plasma IGF-I concentrations postcalving had a significantly greater chance of conceiving (mean plasma IGF-I concentration of conceiving cows = 86 ng/mL; nonconceiving = 70 ng/mL). These results show an association between greater concentrations of plasma IGF-I postcalving and response to CIDR protocol in primiparous animals (mean plasma IGF-I concentration of responders = 116 ng/mL; nonresponders = 95 ng/mL). In contrast no association was detected between concentrations of plasma IGF-I in relation to the response to the CIDR protocol in multiparous cows. In conclusion, changes in circulating concentrations of plasma IGF-I early postpartum may help predict reproductive status of dairy cows.
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Bovinos/fisiologia , Endometrite/veterinária , Sincronização do Estro , Fator de Crescimento Insulin-Like I/metabolismo , Lactação , Progesterona/administração & dosagem , Animais , Endometrite/fisiopatologia , FemininoRESUMO
BACKGROUND: Student feedback has played an important role in the maintenance of quality and standards in higher education. Perhaps the most commonly used method to capture feedback is a series of questions or statements where students indicate their degree of satisfaction or agreement. Focus groups offer an alternative means of capturing 'richer' qualitative data relating to students' thoughts on course structure. Aside from student evaluations, student examination performance has been used as a method to evaluate the efficacy of curriculum changes at programme level. However, this data is utilised less so at a 'finer detail' level to identify specific issues with the delivery of teaching. CASE PRESENTATION: The purpose of this report was to outline the approach taken using qualitative and quantitative data to identify problems with a specific area of teaching, inform a new teaching approach and to assess the impact of those changes. Following quantitative and qualitative analysis, a practical class on dairy herd fertility performance was highlighted as an area for improvement. After the introduction of the newly formatted practical class with a greater focus on self-directed learning, there was a significant increase in the average score (p < 0.001) and a decrease in the proportion of students failing (p < 0.001) the question that assessed the analysis of dairy herd fertility data. In addition, the R-squared value between students' performance in the fertility question and their performance in the overall examination increased from 0.06 to 0.11. CONCLUSIONS: The combination of qualitative focus group data and quantitative analysis of examination performance data represent robust methods for identifying problems associated with specific aspects of veterinary teaching.