Regarding Alzheimer's disease (AD), specific neuronal populations and brain regions exhibit selective vulnerability. Understanding the basis of this selective neuronal and regional vulnerability is essential to elucidate the molecular mechanisms underlying AD pathology. However, progress in this area is currently hindered by the incomplete understanding of the intricate functional and spatial diversity of neuronal subtypes in the human brain.
View Article and Find Full Text PDFMotivation: Fluorophore-assisted seed amplification assays (F-SAAs), such as real-time quaking-induced conversion (RT-QuIC) and fluorophore-assisted protein misfolding cyclic amplification (F-PMCA), have become indispensable tools for studying protein misfolding in neurodegenerative diseases. However, analyzing data generated by these techniques often requires complex and time-consuming manual processes. Additionally, the lack of standardization in F-SAA data analysis presents a significant challenge to the interpretation and reproducibility of F-SAA results across different laboratories and studies.
View Article and Find Full Text PDFPurpose: Perihilar cholangiocarcinoma (pCCA) is a rare malignancy requiring resection of extrahepatic bile ducts with or without hepatectomy. Prognostic models for post-operative outcomes in pCCA are unusable in pre-operative decision-making as most are based on post-operative variables. Additionally, no pre-operative models include futile laparotomy or benign hilar stenosis (BHS) as possible outcomes.
View Article and Find Full Text PDFBackground: Available literature lacks information regarding the accuracy and reliability of the AO/OTA classification for tibial shaft fractures. This study aimed to assess the inter- and intra-observer agreement and accuracy of the AO/OTA 42 classification (4-signs) for adult patients with tibial shaft fractures.
Materials And Methods: The study design is an accuracy, inter- and intra-observer agreement study.
Sensitive and specific antemortem diagnostic tests are a prerequisite for effective management of chronic wasting disease (CWD). Paired with readily accessible samples that accurately reflect CWD status, the real-time quaking-induced conversion (RT-QuIC) assay has the potential to enable more effective CWD surveillance and interventions. We evaluated the feasibility of RT-QuIC as a CWD diagnostic test using 6-mm ear tissue biopsies from elk (Cervus canadensis).
View Article and Find Full Text PDFFree, prior, and informed consent (FPIC) is now a globally established norm and is a condition of equitable engagement with Indigenous peoples and local communities in biodiversity conservation. However, implementation is frequently questioned in terms of its efficacy in top-down-driven governance contexts. Local officials represent core voices often absent from mainstream discourse.
View Article and Find Full Text PDFBackground: Postoperative morbidity can reduce quality of life, physical performance, and tolerability of postoperative chemotherapy in patients with colorectal liver metastases (CRLM). Exercise can improve these outcomes in some cancer populations. However, it remains unknown whether exercise can be delivered in the early postoperative period following surgery for CRLM without increasing the risk of harms.
View Article and Find Full Text PDFThe water channel aquaporin 4 (AQP4) contributes to water flow and waste removal across the blood-brain barrier and its levels, organization and localization are perturbed in various neurological diseases, including Alzheimer's Disease. This renders AQP4 a potentially valuable therapeutic target. However, most functional assays aimed at identifying modulators of AQP4 function are performed with primary rodent cells and do not consider inter-cellular variations in AQP4 abundance and presentation.
View Article and Find Full Text PDFBackground: The aim of this study was to investigate the perioperative outcomes of robotic liver surgery (RLS) and Open liver surgery (OLS) in a centre with a high number of operations.
Methods: A 1:1 propensity score matched (PSM) analysis of a retrospective database of RLS and OLS was performed. Cumulative sum (CUSUM) analysis was performed to identify learning curves.
Background: Biliary tract cancer (BTC) is a malignancy characterized by a low 5-year survival rate (<20 %). Clinical aspects such as tumor resectability, Eastern Cooperative Oncology Group performance status score (ECOG-PS), and molecular profiling are used to determine the treatment for these patients. Diagnosis and treatment are typically established by a multidisciplinary team (MDT).
View Article and Find Full Text PDFIndividuals with inflammatory bowel disease (IBC) and high-risk individuals are advised to discuss participation with their doctor and not to participate in colorectal cancer (CRC) screening. Yet a substantial proportion still participate in the Danish faecal immunochemical test (FIT) screening and have a higher positive FIT rate than the average-risk population. We estimated the risk of false-positive screening among individuals with inflammatory bowel disease and high-risk individuals to improve recommendations regarding screening participation.
View Article and Find Full Text PDFThe rapid geographic spread of chronic wasting disease (CWD) in white-tailed deer (WTD; ) increases the need for the development and validation of new detection tests. Real-time quaking-induced conversion (RT-QuIC) has emerged as a sensitive tool for CWD prion detection, but federal approval in the United States has been challenged by practical constraints on validation and uncertainty surrounding RT-QuIC robustness between laboratories. To evaluate the effect of inter-laboratory variation on CWD prion detection using RT-QuIC, we conducted a multi-institution comparison on a shared anonymized sample set.
View Article and Find Full Text PDFPurpose: Lipopolysaccharide (LPS)-type endotoxins are naturally found in the gut microbiota and there is emerging evidence linking gut microbiota and neuroinflammation leading to retinal neurodegeneration. Thinning of the retinal nerve fiber layer (RNFL) is a biomarker of retinal neurodegeneration, and a hallmark of glaucoma, the second leading cause of blindness worldwide. We assessed the association of a blood biomarker of LPS with peripapillary RNFL thickness (RNFLT) and its longitudinal evolution up to 11 years.
View Article and Find Full Text PDFObjective: The objective of this study was to evaluate the long-term oncological outcomes of patients with colorectal liver metastasis (CRLM) randomized for associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) or 2-stage hepatectomy (TSH).
Introduction: For advanced CRLM, TSH or ALPPS may be needed for tumor freedom. The randomized, controlled, multicenter trial LIGRO showed an increased resection rate in patients who underwent ALPPS but no difference in morbidity or mortality.
Statement Of Problem: The maxillary lateral incisor is often congenitally missing in patients with a cleft palate. The congenital cleft presents the practitioner with challenges including quantity and quality of bone, a surgically managed cleft correction, and limited clinical space.
Purpose: The purpose of this investigation was to calculate the 5-year success and survival rate of narrow-diameter implants used to restore a missing lateral incisor in patients with a cleft palate.
Neurodegenerative diseases (NDs) in mammals, such as Alzheimer's disease (AD), Parkinson's disease (PD), and transmissible spongiform encephalopathies (TSEs), are characterized by the accumulation of misfolded proteins in the central nervous system (CNS). Despite the presence of these pathogenic proteins, the immune response in affected individuals remains notably muted. Traditional immunological strategies, particularly those reliant on monoclonal antibodies (mAbs), face challenges related to tissue penetration, blood-brain barrier (BBB) crossing, and maintaining protein stability.
View Article and Find Full Text PDFMusculoskeletal injuries (MSKI) are one of the biggest challenges for military services globally, contributing to substantial financial burdens and lost training and working days. Effective evidence-based intervention strategies are essential to reduce MSKI incidence, and research has shown the positive effect of both nutritional interventions and physical training (PT) interventions on reducing MSKI incidence. Levels of vitamin D metabolites have been associated with MSKI and bone stress fracture risk, while calcium and vitamin D supplementation has been shown to reduce the incidence of stress fractures during military training.
View Article and Find Full Text PDFPrion diseases are untreatable fatal transmissible neurodegenerative diseases that affect a wide range of mammals, including humans, and are caused by PrP, the infectious self-templating conformation of the host-encoded protein, PrP. Prion diseases can be transmitted via surfaces (e.g.
View Article and Find Full Text PDFBackground: Ablation is an effective, parenchymal-sparing treatment for primary liver cancer and liver metastases. The purpose of this study was to report our initial experience with laparoscopic microwave ablation regarding postoperative complications, rate of conversions to open procedure, and technical efficacy.
Methods: This was a quality improvement project carried out at a tertiary care center in Denmark.
Background: This study aimed to evaluate the patient-reported relevance, test-retest reliability, and responsiveness for each of the five KOOS subscales in patients with lateral tibial plateau fractures.
Methods: Adult patients with surgically treated lateral tibial plateau fractures (AO 41B) were included. The primary outcome measure was the KOOS subscales: Pain, Symptoms, Activity of Daily Living (ADL), Sport and Recreational Activities (Sport/rec), and kne-related Quality of Life (QOL).
Background: Previous researched has demonstrated potent health and survival advantages across three-generations in longevity-enriched families. However, the survival advantage associated with familial longevity may manifest earlier in life than previously thought.
Methods: We conducted a matched cohort study comparing early health trajectories in third-generation grandchildren (n = 5,637) and fourth-generation great-grandchildren (n = 14,908) of longevity-enriched sibships to demographically matched births (n = 41,090) in Denmark between 1973 and 2018.