Transient receptor potential channel 1 (TRPC1) is a widely expressed mechanosensitive ion channel located within the endoplasmic reticulum membrane, crucial for refilling depleted internal calcium stores during activation of calcium-dependent signaling pathways. Here, we demonstrate that TRPC1 activity is protective within cartilage homeostasis in the prevention of cellular senescence associated cartilage breakdown during mechanical and inflammatory challenge. We reveal that TRPC1 loss is associated with early stages of osteoarthritis (OA) and plays a non-redundant role in calcium signaling in chondrocytes.
View Article and Find Full Text PDFObjectives: The American Academy of Pediatrics recommends clinicians who treat pediatric patients screen for prenatal alcohol exposure (PAE) to facilitate the identification of children with fetal alcohol spectrum disorders and promote timely access to behavioral and cognitive interventions. We evaluated how frequently clinicians inquire about PAE in their pediatric patient interactions and the methods used to ascertain this information.
Methods: We analyzed data from the Fall 2020 DocStyles survey, a web-based survey of primary healthcare professionals (n = 1754).
Formation of transcellular pores facilitates the transport of materials across endothelial barriers. In Schlemm's canal (SC) endothelium, impaired pore formation is associated with glaucoma. However, our understanding of the cellular processes responsible for pore formation is limited by lack of assays.
View Article and Find Full Text PDFPremature implant failure, a critical concern in biomedical applications, is often attributed to poor biocompatibility and vulnerability to bacterial colonization. These issues are addressed by creating an endoprosthetic material with natural biocompatibility and antibacterial properties. In this in vitro study, the relaxed and unrelaxed tetrahedral amorphous carbon (ta-C) coatings were examined, both fabricated by the improved patented Pulsed Laser Deposition (PLD) technology.
View Article and Find Full Text PDFUltraviolet (UV) rays prompt a natural response in epidermal cells, particularly within melanocytes. The changes in gene expression and related signaling pathways in melanocytes following exposure to UV radiation are still not entirely understood. Our findings reveal that UVB irradiation suppresses the expression of Dicer (also known as Dicer1).
View Article and Find Full Text PDFBackground And Aims: Prophylactic implantable cardioverter-defibrillators (ICDs) are not recommended until left ventricular ejection fraction (LVEF) has been reassessed 40 to 90 days after an acute myocardial infarction. In the current therapeutic era, the prognosis of sustained ventricular arrhythmias (VAs) occurring during this early post-infarction phase (i.e.
View Article and Find Full Text PDFMeasuring pH with an optical sensor requires the immobilization of a chemical recognition phase on a solid surface. Neutral red (NR), an acid base indicator was used to develop two different optical probe configurations. The chemistry of aryl diazonium salts was chosen for the elaboration of this chemical phase, as it enables strong covalent bonds to be established on the surface of metallized glass or metallic surfaces.
View Article and Find Full Text PDFBackground: Situated within a larger project entitled "Exploring the Need for a Uniquely Different Approach in Northern Ontario: A Study of Socially Accountable Artificial Intelligence," this rapid review provides a broad look into how social accountability as an equity-oriented health policy strategy is guiding artificial intelligence (AI) across the Canadian health care landscape, particularly for marginalized regions and populations. This review synthesizes existing literature to answer the question: How is AI present and impacted by social accountability across the health care landscape in Canada?
Methodology: A multidisciplinary expert panel with experience in diverse health care roles and computer sciences was assembled from multiple institutions in Northern Ontario to guide the study design and research team. A search strategy was developed that broadly reflected the concepts of social accountability, AI and health care in Canada.
Background: Fetal alcohol spectrum disorders (FASDs) are lifelong conditions that can occur in a person with prenatal alcohol exposure. Although studies using intensive, in-person assessments of children in selected communities have found higher estimates of children with FASDs than studies of healthcare claims data, claims-based studies provide more current information about individuals with recognized FASDs from diverse populations. We estimated the proportion of children with administratively reported FASDs in two large healthcare claims databases.
View Article and Find Full Text PDFThis article reports a systematic literature review that examined past research exploring the effectiveness of collaborative Augmented Reality (AR) enabled instruction, in higher education contexts. To be included, an article should consist of an experimental study investigating the use of collaborative AR for learning in higher education settings. An initial search was conducted on five databases that resulted in a total of 2537 articles, of which 20 were finalized for this review.
View Article and Find Full Text PDFAberrant activation of the Hedgehog (Hh) signalling pathway has been associated with the development and progression of pancreatic cancer. For this reason, blockade of Hh pathway by inhibitors targeting the G protein-coupled receptor Smoothened (SMO) has been considered as a therapeutic target for the treatment of this cancer. In our previous work, we obtained a new SMO ligand based on a purine scaffold (compound I), which showed interesting antitumor activity in several cancer cell lines.
View Article and Find Full Text PDFHidradenitis Suppurativa (HS) is a chronic inflammatory skin disease that may have profound effects on the patient's quality of life. A personalized HS combination therapy treatment was prescribed to a 54-year-old female suffering from multiple painful sores, as follows: naltrexone capsules titrated from 0.5 mg up to 4.
View Article and Find Full Text PDFBackground: Although male participation in maternal health has gained increasing recognition and support over the years, little is known about male involvement during pregnancy in the Democratic Republic of the Congo. This paper identified male involvement patterns during pregnancy and evaluated their associations with pregnancy and birth preparedness knowledge, gender-equitable attitudes, self-efficacy, and co-parental relationship factors. Lastly, it explored the moderating effect of gender-equitable attitudes and intimate partner violence on the association between relationship satisfaction and male involvement.
View Article and Find Full Text PDFEven seemingly homogeneous on the surface, the oceans display high environmental heterogeneity across space and time. Indeed, different soft barriers structure the marine environment, which offers an appealing opportunity to study various evolutionary processes such as population differentiation and speciation. Here, we focus on Amphiprion clarkii (Actinopterygii; Perciformes), the most widespread of clownfishes that exhibits the highest colour polymorphism.
View Article and Find Full Text PDFConventional pharmacokinetic (PK) bioequivalence (BE) studies aim to compare the rate and extent of drug absorption from a test (T) and reference (R) product using non-compartmental analysis (NCA) and the two one-sided test (TOST). Recently published regulatory guidance recommends alternative model-based (MB) approaches for BE assessment when NCA is challenging, as for long-acting injectables and products which require sparse PK sampling. However, our previous research on MB-TOST approaches showed that model misspecification can lead to inflated type I error.
View Article and Find Full Text PDFCPT Pharmacometrics Syst Pharmacol
July 2024
The recent SarsCov2 pandemic has disrupted healthcare system notably impacting intensive care units (ICU). In severe cases, the immune system is dysregulated, associating signs of hyperinflammation and immunosuppression. In the present work, we investigated, using a joint modeling approach, whether the trajectories of cellular immunological parameters were associated with survival of COVID-19 ICU patients.
View Article and Find Full Text PDFBcr-Abl is an oncoprotein with aberrant tyrosine kinase activity involved in the progression of chronic myeloid leukemia (CML) and has been targeted by inhibitors such as imatinib and nilotinib. However, despite their efficacy in the treatment of CML, a mechanism of resistance to these drugs associated with mutations in the kinase region has emerged. Therefore, in this work, we report the synthesis of 14 new 2,6,9-trisubstituted purines designed from our previous Bcr-Abl inhibitors.
View Article and Find Full Text PDFBackground: Chagas disease, a condition caused by Trypanosoma cruzi, is an endemic disease in Latin American countries that affects approximately eight million people worldwide. It is a continuing public health problem. As nifurtimox and benznidazole are the two pharmacological treatments currently used to treat it, the present research proposes new therapeutic alternatives.
View Article and Find Full Text PDF