Beta cell function and global glucose metabolism are impaired in Dp(16)1Yey mouse model of Down syndrome.

Aims: Down syndrome (DS) or trisomy 21 is the most prevalent genetic disorder in the world. In addition to common symptoms such as intellectual disabilities and morphological abnormalities, several comorbidities are associated with DS, including metabolic dysfunction. Obesity and diabetes are more prevalent in people with DS compared with the general population.

Pivotal role of exogenous pyruvate in human natural killer cell metabolism.

Resting natural killer (NK) cells display immediate effector functions after recognizing transformed or infected cells. The environmental nutrients and metabolic requirements to sustain these functions are not fully understood. Here, we show that NK cells rely on the use of extracellular pyruvate to support effector functions, signal transduction and cell viability.

Ultrasound diagnosis of cystic cystitis with von Brunn's nest in two cats.

Case Series Summary: Two cats were initially evaluated for recurrent dysuria and haematuria, which were unresponsive to antibiotic and anti-inflammatory treatments. An abdominal ultrasound revealed focal wall thickening with a severe hypoechoic multicystic parietal lesion at the bladder apex. Surgical excision of the lesion (apical cystectomy) led to complete resolution of the clinical signs in both cases.

Assessment of the American College of Surgeons Surgical Risk Calculator (ACS-SRC) for Prediction of Early Postoperative Complications in Patients Undergoing Cytoreductive Surgery for Ovarian Peritoneal Carcinomatosis.

Ovarian cancer (OC) is diagnosed at a locally advanced stage in two-thirds of cases. The first line of treatment consists of cytoreductive surgery (CRS) combined with neoadjuvant and/or adjuvant chemotherapy. However, CRS can be associated with high rates of postoperative complications (POCs), and detection of fragile patients at high risk of POCs is important.

PRIMERS: Polydopamine Radioimmunotherapy with Image-Guided Monitoring and Enhanced Release System.

To overcome the side effects of conventional cancer treatment, multifunctional nanoparticles with image-guidance properties are increasingly desired to obtain enhanced therapeutic efficacy without any toxicity of the treatment. Herein, we introduce the potential of Polydopamine Radioimmunotherapy with Image-guided Monitoring and Enhanced (drug) Release System (PRIMERS) to meet the challenges of currently used cancer therapy. The PDA nanobowls were synthesized using an emulsion-induced interfacial anisotropic assembly method followed by surface modification with high-Z material to obtained the final product PRIMERS.

Efficacy and Safety of a Diet Enriched with EPA and DHA, Turmeric Extract and Hydrolysed Collagen in Management of Naturally Occurring Osteoarthritis in Cats: A Prospective, Randomised, Blinded, Placebo- and Time-Controlled Study.

This study evaluated a therapeutic diet high in eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) of marine source (EPA:DHA ratio 0.69:1), turmeric extract, and hydrolysed collagen in cats ( = 30) with naturally occurring osteoarthritis (OA) over a 13-week (W) period, followed by a 4-W washout, using four previously validated pain/functional outcomes. Compared to the placebo diet, the therapeutic diet significantly improved peak vertical force ( = 0.

Targeted radionuclide therapy against GARP expressing T regulatory cells after tumour priming with external beam radiotherapy in a murine syngeneic model.

Purpose: Radiation therapy (RT) exerts its anti-tumour efficacy by inducing direct damage to cancer cells but also through modification of the tumour microenvironment (TME) by inducing immunogenic antitumor response. Conversely, RT also promotes an immunosuppressive TME notably through the recruitment of regulatory T cells (Tregs). Glycoprotein A repetitions predominant (GARP), a transmembrane protein highly expressed by activated Tregs, plays a key role in the activation of TGF-β and thus promotes the immunosuppressive action of Tregs.

Customizable Lyophilized Agent for Radiotherapy Imaging and TherapY (CLARITY).

Smart radiotherapy biomaterials (SRBs) include seed and liquid biomaterials designed to be employed as fiducial markers during radiotherapy while also delivering therapeutic drug payloads to enhance treatment outcomes. In this study, we investigate a novel Customizable Lyophilized Agent for Radiotherapy Imaging and TherapY (CLARITY) biomaterial, which can be loaded with immunoadjuvants (anti-CD40 monoclonal antibody or Caflanone (FBL-03G)) at the point of care. The CLARITY biomaterial was investigated in an animal model of pancreatic cancer using C57BL6 mice.

Catheter removal after interstitial brachytherapy for breast cancer: Feasibility study for task delegation.

Purpose: This study aims to assess the impact of delegating brachytherapy device removal to radiation therapists (RTTs) in the treatment of breast cancer, in terms of safety and efficacy of treatment.

Material And Methods: A retrospective, observational study was conducted to analyze breast cancer brachytherapy patients. Standardized protocols were drawn up and the RTTs were gradually trained to remove brachytherapy devices under medical supervision.

Loss of embryonically-derived Kupffer cells during hypercholesterolemia accelerates atherosclerosis development.

Hypercholesterolemia is a major risk factor for atherosclerosis and associated cardiovascular diseases. The liver plays a key role in the regulation of plasma cholesterol levels and hosts a large population of tissue-resident macrophages known as Kupffer cells (KCs). KCs are located in the hepatic sinusoids where they ensure key functions including blood immune surveillance.

Histopathology-validated gross tumor volume delineations of intraprostatic lesions using PSMA-positron emission tomography/multiparametric magnetic resonance imaging.

Background And Purpose: Dose escalation in external radiotherapy of prostate cancer shows promising results in terms of biochemical disease-free survival. Boost volume delineation guidelines are sparse which may cause high interobserver variability. The aim of this research was to characterize gross tumor volume (GTV) delineations based on multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen-positron emission tomography (PSMA-PET) in relation to histopathology-validated Gleason grade 4 and 5 regions.

Surgical Management of a Traumatic Brain Herniation Through the Bregmatic Fontanelle in a Dog.

A 1 yr old female Chihuahua was presented for traumatic skull injury. Computed tomography revealed brain herniation through the bregmatic fontanelle. The hernia was manually reduced, and the defect was repaired using a polypropylene mesh.

Therapeutic efficacy of the BKCa channel opener chlorzoxazone in a mouse model of Fragile X syndrome.

Fragile X syndrome (FXS) is an X-linked neurodevelopmental disorder characterized by several behavioral abnormalities, including hyperactivity, anxiety, sensory hyper-responsiveness, and autistic-like symptoms such as social deficits. Despite considerable efforts, effective pharmacological treatments are still lacking, prompting the need for exploring the therapeutic value of existing drugs beyond their original approved use. One such repurposed drug is chlorzoxazone which is classified as a large-conductance calcium-dependent potassium (BKCa) channel opener.

Serotoninergic antidepressants combination in psilocybin-assisted psychotherapy: a case report.

Psilocybin has reemerged as a promising treatment for difficult-to-treat depression (DTD). Although there is limited evidence regarding interactions between psilocybin and other psychotropic drugs, clinical trials require that patients discontinue their antidepressants before study entry to isolate the benefits of psilocybin and to minimize the risk of adverse events. We present the first case of an adult patient with DTD who received psilocybin-assisted psychotherapy (PAP) in combination with two serotoninergic antidepressants (duloxetine and vortioxetine).

Development and validation of an ultrafast method of quantification of rivaroxaban in human serum using laser diode thermal desorption coupled to triple quadrupole mass spectrometry.

Rationale: Rivaroxaban is an anticoagulant prescribed to patients who are at risk of medical conditions such as deep-vein thrombosis, pulmonary embolisms, and strokes caused by blood clots. The administration of this drug is monitored to adjust the dosage and evaluate patients' blood concentration. Rapid quantification of this drug in plasma could make it possible to ensure that the dose present in the blood of patients does not represent a danger for the medical intervention to be carried out.

Immune predictors of response to immune checkpoint inhibitors in mismatch repair-deficient endometrial cancer.

Background: Patients with mismatch repair-deficient (MMRd) endometrial cancer (EC) can derive great benefit from immune checkpoint inhibitors (ICI). However not all responses and predictors of primary resistance are lacking.

Methods: We compared the immune tumor microenvironment of MMRd EC ICI-responders (Rs) and ICI non-responders (NRs), using spatial multiplexed immune profiling and unsupervised hierarchical clustering analysis.

Professional ethics in the French medical physicist community: Survey results and implications.

Introduction: Since 2017, in France, medical physicists (MP) are finally defined by law as health professionals and as such, the roles and responsibilities of an MP lean on those medical professional ethics but MPs lack initial or continuing training in this subject. In order to find out how our colleagues feel about this subject, the following survey was conducted.

Methods: French Society of Medical Physics (SFPM) designed a web survey addressed to its members and non-members concerning ethics based on the 2013 AAPM work; experience and training were highlighted as particularly important within the survey structure.

Accuracy of gross tumour volume delineation with [68Ga]-PSMA-PET compared to histopathology for high-risk prostate cancer.

Background: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.

In vitro to in vivo extrapolation from 3D hiPSC-derived cardiac microtissues and physiologically based pharmacokinetic modeling to inform next-generation arrhythmia risk assessment.

Proarrhythmic cardiotoxicity remains a substantial barrier to drug development as well as a major global health challenge. In vitro human pluripotent stem cell-based new approach methodologies have been increasingly proposed and employed as alternatives to existing in vitro and in vivo models that do not accurately recapitulate human cardiac electrophysiology or cardiotoxicity risk. In this study, we expanded the capacity of our previously established 3D human cardiac microtissue model to perform quantitative risk assessment by combining it with a physiologically based pharmacokinetic model, allowing a direct comparison of potentially harmful concentrations predicted in vitro to in vivo therapeutic levels.

Surveillance of Ancylostoma caninum in naturally infected dogs in Quebec, Canada, and assessment of benzimidazole anthelmintics reveal a variable efficacy with the presence of a resistant isolate in imported dogs.

Ancylostoma caninum is a widely prevalent parasitic nematode in dogs across the world. There has been a notable increase in reports of anthelmintic resistance in A. caninum within the United States of America in recent years, which has led us to investigate the potential of this scenario in Canada.

Democratizing FLASH Radiotherapy.

FLASH radiotherapy (RT) is emerging as a potentially revolutionary advancement in cancer treatment, offering the potential to deliver RT at ultra-high dose rates (>40 Gy/s) while significantly reducing damage to healthy tissues. Democratizing FLASH RT by making this cutting-edge approach more accessible and affordable for healthcare systems worldwide would have a substantial impact in global health. Here, we review recent developments in FLASH RT and present perspective on further developments that could facilitate the democratizing of FLASH RT.

Investigating Associations Between Nonadherence to Guideline-Recommended Treatment of Pediatric Seizures and Adverse Outcomes: A Canadian Feasibility Study.

Background: Emerging evidence suggests that nonadherence to treatment guidelines for seizures may affect patient outcomes. We examined the feasibility of conducting a larger investigation to test this hypothesis in the pediatric population.

Methods: We retrospectively reviewed charts of patients aged ≤18 years who presented with seizure to the emergency departments of two Ontario hospitals in 2019 to 2021.

Effect of radiation therapy on lymph node fluorescence in head and neck squamous cell carcinoma after intravenous injection of indocyanine green: a prospective evaluation.

Background: Indocyanine green (ICG)-guided surgery has proven effective in the identification of neoplastic tissues. The effect of radiation therapy (RT) on lymph node fluorescence after intravenous injection of ICG has not been addressed yet. The objective of this study was to evaluate the influence of RT on node fluorescence during neck dissection in head and neck squamous cell carcinoma (HNSCC).