A novel molecular design based on a quinazolinone scaffold was developed the attachment of aryl alkanesulfonates to the quinazolinone core through a thioacetohydrazide azomethine linker, leading to a new series of quinazolinone-alkanesulfonates 5a-r. The antimicrobial properties of the newly synthesized quinazolinone derivatives 5a-r were investigated to examine their bactericidal and fungicidal activities against bacterial pathogens like , (Gram-positive), , , (Gram-negative), in addition to (unicellular fungal). The tested compounds demonstrated reasonable bactericidal activities compared to standard drugs.
View Article and Find Full Text PDFPurpose: More active high-dose chemotherapy (HDC) regimens are needed for autologous stem-cell transplantation (ASCT) for refractory lymphomas. Seeking HDC enhancement with a poly(ADP-ribose) polymerase (PARP) inhibitor, we observed marked synergy between olaparib and vorinostat/gemcitabine/busulfan/melphalan (GemBuMel) against lymphoma cell lines, mediated by inhibition of DNA damage repair. Our preclinical work led us to clinically study olaparib/vorinostat/GemBuMel with ASCT.
View Article and Find Full Text PDFEpilepsia
January 2025
Objective: This study was undertaken to test the following hypotheses in the Atp1a3 mouse (which carries the most common human ATP1A3 (the major subunit of the neuronal Na/K-adenosine triphosphatase [ATPase]) mutation, D801N): sudden unexpected death in epilepsy (SUDEP) occurs during seizures and is due to terminal apneas in some and due to lethal cardiac arrhythmias in others; and Atp1a3 mice have central cardiorespiratory dysregulation and abnormal respiratory drive.
Methods: Comparison was made of littermate wild-type and Atp1a3 groups using (1) simultaneous in vivo video-telemetry recordings of electroencephalogram, electrocardiogram, and breathing; (2) whole-body plethysmography; and (3) hypoglossal nerve recordings.
Results: In Atp1a3 mice, (1) SUDEP consistently occurred during seizures that were more severe than preterminal seizures; (2) seizure clustering occurred in periods preceding SUDEP; (3) slowing of breathing rate (BR) and heart rate was observed preictally before preterminal and terminal seizures; and (4) the sequence during terminal seizures was as follows: bradypnea with bradycardia/cardiac arrhythmias, then terminal apnea, followed by terminal cardiac arrhythmias.
Objective: To compare fall risk scores of hearing aids embedded with inertial measurement units (IMU-HAs) and powered by artificial intelligence (AI) algorithms with scores by trained observers.
Study Design: Prospective, double-blinded, observational study of fall risk scores between trained observers and those of IMU-HAs.
Setting: Tertiary referral center.
Patients with multiple myeloma (MM) without high-risk cytogenetic abnormalities are classified as having standard-risk MM (SRMM), and data focusing on their outcomes after autologous hematopoietic stem cell transplantation (autoHCT) are limited. To evaluate survival outcomes for patients with SRMM receiving autoHCT, and to elucidate factors that impact these outcomes. Single-center retrospective analysis that included consecutive MM patients who received upfront autoHCT between 2013 and 2021, had available cytogenetic information and had no high-risk chromosomal abnormalities on fluorescence in situ hybridization, defined as t(4;14), t(14;16), del(17p) or 1q21 gain or amplification.
View Article and Find Full Text PDFEndocytosis is a prominent mechanism for SARS-CoV-2 entry into host cells. Upon internalization into early endosomes (EEs), the virus is transported to late endosomes (LEs), where acidic conditions facilitate spike protein processing and viral genome release. Dynein and kinesin motors drive EE transport along microtubules; dynein moves EEs to the perinuclear region, while kinesins direct them towards the plasma membrane, creating a tug-of-war over the direction of transport.
View Article and Find Full Text PDFObjective: To identify patterns of food taxes acceptability among French adults, and to investigate population characteristics associated with them.
Design: Cross-sectional data from the NutriNet-Santé e-cohort. Participants completed an ad-hoc web-based questionnaire to test patterns of hypothetical food taxes acceptability (i.
Hematology Am Soc Hematol Educ Program
December 2024
The remarkable improvement in survival among individuals with hematological malignancies receiving chimeric antigen receptor (CAR) T-cell therapy has highlighted the growing unmet need to incorporate patient-centered assessments in management guidelines for these patients. That CAR T-cell therapy is associated with unique toxicities and relatively high symptom burden in the first few weeks after cell infusion is well known. Magnifying the patient's voice by using patient-reported outcomes (PROs) might support personalized intervention in the acute-care setting, optimize the use of medical resources, improve satisfaction with therapy, and enhance survival benefit.
View Article and Find Full Text PDFBackground: Mindful eating (ME) is a promising approach for promoting healthy eating. Although an association between ME and healthier eating habits has been indicated in the literature, data remain limited. The aim of this cross-sectional study was to investigate the association between ME and several nutritional indicators, including overall diet quality, consumption of ultra-processed foods (UPF), organic foods, food groups, and intake of energy and nutrients in a large population sample.
View Article and Find Full Text PDFIntroduction: The general-purpose rating scales used by clinical pharmacists to rate their activities have not been extensively studied in specialist care units. This study aims to describe drug-related problems (DRPs) and pharmacist interventions (PIs) in a French hematopoietic cell therapy (HCT) unit and to evaluate the PIs' likely clinical, economic, and organizational impacts.
Methods: We retrospectively assessed all DRPs reported and all PIs issued between December 2018 and December 2021.
Achieving bone union remains a significant clinical dilemma. The use of osteoinductive agents, specifically bone morphogenetic proteins (BMPs), has gained wide attention. However, multiple side effects, including increased incidence of cancer, have renewed interest in investigating alternatives that provide safer, yet effective bone regeneration.
View Article and Find Full Text PDFAging of the epidermis partially occurs as a consequence of epidermal cell senescence, a non-proliferative state in which cells remain metabolically active and acquire changes in their secretome. We previously reported that senescent normal human epidermal keratinocytes (NHEKs) have two opposite outcomes: either cell death by excess of autophagic activity or escape from senescence to give rise to post-senescence neoplastic emerging (PSNE) cells. In this study, we investigated the role of PTGS2, the inducible enzyme of the prostaglandin biosynthesis pathway, in the onset of NHEK senescence and in the switch from senescence to pre-transformation.
View Article and Find Full Text PDFBackground: Nutri-Score is a scientifically validated 5-color front-of-pack nutrition label reflecting the nutrient profile of foods. It has been implemented in several European countries on a voluntary basis, pending the revision of the European labeling regulation. Hence, scientific evidence is needed regarding the ability of the nutrient profile underlying the Nutri-Score (uNS-NPS, 2023-updated version) to characterize healthier foods.
View Article and Find Full Text PDFUnlabelled: Nebivolol is a third-generation beta-blocker known for its high selectivity for beta-1 adrenergic receptors and its unique ability to induce vasodilation via nitric oxide (NO) release. Nebivolol, despite its favourable safety profile, can lead to significant liver injury. We describe the case of a 73-year-old hypertensive patient who developed significant liver enzyme elevations following the addition of nebivolol to her treatment regimen.
View Article and Find Full Text PDFThe healthcare system is wrestling with the impact of demographics on demand for care. We hear anecdotally of heightened patient acuity and increased prevalence of chronic disease. Southlake is a leading healthcare organization serving the northern York Region and southern Simcoe County.
View Article and Find Full Text PDFAutologous transplantation remains the standard of care for eligible multiple myeloma (MM) patients, yet optimal CD34 cell dose remains unclear. We conducted a retrospective study on MM patients undergoing upfront transplant between 2005 and 2021 and divided them into low (≤2.5 × 10 cells/kg) and high (>2.
View Article and Find Full Text PDFCurr Res Transl Med
October 2024
Heterogeneous approaches exist in regard to the management of disease-related co-morbidities in potential allogeneic haematopoietic cell transplantation (allo-HCT) candidates with myelofibrosis (MF). The EBMT Chronic Malignancies Working Party launched an electronic survey to evaluate how MF-specific comorbidities are approached and whether they ultimately affect the decision to transplant. A total of 41/63 (65%) Centers, all of whom were experienced in the management of MF allo-HCT, responded.
View Article and Find Full Text PDFClin Med Insights Arthritis Musculoskelet Disord
October 2024
This narrative review aims specifically to explore the relationship between tobacco exposure and systemic sclerosis (SSc), idiopathic inflammatory myositis (IIM), and systemic lupus erythematosus (SLE). Relevant articles were obtained by searching key terms such as "tobacco," "smoking," "scleroderma," "myositis," "lupus," and "Sjögren's" in PubMed and Google Scholar databases. The selected articles ranged from the years 2010 to 2023.
View Article and Find Full Text PDF