Background: Cerebral microbleeds (CMBs) are small brain haemorrhages, identified by magnetic resonance imaging (MRI). They indicate potential for cognitive decline and mortality in memory clinic attendees. The presence of more than four CMBs is exclusionary for some clinical trials of disease-modifying therapies for Alzheimer's disease (AD).
View Article and Find Full Text PDFIntroduction: To compare the efficacy of laser activated and sonic activated irrigation on the removal of debris in mesial root canal systems of mandibular molars using micro-computed tomographic analysis.
Methods: Forty-eight mesial roots of extracted mandibular molars with isthmus were selected and randomly allocated into 2 groups: Sonic Group and Laser Group. The root canals were minimally instrumented to a maximum apical file size of 20/06v (DCTaper, SSWhite, NJ).
Introduction: The increase in the population of immunocompromised patients due to advances in management of end-stage diseases and transplants poses challenges in treating infections caused by multi-drug resistant (MDR) pathogens. Cefiderocol (FDC), a siderophore cephalosporin, has shown efficacy against carbapenem-resistant Gram-negative bacteria.
Methods: This retrospective multicentre study investigated the real-world use of FDC in 114 immunocompromised adults treated for MDR infections in 12 French hospitals (June 2020-November 2023).
Background: Cardiovascular (CV) disease is the leading cause of death among U.S. women, yet women have a limited understanding of their CV-related morbidity and mortality risks.
View Article and Find Full Text PDFMonoclonal antibodies are an important class of biologics with over 160 Food and Drug Administration/European Union-approved drugs. A significant bottleneck to global accessibility of recombinant monoclonal antibodies stems from complexities related to their production, storage, and distribution. Recently, gene-encoded approaches such as mRNA, DNA, or viral delivery have gained popularity, but ensuring biologically relevant levels of antibody expression in the host remains a critical issue.
View Article and Find Full Text PDFA central challenge in evolutionary biology is to uncover mechanisms maintaining functional genetic variation in heterogeneous environments . Population genetics theory suggests that beneficial reversal of dominance, where alleles are dominant when beneficial and recessive when deleterious, can help maintain such variation in temporally varying environments . However, empirical examples are scarce due to difficulties in measuring dominance in fitness in field experiments .
View Article and Find Full Text PDFThis commentary explores the vulnerabilities faced by temporary foreign workers (TFWs) in Manitoba, Canada within the context of the COVID-19 pandemic. TFWs often endure substandard working conditions and lack access to essential healthcare services due to their status as non-citizens. The COVID-19 pandemic has further exacerbated their precarious situation, with TFWs experiencing disproportionately high rates of infection.
View Article and Find Full Text PDFBackground And Aims: Preprocedural ultrasound (PPU) reduces the risk of technical failure in non-obese patients and when technical difficulty is predicted. We conducted this review to determine if PPU improves first-pass needle insertion success for neuraxial anesthesia in patients with obesity.
Methods: We conducted a systematic review without meta-analysis, due to the small number of included studies.
Objective: To investigate the effects of the Affordable Care Act (ACA) and its elimination of cost-sharing on contraception utilization, pregnancy rates, and abortion rates.
Methods: We conducted a retrospective cohort study within a healthcare system serving over 4.5 million insured members across 21 medical centers and 250 clinics.
The β and β' subunits of the RNA polymerase (RNAP) are large proteins with complex multi-domain architectures that include several insertional domains. Here, we analyze the domain organizations of RNAP-β and RNAP-β' using sequence, experimentally determined structures and AlphaFold structure predictions. We observe that lineage-specific insertional domains in bacterial RNAP-β belong to a group that we call BEAN (broadly embedded annex).
View Article and Find Full Text PDFCrowding, the phenomenon of impaired visual discrimination due to nearby objects, has been extensively studied and linked to cortical mechanisms. Traditionally, crowding has been studied extrafoveally; its underlying mechanisms in the central fovea, where acuity is highest, remain debated. While low-level oculomotor factors are not thought to play a role in crowding, this study shows that they are key factors in defining foveal crowding.
View Article and Find Full Text PDFObjective: Cardiovascular events prognosis based on CYP2C19 gene polymorphisms had many applications in clinical practice. Assessed characteristics and predictive performance of cardiovascular events in acute coronary syndrome patients with CYP2C19 gene polymorphisms.
Patients And Methods: The patients were analyzed for CYP2C19 gene polymorphisms by real-time polymerase chain reaction (PCR).
Many patients with cancer experience cancer-related cognitive decline (CRCD). Previous studies have shown that elevated S100β, a calcium-binding protein commonly found in glial cells, can exhibit neurotoxic effects, including disruption of the blood-brain barrier (BBB). We studied changes in S100β levels in patients with breast cancer receiving chemotherapy, and the relationship to changes in cognitive function.
View Article and Find Full Text PDFUnlabelled: To increase the achievement of negative R0 surgical margins and increase the low survival rates of pancreatic cancer, improvements in assessing tumor margins during surgical resections are needed. This can be accomplished by using pancreatic cancer-targeted fluorescence molecular imaging agents to intraoperatively detect tumor margins in real time. Because Toll-like receptor 2 (TLR2) is broadly expressed among many cancer types including pancreatic adenocarcinomas, a high-affinity TLR2-targeted fluorescence molecular imaging agent (TLR2L-800) was developed.
View Article and Find Full Text PDFSET and MYND-domain containing protein 3 (SMYD3) mediates epigenetic repression of type I IFN response genes in human papillomavirus (HPV)-negative HNSCC cells, and Smyd3 depletion using anti-sense oligonucleotides (ASOs) increases the sensitivity of syngeneic mouse oral carcinoma (MOC1) models to anti-PD-1 therapy. In this study, we utilized single-cell RNA-seq of MOC1 tumors treated with Smyd3 ASOs and found enrichment of type I IFN response pathways in cancer cells, a shift of CD8 T-cells toward an activated/memory phenotype, and a shift of neutrophils toward an anti-tumorigenic phenotype. Mechanisms of resistance to the Smyd3 ASO and anti-PD-1 combination were derived from cancer cells, macrophages, and CD8 T-cells, including neutrophil enrichment through the upregulation of , repression of and defective antigen presentation.
View Article and Find Full Text PDFIndividuals with systemic sclerosis (SSc) are particularly susceptible to SARS-CoV-2 infections, yet it remains to be determined if they generate humoral and cellular responses comparable to controls following SARS-CoV-2 vaccinations. Herein, we collected blood and serum after second, third, and fourth SARS-CoV-2 vaccinations in patients with SSc and controls. Following each dose, participants with SSc mounted comparable serum anti-RBD IgG, anti-RBD IgA, and spike-specific CD4 and CD8T cell responses to those found in controls.
View Article and Find Full Text PDFBackground: MicroRNAs (miRs) are emerging targets for the diagnosis, prognosis and treatment of heart failure (HF). Accumulated evidence showed that microRNA-132 (miR-132) and microRNA-152 (miR-152) play critical roles in the development of multiple pathological processes of the heart. Although their upregulations have been detected in the failing hearts of humans and animal models, little is known about the circulating levels of miR-132 and miR-152 in patients with HF.
View Article and Find Full Text PDFObjective: To assess the effectiveness of evidence-based quality improvement (EBQI) as an implementation strategy to expand the use of medications for opioid use disorder (MOUD) within nonspecialty settings.
Data Sources And Study Setting: We studied eight facilities in one Veteran Health Administration (VHA) region from October 2015 to September 2022 using administrative data.
Study Design: Initially a pilot, we sequentially engaged seven of eight facilities from April 2018 to September 2022 using EBQI, consisting of multilevel stakeholder engagement, technical support, practice facilitation, and data feedback.
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a potentially curative treatment for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). However, these transplants are complicated by a high rate of relapse in very high cytogenetic risk or refractory diseases. The benefit of this therapeutic strategy for these serious malignant hemopathies could therefore be reassessed.
View Article and Find Full Text PDFAs DNA sequencing technology continues to rapidly improve, studies investigating the microbial communities of host organisms (i.e., microbiota) are becoming not only more popular but also more financially accessible.
View Article and Find Full Text PDFAlthough broadly used, consolidative autologous hematopoietic stem cell transplantation (auto-HCT) for relapsed/refractory (R/R) T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) has never been specifically investigated. Here, we have analyzed outcomes of auto-HCT for THRLBCL compared with diffuse large cell B-cell lymphoma not otherwise specified (DLBCL). Eligible for this retrospective registry study were adult patients with R/R THRLBCL and DLBCL, respectively, who underwent a first auto-HCT in a salvage-sensitive disease status as assessed by positron emission tomography-computed tomography between 2016 and 2021 and were registered with the European Society for Blood and Marrow Transplantation database.
View Article and Find Full Text PDFBackground: Observational Alzheimer's disease (AD) cohorts including the Australian, Biomarkers, Imaging and Lifestyle (AIBL) Study have enhanced our understanding of AD. The generalizability of findings from AIBL to the general population has yet to be studied.
Objective: We aimed to compare characteristics of people with AD dementia in AIBL to 1) the general population of older Australians using pharmacological treatment for AD dementia, and to 2) the general population of older Australians who self-reported a diagnosis of dementia.