Immune checkpoint inhibitors (ICIs) show limited success in treating pancreatic ductal adenocarcinoma (PDAC), largely due to immune evasion mechanisms, including downregulating expression of major histocompatibility complex class I (MHC-I). Our retrospective analysis demonstrated that smoking - a state of elevated CO exposure - is correlated with increased MHC I expression in pancreatic tumors. Here we tested our hypothesis that introducing exogenous CO augments the anti-cancer effects of immunotherapy.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Cell Biol Lipids
January 2025
The synthesis of n-3 and n-6 polyunsaturated acids (PUFAs) is associated with physiological functions in mammals, being catalyzed by Δ-5D and Δ-6D desaturases and elongases Elovl-2 and Elovl-5. In this context, we aimed to study the chief kinetic features of PUFA liver anabolism, looking upon (i) the time-dependency for the specific activity of Δ-6D, Δ-5D, Elovl2, Elovl2/5 and Elovl5, using n-3 and n-6 precursors between 0 and 240 min ex vivo in mouse liver.; and (ii) the specific activity-substrate (α-linolenic acid; ALA) concentration responses of Δ-6D in the absence and presence of linoleic acid (LA), arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), an enzyme regarded as the rate-limiting step in PUFA anabolism.
View Article and Find Full Text PDFPopulation-level estimates in timeframes for reaching cervical cancer (CC) elimination (ie, <4 cases per 100,000 women) in the United States may mask potential disparities in achieving elimination among sub-populations. We used three independent Cancer Intervention and Surveillance Modeling Network (CISNET) models to estimate differences in the time to CC elimination across seven strata of correlated screening and human papillomavirus vaccination uptake, based on national survey data. Compared to the average population, elimination was achieved ≥22 years earlier for the high-uptake strata and ≥27 years later for the most extreme low-uptake strata.
View Article and Find Full Text PDFThe combat medic (68W) will play a critical role in medical operations in the event of future large-scale combat operations (LSCOs). However, the combat medic is largely not prepared for LSCOs. The revised Medical Education and Demonstration of Individual Competence (TC 8-800) state 68Ws much be able to provide advanced airway and trauma management, medication administration, and advanced casualty movement.
View Article and Find Full Text PDFExercise-associated hyponatremia (EAH) is commonly observed in endurance athletes, where prolonged physical exertion combined with being unaware of personal hydration needs can lead to excessive water consumption or inadequate sodium intake. Marching band (MB) is an emerging setting for sports medicine professionals. However, there is little research on non-musculoskeletal illnesses among these performing artists.
View Article and Find Full Text PDFObjectives: The ICU built environment-including the presence of windows-has long been thought to play a role in delirium. This study investigated the association between the presence or absence of windows in patient rooms and ICU delirium.
Design: Retrospective single institution cohort study.
Tracheoesophageal puncture (TEP) with voice prosthesis (VP) placement is commonly used to restore voice in laryngectomy patients. The conventional procedure utilizes a rigid esophagoscope to open and visualize the pharyngeal inlet. However, this approach is challenging in patients with postradiation changes, reduced neck extension, or trismus.
View Article and Find Full Text PDFBackground: Osteochondral allograft transplantation (OCA) is well established as a viable chondral restoration procedure for the treatment of symptomatic, focal chondral defects of the knee. The efficacy of secondary OCA in the setting of failed index cartilage repair or restoration is poorly understood.
Purpose: To evaluate radiographic and clinical outcomes, failures, and reoperations after OCA after failed index cartilage repair or restoration of the knee.
Arch Dis Child Educ Pract Ed
January 2025
Neonatal encephalopathy (NE) presents as reduced consciousness, often with seizures, abnormal tone, feeding and respiratory difficulties. The most common cause is secondary to a hypoxic-ischaemic event. However, there are many important diagnoses that can also present as NE, so-called 'hypoxic ischaemic encephalopathy (HIE) mimics'.
View Article and Find Full Text PDFBackground: Heart failure (HF) is a risk factor for stroke among people with atrial fibrillation (AF). Prognosis following a HF diagnosis is often poor, but this is not accounted for in existing stroke risk scores.
Aim: To examine stroke incidence in people with HF and AF compared to AF alone, considering the competing risk of death.
Background: The purpose was to investigate the impact of social determinants of health on healthcare utilization among older adults in two cognition groups: normal and dementia/impaired cognition.
Methods: We used cross-sectional data from the Health and Retirement Study (N = 16,339) to assess healthcare utilization: hospital stay, nursing home stay, hospice care, and doctor visits. The respondents were classified into two cognition groups using the Langa-Weir approach.
The glycomacropeptide (GMP) present in the cheese whey byproduct can be an excellent antifreezing agent due to its unique molecular structure. The objective of this study was to concentrate this peptide and investigate its ice recrystallization inhibition (IRI) ability. Heat denaturation of the non-GMP proteins and preparative liquid chromatography were used to create fraction 1 (F1) and fraction 2 (F2) and these were tested using the splat assay and a modified sucrose sandwich assay to investigate their IRI activity.
View Article and Find Full Text PDFPharmacoepidemiol Drug Saf
January 2025
Purpose: To comply with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) Privacy Rule, many real-world data providers mask a patient's date of birth by supplying only year of birth to data users. The lack of granularity around patient age is a challenge when using RWD, especially for pediatric research studies. In this study, a proxy for patient date of birth is evaluated using electronic health record (EHR) data.
View Article and Find Full Text PDFCirculating mature red blood cells (RBCs) from patients and mice with sickle cell disease (SCD) abnormally retain mitochondria, a factor shown to contribute to the disease's pathobiology. To further understand the functional implications of RBC mitochondria retention in SCD, we used mitochondria inhibitors and metabolites/substrates from the tricarboxylic acid cycle, oxidative phosphorylation and glycolysis pathways (ADP, glutamate, malate, pyruvate, succinate or all metabolites combined) and examined RBC bioenergetics, reactive oxygen species (ROS) levels, calcium flux and hydration. In RBCs from sickle mice, mitochondria inhibition reduced ATP levels by 30%-60%, whereas control RBCs were unaffected.
View Article and Find Full Text PDFPatients with large B-cell lymphoma (LBCL) progressing after anti-CD19 CAR T-cell (CAR19) therapy have poor outcomes. Subsequent CAR T-cell therapy shows promise, but the impact of residual CAR19 and early relapse remains unclear. We evaluated 37 CAR19-refractory LBCL patients who received anti-CD22 CAR T-cell (CAR22) in a phase 1b trial (NCT04088890).
View Article and Find Full Text PDFYerba mate (YM, ) is an economically important crop marketed for the elaboration of mate, the third-most widely consumed caffeine-containing infusion worldwide. Here, we report the first genome assembly of this species, which has a total length of 1.06 Gb and contains 53,390 protein-coding genes.
View Article and Find Full Text PDFIn multiple sclerosis (MS), microglia and macrophages within the central nervous system (CNS) play an important role in determining the balance among demyelination, neurodegeneration, and myelin repair. Phagocytic and regenerative functions of these CNS innate immune cells support remyelination, whereas chronic and maladaptive inflammatory activation promotes lesion expansion and disability, particularly in the progressive forms of MS. No currently approved drugs convincingly target microglia and macrophages within the CNS, contributing to the lack of therapies aimed at promoting remyelination and slowing disease progression for individuals with MS.
View Article and Find Full Text PDFSolvent toxicity limits -butanol fermentation titer, increasing the cost and energy consumption for subsequent separation processes and making biobased production more expensive and energy-intensive than petrochemical approaches. Amphiphilic solvents such as -butanol partition into the cell membrane of fermenting microorganisms, thinning the transverse structure, and eventually causing a loss of membrane potential and cell death. In this work, we demonstrate the deleterious effects of -butanol partitioning upon the lateral dimension of the membrane structure, called membrane domains or lipid rafts.
View Article and Find Full Text PDFViscoelastic testing evaluates the formation and lysis of a clot over time, allowing more complete assessment of patient hemostasis in real time, whereas traditional tests, such as prothrombin time and partial thromboplastin time, only measure coagulation factor function. Patient-side viscoelastic coagulation monitors are easy to use, portable, and provide faster turnaround time than commercial laboratories. Viscoelastic testing requires only 0.
View Article and Find Full Text PDFObjectives: To determine the use of epidural anesthesia compared with regional anesthesia as an adjunct to general anesthesia in thoracic surgery over time, and compare length of stay, overall morbidity, serious morbidity, and mortality between epidural and regional anesthesia when utilized as adjuncts to general anesthesia in thoracic surgery.
Design: Retrospective data analysis from the American College of Surgeons National Surgical Quality Improvement Project data registry, years 2014 to 2022.
Setting: Over 800 U.
Background: West Nile virus (WNV), although underdiagnosed, is the most common mosquito-borne disease and the second most common cause of viral encephalitis in the United States. Fewer than 1% of those infected develop neuroinvasive disease.
Methods: We present a cluster of 3 cases of neuroinvasive WNV that occurred between August and September 2023 and a review of the literature for neurologic involvement with this virus.
Aim: This study aimed to explore healthcare experiences of rural-living patients both with (attached) and without (unattached) a local primary care provider.
Background: Primary care providers serve a gatekeeping role in the Canadian healthcare system as the first contact for receiving many health services. With the shortage of primary care providers, especially in rural areas, there is a need to explore attached and unattached patient experiences when accessing healthcare.