A Comprehensive Review of the Antitumor Properties and Mechanistic Insights of Duocarmycin Analogs.

The duocarmycin family is a group of potent cytotoxic agents originally isolated from the bacterium Streptomyces. This discovery has spurred significant interest due to duocarmycins' unique chemical structures and powerful mechanism of action. This review comprehensively details the history of the duocarmycin family, the current understanding of their therapeutic potential, and the major clinical trials that have been conducted.

A baffling case of inferior vena cava filter removal in a patient with transposition of the great arteries.

A 47-year-old man with a history of transposition of the great arteries after a Mustard atrial switch procedure and prior inferior vena cava filter placement for venous thromboembolism presented for removal before being listed for orthotopic heart transplantation in anticipation of cardiopulmonary bypass cannulation. The filter was retrieved using a right transjugular approach without disruption of his existing atrial baffle. Contingency planning in the event of unsuccessful baffle navigation included a transfemoral everted filter approach.

Small non-coding RNAs and pancreatic ductal adenocarcinoma: Linking diagnosis, pathogenesis, drug resistance, and therapeutic potential.

This review comprehensively investigates the intricate interplay between small non-coding RNAs (sncRNAs) and pancreatic ductal adenocarcinoma (PDAC), a devastating malignancy with limited therapeutic options. Our analysis reveals the pivotal roles of sncRNAs in various facets of PDAC biology, spanning diagnosis, pathogenesis, drug resistance, and therapeutic strategies. sncRNAs have emerged as promising biomarkers for PDAC, demonstrating distinct expression profiles in diseased tissues.

miRNA signatures underlie chemoresistance in the gemcitabine-resistant pancreatic ductal adenocarcinoma cell line MIA PaCa-2 GR.

Chemotherapy resistance remains a significant challenge in the treatment of pancreatic adenocarcinoma (PDAC), particularly in relation to gemcitabine (Gem), a commonly used chemotherapeutic agent. MicroRNAs (miRNAs) are known to influence cancer progression and chemoresistance. This study investigates the association between miRNA expression profiles and gemcitabine resistance in PDAC.

Pre-attentive and Attentive Auditory Event-related Potentials in Children With Attention-Deficit Hyperactivity Disorder and Autism.

Abnormalities in auditory processing are believed to play a major role in autism and attention-deficit hyperactivity disorder (ADHD). Both conditions often co-occur in children, causing difficulties in deciding the most promising intervention. Event-related potentials (ERPs) have been investigated and are showing promise to act as potential biomarkers for both conditions.

Impact of superior semicircular canal dehiscence on cochlear implant audiologic outcomes.

Purpose: Determine whether adult cochlear implant users with radiographic superior semicircular canal dehiscence experience clinically significant differences in audiological outcomes when compared to cochlear implant users with normal temporal bone anatomy.

Materials And Methods: Retrospective, single institution review. Adult, post-lingual deaf patients implanted between 2010 and 2020.

Amplifying Curcumin's Antitumor Potential: A Heat-Driven Approach for Colorectal Cancer Treatment.

Introduction: Peritoneal metastases from colorectal cancer (CRC) present a significant clinical challenge with poor prognosis, often unresponsive to systemic chemotherapy. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment approach for select patients. The use of curcumin, a natural compound with antitumor properties, in HIPEC is of interest due to its lower side effects compared to conventional drugs and potential for increased efficacy through direct delivery to the peritoneal cavity.

Psychometric Properties of Instruments That Measure Vaping Outcome Expectancies: A Systematic Review.

Introduction: Vaping is a growing public health concern. Interventions that address vaping must build upon rigorous research that uses psychometrically sound instruments to measure vaping-associated outcome expectancies.

Aims And Methods: The primary aim was to appraise the reporting of psychometric properties of instruments used to measure vaping outcome expectancies.

An Online Program for Primary Care Practitioners to Enhance Confidence in Ability to Care for Patients With or at Risk of Painful Knee Osteoarthritis.

Objective: Primary care practitioners (PCPs) care for the majority of patients with knee osteoarthritis (KOA). Despite the existing evidence-based guidelines, PCPs often feel unequipped to evaluate and effectively treat patients with KOA. To address this need, we designed and implemented a free internet-based program focusing on the diagnosis and treatment of KOA.

A CTB-SARS-CoV-2-ACE-2 RBD Mucosal Vaccine Protects Against Coronavirus Infection.

Mucosal vaccines protect against respiratory virus infection by stimulating the production of IgA antibodies that protect against virus invasion of the mucosal epithelium. In this study, a novel protein subunit mucosal vaccine was constructed for protection against infection by the beta coronavirus SARS-CoV-2. The vaccine was assembled by linking a gene encoding the SARS-CoV-2 virus S1 angiotensin converting enzyme receptor binding domain (ACE-2-RBD) downstream from a DNA fragment encoding the cholera toxin B subunit (CTB), a mucosal adjuvant known to stimulate vaccine immunogenicity.

Pancreatic Cancer Health Disparity: Pharmacologic Anthropology.

Pancreatic cancer (PCa) remains a formidable global health challenge, with high mortality rates and limited treatment options. While advancements in pharmacology have led to improved outcomes for various cancers, PCa continues to exhibit significant health disparities, disproportionately affecting certain populations. This paper explores the intersection of pharmacology and anthropology in understanding the health disparities associated with PCa.

Effect of vaccine dosing intervals on Omicron surrogate neutralization after three doses of BNT162b2.

Background: Increasing the interval between the first and second SARS-CoV-2 vaccine doses enhances vaccine immunogenicity, however the optimal timing of the third vaccine is unknown. In this study, we investigated how the time interval between the first and second (V1-V2), or second and third (V2-V3) doses affects immunogenicity after three doses of the BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine.

Methods: This is an observational cohort consisting of 360 participants enrolled in the (CORSIP) study.

Neonatal Cardiovascular-Progenitor-Cell-Derived Extracellular Vesicles Activate YAP1 in Adult Cardiac Progenitor Cells.

New stem cell and extracellular-vesicle-based therapies have the potential to improve outcomes for the increasing number of patients with heart failure. Since neonates have a significantly enhanced regenerative ability, we hypothesized that extracellular vesicles isolated from Islet-1+ expressing neonatal human cardiovascular progenitors (CPCs) will induce transcriptomic changes associated with improved regenerative capability when co-cultured with CPCs derived from adult humans. In order to test this hypothesis, we isolated extracellular vesicles from human neonatal Islet-1+ CPCs, analyzed the extracellular vesicle content using RNAseq, and treated adult CPCs with extracellular vesicles derived from neonatal CPCs to assess their functional effect.

Determining the Optimal SARS-CoV-2 mRNA Vaccine Dosing Interval for Maximum Immunogenicity.

Objective: Emerging evidence indicates that longer SARS-CoV-2 vaccine dosing intervals results in an enhanced immune response. However, the optimal vaccine dosing interval for achieving maximum immunogenicity is unclear.

Methods: This study included samples from adult paramedics in Canada who received two doses of either BNT162b2 or mRNA-1273 vaccines and provided blood samples six months (170 to 190 days) after the first vaccine dose.

Plasma Exosome Gene Signature Differentiates Colon Cancer from Healthy Controls.

Background: Liquid biopsies have become an integral part of cancer management as minimally invasive options to detect molecular and genetic changes. However, current options show poor sensitivity in peritoneal carcinomatosis (PC). Novel exosome-based liquid biopsies may provide critical information on these challenging tumors.

The association of the post-resuscitation on-scene interval and patient outcomes after out-of-hospital cardiac arrest.

Background: After resuscitation from out-of-hospital cardiac arrest (OHCA) by Emergency Medical Services (EMS), the amount of time that should be dedicated to pre-transport stabilization is unclear. We examined whether the time spent on-scene after return of spontaneous circulation (ROSC) was associated with patient outcomes.

Methods: We examined consecutive adult EMS-treated OHCAs from the British Columbia Cardiac Arrest registry (January 1/2019-June 1/2021) that had on-scene ROSC (sustained to scene departure).

Effect of Portable, In-Hospital Extracorporeal Membrane Oxygenation on Clinical Outcomes.

The time between onset of cardiogenic shock and initiation of mechanical circulatory support is inversely related to patient survival as delays in transporting patients to the operating room (OR) for venoarterial extracorporeal membrane oxygenation (VA ECMO) could prove fatal. A primed and portable VA ECMO system may allow faster initiation of ECMO in various hospital locations and subsequently improve outcomes for patients in cardiogenic shock. We reviewed our institutional experience with VA ECMO based on two time periods: beginning of our VA ECMO program and from initiation of our primed and portable in-hospital ECMO system.

Performance of the medical priority dispatch system in correctly classifying out-of-hospital cardiac arrests as appropriate for resuscitation.

Background: Emergency dispatch centres receive emergency calls and assign resources. Out-of-hospital cardiac arrests (OHCA) can be classified as appropriate (requiring emergent response) or inappropriate (requiring non-emergent response) for resuscitation. We sought to determine system accuracy in emergency medical services (EMS) OHCA response allocation.

Survivin Splice Variant 2β Enhances Pancreatic Ductal Adenocarcinoma Resistance to Gemcitabine.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with poor prognosis, as it is difficult to predict or circumvent, and it develops chemoresistance quickly. One cellular mechanism associated with chemoresistance is alternative splicing dysfunction, a process through which nascent mRNA is spliced into different isoforms. Survivin (Baculoviral IAP Repeat-Containing Protein 5 (BIRC5)), a member of the inhibitor of apoptosis (IAP) protein family and a cell cycle-associated oncoprotein, is overexpressed in most cancers and undergoes alternative splicing (AS) to generate six different splicing isoforms.

Exosomal proteins as a source of biomarkers in colon cancer-derived peritoneal carcinomatosis - A pilot study.

Purpose: Peritoneal carcinomatosis (PC), metastasized from colorectal cancer (CRC), remains a highly lethal disease. Outcomes of PC is significantly influenced by the amount of intra-abdominal tumor burden and therefore diagnostic tests that facilitate earlier diagnosis could improve PC treatment and patient outcomes.

Experimental Design: Using mass-spectrometry-based proteomics, we characterized the protein features of circulating exosomes in the context of CRC PC, CRC with liver metastasis, and primary CRC limited to the colon.

The Relationship Between Anti-Spike SARS-CoV-2 Antibody Levels and Risk of Breakthrough COVID-19 Among Fully Vaccinated Adults.

The relationship between antibodies to wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens and the risk of breakthrough infections is unclear, especially during circulation of the Omicron strain. We investigated the association of anti-spike and anti-receptor binding domain antibody levels and the risk of subsequent breakthrough coronavirus disease 2019 (COVID-19). We included adult paramedics from an observational cohort study who received 2 mRNA vaccines but did not have COVID-19 before the blood collection.

The impact of race/ethnicity on pancreaticoduodenectomy outcomes for pancreatic cancer.

Purpose: To investigate the impact of race/ethnicity on surgical outcomes following pancreaticoduodenectomy for pancreatic cancer.

Methods: A retrospective review of patients undergoing pancreaticoduodenectomy for adenocarcinoma in the National Surgical Quality Improvement Program (NSQIP) database from 2014 to 2019. Patient and tumor characteristics and 30-day postoperative outcomes were compared.