Opioid use patterns following discharge from elective colorectal surgery: a prospective cohort study.

Introduction: Opioid overprescription after colorectal surgery can lead to adverse events, persistent opioid use, and diversion of unused pills. This study aims to assess the extent to which opioids prescribed at discharge after elective colorectal surgery are consumed by patients.

Methods: This prospective cohort study included adult patients (≥ 18 yo) undergoing elective colorectal surgery at two academic hospitals in Montreal, Canada.

Association between patient activation and adherence to a colorectal enhanced recovery pathway: a prospective cohort study.

Background: Low adherence to enhanced recovery pathways (ERPs) may negatively affect postoperative outcomes. The objective of this study was to assess the extent to which patient activation (PA, i.e.

SMAD2/3-SMYD2 and developmental transcription factors cooperate with cell cycle inhibitors to guide tissue formation.

Tissue formation and organ homeostasis is achieved by precise coordination of proliferation and differentiation of stem cells and progenitors. While deregulation of these processes can result in degenerative disease or cancer, their molecular interplays remain unclear. Here we show that the switch of human pluripotent stem cell (hPSC) self-renewal to differentiation is associated with the induction of distinct cyclin dependent kinase inhibitors (CDKIs).

Rates and risk factors for persistent opioid use after cardiothoracic surgery: A cohort study.

Background: This study's aim was to estimate potential risk factors for persistent opioid use after cardiothoracic surgery.

Methods: This study included participants in the McGill University Health Centre clinical trial (2014 to 2016). Provincial medical services, prescription claims, and medical charts data were linked.

KMT2A associates with PHF5A-PHF14-HMG20A-RAI1 subcomplex in pancreatic cancer stem cells and epigenetically regulates their characteristics.

Pancreatic cancer (PC), one of the most aggressive and life-threatening human malignancies, is known for its resistance to cytotoxic therapies. This is increasingly ascribed to the subpopulation of undifferentiated cells, known as pancreatic cancer stem cells (PCSCs), which display greater evolutionary fitness than other tumor cells to evade the cytotoxic effects of chemotherapy. PCSCs are crucial for tumor relapse as they possess 'stem cell-like' features that are characterized by self-renewal and differentiation.

PepFect14 mediates the delivery of mRNA into human primary keratinocytes and .

mRNA-based vaccines and candidate therapeutics have great potential in various medical fields. For the delivery of mRNA into target cells and tissues, lipid formulations are often employed. However, this approach could cause the activation of immune responses, making it unsuitable for the treatment of inflammatory conditions.

Patients' experiences undergoing cancer surgery during the COVID-19 pandemic: a qualitative study.

Purpose: This study aimed to understand patients' experiences undergoing cancer surgery during the COVID-19 pandemic. In response to COVID-19, many elective cancer surgeries were delayed creating a massive backlog of cases. Patients' experiences with surgical delays may inform healthcare systems' responses to the backlog of cases and guide preparations for future healthcare emergencies.

Understanding the Impact of Bowel Dysfunction on Quality of Life After Rectal Cancer Surgery From the Patient's Perspective.

Background: Bowel dysfunction is an important consequence of rectal cancer surgery' and the specific quality-of-life domains that are affected remain unclear and unaddressed by generic surveys.

Objective: This study aimed to identify quality-of-life domains most affected by rectal cancer surgery.

Design: Qualitative content analysis.

BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma.

The dismal prognosis of pancreatic ductal adenocarcinoma (PDAC) is linked to the presence of pancreatic cancer stem-like cells (CSCs) that respond poorly to current chemotherapy regimens. By small molecule compound screening targeting 142 epigenetic enzymes, we identified that bromodomain-containing protein BRD9, a component of the BAF histone remodelling complex, is a key chromatin regulator to orchestrate the stemness of pancreatic CSCs via cooperating with the TGFβ/Activin-SMAD2/3 signalling pathway. Inhibition and genetic ablation of BDR9 block the self-renewal, cell cycle entry into G0 phase and invasiveness of CSCs, and improve the sensitivity of CSCs to gemcitabine treatment.

A new FRDA mouse model [ :YG8s(GAA) > 800] with more than 800 GAA repeats.

Introduction: Friedreich's ataxia (FRDA) is an inherited recessive neurodegenerative disorder caused by a homozygous guanine-adenine-adenine (GAA) repeat expansion within intron 1 of the gene, which encodes the essential mitochondrial protein frataxin. There is still no effective therapy for FRDA, therefore the development of optimal cell and animal models of the disease is one of the priorities for preclinical therapeutic testing.

Methods: We obtained the latest FRDA humanized mouse model that was generated on the basis of our previous YG8sR, by Jackson laboratory [YG8JR, :YG8s(GAA) > 800].

Skin Colonization with S. aureus Can Lead to Increased NLRP1 Inflammasome Activation in Patients with Atopic Dermatitis.

The role of NLRP1 inflammasome activation and subsequent production of IL-1 family cytokines in the development of atopic dermatitis (AD) is not clearly understood. Staphylococcus aureus is known to be associated with increased mRNA levels of IL1 family cytokines in the skin and more severe AD. In this study, the altered expression of IL-1 family cytokines and inflammasome-related genes was confirmed, and a positive relationship between mRNA levels of inflammasome sensor NLRP1 and IL1B or IL18 was determined.

Paradoxical attenuation of neuroinflammatory response upon LPS challenge in miR-146b deficient mice.

The miR-146 family consists of two microRNAs (miRNAs), miR-146a and miR-146b (miR-146a/b), both of which are known to suppress immune responses in a variety of conditions. Here, we studied how constitutive deficiency of miR-146b () affects lipopolysaccharide (LPS)-induced neuroinflammation in mice. Our experiments demonstrated that miR-146b deficiency results in the attenuation of LPS-induced neuroinflammation, as it was evidenced by the reduction of sickness behavior, a decrease in the inflammatory status of microglia, and the loss of morphological signs of microglial activation in the hippocampus.

S110-Opioid-free analgesia after outpatient general surgery: A qualitative study focused on the perspectives of patients and clinicians involved in a pilot trial.

Background: Opioid-free analgesia (OFA) may mitigate opioid-related harms after outpatient general surgery; however, the comparative effectiveness of this approach should be assessed in robust randomized controlled trials (RCTs). Undertaking an RCT on OFA raises important practical concerns, including surgeon and patient hesitation regarding pain management without opioids. We conducted a qualitative study to explore patients' and clinicians' perspectives and experiences with a pilot trial focused on OFA after outpatient general surgery.

Chlorhexidine (di)gluconate locking device for central line infection prevention in intensive care unit patients: a multi-unit, pilot randomized controlled trial.

Purpose: Intensive care unit (ICU) patients are at risk for central line-associated bloodstream infection (CLABSI) with significant attributable mortality and increased hospital length of stay, readmissions, and costs. Chlorhexidine (di)gluconate (CHG) is used as a disinfectant for central line insertion; however, the feasibility and efficacy of using CHG as a locking solution is unknown.

Methods: Patients with a central venous access device (CVAD) in situ were randomized to standard care or a CHG lock solution (CHGLS) within 72 hours of ICU admission.

Feasibility of Prospectively Comparing Opioid Analgesia With Opioid-Free Analgesia After Outpatient General Surgery: A Pilot Randomized Clinical Trial.

Importance: The overprescription of opioids to surgical patients is recognized as an important factor contributing to the opioid crisis. However, the value of prescribing opioid analgesia (OA) vs opioid-free analgesia (OFA) after postoperative discharge remains uncertain.

Objective: To investigate the feasibility of conducting a full-scale randomized clinical trial (RCT) to assess the comparative effectiveness of OA vs OFA after outpatient general surgery.

Frataxin Deficit Leads to Reduced Dynamics of Growth Cones in Dorsal Root Ganglia Neurons of Friedreich's Ataxia YG8sR Model: A Multilinear Algebra Approach.

Computational techniques for analyzing biological images offer a great potential to enhance our knowledge of the biological processes underlying disorders of the nervous system. Friedreich's Ataxia (FRDA) is a rare progressive neurodegenerative inherited disorder caused by the low expression of frataxin, which is a small mitochondrial protein. In FRDA cells, the lack of frataxin promotes primarily mitochondrial dysfunction, an alteration of calcium (Ca) homeostasis and the destabilization of the actin cytoskeleton in the neurites and growth cones of sensory neurons.

A Drug Combination Rescues Frataxin-Dependent Neural and Cardiac Pathophysiology in FA Models.

Friedreich's ataxia (FA) is an inherited multisystemic neuro- and cardio-degenerative disorder. Seventy-four clinical trials are listed for FA (including past and present), but none are considered FDA/EMA-approved therapy. To date, FA therapeutic strategies have focused along two main lines using a single-drug approach: a) increasing frataxin and b) enhancing downstream pathways, including antioxidant levels and mitochondrial function.

DNA methylation in Friedreich ataxia silences expression of frataxin isoform E.

Epigenetic silencing in Friedreich ataxia (FRDA), induced by an expanded GAA triplet-repeat in intron 1 of the FXN gene, results in deficiency of the mitochondrial protein, frataxin. A lesser known extramitochondrial isoform of frataxin detected in erythrocytes, frataxin-E, is encoded via an alternate transcript (FXN-E) originating in intron 1 that lacks a mitochondrial targeting sequence. We show that FXN-E is deficient in FRDA, including in patient-derived cell lines, iPS-derived proprioceptive neurons, and tissues from a humanized mouse model.

Construct validity and responsiveness of the Duke Activity Status Index (DASI) as a measure of recovery after colorectal surgery.

Background: Returning to preoperative levels of physical function is highly valued by patients recovering from surgery. The Duke Activity Status Index (DASI, a 12-item questionnaire) may be a simple yet robust tool to assess postoperative recovery of functional capacity. This study assessed construct validity and responsiveness of the DASI as a measure of recovery after colorectal surgery.

Interruptions of the GAA Repeat Tract Delay the Age at Onset of Friedreich's Ataxia in a Location Dependent Manner.

Friedreich's ataxia (FRDA) is a comparatively rare autosomal recessive neurological disorder primarily caused by the homozygous expansion of a GAA trinucleotide repeat in intron 1 of the gene. The repeat expansion causes gene silencing that results in deficiency of the frataxin protein leading to mitochondrial dysfunction, oxidative stress and cell death. The GAA repeat tract in some cases may be impure with sequence variations called interruptions.

Colon cancer cell differentiation by sodium butyrate modulates metabolic plasticity of Caco-2 cells via alteration of phosphotransfer network.

The ability of butyrate to promote differentiation of cancer cells has important implication for colorectal cancer (CRC) prevention and therapy. In this study, we examined the effect of sodium butyrate (NaBT) on the energy metabolism of colon adenocarcinoma Caco-2 cells coupled with their differentiation. NaBT increased the activity of alkaline phosphatase indicating differentiation of Caco-2 cells.

Impact of AHR Ligand TCDD on Human Embryonic Stem Cells and Early Differentiation.

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, which mediates the effects of a variety of environmental stimuli in multiple tissues. Recent advances in AHR biology have underlined its importance in cells with high developmental potency, including pluripotent stem cells. Nonetheless, there is little data on AHR expression and its role during the initial stages of stem cell differentiation.

HMTase Inhibitors as a Potential Epigenetic-Based Therapeutic Approach for Friedreich's Ataxia.

Friedreich's ataxia (FRDA) is a progressive neurodegenerative disorder caused by a homozygous GAA repeat expansion mutation in intron 1 of the frataxin gene (), which instigates reduced transcription. As a consequence, reduced levels of frataxin protein lead to mitochondrial iron accumulation, oxidative stress, and ultimately cell death; particularly in dorsal root ganglia (DRG) sensory neurons and the dentate nucleus of the cerebellum. In addition to neurological disability, FRDA is associated with cardiomyopathy, diabetes mellitus, and skeletal deformities.