Evaluating the Use of Environmental and Polygenic Risk Scores to Inform Colorectal Cancer Risk-Based Surveillance Intervals.

Introduction: United States Multi-Society Task Force colonoscopy surveillance intervals are based solely on adenoma characteristics, without accounting for other risk factors. We investigated whether a risk model including demographic, environmental, and genetic risk factors could individualize surveillance intervals under an "equal management of equal risks" framework.

Methods: Using 14,069 individuals from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnostic colonoscopy following an abnormal flexible sigmoidoscopy, we modeled the risk of colorectal cancer, considering the diagnostic colonoscopy finding, baseline risk factors (e.

Imaging and Pharmacokinetics of Percutaneously Injected Ultrasound and X-ray Imageable Thermosensitive Hydrogel loaded with Doxorubicin versus Free Drug in Swine.

Intratumoral injections often lack visibility, leading to unpredictable outcomes such as incomplete tumor coverage, off-target drug delivery and systemic toxicities. This study investigated an ultrasound (US) and x-ray imageable thermosensitive hydrogel based on poloxamer 407 (POL) percutaneously delivered in a healthy swine model. The primary objective was to assess the 2D and 3D distribution of the hydrogel within tissue across three different needle devices and injection sites: liver, kidney, and intercostal muscle region.

Generation of nanobodies from transgenic 'LamaMice' lacking an endogenous immunoglobulin repertoire.

Due to their exceptional solubility and stability, nanobodies have emerged as powerful building blocks for research tools and therapeutics. However, their generation in llamas is cumbersome and costly. Here, by inserting an engineered llama immunoglobulin heavy chain (IgH) locus into IgH-deficient mice, we generate a transgenic mouse line, which we refer to as 'LamaMouse'.

Comparison of Force Distribution during Laryngoscopy with the C-MAC D-BLADE and Macintosh-Style Blades: A Randomised Controlled Clinical Trial.

: The geometry of a laryngoscope's blade determines the forces acting on the pharyngeal structures to a relevant degree. Knowledge about the force distribution along the blade may prospectively allow for the development of less traumatic blades. Therefore, we examined the forces along the blades experienced during laryngoscopy with the C-MAC D-BLADE and blades of the Macintosh style.

Topical Versus Intravenous Tranexamic Acid in Patients Undergoing Cardiac Surgery: The DEPOSITION Randomized Controlled Trial.

Background: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared with intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients.

Methods: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass.

Endothelial-Specific Reduction in Arf6 Impairs Insulin-Stimulated Vasodilation and Skeletal Muscle Blood Flow Resulting in Systemic Insulin Resistance in Mice.

Background: Much of what we know about insulin resistance is based on studies from metabolically active tissues such as the liver, adipose tissue, and skeletal muscle. Emerging evidence suggests that the vascular endothelium plays a crucial role in systemic insulin resistance; however, the underlying mechanisms remain incompletely understood. Arf6 (ADP ribosylation factor 6) is a small GTPase that plays a critical role in endothelial cell function.

Disrupted Binding of Cystathionine γ-Lyase to p53 Promotes Endothelial Senescence.

Background: Advanced age is unequivocally linked to the development of cardiovascular disease; however, the mechanisms resulting in reduced endothelial cell regeneration remain poorly understood. Here, we investigated novel mechanisms involved in endothelial cell senescence that impact endothelial cell transcription and vascular repair after injury.

Methods: Native endothelial cells were isolated from young (20±3.

Functional Cardiovascular Characterization of the Common Marmoset ().

Appropriate cardiovascular animal models are urgently needed to investigate genetic, molecular, and therapeutic approaches, yet the translation of results from the currently used species is difficult due to their genetic distance as well as their anatomical or physiological differences. Animal species that are closer to the human situation might help to bridge this translational gap. The common marmoset () is an interesting candidate to investigate certain heart diseases and cardiovascular comorbidities, yet a basic functional characterization of its hemodynamic system is still missing.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

Background: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively.

Objective: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery.

Mobile Cone-Beam CT-Assisted Bronchoscopy for Peripheral Lung Lesions.

Peripheral bronchoscopy with the use of thin/ultrathin bronchoscopes and radial-probe endobronchial ultrasound (RP-EBUS) has been associated with a fair diagnostic yield. Mobile cone-beam CT (m-CBCT) could potentially improve the performance of these readily available technologies. We retrospectively reviewed the records of patients undergoing bronchoscopy for peripheral lung lesions with thin/ultrathin scope, RP-EBUS, and m-CBCT guidance.

Cochlear Implantation: Systematic Approach to Preoperative Radiologic Evaluation.

Sensorineural hearing loss results from abnormalities that affect the hair cells of the membranous labyrinth, inner ear malformations, and conditions affecting the auditory pathway from the cochlear nerve to the processing centers of the brain. Cochlear implantation is increasingly being performed for hearing rehabilitation owing to expanding indications and a growing number of children and adults with sensorineural hearing loss. An adequate understanding of the temporal bone anatomy and diseases that affect the inner ear is paramount for alerting the operating surgeon about variants and imaging findings that can influence the surgical technique, affect the choice of cochlear implant and electrode type, and help avoid inadvertent complications.

Identifying Risk Factors for Blindness From Glaucoma at First Presentation to a Tertiary Clinic.

Purpose: Glaucoma is the leading cause of irreversible blindness, a crippling disability resulting in higher risks of chronic health conditions. To better understand disparities in blindness risk, we identified risk factors of blindness on first presentation to a glaucoma clinic using a large clinical database.

Design: Retrospective cross-sectional study.

CSL324, a granulocyte colony-stimulating factor receptor antagonist, blocks neutrophil migration markers that are upregulated in hidradenitis suppurativa.

Background: Neutrophils have been shown to contribute to the pathophysiology of hidradenitis suppurativa (HS), a chronic, painful and debilitating inflammatory skin disease, yet their exact role remains to be fully defined. Granulocyte colony-stimulating factor (G-CSF), a major regulator of neutrophil development and survival, can be blocked by the novel, fully human anti-G-CSF receptor (G-CSFR) monoclonal antibody CSL324.

Objectives: We investigated the activation and migration of neutrophils in HS and the impact of blocking G-CSFR with CSL324.

Effect of Resident Involvement in Ophthalmic Surgery on Patient Outcomes: A Systematic Review and Meta-analysis.

Purpose: To determine the effect of resident- vs attending-led surgeries on patient outcomes in ophthalmic surgery.

Design: Systematic review and meta-analysis.

Methods: Two independent authors searched PubMed, EMBASE, and Cochrane Library from inception to March 2022.

Quantification of Genome Editing and Transcriptional Control Capabilities Reveals Hierarchies among Diverse CRISPR/Cas Systems in Human Cells.

CRISPR/Cas technologies have revolutionized the ability to redesign genomic information and tailor endogenous gene expression. Nevertheless, the discovery and development of new CRISPR/Cas systems has resulted in a lack of clarity surrounding the relative efficacies among these technologies in human cells. This deficit makes the optimal selection of CRISPR/Cas technologies in human cells unnecessarily challenging, which in turn hampers their adoption, and thus ultimately limits their utility.

Leveraging Nanomechanical Perturbations in Raman Spectro-Immunoassays to Design a Versatile Serum Biomarker Detection Platform.

While immunoassays are pivotal to medical diagnosis and bioanalytical chemistry, the current landscape of public health has catalyzed an important shift in the requirements of immunoassays that demand innovative solutions. For example, rapid, label-free, and low-cost screening of a given analyte is required to inform the best countermeasures to combat infectious diseases in a timely manner. Yet, the current design of immunoassays cannot accommodate such requirements as constraint by accumulative challenges, such as repeated incubation and washing, and the need of two types of antibodies in the sandwich format.

Risk Factors for Mortality in Mechanically Ventilated Patients with COVID-19 in a Mississippi Community Health System.

Objective: To evaluate differences between survivors versus nonsurvivors undergoing mechanical ventilation for coronavirus disease 2019 (COVID-19)-associated respiratory failure at two community medical centers.

Methods: This was a multicenter, retrospective cohort analysis of all adult patients mechanically ventilated for COVID-19-associated respiratory failure in two community hospital intensive care units in southern Mississippi from March 15, 2020 through October 10, 2020.

Results: Among 56 patients requiring mechanical ventilation, the mortality rate was 75% (42/56).

Tranexamic Acid in Patients Undergoing Noncardiac Surgery.

Background: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding.

Methods: We conducted a trial involving patients undergoing noncardiac surgery.

High-Sensitivity Troponin I after Cardiac Surgery and 30-Day Mortality.

Background: Consensus recommendations regarding the threshold levels of cardiac troponin elevations for the definition of perioperative myocardial infarction and clinically important periprocedural myocardial injury in patients undergoing cardiac surgery range widely (from >10 times to ≥70 times the upper reference limit for the assay). Limited evidence is available to support these recommendations.

Methods: We undertook an international prospective cohort study involving patients 18 years of age or older who underwent cardiac surgery.

MicroRNA Expression Profiling in Porcine Liver, Jejunum and Serum upon Dietary DON Exposure Reveals Candidate Toxicity Biomarkers.

Deoxynivalenol (DON), a frequent mycotoxin worldwide, impairs human and animal health. The response of microRNAs, small non-coding RNAs, to DON has been scarcely investigated, but holds remarkable potential for biomarker applications. Hence, we aimed to investigate DON-induced changes in the microRNA expression in porcine liver, jejunum and serum by combining targeted and untargeted analyses.

Aspects of Tertiary Prevention in Patients with Primary Open Angle Glaucoma.

The purpose of the study is to assess the health of patients in the activity of tertiary prevention dedicated to preventing blindness caused by POAG (primary glaucoma with open angle and high tension) and NTG (primary glaucoma with open-angle and statistically normal tension-particular form of glaucoma with open angle) and preservation of the remaining visual function. The design of the study is epidemiological, observational, descriptive and retrospective, and uses only the data recorded in the existing records in the archives of the Ophthalmology office within the Integrated Outpatient Clinic of the Emergency Clinical Hospital of Oradea (IOCECHO) during the years 1999-2019 (anamnestic data; objective examination and paraclinical examination: intraocular pressure-IOP and visual field-VF). The methods of the study included the standardized protocol: anamnesis, physical ophthalmological examination, IOP determination, and computerized perimetry with the "Fast Threshold" strategy performed with the "Opto AP-300" perimeter.

CD4 T Cells in Chronic Hepatitis B and T Cell-Directed Immunotherapy.

The impaired T cell responses observed in chronic hepatitis B (HBV) patients are considered to contribute to the chronicity of the infection. Research on this impairment has been focused on CD8 T cells because of their cytotoxic effector function; however, CD4 T cells are crucial in the proper development of these long-lasting effector CD8 T cells. In this review, we summarize what is known about CD4 T cells in chronic HBV infection and discuss the importance and opportunities of including CD4 T cells in T cell-directed immunotherapeutic strategies to cure chronic HBV.