Involvement of Intestinal Epithelium Aryl Hydrocarbon Receptor Expression and 3, 3'-Diindolylmethane in Colonic Tertiary Lymphoid Tissue Formation.

Tertiary lymphoid tissues (TLTs) are adaptive immune structures that develop during chronic inflammation and may worsen or lessen disease outcomes in a context-specific manner. Immune cell activity governing TLT formation in the intestines is dependent on immune cell aryl hydrocarbon receptor (AhR) activation. Homeostatic immune cell activity in the intestines is further dependent on ligand activation of AhR in intestinal epithelial cells (IECs), yet whether AhR activation and signaling in IECs influences the formation of TLTs in the presence of dietary AhR ligands is not known.

Achievement of LDL-C <55 mg/dL among US adults: Findings from the cvMOBIUS2 registry.

Background: Reflecting clinical trial data showing improved outcomes with lower LDL-C levels, guidelines across the globe are increasingly recommending a goal of LDL-C <55 mg/dL in persons with atherosclerotic cardiovascular disease (ASCVD). What proportion of patients with ASCVD are already meeting those goals in the US remains understudied.

Methods: Using electronic health record data from 8 large US health systems, we evaluated lipid-lowering therapy (LLT), LDL-C levels, and factors associated with an LDL-C <55 mg/dL in persons with ASCVD treated between 1/1/2021-12/31/2021.

International Knee Documentation Committee Subjective Knee Form Latent Growth Model Analysis: Assessing Recovery Trajectories.

Patient-Reported Outcome Measures (PROMs), such as the six-item International Knee Documentation Committee Subjective Knee Form (IKDC-6), play a crucial role in assessing health conditions and guiding clinical decisions. Latent Growth Modeling (LGM) can be employed to understand recovery trajectories in patients post-operatively. Therefore, the purpose of this study was to assess LGM properties of the IKDC-6 in patients with knee pathologies that require surgical intervention and to assess differences between subgroups (i.

Standardized In-harness Ultrasound Protocol Improves Success Rate of Brace Treatment for Dislocated Hips.

Objective: Infant hip dislocations benefit from early detection and treatment for optimal outcomes. Prior studies have identified that there remains wide variability in the success rate of bracing between institutions. Although there are standardized methods to screen infants for hip dysplasia, there are no clear guidelines regarding how to image a child being treated for a hip dislocation with a Pavlik harness.

Aryl hydrocarbon receptor activity in intestinal epithelial cells in the formation of colonic tertiary lymphoid tissues.

After birth, the development of secondary lymphoid tissues (SLTs) in the colon is dependent on the expression of the aryl hydrocarbon receptor (AhR) in immune cells as a response to the availability of AhR ligands. However, little is known about how AhR activity from intestinal epithelial cells (IECs) may influence the development of tertiary lymphoid tissues (TLTs). As organized structures that develop at sites of inflammation or infection during adulthood, TLTs serve as localized centers of adaptive immune responses, and their presence has been associated with the resolution of inflammation and tumorigenesis in the colon.

Design and use of an ex vivo peripheral simulating bioreactor system for pharmacokinetic analysis of a drug coated stent.

Currently, there are no ex vivo systems that can model the motion of peripheral arteries and allow for the evaluation of pharmacokinetics (PK) of endovascular devices. The objective of this study was to develop a novel peripheral simulating bioreactor system to evaluate drug pharmacokinetics of stents. We utilized 3D-printed and off-the-shelf components to construct a peripheral-simulating bioreactor system capable of mimicking the motion of peripheral arteries.

Effect of an Outbound Scheduling Team on the Timeliness of Scheduling Referrals to Pediatric Otolaryngology.

Objective: Families preferring to receive care in a language-other-than-English have disparities in access to care. We studied the effect of implementing an ambulatory outbound scheduling team on the timeliness of scheduling referrals to pediatric otolaryngology. We hypothesized this intervention could increase access to care.

The efficacy of injecting a distillate of the pitcher plant (Sarraceniaceae) adjacent to the palmar digital nerves of horses to ameliorate lameness caused by digital pain.

This study aimed to determine the efficacy of instilling extract of the pitcher plant around the palmar digital nerves of horses to ameliorate digit pain causing lameness. Five mixed breed horses were recruited. Horses were determined to be lame because of pain in the distal portion of one or both thoracic limbs by a positive response to a basisesamoid nerve block using 2%^mepivacaine hydrochloride.

The intestinal microbiota as mediators between dietary contaminants and host health.

The gut microbiota sit at an important interface between the host and the environment, and are exposed to a multitude of nutritive and non-nutritive substances. These microbiota are critical to maintaining host health, but their supportive roles may be compromised in response to endogenous compounds. Numerous non-nutritive substances are introduced through contaminated foods, with three common groups of contaminants being bisphenols, phthalates, and mycotoxins.

Longitudinal Invariance Testing Of The Knee Injury Osteoarthritis Outcome Score For Joint Replacement Scale (KOOS-JR).

Background: The Knee Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) is a seven-item patient reported outcome measure used to assess perceived knee health. Though commonly used, the longitudinal psychometric properties of the KOOS-JR have not been established and further characterization of its structural validity and multi-group invariance properties is warranted.

Purpose: The purpose of this study was to evaluate psychometric properties of the KOOS-JR in a large sample of patients who received care for knee pathology.

Aryl Hydrocarbon Receptor (AhR) Signaling in Colonic Cells and Tumors.

The aryl hydrocarbon receptor (AhR) is overexpressed in many tumor types and exhibits tumor-specific tumor promoter and tumor suppressor-like activity. In colon cancer, most but not all studies suggest that the AhR exhibits tumor suppressor activity which is enhanced by AhR ligands acting as agonists. Our studies investigated the role of the AhR in colon tumorigenesis using wild-type and AhR-knockout mice, the inflammation model of colon tumorigenesis using mice treated with azoxymethane (AOM)/dextran sodium sulfate (DSS) and APC; Kras mice all of which form intestinal tumors.

Tumor-specific intracellular delivery: peptide-guided transport of a catalytic toxin.

There continues to be a need for cancer-specific ligands that can deliver a wide variety of therapeutic cargos. Ligands demonstrating both tumor-specificity and the ability to mediate efficient cellular uptake of a therapeutic are critical to expand targeted therapies. We previously reported the selection of a peptide from a peptide library using a non-small cell lung cancer (NSCLC) cell line as the target.

Multi-group invariance testing of the knee injury osteoarthritis outcome score for joint replacement scale.

Objective: The Knee Osteoarthritis Outcome Score for Joint Replacement (KOOS-JR) scale is commonly used to assess patient progress. Scale structural validity has not been completely assessed. The purpose of this study was to assess the internal consistency, structural validity, and multi-group invariance properties of the KOOS-JR in a large sample of patients receiving knee arthroplasty or non-operative care.

Estrogen Protects Cardiac Function and Energy Metabolism in Dilated Cardiomyopathy Induced by Loss of Cardiac IRS1 and IRS2.

Background: Type 2 diabetes (T2D) is a high-risk factor for incident of cardiovascular diseases. Women at young ages show a reduced incidence of both T2D and cardiovascular diseases compared with men, but these disparities disappear in postmenopausal women versus age-matched men. Thus, ovaries and ovarian hormones, such as estrogen, are expected to protect from T2D and cardiovascular diseases.

Novel Role of Ghrelin Receptor in Gut Dysbiosis and Experimental Colitis in Aging.

Chronic low-grade inflammation is a hallmark of aging, which is now coined as inflamm-aging. Inflamm-aging contributes to many age-associated diseases such as obesity, type 2 diabetes, cardiovascular disease, and inflammatory bowel disease (IBD). We have shown that gut hormone ghrelin, via its receptor growth hormone secretagogue receptor (GHS-R), regulates energy metabolism and inflammation in aging.

Citizen science reveals unexpected solute patterns in semiarid river networks.

Human modification of water and nutrient flows has resulted in widespread degradation of aquatic ecosystems. The resulting global water crisis causes millions of deaths and trillions of USD in economic damages annually. Semiarid regions have been disproportionately affected because of high relative water demand and pollution.

Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon.

Scope: This study investigates the mechanism of action and functional effects of coffee extracts in colonic cells, on intestinal stem cell growth, and inhibition of dextran sodium sulfate (DSS)-induced intestinal barrier damage in mice.

Methods And Results: Aqueous coffee extracts induced Ah receptor (AhR) -responsive CYP1A1, CYP1B1, and UGT1A1 gene expression in colon-derived Caco2 and YAMC cells. Tissue-specific AhR knockout (AhR x Lgr5-GFP-CreERT2 x Villin-Cre), wild-type (Lgr5-CreERT2 x Villin-Cre) mice are sources of stem cell enriched organoids and both coffee extracts and norharman, an AhR-active component of these extracts inhibited stem cell growth.

Estrogen receptor actions in colitis.

In recent years, researchers have demonstrated that estrogen and its receptors, aside from their role in regulating several biological functions, contribute to the development and progression/severity of inflammatory bowel diseases (IBDs). IBDs include both ulcerative colitis (UC) and Crohn's disease (CD). Epidemiological data indicate a clear difference in the incidence, severity, and complications of IBDs between sexes.

Loss of Aryl Hydrocarbon Receptor Promotes Colon Tumorigenesis in Mice.

The mutational genetic landscape of colorectal cancer has been extensively characterized; however, the ability of "cooperation response genes" to modulate the function of cancer "driver" genes remains largely unknown. In this study, we investigate the role of aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, in modulating oncogenic cues in the colon. We show that intestinal epithelial cell-targeted AhR knockout (KO) promotes the expansion and clonogenic capacity of colonic stem/progenitor cells harboring mutations by upregulating Wnt signaling.

Hydroxylated Chalcones as Aryl Hydrocarbon Receptor Agonists: Structure-Activity Effects.

Hydroxylated chalcones are phytochemicals which are biosynthetic precursors of flavonoids and their 1,3-diaryl-prop-2-en-1-one structure is used as a scaffold for drug development. In this study, the structure-dependent activation of aryl hydrocarbon receptor (AhR)-responsive CYP1A1, CYP1B1, and UGT1A1 genes was investigated in Caco2 colon cancer cells and in non-transformed young adult mouse colonocytes (YAMC) cells. The effects of a series of di- and trihydroxychalcones as AhR agonists was structure dependent with maximal induction of CYP1A1, CYP1B1, and UGT1A1 in Caco2 cells observed for compounds containing 2,2'-dihydroxy substituents and this included 2,2'-dihydroxy-, 2,2',4'-trihydroxy-, and 2,2',5'-trihydroxychalcones.

Effect of diet and intestinal AhR expression on fecal microbiome and metabolomic profiles.

Background: Diet, loss of aryl hydrocarbon receptor (AhR) expression and their modification of the gut microbiota community composition and its metabolites affect the development of colorectal cancer (CRC). However, the concordance between fecal microbiota composition and the fecal metabolome is poorly understood. Mice with specific AhR deletion (AhRKO) in intestinal epithelial cell and their wild-type littermates were fed a low-fat diet or a high-fat diet.

Loss of aryl hydrocarbon receptor potentiates FoxM1 signaling to enhance self-renewal of colonic stem and progenitor cells.

The aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor that senses xenobiotics, diet, and gut microbial-derived metabolites, is increasingly recognized as a key regulator of intestinal biology. However, its effects on the function of colonic stem and progenitor cells remain largely unexplored. Here, we observed that inducible deletion of AhR in Lgr5 stem cells increases the percentage of colonic stem cells and enhances organoid initiating capacity and growth of sorted stem and progenitor cells, while AhR activation has the opposite effect.

Dopamine is an aryl hydrocarbon receptor agonist.

Tryptophan metabolites exhibit aryl hydrocarbon receptor (AhR) agonist activity and recent studies show that the phenylalanine metabolites serotonin and carbidopa, a drug used in treating Parkinson's disease, activated the AhR. In this study, we identified the neuroactive hormone dopamine as an inducer of drug-metabolizing enzymes CYP1A1, CYP1B1, and UGT1A1 in colon and glioblastoma cells and similar results were observed for carbidopa. In contrast, carbidopa but not dopamine exhibited AhR activity in BxPC3 pancreatic cancer cells whereas minimal activity was observed for both compounds in Panc1 pancreatic cancer cells.

Concussion-Recovery Trajectories Among Tactical Athletes: Results From the CARE Consortium.

Context: Assessments of the duration of concussion recovery have primarily been limited to sport-related concussions and male contact sports. Furthermore, whereas durations of symptoms and return-to-activity (RTA) protocols encompass total recovery, the trajectory of each duration has not been examined separately.

Objective: To identify individual (eg, demographics, medical history), initial concussion injury (eg, symptoms), and external (eg, site) factors associated with symptom duration and RTA-protocol duration after concussion.

Effects of high-fat diet and intestinal aryl hydrocarbon receptor deletion on colon carcinogenesis.

Consumption of a high-fat diet has been associated with an increased risk of developing colorectal cancer (CRC). However, the effects of the interaction between dietary fat content and the aryl hydrocarbon receptor (AhR) on colorectal carcinogenesis remain unclear. Mainly known for its role in xenobiotic metabolism, AhR has been identified as an important regulator for maintaining intestinal epithelial homeostasis.