The Discovery of MORF-627, a Highly Selective Conformationally-Biased Zwitterionic Integrin αvβ6 Inhibitor for Fibrosis.

Inhibition of integrin αvβ6 is a promising approach to the treatment of fibrotic disease such as idiopathic pulmonary fibrosis. Screening a small library combining head groups that stabilize the bent-closed conformation of integrin αIIbβ3 with αv integrin binding motifs resulted in the identification of hit compounds that bind the bent-closed conformation of αvβ6. Crystal structures of these compounds bound to αvβ6 and related integrins revealed opportunities to increase potency and selectivity, and these efforts were accelerated using accurate free energy perturbation (FEP+) calculations.

Characterization of FGF21 Sites of Production and Signaling in Mice.

Fibroblast growth factor (FGF) 21 is an endocrine hormone that signals to multiple tissues to regulate metabolism. FGF21 and another endocrine FGF, FGF15/19, signal to target tissues by binding to the co-receptor β-klotho (KLB), which then facilitates the interaction of these different FGFs with their preferred FGF receptor. KLB is expressed in multiple metabolic tissues, but the specific cell types and spatial distribution of these cells are not known.

Systemic Factors Affecting Prognosis and Outcomes in Periodontal Disease.

This review delves into the effects of autoimmune conditions like rheumatoid arthritis, inflammatory disorders such as irritable bowel syndrome, cardiovascular disease, diabetes, infectious ailments like human immunodeficiency virus, and their medications on periodontal therapy outcomes. It also explores the influence of hormones. Understanding these systemic factors is crucial for optimizing periodontal health and treatment efficacy.

"All you need is compassion?" a latent profile analysis of neglect and self-compassion on child mental health.

Background: Neglect is a common form of child maltreatment and profoundly affects children's mental health globally. Self-compassion may help children cope with neglect but the role of self-compassion in neglect context has been understudied. This study identifies distinct patterns of self-compassion and child neglect and explores how neglect and self-compassion profiles correlate with child mental health.

Microfluidics produced ATRA-loaded PLGA NPs reduced tuberculosis burden in alveolar epithelial cells and enabled high delivered dose under simulated human breathing pattern in 3D printed head models.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is second only to COVID-19 as the top infectious disease killer worldwide. Multi-drug resistant TB (MDR-TB) may arise because of poor patient adherence to medications due to lengthy treatment duration and side effects. Delivering novel host directed therapies (HDT), like all trans retinoic acid (ATRA) may help to improve drug regimens and reduce the incidence of MDR-TB.

Decreasing utilization for postoperative radiation therapy in locoregionally advanced medullary thyroid cancer.

Background: Use of postoperative radiation therapy (PORT) in locoregionally advanced medullary thyroid cancer (MTC) remains controversial. The objective was to evaluate the effect of PORT on locoregional control (LRC) and overall survival (OS).

Methods: Retrospective cohort study of 346 MTC patients separated into PORT and no-PORT cohorts.

Rapid, tunable, and multiplexed detection of RNA using convective array PCR.

Detection of RNA targets is typically achieved through RT-qPCR or RNAseq. RT-qPCR is rapid but limited in number and complexity of targets detected, while RNAseq is high-throughput but takes multiple days. We demonstrate simultaneous amplification and detection of 28 distinct RNA targets from a single unsplit purified RNA sample in under 40 minutes using our convective array PCR (caPCR) technology.

Comparison of satisfaction with penile prosthesis implantation in patients with prostate cancer radiation therapy versus radical prostatectomy.

Background: Penile prosthesis surgery (PPS) is a commonly used treatment for erectile dysfunction (ED), either as first-line therapy or in cases refractory to other treatment options. In patients with a urologic malignancy such as prostate cancer, surgical interventions like radical prostatectomy (RP) as well as non-surgical treatments such as radiation therapy can all induce ED. PPS as a treatment for ED has high satisfaction rates in the general population.

Pericardial Fluid Analysis in Diagnosis and Prognosis of Patients Who Underwent Pericardiocentesis.

In this study, we aimed to examine the diagnostic yield of pericardial fluid biochemistry and cytology and their prognostic significance in patients with percutaneously drained pericardial effusions, with and without malignancy. This is a single-center, retrospective study of patients who underwent pericardiocentesis between 2010 and 2020. Data were extracted from electronic patient records, including procedural information, underlying diagnosis, and laboratory results.

Fibroblast growth factor-21 is required for weight loss induced by the glucagon-like peptide-1 receptor agonist liraglutide in male mice fed high carbohydrate diets.

Objective: Glucagon-like peptide-1 receptor (GLP-1R) agonists (GLP-1RA) and fibroblast growth factor-21 (FGF21) confer similar metabolic benefits. GLP-1RA induce FGF21, leading us to investigate mechanisms engaged by the GLP-1RA liraglutide to increase FGF21 levels and the metabolic relevance of liraglutide-induced FGF21.

Methods: Circulating FGF21 levels were measured in fasted male C57BL/6J, neuronal GLP-1R knockout, β-cell GLP-1R knockout, and liver peroxisome proliferator-activated receptor alpha knockout mice treated acutely with liraglutide.

Seroepidemiologic Investigation of a COVID-19 Outbreak Aboard a U.S. Navy Ship.

The crew of USS Kidd experienced a COVID-19 outbreak identified in April 2020. This is the earliest documented COVID-19 study with RT-PCR, serology, and pre-exposure test data on the entirety of the exposed population (n=333). Case definitions included 121 confirmed (36.

Liver Fibroblast Growth Factor 21 (FGF21) is Required for the Full Anorectic Effect of the Glucagon-Like Peptide-1 Receptor Agonist Liraglutide in Male Mice fed High Carbohydrate Diets.

Glucagon-like peptide-1 receptor (GLP-1R) agonists and fibroblast growth factor 21 (FGF21) confer similar metabolic benefits. Studies report that GLP-1RA induce FGF21. Here, we investigated the mechanisms engaged by the GLP-1R agonist liraglutide to increase FGF21 levels and the metabolic relevance of liraglutide-induced FGF21.

Two cases of tularemia in hunters from rural Newfoundland.

Background: Tularemia is a rare zoonosis caused by a small gram-negative intracellular coccobacillus. Transmission occurs through direct contact with small mammals such as hares and rabbits, exposure to ticks, or ingestion or inhalation of aerosolized particles. It is a highly variable disease with six subtypes based on clinical features.

Troponin and short-term mortality in hospitalised patients with COVID-19 infection: a retrospective study in an inner-city London hospital.

Objective: To investigate the association between troponin positivity in patients hospitalised with COVID-19 and increased mortality in the short term.

Setting: Homerton University Hospital, an inner-city district general hospital in East London.

Design: A single-centre retrospective observational study.

Central FGF21 production regulates memory but not peripheral metabolism.

Fibroblast growth factor 21 (FGF21) is a liver-derived endocrine hormone that functions to regulate energy homeostasis and macronutrient intake. Recently, FGF21 was reported to be produced and secreted from hypothalamic tanycytes, to regulate peripheral lipid metabolism; however, rigorous investigation of FGF21 expression in the brain has yet to be accomplished. Using a mouse model that drives CRE recombinase in FGF21-expressing cells, we demonstrate that FGF21 is not expressed in the hypothalamus, but instead is produced from the retrosplenial cortex (RSC), an essential brain region for spatial learning and memory.

Pharmacological FGF21 signals to glutamatergic neurons to enhance leptin action and lower body weight during obesity.

Objective: Fibroblast growth factor 21 (FGF21) is a peripherally-derived endocrine hormone that acts on the central nervous system (CNS) to regulate whole body energy homeostasis. Pharmacological administration of FGF21 promotes weight loss in obese animal models and human subjects with obesity. However, the central targets mediating these effects are incompletely defined.

Tany-Seq: Integrated Analysis of the Mouse Tanycyte Transcriptome.

The ability to maintain energy homeostasis is necessary for survival. Recently, an emerging role for ependymogial cells, which line the third ventricle in the hypothalamus in the regulation of energy homeostasis, has been appreciated. These cells are called tanycytes and are physically at the interface of brain communication with peripheral organs and have been proposed to mediate the transport of circulating hormones from the third ventricle into the parenchyma of the hypothalamus.

Bariatric surgery and the endoscopist.

Bariatric surgery is an effective treatment for obesity and its metabolic related disorders. With the numbers of bariatric procedures being performed rising annually endoscopists are now more likely than ever to encounter this patient cohort on routine diagnostic lists. Endoscopy plays a vital role in both the pre and postoperative periods to diagnose and treat certain complications associated with bariatric surgery.

Conditional gene targeting using UCP1-Cre mice directly targets the central nervous system beyond thermogenic adipose tissues.

Objective: Uncoupling protein 1 (UCP1) is a mitochondrial protein critical for adaptive thermogenesis in adipose tissues, and it is typically believed to be restricted to thermogenic adipose tissues. UCP1-Cre transgenic mice are utilized in numerous studies to provide "brown adipose-specific" conditional gene targeting. Here, we examined the distribution of Cre and UCP1 throughout the body in UCP1-Cre reporter mice.

Neuromodulation using ultra low frequency current waveform reversibly blocks axonal conduction and chronic pain.

Chronic pain remains a leading cause of disability worldwide, and there is still a clinical reliance on opioids despite the medical side effects associated with their use and societal impacts associated with their abuse. An alternative approach is the use of electrical neuromodulation to produce analgesia. Direct current can block action potential propagation but leads to tissue damage if maintained.

Laser-Assisted Therapy for the Treatment of Peri-implantitis. Part I. Clinical Outcomes.

The purpose of this 12-month randomized, controlled clinical trial was to evaluate the efficacy of a monotherapy protocol with the neodymium-doped yttrium aluminum garnet (Nd:YAG) laser for treatment of peri-implantitis. Twenty patients with 36 implants exhibiting probing pocket depths (PPDs) > 4 mm and evidence of radiographic bone loss (RBL) were randomly divided into two groups. The test group was treated with the Nd:YAG laser, and the control group was managed with mechanical debridement only.

2019-2020 Bushfire impacts on sediment and contaminant transport following rainfall in the Upper Murray River catchment.

During the 2019-2020 Australian bushfire season, large expanses (~47%) of agricultural and forested land in the Upper Murray River catchment of southeastern (SE) Australia were burned. Storm activity and rainfall following the fires increased sediment loads in rivers, resulting in localized fish kills and widespread water-quality deterioration. We collected water samples from the headwaters of the Murray River for sediment and contaminant analysis and assessed changes in water quality using long-term monitoring data.

Tissue reaction to novel customized calcium silicate cement based dental implants. A pilot study in the dog.

Objectives: The purpose of this study was to determine the level of periodontal tissue regeneration in a canine model following post-extraction placement of an implant molded from a composite material made from extracted tooth dentin and a calcium silicate cement (CSC) material. The investigation used autologous dentin in conjunction with a CSC material to form a composite implant designed for immediate tooth replacement.

Methods: Two (2) beagles had a periodontal and radiographic examination performed to rule out any pre-treatment inflammation, significant periodontal disease, or mobility.

Barriers and Facilitators to Bikeshare Programs: A Qualitative Study in an Urban Environment.

Introduction: Bikeshare programs have emerged across the US to promote bicycling as an active mode of transportation that could potentially improve health and quality of life. However, bikeshare usage is low in some settings. The purpose of this qualitative study is to explore barriers and facilitators of bikeshare use and to identify potential strategies to increase participation in urban environments.