Mast Cell Deficiency in Mice Attenuates Insulin Phenolic Preservative-Induced Inflammation.

One major obstacle that limits the lifespan of insulin infusion pumps is surmounting the tissue site reaction at the device implantation site. All commercial insulin formulations contain insulin phenolic preservatives (IPPs) designed to ensure insulin protein stability and prolong shelf-life. However, our laboratory demonstrated that these preservatives are cytotoxic and induce inflammation.

Prenatal benzene exposure in mice alters offspring hypothalamic development predisposing to metabolic disease in later life.

Maternal exposure to environmental contaminants during pregnancy poses a significant threat to a developing fetus, as these substances can easily cross the placenta and disrupt the neurodevelopment of offspring. Specifically, the hypothalamus is essential in the regulation of metabolism, notably during critical windows of development. An abnormal hormonal and inflammatory milieu during development can trigger persistent changes in the function of hypothalamic circuits, leading to long-lasting effects on the body's energy homeostasis and metabolism.

Growth hormone receptor (GHR) in AgRP neurons regulates thermogenesis in a sex-specific manner.

Evidence for hypothalamic regulation of energy homeostasis and thermoregulation in brown adipose tissue (BAT) during aging has been well recognized, yet the central molecular mediators involved in this process are poorly understood. The arcuate hypothalamus, orexigenic agouti-related peptide (AgRP) neurons control nutrient intake, energy homeostasis, and BAT thermogenesis. To determine the roles of growth hormone receptor (GHR) signaling in the AgRP neurons, we used mice with the AgRP-specific GHR deletion (AgRP).

Stiffness and Strain Properties Derived From Digital Tomosynthesis-Based Digital Volume Correlation Predict Vertebral Strength Independently From Bone Mineral Density.

Vertebral fractures are the most common osteoporotic fractures, but their prediction using standard bone mineral density (BMD) measurements from dual energy X-ray absorptiometry (DXA) is limited in accuracy. Stiffness, displacement, and strain distribution properties derived from digital tomosynthesis-based digital volume correlation (DTS-DVC) have been suggested as clinically measurable metrics of vertebral bone quality. However, the extent to which these properties correlate to vertebral strength is unknown.

The Novel Peptide Chm-273s Has Therapeutic Potential for Metabolic Disorders: Evidence from In Vitro Studies and High-Sucrose Diet and High-Fat Diet Rodent Models.

The aim of this study was to develop a novel peptide potentially applicable for the treatment of metabolic conditions, such as obesity and type 2 diabetes (T2D). We identified CHM-273S from the list of peptides from milk hydrolysate obtained by HPLC/MS-MS. In vitro analysis of primary murine fibroblasts indicated the potential of CHM-273S to upregulate IRS2 mRNA expression.

The Biochemistry and Physiology of A Disintegrin and Metalloproteinases (ADAMs and ADAM-TSs) in Human Pathologies.

Metalloproteinases are a group of proteinases that plays a substantial role in extracellular matrix remodeling and its molecular signaling. Among these metalloproteinases, ADAMs (a disintegrin and metalloproteinases) and ADAM-TSs (ADAMs with thrombospondin domains) have emerged as highly efficient contributors mediating proteolytic processing of various signaling molecules. ADAMs are transmembrane metalloenzymes that facilitate the extracellular domain shedding of membrane-anchored proteins, cytokines, growth factors, ligands, and their receptors and therefore modulate their biological functions.

17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy.

17-α-Estradiol (17aE2) treatment from 4 months of age extends life span in male mice and can reduce neuroinflammatory responses in the hypothalamus of 12-month-old males. Although 17aE2 improves longevity in males, female mice are unaffected, suggesting a sexually dimorphic pattern of life-span regulation. We tested whether the sex-specific effects of 17aE2 on neuroinflammatory responses are affected by gonadal removal and whether hypothalamic changes extend to other brain regions in old age.

ARC Neurons Regulate Muscle Glucose Uptake.

The growth hormone receptor (GHR) is expressed in brain regions that are known to participate in the regulation of energy homeostasis and glucose metabolism. We generated a novel transgenic mouse line (GHR) to characterize GHR-expressing neurons specifically in the arcuate nucleus of the hypothalamus (ARC). Here, we demonstrate that ARC neurons are co-localized with agouti-related peptide (AgRP), growth hormone releasing hormone (GHRH), and somatostatin neurons, which are activated by GH stimulation.

Assessment of Intravertebral Mechanical Strains and Cancellous Bone Texture Under Load Using a Clinically Available Digital Tomosynthesis Modality.

Vertebral fractures are the most common osteoporotic fractures, but clinical means for assessment of vertebral bone integrity are limited in accuracy, as they typically use surrogate measures that are indirectly related to mechanics. The objective of this study was to examine the extent to which intravertebral strain distributions and changes in cancellous bone texture generated by a load of physiological magnitude can be characterized using a clinically available imaging modality. We hypothesized that digital tomosynthesis-based digital volume correlation (DTS-DVC) and image texture-based metrics of cancellous bone microstructure can detect development of mechanical strains under load.

Hypothalamic GHR-SIRT1 Axis in Fasting.

Many aspects of physiological functions are controlled by the hypothalamus, a brain region that connects the neuroendocrine system to whole-body metabolism. Growth hormone (GH) and the GH receptor (GHR) are expressed in hypothalamic regions known to participate in the regulation of feeding and whole-body energy homeostasis. Sirtuin 1 (SIRT1) is the most conserved mamma-lian nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase that plays a key role in controlling life span and sensing nutrient availability in the hypothalamus in response to caloric restriction.

Tissue-specific role and associated downstream signaling pathways of adiponectin.

According to the World Health Organization, metabolic syndrome (MetS) can be defined as a pathological condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. The incidence of MetS keeps rising, as at least 35% of the USA population suffers from MetS. One of the worst comorbidities of metabolic syndrome are cardiovascular diseases that significantly amplifies the mortality associated with this syndrome.

Nourin-Dependent miR-137 and miR-106b: Novel Early Inflammatory Diagnostic Biomarkers for Unstable Angina Patients.

Background: Currently, no blood biomarkers exist that can diagnose unstable angina (UA) patients. Nourin is an early inflammatory mediator rapidly released within 5 min by reversible ischemic myocardium, and if ischemia persists, it is also released by necrosis. Nourin is elevated in acute coronary syndrome (ACS) patients but not in symptomatic noncardiac and healthy subjects.

In Utero Maternal Benzene Exposure Predisposes to the Metabolic Imbalance in the Offspring.

Environmental chemicals play a significant role in the development of metabolic disorders, especially when exposure occurs early in life. We have recently demonstrated that benzene exposure, at concentrations relevant to cigarette smoke, induces a severe metabolic imbalance in a sex-specific manner affecting male but not female mice. However, the roles of benzene in the development of aberrant metabolic outcomes following gestational exposure, remain largely unexplored.

Vertebral stiffness measured via tomosynthesis-based digital volume correlation is strongly correlated with reference values from micro-CT-based DVC.

Digital tomosynthesis (DTS) is a clinically available modality that allows imaging of a patient's spine in supine and standing positions. The purpose of this study was to establish the extent to which vertebral displacement and stiffness derived from DTS-based digital volume correlation (DTS-DVC) are correlated with those from a reference method, i.e.

Advancing continuous subcutaneous insulin infusion in vivo: New insights into tissue challenges.

Continuous Subcutaneous Insulin Infusion (CSII) is superior to conventional insulin therapy as it improves glycemic control thus reducing the probability of diabetic complications. Notwithstanding CSII's benefits, insulin dependent diabetic patients rarely achieve optimal glucose control. Moreover, CSII is only FDA approved for 3 days and often fails prematurely for reasons that have not been fully elucidated.

Efficacy of enhanced emergency department discharge for chronic hypertension management - Results of a randomized controlled trial.

Introduction: Achieve is a randomized controlled trial (RCT) of an education intervention for patients with chronic hypertension who have uncontrolled blood pressure (BP) at discharge from an urban emergency department (ED). The study examined efficacy and moderators of an educational intervention in an RCT on BP control at 180-day post-intervention.

Methods: Participants were recruited from a single, urban ED and randomized to receive or not to receive hypertension education.

Dynamic foraminal dimensions during neck extension and rotation in fusion and artificial disc replacement: an observational study.

Background: Changes in the dimensions of the cervical neural foramina (CNF) are considered to be a key factor in nerve root compression and development of cervical radiculopathy. However, to what extent foraminal geometry differs between patients who underwent anterior cervical discectomy and fusion (ACDF) and those who underwent total disc arthroplasty with an artificial disc (AD) during physiological motion is largely unknown.

Purpose: The objective of this study is to compare CNF dimensions during physiological neck motion between ACDF and AD.

Willingness to pay and willingness to accept in a patient-centered blood pressure control study.

Background: Elevated blood pressure is a major risk factor for cardiovascular disease and stroke but patients often discount recommended behavioral changes and prescribed medications. While effective interventions to promote adherence have been developed, cost-effectiveness from the patient's perspective, has not been well studied. The valuation of patient time and out of pocket expenses should be included while performing cost effectiveness evaluation.

Effect of View, Scan Orientation and Analysis Volume on Digital Tomosynthesis (DTS) Based Textural Analysis of Bone.

Digital tomosynthesis (DTS) derived textural parameters of human vertebral cancellous bone have been previously correlated to the finite element (FE) stiffness and 3D microstructure. The objective of this study was to optimize scanning configuration and use of multiple image slices in the analysis, so that FE stiffness prediction using DTS could be maximized. Forty vertebrae (T6, T8, T11, and L3) from ten cadavers (63-90 years) were scanned using microCT to obtain trabecular bone volume fraction (BV/TV) and FE stiffness.

Public Health, Hypertension, and the Emergency Department.

Hypertension (HTN) is the most common cardiovascular disease worldwide and is associated with severe long-term morbidity when not treated appropriately. Despite this, blood pressure (BP) control remains suboptimal, particularly among underserved populations and those who rely on emergency departments (EDs) as a source of primary care. ED providers encounter patients with severely elevated BP daily, and yet adherence to minimal standards of BP reassessment and referral to outpatient medical care, as recommended by the American College of Emergency Physicians, is limited.