Targeting Mesenchymal Stromal Cells/Pericytes (MSCs) With Pulsed Electromagnetic Field (PEMF) Has the Potential to Treat Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of synovium (synovitis), with inflammatory/immune cells and resident fibroblast-like synoviocytes (FLS) acting as major players in the pathogenesis of this disease. The resulting inflammatory response poses considerable risks as loss of bone and cartilage progresses, destroying the joint surface, causing joint damage, joint failure, articular dysfunction, and pre-mature death if left untreated. At the cellular level, early changes in RA synovium include inflammatory cell infiltration, synovial hyperplasia, and stimulation of angiogenesis to the site of injury. Different angiogenic factors promote this disease, making the role of anti-angiogenic therapy a focus of RA treatment. To control angiogenesis, mesenchymal stromal cells/pericytes (MSCs) in synovial tissue play a vital role in tissue repair. While recent evidence reports that MSCs found in joint tissues can differentiate to repair damaged tissue, this repair function can be repressed by the inflammatory milieu. Extremely-low frequency pulsed electromagnetic field (PEMF), a biophysical form of stimulation, has an anti-inflammatory effect by causing differentiation of MSCs. PEMF has also been reported to increase the functional activity of MSCs to improve differentiation to chondrocytes and osteocytes. Moreover, PEMF has been demonstrated to accelerate cell differentiation, increase deposition of collagen, and potentially return vascular dysfunction back to homeostasis. The aim of this report is to review the effects of PEMF on MSC modulation of cytokines, growth factors, and angiogenesis, and describe its effect on MSC regeneration of synovial tissue to further understand its potential role in the treatment of RA

Role of the Chemokine System in Liver Fibrosis: A Narrative Review

BACKGROUND AND OBJECTIVE: Liver fibrosis is a disease with characteristics of an aberrant wound healing response. Fibrosis is commonly the end-stage for chronic liver diseases like alcohol-associated liver disease (ALD), metabolic-associated liver disease, viral hepatitis, and hepatic autoimmune disease. Innate immunity contributes to the progression of many diseases through multiple mechanisms including production of pro-inflammatory mediators, leukocyte infiltration and tissue injury. Chemokines and their receptors orchestrate accumulation and activation of immune cells in tissues and are associated with multiple liver diseases; however, much less is known about their potential roles in liver fibrosis. This is a narrative review of current knowledge of the relationship of chemokine biology to liver fibrosis with insights into potential future therapeutic opportunities that can be explored in the future. METHODS: A comprehensive literature review was performed searching PubMed for relevant English studies and texts regarding chemokine biology, chronic liver disease and liver fibrosis published between 1993 and 2021. The review was written and constructed to detail the intriguing chemokine biology, the relation of chemokines to tissue injury and resolution, and identify areas of discovery for fibrosis treatment. KEY CONTENT AND FINDINGS: Chemokines are implicated in many chronic liver diseases, regardless of etiology. Most of these diseases will progress to fibrosis without appropriate treatment. The contributions of chemokines to liver disease and fibrosis are diverse and include canonical roles of modulating hepatic inflammation as well as directly contributing to fibrosis via activation of hepatic stellate cells (HSCs). Limited clinical evidence suggests that targeting chemokines in certain liver diseases might provide a therapeutic benefit to patients with hepatic fibrosis. CONCLUSIONS: The chemokine system of ligands and receptors is a complex network of inflammatory signals in nearly all diseases. The specific sources of chemokines and cellular targets lend unique pathophysiological consequences to chronic liver diseases and established fibrosis. Although most chemokines are pro-inflammatory and contribute to tissue injury, others likely aid in the resolution of established fibrosis. To date, very few targeted therapies exist for the chemokine system and liver disease and/or fibrosis, and further study could identify viable treatment options to improve outcomes in patients with end-stage liver disease

Immigration Cyber Prisons: Ending the Use of Electronic Ankle Shackles

The call to end immigration detention has garnered strong support in recent years due to a growing public awareness of its devastating impact on the individuals locked away, their families, and entire communities. Throughout the nation, communities, organizers, advocates, and public officials have demanded the shutdown of Immigration and Customs Enforcement (ICE) detention centers, particularly those operated by private prison companies. However, less attention has been paid to another form of detention that has been insidiously expanding alongside ICE’s brick-and-mortar jails: the Intensive Supervision Assistance Program (ISAP), the primary component of ICE’s so-called “Alternatives to Detention” program. ISAP surveils, monitors, and restricts immigrants by using invasive and evolving forms of technology. Like much of ICE’s sprawling detention system, ISAP is fueled by a multi-billion-dollar contract with the subsidiary of a private prison corporation that profits from detaining and surveilling immigrants. One of the most common and dehumanizing forms of surveillance in ISAP is a GPS enabled ankle monitor that shackles individuals both visibly and invisibly. This report recommends that ICE immediately wind down ISAP and cease its use of electronic ankle shackles, first by removing them from all individuals currently subject to ISAP. To the extent that ankle shackles continue being used while phasing out ISAP, the administration should mandate ICE to track the data needed to prevent discriminatory practices; provide both a clear written justification and review process when deciding to subject an individual to ankle shackles; and allow those subject to ankle shackles to secure employment, participate in family and community activities, and seek medical treatment. This report also recommends a severance of the link between immigration enforcement and service provision through community-based programs, as well as allocation of government funding for community support and legal representation services. As the harms of electronic ankle shackling demonstrate, ISAP is by no means an acceptable reform to the existing detention apparatus; rather it is another form of confinement that must be dismantled alongside physical detention. While the coercive and dehumanizing shackling of humans is unacceptable in any form, the data demonstrating the comparable or superior efficacy of more holistic intervention also lay bare the animus and profit motives at the heart of ICE’s shackling regime. Ending shackling is not just good policy; it is an issue of racial, economic, and health justice

Inverse Force Determination on a Small Scale Launch Vehicle Model Using a Dynamic Balance

A launch vehicle can experience large unsteady aerodynamic forces in the transonic regime that, while usually only lasting for tens of seconds during launch, could be devastating if structural components and electronic hardware are not designed to account for them. These aerodynamic loads are difficult to experimentally measure and even harder to computationally estimate. The current method for estimating buffet loads is through the use of a few hundred unsteady pressure transducers and wind tunnel test. Even with a large number of point measurements, the computed integrated load is not an accurate enough representation of the total load caused by buffeting. This paper discusses an attempt at using a dynamic balance to experimentally determine buffet loads on a generic scale hammer head launch vehicle model tested at NASA Ames Research Center's 11' x 11' transonic wind tunnel. To use a dynamic balance, the structural characteristics of the model needed to be identified so that the natural modal response could be and removed from the aerodynamic forces. A finite element model was created on a simplified version of the model to evaluate the natural modes of the balance flexures, assist in model design, and to compare to experimental data. Several modal tests were conducted on the model in two different configurations to check for non-linearity, and to estimate the dynamic characteristics of the model. The experimental results were used in an inverse force determination technique with a psuedo inverse frequency response function. Due to the non linearity, the model not being axisymmetric, and inconsistent data between the two shake tests from different mounting configuration, it was difficult to create a frequency response matrix that satisfied all input and output conditions for wind tunnel configuration to accurately predict unsteady aerodynamic loads

Comparison of voxel-wise and histogram analyses of glioma ADC maps for prediction of early therapeutic change

Noninvasive imaging methods are sought to objectively predict early response to therapy for high-grade glioma tumors. Quantitative metrics derived from diffusion-weighted imaging, such as apparent diffusion coefficient (ADC), have previously shown promise when used in combination with voxel-based analysis reflecting regional changes. The functional diffusion mapping (fDM) metric is hypothesized to be associated with volume of tumor exhibiting an increasing ADC owing to effective therapeutic action. In this work, the reference fDM-predicted survival (from previous study) for 3 weeks from treatment initiation (midtreatment) is compared to multiple histogram-based metrics using Kaplan-Meier estimator for 80 glioma patients stratified to responders and nonresponders based on the population median value for the given metric. The ADC histogram metric reflecting reduction in midtreatment volume of solid tumor (ADC 8% population-median with respect to pretreatment is found to have the same predictive power as the reference fDM of increasing midtreatment ADC volume above 4%. This study establishes the level of correlation between fDM increase and low-ADC tumor volume shrinkage for prediction of early response to radiation therapy in patients with glioma malignancies

Development of a multiparametric voxel-based magnetic resonance imaging biomarker for early cancer therapeutic response assessment

Quantitative magnetic resonance imaging (MRI)-based biomarkers, which capture physiological and functional tumor processes, were evaluated as imaging surrogates of early tumor response following chemoradiotherapy in glioma patients. A multiparametric extension of a voxel-based analysis, referred as the parametric response map (PRM), was applied to quantitative MRI maps to test the predictive potential of this metric for detecting response. Fifty-six subjects with newly diagnosed high-grade gliomas treated with radiation and concurrent temozolomide were enrolled in a single-site prospective institutional review board-approved MRI study. Apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) maps were acquired before therapy and 3 weeks after therapy was initiated. Multiparametric PRM (mPRM) was applied to both physiological MRI maps and evaluated as an imaging biomarker of patient survival. For comparison, single-biomarker PRMs were also evaluated in this study. The simultaneous analysis of ADC and rCBV by the mPRM approach was found to improve the predictive potential for patient survival over single PRM measures. With an array of quantitative imaging parameters being evaluated as biomarkers of therapeutic response, mPRM shows promise as a new methodology for consolidating physiologically distinct imaging parameters into a single interpretable and quantitative metric

Prostate-Specific Antigen testing in men between 40 and 70 years in Brazil: database from a check-up program

Objectives To evaluate the PSA in a large population of Brazilian men undergone to check up, and correlate the PSA cutoffs with prostate size and urinary symptoms. Materials and Methods This is a cross sectional study performed with men between 40 and 70 years undergone to check-up. All men were undergone to urological evaluation, digital rectal examination, prostate-specific antigen, and ultrasonography The exclusion criteria were men who used testosterone in the last six months, or who were using 5 alpha-reductase inhibitors. Results A total of 5015 men with an average age of 49.0 years completed the study. Most men were white and asymptomatic. The PSA in the three different aging groups were 0.9 ± 0.7ng/dL for men between 40 and 50; 1.2 ± 0.5ng/dL for men between 50 and 60; and 1.7 ± 1.5ng/dL for men greater than 60 years (p=0.001). A total of 192 men had PSA between 2.5 and 4ng/ml. From these men 130 were undergone to prostate biopsy. The predictive positive value of biopsy was 25% (32/130). In the same way, 100 patients had PSA >4ng/mL. From these men, 80 were undergone to prostate biopsy. In this group, the predictive positive value of biopsy was 40% (32/100). The Gleason score was 6 in 19 men (60%), 7 in 10 men (31%) and 8 in 3 men (9%). Conclusions The PSA level of Brazilian men undergone to check up was low. There was a positive correlation with aging, IPSS and prostate size.Universidade Federal de São Paulo (UNIFESP) Department of UrologyHospital Israelita Albert EinsteinWake Forest UniversityUNIFESP, Department of UrologySciEL