Thursday, November 19, 2020

Joint hemorrhage accelerates cartilage degeneration in a rat immobilized knee model

xlomafota.13 shared this article with you from Inoreader

12891.jpg

Abstract

Background

Joint hemorrhage is caused by trauma, ligament reconstruction surgery, and bleeding disorders such as hemophilia. Recurrence of hemorrhage in the joint space induces hemosiderotic synovitis and oxidative stress, resulting in both articular cartilage degeneration and arthropathy. Joint immobilization is a common treatment option for articular fractures accompanied by joint hemorrhage. Although joint hemorrhage has negative effects on the articular cartilage, there is no consensus on whether a reduction in joint hemorrhage would effectively prevent articular cartilage degeneration. The purpose of this study was to investigate the effect of joint hemorrhage combined with joint immobilization on articular cartilage degeneration in a rat immobilized knee model.

Methods

The knee joints of adult male rats were immobilized at the flexion using an internal fixator from 3 days to 8 weeks. The rats were randomly divided into the following groups: immobilized blood injection (Im-B) and immobilized-normal saline injection (Im-NS) groups. The cartilage was evaluated in two areas (contact and non-contact areas). The cartilage was used to assess chondrocyte count, Modified Mankin score, and cartilage thickness. The total RNA was extracted from the cartilage in both areas, and the expression of metalloproteinase (MMP)-8, MMP-13, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α was measured by quantitative real-time polymerase chain reaction.

Results

The number of chondrocytes in the Im-B group significantly decreased in both areas, compared with that in the Im-NS group. Modified Mankin score from 4 to 8 weeks of the Im-B group was significantly higher than that of the Im-NS group only in the contact area. The expression of MMP-8 and MMP-13 from 2 to 4 weeks and TNF-α from 2 to 8 weeks significantly increased in the Im-B group compared with those in the Im-NS group, but there was no significant difference in IL-1β expression.

Conclusions

The results showed that joint hemorrhage exacerbated immobilization-induced articular cartilage degeneration. Drainage of a joint hemorrhage or avoidance of loading may help prevent cartilage degeneration during joint immobilization with a hemorrhage.

View on the web

Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update

xlomafota.13 shared this article with you from Inoreader

40265.jpg

Abstract

Background

A 2017 systematic review (SR) identified 59 studies examining gabapentinoid (pregabalin and gabapentin) misuse/abuse. Evidence of gabapentinoid misuse/abuse has since grown substantially.

Objective

Update previous SR and describe new insights regarding gabapentinoid abuse.

Methods

A SR of PubMed was conducted to identify studies published from 7/29/2016–8/31/2020. Four searches were performed using the following terms: "gabapentin [MeSH] OR pregabalin [MeSH] OR gabapentinoid" AND one of the following substance misuse/abuse-related terms: "substance-related disorders [MeSH]", "overdose", "abuse", or "misuse". Clinicaltrials.gov and the Cochrane Library database were searched to identify ongoing studies or similar SRs. Reference lists of included studies were reviewed to identify additional literature. All studies with novel data related to pregabalin and/or gabapentin abuse, misuse, or overdose conducted during the study period were included. Articles not written in English, review articles, and animal studies were excluded.

Results

Fifty-five studies were included (29 [52.7%] from North America, 17 [30.9%] Europe, 6 [10.9%] Asia, and 3 [5.5%] Australia). Forty-six observational studies and 10 case reports/series were included (one manuscript included both). Twenty (36.4%) studied gabapentin only, 18 (32.7%) pregabalin only, and 17 (30.9%) both pregabalin/gabapentin. These studies corroborate findings from the previous SR that gabapentinoids are increasingly abused or misused to self-medicate, that gabapentinoids can produce desirable effects alone but are often used concomitantly with other drugs, and that opioid use disorder is the greatest risk factor for gabapentinoid abuse. While the original SR identified the largest studies having been published in Europe, this review identified several more generalisable US studies that have subsequently been conducted. The most concerning finding was increased evidence of associated patient harm, including increased hospital utilisation and opioid -related overdose mortality risk.

Conclusion

Evidence suggests that gabapentinoid misuse/abuse represents a growing trend that is causing significant patient harm. Prescribers should exercise appropriate caution with use in high-risk populations and monitor for signs of misuse or abuse.

View on the web

The ground state of the lithium atom in dense plasmas using variational Monte Carlo method

xlomafota.13 shared this article with you from Inoreader

Abstract

In this paper, the variational quantum Monte Carlo method is applied to investigate the ground state of the lithium atom. Moreover, the energy eigenvalues of the lithium atom in dense plasma are also investigated by using the Debye–Hückel model and the exponential cosine screened Coulomb potential model. The calculations are carried out by using trial wave functions in the form of the Slater determinant wave function multiplied by a correlation function due to the interaction between the electrons. Three types of correlation functions are used—with two, three and four variational parameters—one of which satisfies the well-known cusp conditions. Interesting results are obtained in comparison with results obtained by using other trial wave functions.

View on the web

Validation of novel patient-centred juvenile idiopathic arthritis-specific patient-reported outcome and experience measures (PROMs/PREMs)

xlomafota.13 shared this article with you from Inoreader

Abstract

Background

Measuring the outcomes that matter to children and young people (CYP) with juvenile idiopathic arthritis (JIA), is a necessary precursor to patient-centred improvements in quality of clinical care. We present a two-centre validation of novel JIA patient-reported outcome and experience measures (PROM and PREM) developed as part of the CAPTURE-JIA project.

Methods

CYP with JIA were recruited from paediatric rheumatology clinics, completing the CAPTURE-JIA PROM and PREM, CHAQ and CHU 9D. A subset participated in face-to-face interviews and completed the PROM/PREM 1 week later. The OMERACT filter was applied and the three domains of validation assessed. Truth assessments included cognitive interviewing, sensitivity analysis and Spearman's correlations. Discrimination assessments included specificity and reliability testing. Feasibility was assessed using time to form completion and proportion of missing data.

Results

Eighty-two CYP and their families were recruited; ten cognitive interviews and fifteen PROM/PREM test/retests were conducted. Truth: CYP and parents understood the PROM/PREM and felt important areas were covered. PROM criteria had high sensitivities (> 70%) against similar items on the CHU 9D, with the exception of fatigue (58%). Correlations between similar PROM and CHU 9D criteria were moderate to very strong (coefficients 0.40–0.82.) Discrimination: high specificities (> 70%) on corresponding PROM and CHU 9D domains. Feasibility: median completion times for PROM 60 s (IQR 38–75) and PREM 49 s (IQR 30–60) respectively.

Conclusion

The CAPTURE-JIA PROM and PREM are valid and feasible in UK paediatric rheumatology clinics. Embedding routine collection into clinical care would be a major step towards improving quality of care.

View on the web

EndoPil: A Magnetically Actuated Swallowable Capsule for Weight Management: Development and Trials

xlomafota.13 shared this article with you from Inoreader

10439.jpg

Abstract

Intragastric balloons (IGBs), by occupying the stomach space and prolonging satiety, is a promising method to treat obesity and consequently improves its associated comorbidities, e.g. coronary heart disease, diabetes, and cancer. However, existing IGBs are often tethered with tubes for gas or liquid delivery or require endoscopic assistance for device delivery or removal, which are usually uncomfortable, costly, and may cause complications. This paper presents a novel tetherless, magnetically actuated capsule (EndoPil) which can deploy an IGB inside the stomach after being swallowed and being activated by an external magnet. The external magnet attracts a small magnet inside the EndoPil to open a valve, triggering the chemical reaction of citric acid and potassium bicarbonate to produce carbon dioxide gas, which inflates a biocompatible balloon (around 120 mL). A prototype, 13 mm in diameter and 35 mm in length, was developed. Simulations and bench-top tests wer e conducted to test the force capability of the magnetic actuation mechanism, the required force to activate the valve, and the repeatability of balloon inflation. Experiments on animal and human were successfully conducted to demonstrate the safety and feasibility of inflating a balloon inside the stomach by an external magnet.

View on the web

Neck Muscle and Head/Neck Kinematic Responses While Bracing Against the Steering Wheel During Front and Rear Impacts

xlomafota.13 shared this article with you from Inoreader

10439.jpg

Abstract

Drivers often react to an impending collision by bracing against the steering wheel. The goal of the present study was to quantify the effect of bracing on neck muscle activity and head/torso kinematics during low-speed front and rear impacts. Eleven seated subjects (3F, 8 M) experienced multiple sled impacts (Δv = 0.77 m/s; apeak = 19.9 m/s2, Δt = 65.5 ms) with their hands on the steering wheel in two conditions: relaxed and braced against the steering wheel. Electromyographic activity in eight neck muscles (sternohyoid, sternocleidomastoid, splenius capitis, semispinalis capitis, semispinalis cervicis, multifidus, levator scapulae, and trapezius) was recorded unilaterally with indwelling electrodes and normalized by maximum voluntary contraction (MVC) levels. Head and torso kinematics (linear acceleration, angular velocity, angular rotation, and retraction) were measured with sen sors and motion tracking. Muscle and kinematic variables were compared between the relaxed and braced conditions using linear mixed models. We found that pre-impact bracing generated only small increases in the pre-impact muscle activity (< 5% MVC) when compared to the relaxed condition. Pre-impact bracing did not increase peak neck muscle responses during the impacts; instead it reduced peak trapezius and multifidus muscle activity by about half during front impacts. Bracing led to widespread changes in the peak amplitude and timing of the torso and head kinematics that were not consistent with a simple stiffening of the head/neck/torso system. Instead pre-impact bracing served to couple the torso more rigidly to the seat while not necessarily coupling the head more rigidly to the torso.

View on the web

Efficacy of Liraglutide to Prevent Weight Regain After Retrieval of an Adjustable Intra-gastric Balloon—a Case-Matched Study

xlomafota.13 shared this article with you from Inoreader

11695.jpg

Abstract

Purpose

Weight regain after balloon retrieval is a concern with all intra-gastric balloons (IGBs). The aim of this study was to evaluate the efficacy of liraglutide, a glucagon-like peptide-1 (GLP-1) agonist, to prevent weight regain following IGB retrieval.

Materials and Methods

This was a case-matched study of patients undergoing Spatz3 adjustable IGB (Spatz FGIA, Inc. NY, USA) at three outpatient clinics in Brazil between November 2015 and January 2019. Seventy-seven patients that opted to take liraglutide following IGB retrieval (IGB-L) were matched 1:1 to 198 patients that declined the medication—IGB-Alone (IGB-A). Propensity score adjustment was performed at the time of balloon retrieval on factors known to influence the choice of liraglutide. Weight and percent body fat (%BF) was measured at baseline and 9 months after IGB retrieval. % BF is defined as the total mass of fat divided by total body mass, multiplied by 100. The primary outcome was weight regain, and the secondary outcome was change in %BF 9 months after IGB retrieval.

Results

Propensity score matching yielded 53 matched pairs. Weight regain to the starting point was not observed in either group. There was significantly less weight regain in IGB-L compared to IGB-A, − 1.15 ± 0.94 kg versus − 0.66 ± 0.99 kg (p = 0.010) 9 months after balloon retrieval. Additionally, %BF decline in IGB-L was superior to IGB-A − 10.83 ± 1.50 versus − 7.94 ± 2.02 (p < 0.01). There was no difference in weight regain or decline in %BF based on liraglutide dose.

Conclusion

Liraglutide has an additive benefit with respect to efficacy and a reduction in body fat when commenced after IGB retrieval. Future randomized control studies will be needed to determine the optimal dose and duration of liraglutide to achieve superior outcomes.

View on the web

Modeling of Virtual Mechanical Circulatory Hemodynamics for Biventricular Heart Failure Support

xlomafota.13 shared this article with you from Inoreader

13239.jpg

Abstract

Objective

In this study, a mechanical circulatory support simulation tool was used to investigate the application of a unique device with two centrifugal pumps and one motor for the biventricular assist device (BVAD) support application. Several conditions—including a range of combined left and right systolic heart failure severities, aortic and pulmonary valve regurgitation, and combinations of high and low systemic and pulmonary vascular resistances—were considered in the simulation matrix. Relative advantages and limitations of using the device in BVAD applications are discussed.

Methods

The simulated BVAD pump was based on the Cleveland Clinic pediatric continuous-flow total artificial heart (P-CFTAH), which is currently under development. Different combined disease states (n = 10) were evaluated to model the interaction with the BVAD, considering combinations of normal heart, moderate failure and severe systolic failure of the left and right ventricles, regurgitation of the aortic and pulmonary valves and combinations of vascular resistance. The virtual mock loop simulation tool (MATLAB; MathWorks®, Natick, MA) simulates the hemodynamics at the pump ports using a lumped-parameter model for systemic/pulmonary circulation characteristic inputs (values for impedance, systolic and diastolic ventricular compliance, beat rate, and blood volume), and characteristics of the cardiac chambers and valves.

Results

Simulation results showed that this single-pump BVAD can provide regulated support of up to 5 L/min over a range of combined heart failure states and is suitable for smaller adult and pediatric support. However, good self-regulation of the atrial pressure difference was not maintained with the introduction of aortic valve regurgitation or high systemic vascular resistance when combined with low pulmonary vascular resistance.

Conclusions

This initial in silico study demonstrated that use of the P-CFTAH as a BVAD supports cardiac output and arterial pressure in biventricular heart failure conditions. A similar but larger device would be required for a large adult patient who needs more than 5 L/min of support.

View on the web

Urea entrapment in cellulose acetate microparticles obtained by electrospraying

xlomafota.13 shared this article with you from Inoreader

10965.jpg

Abstract

Urea is a widely used source of nitrogen, but its rapid solubilization in water leads to significant wastage on application. Thus, the quest for an efficient and economical polymeric matrix able to encapsulated urea is a long-standing challenge. In this paper, we present a simple and economical method for urea entrapment in cellulose acetate (CA) microparticles produced by the electrospraying process. The morphology and diameter of the microparticles were optimized experimentally by evaluating the solvent composition (binary mixture) and polymer concentration. The electrospraying process parameters, such as particle collection distance, applied voltage and flow rate, were also evaluated. The particle diameter was determined by scanning electron microscopy (SEM) and the CA microparticle characteristics, urea incorporation and in vitro release profile were determined by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetr y (DSC). The morphological characteristics (shape and porosity) of the CA microparticles were affected by the diffusion rate and CA solubility due to solvent evaporation in the electrospraying process. The SEM images showed monodispersed and spherical CA microparticles with a diameter size of 2.2 ± 0.3 µm. The FTIR spectra and SEM images verified the urea entrapment in the CA microparticles (100 mg/g), and the particle morphology did not appear to be affected. The release of urea from the CA microparticles showed a maximum of 79% after 7 h, which is a significant difference in relation to in vitro urea release. The results obtained using the electrospray technology represent a step forward in the search to improve the incorporation of urea into CA microparticles.

View on the web

Overlapping Molecular Pathways Leading to Autism Spectrum Disorders, Fragile X Syndrome, and Targeted Treatments

xlomafota.13 shared this article with you from Inoreader

13311.jpg

Abstract

Autism spectrum disorders (ASD) are subdivided into idiopathic (unknown) etiology and secondary, based on known etiology. There are hundreds of causes of ASD and most of them are genetic in origin or related to the interplay of genetic etiology and environmental toxicology. Approximately 30 to 50% of the etiologies can be identified when using a combination of available genetic testing. Many of these gene mutations are either core components of the Wnt signaling pathway or their modulators. The full mutation of the fragile X mental retardation 1 (FMR1) gene leads to fragile X syndrome (FXS), the most common cause of monogenic origin of ASD, accounting for ~ 2% of the cases. There is an overlap of molecular mechanisms in those with idiopathic ASD and those with FXS, an interaction between various signaling pathways is suggested during the development of the autistic brain. This review summarizes the cross talk between neurobiological pathways found in ASD and FXS. These signaling pathways are currently under evaluation to target specific treatments in search of the reversal of the molecular abnormalities found in both idiopathic ASD and FXS.

View on the web

BDNF rs6265 Variant Alters Outcomes with Levodopa in Early-Stage Parkinson’s Disease

xlomafota.13 shared this article with you from Inoreader

13311.jpg

Abstract

Disease outcomes are heterogeneous in Parkinson's disease and may be predicted by gene variants. This study investigated if the BDNF rs6265 single nucleotide polymorphism (SNP) is associated with differential outcomes with specific pharmacotherapy treatment strategies in the "NIH Exploratory Trials in PD Long-term Study 1" (NET-PD LS-1, n = 540). DNA samples were genotyped for the rs6265 SNP and others (rs11030094, rs10501087, rs1491850, rs908867, and rs1157659). The primary measures were the Unified Parkinson's Disease Rating Scale (UPDRS) and its motor component (UPDRS-III). Groups were divided by genotype and treatment regimen (levodopa monotherapy vs levodopa with other medications vs no levodopa). T allele carriers were associated with worse UPDRS outcomes compared to C/C subjects when treated with levodopa monotherapy (+ 6 points, p = 0.02) and to T allele carriers treated with no levodopa treat ment strategies (UPDRS: + 8 points, p = 0.01; UPDRS-III: + 6 points, p = 0.01). Similar effects of worse outcomes associated with levodopa monotherapy were observed in the BDNF rs11030094, rs10501087, and rs1491850 SNPs. This study suggests the levodopa monotherapy strategy is associated with worse disease outcomes in BDNF rs6265 T carriers. Pending prospective validation, BDNF variants may be precision medicine factors to consider for symptomatic treatment decisions for early-stage PD patients.

View on the web

Collaboration request

Hi there How would you like to earn a 35% commission for each sale for life by selling SEO services Every website owner requires the ...