Functional genomic analyses uncover APOE -mediated regulation of brain and cerebrospinal fluid beta-amyloid levels in Parkinson disease

xlomafota.13 shared this article with you from Inoreader Functional genomic analyses uncover APOE -mediated regulation of brain and cerebrospinal fluid beta-amyloid levels in Parkinson disease Via Latest Results for Acta Neuropathologica Communications Abstract Alpha-synuclein is the main protein component of Lewy bodies, the pathological hallmark of Parkinson's disease. However, genetic modifiers of cerebrospinal fluid (CSF) alpha-synuclein levels remain unknown. The use of CSF levels of amyloid beta1–42, total tau, and phosphorylated tau181 as quantitative traits in genetic studies have provided novel insights into Alzheimer's disease pathophysiology. A systematic study of the genomic architecture of CSF biomarkers in Parkinson's disease has not yet been conducted. Here, genome-wide association studies of CSF biomarker levels in a cohort of individuals with Parkinson's disease and controls (N = 1960) were performed. PD cases exhibited significantly lower CSF biomarker levels compared to controls. A SNP, proxy for APOE ε4, was associated with CSF amyloid beta1–42 levels (effect = − 0.5, p = 9.2 × 10−19). No genome-wide loci assoc iated with CSF alpha-synuclein, total tau, or phosphorylated tau181 levels were identified in PD cohorts. Polygenic risk score constructed using the latest Parkinson's disease risk meta-analysis were associated with Parkinson's disease status (p = 0.035) and the genomic architecture of CSF amyloid beta1–42 (R2 = 2.29%; p = 2.5 × 10−11). Individuals with higher polygenic risk scores for PD risk presented with lower CSF amyloid beta1–42 levels (p = 7.3 × 10−04). Two-sample Mendelian Randomization revealed that CSF amyloid beta1–42 plays a role in Parkinson's disease (p = 1.4 × 10−05) and age at onset (p = 7.6 × 10−06), an effect mainly mediated by variants in the APOE locus. In a subset of PD samples, the APOE ε4 allele was associated with significantly lower levels of CSF amyloid beta1–42 (p� ��= 3.8 × 10−06), higher mean cortical binding potentials (p = 5.8 × 10−08), and higher Braak amyloid beta score (p = 4.4 × 10−04). Together these results from high-throughput and hypothesis-free approaches converge on a genetic link between Parkinson's disease, CSF amyloid beta1–42, and APOE. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Right ventricular outflow tract obstruction caused by sinus of Valsalva aneurysm

xlomafota.13 shared this article with you from Inoreader Right ventricular outflow tract obstruction caused by sinus of Valsalva aneurysm Via Latest Results for General Thoracic and Cardiovascular Surgery Abstract Right ventricular outflow tract (RVOT) obstruction caused by sinus of Valsalva aneurysm is a rare observation. We describe a successful case of valve-sparing root replacement using reimplantation technique for RVOT obstruction by a large right coronary sinus of Valsalva aneurysm in a 76-year-old man. In the pathological examination, the elastic fibers of the medial layer were defective not only in the wall of the aneurysmal Valsalva sinus but also in the remaining two sinus walls. Our experience illustrated that valve-sparing root replacement can be an effective procedure in such a case. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Perfusion in hand arthritis on dynamic contrast-enhanced computed tomography: a randomized prospective study using MRI as a standard of reference

xlomafota.13 shared this article with you from Inoreader Perfusion in hand arthritis on dynamic contrast-enhanced computed tomography: a randomized prospective study using MRI as a standard of reference Via Latest Results Abstract Objective To evaluate the performance of dynamic contrast-enhanced CT (DCE-CT) in detecting and quantitatively assessing perfusion parameters in patients with arthritis of the hand compared with dynamic contrast-enhanced MRI (DCE-MRI) as a standard of reference. Materials and methods In this IRB-approved randomized prospective single-centre study, 36 consecutive patients with suspected rheumatoid arthritis underwent DCE-CT (320-row, tube voltage 80 kVp, tube current 8.25 mAs) and DCE-MRI (1.5 T) of the hand. Perfusion maps were calculated separately for mean transit time (MTT), time to peak (TTP), relative blood volume (rBV), and relative blood flow (rBF) using four different decomposition techniques. Region of interest (ROI) analysis was performed in metacarpophalangeal joints II–V and in the wrist. Pairs of perfusion parameters in DCE-CT and DCE-MRI were compared using a two-tailed t test for paired samples and interpreted for effect size (Cohen's d). According to the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) scoring results, differentiation of synovitis-positive and synovitis-negative joints with both modalities was assessed with the independent t test. Results The two modalities yielded similar perfusion parameters. Identified differences had small effects (d 0.01–0.4). DCE-CT additionally differentiates inflamed and noninflamed joints based on rBF and rBV but tends to underestimate these parameters in severe inflammation. The total dose-length product (DLP) was 48 mGy*cm with an estimated effective dose of 0.038 mSv. Conclusion DCE-CT is a promising imaging technique in arthritis. In patients with a contraindication to MRI or when MRI is not available, DCE-CT is a suitable alternative to detect and assess arthritis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The Effects of Very Low Energy Diets and Low Energy Diets with Exercise Training on Skeletal Muscle Mass: A Narrative Review

xlomafota.13 shared this article with you from Inoreader The Effects of Very Low Energy Diets and Low Energy Diets with Exercise Training on Skeletal Muscle Mass: A Narrative Review Via Latest Results for Advances in T... Abstract In recent years, very-low-energy diets (VLEDs) have been recognised as a viable strategy for improving the extent of weight loss and cardio-metabolic outcomes in people who are either overweight or obese. However, concerns exist regarding the reductions in lean body mass (LBM) during VLEDs, particularly in vulnerable demographic groups, such as middle-aged and older adults already prone to developing sarcopenia. Sarcopenia is itself associated with multiple adverse outcomes, including frailty, cardio-metabolic deterioration and increased mortality. Therefore, a number of studies investigating strategies to ameliorate this detrimental effect of VLEDs have attempted to address this concern. This narrative review explores the potential benefits and limitations of exercise and/or protein supplementation for LBM retention during VLEDs based on the available evidence. Current studies suggest that both protein supplementation and exercise training may result in improved LBM retention (and skeletal muscle function) during VLEDs. However, uncertainty remains concerning the interactions between intervention types, based on discordant outcomes reported in the literature and the heterogeneity of exercise modalities in achieving this particular outcome. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Preparation of a ferroelectric composite film metal–organic framework/PVDF

xlomafota.13 shared this article with you from Inoreader Preparation of a ferroelectric composite film metal–organic framework/PVDF Via Latest Results for Journal of Polymer Research Abstract With increasing of the intellectualized electronics devices, new kinds of flexible ferroelectric polymer materials with high dielectric constant attracted more and more attention in recent decades. Polyvinylidene fluoride (PVDF), as one of the most studied ferroelectric polymer materials, has been studied in many published works. Among these works, lots of efforts have been employed to promote the generation of β crystal phase. We here introduced a concise and effective way for large-scale fabrication of promising ferroelectric polymer films by doping a metal–organic framework (MOF) particles via costing process. Then effects of the addition of MOF on the ferroelectric, dielectric and mechanical properties of PVDF composite film were systematic researched. By comparing the results of XRD and FTIR, we found that the addition of MOF changed the α crystal phase of PVDF to β crystal phase which helped improve the ferroelectric and dielectric properties of PVDF composites. The new PVDF composite film, with very low addition (5wt.%) of MOF, possessed the highest remanent polarization (22μC/cm2 at 80MV/m and 1 Hz electric field), and the highest dielectric constant (21 at 10 Hz). The data of mechanical properties indicated that the fine dispersion of MOF maintained the flexibility of PVDF. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Diagnosis and treatment of intramedullary osteosclerosis: a report of three cases and literature review

xlomafota.13 shared this article with you from Inoreader Diagnosis and treatment of intramedullary osteosclerosis: a report of three cases and literature review Via Latest Results for BMC Musculoskeletal Disorders Abstract Background Intramedullary osteosclerosis (IMOS) is a rare condition without specific radiological findings except for the osteosclerotic lesion and is not associated with family history and infection, trauma, or systemic illness. Although the diagnosis of IMOS is confirmed after excluding other osteosclerotic lesions, IMOS is not well known because of its rarity and no specific feature. Therefore, these situations might result in delayed diagnosis. Hence, this case report aimed to investigate three cases of IMOS and discuss imaging findings and clinical outcomes. Case presentation All three cases were examined between 2015 and 2019. The location of osteosclerotic lesions were femoral diaphyses in the 60-year-old man (Case 1) and 41-year-old woman (Case 2) and tibial diaphysis in the 44-year-old woman (Case 3). All cases complained of severe pain and showed massive diaphyseal osteosclerotic lesions in plain radiograms and computed tomography (CT) scans. Cases 2 and 3 were examined using the triphasic bone scan, and a fusiform-shaped intense area of the tracer uptake on delayed bone image was detected in both cases without (Case 2) or slightly increased vascularity (Case 3) on the blood pool image, which was reported as a specific finding of IMOS. Open biopsy was performed in all cases, and histologic section showed trabecular bone sclerosis with hypocellular fibrous tissues, finally diagnosed as IMOS. The pain was sharply improved after biopsy and kept at the latest follow-up periods (34, 33, and 6 months in Cases 1, 2, and 3, respect ively). Conclusions Massive sclerotic lesions with severe pain in the diaphyseal region of long bones should be considered as IMOS to avoid the delayed diagnosis, although other sclerotic bony lesions should be carefully excluded. Triphasic bone scan with a fusiform-shaped intense area of tracer uptake on delayed bone image and without or slightly increased vascularity on the blood pool image will help confirm IMOS. The role of open biopsy was to confirm the diagnosis of IMOS and to give the severe pain relief immediately in the three cases, although more cases and long-term follow-up are necessary. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Joint hemorrhage accelerates cartilage degeneration in a rat immobilized knee model

xlomafota.13 shared this article with you from Inoreader Joint hemorrhage accelerates cartilage degeneration in a rat immobilized knee model Via Latest Results for BMC Musculoskeletal Disorders 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 Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota.13 shared this article with you from Inoreader Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update Via Latest Results for Drugs 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 Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota.13 shared this article with you from Inoreader The ground state of the lithium atom in dense plasmas using variational Monte Carlo method Via Latest Results for Indian Journal of Physics 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 Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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 Validation of novel patient-centred juvenile idiopathic arthritis-specific patient-reported outcome and experience measures (PROMs/PREMs) Via Latest Results for Pediatric Rheumatology 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 Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota.13 shared this article with you from Inoreader EndoPil: A Magnetically Actuated Swallowable Capsule for Weight Management: Development and Trials Via Latest Results for Annals of Biomedical Engineering 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 Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.