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Anti-VEGF and also other Fresh Therapies regarding Neovascular Age-Related Macular Deterioration: A great Update.
Objectives Natalizumab (NTZ), a treatment indicated for patients with highly active Relapsing - Remitting Multiple Sclerosis (RRMS), is known to induce increased relative frequency of lymphocytes. Progressive Multifocal Leukoencephalitis (PML) is a rare but serious adverse event related to NTZ. Moreover, reduced L-selectin (CD62L) expression in T-cells in cryopreserved samples of patients with RRMS under NTZ has been proposed as a biomarker of pre-PML state. We explore the association between L-selectin expression in T-cells and hematological parameters in freshly processed samples of patients with RRMS under NTZ.Methods We studied L-selectin expression in patients with RRMS under NTZ (n=34), fingolimod (FTY, n=14), interferon-beta (IFNβ, n=22), glatiramer acetate (GA, N=17); in 9 patients with secondary progressive (SP) MS and in 6 healthy controls. Twenty-two patients under NTZ and 6 patients under FTY were followed for 18 months. One NTZ-treated patient developed PML during the study.Results Patients under NTZ exhibited increased relative frequency of lymphocytes (40.02±1.45) compared to patients under first-line treatment (30.57±1.68, p less then 0.001) and to patients with SPMS (29±1.56, p=0.02), and a lower mean L-selectin expression in (69.39±1.73) compared to patients under first-line treatment (79.1±1.17, p=0.003). A negative correlation between the relative frequency of CD4+CD62L+ T-cells and the absolute lymphocyte counts (Pearson's r=0.367, p=0.033) was observed.Discussion We hereby provide mechanistic insight in a possible pathway implicated in NTZ-related PML risk. These results further underline the need for thorough validation of L-selectin expression in T-cells as a potential pre-PML biomarker.We analyze the intersection of femme, aging, and later-in-life disability by using the popular, contemporary slogan "femme ain't frail" to explore who is erased, excluded, and overlooked when fem(me)ininity is conceptualized as strong, fierce, and chosen. Building from Lisa Walker's position that dominant femme discourse marginalizes the experiences of aging femmes, we analyze the narratives of Amber Hollibaugh, Joan Nestle, Mary Frances Platt and Sharon Wachsler to explore femme experiences of later-in-life disability and aging, and to further trouble existing, popular constructions of femme identity that are predicated upon youth and able-bodiedness. ZD1839 We elaborate on discourses of femme and frailty, bringing them together to explore the ways femme is or, can be, frail. link2 Insofar as femme is located in vulnerability, and vulnerability is associated with frailty, we see how femme might, indeed, be frail, and why this relationship is important to explore, not disavow. We contend that considerations of the frailty of fem(me)ininity can challenge the ageist and ableist orientation of contemporary femme politics and the broader cultural devaluation of fem(me)ininity.Functional foods are emerging as essential healthy nutritional component due to their abundant wellbeing benefits. Especially the food-derived peptides are considered as key components for playing their biologically active roles. One such robust therapeutics that already exploited with food peptides that help treating high blood pressure via targeting Angiotensin-Converting Enzyme (ACE). This in silico study demonstrated the inhibitory potential of antihypertensive peptides derived from food sources. This study involves an intensive structure-based analysis of enzyme-peptide interactions using Molecular Dynamics (MD) simulations. Interestingly, this study will help us to get deeper understanding on how food peptides achieve successful inhibition of ACE. In this study, the peptide-enzyme complexes revealed two binding pockets, A and B, on either side of the active site Zn atom. Pocket B has a smaller binding site volume than pocket A, comprised of β-sheets and the active site opening cleft. The interface of the binding sites showed that the enzyme structure was negative to neutral charge, and the peptide structure was positive to neutral charge. The dynamics of complex structures of seven highly potential peptides were performed for 20 ns each at 300 K. Comparative analysis of RMSD, RMSF and binding energies show the enzyme-peptide complexes and the overall stability of apo-enzyme. Importantly, two peptides AFKAWAVAR and IWHHTF showed the highest variation in their RMSD as compared to the apo-enzyme. This study will further be useful for the assessment of the characteristics to predict novel inhibitory peptides that can be generated from food proteins.Communicated by Ramaswamy H. Sarma.Aims To compare the efficacy of ginkgolide in the treatment of Chinese patients with ischemic stroke between pre-marketing and post-marketing studies.Methods This is a re-analysis of a pre-marketing (phase II/III, multicenter, double-blind, parallel-controlled; February 2005 to September 2005) and post-marketing (phase IV, multicenter, open, single-arm registration; April 2013 to June 2014) studies. The intervention groups received intravenous ginkgolide (10 mL daily, 14 days). Primary outcome was an improvement of National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores after 14 days.Results In pre- and post-marketing studies, NIHSS and mRS scores all improved, compared to that of baseline (P 8 points). Incidences of adverse reactions in the pre-marketing and post-marketing studies were 0.46% and 5.28%, respectively (P less then 0.001).Conclusion Intravenous ginkgolide may improve the outcome of acute ischemic stroke. Differences in effect between pre-marketing and post-marketing studies may be associated with gender, time of onset to enrollment and severity of stroke.BACKGROUND The International Society for Peritoneal Dialysis guidelines for small solute clearance and fluid removal in peritoneal dialysis (PD) were published in 2005. The aim of this article is to update those guidelines by reviewing the literature that supported those guidelines and examining publications since then. METHODS An extensive search of publications was performed through electronic databases and a hand search through reference lists from the existing guideline and selected articles. RESULTS There have been no prospective intervention trials to inform the area of small solute clearance in PD since the publication of the original guideline in 2005. The trials to date are largely limited to a few prospective cohort studies and retrospective studies. These have, however, consistently demonstrated that residual renal function (RRF) is more often associated with patient outcome than peritoneal clearance. One of the few randomised controlled trials performed in this area does suggest that a weekly Kt/V of 2.27 ± 0.02 provides no statistically significant survival advantage over a weekly Kt/V of 1.80 ± 0.02. The lower limit of Kt/V is unknown but there is weak evidence to suggest that anuric people doing PD should have a weekly Kt/V of at least 1.7. CONCLUSIONS There continues to be very poor evidence in the area of small solute clearance and fluid removal in PD. The evidence that exists suggests that RRF is more important than peritoneal clearance and that there appears to be no survival advantage in aiming for a weekly Kt/V >1.70.Large quantities of construction and demolition waste is generated annually around the world. Part of this material is processed in recycling plants. After removing metals, fines and lights, the construction and demolition waste is crushed and sized and can be used as aggregates for low resistance concrete, for road sub-base, city landfill and other low value-added applications. For their use as coarse aggregate in structural concretes, construction and demolition waste must exhibit high densities and regularity of the material. This material usually is presented in demolished concretes. About 20% of the particles from demolished concretes can be used as coarse aggregates substituting part of natural aggregates in structural concretes. This article presents studies of demolished concretes recycling by the use of a pneumatic jig. All jigging tests were carried out with three different concretes produced in three strength classes C16/20, ordinary concrete; C50/60, high strength concrete; and C70/85, very high strength concrete. Based on density distribution of the three concretes, there are reasonable masses with densities over 2.7 g cm-3, particle density considered appropriate to the used as coarse aggregate for structural concretes. The concretes present different mass recoveries of the denser particles (different liberation). Coarse aggregates can be recovered with reasonable masses by the use of air jigs About 65% for high strength concretes and about 75% for the low strength concrete. The jigging concentration efficiency depends on the concrete liberation, density and size distribution.BACKGROUND Serotonin 2A receptors, the molecular target of psychedelics, are expressed by neuronal and vascular cells, both of which might contribute to brain haemodynamic characteristics for the psychedelic state. AIM Aiming for a systemic understanding of psychedelic vasoactivity, here we investigated the effect of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine - a new-generation agonist with superior serotonin 2A receptor selectivity - on brain-supplying neck-arterial blood flow. METHODS We recorded core body temperature and employed non-invasive, collar-sensor based pulse oximetry in anesthetised mice to extract parameters of local blood perfusion, oxygen saturation, heart and respiration rate. Hypothesising an overlap between serotonergic pulse- and thermoregulation, recordings were done under physiological and elevated pad temperatures. RESULTS N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine (1.5 mg/kg, subcutaneous) significantly increased the frequency of heart beats accompanied bical last hub to channel cardiovascular output to or away from the brain, our results might have implications for the brain haemodynamics associated with psychedelia.Introduction Population-based data on the implementation of guidelines for cancer patients in daily practice are scarce, while practice variation may influence patient outcomes. Therefore, we evaluated treatment patterns and associated variables in the systemic treatment of metastatic colorectal cancer (mCRC) in the Netherlands.Material and methods We selected a random sample of adult mCRC patients diagnosed from 2008 to 2015 from the National Cancer Registry in 20 (4 academic, 8 teaching and 8 regional) Dutch hospitals. We examined the influence of patient, demographic and tumour characteristics on the odds of being treated with systemic therapy according to the current guideline and assessed its association with survival.Results Our study population consisted of 2222 mCRC patients of whom 1307 patients received systemic therapy for mCRC. link3 Practice variation was most obvious in the use of bevacizumab and anti-EGFR therapy in patients with (K)RAS wild-type tumours. Administration rates did not differ between h hospital strategies are an additional factor that may explain the observed differences between real-life data and results obtained from clinical trials.
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