Lowryharding2421
Immune system dysfunction has been proposed to play a critical role in the pathophysiology of autism spectrum disorders (ASD). Conflicting reports of lymphocyte subpopulation abnormalities have been described in numerous studies of patients with ASD. To better define lymphocytes abnormalities in ASD, we performed a meta-analysis of the lymphocyte profiles from subjects with ASD.
We used the PRISMA recommendations to query PubMed, Embase, PsychoINFO, BIOSIS, Science Direct, Cochrane CENTRAL, and Clinicaltrials.gov for terms related to clinical diagnosis of ASD and to lymphocytes' populations. We selected studies exploring lymphocyte subpopulations in children with ASD. The search protocol has been registered in the international Prospective Register of Systematic Reviews (CRD42019121473).
We selected 13 studies gathering 388 ASD patients and 326 healthy controls. A significant decrease in the CD4+ lymphocyte was found in ASD patients compared to controls [- 1.51 (95% CI - 2.99; - 0.04) p = 0.04] (I
= 9herapies in the field of ASD.
Our meta-analysis indicates defects in CD4+ lymphocytes, specifically decrease oin Tregs and increase in Th17 in ASD patients and supports the development of targeted immunotherapies in the field of ASD.
Percutaneous coronary interventions (PCI) of bifurcation stenoses are both complex and challenging. Stenting strategies share that the stents' side cells must be carefully explored and appropriately prepared using balloons or stents. So far, stent manufacturers have not provided any information regarding side-branch expansion capacity of their stent platforms.
Given that drug-eluting stent (DES) information regarding their mechanical capacity of side-branch expansion is not available, we aimed to evaluate contemporary DES (Orsiro, BIOTRONIK AG; Xience Sierra, Abbott Vascular; Resolute Integrity, Medtronic; Promus Premier Select, Boston Scientific; Supraflex Cruz, Sahajan and Medical Technologies) by their side-branch expansion behavior using in vitro bench testing.
In this in vitro study, we analyzed five commercially available DES (diameter 3.0mm), measuring their side-branch expansion following inflation of different high-pressure non-compliant (NC) balloons (balloon diameter 2.00-4.00mm), thereby revealing the morphological characteristics of their side-branch expansion capacities.
We demonstrated that all tested contemporary DES platforms could withstand large single-cell deformations, up to 4.0mm. As seen in our side-branch experiments, DES designs consisting of only two connectors between strut rings did not only result in huge cell areas, but also in larger cell diameters following side-branch expansion compared with DES designs using three or more connectors. Furthermore, the stent cell diameter attained was below the balloon diameter at normal pressure.
We recommend that the expansion capacity of side-branches should be considered in stent selection for bifurcation interventions.
We recommend that the expansion capacity of side-branches should be considered in stent selection for bifurcation interventions.
Immune checkpoint blockade (ICB) shows lasting benefits in advanced melanoma; however, not all patients respond to this treatment and many develop potentially life-threatening immune-related adverse events (irAEs). Identifying individuals who will develop irAEs is critical in order to improve the quality of care. Here, we prospectively demonstrate that the gut microbiome predicts irAEs in melanoma patients undergoing ICB.
Pre-, during, and post-treatment stool samples were collected from 27 patients with advanced stage melanoma treated with IPI (anti-CTLA-4) and NIVO (anti-PD1) ICB inhibitors at NYU Langone Health. We completed 16S rRNA gene amplicon sequencing, DNA deep shotgun metagenomic, and RNA-seq metatranscriptomic sequencing. The divisive amplicon denoising algorithm (DADA2) was used to process 16S data. Taxonomy for shotgun sequencing data was assigned using MetaPhlAn2, and gene pathways were assigned using HUMAnN 2.0. Compositionally aware differential expression analysis was performed using ANCeks after the start of treatment revealed that the microbiome remained stable over the course of treatment (R
= 0.88, p < 0.001).
We identified two distinct fecal bacterial community clusters which are associated differentially with irAEs in ICB-treated advanced melanoma patients.
We identified two distinct fecal bacterial community clusters which are associated differentially with irAEs in ICB-treated advanced melanoma patients.
Fear of cancer recurrence, depressive symptoms, and cancer-related fatigue are prevalent symptoms among cancer survivors, adversely affecting patients' quality of life and daily functioning. Effect sizes of interventions targeting these symptoms are mostly small to medium. Personalizing treatment is assumed to improve efficacy. However, thus far the empirical support for this approach is lacking. The aim of this study is to investigate if systematically personalized cognitive behavioral therapy is more efficacious than standard cognitive behavioral therapy in cancer survivors with moderate to severe fear of cancer recurrence, depressive symptoms, and/or cancer-related fatigue.
The study is designed as a non-blinded, multicenter randomized controlled trial with two treatment arms (ratio 11) (a) systematically personalized cognitive behavioral therapy and (b) standard cognitive behavioral therapy. In the standard treatment arm, patients receive an evidence-based diagnosis-specific treatment protocol for feahavioral therapy in cancer survivors. The study has several innovative characteristics, among which is the personalization of interventions on several dimensions. If proven effective, the results of this study provide a first step in developing an evidence-based framework for personalizing therapies in a systematic and replicable way.
The Dutch Trial Register (NTR) NL7481 (NTR7723). Registered on 24 January 2019.
The Dutch Trial Register (NTR) NL7481 (NTR7723). Registered on 24 January 2019.
Atypical reactions to the sensory environment are often reported in autistic individuals, with a high degree of variability across the sensory modalities. These sensory differences have been shown to promote challenging behaviours and distress in autistic individuals and are predictive of other functions including motor, social, and cognitive abilities. Preliminary research suggests that specific sensory differences may cluster together within individuals creating discrete sensory phenotypes. However, the manner in which these sensory differences cluster, and whether the resulting phenotypes are associated with specific cognitive and social challenges is unclear.
Short sensory profile data from 599 autistic children and adultsbetween the ages of 1 and 21years were subjected to a K-means cluster analysis. Analysis of variances compared age, adaptive behaviour, and traits associated with autism, attention-deficit and hyperactivity disorder, and obsessive and compulsive disorder across the resultant clusters difficulties.
Mechanical interactions between tumor cells and microenvironments are frequent phenomena during breast cancer progression, however, it is not well understood how these interactions affect Epithelial-to-Mesenchymal Transition (EMT). EMT is associated with the progression of most carcinomas through induction of new transcriptional programs within affected epithelial cells, resulting in cells becoming more motile and adhesive to endothelial cells.
MDA-MB-231, SK-BR-3, BT-474, and MCF-7 cells and normal Human Mammary Epithelial Cells (HMECs) were exposed to fluid flow in a parallel-plate bioreactor system. Changes in expression were quantified using microarrays, qPCR, immunocytochemistry, and western blots. Gene-gene interactions were elucidated using network analysis, and key modified genes were examined in clinical datasets. Potential involvement of Smads was investigated using siRNA knockdown studies. click here Finally, the ability of flow-stimulated and unstimulated cancer cells to adhere to an endothelial monolaye and identified biomarkers were distinctly expressed in patient populations. A better understanding of how biophysical forces such as shear stress affect cellular processes involved in metastatic progression of breast cancer is important for identifying new molecular markers for disease progression, and for predicting metastatic risk.
This study shows that fluid forces on the order of 1 Pa promote EMT and adhesion of breast cancer cells to an endothelial monolayer and identified biomarkers were distinctly expressed in patient populations. A better understanding of how biophysical forces such as shear stress affect cellular processes involved in metastatic progression of breast cancer is important for identifying new molecular markers for disease progression, and for predicting metastatic risk.
It is now well established that factors (free or in extracellular vesicles) secreted by mesenchymal stromal cells (MSC) are important mediators of MSC regenerative actions. Herein we produced the secretome (conditioned medium, CM) from MSC isolated from the amniotic membrane (hAMSC) and CM from the intact amniotic membrane (hAM, no manipulation or enzymatic digestion) in order to potentially identify an effective, easy and less expensive secretome to produce for potential applications in regenerative medicine. Given that immunomodulation is a key mechanism of action through which hAMSC contributes to tissue regeneration, we used a comprehensive panel of in vitro immunomodulatory tests to compare the CMs.
Amniotic membranes were either cut into fragments or used for hAMSC isolation. CMs from hAMSC at passages 0 and 2 were collected after a standard 5-day culture while CM from hAM was collected after a 2- and 5-day culture. Immunomodulation was assessed in terms of PBMC and T-cell proliferation, T-cell subs properties would allow for a ready-to-use product with easier handling, shipping and storage. The use of a lyophilized product will also facilitate clinicians by permitting customized reconstitution volumes and methods according to the most suitable formula required by the clinical application.
The results presented herein support the possibility to produce secretome from intact hAM and open the prospect to highly improve the scalability of the GMP production process while reducing the costs and time related to the process of cell isolation and expansion. Moreover, the possibility of having a lyophilized secretome that maintains its original properties would allow for a ready-to-use product with easier handling, shipping and storage. The use of a lyophilized product will also facilitate clinicians by permitting customized reconstitution volumes and methods according to the most suitable formula required by the clinical application.
This study investigated the protective effects of L. reuteri ZJ617 on intestinal and liver injury and the underlying mechanisms in modulating inflammatory, autophagy, and apoptosis signaling pathways in a piglet challenged with lipopolysaccharide (LPS).
Duroc×Landrace×Large White piglets were assigned to 3 groups (n = 6/group) control (CON) and LPS groups received oral phosphate-buffered saline for 2 weeks before intraperitoneal injection (i.p.) of physiological saline or LPS (25 μg/kg body weight), respectively, while the ZJ617 + LPS group was orally inoculated with ZJ617 for 2 weeks before i.p. of LPS. Piglets were sacrificed 4 h after LPS injection to determine intestinal integrity, serum biochemical parameters, inflammatory signaling involved in molecular and liver injury pathways.
Compared with controls, LPS stimulation significantly increased intestinal phosphorylated-p38 MAPK, phosphorylated-ERK and JNK protein levels and decreased IκBα protein expression, while serum LPS, TNF-α, and IL-6 concentrations (P < 0.