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On the one hand, the emotional state can influence food intake and on the other hand, hunger can have an impact on the emotional state. Oxalaceticacid Leptin, which is encoded by the ob gene, is involved in the energy homeostasis and plays a role in development of obesity. Mice deficient for leptin (ob/ob) are obese and display several behavioral alterations. It has been shown that ob/ob mice display striking changes in neuronal plasticity within the limbic system, e.g., hippocampal formation. We focus on alterations in ob/ob mice that can be related to alter processing in another part of the limbic system, the amygdala. ob/ob mice have a higher food consumption than age-matched controls, which might have an impact on the emotional state of these mice. Since the amygdala is involved in emotional processing, we analyze whether ob/ob mice display alterations in plasticity at the electrophysiological and structural level. No changes were seen in dendritic spine densities in the basolateral and lateral (LA) nucleus of the amygdala. Interestingly and in contrast to the hippocampus (Porter et al. 2013), long-term potentiation in the LA was increased in ob/ob mice. Our results indicate that amygdalar and hippocampal synaptic plasticity are regulated in different ways by leptin deficiency in accordance with the different functions of these limbic structures in stress and anxiety.The hematopoietic niche is a specialized microenvironment that supports the survival, proliferation and differentiation of hematopoietic stem progenitor cells (HSPCs). Three-dimensional (3D) models mimicking hematopoiesis might allow in vitro and in vivo studies of the hematopoietic (HP) process. Here, we investigate the capacity of a 3D construct based on non-adherent murine bone marrow mononuclear cells (NA-BMMNCs), mesenchymal stromal cells (MSCs) and collagen microspheres (CMs), all embedded into plasma clot (PC) to support in vitro and in vivo hematopoiesis. Confocal analysis of the 3D hematopoietic construct (3D-HPC), cultured for 24 h, showed MSC lining the CM and the NA-BMMNCs closely associated with MSC. In vivo hematopoiesis was examined in 3D-HPC subcutaneously implanted in mice and harvested at different intervals. Hematopoiesis in the 3D-HPC was evaluated by histology, cell morphology, flow cytometry, confocal microscopy and hematopoietic colony formation assay. 3D-HPC implants were integrated and vascularized in the host tissue, after 3 months of implantation. Histological studies showed the presence of hematopoietic tissue with the presence of mature blood cells. Cells from 3D-HPC showed viability greater than 90%, expressed HSPCs markers, and formed hematopoietic colonies, in vitro. Confocal microscopy studies showed that MSCs adhered to the CM and NA-BMMNCs were scattered across the 3D-HPC area and in close association with MSC. In conclusion, the 3D-HPC mimics a hematopoietic niche supporting the survival, proliferation and differentiation of HSPCs, in vivo. 3D-HPC may allow evaluation of regulatory mechanisms involved in hematopoiesis.
Our aim was to investigate whether the surgical approach, i.e. endoscopic (ET) versus conventional/open thyroidectomy (ConT), contributes towards the improvement in quality of life (QoL), cosmetic outcomes and overall patient satisfaction with treatment.
We conducted a prospective study (October 2016-August 2018) consisting of patients undergoing hemithyroidectomy for euthyroid, non-malignant solitary thyroid nodules (STNs). Patients were divided into two groups Group I (ET)-41 patients and Group II (ConT)-52 patients. ET was performed via bilateral-axillo breast approach (BABA). A thyroid disease-specific questionnaire "ThyPRO-39hin" was used to evaluate pre- and post-operative QoL. Visual analogue scale (VAS) was used for post-operative pain. Cosmetic satisfaction, paraesthesia and overall satisfaction with treatment were evaluated using Likert-type verbal response scales. Pre- and post-operative scores (>6months) were compared, and p value < 0.05 was considered significant.
Mean age (p = 0.26),reatment as compared to conventional/open thyroidectomy.
The objective of this study was to evaluate whether
Ga-PSMA PET/CT whole-body tumor burden (PSMAwbtb) is associated with clinical parameters and laboratory parameters in prostate cancer patients.
We retrospectively evaluated prostate cancer patients submitted to PSMA PET/CT for primary staging purposes or due to biochemical recurrence (BR). PSMAwbtb metrics (total volume of PSMA-avid tumor (PSMA-TV)) and total uptake of PSMA-avid lesions (PSMA-TL) were calculated semi-automatically. Spearman's rank correlations between PSMAwbtb metrics and clinical, laboratory parameters (age, time-to-BR, years of diagnosis of prostate cancer, free and total serum PSA levels, and the Gleason score) and with the highest SUVmax of a lesion (hSUVmax) were analyzed.
Among the 257 PSMA PET/CT studies, there were 46 scans (17.9%) performed for primary staging and 211 (82.1%) for BR. PSMA-TV and PSMA-TL were calculated for the 157 positive scans (58.8%), which were 43 patients (93.5%) in the primary staging group and 114 patients (54.0%) in the BR group. In the primary staging group, we observed a significant correlation between PSMA-TL and hSUVmax (p = 0.0021). In the BR group, there was a significant direct correlation between PSMA-TL and the variables age (p = 0.0031), total serum PSA values (p = < 0.0001), free serum PSA values (p= < 0.0001), and the hSUVmax (p = < 0.0001). Similar results were obtained for PSMA-TV.
PSMAwbtb has a direct and positive correlation with serum PSA values and age in prostate cancer patients with BR.
PSMAwbtb has a direct and positive correlation with serum PSA values and age in prostate cancer patients with BR.Superior capsular reconstruction (SCR) is an emerging surgical technique used to treat patients with irreparable rotator cuff tears. In this procedure, a graft is attached between the superior glenoid and the greater tuberosity, with the aim of optimising glenohumeral joint function and stability. Pre-operative radiological evaluation of patients having such cuff tears is crucial for appropriate patient selection. Such imaging is particularly useful for the assessment of the cuff tear size and location, muscle wasting, fatty infiltration and the presence of any glenohumeral joint arthritis. In addition, post-operative imaging is useful in assessing graft integrity, with specific patterns of graft failure now being recognised on imaging. This article will discuss the indications and contraindications for this procedure, and review the biomechanical concepts of SCR in improving glenohumeral joint stability and restoring the force couples around the joint. The radiological appearances of the intact graft and the various patterns of graft failure will be illustrated, along with various radiological examples.
Patients with diabetes who had a recent myocardial infarction (MI) are at high risk of cardiovascular events. Therefore, risk assessment is important for treatment and shared decisions. We used data from EXAMINE trial to investigate whether a multi-proteomic approach would provide specific proteomic signatures and also improve the prognostic capacity for determining the risk of cardiovascular death, MI, stroke, heart failure [HF], all-cause death, and combinations of these outcomes.
93 circulating proteins (92 from the Olink® CVDII plus troponin) were assessed in 5131 patients. Cox, competing risks, and reclassification measures were applied.
The clinical model showed good discrimination and calibration for all outcomes. On top of theclinical model that included age, sex, smoking, diabetes duration, history of MI (prior to the index MI of inclusion), history of HF hospitalization, history of stroke, atrial fibrillation, hypertension, systolic blood pressure, statin therapy, estimated glomerular filtratil receptor 2 (or death receptor 5), Gal-9 galectin-9, FGF23 fibroblast growth factor 23.
The present study investigated a pathogenic mutation and its mechanism on membranous cataract in a congenital membranous cataract family.
An autosomal dominant four-generation Chinese congenital membranous cataract family was recruited and whole-exome sequencing was performed to screen for sequence variants. Candidate variants were validated using polymerase chain reaction and Sanger sequencing. Wild-type and mutant low-density lipoprotein receptor-related protein 5-like (LRP5L) plasmids were constructed and transfected into human lens epithelial cells (HLE B-3) and human anterior lens capsules. The cell lysates, nuclear and cytoplasmic proteins, and basement membrane components of HLE B-3 cells were harvested. LRP5L and laminin γ1 were knocked down in HLE B-3 cells using specific small-interfering RNA. The protein expression levels of LRP5L, laminin γ1, and c-MAF were detected using immunoblotting and immunofluorescence.
We identified a novel suspected pathogenic mutation in LRP5L (c.107C > G, p.P36R) in the congenital membranous cataract family. This mutation was absent in 300 normal controls and 300 age-related cataract patients. Bioinformatics analysis with PolyPhen-2 and SIFT suggested that LRP5L-P36R was pathogenic. LRP5L upregulated laminin γ1 expression in the cytoplasmic proteins of HLE B-3 cells and human anterior lens capsules, and LRP5L-P36R inhibited the effects of LRP5L. LRP5L upregulated c-MAF expression in the nucleus and cytoplasm of HLE B-3 cells, and LRP5L-P36R inhibited c-MAF expression via inhibition of laminin γ1.
Our study identified a novel gene, LRP5L, associated with congenital membranous cataract, and its mutant LRP5L-P36R contributed to membranous cataract development via inhibition of laminin γ1 and c-MAF.
Our study identified a novel gene, LRP5L, associated with congenital membranous cataract, and its mutant LRP5L-P36R contributed to membranous cataract development via inhibition of laminin γ1 and c-MAF.Forensic diatom test has been widely accepted as a way of providing supportive evidences in the diagnosis of drowning. The current workflow is primarily based on the observation of diatoms by forensic pathologists under a microscopy, and this process can be very time-consuming. In this paper, we demonstrate a deep learning-based approach for automatically searching diatoms in scanning electron microscopic images. Cross-validation studies were performed to evaluate the influence of magnification on performance. Moreover, various training strategies were tested to improve the performance of detection. The conclusion shows that our approach can satisfy the necessary requirements to be integrated as part of an automatic forensic diatom test.Rapastinel is a novel psychoactive substance that acts as an N-methyl-D-aspartate-receptor (NMDAR) agonist and triggers antidepressant- and antipsychotic-like effects in animal models. However, it is unknown if rapastinel possesses a better side-effect profile than fast-acting glutamatergic antidepressants, like ketamine, which trigger neurotoxicity in the perinatal rodent cortex and protracted schizophrenia-like alterations. Here we found a remarkable neuroprotective effect of rapastinel against apoptosis induced by the NMDAR antagonist MK-801 in comparison to that elicited by clozapine and the mGlu2/3 agonist LY354740. These results suggest the potential therapeutic/prophylactic effect of rapastinel in ameliorating deleterious effects induced by NMDAR blockade during neurodevelopment.
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