LDL receptor expression on T lymphocytes in old patients with Down syndrome

BACKGROUND: In Down syndrome patients several metabolic abnormalities have been reported, some involving the lipid metabolism. The level of LDL in plasma is the major determinant of the risk of vascular disease. There appear to be no studies on the LDL receptor in Down syndrome patients. METHODS: Flow cytometric methods for measuring the LDL receptor in peripheral blood mononuclear cells (PBMC) can identify patients with hypercholesterolemia. We applied this method in 19 old patients with Down syndrome and 23 healthy controls. RESULTS: Down syndrome patients had high levels of triglycerides and low levels of HDL, and high levels of CRP. We also found a down-regulation of LDL receptor expression. CONCLUSIONS: Down syndrome patients show no increase in the frequency of cardiovascular disease. The low incidence in cardiovascular disease despite the low level of HDL, high levels of CRP and reduction of LDL receptor expression lead to the conclusion that either these are not risk factors in these patients or that other risks factors – not yet identified – are considerably lower

Robotic total gastrectomy with intracorporeal robot-sewn anastomosis. A novel approach adopting the double-loop reconstruction method

Gastric cancer constitutes a major health problem. Robotic surgery has been progressively developed in this field. Although the feasibility of robotic procedures has been demonstrated, there are unresolved aspects being debated, including the reproducibility of intracorporeal in place of extracorporeal anastomosis. Difficulties of traditional laparoscopy have been described and there are well-known advantages of robotic systems, but few articles in literature describe a full robotic execution of the reconstructive phase while others do not give a thorough explanation how this phase was run. A new reconstructive approach, not yet described in literature, was recently adopted at our Center. Robotic total gastrectomy with D2 lymphadenectomy and a socalled ‘‘double-loop’’ reconstruction method with intracorporeal robotsewn anastomosis (Parisi’s technique) was performed in all reported cases. Preoperative, intraoperative, and postoperative data were collected and a technical note was documented. All tumors were located at the upper third of the stomach, and no conversions or intraoperative complications occurred. Histopathological analysis showed R0 resection obtained in all specimens. Hospital stay was regular in all patients and discharge was recommended starting from the 4th postoperative day. No major postoperative complications or reoperations occurred. Reconstruction of the digestive tract after total gastrectomy is one of the main areas of surgical research in the treatment of gastric cancer and in the field of minimally invasive surgery. The double-loop method is a valid simplification of the traditional technique of construction of the Roux-limb that could increase the feasibility and safety in performing a full hand-sewn intracorporeal reconstruction and it appears to fit the characteristics of the robotic system thus obtaining excellent postoperative clinical outcome

Safe and Efficient Reinforcement Learning for Environmental Monitoring

This paper discusses the challenges of applying reinforcement techniques to real-world environmental monitoring problems and proposes innovative solutions to overcome them. In particular, we focus on safety, a fundamental problem in RL that arises when it is applied to domains involving humans or hazardous uncertain situations. We propose to use deep neural networks, formal verification, and online refinement of domain knowledge to improve the transparency and efficiency of the learning process, as well as the quality of the final policies. We present two case studies, specifically (i) autonomous water monitoring and (ii) smart control of air quality indoors. In particular, we discuss the challenges and solutions to these problems, addressing crucial issues such as anomaly detection and prevention, real-time control, and online learning. We believe that the proposed techniques can be used to overcome some limitations of RL, providing safe and efficient solutions to complex and urgent problems

Sporadic High-Grade Malignant Peripheral Nerve Sheath Tumor of the Hypoglossal Nerve

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Adding systematic biopsy to magnetic resonance ultrasound fusion targeted biopsy of the prostate in men with previous negative biopsy or enrolled in active surveillance programs

Magnetic resonance imaging (MRI) targeted biopsy (TBx) of the prostate demonstrated to improve detection rate (DR) of clinically significant prostate cancer (csPCa) in biopsy-naive patients achieving strong level of evidence. Nevertheless, the csPCa yield for TBx alone versus TBx plus systematic biopsy (SBx) after accounting for overlapping of SBx cores with TBx cores, in prior-negative or active surveillance (AS) patients has not been well established.The objective of the study was to investigate benefits in terms of detection rate and pathological stratification of prostate cancer (PCa) using contextual SBx during MRI-TBx.Patients previously submitted to negative-SBx (cohort A) and those enrolled in an AS program (cohort B) who showed at least 1 suspicious area with a PIRADSv2 score ≥ 3 were prospectively and randomly assigned to only TBx strategy versus TBx plus SBx strategy. SBx locations could not encompass the TBx sites, so that the results of each type of biopsy were independent and did not overlap.A total of 312 patients were included in the 2 cohorts (cohort A: 213 cases; cohort B: 99 cases). No significant differences were found in terms of overall PCa-DR (77.6% vs 69.6% respectively; P = .36) and csPCa-DR (48.2% vs 60.9 respectively; P = .12). The MRI-TBx alone cohort showed higher csPCa/PCa ratio (87.5% vs 62.2%; P = .03). The MRI-TBx plus SBx group subanalysis showed significantly higher csPCa-DR obtained at the MRI-TBx cores when compared with the SBx cores (43.7% vs 24.1%, respectively; P = .01). Independently to age, prostatic-specific antigen and prostate imaging-reporting and data system score, either in rebiopsy (OR 0.43, 0.21-0.97) or AS (OR 0.46, 0.32-0.89) setting, SBx cores were negatively associated with the csPCa-DR when combined to TBx cores.MRI-TBx should be considered the elective method to perform prostate biopsy in patients with previous negative SBx and those considered for an AS program. Adding SBx samples to MRI-TBx did not improve detection rate of csPCa

Posterior muscle-fascial reconstruction and knotless urethro-neo bladder anastomosis during robot-assisted radical cystectomy: Description of the technique and its impact on urinary continence

Objective: The aim of our study is to describe the use of posterior muscle-fascial reconstruction during urethro-ileal anastomosis in bladder cancer (BC) patients submitted to robot-assisted radical cystectomy (RC) with orthotopic neobladder (ON) and its role in facilitating day- and night-time continence recovery during a 12-month follow up. Materials and methods: We prospectively collected data from 42 consecutive patients who underwent RARC with totally intracorporeal ON and extended pelvic lymph node dissection (PLND) at our Institution from June 2014 to October 2017. Prior to the urethro-neobladder anastomosis we reconstructed the Denonvilliers Fascia (DF) as previously described for radical prostatectomy using a bidirectional barbed suture. Day and night-time recovery rates were reported at 3, 6 and 12 months after surgery, with continent patients being those using either no urinary pads or 1 safety pads. Results: Median age at surgery was 63 yrs, 41 (97.6%) patients were male. 28 (66.7%) patients presented a clinical T2 disease. Median operative time and median ON reconstruction time were 450 minutes and 180 minutes respectively. 13 (31%) individuals had non-organ confined disease, with 11 (26.2%) patients with positive lymph nodes (median 3 positive lymph nodes) and 2 (4.8%) with non-urothelial cancer at final pathologic examination. Median hospital stay and median catheterization time were 7 (IQR 7-8) and 21 (IQR 19-22). During first 30 post-operative days we recorded 7 (16.7%) low-grade Clavien and 2 (4.8%) IIIa Clavien complications, whereas between 30 and 90 postoperative days we recorded 4 (9.5%) low-grade, 4 (9.5) IIIa and 1 (2.4%) IIIb complications. Day-time and night-time continence rates were 61.9% vs 52.4%, 73.8% vs 64.3% and 90.5% vs 73.8% at three, six and twelve months follow up. Day-time continence was significantly superior in the younger group (97% vs 57%, p 0.01); night-time continence rates were also superior among < 70 yrs patients, despite not reaching statistical significance (77% vs 57%, p 0.3). Conclusions: Posterior muscle-fascial reconstruction aids continence recovery in BC patients undergoing RARC with ON, with younger and fitter patients most benefitting from ON reconstruction

Cellular response to photodynamic therapy in chronic wounds

A wound is considered chronic if it does not heal timely. Basic processes at work are similar to acute healing, but their persistence leads to abundant granulation tissue and possibly fibrosis, scar contraction and loss of function [1]. Wounds may become chronic because of local and systemic conditions and are a major concern in clinical dermatology. Photodinamic therapy (PDT) has been proposed for these cases, through the administration of aminolaevulinic acid (ALA), leading to the synthesis of the photosensitizer protoporphyrin IX (PpIX), followed by illumination with visible light [2]. To study the effects of this therapy on the cell infiltrate of chronic wounds, cryosections of lesions before and after PDT were post fixed in cold acetone and stained with haematoxilin and eosin or immunolabeled with antibodies to laminin 5 (for basement membrane), HSP47 (for fibroblasts), alpha-smooth muscle actin (for myofibroblasts), SPM250 (for granulocytes). Intact neighbor skin was used as control. The cellular infiltrate, as well as the thickness of epidermis, the vascularization and the number of fibroblasts appeared increased in chronic wounds over healthy skin. After completion of PDT, fibroblasts appeared further increased in number, the treatment seemed to stimulate the connective tissue cells responsible for tissue repair rather than the inflammatory infiltrate (Supported by Ente Cassa di Risparmio di Firenze, grant 3681 to S.B.)

Elevated Brain Cannabinoid CB1 Receptor Availability in Posttraumatic Stress Disorder: A Positron Emission Tomography Study

Endocannabinoids and their attending cannabinoid type 1 receptor (CB1) have been implicated in animal models of posttraumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [11C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma controls [TC]) and those without such histories (healthy controls [HC]). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance (MR) imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [11C]OMAR, which measures volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [11C]OMAR VT values (F(2,53)=7.96, p=.001; 19.5% and 14.5% higher, respectively) which were most pronounced in women (F(1,53)=5.52, p=.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively—OMAR VT, anandamide, and cortisol—correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder

Fabrication and Characterisation of 3D Diamond Pixel Detectors With Timing Capabilities

Diamond sensors provide a promising radiation hard solution to the challenges posed by the future experiments at hadron machines. A 3D geometry with thin columnar resistive electrodes orthogonal to the diamond surface, obtained by laser nanofabrication, is expected to provide significantly better time resolution with respect to the extensively studied planar diamond sensors. We report on the development, production, and characterisation of innovative 3D diamond sensors achieving 30% improvement in both space and time resolution with respect to sensors from the previous generation. This is the first complete characterisation of the time resolution of 3D diamond sensors and combines results from tests with laser, beta rays and high energy particle beams. Plans and strategies for further improvement in the fabrication technology and readout systems are also discussed