Efficacy of profound versus moderate neuromuscular blockade in enhancing postoperative recovery after laparoscopic donor nephrectomy: A randomised controlled trial.

Background: Profound neuromuscular blockade (NMB) during anaesthesia has been shown to reduce postoperative pain scores, when compared with a moderate block. We hypothesised that profound NMB during laparoscopic donor nephrectomy (LDN) could also improve the early quality of recovery after surgery.

Objectives: To compare the effectiveness of profound versus moderate NMB during LDN in enhancing postoperative recovery.

Synthesis of New GABA Receptor Modulator with Pyrazolo[1,5-a]quinazoline (PQ) Scaffold.

We previously published a series of 8-methoxypirazolo[1,5-a]quinazolines (PQs) and their 4,5-dihydro derivatives (4,5()PQ) bearing the (hetero)arylalkylester group at position 3 as ligands at the γ-aminobutyric type A (GABA) subtype receptor. Continuing the study in this field, we report here the design and synthesis of 3-(hetero)arylpyrazolo[1,5-a]quinazoline and 3-(hetero)aroylpyrazolo[1,5-a]quinazoline 8-methoxy substituted as interesting analogs of the above (hetero)arylalkylester, in which the shortening or the removal of the linker between the 3-(hetero)aryl ring and the PQ was performed. Only compounds that are able to inhibit radioligand binding by more than 80% at 10 μM have been selected for electrophysiological studies on recombinant α1β2γ2L GABA receptors.

Memantine prodrug as a new agent for Alzheimer's Disease.

Hydrogen sulphide has recently drawn much attention due to its potent anti-inflammatory and neuroprotective roles in brain functions. The purpose of the current study was to exploit these beneficial properties of HS to design a new agent for the treatment of Alzheimer's disease (AD). To pursue our aims, we replaced the free amine group of memantine with an isothiocyanate functionality as a putative HS-donor moiety.

Prevalence of metabolic syndrome and non-alcoholic fatty liver disease in a cohort of italian patients with spinal-bulbar muscular atrophy.

Spinal-bulbar muscular atrophy (SBMA), is an X-linked motor neuron disease caused by a CAG-repeat expansion in the first exon of the androgen receptor gene (AR) on chromosome X. In SBMA, non-neural clinical phenotype includes disorders of glucose and lipid metabolism. We investigated the prevalence of metabolic syndrome (MS), insulin resistance (IR) and non alcoholic fatty liver disease (NAFLD) in a group of SBMA patients.

Nociception-guided versus Standard Care during Remifentanil-Propofol Anesthesia: A Randomized Controlled Trial.

Background: The multidimensional index of nociception, the nociception level, outperforms blood pressure and heart rate in detection of nociceptive events during anesthesia. We hypothesized that nociception level-guided analgesia reduces opioid consumption and suboptimal anesthesia events such as low blood pressure and use of vasoactive medication.

Methods: In this single-blinded randomized study, 80 American Society of Anesthesiologists class I-III adult patients of either sex, scheduled for major abdominal procedures under remifentanil/propofol anesthesia by target-controlled infusion, were included.

Potential Diagnostic Value of Red Blood Cells α-Synuclein Heteroaggregates in Alzheimer's Disease.

A plethora of complex misfolded protein combinations have been found in Alzheimer disease (AD) brains besides the classical pathological hallmarks. Recently, α-synuclein (α-syn) and its heterocomplexes with amyloid-β (Aβ) and tau have been suggested to be involved in the pathophysiological processes of neurodegenerative diseases. These pathological features are not limited to the brain, but can be also found in peripheral fluids.

Epidural and Non-epidural Analgesia in Patients Undergoing Open Pancreatectomy: a Retrospective Cohort Study.

Background: The use of epidural analgesia (EA) in pancreatic surgery remains under debate. This study compares patients treated with EA versus non-EA after open pancreatectomy in a tertiary referral center.

Methods: All patients undergoing open pancreatectomy from 2013 to 2017 were retrospectively reviewed.

An Early Tailored Approach Is the Key to Effective Rehabilitation in the Intensive Care Unit.

Objective: To investigate the effectiveness, feasibility, and safety of an evidence-based rehabilitation care pathway in the intensive care unit (ICU) in different patient populations.

Design: Observational prospective cohort study, with retrospective controls.

Setting: ICUs of a university hospital.

Correction to: do patients consider computer-adaptive measures more appropriate than static questionnaires?

Following publication of the original article [1], the authors reported three of their given name have been erroneously tagged as their family names. The correct names are: give name Caroline family name Martini, give name Irene family name Virgolini, give name Bernhard family name Holzner.

Safety of Percutaneous Hepatic Perfusion with Melphalan in Patients with Unresectable Liver Metastases from Ocular Melanoma Using the Delcath Systems' Second-Generation Hemofiltration System: A Prospective Non-randomized Phase II Trial.

Purpose: To investigate the safety and toxicity of percutaneous hepatic perfusion with melphalan (M-PHP) with the Delcath Systems' second-generation (GEN 2) filter and compare the outcomes with historical data from studies using the first-generation filter.

Materials And Methods: A prospective, single-arm, single-center phase II study was carried out including 35 patients with unresectable, histologically confirmed liver metastases from ocular melanoma between February 2014 and June 2017. Main exclusion criteria were extrahepatic disease and age > 75 years.

Long lasting inhibition of Mdm2-p53 interaction potentiates mesenchymal stem cell differentiation into osteoblasts.

The osteoblast generation from Mesenchymal stem cells (MSCs) is tightly coordinated by transcriptional networks and signalling pathways that control gene expression and protein stability of osteogenic "master transcription factors". Among these pathways, a great attention has been focused on p53 and its physiological negative regulator, the E3 ligase Murine double minute 2 (Mdm2). Nevertheless, the signalling that regulates Mdm2-p53 axis in osteoblasts remain to be elucidated, also considering that Mdm2 possesses numerous p53-independent activities and interacts with additional proteins.

Do patients consider computer-adaptive measures more appropriate than static questionnaires?

Objective: Computer-adaptive tests (CAT) use individualised sets of questions to assess patient-reported health states, whereas static (conventional) questionnaires present the same questions to all patients. CAT has been shown to increase measurement precision and reduce assessment length. In our study, we investigated if patients perceive CAT questions as more appropriate than static questionnaires, a claim that is frequently associated with CAT measures.

Oropouche Virus-Associated Aseptic Meningoencephalitis, Southeastern Brazil.

Oropouche fever is a neglected arthropodborne disease and zoonosis responsible for several outbreaks of a febrile disease in Central and South America. We present a clinical case of aseptic meningoencephalitis in an immunocompetent patient that resulted from Oropouche virus acquired in northern Brazil but diagnosed in a nonendemic region.

The synthesis and characterization of giant Calixarenes.

Calixarenes are cyclic oligomers obtained by condensation of suitable p-functionalised phenols with formaldehyde, usually allowing for the synthesis of the well known small calixarenes (including up to eight phenolic subunits). We report here the discovery of much larger members of this family, exhibiting sizes up to 90 phenolic subunits: the giant calixarenes. These macrocycles are obtained according to simple, easily scalable processes, in yields up to 65%.

Variable Responses to CFTR Correctors : Estimating the Design Effect in Precision Medicine.

Interest in precision medicine has grown in recent years due to the variable clinical benefit provided by some medications, their cost, and by new opportunities to tailor therapies to individual patients. In cystic fibrosis it may soon be possible to test several corrector drugs that improve the folding and functional expression of mutant cystic fibrosis transmembrane conductance regulator (CFTR) prospectively using cells from a patient to find the one that is best for that individual. Patient-to-patient variation in cell culture responses to correctors and the reproducibility of those responses has not been studied quantitatively.

A protein chimera self-assembling unit for drug delivery.

In the modern view of selective drug delivery of bioactive molecules, the attention is moving onto the setup of the perfect carrier more than in the optimization of the active compound. In this respect, virus-like particles constitute bioinspired nanodevices with the intrinsic ability to transport a large class of molecules, ranging from smart drugs to small interfering RNAs. In this work, we demonstrate the efficacy of a novel construct obtained by fusing a self-assembling protein from the human Rotavirus A, VP6, with the Small Ubiquitin Modifier domain, which maintains the ability to form nanoparticles and nanotubes and is able to be used as a drug carrier, even without specific targeting epitopes.

Development and testing of a deep learning-based strategy for scar segmentation on CMR-LGE images.

Objective: The aim of this paper is to investigate the use of fully convolutional neural networks (FCNNs) to segment scar tissue in the left ventricle from cardiac magnetic resonance with late gadolinium enhancement (CMR-LGE) images.

Methods: A successful FCNN in the literature (the ENet) was modified and trained to provide scar-tissue segmentation. Two segmentation protocols (Protocol 1 and Protocol 2) were investigated, the latter limiting the scar-segmentation search area to the left ventricular myocardial tissue region.

Novel fluorescent triazinobenzimidazole derivatives as probes for labelling human A and A adenosine receptor subtypes.

The expression levels and the subcellular localization of adenosine receptors (ARs) are affected in several pathological conditions as a consequence of changes in adenosine release and metabolism. In this respect, labelled probes able to monitor the AR expression could be a useful tool to investigate different pathological conditions. Herein, novel ligands for ARs, bearing the fluorescent 7-nitrobenzofurazan (NBD) group linked to the N (1,2) or N (3,4) nitrogen of a triazinobenzimidazole scaffold, were synthesized.

Brain ageing and neurodegenerative disease: The role of cellular waste management.

Ageing is defined as a time-dependent functional decline that occurs in most of live organisms. Brain modification during the ageing process has been considered to predispose to neurodegenerative disorders. Despite intensive research, the exact mechanisms accounting for the switch from physiological brain ageing to neurodegeneration remain to be fully elucidated.

Wakeful resting and memory retention: a study with healthy older and younger adults.

Studies indicate that a brief period of wakeful rest after learning supports memory retention, whereas distraction weakens it. It is open for investigation whether advanced age has a significant effect on the impact of post-learning wakeful rest on memory retention for verbal information when compared to a cognitively demanding distraction task. In this study, we examined (1) whether post-learning rest promotes verbal memory retention in younger and older adults and (2) whether the magnitude of the rest benefit changes with increasing age.

Remarkable Enhancement in Boron Uptake Within Glioblastoma Cells With Carboranyl-Indole Carboxamides.

Novel boron-rich, carboranyl-indole carboxamide ligands were prepared and found to effectively target the 18 kDa translocator protein (TSPO), an upregulated mitochondrial membrane-bound protein which has been observed in variety of tumor cell lines and its expression appears to be proportional to the degree of tumorigenicity, emphasizing a key role in cancer cell proliferation. Both boronated compounds displayed remarkably high affinities for the TSPO. In addition, the in vitro uptake of these compounds into T98G human glioma cells was found to be 25- to 100-fold greater than that of clinical boron neutron capture therapy (BNCT) agents.

Liver Injury, Endotoxemia, and Their Relationship to Intestinal Microbiota Composition in Alcohol-Preferring Rats.

Background: There is strong evidence that alcoholism leads to dysbiosis in both humans and animals. However, it is unclear how changes in the intestinal microbiota (IM) relate to ethanol (EtOH)-induced disruption of gut-liver homeostasis. We investigated this issue using selectively bred Sardinian alcohol-preferring (sP) rats, a validated animal model of excessive EtOH consumption.

Post-encoding wakeful resting supports the retention of new verbal memories in children aged 13-14 years.

Evidence primarily exists in adults that engaging in task-related mental activity after new learning results in increased forgetting of learned information, compared with quietly resting in the minutes that follow learning, where less forgetting is observed. The current study investigated whether the beneficial effect of post-encoding rest can be observed in children aged 13-14 years. Each child (N = 102) encoded two word lists.

Preclinical markers of atherosclerosis in acromegaly: a systematic review and meta-analysis.

Objective: Multiple studies investigated preclinical markers of peripheral vascular damage in acromegaly (ACRO) reporting discordant results. The aim of this study was to run a meta-analysis to examine whether intima media thickness (IMT), flow mediated dilation (FMD) and arterial pulse wave velocity (PWV) are affected in acromegalic patients and to assess the impact of effective treatment of growth hormone excess on these outcomes.

Study Selection: Twenty-seven studies comparing ACRO vs control (CON) populations and active (ACT) vs inactive (INACT) ACRO were included in the meta-analysis.