Vacuolated PAS-positive lymphocytes as an hallmark of Pompe disease and other myopathies related to impaired autophagy.

Autosomal recessive Pompe disease is a lysosomal disorder caused by mutations of the acid-α-glucosidase (GAA) gene. Deficiency of GAA enzyme leads to glycogen accumulation and autophagy impairment in cardiac and skeletal muscles, but also in lymphocytes. Since an effective therapy is available, a rapid, sensitive, and specific test is crucial to early identify affected subjects.

Prognostic performance of MR-pro-adrenomedullin in patients with community acquired pneumonia in the Emergency Department compared to clinical severity scores PSI and CURB.

Aim: (i) evaluate the performance of MR-pro-ADM in reflecting the outcome and risk for CAP patients in the emergency department, and (ii) compare the prognostic performance of MR-pro-ADM with that of clinical scores PSI and CURB65.

Methods: Observational prospective, single-center study in patients with suspected community acquired pneumonia (CAP). Eighty one patients underwent full clinical and laboratory assessment as by protocol, and were followed up a 28 days.

Validation of the Six Sigma Z-score for the quality assessment of clinical laboratory timeliness.

Background: The International Federation of Clinical Chemistry and Laboratory Medicine has introduced in recent times the turnaround time (TAT) as mandatory quality indicator for the postanalytical phase. Classic TAT indicators, namely, average, median, 90th percentile and proportion of acceptable test (PAT), are in use since almost 40 years and to date represent the mainstay for gauging the laboratory timeliness. In this study, we investigated the performance of the Six Sigma Z-score, which was previously introduced as a device for the quantitative assessment of timeliness.

Complement system dysregulation in patients affected by Idiopathic Generalized Epilepsy and the effect of antiepileptic treatment.

Complement system dysregulation has been hypothesized as a possible pathogenetic factor triggering epileptogenesis in both animal models and human studies. The aim of the present study is to evaluate the complement system in adult patients affected by idiopathic generalized epilepsy (IGE), either untreated or treated by antiepileptic drugs (AEDs). Thirty-seven IGE patients were compared to a population of 20 matched healthy controls.

Hypothalamic dysfunction is related to sleep impairment and CSF biomarkers in Alzheimer's disease.

Hypothalamus is a key brain region regulating several essential homeostatic functions, including the sleep-wake cycle. Alzheimer's disease (AD) pathology affects nuclei controlling sleep-wake rhythm sited in this brain area. Since only post-mortem studies documented the relationship between hypothalamic atrophy and sleep-wake cycle impairment, we investigated in AD patients the possible hypothalamic in vivo alteration using 2-deoxy-2-(18F) fluoro-D-glucose ([18F]FDG) positron emission tomography ([18F]FDG PET), and its correlations with sleep impairment and cerebrospinal-fluid (CSF) AD biomarkers (tau proteins and β-amyloid).

Performance characteristics of lipoprotein-associated phospholipase A2 activity assay on the Dimension Vista analyser and preliminary study of a healthy Italian population.

Introduction: Lipoprotein-associated phospholipase A2 (Lp-PLA) is a marker of vascular inflammation associated with coronary heart disease and stroke. We evaluated analytical performance of the PLAC® Activity Test on Siemens Dimension Vista® 1500 analyzer and measured Lp-PLA activity in Italian adults to establish reference intervals (RIs) and evaluate correlation with circulating lipids and age.

Materials And Methods: The evaluation protocol consisted of precision, linearity, sensitivity, method comparison, substrate depletion ("hook") effect and interference assessment.

Antioxidant Effects of a Hydroxytyrosol-Based Pharmaceutical Formulation on Body Composition, Metabolic State, and Gene Expression: A Randomized Double-Blinded, Placebo-Controlled Crossover Trial.

Hydroxytyrosol (HT) plays a significant role in cardiovascular disease (CVD) protection, and its metabolites are able to protect from the endothelial dysfunction commonly present in atherosclerosis. This randomized double-blinded, placebo-controlled crossover trial determined the effect in healthy volunteers of two gastroresistant capsules containing 15 mg/day of HT, for a 3-week period (HTT). Evaluation of nutritional status, serum metabolites, oxidative stress biomarkers, and gene expression of 9 genes related to oxidative stress, inflammation, and CVDs was performed.

Local vibration inhibits H-reflex but does not compromise manual dexterity and does not increase tremor.

The present work aimed at investigating the effects of local vibration on upper limb postural and kinetic tremor, on manual dexterity and on spinal reflex excitability. Previous studies have demonstrated a decrease in spinal reflex excitability and in force fluctuations in the lower limb but an increase in force fluctuation in the upper limbs. As hand steadiness is of vital importance in many daily-based tasks, and local vibration may also be applied in movement disorders, we decided to further explore this phenomenon.

Levamisole in Illicit Trafficking Cocaine Seized: A One-Year Study.

Cocaine use is increasing around the world and its purity is frequently altered through dilution, substitution, contamination, and adulteration. Sugars, talc, starch, and carbonates represent the principal diluents of cocaine, while phenacetin, levamisole, caffeine, and lidocaine are its major adulterants in Europe. Levamisole is used because it is an odorless powder, with physical properties similar to cocaine, and it has reasonable cost and availability, being widely used in veterinary medicine.

Effects of parasitic infection and reproduction on corticosterone plasma levels in Galápagos land iguanas, and .

In vertebrates, one main feature of stress response is the release of glucocorticoids (corticosterone in reptiles), steroid hormones whose synthesis is regulated by the hypothalamic-pituitary-adrenal axis (HPA). In the Galápagos Islands, populations of land iguanas are differentially impacted by a tick-transmitted apicomplexan hemoparasite of genus , which could cause diseases and ultimately reduce fitness. Using competitive enzyme-linked immunosorbent assays (ELISA), we examined baseline plasma corticosterone levels of two syntopic and highly parasitized populations of the land iguana species and in Wolf volcano (Isabela Island).

Natural products for human health: an historical overview of the drug discovery approaches.

Natural products (NPs) are secondary metabolites produced and used by organisms for defending or adapting purposes. These molecules were naturally selected during thousands of years to improve the specificity and cover a very wide range of functions, depending on the origin, the habitat and the specific activity carried out in the organism of origin. Due to these intrinsic features, NPs have been used as healing agents since thousands of years and still today continue to be the most important source of new potential therapeutic preparations.

An LC-MS Assay with Isocratic Separation and On-line Solid Phase Extraction to Improve the Routine Therapeutic Drug Monitoring of Busulfan in Plasma.

Background: Busulfan (Bu) requires therapeutic drug monitoring (TDM) in subjects undergoing a conditioning regimen for hematopoietic stem cell transplantation (HSCT). To speed up the procedure and increase reproducibility, we improved our routine LC-MS/MS assay using the on-line solid-phase extraction (SPE) of samples.

Methods: A protein precipitation (PP) step was performed before the on-line SPE of Bu from 200 µL of plasma spiked with octa-deuterated Bu (D8-Bu) as the internal standard.

KFLC Index utility in multiple sclerosis diagnosis: Further confirmation.

The Multiple Sclerosis (MS) diagnosis is based on dissemination of focal lesions in time and space. The free light chains (FLCs) determination might be a sensitive alternative to oligoclonal bands assay. The study aim was to redefine sensitivity, specificity of the kFLC Index cut-off.

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens.

Background: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR.

Study Design: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR.

Efficacy and safety of very-low-calorie ketogenic diet: a double blind randomized crossover study.

Objective: To verify safety respect to weight loss, cardiometabolic diseases of short-term Very low-calorie ketogenic diets (VLCKDs, <800 kcal day-1).

Patients And Methods: Randomized cross-over trial with placebo. The study had no.

Combination of biochemical and mechanical cues for tendon tissue engineering.

Tendinopathies negatively affect the life quality of millions of people in occupational and athletic settings, as well as the general population. Tendon healing is a slow process, often with insufficient results to restore complete endurance and functionality of the tissue. Tissue engineering, using tendon progenitors, artificial matrices and bioreactors for mechanical stimulation, could be an important approach for treating rips, fraying and tissue rupture.

Carotid-Carotid Bypass Graft for Internal Carotid Artery Kinking Causing Dysphagia.

Elongation, coils, and kinks of carotid vessels are rare conditions, and these are often asymptomatic. Rarely, kinking may provide functional symptoms, requiring surgical correction. We report an unusual case of internal carotid artery kinking causing pharynx compression with dysphagia.

Preanalytical investigations of phlebotomy: methodological aspects, pitfalls and recommendations.

Phlebotomy is often addressed as a crucial process in the pre-analytical phase, in which a large part of laboratory errors take place, but to date there is not yet a consolidated methodological paradigm. Seeking literature, we found 36 suitable investigations issued between 1996 and 2016 (April) dealing with the investigation of pre-analytical factors related to phlebotomy. We found that the largest part of studies had a cohort of healthy volunteers (22/36) or outpatients (11/36), with the former group showing a significantly smaller median sample size (N = 20, IQR: 17.

Microfluidic-enhanced 3D bioprinting of aligned myoblast-laden hydrogels leads to functionally organized myofibers in vitro and in vivo.

We present a new strategy for the fabrication of artificial skeletal muscle tissue with functional morphologies based on an innovative 3D bioprinting approach. The methodology is based on a microfluidic printing head coupled to a co-axial needle extruder for high-resolution 3D bioprinting of hydrogel fibers laden with muscle precursor cells (C2C12). To promote myogenic differentiation, we formulated a tailored bioink with a photocurable semi-synthetic biopolymer (PEG-Fibrinogen) encapsulating cells into 3D constructs composed of aligned hydrogel fibers.

Minimal residual disease in melanoma: circulating melanoma cells and predictive role of MCAM/MUC18/MelCAM/CD146.

Circulating tumour cells (CTCs), identified in numerous cancers including melanoma, are unquestionably considered valuable and useful as diagnostic and prognostic markers. They can be detected at all melanoma stages and may persist long after treatment. A crucial step in metastatic processes is the intravascular invasion of neoplastic cells as circulating melanoma cells (CMCs).

Effects of very-low-calorie diet on body composition, metabolic state, and genes expression: a randomized double-blind placebo-controlled trial.

Objective: Very low-calorie diets (VLCDs, < 800 kcal day-1) and Ketogenic diet (KD) are generally used as part of integrated intervention, medical monitoring and a program of lifestyle modification, to improve a multitude of clinical states. The effect of three different very low calories KD (VLCKD), with (VLCKD1) or without (VLCKD2,3) synthetic amino acid replacement of the 50% protein intake, were analyzed after weight loss.

Patients And Methods: The clinical study used a cross-over randomized double-blind placebo-controlled trial.

Cutaneous features of myotonic dystrophy types 1 and 2: Implication of premature aging and vitamin D homeostasis.

Skin changes have been described in myotonic dystrophy type 1 (DM1). However, whether and in which way skin is a target of specific disease alterations in DM1 and DM2 has not been yet clarified. This study aims to explore cutaneous features of DM1 and DM2 patients.

Combining temporal planning with probabilistic reasoning for autonomous surveillance missions.

It is particularly challenging to devise techniques for underpinning the behaviour of autonomous vehicles in surveillance missions as these vehicles operate in uncertain and unpredictable environments where they must cope with little stability and tight deadlines in spite of their restricted resources. State-of-the-art techniques typically use probabilistic algorithms that suffer a high computational cost in complex real-world scenarios. To overcome these limitations, we propose a approach that combines the probabilistic reasoning based on the target motion model offered by Monte Carlo simulation with long-term strategic capabilities provided by automated task planning.