Vitamin D and atopic dermatitis in childhood.

Vitamin D features immunomodulatory effects on both the innate and adaptive immune systems, which may explain the growing evidence connecting vitamin D to allergic diseases. A wealth of studies describing a beneficial effect of vitamin D on atopic dermatitis (AD) prevalence and severity are known. However, observations linking high vitamin D levels to an increased risk of developing AD have also been published, effectively creating a controversy. In this paper, we review the existing literature on the association between AD and vitamin D levels, focusing on childhood. As of today, the role of vitamin D in AD is far from clear; additional studies are particularly needed in order to confirm the promising therapeutic role of vitamin D supplementation in childhood AD

Expression of bovine cytosolic 5’-nucleotidase (cN-II) in yeast: nucleotide pools disturbance and its consequences on growth and homologous recombination

Cytosolic 5′-nucleotidase II is a widespread IMP hydrolyzing enzyme, essential for cell vitality, whose role in nucleotide metabolism and cell function is still to be exactly determined. Cytosolic 5′-nucleotidase overexpression and silencing have both been demonstrated to be toxic for mammalian cultured cells. In order to ascertain the effect of enzyme expression on a well-known eukaryote simple model, we expressed cytosolic 5′-nucleotidase II in Saccharomyces cerevisiae, which normally hydrolyzes IMP through the action of a nucleotidase with distinct functional and structural features. Heterologous expression was successful. The yeast cells harbouring cytosolic 5′-nucleotidase II displayed a shorter duplication time and a significant modification of purine and pyrimidine derivatives concentration as compared with the control strain. Furthermore the capacity of homologous recombination in the presence of mutagenic compounds of yeast expressing cytosolic 5′-nucleotidase II was markedly impaired

The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat

PURPOSE: Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the α-galactosidase A gene. Migalastat, a pharmacological chaperone, binds to specific mutant forms of α-galactosidase A to restore lysosomal activity. METHODS: A pharmacogenetic assay was used to identify the α-galactosidase A mutant forms amenable to migalastat. Six hundred Fabry disease-causing mutations were expressed in HEK-293 (HEK) cells; increases in α-galactosidase A activity were measured by a good laboratory practice (GLP)-validated assay (GLP HEK/Migalastat Amenability Assay). The predictive value of the assay was assessed based on pharmacodynamic responses to migalastat in phase II and III clinical studies. RESULTS: Comparison of the GLP HEK assay results in in vivo white blood cell α-galactosidase A responses to migalastat in male patients showed high sensitivity, specificity, and positive and negative predictive values (≥0.875). GLP HEK assay results were also predictive of decreases in kidney globotriaosylceramide in males and plasma globotriaosylsphingosine in males and females. The clinical study subset of amenable mutations (n = 51) was representative of all 268 amenable mutations identified by the GLP HEK assay. CONCLUSION: The GLP HEK assay is a clinically validated method of identifying male and female Fabry patients for treatment with migalastat

Exploring the range of applicability of anisotropic optical detection in axially coordinated supramolecular structures

Ensuring the highest accuracy in determining the molecular assembling and the preservation of the chemical and physical properties of the molecules during the growth of organic layers requires a real-time monitoring of film formation. In this respect, optical techniques are preferred since they result in minimum organic film damage. Among these techniques, Reflectance Anisotropy Spectroscopy (RAS) proved to be the one with the highest sensitivity due to the development of intrinsic anisotropies in the optical response of molecular films, where molecular packing is driven by Van der Waals interactions. Recently, we proposed an original strategy to enable the growth of organic films via molecular self-assembly through highly directional coordination bonds. Herein, we consider a straightforward supramolecular structure employing axial bonds, based on the 1:1 assembly of a CoII porphyrin (CoTPP) and a linear ligand (DPNDI). This system is characterized by a rather isotropic structure that might, in principle, result in a weak RAS signal. Therefore, in the present work, we critically assess the range of applicability of such a spectroscopy. A number of other surface science techniques, including Low Energy Electron Diffraction (LEED), photoemission spectroscopies (PES and IPES) and Atomic Force Microscopy (AFM) is employed to fully characterize the axially coordinated molecular film

Neurophysiological and Clinical Effects of Upper Limb Robot-Assisted Rehabilitation on Motor Recovery in Patients with Subacute Stroke: A Multicenter Randomized Controlled Trial Study Protocol

Background: The efficacy of upper limb (UL) robot-assisted therapy (RAT) on functional improvement after stroke remains unclear. However, recently published randomized controlled trials have supported its potential benefits in enhancing the activities of daily living, arm and hand function, and muscle strength. Task-specific and high-intensity exercises are key points in facilitating motor re-learning in neurorehabilitation since RAT can provide an assisted-as-needed approach. This study aims to investigate the clinical effects of an exoskeleton robotic system for UL rehabilitation compared with conventional therapy (CT) in people with subacute stroke. As a secondary aim, we seek to identify patients’ characteristics, which can predict better recovery after UL-RAT and detects whether it could elicit greater brain stimulation. Methods: A total of 84 subacute stroke patients will be recruited from 7 Italian rehabilitation centers over 3 years. The patients will be randomly allocated to either CT (control group, CG) or CT plus UL-RT through an Armeo®Power (Hocoma AG, CH, Volketswil, Switzerland) exoskeleton (experimental group, EG). A sample stratification based on distance since onset, DSO (DSO ≤ 30; DSO > 30), and Fugl–Meyer Assessment (FM)-UL (FM-UL ≤ 22; 22 < FM-UL ≤ 44) will be considered for the randomization. The outcomes will be recorded at baseline (T0), after 25 + 3 sessions of intervention (T1), and at 6 months post-stroke (T2). The motor functioning assessed by the FM-UL (0–66) will be considered the primary outcome. The clinical assessments will be set based on the International Classification of Function, Disability and Health (ICF). A patient satisfaction questionnaire will be evaluated in the EG at T1. A subgroup of patients will be evaluated at T0 and T1 via electroencephalography. Their brain electrical activity will be recorded during rest conditions with their eyes closed and open (5 min each). Conclusion: The results of this trial will provide an in-depth understanding of the efficacy of early UL-RAT through a whole arm exoskeleton and how it may relate to the neural plasticity process. The trial was registered at ClinicalTrial.gov with the registration identifier NCT04697368