Expanding the Clinical and Mutational Spectrum of the PLP1-Related Hypomyelination of Early Myelinated Structures (HEMS)

the PLP1 gene, located on chromosome Xq22, encodes the proteolipid protein 1 and its isoform DM20. mutations in PLP1 cause a spectrum of white matter disorders of variable severity. Here we report on four additional HEMS patients from three families harboring three novel PLP1 mutations in exon 3B detected by targeted next-generation sequencing. patients experienced psychomotor delay or nystagmus in the first year of age and then developed ataxic-spastic or ataxic syndrome, compatible with a phenotype of intermediate severity in the spectrum of PLP1-related disorders. regression occurred at the beginning of the third decade of the eldest patient. extrapyramidal involvement was rarely observed. brain MRI confirmed the involvement of structures that physiologically myelinate early, although the pattern of abnormalities may differ depending on the age at which the study is performed. these new cases contribute to expanding the phenotypic and genotypic spectrum of HEMS. additional studies, especially enriched by systematic functional evaluations and long-term follow-up, are welcome to better delineate the natural history of this rare hypomyelinating leukodystrophy

Wearable Sensor for Real-time Monitoring of Hydrogen Peroxide in Simulated Exhaled Air

In this work, an innovative and cheap electrochemical sensor for hydrogen peroxide quantification in exhaled breath was developed. H2O2 is the most used biomarker among the Reactive Oxygen Species (ROS) for monitoring the level of oxidative stress in the respiratory system. This is due to its stability and ability to cross biological membranes and also because it is detectable in extracellular space. The electrochemical sensor was obtained using the silver layer of wasted compact discs (CDs). All three electrodes, working (WE), counter (CE), and pseudo-reference electrode (RE), were fabricated using a laser cutter. The working electrode was used directly, while an Ag/AgCl paste and a graphite paste were applied respectively on the RE and the CE. In addition, a chitosan layer was deposited by Electro-Phoretic Deposition (EPD) on the surface of the sensor. This biopolymer improves the wettability of the sensor in presence of a humid atmosphere such as that given by exhaled air. The sensor was tested in both liquid and nebulized solutions containing different concentrations of hydrogen peroxide. The detection of H2O2 was evaluated using Linear Sweep Voltammetry (LSV) as electrochemical technique. The results show that the peak current increases linearly with hydrogen peroxide concentration from 100 to 500 μM with a sensitivity of 0.068 µA µM−1 cm−2 and 0.108 µA µM−1 cm−2, a Limit Of Detection (LOD) of 60 μM and 30 μM respectively for liquid and nebulized solutions. Therefore, the use of the electrochemical sensor can allow the monitoring of hydrogen peroxide in real time with good results

A multi-organ-on-chip to recapitulate the infiltration and the cytotoxic activity of circulating NK cells in 3D matrix-based tumor model

The success of immunotherapeutic approaches strictly depends on the immune cells interaction with cancer cells. While conventional in vitro cell cultures under-represent the complexity and dynamic crosstalk of the tumor microenvironment, animal models do not allow deciphering the anti-tumor activity of the human immune system. Therefore, the development of reliable and predictive preclinical models has become crucial for the screening of immune-therapeutic approaches. We here present an organ-on-chip organ on chips (OOC)-based approach for recapitulating the immune cell Natural Killer (NK) migration under physiological fluid flow, infiltration within a 3D tumor matrix, and activation against neuroblastoma cancer cells in a humanized, fluid-dynamic environment. Circulating NK cells actively initiate a spontaneous "extravasation " process toward the physically separated tumor niche, retaining their ability to interact with matrix-embedded tumor cells, and to display a cytotoxic effect (tumor cell apoptosis). Since NK cells infiltration and phenotype is correlated with prognosis and response to immunotherapy, their phenotype is also investigated: most importantly, a clear decrease in CD16-positive NK cells within the migrated and infiltrated population is observed. The proposed immune-tumor OOC-based model represents a promising approach for faithfully recapitulating the human pathology and efficiently employing the immunotherapies testing, eventually in a personalized perspective. An immune-organ on chip to recapitulate the tumor-mediated infiltration of circulating immune cells within 3D tumor model

Stage of Change and Motivation to a Healthier Lifestyle before and after an Intensive Lifestyle Intervention

Objective. Lifestyle modification programs are different but typically include both nutritional aspects and physical activity as main domains with different behavioral and/or psychological strategies designed to affect change. A fundamental role in modifying unhealthy habits is played by personal motivation for change. The present study sought to investigate, in a group of 100 overweight/obese outpatients with and/or without TMD2, treatment seeking, the effect of an intensive lifestyle program on medical measures and motivational profile for physical activity (PA) and healthy nutrition (NUTR). Method. Subjects participated in an intensive multidisciplinary lifestyle intervention at C.U.R.I.A.MO. Before and after the intervention, patients received a comprehensive evaluation of their clinical, anthropometric, and metabolic states and motivation to lifestyle changes. Results. Data showed differences before and after intervention in both medical and motivational measures. Before the intervention patients reported to be ready, open, and determined to change and gave importance to healthy habits. After the intervention patients continued to be determined but increased the actions toward the change showing a higher degree of maintenance and of acquisition of habits especially in the physical domain of the new lifestyle. Conclusion. Data support the notion that the motivation should be followed during all the lifestyle interventions to support the change on both domains of the lifestyle program

Long-term cardiac sequelae in patients referred into a diagnostic post-COVID-19 pathway: the Different Impacts on the Right and Left Ventricles

Most patients who had COVID-19 are still symptomatic after many months post infection, but the long-term outcomes are not yet well-defined. The aim of our prospective/retrospective study was to define the cardiac sequelae of COVID-19 infection. This monocentric cohort study included 160 consecutive patients who had been discharged from the ward or from the outpatient clinic after a diagnosis of COVID-19 and subsequently referred for a follow up visit. Clinical features data about the acute phase along with information about the follow up visit, including ECG and Echocardiographic parameters, were recorded. At an average follow-upfollow up of 5 months, echocardiography showed morpho-functional changes characteristics of both right (RV) and left (LV) ventricles, such as RV dilation, increased pressure in the pulmonary circulation, and biy-ventricular systolic-diastolic dysfunction. When examined using multivariate analysis, independent of age, sex, and co-morbidities, RV and LV changes were significantly associated with chest High Resolution computed tomography score and hemodynamic Instability (HI) and with C-reactive protein, respectively. Our results suggest that COVID-19 may impact RV and LV differently. Notably, the extent of the pneumonia and HI may affect RV, whereas the inflammatory status may influence LV. A long-term follow-up is warranted to refine and customize the most appropriate therapeutic strategies

Gold nanowires-based sensor for quantification of H2O2 released by human airway epithelial cells

Hydrogen peroxide (H2O2) is a biomarker relevant for oxidative stress monitoring. Most chronic airway diseases are characterized by increased oxidative stress. To date, the main methods for the detection of this analyte are expensive and time-consuming laboratory techniques such as fluorometric and colorimetric assays. There is a growing interest in the development of electrochemical sensors for H2O2 detection due to their low cost, ease of use, sensitivity and rapid response. In this work, an electrochemical sensor based on gold nanowire arrays has been developed. Thanks to the catalytic activity of gold against hydrogen peroxide reduction and the high surface area of nanowires, this sensor allows the quantification of this analyte in a fast, efficient and selective way. The sensor was obtained by template electrodeposition and consists of gold nanowires about 5 high and with an average diameter of about 200 nm. The sensor has excellent properties in terms of reproducibility, repeatability and selectivity. The sensor was validated by quantifying the hydrogen peroxide released by human airways A549 cells exposed or not to the pro-oxidant compound rotenone. The obtained results were validated by comparing them with those obtained by flow cytometry after staining the cells with the fluorescent superoxide-sensitive Mitosox Red probe giving a very good concordance