The will of young minors in the terminal stage of sickness: A case report

AbstractIntroductionIn Italy, both parents have parental responsibility, so they have the power to give or withhold consent to medical procedures on their children.MethodsThe present work reports the case of a 5-year-old boy diagnosed with neuroblastoma in the right adrenal loggia, who underwent several chemotherapy treatments that prolonged his life until the age of 10. Informed consent for treatments was requested exclusively of the parents, without taking into consideration the minor's will, not even when he asked for increased pain relief medication instead of other palliative treatments.ResultsThe authors thought it interesting to examine the case in the light of new Italian legislation on informed consent and to verify whether it promotes greater participation of minors in healthcare choices, given that the issue of acquisition of informed consent is becoming increasingly broad and complex.ConclusionThe case examined here indicates that current Italian legislation, even including the modifications introduced, does not allow for concrete and active participation of minors, especially those under the age of 12, in the discussion of choices about their health, not even in choices regarding the end of life, and not even when the minor manifests a mature capacity for discernment

Advanced Computational Methods in Molecular Medicine

The dauntingly complex functioning of human cells is often the outcome of several molecular processes. Understanding such processes is crucial for modern drug discovery, defining interaction cascades, assessing the effects of mutations changes in local concentrations of ligands, and so forth. Computational methods, from systems biology to bioinformatics and molecular simulation, allow to access features difficult or impossible to be measured. Models (if properly validated against experimental data) help understand the intricate molecular mechanisms of life processes. Bolstering the predictive power of these models calls upon the computational biologist to improve algorithms and methods. This issue reports on procedures and on applications facing current challenges in computational biology.Modern biological sciences are becoming more and more multidisciplinary. At the same time, theoretical and computational approaches gain in reliability and their field of application widens. O. Fisette at al. discuss recent advances in the areas of solution nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations that were made possible by the synergistic combination of both methods.Interaction of proteins is of vital importance for many cellular processes and when altered may cause significant health problems, thus the availability of reliable tools to predict and study the determinants of protein-protein interactions is needed. In this regard, X. -Y. Meng et al. present a newly adapted, computationally efficient Brownian Dynamics- (BD-) based protein docking method for predicting native protein complexes. The approach includes global BD conformational sampling, compact complex selection, and local energy minimization. A shell-based grid force field represents the receptor protein and solvation effects, partially considering protein flexibility.Hybrid quantum mechanics/molecular mechanics (QM/MM) calculations are routinely used to study quantum mechanical processes in biological systems. J. Kang et al. present a review paper describing an UNIX shell-based interface program connecting two widely used QM and MM calculation engines, GAMESS and AMBER. The tool was used to investigate a metalloenzyme, azurin, and PU.1-DNA complex and mechanisms of hydrolysis (editing reaction) in leucyl-tRNA synthetase complexed with the mis-aminoacylated tRNALeu. The authors investigate the influence of environmental effects on the electronic structure.Electron transfer in proteins constitutes key steps in several biological processes, ranging from photosynthesis to aerobic respiration. T. Hayashi and A. Stuchebrukhov investigate electron tunneling in NADH : ubiquinone oxidoreductase (Complex I), a key enzyme in cellular respiration as an entry point of the electron transport chain of mitochondria and bacteria, by evaluating the transition flux between donor and acceptor at atomistic resolution. The study suggests that the diffusion of internal water molecules dynamically controls tunneling efficiency

Clinical nutrition in internal medicine: An Italian survey by the scientific societies FADOI and SINPE

Objectives: Patients hospitalized in internal medicine are frequently malnourished or at risk for malnutrition. The aim of this study, conducted by the Federation of Associations of Hospital Internists (FADOI) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) was to assess the nutritional management of internal medicine inpatients in Italy, to identify critical issues and formulate practical proposals to improve nutritional treatment.Methods: From February to April 2021, FADOI and SINPE conducted a national web-based survey, including a 13 multiple-choice item questionnaire related to three key areas:screening and assessment of malnutrition and associated/overlapping sarcopenia and dysphagia;specialist consultations; andmanagement of nutritional support.Results: Responding to the questionnaire were 266 physicians among FADOI members (10.76%). Screening for malnutrition is performed with validated tests, within standardized care pathways, or routinely, only by 22% of participants. Global Leadership Initiative on Malnutrition criteria for diagnosis of malnutrition are little used (20%). Screening for sarcopenia was insufficient as the systematic use of assessment tools (handgrip/chair test) was minimal (3%). Screening for dysphagia is not a routine procedure for at-risk patients according to 33% of participants. Systematic involvement of clinical nutrition services/units in the management of malnourished/sarcopenic patients was reported by only 17% of internists.Conclusions: To overcome the critical issues that emerged from the present study, FADOI and SINPE experts proposed practical solutions to promote the application of the most recent guidelines and to improve awareness and sensitivity to nutritional management in internal medicine real-life settings

Novel Polydiacetylene-Functionalized Nanostructures for Sensing Applications

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Analysis of protein-coding mutations in hiPSCs and their possible role during somatic cell reprogramming

Recent studies indicate that human-induced pluripotent stem cells contain genomic structural variations and point mutations in coding regions. However, these studies have focused on fibroblast-derived human induced pluripotent stem cells, and it is currently unknown whether the use of alternative somatic cell sources with varying reprogramming efficiencies would result in different levels of genetic alterations. Here we characterize the genomic integrity of eight human induced pluripotent stem cell lines derived from five different non-fibroblast somatic cell types. We show that protein-coding mutations are a general feature of the human induced pluripotent stem cell state and are independent of somatic cell source. Furthermore, we analyse a total of 17 point mutations found in human induced pluripotent stem cells and demonstrate that they do not generally facilitate the acquisition of pluripotency and thus are not likely to provide a selective advantage for reprogramming

Identification of a specific reprogramming-associated epigenetic signature in human induced pluripotent stem cells

Generation of human induced pluripotent stem cells (hiPSCs) by the expression of specific transcription factors depends on successful epigenetic reprogramming to a pluripotent state. Although hiPSCs and human embryonic stem cells (hESCs) display a similar epigenome, recent reports demonstrated the persistence of specific epigenetic marks from the somatic cell type of origin and aberrant methylation patterns in hiPSCs. However, it remains unknown whether the use of different somatic cell sources, encompassing variable levels of se- lection pressure during reprogramming, influences the level of epigenetic aberrations in hiPSCs. In this work, we characterized the epigenomic integrity of 17 hiPSC lines derived from six different cell types with varied reprogramming efficiencies. We demonstrate that epigenetic aberrations are a general feature of the hiPSC state and are independent of the somatic cell source. Interestingly, we observe that the reprogramming efficiency of somatic cell lines inversely correlates with the amount of methylation change needed to acquire pluripotency. Additionally, we determine that both shared and line- specific epigenetic aberrations in hiPSCs can directly translate into changes in gene expression in both the pluripotent and differenti- ated states. Significantly, our analysis of different hiPSC lines from multiple cell types of origin allow us to identify a reprogramming- specific epigenetic signature comprised of nine aberrantly methyl- ated genes that is able to segregate hESC and hiPSC lines regardless of the somatic cell source or differentiation state

A Latency-Aware Real-Time Video Surveillance Demo: Network Slicing for Improving Public Safety

© 2021 IEEE.  Personal use of this material is permitted.  Permission from IEEE must be obtained for all other uses, in any current or future media, including reprinting/republishing this material for advertising or promotional purposes, creating new collective works, for resale or redistribution to servers or lists, or reuse of any copyrighted component of this work in other worksWe report the automated deployment of 5G services across a latency-aware, semidisaggregated, and virtualized metro network. We summarize the key findings in a detailed analysis of end-to-end latency, service setup time, and soft-failure detection timeThe research leading to these results has received funding from the EC and BMBF through the METRO-HAUL project (G.A. No. 761727) and OTB-5G+ project (reference No. 16KIS0979K

Somatic coding mutations in human induced pluripotent stem cells

Defined transcription factors can induce epigenetic reprogramming of adult mammalian cells into induced pluripotent stem cells. Although DNA factors are integrated during some reprogramming methods, it is unknown whether the genome remains unchanged at the single nucleotide level. Here we show that 22 human induced pluripotent stem (hiPS) cell lines reprogrammed using five different methods each contained an average of five protein-coding point mutations in the regions sampled (an estimated six protein-coding point mutations per exome). The majority of these mutations were non-synonymous, nonsense or splice variants, and were enriched in genes mutated or having causative effects in cancers. At least half of these reprogramming-associated mutations pre-existed in fibroblast progenitors at low frequencies, whereas the rest occurred during or after reprogramming. Thus, hiPS cells acquire genetic modifications in addition to epigenetic modifications. Extensive genetic screening should become a standard procedure to ensure hiPS cell safety before clinical use

Treatment of Relapsing Mild-to-Moderate Ulcerative Colitis With the Probiotic VSL#3 as Adjunctive to a Standard Pharmaceutical Treatment: A Double-Blind, Randomized, Placebo-Controlled Study

OBJECTIVES: VSL#3 is a high-potency probiotic mixture that has been used successfully in the treatment of pouchitis. The primary end point of the study was to assess the effects of supplementation with VSL#3 in patients affected by relapsing ulcerative colitis (UC) who are already under treatment with 5-aminosalicylic acid (ASA) and/or immunosuppressants at stable doses. METHODS: A total of 144 consecutive patients were randomly treated for 8 weeks with VSL#3 at a dose of 3,600 billion CFU/day (71 patients) or with placebo (73 patients). RESULTS: In all, 65 patients in the VSL#3 group and 66 patients in the placebo group completed the study. The decrease in ulcerative colitis disease activity index (UCDAI) scores of 50% or more was higher in the VSL#3 group than in the placebo group (63.1 vs. 40.8; per protocol (PP) P=0.010, confidence interval (CI)\u2089\u2085(%) 0.51-0.74; intention to treat (ITT) P=0.031, CI\u2089\u2085(%) 0.47-0.69). Significant results with VSL#3 were recorded in an improvement of three points or more in the UCDAI score (60.5% vs. 41.4%; PP P=0.017, CI\u2089\u2085(%) 0.51-0.74; ITT P=0.046, CI\u2089\u2085(%) 0.47-0.69) and in rectal bleeding (PP P=0.014, CI\u2089\u2085(%) 0.46-0.70; ITT P=0.036, CI\u2089\u2085(%) 0.41-0.65), whereas stool frequency (PP P=0.202, CI\u2089\u2085(%) 0.39-0.63; ITT P=0.229, CI\u2089\u2085(%) 0.35-0.57), physician's rate of disease activity (PP P=0.088, CI\u2089\u2085(%) 0.34-0.58; ITT P=0.168, CI\u2089\u2085(%) 0.31-0.53), and endoscopic scores (PP P=0.086, CI\u2089\u2085(%) 0.74-0.92; ITT P=0.366, CI\u2089\u2085(%) 0.66-0.86) did not show statistical differences. Remission was higher in the VSL#3 group than in the placebo group (47.7% vs. 32.4%; PP P=0.069, CI\u2089\u2085(%) 0.36-0.60; ITT P=0.132, CI\u2089\u2085(%) 0.33-0.56). Eight patients on VSL#3 (11.2%) and nine patients on placebo (12.3%) reported mild side effects. CONCLUSIONS: VSL#3 supplementation is safe and able to reduce UCDAI scores in patients affected by relapsing mild-to-moderate UC who are under treatment with 5-ASA and/or immunosuppressants. Moreover, VSL#3 improves rectal bleeding and seems to reinduce remission in relapsing UC patients after 8 weeks of treatment, although these parameters do not reach statistical significance