Interactions between Immunosuppressive Therapy and Direct-Acting Antivirals in Kidney Transplant Recipient with Hepatitis C Infection

Hepatitis C virus (HCV) causes increased mortality and morbidity in kidney transplant patients. Interferon-based therapies are poorly tolerated and involve the risk of rejection. The new direct-acting antiviral drugs (DAAs) have revolutionized the treatment of HCV infection in transplant patients. This observational study evaluates changes in immunosuppressive therapy during treatment with DAA in renal transplant recipients. In our transplant center, we selected seven HCV-positive patients at the time of transplantation, four men and three women, with an average age of 61 ± 7 years, in therapy with DAA. The dose and the blood levels of the immunosuppressive drugs were evaluated at the beginning and end of antiviral therapy, together with creatinine and proteinuria. Viremia was negativized in all patients within the initial 8 weeks of therapy. Currently, the number of patients is too limited to perform a statistical analysis and obtain significant results. In one patient, the dose of Cyclosporine was lowered to 10 mg, while for the remaining patients it was not necessary to change the dose of immunosuppressive drugs. DAAs give encourag-ing results in the eradication of HCV in renal transplant recipients, although they are associated with potential adverse drug interactions. The preliminary data of our study suggest that it is not necessary to change the dose of immunosuppressive drugs during therapy and that creatinine and proteinuria remain stationary. We will achieve more significant results in the future, adding more patients to our study. However, further randomized trials are necessary to confirm the safety of DAAs. Monocentric experience of the use of DAAS in kidney transplant patients with HCV infection

Conversion from Extended-Dose-Release Tacrolimus to Melt-Dose Tacrolimus in High Metabolizer Patients: Is the New Formulation of LPCT the Best Option for High Metabolizer Kidney Transplanted Patients?

Tacrolimus (FK506) is the most widely used anti-rejection drug in kidney transplantation, especially its extended release Tacrolimus formulation (ER-Tac, Advagraf), which is used when target blood levels can be difficult to reach in high metabolizer patients. In this retrospective monocentric study, we analyzed the effect of a switch from ER-Tac to LifeCycle Pharma Tacrolimus (LPCT, Envarsus) on the dose/level ratio of FK506 in high metabolizer patients that cannot achieve target blood levels in the first 6 months after transplantation. We observed a statistically significant improvement in the level to dose ratio after the switch. Renal function remained stable. We also observed a reduction in the development of tremors. Our data suggest that LPCT can be used in a safer way in high metabolizer kidney transplant recipients

Caso di Neurofibromatosi diagnosticata a 71 anni

Introduzione: La neurofibromatosi di tipo 1 (NF1) è una malattia genetica a trasmissione autosomica dominante caratterizzata da mutazioni a carico del gene NF1, localizzato sul cromosoma 17q11.2. La sindrome ha un’incidenza di 1 su 3500 ed è caratterizzata da diverse manifestazioni a livello cutaneo, osseo, oculare e nervoso. La diagnosi di NF1 si basa sui criteri clinici che includono macchie caffè-latte, neurofibromi, lentigginosi a livello della regione ascellare o inguinale, glioma del nervo ottico e noduli di Lisch. Dal punto di vista delle funzioni cognitive si possono riscontrare disturbi del linguaggio e ritardo mentale. I pazienti con neurofibromatosi hanno un rischio di sviluppare tumori da 3 a 4 volte maggiore rispetto alla popolazione generale; in particolare, il tumore di Wilms, tumori gastrointestinali stromali (GIST), rabdomiosarcomi, meningiomi, gliomi del nervo ottico e feocromocitomi. Molto raramente la diagnosi clinica e biomolecolare di NF1 viene posta in età avanzata essendo le manifestazioni cliniche della sindrome relativamente precoci e talora presenti fin dalla nascita. Tuttavia, sono riportati in letteratura casi di neurofibromi plessiformi ad esordio molto tardivo. Case Report: Riportiamo il caso di un paziente di 71 anni, ricoverato con la diagnosi di stato di male parziale motorio ed esiti di ematoma cerebrale su base ischemica, che veniva valutato in consulenza dermatologica per il rilievo di numerose lesioni cutanee esofitiche a livello del tronco. Tali lesioni di differente diametro e morfologia erano clinicamente compatibili con la diagnosi di neurofibromi, che veniva confermata successivamente all’esame istologico. Il paziente si mostrava poco collaborante e scarsamente orientato nel tempo e nello spazio. All’esame obiettivo venivano rilevate, inoltre, lentiggini ascellari bilaterali, numerose chiazze caffè-latte, scoliosi ed ipoacusia bilaterale. L’anamnesi familiare era negativa per il rilievo di neurofibromi e altri segni riconducibili a tale patologia. Attualmente è in corso lo studio genetico per la ricerca mutazionale a carico del gene NF1. Conclusioni: La diagnosi tardiva di NF1 nel paziente che presentiamo può essere addotta in parte alla comparsa in età avanzata del fenotipo cutaneo ed in parte al disagiato contesto familiare che non ha contribuito all’attuazione di adeguate strategie diagnostiche e di follow-up clinico-strumentale. Tale caso clinico ci rammenta che la diagnosi di Neurofibromatosi può essere posta anche in pazienti con anamnesi familiare completamente negativa per la comparsa di mutazioni de novo. E’ noto che il 50% dei pazienti con diagnosi di NF1 non presenta storia familiare per tale patologia

Transcript Regulation of the Recoded Archaeal α-L-Fucosidase In Vivo

Genetic decoding is flexible, due to programmed deviation of the ribosomes from standard translational rules, globally termed “recoding”. In Archaea, recoding has been unequivocally determined only for termination codon readthrough events that regulate the incorporation of the unusual amino acids selenocysteine and pyrrolysine, and for −1 programmed frameshifting that allow the expression of a fully functional α-l-fucosidase in the crenarchaeon Saccharolobus solfataricus, in which several functional interrupted genes have been identified. Increasing evidence suggests that the flexibility of the genetic code decoding could provide an evolutionary advantage in extreme conditions, therefore, the identification and study of interrupted genes in extremophilic Archaea could be important from an astrobiological point of view, providing new information on the origin and evolution of the genetic code and on the limits of life on Earth. In order to shed some light on the mechanism of programmed −1 frameshifting in Archaea, here we report, for the first time, on the analysis of the transcription of this recoded archaeal α-l-fucosidase and of its full-length mutant in different growth conditions in vivo. We found that only the wild type mRNA significantly increased in S. solfataricus after cold shock and in cells grown in minimal medium containing hydrolyzed xyloglucan as carbon source. Our results indicated that the increased level of fucA mRNA cannot be explained by transcript up-regulation alone. A different mechanism related to translation efficiency is discusse

SERIOUS GAMES FOR CYBERSECURITY: EVALUATING A DESIGN FRAMEWORK

Serious games indicate “games that do not have entertainment, enjoyment or fun as their primary purpose” (Kalmpourtzis, 2018). They are incredibly helpful in learning new topics, developing skills, and acquiring new knowledge and can be used in several contexts (health, politics, marketing, etc.). One of the main problems in designing serious games is the lack of models or frameworks able to support it. A framework called “Design Framework for Serious Games”, was developed to face this limitation; it contains various properties that range from design to virtual reality. The goal of the study is to determine whether it is suitable and applicable to serious games concerning cybersecurity that lack virtual reality aspects. More specifically, the framework is composed of five main sections: technology properties, design properties, serious games design properties, immersive properties, and observations, each associated with sub-properties. Technology Properties concern the output and input devices and the integrated development environment (IDE) used to develop the game. Design Properties involve the methodology used when developing the game and the team involved in the process, respectively corresponding to the sections Design Methodology and Design Team. Serious Games Design Properties refer to how the games are built and their characteristics: competition/cooperation mode, mechanics, UI elements, camera model, interaction model, scenario, characters, storyline, and navigation mechanism. Immersion Properties de- scribe the extent to which the games can deliver a vivid illusion of reality to the senses of a human participant. This section is composed of five sub-properties: inclusive, extensive, surrounding, vivid and proprioceptive matching (Slater & Wilbur, 1997). Finally, in the section Observations, the pros, cons, and annotations about the game can be written down. With the aim to assess whether the framework is suitable to the context of cybersecurity educational games, the study maps the framework using fifteen serious games for cybersecurity. The selected games address various branches of the topic, such as threats, types of attacks and defense mechanisms, with the goal of spreading awareness and training novice people to understand the severity and importance of security issues. The mapping brought some interesting results: the framework offers a clear and systematic methodology to examine and evaluate serious games; at the same time, negative aspects were identified, which were subject of review and improvement. A new version of the framework is proposed in which a refinement of each section was performed by adding specialization and further categorization. The removal of some unused or unmappable properties was also carried out

Serious Games for Cybersecurity: How to Improve Perception and Human Factors

Cybersecurity is a growing problem in today’s technological innovation and new digital economy. Threat actors cause a danger to people’s safety or lead to the compromise of intellectual property, either sold on the dark web or used as leverage for ransom. Many executives believe cybersecurity is the responsibility of Information Technologies (IT). It is everyone’s responsibility. Countering cyber threats requires focusing on people and behaviors and cognitive models; the mere technicalities are not enough to face the issue. With this in mind, the following research analyzes existing frameworks in the literature for developing serious games for cybersecurity. They are developed to train and educate individuals in various aspects of cybersecurity, including threat detection, incident response, and risk management. Moreover, combining serious games and Explainable Artificial Intelligence (AI) can be a powerful approach to cybersecurity training and education. By integrating Explainable AI techniques into serious games, users can better understand the decision-making processes within the game environment. Players can learn how to interpret the explanations provided by AI models, identify potential limitations or errors, and make decisions based on both AI-generated insights and their own domain knowledge. This combination equips individuals with the skills to improve perception and human factors in cybersecurity

High albedo materials to counteract heat waves in cities: An assessment of meteorology, buildings energy needs and pedestrian thermal comfort

Climatological data show that the frequency of Heat Waves (HWs) has increased since the 1950s and that it will continue to increase. These phenomena exasperate the urban heat island (UHI) phenomenon. In this study, we investigated the impact of a HW on the UHI in Milan (Italy); we also analyzed the effects of the application of high albedo materials on the vertical and horizontal urban built surfaces. We performed numerical experiments with the Weather Research and Forecasting model, whose output were used as input for the EnergyPlus software and the computation of the Mediterranean Outdoor Comfort Index (MOCI). Our results showed that the HW induces a maximum increase of about 4 °C in the temperature at 2 m height and that the use of high albedo materials covering all urban surfaces only partially counteracts this increase. The wind speed decreases due to the HW and the introduction of high albedo materials leads to its further decrease. The cooling energy consumption for a building located in the city doubles in the presence of HW and high albedo materials have a negligible positive effect when applied to the surrounding urban environment. The HW brings an increase up to about 0.7 of the MOCI and the use of high albedo materials further worsens thermal sensation. Therefore, this mitigation strategy leads to considerable benefits in terms of temperature and energy, while it determines a penalization of the well-being of the pedestrian. Its application requires a careful evaluation of benefits and side effects

Decision Making and Fibromyalgia: A Systematic Review

Decision making (DM) is the ability to choose among multiple options, considering external and internal variables and identifying potential paths of action that need to be assessed. Some brain areas involved in decision making are also implicated in pain processing, such as in fibromyalgia (FM). FM is a syndrome characterized by chronic widespread musculoskeletal pain and cognitive difficulties. We conducted a systematic review with the aim of identifying articles that evaluated DM in people with fibromyalgia, highlighting the main assessment tools. This work was conducted according to the PRISMA statement by consulting six online databases and providing a quality assessment of each search that met the inclusion criteria. In line with the limited interest in this in the scientific landscape to date, we found nine studies that evaluated the performance of DM in patients with FM; furthermore, we discovered that only certain types of DM were tested. The importance of our work lies in shedding light on a cognitive ability that is often undervalued in the scientific landscape but essential in everyday life. This review can serve as a starting point for further studies to clarify the relationship between DM and FM, improving understanding of the topic

A simple method for the calculation of dialysis Kt factor as a quantitative measure of removal efficiency of uremic retention solutes: Applicability to high-dialysate vs low-dialysate volume technologies.

Dialysis urea removal metrics may not translate into proportional removal efficiency of non-urea solutes. We show that the Kt factor (plasma volume totally cleared of any solutes) differentiates removal efficiency of non-urea solutes in different technologies, and can easily be calculated by instant blood-dialysate collections. We performed mass balances of urea, creatinine, phosphorus and beta2-microglobulin by whole dialysate collection in 4 low-flux and 3 high-flux hemodialysis, 2 high-volume post-hemodiafiltration and 7 short-daily dialysis with the NxStage-One system. Instant dialysate/blood determinations were also performed at different times, and Kt was calculated as the product of the D/P ratio by volume of delivered dialysate plus UF. There were significant differences in single session and weekly Kt (whole dialysate and instant calculations) between methodologies, most notably for creatinine, phosphorus and beta2-microglobulin. Urea Kt messured in balance studies was almost equal to that derived from the usual plasma kinetic model-based Daugirdas' equation (eKt/V) and independent V calculation, indicating full correspondence. Non-urea solute Kt as a fraction of urea Kt (i.e. fractional removal relative to urea) showed significant differences between technologies, indicating non-proportional removal of non-urea solutes and urea. Instant Kt was higher than that in full balances, accounting for concentration disequilibrium between arterial and systemic blood, but measured and calculated quantitative solute removal were equal, as were qualitative Kt comparisons between technologies. Thus, we show that urea metrics may not reliably express removal efficiency of non-urea solutes, as indicated by Kt. Kt can easily be measured without whole dialysate collection, allowing to expand the metrics of dialytic efficiency to almost any non-urea solute removed by dialysis

Cognitive, Emotional, and Daily Functioning Domains Involved in Decision-Making among Patients with Mild Cognitive Impairment: A Systematic Review

Mild cognitive impairment (MCI) is a transitional or prodromal stage of dementia in which autonomies are largely preserved (autonomies are not particularly affected). However, this condition may entail a depletion of decision-making (DM) abilities likely due to a gradual deterioration of the prefrontal cortex and subcortical brain areas underlying cognitive–emotional processing. Given the clinical implications of a decline in self-determination observed in some MCI sufferers, the present systematic review was aimed at investigating the literature addressing DM processes in patients with MCI, consistent with PRISMA guidelines. The six online databases inquired yielded 1689 research articles that were screened and then assessed based on eligibility and quality criteria. As a result, 41 studies were included and classified following the PICOS framework. Overall, patients with MCI who underwent neuropsychological assessment were found to be slightly or moderately impaired in DM abilities related to financial management, medical adherence, specific cognitive performances, risky conditions, and especially uncertain life circumstances. Comparative cross-sectional studies indicated not only mid-stage cognitive functioning in MCI but also borderline or deficit DM patterns evaluated through different tasks and procedures. Further research addressing MCI profiles suggested an association between explicit memory, executive functions, and DM performance. These findings highlight the diversity of MCI manifestations, in addition to the critical importance of DM features and correlates in patients’ daily functioning. Due to a lack of consensus on both MCI and DM, this review paper sought to shed light on assessment and intervention strategies accounting for the interplay between emotion, motivation, and learning to foster DM in cognitively impaired individual