Development of technology for fluid-structure interaction modelling of a 1/8-scale dynamic model of the shuttle External Tank (ET). Volume 2: Supporting data appendixes A through C

For abstract, see N75-21359

Facing the blockchain endpoint vulnerability, an SGX-based solution for secure eHealth auditing

According to McAfee Labs, even in 2019, the eHealth sector is confirmed as one of the most critical in terms of cybersecurity incidents. It is estimated that more than 176 million patient records were target of attacks between 2009 and 2017, and with a single attack, in 2018, more than 1.4 million patient records were affected at UnityPoint Health. To cope with such a dramatic situation, one of the main strategic priority in the eHealth field is represented by the adoption of Blockchain. Specifically, according to a Deloittes survey, 55% of healthcare executives believe that blockchain technology will disrupt the healthcare industry. Unfortunately, while blockchain provides a valuable tool for enhancing the security of health applications and related data, it cannot be assumed as a panacea for data security. As an example, the so-called Endpoint Vulnerability issue is a well-known problem of Blockchain-based solutions: in such a case the attacker successful in gaining control of the end-point can tamper data off-chain during its generation and/or before it is sent to the chain. In this paper, we face such an issue by shielding the endpoint through the Intel Software Guard eXtension (SGX) technology. We demonstrate our solution for an auditing software belonging to the European eHealth management system (namely OpenNCP). We also discuss how our solution can be generalized to any other Blockchain-based solution. Finally, an experimental evaluation has been conducted to prove the actual feasibility of the proposed solution under the requirements of the real eHealth system

Capsaicin 8% patch and chronic postsurgical neuropathic pain

(1) Background: Surgery is a frequent cause of persistent pain, defined chronic post-surgical pain (CPSP). The capsaicin 8% patch (Qutenza®) is approved for the treatment of postherpetic neuralgia (PHN) and for diabetic peripheral neuropathy (DPN) of the feet. We propose a review of the literature on use of the capsaicin 8% patch to treat neuropathic pain associated with surgery; (2) Methods: We identified the articles by searching electronic databases using a combination of such terms as “capsaicin 8% patch”, “Qutenza®”, and “chronic postsurgical pain”; (3) Results: We identified 14 selected studies reporting on a total of 632 CPSP cases treated with capsaicin 8% patch. Treatment with the capsaicin 8% patch significantly reduced the average pain intensity. Only 5 studies reported adverse events (AEs) after the patch application. The most common AEs were erythema, burning sensation and pain; (4) Conclusions: Our review indicate that capsaicin 8% patch treatment for CPSP is effective, safe and well tolerated, but randomized controlled trials on efficacy, safety and tolerability should be conducted

The feasibility and applications of non-invasive cardiac monitoring in obese patients undergoing day-case surgery: Results of a prospective observational study

Aims: This prospective observational study evaluates the utility of non-invasive cardiac monitoring in obese patients in the day-surgery case, considering factors, such as Body Mass Index (BMI) and anaesthesia technique. Background: Obese patients are more likely to be admitted to hospital or to get hospitalized because they are more prone to concomitant diseases and obesity itself is not a contraindication to day surgery. Obese patients are a high-risk patient population that may particularly benefit from monitoring perioperative haemodynamic variations. Methods: In this observational study, we compared haemodynamic variations between overweight or obese and normal weight patients undergoing day-case surgery. We adopted NICOM® as a non-invasive cardiac output monitoring. Objective: The aim of the current study was to investigate the haemodynamic impact of BMI and anaesthesia technique during day-case surgery procedures. The other goal was to evaluate the feasibility and applications of non-invasive cardiac output monitoring among the obese population in day-surgery. Results: 74 patients were included in the study. 34 were overweight or obese (weight 84 ± 10 kg, height 160 ± 10 cm, BMI ≈ 30 kg/m2), 40 were normal weight (weight 63 ± 15 kg, height 160 ± 10 cm, BMI ≈ 22 kg/m2). Compared to normal-weight patients, obese patients show an increase in blood pressure with a return to baseline values at the end of surgery (p < 0.05). The Cardiac Output (CO) shows a similar trend, whereas the heart rate is normal. A decrease in the Cardiac Index (CI) during the operation was noticed in both groups, the one in obese patients (p = 0.24) being greater. In the same way, the Stroke Volume Index (SVI) was lower in obese patients during surgery (p < 0.05). In spinal anaesthesia, the Total Peripheral Resistance Index (TPRI) was not statistically different between the groups of study. As for the TPRI in obese patients, we reported values similar to the ones in non-obese patients in spinal anaesthesia. In local anesthesia, TPRI was higher in obese patients than in non-obese. Conclusion: Cardiovascular alterations in relation to obesity include an increase in blood pressure, CO and SV. An inadequate monitoring of haemodynamic parameters is a risk factor for perioperative complications. NICOM® provides a continuous, non-invasive haemodynamic measurement

Role of the mucins in pathogenesis of COPD: implications for therapy.

Introduction: Evidence accumulated in the last decade has started to reveal the enormous complexity in the expression, interactions and functions of the large number of different mucins present in the different compartments of the human lower airways. This occurs both in normal subjects and in COPD patients in different clinical phases and stages of severity.Areas covered: We review the known physiological mechanisms that regulate mucin production in human lower airways of normal subjects, the changes in mucin synthesis/secretion in COPD patients and the clinical efficacy of drugs that modulate mucin synthesis/secretion.Expert opinion: It is evident that the old simplistic concept that mucus hypersecretion in COPD patients is associated with negative clinical outcomes is not valid and that the therapeutic potential of 'mucolytic drugs' is under-appreciated due to the complexity of the associated molecular network(s). Likewise, our current knowledge of the effects of the drugs already available on the market that target mucin synthesis/secretion/structure in the lower airways is extremely limited and often indirect and more well-controlled clinical trials are needed in this area

Developing an infrastructure for secure patient summary exchange in the EU context: Lessons learned from the KONFIDO project

Background: The increase of healthcare digitalization comes along with potential information security risks. Thus, the EU H2020 KONFIDO project aimed to provide a toolkit supporting secure cross-border health data exchange. Methods: KONFIDO focused on the so-called “User Goals”, while also identifying barriers and facilitators regarding eHealth acceptance. Key user scenarios were elaborated both in terms of threat analysis and legal challenges. Moreover, KONFIDO developed a toolkit aiming to enhance the security of OpenNCP, the reference implementation framework. Results: The main project outcomes are highlighted and the “Lessons Learned,” the technical challenges and the EU context are detailed. Conclusions: The main “Lessons Learned” are summarized and a set of recommendations is provided, presenting the position of the KONFIDO consortium toward a robust EU-wide health data exchange infrastructure. To this end, the lack of infrastructure and technical capacity is highlighted, legal and policy challenges are identified and the need to focus on usability and semantic interoperability is emphasized. Regarding technical issues, an emphasis on transparent and standards-based development processes is recommended, especially for landmark software projects. Finally, promoting mentality change and knowledge dissemination is also identified as key step toward the development of secure cross-border health data exchange services

Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus During Macrophage Cell Death.

RATIONALE: Pulmonary aspergillosis is a lethal mould infection in the immunocompromised host. Understanding initial control of infection, and how this is altered in the immunocompromised host, is a key goal for understanding the pathogenesis of pulmonary aspergillosis. OBJECTIVES: To characterise the outcome of human macrophage infection with Aspergillus fumigatus, and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants. METHODS: We defined the outcome of human macrophage infection with Aspergillus fumigatus, and the impact of calcineurin inhibitors, through a combination of single cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies. MEASUREMENTS AND MAIN RESULTS: Macrophage phagocytosis of Aspergillus fumigatus enabled control of 90% of fungal germination. However fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell-cell transfer of Aspergillus fumigatus between macrophages which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein (VASP) envelope. Its relevance to the control of fungal germination was also shown by direct visualisation in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506/tacrolimus reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and hyphal escape. CONCLUSIONS: These observations identify programmed necrosis-dependent lateral transfer of Aspergillus fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host

Differential local tissue permissiveness influences the final fate of GPR17-expressing oligodendrocyte precursors in two distinct models of demyelination

Promoting remyelination is recognized as a novel strategy to foster repair in neurodegenerative demyelinating diseases, such as multiple sclerosis. In this respect, the receptor GPR17, recently emerged as a new target for remyelination, is expressed by early oligodendrocyte precursors (OPCs) and after a certain differentiation stage it has to be downregulated to allow progression to mature myelinating oligodendrocytes. Here, we took advantage of the first inducible GPR17 reporter mouse line (GPR17-iCreERT2xCAG-eGFP mice) allowing to follow the final fate of GPR17+cells by tamoxifen-induced GFP-labeling to unveil the destiny of these cells in two demyelination models: experimental autoimmune encephalomyelitis (EAE), characterized by marked immune cell activation and inflammation, and cuprizone induced demyelination, where myelin dysfunction is achieved by a toxic insult. In both models, demyelination induced a strong increase of fluorescent GFP+cells at damaged areas. However, only in the cuprizone model reacting GFP+cells terminally differentiated to mature oligodendrocytes, thus contributing to remyelination. In EAE, GFP+cells were blocked at immature stages and never became myelinating oligodendrocytes. We suggest these strikingly distinct fates be due to different permissiveness of the local CNS environment. Based on previously reported GPR17 activation by emergency signals (e.g., Stromal Derived Factor-1), we propose that a marked inflammatory milieu, such as that reproduced in EAE, induces GPR17 overactivation resulting in impaired downregulation, untimely and prolonged permanence in OPCs, leading, in turn, to differentiation blockade. Combined treatments with remyelinating agents and anti-inflammatory drugs may represent new potential adequate strategies to halt neurodegeneration and foster recovery