Trusting telemedicine: A discussion on risks, safety, legal implications and liability of involved stakeholders.

OBJECTIVES: The main purpose of the article is to raise awareness among all the involved stakeholders about the risks and legal implications connected to the development and use of modern telemedicine systems. Particular focus is given to the class of "active" telemedicine systems, that imply a real-world, non-mediated, interaction with the final user. A secondary objective is to give an overview of the European legal framework that applies to these systems, in the effort to avoid defensive medicine practices and fears, which might be a barrier to their broader adoption. METHODS: We leverage on the experience gained during two international telemedicine projects, namely MobiGuide (pilot studies conducted in Spain and Italy) and AP@home (clinical trials enrolled patients in Italy, France, the Netherlands, United Kingdom, Austria and Germany), whose development our group has significantly contributed to in the last 4 years, to create a map of the potential criticalities of active telemedicine systems and comment upon the legal framework that applies to them. Two workshops have been organized in December 2015 and March 2016 where the topic has been discussed in round tables with system developers, researchers, physicians, nurses, legal experts, healthcare economists and administrators. RESULTS: We identified 8 features that generate relevant risks from our example use cases. These features generalize to a broad set of telemedicine applications, and suggest insights on possible risk mitigation strategies. We also discuss the relevant European legal framework that regulate this class of systems, providing pointers to specific norms and highlighting possible liability profiles for involved stakeholders. CONCLUSIONS: Patients are more and more willing to adopt telemedicine systems to improve home care and day-by-day self-management. An essential step towards a broader adoption of these systems consists in increasing their compliance with existing regulations and better defining responsibilities for all the involved stakeholders.

Low-radiation environment affects the development of protection mechanisms in V79 cells.

Very little is known about the influence of environmental radiation on living matter. In principle, important information can be acquired by analysing possible differences between parallel biological systems, one in a reference-radiation environment (RRE) and the other in a low-radiation environment (LRE). We took advantage of the unique opportunity represented by the cell culture facilities at the Gran Sasso National Laboratories of the Istituto Nazionale di Fisica Nucleare, where environment dose rate reduction factors in the underground (LRE), with respect to the external laboratory (RRE), are as follows: 10(3) for neutrons, 10(7) for directly ionizing cosmic rays and 10 for total γ-rays. Chinese hamster V79 cells were cultured for 10 months in both RRE and LRE. At the end of this period, all the cultures were kept in RRE for another 6 months. Changes in the activities of antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX) and spontaneous mutation frequency at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus were investigated. The results obtained suggest that environmental radiation might act as a trigger of defence mechanisms in V79 cells, specifically those in reference conditions, showing a higher degree of defence against endogenous damage as compared to cells grown in a very low-radiation environment. Our findings corroborate the hypothesis that environmental radiation contributes to the development of defence mechanisms in today living organisms/systems.

Deregulation of DNA-dependent protein kinase catalytic subunit contributes to human hepatocarcinogenesis development and has a putative prognostic value.

BACKGROUND: The DNA-repair gene DNA-dependent kinase catalytic subunit (DNA-PKcs) favours or inhibits carcinogenesis, depending on the cancer type. Its role in human hepatocellular carcinoma (HCC) is unknown. METHODS: DNA-dependent protein kinase catalytic subunit, H2A histone family member X (H2AFX) and heat shock transcription factor-1 (HSF1) levels were assessed by immunohistochemistry and/or immunoblotting and qRT-PCR in a collection of human HCC. Rates of proliferation, apoptosis, microvessel density and genomic instability were also determined. Heat shock factor-1 cDNA or DNA-PKcs-specific siRNA were used to explore the role of both genes in HCC. Activator protein 1 (AP-1) binding to DNA-PKcs promoter was evaluated by chromatin immunoprecipitation. Kaplan-Meier curves and multivariate Cox model were used to study the impact on clinical outcome. RESULTS: Total and phosphorylated DNA-PKcs and H2AFX were upregulated in HCC. Activated DNA-PKcs positively correlated with HCC proliferation, genomic instability and microvessel density, and negatively with apoptosis and patient's survival. Proliferation decline and massive apoptosis followed DNA-PKcs silencing in HCC cell lines. Total and phosphorylated HSF1 protein, mRNA and activity were upregulated in HCC. Mechanistically, we demonstrated that HSF1 induces DNA-PKcs upregulation through the activation of the MAPK/JNK/AP-1 axis. CONCLUSION: DNA-dependent protein kinase catalytic subunit transduces HSF1 effects in HCC cells, and might represent a novel target and prognostic factor in human HCC.

Nasal cavity lobular capillary hemangioma due to insect sting.

INTRODUCTION: Lobular capillary hemangioma is a frequent benign vascular inflammatory lesion of the skin tissue. It rarely reaches the mucous membrane, and the nasal fossa involvement is exceptional. CASE REPORT: A 68-year-old woman presented with an ulcerous hemorrhagic mass blocking the left nasal fossa, which had appeared a few weeks after a wasp sting in the nose. The insect was evacuated only three weeks after the sting. The clinical and radiological data suggested malignancy. Biopsy under local anesthesia proved non-contributory and was complicated by 1 week's hospitalization for severe nosebleed. Surgical excision under video-endoscopy confirmed diagnosis. At 31 months' follow-up, the patient was free of recurrence. DISCUSSION/CONCLUSION: The pathogeny of lobular capillary hemangioma is uncertain. No previous cases affecting the mucous membrane after insect sting have been reported. Except in the typical contexts of long-term packing or pregnancy, diagnosis can be difficult and misleading. It can mimic a malignant pathology. Its rich vascularization requires caution during biopsy, and the risk of recurrence requires excision to be complete.

The protective effects of temporary immunity under imposed infection pressure.

The aim of this paper is to show in explicit detail that, due to the effects of waning and boosting of immunity, an increasing force of infection does not necessarily lead to an increase in the incidence of disease. Under certain conditions, a decrease of the force of infection may in fact lead to an increase of the incidence of disease. Thus we confirm and reinforce the conclusions from Águas et al. (2006), concerning pertussis. We do so, however, in the context of Campylobacter infections in humans deriving from animal reservoirs. For such an externally 'driven' epidemic we can ignore the transmission feedback cycle and treat the force of infection as a parameter. As this parameter is, to a certain extent, under public health control, our findings constitute an important warning: reducing exposure may not necessarily lead to a reduction in the occurrence of clinical illness. In a second part of the paper we relate the model parameters to the available data concerning campylobacteriosis.

Temporary off-frequency listening after noise trauma.

Hearing loss is routinely estimated from the audiogram, even though this measure gives only a rough approximation of hearing. Indeed, cochlear regions functioning poorly, if at all, called dead regions, are not detected by a simple audiogram. To detect cochlear dead regions, additional measurements of psychophysical tuning curves or thresholds in background noise (TEN test) are required. A first aim of this study was to assess the presence of dead regions after impulse noise trauma using psychophysical tuning curves. The procedure we used was based on a compromise between the need to collect reliable estimates of psychophysical tuning curves and the limited time available to obtain these estimates in a hospital setting. Psychophysical tuning curves were measured using simultaneous masking with a 2-alternative forced choice paradigm, where the target was randomly placed in one of the two masker presentations. It is well known that some components of noise-induced hearing loss are reversible. A second aim of this study was to examine the potential recovery of dead regions after acoustic trauma. A third issue addressed in this article was the relationship between noise-induced dead regions and tinnitus. We found that 70% of the subjects had dead regions after noise trauma, while 88% reported tinnitus. Moreover, we found that the extent of dead regions probably diminished in about 50% of subjects, which highlights the ability of the human auditory system to recover from noise-induced hearing loss.

[Parathyroïd adenoma induced by long term lithium therapy: case report and review]. / Adénome parathyroïdien induit par le traitement au long cours par lithium: cas clinique et revue.

UNLABELLED: We report a case of a parathyroid adenoma during a long term lithium treatment without therapeutic overdose. CASE REPORT: A 73-years-old woman presented a demonstrative biological syndrome with hypercalcemia, elevated parathormone, normal urinary cyclic AMP, normocalciuria. CONCLUSION: This lithium induced hyperparathyroidism differs from the classic primary hyperparathyroidism with parthyroid adenoma where urinary cyclic AMP excretion is elevated and where there is hypercalciuria. Lithium is blocking the negative feedback of calcium on parathormone secretion and stimulates the growth of parathyroid adenoma. Treatment is surgical and consists in adenoma ablation. Calcemia follow up is indicated in patients with long term lithium therapy

Forkhead box M1B is a determinant of rat susceptibility to hepatocarcinogenesis and sustains ERK activity in human HCC.

BACKGROUND AND AIMS: Previous studies indicate unrestrained cell cycle progression in liver lesions from hepatocarcinogenesis-susceptible Fisher 344 (F344) rats and a block of G(1)-S transition in corresponding lesions from resistant Brown Norway (BN) rats. Here, the role of the Forkhead box M1B (FOXM1) gene during hepatocarcinogenesis in both rat models and human hepatocellular carcinoma (HCC) was assessed. METHODS AND RESULTS: Levels of FOXM1 and its targets were determined by immunoprecipitation and real-time PCR analyses in rat and human samples. FOXM1 function was investigated by either FOXM1 silencing or overexpression in human HCC cell lines. Activation of FOXM1 and its targets (Aurora Kinose A, Cdc2, cyclin B1, Nek2) occurred earlier and was most pronounced in liver lesions from F344 than BN rats, leading to the highest number of Cdc2-cyclin B1 complexes (implying the highest G(2)-M transition) in F344 rats. In human HCC, the level of FOXM1 progressively increased from surrounding non-tumorous livers to HCC, reaching the highest levels in tumours with poorer prognosis (as defined by patients' length of survival). Furthermore, expression levels of FOXM1 directly correlated with the proliferation index, genomic instability rate and microvessel density, and inversely with apoptosis. FOXM1 upregulation was due to extracellular signal-regulated kinase (ERK) and glioblastoma-associated oncogene 1 (GLI1) combined activity, and its overexpression resulted in increased proliferation and angiogenesis and reduced apoptosis in human HCC cell lines. Conversely, FOXM1 suppression led to decreased ERK activity, reduced proliferation and angiogenesis, and massive apoptosis of human HCC cell lines. CONCLUSIONS: FOXM1 upregulation is associated with the acquisition of a susceptible phenotype in rats and influences human HCC development and prognosis.

[Fractures of the nose: simplified diagnosis and management]. / Fractures du nez: diagnostic et prise en charge simplifiée.

Fracture of the nose is a frequent injury. Careful management is necessary to avoid not only cosmetic but also functional sequels. Therapeutic modalities are simple and can easily be carried out under local anesthesia.

[Extracting a foreign body from the nasal fossa without an ENT specialist]. / Extraction d'un corps étranger de la fosse nasale sans recours au spécialiste.

Foreign bodies in the nasal fossa are frequent and generally occur in children. In developing countries, access to an ENT specialist can be difficult or impossible. The authors describe several extraction techniques with special emphasis on those best suited to areas with limited access to specialist facilities. Using illustrations, a step-by-step description of the so-called "hook" technique is given. This simple technique allows successful removal of a foreign body from the nasal fossa in almost all cases.