Development and validation of a patient-reported outcome in systemic sclerosis: the Hand scleroDerma lived Experience (HAnDE) scale.

BACKGROUND: Hand involvement in systemic sclerosis (SSc) is at the core of the disease, with a substantial impact on both functional aspects and quality of life. There is no patient-reported outcome (PRO) scale globally assessing hand involvement in SSc. OBJECTIVES: To develop and validate a PRO scale, the Hand scleroDerma lived Experience (HAnDE) scale, to assess the lived experience of hand involvement in patients with SSc. METHODS: This was an exploratory sequential mixed-methods study with two phases: (i) PRO development through an inductive process to analyse the structure of lived experience, involving 21 patients with SSc; and (ii) PRO validation by assessing the psychometric properties of the scale among 105 patients with SSc. RESULTS: Phase 1 enabled us to generate the 18-item provisional scale. From Phase 2, the mean (SD) total score of the scale was 29·16 (16·15). The item reduction process retained 16 items with five levels of answers (range 0-64). Internal consistency of the 16-item version was excellent (Cronbach's alpha = 0·946). Construct validity was very good, principal component analysis pointing towards a unidimensional instrument, with one factor explaining 56% of the variance, and concurrent validity being confirmed: Cochin Hand Function Scale r = 0·66; Health Assessment Questionnaire - Disability index r = 0·58; Hospital Anxiety and Depression Scale, anxiety r = 0·51, depression r = 0·4; Mouth Handicap in Systemic Sclerosis scale r = 0·61; 36-Item Short Form Health Survey, physical component r = -0·48, mental component r = -0·46; and Kapandji score r = -0·46. The correlations were statistically significant (P < 0·05). CONCLUSIONS: We propose, for future trials and clinical practice in SSc, a new PRO, the HAnDE scale, that assesses all the dimensions - functional, aesthetic, relational, existential and emotional - of the lived experience of hand involvement in SSc.

Stage IV cutaneous squamous cell carcinoma: treatment outcomes in a series of 42 patients.

BACKGROUND: The prevalence and incidence of cutaneous squamous cell carcinoma (cSCC) are increasing due to the ageing of the population and sun exposure. Advanced cSCC forms (locally advanced and/or locoregional metastatic and/or distant metastatic) account for approximately 3% of cSCC and can result in death. OBJECTIVE: Analysis of the clinical characteristics and treatment outcomes in stage IV cSCC with unresectable locoregional extension and/or the presence of metastases. METHODS: A retrospective study was conducted at a single-centre university hospital for stage IV cSCC patients followed between 1 January 2008 and 31 December 2015. Descriptive analyses (demographic, anatomo-clinical characteristics, treatment sequences, response to treatment and survival analysis) were performed. RESULTS: The study included 42 patients (median age = 75.5 years) with a diagnosis of stage IV cSCC who were treated with at least one line of chemotherapy and/or cetuximab. At the time of diagnosis, 85.7% of the patients had locoregional extension (19% of locally advanced and 67% of locoregional metastatic) and 14.3% had distant metastatic disease. Regarding treatment, 40% and 36% of patients received no more than 1 and 2 systemic treatment lines, respectively. The 4-year overall survival was 6%, and the median follow-up was 18.6 months. The objective response rate was 55% after the first line of treatment with a median progression-free survival (PFS) of 6.18 months and 12% after the second line with a median PFS of 6.51 months. Grade 3 and 4 adverse events were observed for 33% of patients. CONCLUSION: Our study confirms a very poor prognosis of stage IV cSCC and a poor response to conventional therapies, indicating that the stage IV cSCC patient population remains with unmet medical needs.

[Staphylococcal toxic shock syndrome should be considered in the event of diffuse erythema with fever and shock]. / Érythème généralisé fébrile et choc : choc toxinique staphylococcique.

BACKGROUND: Toxic shock syndrome (TSS) was first described by Todd in 1978. The relevant Lancet publication reported 7 cases of children with fever, exanthema, hypotension and diarrhoea associated with multiple organ failure. An association between TSS and use of hyper-absorbent tampons in menstruating women was discovered in the 1980s. Following the market withdrawal of such tampons, TSS virtually disappeared. Herein we report a new case of TSS in a 15-year-old girl. PATIENTS AND METHODS: A 15-year-old patient was admitted to intensive care for severe sepsis and impaired consciousness associated with diffuse abdominal pain. Dermatological examination revealed diffuse macular exanthema. Laboratory tests showed hepatic cytolysis (ASAT 101 U/L, ALAT 167 U/L, total bilirubin 68µmol/L) and an inflammatory syndrome. Lumbar puncture and blood cultures were sterile while thoraco-abdomino-pelvic and brain scans were normal. The patient was menstruating and had been using a tampon over the previous 24hours. Vaginal sampling and tampon culture revealed TSST-1 toxin-producing S. aureus. Management consisted of intensive care measures and treatment with amoxicillin-clavulanic acid and clindamycin for 10 days. CONCLUSION: In case of septic shock associated with diffuse macular exanthema a diagnosis of TSS must be envisaged, particularly in menstruating women.

Live-cell imaging of new polyene sterols for improved analysis of intracellular cholesterol transport.

Analysis of intracellular cholesterol transport by fluorescence microscopy requires suitable fluorescent analogues of cholesterol. Most existing cholesterol analogues contain lipophilic dyes which can compromise the sterol properties in membranes. An alternative strategy is to introduce additional double bonds into the sterol ring system resulting in intrinsic fluorescence, while at the same time keeping the cholesterol-like properties of the analogues. Existing polyene sterols, such as dehydroergosterol (DHE) or cholestatrienol (CTL), however, contain only three double bonds and suffer from low brightness, significant photobleaching and excitation/emission in the ultraviolet region. Thus, special equipment is required to image such sterols. Here, we describe synthesis, characterization and intracellular imaging of new polyene sterols containing four conjugated double bonds in the sterol ring system. We show that such analogues have red-shifted excitation and emission by ∼20 nm compared to DHE or CTL. The red shift was even more pronounced when preventing keto-enol tautomer equilibration by protecting the 3'-hydroxy group with acetate. We show that the latter analogue can be imaged on a conventional wide field microscope with a DAPI/filipin filter cube. The new polyene sterols show reduced photobleaching compared to DHE or CTL allowing for improved deconvolution microscopy of sterol containing cellular membranes.

[Methods of data selection from the French medical information system program for trauma patient's analysis: Burns and traumatic brain injuries]. / Méthodes de sélection des données du PMSI pour l'analyse des victimes de traumatismes : brûlures et lésions cérébrales traumatiques.

BACKGROUND: Data from the French medical information system program in medicine, surgery, obstetrics and dentistry can be adapted in some cases and under certain conditions, to account for hospitalizations for injuries. Two areas have been explored: burn and traumatic brain injury victims. METHODS: An algorithm selecting data from the Medical information system program was established and implemented for several years for the study of burn victims. The methods of selection of stays for traumatic brain injuries, which are the subject of a more recent exploration, are described. RESULTS: Production of results in routine on the hospitalization for burns. Expected production of results on the hospitalization for traumatic brain injuries. CONCLUSION: In both cases, the knowledge obtained from these utilizations of the Medical information system program contributes to epidemiological surveillance and prevention and are useful for health care organization.

Differences in soil micro-eukaryotic communities over soil pH gradients are strongly driven by parasites and saprotrophs.

A recent large-scale assessment of bacterial communities across a range of UK soil types showed that bacterial community structure was strongly determined by soil pH. We analysed a data set of eukaryotic 454 sequencing 18S rDNA from the surveyed samples and showed significant differences in eukaryotic assemblages according to pH class, mostly between low pH and higher pH soils. Soil eukaryote communities (per sample) differed most at the taxonomic rank approximating to order level. Taxonomies assigned with the Protist Ribosomal Reference and the Silva 119 databases were taxonomically inconsistent, mostly due to differing 18S annotations, although general structure and composition according to pH were coherent. A relatively small number of lineages, mostly putative parasitic protists and fungi, drive most differences between pH classes, with weaker contributions from bacterivores and autotrophs. Overall, soil parasites included a large diversity of alveolates, in particular apicomplexans. Phylogenetic analysis of alveolate lineages demonstrates a large diversity of unknown gregarines, novel perkinsids, coccidians, colpodellids and uncharacterized alveolates. Other novel and/or divergent lineages were revealed across the eukaryote tree of life. Our study provides an in-depth taxonomic evaluation of micro-eukaryotic diversity, and reveals novel lineages and insights into their relationships with environmental variables across soil gradients.

Clinical trials with direct oral anticoagulants for stroke prevention in atrial fibrillation: how representative are they for real life patients?

PURPOSE: To identify the proportion of real-life patients with atrial fibrillation (AF) eligible for direct oral anticoagulant (DOAC) therapy, based on the inclusion and exclusion criteria used in the clinical studies and based on the officially approved indications as mentioned in the Summary of Product Characteristics (SmPC). METHODS: Data for this retrospective cross-sectional study was extracted from the UZ Brussel Stroke Registry, containing anonymized data of 2205 patients with a suspected stroke. Characteristics of patients with documented AF were compared with the patient characteristics in clinical trials and the approved indications in the SmPC. RESULTS: Data of 468 patients with AF was analyzed. Based on the selection criteria of the clinical trials, significantly less patients were eligible for treatment with rivaroxaban compared to dabigatran etexilate (39.3 versus 47.6 %; p = 0.010), but not compared to apixaban (45.5 %; p = 0.055). Based on the indications and contraindications in the SmPC, significantly fewer patients were eligible for apixaban compared to dabigatran etexilate and rivaroxaban (62.0 % for apixaban, 72.9 % for dabigatran etexilate, and 75.6 % for rivaroxaban; p < 0.001 and p < 0.001, respectively). Significantly, more patients were eligible for DOAC therapy based on the indications and contraindications in the SmPC compared to the inclusion and exclusion criteria of the clinical trials (72.9 versus 47.6 %; p < 0.001 for dabigatran; 75.6 versus 39.3 %; p < 0.001 for rivaroxaban and 62.0 versus 45.5 %; p < 0.001 for apixaban). CONCLUSION: When taking into account the selection criteria from the pivotal clinical trials with DOACs for stroke prevention in AF, less than half of real-life patients are eligible for therapy with one of the DOACs. However, the indications mentioned in the SmPCs of these drugs are less strict.

Relationship between pre-stroke cardiovascular medication use and stroke severity.

INTRODUCTION: Stroke is a major health problem with important morbidity and mortality. Various risk factors and cardiovascular medication groups are known to have an influence on stroke incidence, but less is known about the relation between medication use and stroke severity. AIM: To determine if relationships exist between the pre-stroke cardiovascular medication use and stroke severity. METHODS: A retrospective study was conducted on a database with anonymized data of 1974 patients with a suspected stroke, admitted to the Universitair Ziekenhuis (UZ) Brussel. Stroke severity was quantified using the National Institute of Health Stroke Scale (NIHSS). Cardiovascular medication groups were first included in a multivariable linear regression model. Second, to obtain clinically interpretable results, all variables that were retained in the final linear regression model were introduced in a cumulative odds ordinal logistic regression model with proportional odds. RESULTS: Angiotensin II receptor blockers (ARBs), statins, and antiarrhythmics were significantly associated with stroke severity at the 10 % α level in a multivariable linear regression model, suggesting a possible effect of these medication groups on stroke severity. Only pre-stroke statin use showed a significant relationship with the NIHSS score in the ordinal logistic regression model with an adjusted odds ratio of 0.740 (95 % CI 0.580-0.944; p = 0.015). CONCLUSION: Pre-stroke use of statins is significantly associated with lower stroke severity. No significant relationship was detected between pre-stroke use of other medication groups and stroke severity, defined by the NIHSS score.

Postpartum haemorrhage related early increase in D-dimers is inhibited by tranexamic acid: haemostasis parameters of a randomized controlled open labelled trial.

BACKGROUND: Beneficial effects of tranexamic acid (TA) have been established in surgery and trauma. In ongoing postpartum haemorrhage (PPH), a moderate reduction of blood loss was observed in a previously published randomized controlled trial. Analysis of haemostasis parameters obtained from samples collected as part of this study are presented. METHODS: Women with PPH >800 ml after vaginal delivery were assigned to receive either TA (4 g over 1 h, then 1 g per h over six h) (TA) or not (H). A non-haemorrhagic group (NH), <800 ml blood loss, was included as postpartum reference. At four time-points (enrolment, +30 min, +2 h, +6 h), haemostasis was assessed. Haemostasis assays were performed blinded to group allocation. Data were expressed as median [interquartiles] and compared with non-parametric tests. RESULTS: In H compared with NH group, D-dimers increase (3730 ng ml(-1) [2468-8493] vs 2649 [2667-4375]; P=0.0001) and fibrinogen and factor II decrease were observed at enrolment and became maximal 2 h later. When comparing TA to H patients, the increase in Plasmin-Antiplasmin-complexes at +30 min (486 ng ml(-1) [340-1116] vs 674 [548-1640]; P=0.03) and D-dimers at +2 h (3888 ng ml(-1) [2688-6172] vs 7495 [4400-15772]; P=0.0001) was blunted. TA had no effect on fibrinogen decrease. CONCLUSIONS: This study provides biological evidence of an early increase in D-dimers and plasmin-antiplasmin complexes associated with active post-partum haemorrhage and its attenuation by the early use of a clinically effective high dose of TA, opening the perspective of dose ranging studies to determinate the optimal dose and timing in this setting. CLINICAL TRIAL REGISTRATION: ISRCTN09968140.

Investigating the functionalization of liposomes with NFL-TBS. 40-63 peptide as a promising drug delivery system.

The NFL-peptide was discovered almost 20 years ago, and its targeting properties were assessed alone or in combination with lipid nanocapsules (LNC), magnetic porous silicon nanorods, or gold nanoparticles. Results highlighted a better targeting of cancer cells, in particular glioblastoma and pancreas cancer. Considering the large use of liposomes (LPs) as an hydrophilic drug delivery system, this study explored the possibility to functionalize liposomes with three different sequences of NFL-peptides: native (NFL-peptide), biotinylated (BIOT-NFL) and coupled to fluorescein (FAM-NFL). Dynamic Light Scattering (DLS) complemented by cryo-electron microscopy (CEM) showed a peculiar ultrastructural arrangement between NFL-peptides and liposomes. Based on this architectural interaction, we investigated the biological contribution of these peptides in LPs-DiD glioblastoma cellular uptake. Flow cytometry complemented by confocal microscopy experiments demonstrated a consequent and systematic increased uptake of LPs-DiD into F98 cells when their surface was decorated with NFL-peptides. The intra-cellular distribution of these liposomes via an organelle tracker indicated the presence of LPs-DiD in lysosomes after 4 h. Based on the properties of this NFL-peptide, we showed in this work the crucial role of NFL peptide as an effective and promising actor to potentiate nanoparticles entry in glioblastoma cell lines.

Improving management of intravenous maintenance fluids in the emergency department of a university hospital.

OBJECTIVE: Intravenous (IV) fluid therapy is a known source of iatrogenic complications. Guideline implementation can be used to educate and guide physicians on adequate fluid management. In the emergency department (ED), a complex and interruption-driven environment, workload is high and active documentation is required to facilitate audits of fluid management quality. PATIENTS AND METHODS: Fluid management was evaluated in the ED records of adult non-critically ill patients admitted to a tertiary care center before (PRE: 1/12/2016-31/3/2017) and after (POST: 1/12/2018-31/3/2019) implementation of an educational intervention aiming to optimize IV fluid therapy in November 2018. First, the appropriateness of the 24-hour IV maintenance fluid prescription was evaluated, as prescribed by the emergency physician. Second, factors associated with appropriate prescribing were assessed, as well as the quality of fluid management documentation practice. Prescription appropriateness and documentation quality were evaluated retrospectively using a structured audit instrument and additional review by experts. RESULTS: A total of 237 patients (2.3%) were included in the PRE-intervention group and 253 patients (2.4%) in the POST-intervention group. The expert panel evaluated 214 prescriptions in 82.3% of patients (PRE: 99, POST: 115), and appropriateness increased significantly (19.2% vs. 61.2%, p=0.002). A higher odds of an appropriate IV maintenance fluid prescription was determined, attributed to the intervention (adjOR=2.580; 95% CI 1.363-4.884) and in patients having a prehospital intervention (adjOR=1.914, 95% CI 1.022-3.586). Appropriateness of fluid management documentation did not significantly improve after the implementation of the intervention (15.6% vs. 16.2%, p=0.858). CONCLUSIONS: The IV fluid prescriptions' appropriateness was significantly higher after guideline implementation. However, documentation quality of fluid management was poor in the studied ED records. Active stewardship programs are warranted to further monitor fluid management quality in the ED.

Tracking image correlation: combining single-particle tracking and image correlation.

The interactions and coordination of biomolecules are crucial for most cellular functions. The observation of protein interactions in live cells may provide a better understanding of the underlying mechanisms. After fluorescent labeling of the interacting partners and live-cell microscopy, the colocalization is generally analyzed by quantitative global methods. Recent studies have addressed questions regarding the individual colocalization of moving biomolecules, usually by using single-particle tracking (SPT) and comparing the fluorescent intensities in both color channels. Here, we introduce a new method that combines SPT and correlation methods to obtain a dynamical 3D colocalization analysis along single trajectories of dual-colored particles. After 3D tracking, the colocalization is computed at each particle's position via the local 3D image cross correlation of the two detection channels. For every particle analyzed, the output consists of the 3D trajectory, the time-resolved 3D colocalization information, and the fluorescence intensity in both channels. In addition, the cross-correlation analysis shows the 3D relative movement of the two fluorescent labels with an accuracy of 30 nm. We apply this method to the tracking of viral fusion events in live cells and demonstrate its capacity to obtain the time-resolved colocalization status of single particles in dense and noisy environments.

Relative efficacy and effectiveness assessment of new pharmaceuticals in three EU member states: current practices and outcome agreement between Belgium, the Netherlands and France.

PURPOSES: Relative efficacy and effectiveness assessment (REA) of a pharmaceutical product is critical in reimbursement decisions. The Pharmaceutical Forum (2005-2008) asked European Union (EU) member states (MS) to strengthen the methodological quality and rigor of REA and identify any scope for common approaches. Here, we have compared REA practices and results within three EU MS with similar reimbursement procedures for the period 2007-2010 to describe the actual situation. METHODS: Assessment procedures and reports from the Belgian, Dutch and French Agency websites were retrieved and corresponding products matched. The REA-outcome was coded as added therapeutic value (ATV) yes or no. The strength of agreement between the three MS was estimated and analyzed in relation to some explanatory variables. RESULTS: Of the 144 Belgian, 122 Dutch and 236 French assessment reports retrieved, ATV was granted in 35, 39 and 23 % of cases, respectively, with 72 matches between the three MS. In all MS the results of at least one randomized trial were available in >90 % of reports. Between two MS significant agreement was achieved in ≥ 72 % of cases; this was 54 % between the three MS. Differences in ATV existed for treatments in severe chronic diseases. Assessment procedures were poorly documented in Belgium and France. CONCLUSIONS: Our findings reveal that the three similar EU MS under study agree on the REA-outcome of only half of the new drugs. Differences in applied methodology (e.g. inferences from study results, handling of uncertainty) between MS may exist. We suggest that a joint REA approach would benefit from a common understanding and application of the scientific assessment process using shared guidelines.

Paediatric community-acquired septic shock: results from the REPEM network study.

UNLABELLED: INTRODUCTION AND PURPOSE OF THE STUDY: With this study we aimed to describe a "true world" picture of severe paediatric 'community-acquired' septic shock and establish the feasibility of a future prospective trial on early goal-directed therapy in children. During a 6-month to 1-year retrospective screening period in 16 emergency departments (ED) in 12 different countries, all children with severe sepsis and signs of decreased perfusion were included. RESULTS: A 270,461 paediatric ED consultations were screened, and 176 cases were identified. Significant comorbidity was present in 35.8 % of these cases. Intensive care admission was deemed necessary in 65.7 %, mechanical ventilation in 25.9 % and vasoactive medications in 42.9 %. The median amount of fluid given in the first 6 h was 30 ml/kg. The overall mortality in this sample was 4.5 %. Only 1.2 % of the survivors showed a substantial decrease in Paediatric Overall Performance Category (POPC). 'Severe' outcome (death or a decrease ≥2 in POPC) was significantly related (p < 0.01) to: any desaturation below 90 %, the amount of fluid given in the first 6 h, the need for and length of mechanical ventilation or vasoactive support, the use of dobutamine and a higher lactate or lower base excess but not to any variables of predisposition, infection or host response (as in the PIRO (Predisposition, Infection, Response, Organ dysfunction) concept). CONCLUSION: The outcome in our sample was very good. Many children received treatment early in their disease course, so avoiding subsequent intensive care. While certain variables predispose children to become septic and shocked, in our sample, only measures of organ dysfunction and concomitant treatment proved to be significantly related with outcome. We argue why future studies should rather be large multinational prospective observational trials and not necessarily randomised controlled trials.

Insights into Populus XIP aquaporins: evolutionary expansion, protein functionality, and environmental regulation.

A novel category of major intrinsic proteins which share weak similarities with previously identified aquaporin subfamilies was recently identified in land plants, and named X (for unrecognized) intrinsic proteins (XIPs). Because XIPs are still ranked as uncharacterized proteins, their further molecular characterization is required. Herein, a systematic fine-scale analysis of XIP sequences found in flowering plant databases revealed that XIPs are found in at least five groups. The phylogenetic relationship of these five groups with the phylogenetic organization of angiosperms revealed an original pattern of evolution for the XIP subfamily through distinct angiosperm taxon-specific clades. Of all flowering plant having XIPs, the genus Populus encompasses the broadest panel and the highest polymorphism of XIP isoforms, with nine PtXIP sequences distributed within three XIP groups. Comprehensive PtXIP gene expression patterns showed that only two isoforms (PtXIP2;1 and PtXIP3;2) were transcribed in vegetative tissues. However, their patterns are contrasted, PtXIP2;1 was ubiquitously accumulated whereas PtXIP3;2 was predominantly detected in wood and to a lesser extent in roots. Furthermore, only PtXIP2;1 exhibited a differential expression in leaves and stems of drought-, salicylic acid-, or wounding-challenged plants. Unexpectedly, the PtXIPs displayed different abilities to alter water transport upon expression in Xenopus laevis oocytes. PtXIP2;1 and PtXIP3;3 transported water while other PtXIPs did not.

Evidence of transient amorphization during the polymorphic transformation of sorbitol induced by milling.

In this paper, we show that the polymorphic transformation γ â†’ α of sorbitol upon milling involves a transient amorphization of the material. This could be done by comilling sorbitol with a high Tg amorphous material (Hydrochlorothiazide, Tg = 115 °C) to stabilize any transient amorphous fractions of sorbitol through the formation of a molecular alloy. The results indicate that for large sorbitol concentration (50%), the comilling leads to a heterogeneous mixture made of sorbitol crystallites in the form α embedded into an amorphous molecular alloy sorbitol / HCT. Interestingly, the kinetic investigation of this transformation reveals that these two components are not produced simultaneously. On the contrary, they are produced one after the other, during two distinct consecutive stages. The first stage concerns the formation of the amorphous alloy while the second one concerns the polymorphic transformation γ â†’ α of the fraction of crystalline sorbitol not involved in the alloy. These results clearly indicate that the polymorphic transformation of sorbitol upon milling results from the recrystallization of a transient amorphous state generated by the mechanical shocks. The investigations were mainly performed by calorimetry and powder X-ray diffraction.

Characterization and quantification of the interaction between the NFL-TBS.40-63 peptide and lipid nanocapsules.

Several studies previously showed that the NFL-TBS.40-63 peptide (NFL-peptide) is capable to specifically penetrating several glioblastoma cell lines (rat, mouse, human) and inhibiting their cell division in vitro and their tumor development in vivo. When lipid nanocapsules (LNCs) are functionalized with the NFL-peptide, their absorption is targeted in glioblastoma cells both in vitro and in vivo. In the present study, we investigated the molecular architecture of these nanovectors (LNC-NFL) by using several microscopy techniques (transmission electron microscopy, cryo-electron microscopy, and cryo-electron tomography). We also used high-performance liquid chromatography (UPLC) technique to evaluate the interaction between LNCs and peptides. The work shows that the NFL-peptide forms stable long filaments along which the lipid nanocapsules interact strongly to form some sort of nanomolecular bracelets. This new construction composed of the NFL-peptide and lipid nanocapsules shows a better internalization in rat glioblastoma cells (F98 cells) than lipid nanocapsules alone.

Investigation on the self-assembly of the NFL-TBS.40-63 peptide and its interaction with gold nanoparticles as a delivery agent for glioblastoma.

NFL-TBS.40-63 peptide is a recently discovered peptide derived from the light neurofilament chain (NFL). In this study, we demonstrated that the Biotinylated-NFL-peptide (BIOT-NFL) can spontaneously self-assemble into well-organized nanofibers (approximately 5 nm width and several micrometers in length) in several solutions, whereas the typical self-assembly was not systematically observed from other peptides with or without coupling. The critical aggregation concentration that allows the BIOT-NFL-peptide to aggregate and auto associate was determined at 10-4 mol/L by surface tension measurements. X-ray scattering of BIOT-NFL-peptide also demonstrated its beta-sheet structure that can facilitate the intermolecular interactions involved in the self-assembly process. The possible disassembly of self-assembled BIOT-NFL-peptide-nanofibers was examined via a dialysis membrane study. We further investigated the interaction between nanofibers formed by BIOT-NFL-peptide and gold nanoparticles. Interestingly, a strong interaction was demonstrated between these nanoparticles and BIOT-NFL-peptide resulted in the formation of BIOT-NFL-peptide-nanofibers grandly decorated by gold nanoparticles. Finally, we investigated the internalization of gold nanoparticles coupled with BIOT-NFL-nanofibers into F98 rat glioblastoma cells, which was increased compared to the non-coupled control gold nanoparticles. All these results indicate that this peptide could be a promising therapeutic agent for targeted delivery.

Using dense seismo-acoustic network to provide timely warning of the 2019 paroxysmal Stromboli eruptions.

Stromboli Volcano is well known for its persistent explosive activity. On July 3rd and August 28th 2019, two paroxysmal explosions occurred, generating an eruptive column that quickly rose up to 5 km above sea level. Both events were detected by advanced local monitoring networks operated by Istituto Nazionale di Geofisica e Vulcanologia (INGV) and Laboratorio di Geofisica Sperimentale of the University of Firenze (LGS-UNIFI). Signals were also recorded by the Italian national seismic network at a range of hundreds of kilometres and by infrasonic arrays up to distances of 3700 km. Using state-of-the-art propagation modeling, we identify the various seismic and infrasound phases that are used for precise timing of the eruptions. We highlight the advantage of dense regional seismo-acoustic networks to enhance volcanic signal detection in poorly monitored regions, to provide timely warning of eruptions and reliable source amplitude estimate to Volcanic Ash Advisory Centres (VAAC).

[Tick-borne relapsing fever : An unrecognized cause of fever in travellers]. / La fièvre récurrente à tiques : une cause méconnue de fièvre du voyageur.

INTRODUCTION: Tick-borne relapsing fever is a usual cause of fever in West Africa. Except relapsing febrile episodes, there are no pathognomonic signs and diagnosis is difficult because Borrelia density in patient's blood is low. CASE REPORTS: Tick-borne relapsing fever was revealed by the presence of spirochetes in a blood sample to search malaria in two men, 24 and 31 year-old, returned from Mali. CONCLUSION: This diagnosis should be evocated in patients having fever after a trip in infested area, as malaria, both infections can be associated.