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Cysteamine is currently the only therapy for nephropathic cystinosis. It significantly improves life expectancy and delays progression to end-stage kidney disease; however, it cannot prevent it. Unfortunately, compliance to therapy is often weak, particularly during adolescence. Therefore, finding better treatments is a priority in the field of cystinosis. Previously, we found that genistein, an isoflavone particularly enriched in soy, can revert part of the cystinotic cellular phenotype that is not sensitive to cysteamine in vitro. To test the effects of genistein in vivo, we fed 2-month-old wild-type and Ctns−/− female mice with either a control diet, a genistein-containing diet or a cysteamine-containing diet for 14 months. Genistein (160 mg/kg/day) did not affect the growth of the mice or hepatic functionality. Compared with untreated mice at 16 months, Ctns−/− mice fed with genistein had lower cystine concentrations in their kidneys, reduced formation of cystine crystals, a smaller number of LAMP1-positive structures and an overall better-preserved parenchymal architecture. Cysteamine (400 mg/kg/day) was efficient in reverting the lysosomal phenotype and in preventing the development of renal lesions. These preclinical data indicate that genistein ameliorates kidney injury resulting from cystinosis with no side effects. Genistein therapy represents a potential treatment to improve the outcome for patients with cystinosis.

In 2019, entomological survey on mosquitoes was carried out in Abruzzo and Molise regions in central Italy to obtain data on local mosquito fauna. Collection sites were selected based on a previous ecoregion classification of the territory. From 2019 to 2021 virological surveillance for West Nile virus (WNV) and Usutu virus (USUV) on mosquitoes was carried out in the same regions, selecting ecoregions where virus circulation and vector presence were more likely, all mosquitoes were collected and identified, and the female mosquitoes were sorted in 3046 pools and tested for the presence of WNV and USUV by Real-time PCR. All pools tested negative for WND, while USUV was detected in 7 pools of Aedes caspius collected in Molise region, 17 pools of Culex pipiens s.l. (2 collected in Molise, 15 in Abruzzo), and 1 pool of Culiseta longiareolata collected in Molise. These results suggests the presence of an USUV enzootic cycle, maintained by Culex pipiens s.l. and Aedes caspius in both Italian regions, as well as providing a useful picture in terms of species presence and abundance for both regions. Ecoregions proved to be a very valuable tool in determining high risk areas for vector borne diseases.

Our knowledge on the diversity of eukaryotic viruses has recently undergone a massive expansion. This diversity could influence host physiology through yet unknown phenomena of potential interest to the fields of health and food production. However, the assembly processes in eukaryotic viromes of terrestrial animals remain elusive. This situation hinders hypothesis-driven tests of virome influence on host physiology. Here, we explore virome assembly at different spatial scales in the eukaryotic virome of the mosquitoCulex pipiens. This mosquito is a vector of human pathogens worldwide. Several new aspects of virome assembly were unveiled through a sampling involving five countries in Africa and Europe and large sample sizes. A group of viruses was conserved inC. pipienspopulations in all countries. This core group represented a relatively large and diverse fraction of the virome. However, core viruses were not shared by all host individuals in a given country, and their infection rates fluctuated between countries and years. Moreover, the distribution of co-infections in individual mosquitoes suggested random co-occurrence of certain core viruses. We also observed differences in the virome depending on geography, with viromes tending to cluster depending on the continent. Thus, our results unveil that taxon conservation in a eukaryotic virome changes with spatial scale. Thus, predictions on virome assembly seem possible at a large geographical scale inC. pipiens.IMPORTANCEThe study of the eukaryotic virome of mosquitoes is an emerging research field. Beyond its fundamental interest, this field could lead to the development of control tools against the transmission of mosquito-borne human pathogens. However, we yet know little on the assembly patterns in the eukaryotic viromes of mosquitoes, as well as of terrestrial animals in general. This situation hampers the design of hypothesis-driven studies on the influence of the virome on pathogen transmission. Here, we have analyzed virome assembly in the mosquito vectorCulex pipienswithin and between countries in Africa and Europe. Our results show that integrating contrasted spatial scales allows to identify deterministic patterns in virome assembly. Such patterns can guide future studies of virome influence on mosquito physiology.

Quinidine (QND) is an old antimalarial drug that was used in the early 20th century as an antiarrhythmic agent. Currently, QND is receiving attention for its use in epilepsy of infancy with migrating focal seizures (EIMFS) due to potassium sodium-activated channel subfamily T member 1 (

Due to complex maturational and physiological changes that characterize neonates and affect their response to pharmacological treatments, neonatal pharmacology is different from children and adults and deserves particular attention. Although preterms are usually considered part of the neonatal population, they have physiological and pharmacological hallmarks different from full-terms and, therefore, need specific considerations. Antibiotics are widely used among preterms. In fact, during their stay in neonatal intensive care units (NICUs), invasive procedures, including central catheters for parental nutrition and ventilators for respiratory support, are often sources of microbes and require antimicrobial treatments. Unfortunately, the majority of drugs administered to neonates are off-label due to the lack of clinical studies conducted on this special population. In fact, physiological and ethical concerns represent a huge limit in performing pharmacokinetic (PK) studies on these subjects, since they limit the number and volume of blood sampling. Therapeutic drug monitoring (TDM) is a useful tool that allows dose adjustments aiming to fit plasma concentrations within the therapeutic range and to reach specific drug target attainment. In this review of the last ten years’ literature, we performed Pubmed research aiming to summarize the PK aspects for the most used antibiotics in preterms.

Background: Eltrombopag (EPAG) is an oral thrombopoietin receptor agonist, approved for refractory primary immune thrombocytopenia (ITP) in pediatric patients. In two pediatric RCTs, EPAG led to an improvement of platelet counts and a reduction in bleeding severity. However, a significant number of pediatric patients did not achieve the primary endpoints. We performed a pharmacokinetic evaluation of EPAG in pediatric patients with refractory ITP.Methods: Outpatients aged from 1 to 17 y, affected by refractory ITP to first-line treatment, were enrolled for a pharmacokinetic assessment. The analysis of drug plasma concentration was performed by the LC-MS/MS platform. Non-compartmental and statistical subgroup analyses were carried out using the R package ncappc.Results: Among 36 patients eligible for PK analysis, the median dose of EPAG given once daily was 50 mg. The EPAG peak occurs between 2 and 4 h with a population Cmax and AUC 0–24 geo-mean of 23, 38 μg/ml, and 275, 4 µg*h/mL, respectively. The pharmacokinetic profile of EPAG did not show a dose proportionality. Female patients showed a statistically significant increase of dose-normalized exposure parameters, increasing by 110 and 123% for Cmax and AUC 0–24, respectively, when compared to male patients. Patients aged 1–5 y showed values increased by more than 100% considering both exposure parameters, compared to older children. Furthermore, patients presenting complete response (83%), showed augmented EPAG exposure parameters compared to subjects with partial or no response.Conclusion: These data highlight the need to further explore the variability of EPAG exposure and its pharmacokinetic/pharmacodynamic profile in pediatric patients also in a real-life setting.

Early diagnosis and effective therapy are essential for improving the overall prognosis and quality of life of patients with nephropathic cystinosis. The severity of kidney dysfunction and the multi-organ involvement as a consequence of the increased intracellular concentration of cystine highlight the necessity of accurate monitoring of intracellular cystine to guarantee effective treatment of the disease. Cystine depletion is the only available treatment, which should begin immediately after diagnosis, and not discontinued, to significantly slow progression of renal and extra-renal organ damage. This review aims to discuss the importance of the close monitoring of intracellular cystine concentration to optimize cystine depletion therapy. In addition, the role of new biomarkers in the management of the disease, from timely diagnosis to implementing treatment during follow-up, is overviewed. ispartof: CELLS vol:11 issue:11 ispartof: location:Switzerland status: published

(1) Background: Newborns admitted to Neonatal Intensive Care Units (NICUs) often require the placement of central vascular catheters (CVC), which are a major risk factor for hospital infection. Numerous strategies exist to prevent central line-associated blood stream infections (CLABSIs) and catheter-related bloodstream infections (CRBSIs), with only a few offering options to save the catheter when it is impossible to replace. CRBSIs continue to be a major problem for neonates in NICUs. Most CRBSIs are resistant to systemic antibiotics due to the presence of intraluminal bacterial biofilm. Therefore, catheter removal is frequently necessary when a CRBSI occurs. The so-called Antibiotic Lock Therapy (ALT) is an antimicrobial therapeutic strategy which seems to be promising in neonates when catheter removal is difficult due to critical conditions. To date, evidence about the use of ALT in the neonatal period is still fragmentary, since only poor and heterogeneous data exist. (2) Methods: We report our successful experience with ALT in seriously ill neonates with CRBSI for whom the replacement of the catheter could have been life threatening. (3) Results: ALT repetitively performed for at least 12 h was effective in 11 out of 13 infants (84.6%). It was not effective in two infants in whom ALT was performed for only 6 h. Moreover, we present new data about the stability testing of meropenem for its use during ALT in neonates. (4) Conclusions: When CRBSI occurs—bearing in mind that the optimal management is catheter removal if antibiotic therapy is not effective within 48 h—ALT seems to be a valid alternative therapy when removal is impractical due to critical conditions.

Quinidine (QND) is an old antimalarial drug that was used in the early 20th century as an antiarrhythmic agent. Currently, QND is receiving attention for its use in epilepsy of infancy with migrating focal seizures (EIMFS) due to potassium sodium-activated channel subfamily T member 1 (KCNT1) genetic variants. Here, we report the application of Therapeutic Drug Monitoring (TDM) in pediatric patients carrying KCNT1 genetic variants and orally treated with QND for developmental and epileptic encephalopathies (DEE). We measured plasma levels of QND and its metabolite hydroquinidine (H-QND) by using a validated method based on liquid chromatography coupled with mass spectrometry (LC-MS/MS). Three pediatric patients (median age 4.125 years, IQR 2.375–4.125) received increasing doses of QND. Cardiac toxicity was monitored at every dose change. Reduction in seizure frequency ranged from 50 to 90%. Our results show that QND is a promising drug for pediatric patients with DEE due to KCNT1 genetic variants. Although QND blood levels were significantly lower than the therapeutic range as an anti-arrhythmic drug, patients showed a significant improvement in seizure burden. These data underlie the utility of TDM for QND not only to monitor its toxic effects but also to evaluate possible drug–drug interactions.

Background: Neonates may require higher doses of micafungin than adults to reach the therapeutic effect for increased plasma clearance. Only poor and inconclusive data are available still now to support this hypothesis, especially with regard to central nervous system micafungin concentrations. To assess the pharmacokinetics of increased doses (8 to 15 mg/kg/day) of micafungin in preterm and term neonates with invasive candidiasis and to complete previously presented results, we analyzed the pharmacokinetic data on a total of 53 newborns treated with micafungin, whereby 3 of them had Candida meningitis and hydrocephalus. Methods: Fifty-three neonates with systemic candidiasis, three of them with meningitis, were treated for at least 14 days with intravenous micafungin (Mycamine®) at a dosage ranging from 8 to 15 mg/kg/day. Plasma and cerebrospinal fluid (CSF) concentrations of micafungin were measured before the drug administration and at 1, 2, and 8 h after the end of the infusion using high-performance liquid chromatography (HPLC). Systemic exposure was assessed according to AUC0–24, plasma clearance (CL), and half-life measured in 52/53 patients, divided by chronological age. Results and conclusions: The mean micafungin clearance is higher in neonates than in older infants (0.036 L/h/kg before 28 days of life versus 0.028 L/h/kg after 120 days). The drug half-life is shorter in neonates than in older patients (13.5 h before 28 days of life versus 14.4 h after 120 days). With doses ranging between 8 and 15 mg/kg/day, micafungin crosses the blood–brain barrier reaching therapeutic levels in CSF.

The role of therapeutic drug monitoring (TDM) of valaciclovir (VA)/aciclovir (A) and valganciclovir/ganciclovir (VG/G) in critically ill patients is still a matter of debate. More data on the dose–concentration relationship might therefore be useful, especially in pediatrics where clinical practice is not adequately supported by robust PK studies. We developed and validated a new liquid chromatography-tandem mass spectrometry (LC-MS/MS) micro-method to simultaneously quantify A and G from plasma and dried plasma spots (DPS). The method was based on rapid organic extraction from DPS and separation on a reversed-phase C-18 UHPLC column after addition of deuterated internal standards. Accurate analyte quantification using SRM detection was then obtained using a Thermo Fisher Quantiva triple-quadrupole MS coupled to an Ultimate 3000 UHPLC. It was validated following international (EMA) guidelines for bioanalytical method validation and was tested on samples from pediatric patients treated with A, VG, or G for cytomegalovirus infection following solid organ or hematopoietic stem cell transplantation. Concentrations obtained from plasma and DPS were compared using Passing–Bablok and Bland–Altman statistical tests. The assay was linear over wide concentration ranges (0.01–20 mg/L) in both plasma and DPS for A and G, suitable for the expected therapeutic ranges for both Cmin and Cmax, accurate, and reproducible in the absence of matrix effects. The results obtained from plasma and DPS were comparable. Using an LC-MS/MS method allowed us to obtain a very specific, sensitive, and rapid quantification of these antiviral drugs starting from very low volumes (50 μL) of plasma samples and DPS. The stability of analytes for at least 30 days allows for cost-effective shipment and storage at room temperature. Our method is suitable for TDM and could be helpful for improving knowledge on PK/PD targets of antivirals in critically ill pediatric patients.

Cystinosis is an inherited metabolic disorder caused by recessive mutations in the CTNS gene. The disease primarily affects the kidneys followed by extra-renal organ involvement later in life. Azoospermia is one of the unclarified complications which is not improved by cysteamine treatment, the only available disease-modifying treatment. We aimed at unravelling the origin of azoospermia in cysteamine-treated cystinosis by confirming or excluding an obstructive factor, and investigating the effect of cysteamine on fertility in the Ctns-/- mice model compared to wild-type. Azoospermia was present in the vast majority of infantile type cystinosis patients. While spermatogenesis was intact either at testicular or epididymal level in cystinosis patients, an enlarged caput epididymis and reduced levels of seminal markers for obstruction Neutral α-Glucosidase (NAG) and extracellular matrix protein 1 (ECM1) pointed towards an epididymal obstruction. Transcriptomic analysis of CTNS KD in a fertile human caput epididymal cell line demonstrated upregulation of pathways related to inflammation and cell polarization. Interestingly, histopathological examination in human and mice revealed a disturbed blood-testis barrier (BTB) characterized by an altered zonula occludens-1 (ZO-1) protein expression. Animal studies ruled out a negative effect of cysteamine on fertility, and showed that cystine in the testes is irresponsive to regular cysteamine treatment. We conclude that the azoospermia in infantile cystinosis is due to an obstruction related to epididymal dysfunction, irrespective of the severity of an evolving primary hypogonadism as an additional non-obstructive process. Regular cysteamine treatment does not affect fertility but has subtherapeutic effects on cystine accumulation in testes. This article is protected by copyright. All rights reserved.

Cystinosis is a rare, incurable, autosomal recessive disease caused by mutations in the CTNS gene. This gene encodes the lysosomal cystine transporter cystinosin, leading to lysosomal cystine accumulation in all cells of the body, with kidneys being the first affected organs. The current treatment with cysteamine decreases cystine accumulation, but does not reverse the proximal tubular dysfunction, glomerular injury or loss of renal function. In our previous study, we have developed a zebrafish model of cystinosis through a nonsense mutation in the CTNS gene and have shown that zebrafish larvae recapitulate the kidney phenotype described in humans. In the current study, we characterized the adult cystinosis zebrafish model and evaluated the long-term effects of the disease on kidney and extra renal organs through biochemical, histological, fertility and locomotor activity studies. We found that the adult cystinosis zebrafish presents cystine accumulation in various organs, altered kidney morphology, impaired skin pigmentation, decreased fertility, altered locomotor activity and ocular anomalies. Overall, our data indicate that the adult cystinosis zebrafish model reproduces several human phenotypes of cystinosis and may be useful for studying pathophysiology and long-term effects of novel therapies. ispartof: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES vol:22 issue:17 ispartof: location:Switzerland status: published

Candida parapsilosis infections are increasingly reported in preterm neonates, but the optimal treatment remains uncertain. We report the clinical history of an extremely preterm neonate, who developed a devastating skin necrosis due to terlipressin administration, with subsequent superinfection by Candida parapsilosis. The infant underwent multiple curettages and skin grafts to resolve skin lesions and was treated with systemic micafungin administration at a high dose (8 mg/kg/day), with resolution of the fungal infection.

Dear editor,Digoxin is a cardioactive drug with a narrow therapeutic window. Severe intoxication may require urgent treatment. The clinical picture is represented by dangerous dysrhythmias and the ...

Limited data are available on the most appropriate dosing, efficacy, and safety of micafungin in neonates and young infants with invasive candidiasis (IC). This study evaluated plasma levels, efficacy, and safety of micafungin at a dose of 8 mg/kg daily for a mean of 13.3 days (±5.2 days) in 35 neonates and young infants with IC. Micafungin plasma concentrations were 5.70 mg/liter preadministration and 17.23, 15.59, and 10.27 mg/liter after 1, 2, and 8 h, respectively. The resolution of the infection was achieved in 86.7% of patients treated for ≥14 days. In 20.0% of patients, we observed a transient hypertransaminasemia. Micafungin at a dose of 8 mg/kg daily is effective and well tolerated in neonates and young infants with IC. (This study has been registered at ClinicalTrials.gov under identifier NCT03421002 and in the EU Clinical Trials Register under number 2014-003087-20.).

MYCN drives aggressive behavior and refractoriness to chemotherapy, in several tumors. Since MYCN inactivation in clinical settings is not achievable, alternative vulnerabilities of MYCN-driven tumors need to be explored to identify more effective and less toxic therapies. We previously demonstrated that PARP inhibitors enhance MYCN-induced replication stress and promote mitotic catastrophe, counteracted by CHK1. Here, we showed that PARP and CHK1 inhibitors synergized to induce death in neuroblastoma cells and in primary cultures of SHH-dependent medulloblastoma, their combination being more effective in MYCN amplified and MYCN overexpressing cells compared to MYCN non-amplified cells. Although the MYCN amplified IMR-32 cell line carrying the p.Val2716Ala ATM mutation showed the highest sensitivity to the drug combination, this was not related to ATM status, as indicated by CRISPR/Cas9-based correction of the mutation. Suboptimal doses of the CHK1 inhibitor MK-8776 plus the PARP inhibitor olaparib led to a MYCN-dependent accumulation of DNA damage and cell death in vitro and significantly reduced the growth of four in vivo models of MYCN-driven tumors, without major toxicities. Our data highlight the combination of PARP and CHK1 inhibitors as a new potential chemo-free strategy to treat MYCN-driven tumors, which might be promptly translated into clinical trials.

Fungal infections represent a serious complication during the post-liver transplantation period. Abdominal infections can occur following pre-existing colonization, surgical procedures, and permanence of abdominal tubes. In our center, liposomal amphotericin-B is used as antifungal prophylaxis in pediatric patients undergoing liver transplantation. The aim of this study is to evaluate peritoneal levels of amphotericin-B following intravenous administration. Six liver recipients received liposomal amphotericin-B. Three of them were treated as prophylaxis; meanwhile, three patients received liposomal amphotericin-B to treat Candida albicans infection. Plasma and peritoneal amphotericin-B levels were measured by LC-MS/MS in two consecutive samplings. Cmin (pre-dose) and Cmax (2 h after the end of infusion) were evaluated as drug exposure parameters for both plasma and peritoneum. Our results showed that peritoneal amphotericin-B levels were significantly lower than plasma and that the correlation coefficient was 0.72 (p = 0.03) between plasma and peritoneal Cmin. Moreover, although peritoneal levels were within the therapeutic range, they never reached the PK/PD target (Cmax/MIC > 4.5). In conclusion, PK exposure parameters could be differently used to analyze amphotericin-B concentrations in plasma and peritoneum. However, liposomal amphotericin-B should be preferred in these patients as prophylactic rather than therapeutic treatment for fungal infections.

Background Culicoides biting midges are vectors involved in the biological transmission cycle of important animal diseases such as bluetongue and African horse sickness. In Romania, the first outbreaks of bluetongue were reported in 2014, leading to increased activities within the existing entomological surveillance network. The main goals of the surveillance activities were the establishment of the vector free period in relation to animal trade and the identification of Culicoides species involved in the transmission of the pathogen. This study was conducted on the composition and relative abundance of the species belonging to the genus Culicoides (Diptera: Ceratopogonidae) in certain regions of Romania and provided the opportunity to update the existing checklist of Culicoides species of this country. Methods The study was conducted in 33 of the 42 administrative units (counties), including a total of 659 catches, in 102 locations. The collections were carried out with UV blacklight suction traps (OVI type). The collected insects were preserved in 70% ethanol. Morphological insect identification was carried out using a stereomicroscope, according to established identification keys. In ten localities the relative abundance of the cryptic species of the Obsoletus complex was determined by multiplex PCR assay based on the ITS2 segment. The identification of the Culicoides chiopterus (Meigen) species by morphological examination was confirmed by PCR assay based on the ITS1 segment. Results Eleven species were identified using morphological and PCR tools. The rest of the individuals were separated into five taxa. The species of the Obsoletus complex (grouping Culicoides obsoletus (Meigen) and Culicoides scoticus Downes & Kettle) were the most abundant, accounting for 59% of the total number of captured Culicoides spp. Three of the identified species are mentioned, according to our knowledge, for the first time in Romania: Culicoides newsteadi Austen, Culicoides flavipulicaris Dzhafarov and Culicoides bysta Sarvašová, Kočisová, Candolfi & Mathieu. Conclusions Our study demonstrates that the Culicoides species most commonly cited as being involved in the transmission of arboviruses in Europe (i.e. bluetongue and Schmallenberg viruses) make up a high proportion of adult Culicoides trapped in Romania.

The present study reports the results of the first survey of mosquito species in four of the minor Sicilian Islands, namely Lampedusa, Linosa, Pantelleria and Ustica. These surveys were carried out during field activities aimed at recording the occurrence of Aedes albopictus, now reported in all these territories. Adult mosquitoes were collected by traps or by handheld electric aspirators. Larval collections were performed using dippers and droppers. Samples were morphologically identified and molecular investigations were carried out when needed. A total of 6 species were found, namely Aedes (Stegomyia) albopictus, Culex (Culex) pipiens, Culex (Culex) laticinctus, Aedes (Ochlerotatus) mariae, Aedes (Ochlerotatus) zammitii, and Culiseta (Allotheobaldia) longiareolata, the first 2 of which are already a known health concern. This checklist of mosquito species shows the widespread occurrence of Culex laticinctus whose distribution in Italy has still not been thoroughly investigated, whose ecology is poorly known and whose competence as a vector of pathogens is unknown. In Pantelleria, we found larvae of an Aedes species worthy of further investigation.

The common practice of therapeutic drug monitoring (TDM) involves the quantification of drug plasma concentrations at a specific time in a dosing window. Although TDM for antibiotics is not considered mandatory, it may represent a valid tool for clinicians in order to limit antibiotic resistance and avoid therapeutic failures. The aim of our study was to develop and validate a high-performance liquid chromatography-diode array detection method for simultaneous quantification of 10 antibiotics in plasma. This method has a fast analytical procedure that uses the same chromatographic conditions to quantify ceftazidime, ceftriaxone, meropenem, ertapenem, ciprofloxacin, tigecycline, ampicillin, levofloxacin and piperacillin, plus the β-lactamase inhibitor tazobactam. Method validation was ensured by testing selectivity, accuracy, precision, limits of detection and quantification, recovery and stability. The calibration ranges, established accordingly to the expected plasma concentration in patients, showed a coefficient of determination >0.996 for all compounds. Within- and between-days precisions reported a coefficient of variation >15%. Similarly, the accuracy evaluation reported a relative standard deviation of

The role of resident or migratory birds in dispersal of tick species and tick-borne pathogens is still poorly known in Italy. We report here the results of a 3-year project based on sampling ticks from migratory birds, as well as from the vegetation at three stop-over sites for migrants, namely the islands of Ventotene (Latium), Asinara (Sardinia) and Ustica (Sicily). During the spring seasons from 2017-2019, in total 2681 ticks were collected, 2344 of which were sampled from migratory birds and 337 from the vegetation. Ticks were identified by morphology or by molecular tools when necessary. In total, 16 tick species were identified among which the following were exclusively found on birds: Hyalomma rufipes (43.3%), Hy. truncatum (0.1%), Ixodes frontalis (11.8%), Ix. inopinatus (0.2%), Ix. ricinus (3%), Haemaphysalis punctata (0.08%), Hae. erinacei (0.1%), Amblyomma variegatum (0.08%) and Argas vulgaris 0.1%), whereas five species were exclusively collected from the vegetation: Rhipicephalus bursa (10.5%), Rh. turanicus (5.9%), Rh. sanguineus sensu lato (2%), Rh. pusillus (2.4%), Hae. sulcata (0.08%). Hy. marginatum (10.3%) and Ix. ventalloi (9.3%) were found both on birds and on the vegetation on the island Ustica. It is worth noting that the search for ticks on the vegetation did not detect allochthonous tick species. Although we found several interesting local species and allochthonous ticks like Hy. rufipes, Am. variegatum and Ar. vulgaris on birds, further investigations are needed to better define the possible role of migratory birds in the introduction of ticks and tick-borne diseases in Italy, above all after the evidence of imported ticks positive to Crimean Congo hemorrhagic fever (CCHF) virus in several European countries.

Background Linezolid is a synthetic antibiotic which is active against most Gram-positive bacteria, especially on Staphylococcus aureus. Its administration can be required when the infection is due to staphylococcus strains, which are resistant to vancomycin. Although mostly well tolerated, some mild to moderate side effects have been reported. Case presentation This case report describes an infant with multiloculated hydrocephalus, staphylococcal meningitis and prolonged linezolid therapy, in which we observed the association between linezolid administration and a lengthened QTc interval at the electrocardiogram (ECG). To rule out toxic levels during the therapy, plasma and cerebro-spinal fluid concentrations of linezolid were measured and reported. Conclusions Although generally well tolerated in neonates and infants, linezolid prolonged administration seems be able to cause QTc interval prolongation. Therefore, its administration in such patients should be limited to cases of bacterial resistance to other antibiotics. In addition to well-known close monitoring of the platelet level, we suggest serial ECG controls before and during linezolid administration. In the case we report, linezolid plasma concentrations resulted within the therapeutic range during therapy, while cerebrospinal fluid (CSF) concentrations appeared lower than those considered effective.

This is the third in a planned series of data papers presenting modelled vector distributions produced during the ECDC and EFSA funded VectorNet project. The data package presented here includes those 'Culicoides' vectors species first modelled in 2015 as part of the VectorNet gap analysis work namely 'C. imicola, C. obsoletus, C. scoticus, C. dewulfi, C. chiopterus, C. pulicaris, C. lupicaris, C. punctatus, and C. newsteadi'. The known distributions of these species within the Project area (Europe, the Mediterranean Basin, North Africa, and Eurasia) are currently incomplete to a greater or lesser degree. The models are designed to fill the gaps with predicted distributions, to provide a) first indication of vector species distributions across the project geographical extent, and b) assistance in targeting surveys to collect distribution data for those areas with no field validated information. The models are based on input data from light trap surveillance of adult 'Culicoides' across continental Europe and surrounding regions (71.8°N –33.5°S, – 11.2°W – 62°E), concentrated in Western countries, supplemented by transect samples in eastern and northern Europe. Data from central EU are relatively sparse. Funding statement: This work was carried out with support from the VectorNet framework contract OC/EFSA/AHAW/2013/02-FWC1 funded by the European Centre for Disease prevention and Control (ECDC) and the European Food Safety Agency (EFSA) and the PALE-Blu H2020 Project ID: 727393.

Point-of-care devices have attracted a huge interest by the scientific community because of the valuable potentiality for rapid diagnosis and precision medicine through cost-effective and easy-to-use devices for on-site measurement by unskilled personnel. Herein, we reported a smartphone-assisted electrochemical device consisted of a screen-printed electrode modified with carbon black nanomaterial and a commercially available smartphone potentiostat i.e. EmStat3 Blue, for sensitive detection of tyrosine. Once optimized the conditions, tyrosine was detected in standard solutions by square wave voltammetry, achieving a linear range comprised between 30 and 500 μM, with a detection limit equal to 4.4 μM. To detect tyrosine in serum, the interference of another amino acid i.e. tryptophan was hindered using a sample treatment with an extraction cartridge. The agreement of results analyzing serum samples with HPLC reference method and with the developed smart sensing system demonstrated the suitability of this smartphone-assisted sensing tool for cost-effective and rapid analyses of tyrosine in serum samples.

We detected Crimean-Congo hemorrhagic fever virus in a Hyalomma rufipes nymph collected from a whinchat (Saxicola rubetra) on the island of Ventotene in April 2017. Partial genome sequences suggest the virus originated in Africa. Detection of the genome of this virus in Italy confirms its potential dispersion through migratory birds.