Cellular mediators in human leishmaniasis: Critical determinants in parasite killing or disease progression.

Data on cellular immunity mediators in the early phase of human leishmaniasis are still limited and controversial. In order to mimic the changes of humoral mediators during the early phase of human natural infection, some Th1, Th2, Treg, and Breg cytokines, MCP-1, and the nitric oxide (NO) from human PBMC, stimulated by Leishmania infantum, Leishmania major, Leishmania donovani and Leishmania tropica infective metacyclic promastigotes, were determined. After 4 h of L. major, L. donovani, and L. tropica challenge, TNFα, IL-1ß, IL-6 levels were significantly higher than negative control cultures with saline (SF) instead of Leishmania promastigotes, unlike L. infantum-stimulated TNFα and L. major-stimulated IL-1ß. We obtained higher levels of IL-4 and IL-10 cytokines after stimulation of human PBMCs by L. infantum and L. donovani, compared to those observed after the challenge of PBMCs by L. major and L. tropica. Regarding IL-35, such cytokine levels were significantly increased following infection with L. infantum and L. donovani, in contrast to L. major and L. tropica. Up to our knowledge, we are the first to study the effect of four different species of Leishmania on IL-35 levels in human cells. Our study highlights how several Leishmania species can up-regulate different groups of cytokines (Th1, Th2, Treg and Breg) and modulate NO release in a different way. This original aspect can be explained by different Leishmania cell products, such as LPG, obtained from different strains/species of live parasites. Our findings would contribute to the development of new therapeutics or vaccination strategies.

Direct antimicrobial susceptibility testing (AST) from positive blood cultures using Microscan system for early detection of bacterial resistance phenotypes.

Antimicrobial Susceptibility Testing is mandatory for Bloodstream Infections management in order to establish appropriate antimicrobial therapy. Herein we evaluated new approach based on AST results directly from positive blood cultures, using Microscan WA to carry out rapid phenotypical profile of antibiotic resistance. Our investigations allow to reduce time versus traditional results.

Line-field confocal optical coherence tomography for actinic keratosis and squamous cell carcinoma: a descriptive study.

BACKGROUND: Early and accurate diagnosis of cutaneous squamous cell carcinomas (SCCs) and actinic keratoses (AK) is fundamental to reduce their associated morbidity and to select the correct treatment. Line-field confocal optical coherence tomography (LC-OCT) is a new imaging device that can characterize healthy skin and basal cell carcinoma, but no large studies on keratinocyte cell tumours have yet been published. AIM: To identify and describe LC-OCT criteria associated with SCC and AK, and to compare LC-OCT findings in these tumours. METHODS: A retrospective observational multicentre study was conducted. Lesions were imaged with the LC-OCT device before surgery and examined histologically. LC-OCT criteria for AK/SCC were identified and their presence was evaluated in all study lesions. Univariate and multivariate analyses were performed to compare AK and SCCs, and to investigate differences between in situ and invasive tumours. RESULTS: In total, 158 patients with 50 AK and 108 SCCs (62 in situ and 46 invasive) were included. Cytological and architectural alterations were found in most lesions, and differences were found between AK and SCCs. Although the visualization of the dermoepidermal junction (DEJ) was often hampered by hyperkeratosis and acanthosis, an outlined DEJ without broad strands was observed in almost all AK and almost all in situ SCCs, but in only three invasive SCCs (P < 0.001) when the DEJ was detectable. CONCLUSION: Our results suggest that LC-OCT can help clinicians in the identification of AK and SCC and their differentiation, providing a real-time and noninvasive examination. Further studies are needed to confirm our data.

Scalable nanophotonic neural probes for multicolor and on-demand light delivery in brain tissue.

Neural probes arein vivobrain-invasive devices that record and manipulate neural circuits using electricity, light, or drugs. The capability to shine distinct wavelengths and control their respective output locations for activation or deactivation of specific groups of neurons is desirable but remains unachieved. Here, we discuss our probe's capability to deliver two independently controllable wavelengths (450 and 655 nm) in the location(s) of interest using nanophotonic directional couplers and ring resonators. These nanophotonics are scalable to dozens of outputs without significantly increasing the device's lateral dimensions. Furthermore, they are entirely passive and thus do not require electrical input that results in heat generation. Besides, we integrate a high number of electrodes for a simultaneous neural activity readout. Thus, we overcome the challenges associated with multicolor illumination for neural devices by exploiting the capability of miniaturizable, passive probes to deliver two different frequencies in several areas of interest. These devices open the path towards investigating thein vivoelectrical signal propagation under the individual or simultaneous activation or inhibition of distinct brain regions.

Genetic characterisation of Measles virus variants identified during a large epidemic in Milan, Italy, March-December 2017.

In 2017, Italy experienced a large measles epidemic with 5408 cases and four deaths. As Subnational Reference Laboratory of the Measles and Rubella surveillance NETwork (MoRoNET), the EpiSoMI (Epidemiology and Molecular Surveillance of Infections) Laboratory (University of Milan) set up rapid and active surveillance for the complete characterisation of the Measles virus (Mv) responsible for the large measles outbreak in Milan and surrounding areas (Lombardy, Northern Italy). The aims of this study were to describe the genetic profile of circulating viruses and to track the pathway of measles transmission. Molecular analysis was performed by sequencing the highly variable 450 nucleotides region of the N gene (N-450) of Mv genome. Two-hundred and ninety-nine strains of Mv were analysed. The phylogenetic analysis showed five different variants, two not previously described in the studied area, belonging to D8 and B3 genotypes. Three events of continuous transmission of autochthonous variants (D8-Osaka, D8-London and B3-Milan variants) and two events of continuous transmission of imported variants (B3-Dublin and D8-Hulu Langat) tracked five different transmission pathways. These pathways outlined two epidemic peaks: the first in April and the second in July 2017. The correlation between Mv variant and the epidemiological data may enable us to identify the sources of virus importation and recognise long-lasting virus transmission pathways.

Retinal vascular density in multiple sclerosis: a 1-year follow-up.

BACKGROUND AND PURPOSE: Vascular pathology is increasingly acknowledged as a risk factor for multiple sclerosis (MS). Vascular density (VD) is reduced in the eyes of patients with MS on optical coherence tomography (OCT) angiography. We performed a 1-year prospective study to estimate VD variations over time and possible clinical correlates. METHODS: A total of 50 patients with MS underwent spectral domain-OCT and OCT angiography at baseline and after 1-year follow-up. Mixed-effect linear regression models were used to assess variations of each OCT measure and its relation to treatment and clinical outcomes. RESULTS: We observed an increase in parafovea VD (coefficient, 1.147; 95% confidence interval, 0.081-2.214; P = 0.035). Reduction in parafovea VD was associated with increase in Expanded Disability Status Scale score (coefficient, -0.969; 95% confidence interval, -1.732/-0.207; P = 0.013). CONCLUSIONS: Retinal VD can improve over time in MS, particularly in patients experiencing disease stability. Longer follow-up, inclusion of early MS cases and combination with conventional markers of MS severity (i.e. brain atrophy) are needed to better define VD as a potential new biomarker.

Measles surveillance activities in the Metropolitan Area of Milan during 2017-2018.

INTRODUCTION: In Italy, the transmission of measles is still endemic, and 7,919 cases were reported to the National Surveillance System between January 2017 and December 2018. Aim of this study is to report the results of the measles surveillance activities in the Metropolitan City of Milan from March 2017 to December 2018, and to evaluate the surveillance performance WHO indicators. METHODS: The Local Health Units (LHUs) carried out case investigations and collected specimens to send to the EpiSoMI Lab (Subnational Reference Laboratory, SRL) of the University of Milan for cases/outbreaks confirmation and genotyping performed according to the WHO Guidelines. RESULTS: Overall, 610 suspected measles cases were reported by the surveillance system of the Metropolitan City of Milan. A total of 439 out of 540 cases with adequate specimens were laboratory-confirmed by molecular and/or serological assays. Two-hundred and thirty-six cases were notified as sporadic and 203 as related to 94 outbreaks. The most confirmed cases were aged 15-39 years, almost all not vaccinated. Overall, 282 cases were genotype D8 and 118 genotype B3.The evaluation of a set of indicators to monitor the quality of surveillance activities demonstrated the proficiency of the EpiSoMI Lab. CONCLUSIONS: A well-done investigation of cases and outbreaks by the surveillance local system, in a timely manner, in order to notify and investigate suspected cases and to laboratory confirm or discard cases is fundamental to reduce morbidity, to prevent further virus transmission and to achieve measles elimination.

Melanoma arising from a plaque-type blue naevus with subcutaneous cellular nodules of the scalp.

Plaque-type blue naevus (PTBN) is a very rare variant of blue naevus (BN). The potential malignancy of subcutaneous cellular nodules (SCN) in PTBN was discovered in 2012, and there is currently no clear consensus on prognostic factors or management guidelines of such lesions. PTBN on the scalp have not been described in the literature. We report the clinical, histopathological and immunohistological features of a 50-year-old man who presented with a 30-year history of scalp PTBN, with malignant proliferation of nodular elements and fatal outcome 8 years later. This case suggests that long-term monitoring of patients with PTBN is required. Early surgical removal of such lesions should be considered, especially in the presence of any case of enlargement or change.

Hepatitis C virus outbreak in a haemodialysis unit: learning from failures.

The investigation of an outbreak of hepatitis C virus in an Italian haemodialysis (HD) centre showed that three patients acquired infection with the same strain, affecting a chronically hepatitis C virus (HCV)-infected patient receiving HD in the same room and during the same shifts. Through our observational analysis many possible modes of transmission were identified, but none could be definitively identified as the route of HCV spread in this small cluster. This outbreak confirms that repeated opportunities for nosocomial HCV transmission may occur among HD patients due to several breaches in the standard precautions for bloodborne infections by healthcare staff.

Nanostructural evolution of one-dimensional BaTiO3 structures by hydrothermal conversion of vertically aligned TiO2 nanotubes.

The use of TiO2 nanotube (NT) arrays as templates for hydrothermal conversion of one-dimensional barium titanate (BaTiO3) structures is considered a promising synthesis approach, even though the formation mechanisms are not yet fully understood. Herein we report a nanostructural study by means of XRD and (HR)TEM of high aspect ratio TiO2-NTs hydrothermally converted into BaTiO3. The nanostructure shows two different and well-defined regions: at the top the conversion involves complete dissolution of NTs and subsequent precipitation of BaTiO3 crystals by homogeneous nucleation, followed by the growth of dendritic structures by aggregation and oriented attachment mechanisms. Instead, at the bottom, the low liquid/solid ratio, due to the limited amount of Ba solution that infiltrates the NTs, leads to the rapid crystallization of such a solution into BaTiO3, thus allowing the NTs to act as a template for the formation of highly oriented one-dimensional nanostructures. The in-depth analysis of the structural transformations that take place during the formation of the rod-like arrays of BaTiO3 could help elucidate the conversion mechanism, thus paving the way for the optimization of the synthesis process in view of new applications in energy harvesting devices, where easy and low temperature processing, controlled composition, morphology and functional properties are required.

Differences in clinicopathological features and distribution of risk factors in Italian melanoma patients.

BACKGROUND: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. OBJECTIVE: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. METHODS: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. RESULTS: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. CONCLUSIONS: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

Severe obesity prevalence in 8- to 9-year-old Italian children: a large population-based study.

BACKGROUND AND OBJECTIVES: Little information is available on severe obesity in childhood. This study estimates the prevalence of severe obesity in 8- to 9-year-old children resident in Italy and its association with gender, age, geographical area and parents' nutritional status and education using the World Health Organization (WHO) and International Obesity Task Force (IOTF) criteria. SUBJECTS/METHODS: A nationally representative sample of grade 3 Italian students was measured in 2010 (N=42,431) using standardized instruments and methodology. Severe obesity in children was assessed using definitions provided by the WHO and by the IOTF. Prevalence was estimated within categories of sociodemographic variables and their independent effects were estimated using multivariate logistic regression. RESULTS: The estimated prevalence of severe obesity in 2010 was 4.5% (95% confidence interval (CI): 4.2-4.7) according to the WHO definition and 2.7% (95% CI: 2.5-2.9) with IOTF cutoffs. These values were slightly lower than those observed in 2008. The prevalence was higher in males, in 8-year-old children and in the South. Parental low education and high body mass index were strongly associated with childhood severe obesity. CONCLUSION: According to the definition used, between 30,000 and 50,000 children aged 8-9 years suffer severe obesity in Italy.

A flow-through holed PDMS membrane as a reusable microarray spotter for biomedical assays.

We propose the exploitation of a holed-designed poly(dimethyl)siloxane (PDMS) membrane as an innovative microarray spotter. The membrane is fabricated by a simple technological approach and can be reused several times. A good level of reproducibility is found upon spotting fluorescent proteins at different concentrations over large areas.

Dermatological conditions presenting at the Emergency Department in Siena University Hospital from 2006 to 2011.

BACKGROUND: Published studies on emergency dermatology consultations are few because there are few dermatology emergency units in the world. No study has yet described the Italian situation. OBJECTIVES: To quantify and characterize patients evaluated in our dermatology emergency unit from 2006 to 2011. METHODS: We studied personal details, diagnosis, annual trend of cases, emergency level and hospitalization of dermatology cases over the 6-year period. RESULTS: A total of 12,226 patients were evaluated. The most numerous diagnostic group was infections (27.1%), followed by non-specific and descriptive diagnosis (22.5%), skin conditions caused by mechanical or physical agents (13.1%), eczematous diseases (10.5%), insect bites (9.5%) and urticaria/angio-oedema (8.8%). The most common indications for admission to hospital were skin conditions caused by mechanical or physical agents (33.3%), infections (27.5%), drug eruption (15.9%) and autoimmune or inflammatory disorders (7.4%). Emergency dermatology cases followed a variable annual trend, with more consultations in the summer months. CONCLUSION: This is the first long-term retrospective analysis of a large series of dermatology emergency patients. It provides useful quantitative and qualitative information on cases for physicians and the national health system for the purposes of improving patient care and cost-effectiveness.

In-plane 2D focusing of surface waves by ultrathin refractive structures.

In an attempt to provide a fully dielectric platform for two-dimensional optical circuitry, we report on the focusing features of an ultrathin polymeric lens fabricated on a planar multilayer. The radiation coupled to surface modes sustained by the multilayer can be focused or waveguide-injected into linear ridges by exploiting a dielectric-loading mechanism successfully exploited for plasmons. The low losses of this photonic system also allow long propagation lengths in the visible spectral range. Experimental observations made by fluorescence imaging of the multilayer surface are well supported by computational data obtained through an effective index approach.

A novel fast phase correlation algorithm for peak wavelength detection of Fiber Bragg Grating sensors.

Fiber Bragg Gratings (FBGs) can be used as sensors for strain, temperature and pressure measurements. For this purpose, the ability to determine the Bragg peak wavelength with adequate wavelength resolution and accuracy is essential. However, conventional peak detection techniques, such as the maximum detection algorithm, can yield inaccurate and imprecise results, especially when the Signal to Noise Ratio (SNR) and the wavelength resolution are poor. Other techniques, such as the cross-correlation demodulation algorithm are more precise and accurate but require a considerable higher computational effort. To overcome these problems, we developed a novel fast phase correlation (FPC) peak detection algorithm, which computes the wavelength shift in the reflected spectrum of a FBG sensor. This paper analyzes the performance of the FPC algorithm for different values of the SNR and wavelength resolution. Using simulations and experiments, we compared the FPC with the maximum detection and cross-correlation algorithms. The FPC method demonstrated a detection precision and accuracy comparable with those of cross-correlation demodulation and considerably higher than those obtained with the maximum detection technique. Additionally, FPC showed to be about 50 times faster than the cross-correlation. It is therefore a promising tool for future implementation in real-time systems or in embedded hardware intended for FBG sensor interrogation.

The methodology of the Italian HBSC 2010 study (Health Behaviour in School-aged Children).

Italy has participated in the Health Behaviour in School-aged Children (HBSC) study since 2000. These surveys collect data every four years on the well-being and health behaviour of boys and girls aged 11, 13 and 15. Until 2007, the coordination group of the University of Turin, Siena and Padua directly sent the questionnaires to each sampled school to collect the data. The sample of about 4500 students was nationally representative. In 2008 the HBSC became part of the project "Surveys on behavioral risks in children aged 6-17 years", coordinated by the National Institute of Health (ISS) and promoted by the Ministry of Health, in collaboration with the Ministry of Education, University and Research. For the first time, in 2010, the survey was conducted by health workers in collaboration with teachers in all regions with a representative sample, not just at the national level, but also at regional level. In the 2,504 sampled schools, 77,113 students (25,079 eleven-year-old, 26,048 thirteen-year-old and 25,986 fifteen-year-old) completed an anonymous questionnaire. Knowledge of the health-related behaviour of school-aged adolescents may help monitoring and enable policies for young people to be formulated and implemented.