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Purpose Preliminary reports suggest that extracellular vesicles (EVs) might be a promising biomarker for breast cancer (BC). However, the quantification of plasmatic levels of EVs is a complex task. To overcome these limitations, we developed a new, fast, and easy to use assay for the quantification of EVs directly in plasma based on the use of Single-Molecule Array (SiMoA). Methods By using SiMoA to identify CD9+/CD63+ EVs, we analyzed plasma samples of 181 subjects (95 BC and 86 healthy controls, HC). A calibration curve, made of a serial dilution of lyophilized standards from human plasma, was used in each run to ensure the obtainment of quantitative results from the assay. In a subgroup of patients, EVs concentrations were estimated in plasma before and after 30 days from cancer surgery. Additional information on the size of EVs were also acquired using a Nanosight system to obtain a clearer understanding of the mechanism underlying the releases of EVs associated with the presence of cancer. Results The measured levels of EVs resulted significantly higher in BC patients (median values 1179.1 ng/µl vs 613.0 ng/µl, p p = 0.014). No correlation was found between EVs concentration and clinical features of BC. Conclusion SiMoA assay allows plasmatic EVs levels detection directly without any prior processing. EVs levels are significantly higher in BC patients and significantly decreases after cancer surgery.

Neurofilament light chains (NfL) are neuron-specific cytoskeletal proteins whose plasmatic concentrations have been explored as a clinically useful marker in several types of dementia. Plasma concentrations of NfL are extremely low, and just two assays are commercially available for their study: one based on the SiMoA™ technology and one based on Ella™. We thus studied plasma levels of NfL with both platforms to check the correlation between them and to assess their potential in the diagnosis of dementia. Plasma NfL levels were measured on 50 subjects: 18 healthy controls, 20 Alzheimer’s disease, and 12 frontotemporal dementia patients. Ella™ returned plasmatic NfL levels significantly higher than SiMoA™, however the results were strongly correlated (r = 0.94), and a proportional coefficient of 0.58 between the two assays was calculated. Both assays detected higher plasma NfL levels in patients with dementia than in the control group (p 0.95). No difference was found between Alzheimer’s and Frontotemporal dementia either using SiMoA™ or Ella™. In conclusion, both the analytical platform resulted effective in analysing plasma levels of NfL. However, the correct interpretation of results requires the precise knowledge of the assay used.

Interleukin (IL)-10 is the primary cytokine driving the modulation of the host response in filarial infections. We performed binding assays with Brugia malayi antigen extracts and human IL-10R1. Bm5539 was the top-binding hit. We identified a short sequence, termed truncated Bm5339, that has structural similarities to the human IL-10 functional dimer. Sequence comparisons revealed that other filarial parasites possess Bm5539 orthologues. Using recombinant Bm5539 in a modified Luciferase Immunoprecipitation System assay, we confirmed that both the truncated and full-length forms of the protein can bind to human IL-10R1. Truncated Bm5539 could inhibit human IL-10-driven phosphorylation of STAT3, thereby demonstrating that Bm5539 acts as an IL-10 antagonist, most likely through competitive binding to the receptor. We provide a structural basis for these observations using computational modeling and simulations. This parasite-encoded cytokine receptor antagonist provides an additional lens through which parasite-induced modulation of the host immune response can be examined.

Identification of reliable and accessible biomarkers to characterize ischemic stroke patients’ prognosis remains a clinical challenge. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are markers of brain injury, detectable in blood by high-sensitive technologies. Our aim was to measure serum NfL and GFAP after stroke, and to evaluate their correlation with functional outcome and the scores in rehabilitation scales at 3-month follow-up. Stroke patients were prospectively enrolled in a longitudinal observational study within 24 hours from symptom onset (D1) and monitored after 7 (D7), 30 ± 3 (M1) and 90 ± 5 (M3) days. At each time-point serum NfL and GFAP levels were measured by Single Molecule Array and correlated with National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), Trunk Control Test (TCT), Functional Ambulation Classification (FAC) and Functional Independence Measure (FIM) scores. Serum NfL and GFAP showed different temporal profiles: NfL increased after stroke with a peak value at D7; GFAP showed an earlier peak at D1. NfL and GFAP concentrations correlated with clinical/rehabilitation outcomes both longitudinally and prospectively. Multivariate analysis revealed that NfL-D7 and GFAP-D1 were independent predictors of 3-month NIHSS, TCT, FAC and FIM scores, with NfL being the biomarker with the best predictive performance.

Background Interleukin-10 (IL-10) has been implicated as the major cytokine responsible for the modulation of parasite-specific responses in filarial infections; however, the role of other IL-10 superfamily members in filarial infection is less well studied. Methods Peripheral blood mononuclear cells from loiasis patients were stimulated with or without filarial antigen. Cytokine production was quantified using a Luminex platform and T-cell expression patterns were assessed by flow cytometry. Results All patients produced significant levels of IL-10, IL-13, IL-5, IL-4, and IL-9 in response to filarial antigen, indicating a common infection-driven response. When comparing microfilaria (mf)-positive and mf-negative patients, there were no significant differences in spontaneous cytokine nor in parasite-driven IL-10, IL-22, or IL-28a production. In marked contrast, mf-positive individuals had significantly increased filarial antigen-driven IL-24 and IL-19 compared to mf-negative subjects. mf-positive patients also demonstrated significantly higher frequencies of T cells producing IL-19 in comparison to mf-negative patients. T-cell expression of IL-19 and IL-24 was positively regulated by IL-10 and IL-1β. IL-24 production was also regulated by IL-37. Conclusion These data provide an important link between IL-10 and its related family members IL-19 and IL-24 in the modulation of the immune response in human filarial infections. Clinical Trials Registration NCT00001230.

Background Strongyloidiasis can cause devastating morbidity and death in immunosuppressed patients. Identification of reliable biomarkers for strongyloidiasis in immunosuppressed patients is critical for the prevention of severe disease. Methods In this cross-sectional study of solid organ transplant (SOT) candidates and recipients, we quantified Strongyloides-specific IgG to the recombinant NIE-Strongyloides antigen and/or to a soluble extract of S. stercoralis somatic antigens (“crude antigen”) using enzyme-linked immunosorbent assays (ELISAs). We also measured peripheral eosinophilia, 4 different eosinophil granule proteins, and intestinal fatty acid–binding protein (IFABP). Results We evaluated serum biomarkers in 149 individuals; 77 (52%) pre-SOT and 72 (48%) post-SOT. Four percent (6/149) tested positive by NIE ELISA and 9.6% (11/114) by crude antigen ELISA (overall seropositivity of 9.4% [14/149]). Seropositive patients had higher absolute eosinophil counts (AECs) than seronegative patients (P = .004). AEC was positively correlated to the levels of eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) (P Conclusions This study suggests that, in SOT patients, strongyloidiasis triggers both eosinophilia and eosinophil activation, the latter being associated with intestinal inflammation. These data provide insight into the pathogenesis of S. stercoralis infection in the immunocompromised population at high risk of severe strongyloidiasis syndromes.

Early therapies to prevent severe COVID-19 have an unclear impact on patients with hematological malignancies. The aim of this study was to assess their efficacy in this group of high-risk patients with COVID-19 in preventing hospitalizations and reducing the SARS-CoV-2 shedding. This was a single-center, retrospective, observational study conducted in the Fondazione IRCSS Policlinico San Matteo of Pavia, Northern Italy. We extracted the data of patients with hematologic malignancies and COVID-19 who received and did not receive early COVID-19 treatment between 23 December 2021, and May 2022. We used a Cox proportional hazard model to assess whether receiving any early treatment was associated with lower rates of hospitalization and reduced viral shedding. Data from 88 patients with hematologic malignancies were extracted. Among the patients, 55 (62%) received any early treatment, whereas 33 (38%) did not. Receiving any early therapy did not significantly reduce the hospitalization rate in patients with hematologic malignancies (HR 0.51; SE 0.63; p-value = 0.28), except in the vaccinated non-responders subgroup of patients with negative anti SARS-CoV-2 antibodies at the time of infection, who benefited from early therapies against SARS-CoV-2 (HR 0.07; SE 1.04; p-value = 0.001). Moreover, no difference on viral load decay was observed. In our cohort of patients with hematologic malignancies infected with SARS-CoV-2, early treatment were not effective in reducing the hospitalization rate due to COVID-19, neither in reducing its viral shedding.

This study investigates the relationship between helminth infection and allergic sensitization by assessing the influence of preexisting allergy on the outcome of helminth infections, rather than the more traditional approach in which the helminth infection precedes the onset of allergy. Here we used a murine model of house dust mite–induced (HDM-induced) allergic inflammation followed by Ascaris infection to demonstrate that allergic sensitization drives an eosinophil-rich pulmonary type 2 immune response (Th2 cells, M2 macrophages, type 2 innate lymphoid cells, IL-33, IL-4, IL-13, and mucus) that directly hinders larval development and reduces markedly the parasite burden in the lungs. This effect is dependent on the presence of eosinophils, as eosinophil-deficient mice were unable to limit parasite development or numbers. In vivo administration of neutralizing antibodies against CD4 prior to HDM sensitization significantly reduced eosinophils in the lungs, resulting in the reversal of the HDM-induced Ascaris larval killing. Our data suggest that HDM allergic sensitization drives a response that mimics a primary Ascaris infection, such that CD4(+) Th2-mediated eosinophil-dependent helminth larval killing in the lung tissue occurs. This study provides insight into the mechanisms underlying tissue-specific responses that drive a protective response against the early stages of the helminths prior to their establishing long-lasting infections in the host.

SERS tags are a class of nanoparticles with great potential in advanced imaging experiments. The preparation of SERS tags however is complex, as they suffer from the high variability of the SERS signals observed even at the slightest sign of aggregation. Here, we developed a method for the preparation of SERS tags based on the use of gold nanostars conjugated with neutravidin. The SERS tags here obtained are extremely stable in all biological buffers commonly employed and can be prepared at a relatively large scale in very mild conditions. The obtained SERS tags have been used to monitor the expression of fibroblast activation protein alpha (FAP) on the membrane of primary fibroblasts obtained from patients affected by Crohn’s disease. The SERS tags allowed the unambiguous identification of FAP on the surface of cells thus suggesting the feasibility of semi-quantitative analysis of the target protein. Moreover, the use of the neutravidin–biotin system allows to apply the SERS tags for any other marker detection, for example, different cancer cell types, simply by changing the biotinylated antibody chosen in the analysis.

We have previously shown that the microfilarial (mf) stage of Brugia malayi can inhibit the mammalian target of rapamycin (mTOR; a conserved serine/threonine kinase critical for immune regulation and cellular growth) in human dendritic cells (DC) and we have proposed that this mTOR inhibition is associated with the DC dysfunction seen in filarial infections. Extracellular vesicles (EVs) contain many proteins and nucleic acids including microRNAs (miRNAs) that might affect a variety of intracellular pathways. Thus, EVs secreted from mf may elucidate the mechanism by which the parasite is able to modulate the host immune response during infection. EVs, purified from mf of Brugia malayi and confirmed by size through nanoparticle tracking analysis, were assessed by miRNA microarrays (accession number GSE157226) and shown to be enriched (>2-fold, p-value, Author summary Lymphatic filariasis, a neglected tropical disease caused by parasitic worms which affects millions of individuals, represents an important public health concern due to its high morbidity that significantly diminishes quality of life. The parasite is able to establish a chronic infection by manipulating its host’s immune responses. The larval mf stage of the parasite is of particular interest as the parasites are present in the peripheral blood and in constant contact with the host’s immune cells. We decided to investigate the role of mf-derived EVs in the modulation of human antigen presenting cells during infection. We showed that mf release EVs that are similar to exosomes, and these parasite vesicles are readily internalized by human DC. The mf-derived EVs possess a unique miRNA profile and are enriched in miRNAs that can target the mTOR pathway. We have also demonstrated that purified mf-derived EVs are capable of inhibiting mTOR signaling in human monocytes. Collectively, our results suggest that mf release exosome-like vesicles that modulate the immune metabolism of host antigen presenting cells.

Many parasitic infections have different presenting features in endemic individuals (ENDs) and immunologically naive temporary residents (TRs). Temporary residents with loiasis often display acute symptoms and hypereosinophilia, in contrast to a parasite-induced subclinical state in chronically infected ENDs. Few studies have examined differences in ENDs and TRs infected with the related filarial parasite Onchocerca volvulus. We identified 40 TRs and 36 ENDs with imported onchocerciasis at the National Institutes of Health between 1976 and 2016. All study subjects received an extensive pretreatment medical history, physical examination, and laboratory investigations. We performed additional parasite-specific serologic testing on stored patient sera. Asymptomatic infection occurred in 12.5% of TRs and no ENDs (P = 0.06). Papular dermatitis was more common in TRs (47.5% versus 2.7%, P < 0.001), whereas more pigmentation changes occurred in ENDs (41.7% versus 15%, P = 0.01). Only endemic patients reported visual disturbance (13% versus 0%, P = 0.03). One TR (3.3%) had onchocercal eye disease, compared with 22.6% of ENDs (P = 0.053). Absolute eosinophil counts (AECs) were similar in ENDs and TRs (P = 0.5), and one-third of subjects had a normal AEC. Endemic individuals had higher filarial-specific IgG4 and were more likely to be positive for IgG4 antibodies to Ov-16. Temporary residents and ENDs with imported O. volvulus infection presented with different dermatologic manifestations; ocular involvement occurred almost exclusively in ENDs. Unlike Loa loa, clinical differences appear not to be eosinophil-mediated and may reflect chronicity, intensity of infection, or the presence of Wolbachia in O. volvulus.

The study was undertaken in order to provide a snapshot from real clinical practice of virological presentation and outcome of patients developing immunosuppression-driven HBV reactivation. Seventy patients with HBV reactivation were included (66.2% treated with rituximab, 10% with corticosteroids and 23.8% with other immunosuppressive drugs). Following HBV reactivation, patients received anti-HBV treatment for a median (IQR) follow-up of 31(13-47) months. At baseline-screening, 72.9% of patients were HBsAg-negative and 27.1% HBsAg-positive. About 71.4% had a diagnosis of biochemical reactivation [median (IQR) HBV DNA and ALT: 6.9 (5.4-7.8) log IU/mL and 359 (102-775) U/L]. Moreover, 10% of patients died from hepatic failure. Antiviral prophylaxis was documented in 57.9% and 15.7% of HBsAg-positive and HBsAg-negative patients at baseline-screening (median [IQR] prophylaxis duration: 24[15-33] and 25[17-36] months, respectively). Notably, HBV reactivation occurred 2-24 months after completing the recommended course of anti-HBV prophylaxis in 35.3% of patients. By analysing treatment outcome, the cumulative probability of ALT normalization and of virological suppression was 97% and 69%, respectively. Nevertheless, in patients negative to HBsAg at baseline-screening, only 27% returned to HBsAg-negative status during prolonged follow-up, suggesting the establishment of chronic infection. In conclusion, most patients received a diagnosis of HBV reactivation accompanied by high ALT and 10% died for hepatic failure, supporting the importance of strict monitoring for an early HBV reactivation diagnosis. Furthermore, HBV reactivation correlates with high risk of HBV chronicity in patients negative for HBsAg at baseline-screening, converting a silent into a chronic infection, requiring long-term antiviral treatment. Finally, a relevant proportion of patients experienced HBV reactivation after completing the recommended course of anti-HBV prophylaxis, suggesting the need to reconsider proper duration of prophylaxis particularly in profound immunosuppression.

Lipofilling (LF) is a largely employed technique in reconstructive and esthetic breast surgery. Over the years, it has demonstrated to be extremely useful for treatment of soft tissue defects after demolitive or conservative breast cancer surgery and different procedures have been developed to improve the survival of transplanted fat graft. The regenerative potential of LF is attributed to the multipotent stem cells found in large quantity in adipose tissue. However, a growing body of pre-clinical evidence shows that adipocytes and adipose-derived stromal cells may have pro-tumorigenic potential. Despite no clear indication from clinical studies has demonstrated an increased risk of cancer recurrence upon LF, these observations challenge the oncologic safety of the procedure. This review aims to provide an updated overview of both the clinical and the pre-clinical indications to the suitability and safety of LF in breast oncological surgery. Cellular and molecular players in the crosstalk between adipose tissue and cancer are described, and heterogeneous contradictory results are discussed, highlighting that important issues still remain to be solved to get a clear understanding of LF safety in breast cancer patients.

Raman spectroscopy has been vastly employed for the characterization of different bio-molecular species spanning from single protein to the in-vivo analysis of tissues. However, despite the huge work done, a detailed description of the Raman spectra acquired from the main classes of plasma lipoproteins is still missing. In this work, we extracted, the major classes of lipoproteins: the triacylglycerol-rich very low density lipoproteins (VLDL); the more cholesterol-rich low density lipoproteins (LDL); and the high density lipoproteins (HDL); from human plasma of six fasting healthy volunteers. The extracted lipoproteins were dried on CaF2 slides and analysed using a 633 nm laser line non-in resonance with the carotenoids present in the sample. The obtained spectra showed peaks relative to the different biomolecules composing lipoproteins: cholesterol, triglycerides, membrane lipids, carotenoids, and apolipoproteins (proteins). The intensity of the peaks from lipids and proteins are well in accordance with the measured composition of lipoproteins; but the information is acquired in a much faster way by Raman spectroscopy. Besides, Raman spectroscopy provides easily information on the levels of carotenoids and unsaturated fatty acid present in the samples. Overall, our data provide a clear comprehension of the Raman spectra from lipoproteins ad suggest that Raman spectroscopy could be a viable approach for the fast characterization of lipoproteins.

Methods for the diagnosis of parasitic infections have stagnated in the past three decades. Labor-intensive methods such as microscopy still remain the mainstay of several diagnostic laboratories. There is a need for more rapid tests that do not sacrifice sensitivity and that can be used in both clinical settings as well as in poor resource field settings. The fields of diagnostic medical parasitology, treatment, and vaccines are undergoing dramatic change. In recent years, there has been tremendous effort to focus research on the development of newer diagnostic methods focusing on serological, molecular, and proteomic approaches. This article examines the various diagnostic tools that are being used in clinical laboratories, optimized in reference laboratories, and employed in mass screening programs.

Rationale: Hepatitis E is an infectious disease due to inflammation of the liver caused by hepatitis E virus (HEV) and represents one of the most common causes of acute hepatitis and jaundice in the world. Although data of hepatitis E infection in patients with rheumatoid arthritis (RA) are accumulating, little is known on the course of HEV infection. We reported, for the 1st time, a case of patient with RA with hepatitis E that developed during leflunomide therapy in combination with low-dose steroids. Patient concerns: We present a 39-year-old woman, affected by RA and treated with leflunomide, reported diffuse itching and persistent fatigue laboratory data revealed elevated liver enzyme levels. Diagnosis: Positivity for anti-HEV IgM and IgG was observed. HEV-RNA of the genotype 3 was detected, indicating acute E hepatitis. Interventions and outcomes: Leflunomide was stopped and restarted 5 months after the initial diagnosis at the same dosage, with a close clinical and laboratory follow-up. The virus was eradicated from the serum without chronic transformation. The patient is alive and well 7 months after the initial diagnosis. Lessons: To our knowledge, this report is the 1st case of acute E hepatitis in a patient with RA developed during leflunomide therapy in combination with low-dose steroids. Moreover, geoepidemiology of infection is important, due to the fact that Abruzzo, a central region of Italy, has the highest HEV seroprevalence in general population, related to the zoonotic transmission of the infection from domestic and wild animals. Our case highlighted that immunosuppressive therapy, and in particular leflunomide, could be safely reintroduced after the resolution of the infection and the clearance of the virus. Further studies are needed to evaluate potential advantages in serologic testing for HEV infection as a part of the routine workup done to patients with rheumatic diseases and selected for immunosuppressive therapy.

SUMMARYEncephalitis generally results in a serious illness requiring hospitalization. The aim of this study was to describe the epidemiology of hospitalization for encephalitis in Italy, taking into account the geographical distribution, aetiology, seasonality and evolution of hospitalization rates over recent years. The mean hospitalization rate was 5·88/100 000. For most of these hospitalizations (n=13 119, 55·6%), no specific cause of encephalitis was reported. The most common aetiological category was ‘viral’, which accounted for 40·1% (n=4205) of such hospitalizations (rate 1·05/100 000). Within this category, herpes virus was the leading causative agent (n=1579, 0·39/100 000). This report highlights a significant increase of ‘viral encephalitis not otherwise specified’ (ICD-9 code 049·9)vs. a reduction of all other causes. A seasonal pattern was noted in people aged ⩾65 years in this group. Specific surveillance of encephalitis without known origin should be reinforced in order to identify the potential role of emerging pathogens and to design preventive interventions.

Background Schistosomiasis is the most important human helminth infection due to its impact on public health. The clinical manifestations are chronic and significantly decrease an individual’s quality of life. Infected individuals suffer from long-term organ pathologies including fibrosis which eventually leads to organ failure. The development of a vaccine against this parasitic disease would contribute to a long-lasting decrease in disease spectrum and transmission. Method Our group has chosen Schistosoma mansoni (Sm) cathepsin B, a peptidase involved in parasite feeding, as a prospective vaccine candidate. Our experimental formulation consisted of recombinant Sm-cathepsin B formulated in Montanide ISA 720 VG, a squalene based adjuvant containing a mannide mono-oleate emulsifier. Parasitological burden was assessed by determining adult worm, hepatic egg, and intestinal egg numbers in each mouse. Serum was used in ELISAs to evaluate production of antigen-specific antibodies, and isolated splenocytes were stimulated with the antigen for the analysis of cytokine secretion levels. Results The Sm-cathepsin B and Montanide formulation conferred protection against a challenge infection by significantly reducing all forms of parasitological burdens. Worm burden, hepatic egg burden and intestinal egg burden were decreased by 60 %, 62 %, and 56 %, respectively in immunized animals compared to controls (P = 0.0002, P

Schistosomiasis is a parasitic disease caused by helminths belonging to the Schistosoma genus. Approximately 700 million people are at risk of infection and 200 million people are currently infected. Schistosomiasis is the most important helminth infection, and treatment relies solely on the drug praziquantel. Worries of praziquantel resistance as well as high disease burden are only some of the justifications which support the development of a vaccine against schistosomiasis. To date, only 2 schistosome vaccines have made it into clinical trials: Sh28GST (Bilhvax) and Sm14. However, there are several vaccine candidates, such as TSP-2, sm-p8, and Sm-Cathepsin B, which are generating promising results in pre-clinical studies. Schistosomiasis vaccine development has been an uphill battle, and there are still several hurdles to overcome in the future. Fortunately, the research groups involved in the research for vaccine development have not abandoned their work. Furthermore, in the last few years, schistosomiasis has garnered some additional attention on a global scale due to its significant impact on public health.

Lubricant systems are fundamental in engines (automotive, aviation, rail etc.) and in any industrial system where surfaces of moving mechanical parts are in contact [1]. An improper lubrication due to oil degradation over a long period of time can lead to unwanted component failure and increased maintenance costs. Present study, unlike methods developed until now for detecting oil degradation (loss of mechanical, physical, chemical and optical properties) focuses on the development of a Surface Plasmon Resonance (SPR) transduction methodology able to measure lubricant degradation in real time observing the change in the refractive index. This approach answers to environmental regulation and user requirements on performance, lifetime expectancy and engine efficiency

In the yeast Saccharomyces cerevisiae, fermentation is the major pathway for energy production, even under aerobic conditions. However, when glucose becomes scarce, ethanol produced during fermentation is used as a carbon source, requiring a shift to respiration. This adaptation results in massive reprogramming of gene expression. Increased expression of genes for gluconeogenesis and the glyoxylate cycle is observed upon a shift to ethanol and, conversely, expression of some fermentation genes is reduced. The zinc cluster proteins Cat8, Sip4, and Rds2, as well as Adr1, have been shown to mediate this reprogramming of gene expression. In this study, we have characterized the gene YBR239C encoding a putative zinc cluster protein and it was named ERT1 (ethanol regulated transcription factor 1). ChIP-chip analysis showed that Ert1 binds to a limited number of targets in the presence of glucose. The strongest enrichment was observed at the promoter of PCK1 encoding an important gluconeogenic enzyme. With ethanol as the carbon source, enrichment was observed with many additional genes involved in gluconeogenesis and mitochondrial function. Use of lacZ reporters and quantitative RT-PCR analyses demonstrated that Ert1 regulates expression of its target genes in a manner that is highly redundant with other regulators of gluconeogenesis. Interestingly, in the presence of ethanol, Ert1 is a repressor of PDC1 encoding an important enzyme for fermentation. We also show that Ert1 binds directly to the PCK1 and PDC1 promoters. In summary, Ert1 is a novel factor involved in the regulation of gluconeogenesis as well as a key fermentation gene.

The aim of this study is to identify the use of cervical cancer screening and sociodemographic determinants associated with proper screening, overscreening, and underscreening in the Italian target population. Cross-sectional data from the national last available survey 'Health and use of health care in Italy,' conducted between December 2004 and September 2005, were analyzed. Multiple logistic regression was used to evaluate the risk factors associated independently with Pap test utilization. Our final sample included 36,161 women aged 25-64 years. Among women who reported having a Pap smear at least once, 20,920 (81.6%) repeated the Pap smear after the first one: 15,454 (74.3%) more than once every 3 years ('OVER' screening) and 2599 (12.4%) less than once every 3 years ('UNDER' screening). Among the independent risk factors associated with 'OVER' screening were higher social class [odds ratio (OR)=1.26, 95% confidence interval (CI) 1.15-1.39], being a former smoker (OR=1.16, 95% CI 1.05-1.28), and having had two or more pregnancies in the last 5 years (OR=1.43, 95% CI 1.20-1.70), whereas 'UNDER' screening was associated with the age group of 55-64 years (OR=2.11, 95% CI 1.76-2.53) and being divorced (OR=1.32, 95% CI 1.02-1.71). Improving Pap test compliance according to the proper timing is important for future reduction in cervical cancer mortality.

In the rapid change of drug scenarios, as the powerful development in the drug market, particularly in the number and the kind of the compound available, Internet plays a dominant role to become one of the major "drug market". The European Commission funded the Psychonaut Web Mapping Project (carried out in the time-frame January 2008-December 2009), with the aim to start/implement an Early Warning System (through the data/information collected from the Web virtual market), to identify and categorise novel recreational drugs/psychoactive compounds (synthetical/herbal drugs), and new trends in drug use to provide information for immediate and prevention intervention. The Psychonaut is a multi-site research project involving 8 research centres (De Sleutel, Belgium; University of Hertfordshire School of Pharmacy, St George's University of London, England; A-klinikkasäätiö, Finlandia; Klinik für Psychiatrie und Psychotherapie, Germany; Assessorato Salute Regione Marche, Italy; Drug Abuse Unit, Spain; Centre of Competence Bergen Clinics Foundation, Norway) based in 7 European Countries (England, Italy, Belgium, Finland, Germany, Spain, Norway).

We analyzed seasonal flu vaccination rates among the Italian population suffering from Chronic Obstructive Pulmonary Disease (COPD) in order to identify socio-demographic and clinical determinants for vaccination. We used data from the survey "Health and health care use in Italy", which interviewed 5,935 persons (age 15 - 102 years) suffering from COPD in the period 2004-2005. For each respondent, information on socioeconomic and health conditions, smoking status and patterns of health care utilization were retrieved. After bivariate analysis, we used two multilevel regression models to assess determinants of vaccination among the adult and the older Italian population. Overall 30.5% of adults (N=670) and 74.8% (N=2,796) of older people reported being vaccinated against seasonal flu. After controlling for potential confounders, older age increases the odds of vaccine uptake. Single marital status among the older people, smoking and not having contact with GPs in both age groups, are factors associated with non vaccination. Higher-educated elderly are less likely to be vaccinated, while coverage is higher among the wealthier adults. Vaccine coverage among adults with COPD in Italy remains low, especially among those with no comorbidities, and aged less than 44 years. It is only in older age that vaccination rates increase substantially. We found several risk factors for non vaccination, such as smoking, single marital status, and not having contacts with GPs, which should be considered in developing strategies to increase the coverage of influenza vaccine among people with COPD in Italy.

This work attempts to describe the peculiar kinetics that take place in template polymerization which proceeds according to the zip-mechanism. The unique situation of the molecules adsorbed on a template chain, which, with respect to the template propagation and termination reactions, are bound to react with the molecules that are positioned on their sides, is characterized. The definition of different species according both to their nature and to the nature of their neighbors leads to the construction of a kinetic model that, despite its analytical complexity, is characterized by a quite limited number of unknown kinetic constants. The model is developed by deriving the dynamic equations that describe the conversion versus time behavior all along the course of the reaction. The model predictions are compared with experimental data referring to the radical polymerization of sodium methacrylate (MAA · Na) in the presence of poly(allylamine) hydrochloride (PAAm · HCl). The good agreement confirms the validity of the model. Moreover, the model offers a significant contribution into understanding the peculiarities of template polymerization systems.