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Mumps is a vaccine-preventable infectious disease diffuse worldwide. The implementation of mumps vaccination reduced largely the spread of infection. On 11,327 Medical School students the prevalence of mumps positive antibodies was evaluated according to dose/doses of vaccine, year of birth and sex. Compliance to mumps vaccine was low in students born before 1990 but increased consistently after this year, above all compliance to two doses, due to the implementation of the vaccine offer. Positivity of mumps antibodies is significantly (p &lt, 0.0001) lower in students vaccinated once (71.2%) compared to those vaccinated twice (85.4%). In addition, students born after 1995, largely vaccinated twice, showed a seropositivity near to 90%. Further, females had a significantly (p &lt, 0.0001) higher proportion of positive antibodies after vaccination than males, both one (74.6% vs. 64.7%) and two doses (86.8% vs. 82.9%). Finally, seropositivity after two vaccine doses remains high (86.1%) even 15 years after the second dose. In conclusion, the research highlighted that vaccination against mumps reaches a good level of coverage only after two doses of vaccine persisting at high levels over 15 years and induces a more significant response in females.

In 2017 in Italy, a number of vaccinations became mandatory or started to be recommended and offered free of charge. In this study, we aimed at assessing the coverage rates for those vaccinations in the pre-mandatory era among students at the School of Medicine of Padua University studying the degree course in medicine and surgery (future physicians) on the basis of the vaccination certificates presented during health surveillance. The vaccinations considered were those against pertussis, rubella, mumps, measles, varicella, Haemophilus influenzae type b (which became mandatory in 2017), pneumococcus, meningococcus C and meningococcus B (only suggested and offered for free since 2017). The study enrolled 4706 students of medicine and surgery. High vaccine uptake was observed, especially in younger students (born after 1990), with vaccines against pertussis, rubella, mumps and measles. Good completion for Haemophilus influenzae type b and meningococcus C was also observed. Very low coverage rates (all under 10%) for vaccination against varicella, pneumococcus and meningococcus B were observed. In conclusion, uptake for some non-mandatory vaccines was below the recommended threshold, although younger generations showed a higher uptake, possibly as a results of policy implemented at the national level. Our findings support the idea to consider health surveillance visits also as an additional opportunity to overcome confidence and convenience barriers and offer vaccine administration.

This work is focused on the synthesis, characterization, and preliminary biological evaluation of bio-conjugated Au-III and Cu-II complexes with the aim of overcoming the well-known side effects of chemotherapy by improving the selective accumulation of an anticancer metal payload in malignant cells. For this purpose, carbohydrates were chosen as targeting agents, exploiting the Warburg effect that accounts for the overexpression of glucose-transporter proteins (in particular GLUTs) in the phospholipid bilayer of most neoplastic cells. We linked the dithiocarbamato moiety to the C1 position of three different monosaccharides: d-glucose, d-galactose, and d-mannose. Altogether, six complexes with a 1:2 metal-to-ligand stoichiometry were synthesized and in vitro tested as anticancer agents. One of them showed high cytotoxic activity toward the HCT116 colorectal human carcinoma cell line, paving the way to future in vivo studies aimed at evaluating the role of carbohydrates in the selective delivery of whole molecules into cancerous cells.

Before the introduction of universal vaccination, hepatitis B caused high morbidity and mortality, especially among healthcare workers. In the present study, the immune status against hepatitis B was assessed in a cohort of 11,188 students of the degree courses of the School of Medicine of the University of Padua (Italy) who had been subjected to mandatory vaccination in childhood or adolescence and who will be future healthcare workers. The variables that influence the antibody response to vaccination are mainly the age at which the vaccine was administered and sex. If vaccination was administered before one year of age, there is a high probability (around 50%) of having an antibody titer lower than 10 IU/L compared to those vaccinated after one year of age (12.8%). The time between vaccine and analysis is not decisive. Furthermore, female sex, but only if vaccination was administered after one year of age, shows a significant (p = 0.0008) lower percentage of anti-HBs below 10 IU/L and a greater antibody titer (p &lt, 0.0001). In conclusion, the differences related to the age of vaccination induce more doubts than answers. The only plausible hypothesis, in addition to the different immune responses (innate and adaptive), is the type of vaccine. This is not easy to verify because vaccination certificates rarely report it.

Serum antibody levels can be used to measure the humoral immune response against human papillomaviruses (HPV). We developed and validated a rapid, technically simple and relatively inexpensive multiplex non-competitive Luminex-based immunoassay (ncLIA) to measure total IgG antibody levels against four HPV types. For the assay’s solid phase, virus-like particles (VLPs) of HPV6, 11, 16 and 18 were bound to heparin-coated beads. HPV serum antibody levels binding to the VLPs were quantified using a phycoerithrin-conjugated secondary polyclonal donkey anti-human IgG antibody. Standardization and validation of the ncLIA were performed using 96 paired serum and genital samples from participants in the HITCH cohort study, including young women (aged 18–24 years) and their male sexual partners (aged 18+) in Montreal, Canada. Results from the ncLIA were compared to a validated Luminex immunoassay from PPD laboratories using Pearson’s correlation coefficients, receiver operating characteristic curves and logistic regression. Our assay had good inter- and intra-assay variability. The correlation of serum antibody levels between the ncLIA and validation assay was highest for HPV16 and HPV11 (r=0.90), followed by HPV6 (r=0.86) and HPV18 (r=0.67). The ncLIA was better able to predict HPV DNA positivity in genital samples than the validation assay for HPV16 [area under the curve (AUC) 0.65 versus 0.52, P=0.001] and HPV18 [AUC 0.71 versus 0.57, P=0.024]. AUCs for HPV6 and HPV11 were similar between the two assays (0.70 versus 0.71, P=0.59, and 0.88 versus 0.96, P=0.08, respectively). The developed ncLIA is useful for measuring total IgG antibody response following natural infection or vaccination against four HPV VLPs included in the quadrivalent vaccine.

Measles is a very contagious infectious disease, and vaccination is the only medical aid to counter the spread of the infection. The aim of this study was to evaluate the influence of vaccination schedule and type of vaccine, number of doses, and sex on the immune response. In a population of Italian medical students (8497 individuals born after 1980 with certificate of vaccination and quantitative measurement of antibodies against measles), the prevalence of positive antibodies to measles and antibody titer was measured. Vaccination schedule such as number of doses and vaccine type (measles alone or combined as measles, mumps and rubella (MMR)) and sex were the variables considered to influence the immune response. The vaccination schedule depends on the year of birth: students born before 1990 were prevalently vaccinated once and with measles vaccine alone (not as MMR). One dose of vaccine induces a significantly (p &lt, 0.0001) higher positive response and antibody titer than two doses, in particular when measles alone is used (p &lt, 0.0001). Females have a significantly higher percentage of positive response (p = 0.0001) than males but only when the MMR formulation was used. Multiple linear regression confirms that sex significantly influences antibody titer when only MMR is used, after one (p = 0.0002) or two (p = 0.0060) doses. In conclusion, vaccination schedule and, partially, sex influence immune response to measles vaccination. Most notably, the measles vaccine alone (one dose) is more effective than one and two doses of MMR.

The burden of hepatitis B virus (HBV) infection is a serious public health problem all over the world. Vaccination remains the most effective prevention measure, and safe and effective HBV vaccines have been available since 1982. Health care workers (HCWs) vaccinated against HBV and prospectively followed up for at least 14 years were classified by their antibody titers after primary vaccination as: poor responders (10–99 mIU/mL), moderate responders (100–999 mIU/mL), and good responders (≥1000 mIU/mL). The incidence of antibody loss was calculated for 1000 person-years and the anti-HBs persistence was calculated. The analysis concerned 539 HCWs: 494 good responders (91.7%), 37 moderate responders (6.9%), and eight poor responders (1.5%). The incidence of anti-HBs loss was 52.1 per 1000 person-years for the poor responders, 11.3 per 1000 person-years for the moderate responders, and 1.4 per 1000 person-years for the good responders. The mean persistence of anti-HBs differed significantly between the three groups, being: 19.2 years (95% CI: 15.6–22.8), 25.4 years (95% CI: 23.0–27.9), and 31.0 years (95% CI: 30.5–31.5) for the poor, moderate and good responders, respectively. In conclusion, our findings demonstrate a good persistence of protective anti-HBs titers in HCWs exposed to occupational risk for up to 30 years after a primary vaccination cycle (even without a booster dose) if their titer was initially higher than 100 mIU/mL.

Simple Summary Neurofibromatosis type 1 is a genetic disease that predisposes to tumors of the nervous system, primarily the neurofibroma. Plexiform neurofibromas (Pnfs) are of the greatest concern because of location, size, and frequent progression to malignancy. Although research is making great progress, the lack of in-depth understanding of the molecular mechanisms driving neoplastic progression results in the absence of prognostic indicators and therapeutic targets. We document that cell–cell cooperativity and the dynamics of the extracellular matrix play important roles in the growth and transformation of Pnf cells, directly through the cooperation of RAS and focal adhesion kinase (FAK) signaling. In turn, we found that treatment of Pnf cells with both MEK and FAK inhibitors is effective in abolishing the transforming ability of these cells. Abstract Plexiform neurofibromas (Pnfs) are benign peripheral nerve sheath tumors that are major features of the human genetic syndrome, neurofibromatosis type 1 (NF1). Pnfs are derived from Schwann cells (SCs) undergoing loss of heterozygosity (LOH) at the NF1 locus in an NF1+/− milieu and thus are variably lacking in the key Ras-controlling protein, neurofibromin (Nfn). As these SCs are embedded in a dense desmoplastic milieu of stromal cells and abnormal extracellular matrix (ECM), cell–cell cooperativity (CCC) and the molecular microenvironment play essential roles in Pnf progression towards a malignant peripheral nerve sheath tumor (MPNST). The complexity of Pnf biology makes treatment challenging. The only approved drug, the MEK inhibitor Selumetinib, displays a variable and partial therapeutic response. Here, we explored ECM contributions to the growth of cells lacking Nfn. In a 3D in vitro culture, NF1 loss sensitizes cells to signals from a Pnf-mimicking ECM through focal adhesion kinase (FAK) hyperactivation. This hyperactivation correlated with phosphorylation of the downstream effectors, Src, ERK, and AKT, and with colony formation. Expression of the GAP-related domain of Nfn only partially decreased activation of this signaling pathway and only slowed down 3D colony growth of cells lacking Nfn. However, combinatorial treatment with both the FAK inhibitor Defactinib (VS-6063) and Selumetinib (AZD6244) fully suppressed colony growth. These observations pave the way for a new combined therapeutic strategy simultaneously interfering with both intracellular signals and the interplay between the various tumor cells and the ECM.

The standard theoretical descriptions of the dynamics of open quantum systems rely on the assumption that the correlations with the environment can be neglected at some reference (initial) time. While being reasonable in specific instances, such as when the coupling between the system and the environment is weak or when the interaction starts at a distinguished time, the use of initially uncorrelated states is questionable if one wants to deal with general models, taking into account the mutual influence that the open-system and environmental evolutions perform on each other. Here, we introduce a perturbative method that can be applied to any microscopic modeling of the system-environment interaction, including fully general initial correlations. Extending the standard technique based on projection operators that single out the relevant part of the global dynamics, we define a family of projections adapted to a convenient decomposition of the initial state, which involves a convex mixture of product operators with proper environmental states. This leads us to characterize the open-system dynamics via an uncoupled system of differential equations, which are homogeneous and whose number is limited by the dimensionality of the open system, for any kind of initial correlations. Our method is further illustrated by means of two cases study, for which it reproduces the expected dynamical behavior in the long-time regime more consistently than the standard projection technique., Comment: 17+2 pages, 8 figures; v2: close to the published version

Objective: Rubella is a very diffusive but relatively benign infectious disease unless contracted during pregnancy, when it causes congenital rubella syndrome. The aim of this research was to determine the prevalence and titer of antirubella antibodies in a population of future healthcare workers (students at the school of medicine).Methods: The cohort consisted of 11,022 students who underwent antibody analysis after the presentation of a vaccine certificate.Results: Vaccination compliance was very high, particularly in younger students (born after 1995), reaching almost 100% (at least one dose). Unvaccinated students born before 1990 had high seropositivity (>95%), but this percentage dropped to zero among the youngest students. Variables affecting antibody titer included year of birth and sex. Considering only vaccinated students, a greater antibody response was observed if the vaccine was administered between 8 and 10 years of age. Female sex was associated with more significant (p < 0.0001) positivity and higher antibody titer after one and two doses. However, this difference appeared less consistent in relation to year of birth.Conclusions: The studied population exhibited excellent vaccination compliance, high seropositivity, and high antibody titer. Vaccine and immune coverage were higher than what is deemed necessary to achieve herd immunity.

The present research evaluated the course of cobalt and chromium in the blood and urine after the revision of metal-on-metal with a ceramic-on-polyethylene total hip arthroplasty. Seven patients were enrolled for hip prosthesis revision owing to ascertained damage of the implant. Metals in the blood and urine were evaluated before and after the hip revision. The double measurement before the total hip revision revealed high levels of metal ions (on average, 88.1 µg/L of cobalt in the blood, 399.0 µg/g of creatinine cobalt in the urine, 46.8 µg/L of chromium in the blood, and 129.6 µg/g of creatinine chromium in the urine at the first measurements), with an increasing trend between the first and second dosage. Within a week after the hip revision, the levels of metal ions significantly decreased by approximately half. Four to six months after the operation, the cobalt levels were found near to the reference values, whereas the chromium levels reached 25% of the values measured before the revision. The revision of malfunctioning metal-on-metal implants produced a dramatic decrease of metal ions in biological fluids, although it did not completely rescue the chromium level.

Background Switching antiretroviral regimens when human immunodeficiency virus (HIV) viremia is controlled for a new regimen is challenging when there is the potential for prior nucleoside reverse-transcriptase inhibitor (NRTI) resistance. The objective was to study virologic outcomes after switching to dolutegravir compared with remaining on a boosted protease inhibitor (protease inhibitor/ritonavir [PI/r]) regimen in people with HIV (PWH) with prior documented virologic failure and/or exposure to mono/dual NRTIs. Methods We used the Quebec HIV Cohort including 10 219 PWH whose data were collected at 4 sites in Montreal, Canada. We included all PWH with documented virologic failure or exposure to mono/dual NRTI therapy who were virologically suppressed on a PI/r-based regimen for at least 6 months on or after January 1, 2014 (n = 532). A marginal structural Cox model analysis was used to estimate the effect of the switch to dolutegravir on virologic outcome compared with remaining on PI/r. The outcome was defined as 2 consecutive viral loads (VLs) >50 copies/mL or 1 VL >50 copies/mL if it occurred at the last VL available. Results Among 532 eligible participants, 216 (40.6%) had their regimen switched to dolutegravir with 2 NRTIs, whereas 316 (59.4%) remained on the PI/r with 2 NRTIs. The weighted hazard ratio for the effect of dolutegravir switch on virologic failure compared with patients whose regimen remained on PI/r was 0.57 (95% confidence interval, 0.21–1.52). Conclusions We did not find evidence of an increased risk for virologic failure after switching to dolutegravir from PI/r among patients with previous virologic failure or prior exposure to mono/dual NRTI., Therapeutic switches to dolutegravir with 2 NRTIs provide a safe option for patients with a viremia suppressive antiretroviral regimen in the presence of prior documented virologic failure and prior exposure to mono/dual NRTI therapy.

In the past two decades, a ponderous epidemiological literature has causally linked tumor onset to environmental exposure to carcinogens. As consequence, risk assessment studies have been carried out with the aim to identify both predictive models of estimating cancer risks within exposed populations and establishing rules for minimizing hazard when handling carcinogenic compounds. The central assumption of these works is that neoplastic transformation is directly related to the mutational burden of the cell without providing further mechanistic clues to explain increased cancer onset after carcinogen exposure. Nevertheless, in the last few years, a growing number of studies have implemented the traditional models of cancer etiology, proposing that neoplastic transformation is a complex process in which several parameters and crosstalk between tumor and microenvironmental cells must be taken into account and integrated with mutagenesis. In this conceptual framework, the current strategies of risk assessment that are solely based on the ‘mutator model’ require an urgent update and revision to keep pace with advances in our understanding of cancer biology. We will approach this topic revising the most recent theories on the biological mechanisms involved in tumor formation in order to envision a roadmap leading to a future regulatory framework for a new, protective policy of risk assessment.

The adverse effects associated with exposure to flour dust have been known since the 1700s. The aim of the study was to assess the occupational exposure to flour dust in Italian facilities, identify the activities characterized by the highest exposure, and provide information to reduce workers&rsquo, exposure. The study was performed in different facilities such as flourmills (n = 2), confectioneries (n = 2), bakeries (n = 24), and pizzerias (n = 2). Inhalable flour dust was assessed by personal and area samplings (n = 250) using IOM (Institute of Occupational Medicine) samplers. The results showed personal occupational exposure to flour dust over the American Conference of Governmental Industrial Hygiene (ACGIH) and the Scientific Committee on Occupational Exposure Limit (SCOEL) occupational limits (mean 1.987 mg/m3, range 0.093&ndash, 14.055 mg/m3). The levels were significantly higher for dough makers in comparison to the dough formers and packaging area subjects. In four bakeries the industrial hygiene surveys were re-performed after some control measures, such as installation of a sleeve to the end of pipeline, a lid on the mixer tub or local exhaust ventilation system, were installed. The exposure levels were significantly lower than those measured before the introduction of control measures. The exposure level reduction was observed not only in the dough making area but also in all bakeries locals.

The aim of this study was to evaluate the levels of As, Be, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V, and Zn, by inductively coupled plasma-mass spectrometry (ICP-MS) in the urine of two groups of patients with two different types of metal-on-metal (MoM) total hip prostheses (ASR DePuy&reg, group A, 25 patients, total Met-Met System Lima&reg, group B, 28 patients). The determination of metals reflected a steady-state release (group A: 9 years after surgery and group B: 6 years after surgery). The results obtained confirmed the increase of Co and Cr urinary levels in both group when compared with the reference values for the general population adopted by the Italian Society of Reference Values (SIVR). In particular, Co and Cr levels exceeded the threshold values in urine, respectively, of 30 &mu, g and 21 &micro, g, adjusted to creatinine based on the threshold in whole blood of 7 &mu, g/L proposed by the Medicines and Healthcare Products Regulatory Agency (MHRA). Regarding the other investigated metals, significantly higher values were found in Group A than in Group B. These differences could be due to the type of hip prosthesis implanted, the longer period of time since the implantation, as well as many other factors such as diet, age, drug consumption, physical activity, or presence of dental fillings. The continuous monitoring over the years of metal concentrations in patients carrying a prosthesis could be useful to better identify the sources of these metals.

Hepatitis B virus (HBV) infection is one of the major infectious hazards for health-care workers (HCWs) because of the frequency of percutaneous exposures to blood or body fluids. For this reason, all HCWs should be vaccinated, including students in medicine and health professional degree programs. The aim of this study was to assess the immune coverage to anti-HBV vaccine and long-lasting protective titres of anti-HBs antibodies in female and male students to evaluate gender-related differences in response to HBV vaccination. Data relative to anti-HBs antibody titre, sex, age, and age at vaccination were collected and analyzed from 5291 Italian students (1812 males and 3479 females) of the graduate courses at the School of Medicine, who underwent the mandatory health surveillance of workers exposed to biological risk. The results indicated that gender affects the immune response to HBV vaccine, particularly evident in the case of females vaccinated after one year of age who exhibited a statistically significant (p = 0.0023) 1.21-fold increase in median antibody titre with respect to males. Our findings could contribute to the optimization of HBV vaccination schedules in health surveillance of HCWs.

Non-occupational lead poisoning is not rare, mainly occurring in domestic situations in children, but also in adults. Lead poisoning was observed in a 65 years-old woman non-exposed to risk that caught our attention with a diagnostic suspicion of acute intermittent porphyria according to recurrent episodes of abdominal pain and neuropathy of upper limbs. Acute intermittent porphyria was excluded by a laboratory investigation that showed instead severe lead poisoning. After several thorough examinations of the domestic environment, the source of intoxication has been detected in some cooking pots that released high concentrations of lead. Ethylenediamine tetracetic acid disodium calcium therapy (three cycles) reduced consistently blood lead concentration and, after one year, neuropathy was almost entirely recovered.

Total hip arthroplasty (THA) with metal-on-metal (MoM) bearings have shown problems of biocompatibility linked to metal ion release at the local level causing an adverse reaction to metal debris (ARMD) and at a systemic level. The aim of this study was to evaluate clinical and radiological outcomes, and metal ion concentrations in the blood and urine of patients who underwent THA with the LIMA Met-Met hip system. Patients with ceramic-on-ceramic (CoC) bearings were included as a control group. In this study, 68 patients were enrolled: 34 with MoM THAs and 34 with CoC THAs. Patients were evaluated clinically (Harris Hip Score, SF-36) and radiologically at a median of 7.4 years after surgery. Whole blood and urinary cobalt and chromium levels were also assessed. Both types of implants were comparable in terms of clinical and functional results. Ion levels were significantly higher in the MoM group compared with CoC group 7 years after surgery. No correlations were found between metal ion levels and patient demographics, functional and radiological outcomes, and prosthesis features. Patient monitoring is thus advised to establish if prosthesis revision is necessary, especially in the case of MoM THA.

The purpose of the study is to evaluate the urinary levels of free 2,5-hexanedione (2,5-HD) in Italian subjects non-occupationally exposed to n-hexane, in order to define background values in non-occupational settings. The study was carried out on 99 subjects of the general population. The analysis of free 2,5-HD was performed by gas chromatography-mass spectrometry. Personal information about the subjects was ascertained by means of a self-administered questionnaire. The urinary levels of free 2,5-HD were in the range of &lt, 12.0&ndash, 77.9 &micro, g/L (5th&ndash, 95th percentiles). The urinary excretion of the metabolite did not seem to be influenced by gender, age, smoking habit or area of residence. Statistically significant differences (p = 0.03) were found between the free 2,5-HD urinary levels according to the vehicular traffic intensity within the area of residence and to body mass index of subjects. The background levels of free 2,5-HD found in this study could contribute to the definition of reference values of general population non-occupationally exposed and could be useful to the toxicologists and industrial hygienists to determine whether workers have been exposed to higher levels of n-hexane than the general population.

Porphyrias are a group of diseases that are clinically and genetically heterogeneous and originate mostly from inherited dysfunctions of specific enzymes involved in heme biosynthesis. Such dysfunctions result in the excessive production and excretion of the intermediates of the heme biosynthesis pathway in the blood, urine, or feces, and these intermediates are responsible for specific clinical presentations. Porphyrias continue to be underdiagnosed, although laboratory diagnosis based on the measurement of metabolites could be utilized to support clinical suspicion in all symptomatic patients. Moreover, the measurement of enzymatic activities along with a molecular analysis may confirm the diagnosis and are, therefore, crucial for identifying pre-symptomatic carriers. The present review provides an overview of the laboratory assays used most commonly for establishing the diagnosis of porphyria. This would assist the clinicians in prescribing appropriate diagnostic testing and interpreting the testing results.

SUMMARYThe aim of the present research is to verify the immune status against tetanus in students and workers exposed to risk and to ascertain whether a decennial booster is necessary. Antibodies against tetanus were measured in 1433 workers and students of Padua University (Italy). The enrolment criterion was the ability to provide a booklet of vaccinations released by a public health office. The influence of age, gender, the number of vaccine doses, and the interval since the last dose was determined. Ten years after the last dose, the majority of subjects (95·0%) displayed an antibody titre above the protective level (⩾0·10 IU/ml), and half of these (49·1%) had a long-term protective level (⩾1·0 IU/ml). According to our data, titre depends on both the number of vaccine doses and the interval since the last dose (P< 0·0001). Five vaccine doses and an interval of at least 10 years since the last dose are predictive of a long-term protective titre in absence of a booster (1·97 IU/ml). These data suggest that when primary series are completed, a decennial booster is unnecessary for up to 20 years. Furthermore, we recommend measuring the antibody level before a new booster is given to prevent problems related to over-immunisation.

Since the discovery of cisplatin in the 1960s, other metal complexes have been investigated as potential antitumor agents to overcome the side-effects associated with the administration of the Pt-based drug. In line with our previous research, in this work we report the synthesis and characterization of mono- and dinuclear Ru(III) complexes with the pyrrolidinedithiocarbamate (PDT) ligand and the more sterically-hindered carbazole-dithiocarbamato ligand (CDT), to compare their properties (both at the chemical and antiproliferative level), in an attempt to assess a structure-activity rationale. Moreover, to overcome the scarce solubility under physiological conditions of the Ru(III)-dithiocarbamato compounds, the biocompatible copolymer Pluronic® F127 has been used, to encapsulate the metal derivatives in water-soluble micellar carriers. Finally, preliminary biological evaluations on CDT and PDT compounds along with their nanoformulations, open intriguing perspectives in anticancer chemotherapy. In particular, comparing the structure of the Ru(III) derivatives, the ionic dinuclear PDT complex shows an important cytotoxic action in comparison to its neutral counterparts. Moreover, the micellar carrier improves the overall activity of the encapsulated Ru(III)-PDT chemotherapeutics. On the other hand, the nanoformulation of the CDT derivatives allows us to solubilize both the 1:3 and the 2:5 complexes and to state their inactivity.

Background: There is a paucity of data on the dynamics of human papillomavirus (HPV) antibodies in children. We aimed to describe the vertical transmission and clearance of antibodies against HPV6, 11, 16 and 18 in children.Methods: We used data from pregnant women recruited into the HERITAGE cohort study between 2009 and 2012 who were positive for HPV-DNA at baseline. Dried blood spots were collected during the first trimester in pregnant participants, and at birth, 6, 12, and 24 months of age in children. The level of total immunoglobulin G (IgG) against HPV6, 11, 16 and 18 were measured using Luminex immunoassays. Spearman's coefficients were used to correlate HPV antibody levels between newborns and mothers. Panel and Kaplan-Meier graphics described antibody dynamics in the first 24 months of life.Findings: Antibodies from newborns and mothers (n = 58 pairs) were moderately to highly correlated with coefficients of 0·81 (95% confidence intervals (CI):0·70–0·88), 0·68 (95% CI:0·5–0·80), 0·90 (95% CI:0·83–0·94) and 0·85 (95% CI:0·76–0·91) against HPV6, 11, 16 and 18, respectively. In newborns seropositive at birth, anti-HPV antibodies were cleared by 80% and 100% at 12 and 24 months, respectively. Only two children presented detectable HPV antibodies at 24 months. The first child had no detectable antibodies at birth and the second presented increasing levels after two undetected measures.Interpretation: Correlation between mother and newborn IgG antibodies against HPV suggests vertical transfer. Most children cleared anti-HPV antibodies within six to 12 months.Funding: The Canadian Institutes of Health Research (CIHR) Keywords: Human papillomavirus, Serology, Mother-newborn correlation, Vertically acquired immunity, Antibody clearance, Antibody dynamics

This work is focused on the synthesis, characterization, and preliminary biological evaluation of bio-conjugated Au

A group of 142 bakers was studied in order to investigate the relationship between higher/lower respiratory signs/symptoms and inflammation biomarkers and occupational exposure to flour dust. A complete upper and lower respiratory tract evaluation was performed. Seven percent of bakers complained of lower respiratory symptoms, while 22% of them complained of upper respiratory symptoms. Fifty five percent of the bakers were allergic, and 37.1% showed sensitization to occupational allergens. Abnormal spirometries were found in 15% of bakers, while fractional exhaled nitric oxide (FeNO) was above the normal reference in 24.5% of them. Moreover, 23.8% of bakers were found to be hyposmic. Population mean peak nasal inspiratory flow (PNIF) was in the normal range even if almost all the workers suffered from neutrophilic rhinitis at nasal cytology with the number of nasal neutrophils increasing with the increase of the duration of exposure to flour dust (p = 0.03). PNIF and FEV1 (forced expiratory volume in the 1st second) showed a positive correlation (p = 0.03, r = 0.19). The Tiffeneau index decreased with the increase of dust (p = 0.017). A similar result was obtained once we divided our population into smokers and non-smokers (p = 0.021). Long-term exposure to bakery dusts can lead to a status of minimal nasal inflammation and allergy.

Healthcare workers are a population exposed to several infectious diseases, and an immunization programme is essential for the maintenance of good vaccination coverage to protect workers and patients. A population of 10,653 students attending degree courses at Padua Medical School (medicine and surgery, dentistry and health professions) was screened for vaccination coverage and antibody titres against rubella, mumps, and measles. The students were subdivided into five age classes according to their date of birth: those born before 1980, between 1980 and 1985, between 1986 and 1990, between 1991 and 1995, and after 1995. Vaccination coverage was very low in students born before 1980, but the rate of positive antibody titre was high due to infection in infancy. Increasing date of birth showed increased vaccination coverage. In contrast, immune coverage was high for rubella (more than 90%) but not for mumps and measles (approximately 80%). An &ldquo, anomaly&rdquo, was observed for mumps and measles in the cohort born between 1991 and 1995, probably due to the trivalent vaccine formulation. Students born after 1990 showed vaccination coverage that exceeded 90%. It is therefore very likely that we will have a future generation of healthcare workers with optimal vaccination coverage.

Health care workers (HCWs) are prone to a heavy psycho-physical workload. Health promotion programs can help prevent the onset of chronic and work-related diseases. The aim of the STI-VI &lsquo, before-and-after&rsquo, study, with assessments scheduled at 6 and 12 months, was to improve the lifestyle of HCWs with at least one cardiovascular risk factor. A tailored motivational counseling intervention, focusing on dietary habits and physical activity (PA) was administered to 167 HCWs (53 males, 114 females). BMI, waist circumference, blood pressure, and cholesterol, triglyceride, and blood glucose levels were measured before and after the intervention. The 6-month results (total sample and by gender) showed a marked effect on lifestyle: PA improved (+121.2 MET, p = 0.01), and diets became more similar to the Mediterranean model (+0.8, p &lt, 0.001). BMI dropped (&minus, 0.2, p &lt, 0.03), and waist circumference improved even more (&minus, 2.5 cm, p &lt, 0.001). Other variables improved significantly: total and LDL cholesterol (&minus, 12.8 and &minus, 9.4 mg/dL, p &lt, 0.001), systolic and diastolic blood pressure (&minus, 4.4 and &minus, 2.5 mmHg, p &lt, blood glucose (&minus, 1.5 mg/dL, p = 0.05), and triglycerides (significant only in women), (&minus, 8.7 mg/dL, p = 0.008), but HDL cholesterol levels dropped too. If consolidated at 12 months, these results indicate that our intervention can help HCWs maintain a healthy lifestyle and work ability.

In this paper, we focused on the analysis of the effects mediated by different cyclic dithiocarbamic ligands (DTC) on three classes of antiproliferative coordination compounds, namely, Ru(III) complexes with the general formulae [Ru(DTC)3] and [Ru2(DTC)5]Cl, and the neutral Cu(II) derivatives of the type [Cu(DTC)2]. In particular, we present the synthesis and characterization of a library of total 23 coordination compounds containing Ru(III) or Cu(II) as the biologically-active metal center and two or more dithiocarbamato (DTC) ligands derived from cyclic amines (aliphatic or aromatic). Several techniques including elemental analysis, X-ray crystallography, ESI-MS, 1H-NMR spectroscopy, FT-IR and UV-Vis spectrophotometry were used to characterize the compounds, which highlighted the different electronic behaviors generated by the substituents within the DTC moiety. Moreover, the synthesized compounds were tested for their stability in order to investigate their antiproliferative activity against 3 human cancer cell lines, namely, HeLa, HepG2 and HepG2/SB3. In particular, HepG2/SB3 was chosen for its aggressiveness due to upregulation of the anti-apoptotic protein SerpinB3. Finally, the most promising compounds are studied in terms of log P. Overall, the results reveal the drug-likeness of some of the derivatives of copper(II) and ruthenium(III).

All buses were tested over the bus Route 7 through the city of Brighton & Hove which is an important central corridor for public transport in the east and west directions and has the characteristics of inclination, traffic congestion and road junctions where road-side air quality measurements show elevated levels of NOx and NO2. The outward journey is about 9 km and contains both uphill and downhill driving, but is net downhill. The return journey follows a highly similar 9 km route and is net uphill. The route altitude varies from sea-level up to 60 m with several sharp inclines and declines, operation on flat terrain is minimal, Figure 2. Open image in new window FIGURE 2 Route 7 — Altitude versus distance on route outbound (to Marina) and inbound (to depot) journeys (© Ricardo) The busses were driven around the route in a manner that was considered to be representative of normal service, including specified dwell times at each bus stop and a fixed break period between the outbound journey and the return. Each bus drove Route 7 three times with the same driver and the Euro IV bus was driven on two further runs, each by an additional driver with a different characteristic style. In order to replicate the true duty cycle, all buses were loaded with ballast equal to 70 % of the maximum passenger loading. For safety reasons the truck undertook a slightly modified route to avoid tight corners, and made fewer halts. Truck tests were conducted with an empty trailer and with a trailer loaded with 20 t of concrete ballast. Data were continuously acquired and careful extraction of the data permitted the emissions within specific geographic zones to be evaluated within the resolution of the GPS, against traffic control measures, the air quality monitoring stations and bus stops. In agreement with the Brighton & Hove Bus and Coach Company, it was analysed the emissions profiles from Route 7 in both directions and in particular from North Street which is a congested 420 m road restricted to buses, taxis and occasional delivery truck. It is in the centre of Brighton, frequented by many pedestrians, with an average slope of 3 % and an air quality monitoring station situated close to the roadside.

Alle Omnibusse wurden entlang der Linie 7 durch Brighton and Hove getestet. Diese Linie ist eine wichtige zentrale Ost-West-Verkehrsachse, charakterisiert durch Steigungen, dichten Verkehr und Kreuzungen, an denen Messungen der Luftqualitat haufig erhohte Werte von NOx und NO2 ergeben. Die Hinfahrt ist etwa 9 km lang und enthalt Steigungen und Gefallestrecken. Die Meereshohe variiert von 0 bis 60 m mit verschieden steilen Steigungen, Gefallen und minimalen ebenen Strecken, Bild 2. Open image in new window BILD 2 Linie 7 — Meereshohe versus Strecke Hinweg (zur Marina) und Ruckweg (zum Betriebshof) (© Ricardo) Die Busse wurden so gefahren, dass es reprasentativ fur den Alltagseinsatz war. Dies betraf Aufenthalte an den Haltestellen und die Dauer einer Pause am Ende der Hinfahrt vor dem Antritt des Ruckwegs. Die Route wurde mit allen Bussen vom gleichen Fahrer dreimal befahren. Der Euro-IV-Bus wurde bei zwei zusatzlichen Fahrten von anderen Fahrern gesteuert. Alle Busse wurden mittels Ballast auf 70 % der maximalen Passagierlast ausgelastet, um eine realistische Versuchsdurchfuhrung zu gewahrleisten. Aus Grunden der Sicherheit wurde die Strecke fur den Lkw geringfugig angepasst, enge Kurven vermieden und weniger Haltepunkte definiert. Die Testfahrten des Lkws wurden mit leerem Anhanger und mit 20 t Betonballast durchgefuhrt. Die Daten wurden kontinuierlich aufgenommen und eine sorgfaltige Aufarbeitung ermoglichte eine geografische Auswertung der Emissionen anhand der GPS-Daten bezuglich Verkehrsleitungsmasnahmen, Messstationen fur Luftqualitat und Haltestellen. In Zusammenarbeit mit Brighton and Hove wurden die Emissionsprofile der Linie 7 in beiden Richtungen ausgewertet. Besondere Aufmerksamkeit wurde dabei einem stets uberlasteten Abschnitt der North Street im Zentrum von Brighton gewidmet, der Bussen, Taxis und Lieferverkehr vorbehalten ist und stets von vielen Fusgangern genutzt wird. Dieser weist eine Steigung von 3 % auf und ist mit einer direkt am Strasenrand gelegenen Luftmessstation ausgestattet.

Aims: The goal of the present study was to establish the efficacy of the measles vaccine and the validity of the vaccination schedule adopted in Italy. Materials & methods: The following procedures are adopted: analyze the compliance to the vaccination schedule; assess the seroprevalence of measles antibodies according to the year of birth and the number of doses; and investigate the persistence of positive antibodies post-vaccination. We gathered and elaborated data of both vaccination history and seroprevalence against measles in a large population of students (4195) belonging to the Medical School of Padua University (Italy). Results: Our results reveal a requirement for a two-dose vaccination schedule to ensure protection from the disease. Nevertheless, these results clearly indicate that the percentage of seropositivity reached using the two-dose strategy is below the percentage (95%) that ensures optimal population immunity. Conclusion: It is uncertain whether immune coverage persists when circulating antibodies vanish, but two vaccine doses should prevent disease outbreaks.

This randomized, blinded study evaluated the immunogenicity and safety of a booster dose of Gardasil (qHPV) or Cervarix (bHPV) when administered to 12–13 year-old girls who were vaccinated at the age of 9–10 with 2 doses of qHPV (0–6 months). 366 out of 416 eligible girls participated in this follow-up study. Antibody titers were measured just before and one month post-booster. A Luminex Total IgG assay was used for antibody assessment and results are presented in Liminex Units (LU). Three years post-primary vaccination, 99–100% of subjects had detectable antibodies to 4HPV genotypes included in the qHPV with GMTs varying from 50 to 322 LU depending on genotype. After a booster dose of qHPV, a ≥4 fold increase of antibody titers to genotypes included in the vaccine was observed in 88–98% of subjects. Post-booster GMTs varied from 1666 to 4536 LU depending on genotype. These GMTs were 1.1 to 1.8-fold higher when compared to those observed one month post-second dose. After a booster of bHPV, a ≥4 fold increase of antibody titers to HPV16 and HPV18 was observed in 93–99% of subjects. The anti-HPV16 and HPV18 GMTs were 5458 and 2665 LU, respectively. These GMTs were 1.2 and 1.8 higher than those observed in the qHPV group (both P < 0.01). In bHPV group a 1.4–1.6-fold increase of antibody GMTs to HPV6 and HPV11was also observed (P < 0.001). The safety profile was acceptable for both vaccines. Both qHPV and bHPV increase antibody titers when given as a booster to girls previously vaccinated with 2 doses of qHPV. The magnitude of the immune response after booster is vaccine-dependent and has the same pattern as that reported after primary vaccination with qHPV or bHPV. When given as a booster, both vaccines have an acceptable safety profile. Longer follow-up studies are warranted to assess the need of booster doses.