Naturally developed HPV16 antibodies and risk of newly detected cervical HPV infection outcomes.

Little is known about the protection conferred by antibodies from natural human papillomavirus (HPV) infection. Our objective was to evaluate the association between HPV16 seroreactivity and HPV16 redetection, newly detected HPV infections, and loss of HPV DNA detection during follow-up. We analyzed data from 2462 unvaccinated Brazilian women. HPV16 IgG and neutralizing antibodies at baseline were assessed by enzyme-linked immunosorbent assay (n = 1975) and by the pseudovirus-based papillomavirus neutralization assay (n = 487). HPV detection, genotyping, and viral load were assessed by PCR-based methods. The associations were analyzed by Cox proportional hazards models. We observed a positive association between HPV16 IgG seroreactivity and redetection of HPV16 infections. Age-adjusted hazard ratios (HR) with 95% confidence intervals (CI) ranged from 2.45 (1.04-5.74) to 5.10 (1.37-19.00). Positive associations were also observed between HPV16 IgG antibodies and (1) newly detected HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.32 [1.08-1.2]) and (2) loss of detection of HPV infections by genotypes unrelated to HPV16 (age-adjusted HR [95% CI] = 1.24 [1.03-1.50]). Naturally developed HPV16 antibodies do not prevent recurrent HPV infections. Overall HPV16 IgG and neutralizing antibodies seem to be serological markers for latent or past infections.

Filling the gap between risk assessment and molecular determinants of tumor onset.

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.

Development and evaluation of a new non-competitive Luminex immunoassay detecting antibodies against human papillomavirus types 6, 11, 16 and 18.

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.

Course of Metal Ions after a Revision of Malfunctioning Metal-on-Metal Total Hip Prostheses.

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.

Assessment of exposure to oak wood dust using gallic acid as a chemical marker.

OBJECTIVES: The American Conference of Governmental Industrial Hygienists (ACGIH) has classified oak dust as a human carcinogen (A1), based on increased sinus and nasal cancer rates among exposed workers. The aims of this study were to investigate the use of gallic acid (GA) as a chemical marker of occupational exposure to oak dusts, to develop a high-performance liquid chromatography-diode array detector method to quantify GA and to apply the method in the analysis of oak dust samples collected in several factories. METHODS: A high-performance liquid chromatography method was developed to detect GA in oak wood dust. The method was tested in the field, and GA was extracted from inhalable oak wood dust collected using the Institute of Occupational Medicine inhalable dust sampler in the air of five woodworking plants where only oak wood is used. RESULTS: A total of 57 samples with dust concentrations in the range of 0.27-11.14 mg/m(3) were collected. Five of these samples exceeded the Italian threshold limit value of 5 mg/m(3), and 30 samples exceeded the ACGIH TLV of 1 mg/m(3). The GA concentrations were in the range 0.02-4.18 µg/m(3). The total oak dust sampled was correlated with the GA content with a correlation coefficient (r) of 0.95. CONCLUSIONS: The GA in the tannic extracts of oak wood may be considered a good marker for this type of wood, and its concentration in wood dust sampled in the work environment is useful in assessing the true exposure to carcinogenic oak dust.

Three common pathways of nephrotoxicity induced by halogenated alkenes.

Glutathione-dependent bioactivation is a common pathway in nephrotoxicity caused by haloalkanes and haloalkenes. Glutathione conjugation forms the link between halogenated hydrocarbons, based on the formation of an episulfonium ion (vicinal halomethanes) or a cysteine conjugate (haloalkenes). Herein, we review the metabolic pathways underlying the nephrotoxic effects of the three well-known haloalkenes trichloroethylene, tetrachloroethylene, and hexachloro-1:3-butadiene to emphasize the role of cysteine-conjugate ß-lyase and the oxidative metabolism in renal toxicity. Activation by cysteine-conjugate ß-lyase is the best-characterized mechanism causing toxicity due to haloalkene treatment in experimental models. However, the severity of toxicity differs considerably, with S-(1,2,2-trichlorovinyl)-L-cysteine being more toxic than S-(1,2-dichlorovinyl)-L-cysteine, which is in turn more toxic than S-(1,2,3,4,4-pentachloro-1:3-butadienyl)-L-cysteine. Moreover, two oxidative pathways involving cysteine S-conjugates (mediated by flavin-containing monooxigenase 3) and N-acetyl-L-cysteine conjugates (mediated by cytochrome P-450 3A) form derived sulfoxides, which represent alternative metabolites with toxic effects. In vitro and in vivo studies showed that sulfoxide metabolites are more toxic than cysteine-conjugate derivates. The cytochrome P-450 3A family, on the other hand, is sex specific, and its expression has only been reported in adult male rats and rabbits. In summary, haloalkenes are highly nephrotoxic in vivo and in vitro and their toxicity mechanisms are well documented experimentally. However, little information is available on their toxicity in humans, except for the carcinogenic effects established for high exposure levels of trichloroethylene and tetrachloroethylene.

High-frequency hearing thresholds: effects of age, occupational ultrasound and noise exposure.

PURPOSE: It has been suggested that high-frequency audiometry (HFA) could represent a useful preventive measure in exposed workers. The aim was to investigate the effects of age, ultrasound and noise on high-frequency hearing thresholds. METHODS: We tested 24 industrial ultrasound-exposed subjects, 113 industrial noise-exposed subjects and 148 non-exposed subjects. Each subject was tested with both conventional-frequency (0.125-8 kHz) and high-frequency (9-18 kHz) audiometry. RESULTS: The hearing threshold at high frequency deteriorated as a function of age, especially in subjects more than 30 years old. The ultrasound-exposed subjects had significantly higher hearing thresholds than the non-exposed ones at the high frequencies, being greatest from 10 to 14 kHz. This hearing loss was already significantly evident in subjects with exposure <5 years and increased with years of exposure and advancing age. The noise exposure group had significantly higher hearing thresholds than the non-exposed group at the conventional frequencies 4 and 6 kHz and at the high frequency of 14 kHz. After stratification for age, there was a significant difference between the two groups at 9-10 and 14-15 kHz only for those under 30 years of age. CONCLUSION: Multivariate analysis indicated that age was the primary predictor, and noise and ultrasound exposure the secondary predictors of hearing thresholds in the high-frequency range. The results suggest that HFA could be useful in the early diagnosis of noise-induced hearing loss in younger groups of workers (under 30 years of age).

Determinants of baseline seroreactivity to human papillomavirus type 16 in the Ludwig-McGill cohort study.

BACKGROUND: Immunity plays an important role in controlling human papillomavirus (HPV) infection and associated lesions. Unlike infections caused by other viruses, natural HPV infection does not always result in a protective antibody response. Therefore, HPV antibodies are also considered markers of cumulative exposure. The aim of this study was to identify determinants of HPV16 seroreactivity at enrollment among women from the Ludwig-McGill cohort, a natural history study of HPV infection and risk of cervical neoplasia. METHODS: HPV16 serology was assessed by ELISA for L1 and L2 capsid antigens, while HPV typing and viral load measurements were performed by PCR-based methods. The associations were analyzed by unconditional logistic regression. RESULTS: Of 2049 subjects, 425 (20.7%) were strongly seropositive for HPV16. In multivariate analysis, seroreactivity was positively correlated with age, lifetime number of sexual partners, frequency of sex, and HPV16 viral load, and negatively associated with duration of smoking. CONCLUSIONS: HPV16 seroreactivity is determined by factors that reflect viral exposure.

Predictivity and fate of metal ion release from metal-on-metal total hip prostheses.

Blood metal ion levels in 72 patients with large head metal-on-metal hip arthroplasty were studied to determine the correlation between the values measured in whole blood and urine. Urinary cobalt and chromium levels of 30µg and 21µg, respectively, adjusted to creatinine were found to correspond to the 7µg/l cut-off value that has been accepted in whole blood. Cobalt and chromium levels in whole blood and urine both significantly correlated with increased acetabular component inclination angle over 50 degrees and pain scores. There was no correlation with socket anteversion angle or femoral head diameter. The data support the use of urinary measurement of metal ions adjusted to creatinine to monitor patients with large head metal-on-metal total hip arthroplasty.

The Impact of Smoking on Long-Term Protection Following Hepatitis B Vaccination: A 24-Year Cohort Study.

The hepatitis B vaccination-induced immune response has been demonstrated to be associated with a number of factors, including age, sex, BMI, and the presence of comorbidities. Additionally, modifiable determinants such as smoking have been identified as influencing the response to vaccination. However, despite the evidence that smokers are at an increased risk of not responding to vaccination, the long-term effects of smoking on antibody persistence remain poorly understood. This study aims to assess the impact of smoking habits on long-term immunity following the primary vaccination cycle. Participants were required to have received a standard three-dose vaccine schedule in childhood, without subsequent doses, and to be between 18 and 24 years of age. Data on age, sex, BMI, age of administration of the first vaccine dose, and time between doses were collected. An antibody concentration < 10 IU/L was considered as non-protective. A total of 2133 individuals were included, 14.2% of whom were smokers. The mean age was 20.28 ± 0.92 years. The probability of having a non-protective antibody concentration was significantly higher in smokers than in non-smokers (AOR: 1.287; 95% CI: 1.002-1.652). The detrimental effects of smoking extend beyond the immediate effects on the vaccine response, also impairing the long-term immune response in individuals who received vaccinations during childhood.

Do we protect ourselves against West Nile Virus? A systematic review on knowledge, attitudes, and practices and their determinants.

BACKGROUND: West Nile virus (WNV) is a mosquito-borne flavivirus. In humans, 80% of infections are asymptomatic, while approximately 20% experience influenza-like symptoms. Fewer than 1% develop the neuroinvasive form which can lead to encephalitis, meningitis, acute flaccid paralysis, and even death. The global spread of the virus to areas where it was not previously present has become a growing concern. Since the 2000 s, there have been numerous outbreaks affecting local and travelling populations worldwide. Given the lack of a vaccine, preventative measures are primarily focused on surveillance, vector control, and the use of personal protective behaviours (PPBs). The importance of PPBs is central to public health recommendations. However, translating these messages into coherent action by the public can prove challenging, as the uptake of such measures is inevitably influenced by socio-economic factors, awareness, knowledge, and risk perception. METHODS: A PRISMA-based systematic research was conducted on EMBASE, PubMed/MEDLINE, and Web of Science databases. PROSPERO registration number CRD42023459714. Quality of studies included in the final stage was evaluated using the Critical Appraisal Checklist for Cross-Sectional Study (CEBMa). RESULTS: 2963 articles were screened, and 17 studies were included in the final round. Out of these, six were deemed of high quality, ten were of medium quality, and one was of low quality. In almost all studies considered, both awareness and knowledge of WNV transmission were above 90%, while concern about WNV ranged from 50% to 80%. Concern about the safety of repellents, either with or without DEET, ranged from 27% to 70%. The percentage of people actually using repellents ranged from 30% to 75%, with the lowest usage reported among individuals over 60 years old (29%) and pregnant women (33%), and the highest among students aged 9-11 (75%). Concern for West Nile Virus (WNV) was consistently linked to an increase in taking preventative measures, including the use of repellents, by two to four times across studies. The school-based intervention was effective in increasing the practice of removing standing water (AOR=4.6; 2.7-8.0) and wearing long clothing (AOR=2.4; 95%CI: 1.3-4.3), but did not have a significant impact on the use of repellents. CONCLUSIONS: The present systematic review provides an overview of the knowledge, attitudes, and practices (KAP) of WNV and their determinants. While concern about West Nile Virus (WNV) and its effects can be a significant motivator, it is important to promote evidence-based personal protective behaviours (PPBs) to counter unwarranted fears. For example, the use of repellents among the most vulnerable age groups. Given the geographical expansion of WNV, it is necessary to target the entire population preventively, including those who are difficult to reach and areas not yet endemic. The findings of this investigation could have significant implications for public health and support well-informed and effective communication strategies and interventions.

Human papillomavirus type 16 viral load measurement as a predictor of infection clearance.

Viral load measurements may predict whether human papillomavirus (HPV) type 16 infections may become persistent and eventually lead to cervical lesions. Today, multiple PCR methods exist to estimate viral load. We tested three protocols to investigate viral load as a predictor of HPV clearance. We measured viral load in 418 HPV16-positive cervical smears from 224 women participating in the Ludwig-McGill Cohort Study by low-stringency PCR (LS-PCR) using consensus L1 primers targeting over 40 known HPV types, and quantitative real-time PCR (qRT-PCR) targeting the HPV16 E6 and L1 genes. HPV16 clearance was determined by MY09/11 and PGMY PCR testing on repeated smears collected over 5 years. Correlation between viral load measurements by qRT-PCR (E6 versus L1) was excellent (Spearman's rank correlation, ρ = 0.88), but decreased for L1 qRT-PCR versus LS-PCR (ρ = 0.61). Viral load by LS-PCR was higher for HPV16 and related types independently of other concurrent HPV infections. Median duration of infection was longer for smears with high copy number by all three PCR protocols (log rank P<0.05). Viral load is inversely related to HPV16 clearance independently of concurrent HPV infections and PCR protocol.

Cervical human papillomavirus detection is not affected by menstrual phase.

OBJECTIVES: In many settings, human papillomavirus (HPV) DNA testing already plays an important role in cervical cancer screening. It is unclear whether hormonal fluctuations associated with menstrual phase or oral contraceptive (OC) use have any effect on HPV detection. We evaluated the effects of OC use and timing of cervical sampling in relation to women's last menstrual period (LMP) on HPV detection, and viral load in the Brazilian Ludwig-McGill cohort study. METHODS: Women in the cohort were followed every 4-6 months, and at each clinic visit they were asked to complete a questionnaire and to provide a cervical sample for HPV testing. Specimens from 6093 patient visits (n=2209 women) were categorised according to date of LMP into four distinct phases: follicular (days 5-9), midcycle (days 10-15), luteal (days 16-22), or late luteal (days 23-31). RESULTS: Compared with follicular phase (referent group), HPV detection did not differ according to reported LMP for midcycle (OR=1.14, 95% CI 0.95 to 1.37), luteal (OR=1.03, 95% CI 0.85 to 1.25), or late luteal menstrual phase (OR=1.01, 95% CI 0.83 to 1.24), and was also not influenced by OC use. Analyses restricted to high-risk HPV types (grouped) and HPVs 16 and 18 (separately), produced similar non-significant associations. For HPV-positive samples, we found that the menstrual phase did not influence the total viral load. CONCLUSIONS: These results indicate HPV detection is not associated with menstrual phase. Our findings suggest that standardising the timing of specimen collection for HPV testing is not necessary.

Hyaline droplet accumulation in kidney of rats treated with hexachloro-1:3-butadiene: influence of age, dose and time-course.

The present research investigates the occurrence of hyaline droplet (HD) accumulation related to age, dose and time after treatment in male Wistar rats given a single i.p. injection of hexachloro-1:3-butadiene (HCBD). In the study on age, rats from 1 to 12 months of age were treated with 100 mg kg(-1) body weight (b.w.) HCBD dose. Rats treated at 2 months of age showed a greater accumulation of HD than the other age groups; HD accumulation was not observed in 1-month-old rats. In the dose-response study, the treatment with 25, 50 and 100 mg kg(-1) b.w. at 2 months of age caused HD accumulation in the proximal convoluted tubule at all doses, with the 100 mg kg(-1) b.w. group slightly more affected. Finally, in the time-course study, rats treated with a 100 mg kg(-1) b.w. dose at 2 months of age and sacrificed at 6, 12, 24, 48, 72 and 96 h post-dosing showed a time-related HD accumulation in terms of incidence and severity, after 6 h, with a peak at 24 and 48 h and decreasing at 72 and 96 h. The present results show that HD accumulation is an early finding, and is unrelated to dose level and particularly evident in rats of 2 month of age. These findings in male rats treated with HCBD emphasize the importance of considering the age of rats at the start of a study. The more sensitive model was used in the detection of nephrotoxic effects of chemicals.

Emergency Department Syndromic Surveillance to Monitor Tick-Borne Diseases: A 6-Year Small-Area Analysis in Northeastern Italy.

Tick-borne diseases (TBD) are endemic in Europe. However, surveillance is currently incomplete. Alternative strategies need to be considered. The aim of this study was to test an Emergency Department Syndromic Surveillance (EDSyS) system as a complementary data source to describe the impact of tick bites and TBD using a small-area analysis approach and to monitor the risk of TBD to target prevention. ED databases in the Local Health Authority 8 District (Veneto, Italy) were queried for tick-bite and TBD-related visits between January 2017 and December 2022. Hospitalisations were also collected. Events involving the resident population were used to calculate incidence rates. A total of 4187 ED visits for tick-bite and 143 for TBD were recorded; in addition, 62 TBD-related hospitalisations (of which 72.6% in over 50 s and 22.6% in over 65 s). ED visits peaked in spring and in autumn, followed by a 4-week lag in the increase in hospital admissions. The small-area analysis identified two areas at higher risk of bites and TBD. The use of a EDSyS system allowed two natural foci to be identified. This approach proved useful in predicting temporal and geographic risk of TBD and in identifying local endemic areas, thus enabling an effective multidisciplinary prevention strategy.

Comparison of Adverse Effects of Two SARS-CoV-2 Vaccines Administered in Workers of the University of Padova.

Introduction: In Italy, on December 2020, workers in the education sector were identified as a priority population to be vaccinated against COVID-19. The first authorised vaccines were the Pfizer-BioNTech mRNA (BNT162b2) and the Oxford-AstraZeneca adenovirus vectored (ChAdOx1 nCoV-19) vaccines. Aim: To investigate the adverse effects of two SARS-CoV-2 vaccines in a real-life preventive setting at the University of Padova. Methods: Vaccination was offered to 10116 people. Vaccinated workers were asked to voluntarily report symptoms via online questionnaires sent to them 3 weeks after the first and the second shot. Results: 7482 subjects adhered to the vaccination campaign and 6681 subjects were vaccinated with ChAdOx1 nCoV-19 vaccine and 137 (fragile subjects) with the BNT162b2 vaccine. The response rate for both questionnaires was high (i.e., >75%). After the first shot, the ChAdOx1 nCoV-19 vaccine caused more fatigue (p < 0.001), headache (p < 0.001), myalgia (p < 0.001), tingles (p = 0.046), fever (p < 0.001), chills (p < 0.001), and insomnia (p = 0.016) than the BNT162b2 vaccine. After the second dose of the BNT162b2 vaccine, more myalgia (p = 0.033), tingles (p = 0.022), and shivers (p < 0.001) than the ChAdOx1 nCoV-19 vaccine were elicited. The side effects were nearly always transient. Severe adverse effects were rare and mostly reported after the first dose of the ChAdOx1 nCoV-19 vaccine. They were dyspnoea (2.3%), blurred vision (2.1%), urticaria (1.3%), and angioedema (0.4%). Conclusions: The adverse effects of both vaccines were transient and, overall, mild in severity.

Factors influencing long-term persistence of anti-HBs after hepatitis B vaccination.

Long-term immunity after HBV vaccination is still debated. When assessing immune persistence, several variables must be considered, the clear definition of which is crucial. Our aim was to assess protection 10-20 years after primary vaccination and to estimate the effect of age at first dose, sex and time elapsed between doses on long-term protection. We conducted a retrospective cohort study between January 2004 and December 2020. Antibody titres above 10 IU/L were considered protective. Geometric mean titres (GMT) were calculated. The effect of the above variables on long-term protection was assessed by logistic regression analysis. Included participants were 9459. Among those vaccinated during infancy, GMT gradually increased from 11 IU/L (first dose in 1st trimester of life) to 68 IU/L (4th trimester), while the proportion of individuals <10 IU/L remained stable between 1st and 2nd trimester (51%) and it decreased substantially in 3rd (28%) and even more so in the 4th (18%). A one-month delay in first and third dose administration was correlated with a -16% (AOR: 0.84; 95% CI: 0.78-0.91) and a -11% (AOR: 0.89; 95% CI: 0.85-0.94) risk of a titre <10 IU/L, respectively, ~20 years after immunisation. In contrast, similar changes do not comparably affect vaccination in adolescence. The start of vaccination at the third month of age is a compromise between the development of acceptable immunogenicity and the need to protect the infant as early as possible. However, the chance of slightly delaying the vaccine administration within the first year of life may be considered given the impact on long-term persistence of anti-HBs.

Body Mass Index and Antibody Persistence after Measles, Mumps, Rubella and Hepatitis B Vaccinations.

Overweight and obesity may cause a reduced response to vaccination. The purpose of the present research was to study the relationship between current body mass index (BMI) and antibody persistence after vaccination against measles, mumps, and rubella (MMR) and hepatitis B virus (HBV) given during childhood, as per the current vaccination schedule. The study was conducted on 2185 students at the School of Medicine, University of Padua, Italy. The mean age of the participants was 20.3 years. After adjusting for sex, age at first dose of vaccine administered, age at last dose, and age at study enrollment, no significant association was found between lack of serologic protection and BMI for either the HBV vaccine or each component of the MMR vaccine. For the first time, the absence of this relationship was demonstrated for the MMR vaccine. Given the evidence currently available, further research on BMI and vaccines in general remains desirable.

Gold(III)-dithiocarbamato anticancer agents: activity, toxicology and histopathological studies in rodents.

Gold(III)-dithiocarbamato complexes have recently gained increasing attention as potential anticancer agents because of their strong tumor cell growth--inhibitory effects, generally achieved by exploiting non-cisplatin-like mechanisms of action. The rationale of our research work is to combine the antitumor properties of the gold(III) metal center with the potential chemoprotective function of coordinated dithiocarbamates in order to reduce toxic side effects (in particular nephrotoxicity) induced by clinically established platinum-based drugs. In this context, [Au(III) Br(2) (ESDT)] (AUL12) was proved to exert promising and outstanding antitumor activity in vitro and to overcome both acquired and intrinsic resistance showed by some types of tumors toward cisplatin. As a subsequent extension of our previous work, we here report on detailed in vivo studies in rodents, including antitumor activity toward three transplantable murine tumor models, toxicity, nephrotoxicity and histopathological investigations. Remarkably, the gold(III) complex AUL12 stands out for higher anticancer activity than cisplatin toward all the murine tumor models examined, inducing up to 80% inhibition of tumor growth. In addition, it shows low acute toxicity levels (lethal dose, LD(50) = 30 mg kg(-1) ) and reduced nephrotoxicity. Altogether, these results confirm the reliability of our drug design strategy and support the validation of this gold(III)-dithiocarbamato derivative as a suitable candidate for clinical trials.

Rubella Serosurvey Among Future Healthcare Workers.

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.