The clinical outcomes of vital intact teeth close to large cystic lesions of endodontic origin: A prospective clinical study.

AIM: To evaluate the indication of the endodontic treatment for vital intact teeth with the root apex involved in large radicular cystic lesions of endodontic origin. METHODOLOGY: This prospective cohort study enrolled healthy participants with radicular cysts of endodontic origin and with the root apex of vital intact teeth involved in the bone defect, as determined by cone beam computed tomography (CBCT). Thirty-two sound vital teeth were analysed by thermal (TPT) and electric pulp tests (EPT) before surgery (T0) and 1 week (T1), 2 weeks (T2), 3 months (T3) and 6 months (T4) post-surgery. Student's t-test (p < .05) was used to compare the EPT values at baseline and T4. anova (p < .05) was used to analyse the EPT variations for all maxillary and mandibular teeth. McNemar test (p < .05) was used to compare the results according to variation in EPT values gathering by variation, no variation and no response. RESULTS: At T1, 75 and 65.7% of teeth responded positively whilst 25 and 34.3% did not respond to EPT and TPT, respectively. The variation of the EPT values between T0 and T1 was observed for 50.0% of teeth, whilst no variation was noticed in 25.0% of teeth. At T4, 90.6 and 87.5% of teeth responded positively whilst 9.4 and 12.5% did not respond to EPT and TPT, respectively. At T4, variation of the EPT values between T0 and T4 was observed for 28.1%, whilst no variation was noticed in 62.5% of teeth. There were no statistical differences in EPT results between T0 and T4 (p > .05), but significant differences were observed for EPT values between T1 and T4 (p < .05), and between mandibular and maxillary teeth. The pulp sensibility of maxillary teeth worsened after surgery, before reverting progressively to T0 values, whilst no statistically significant differences were observed for mandibular teeth at the different time points. CONCLUSIONS: These data support the inconsistence of the prophylactic endodontic treatment in healthy vital teeth with apex involvement in large cystic lesions of endodontic origin. Post-surgery follow-up with TPT and EPT is recommended to assess pulp status.

The Italian fund for Alzheimer's and other dementias: strategies and objectives to face the dementia challenge.

The Italian Fund for Alzheimer's and other dementias was approved and signed in December 2021. The Fund is financed with 15 million euros in three years. The main goal is to provide new strategies in the field of dementia with a Public Health perspective. The Fund includes eight main activities that will be monitored and supervised by the Italian National Institute of Health: 1) development of a guideline for the assessment, management and support for people with dementia and their families/carers; 2) updating of the Dementia National Plan (DNP); 3) implementation of the documents of the DNP; 4) conducting surveys dedicated to the Italian Dementia Services; 5) promotion of dementia prevention strategies; 6) training strategies for healthcare professionals, families and caregivers; 7) creation of a National Electronic Record for Dementia; 8) evaluation and monitoring of activities promoted by Regions and Autonomous Provinces in the field of dementia, together with the dementia National Permanent Table. These activities are outlined in detail in the present paper.

Endodontic Treatment of a Molar with Peculiar Anatomy: Case Study with CBCT and 3D Printed Model.

AIM: The aim of the study was to achieve the endodontic treatment of a second maxillary molar with abnormal anatomy through cone-beam computed tomography (CBCT) analysis and three-dimensional (3D) printing. BACKGROUND: A patient arrived referring recurrent abscesses, spontaneous pain, and the difficulty to eat properly; a diagnosis of tooth necrosis was made. The periapical X-ray showed an abnormal anatomy of the tooth. CASE DESCRIPTION: The preoperative analysis of the tooth morphology was performed through CBCT analysis. The 3D scans were reconstructed through a dedicated software application (Mimics) to visualize the abnormal anatomy and detect the root canal morphology. Moreover, a 3D printed model was created to plan the clinical stage. Canal shaping was achieved with ProGlider and ProTaper Next techniques, and the root canal filling was performed with a carrier-based technique. CONCLUSION: The limits of this case were the low definition of the CBCT owned by the patient and the difficulties during the scouting of the canals due to the abnormal endodontic space complicated by narrow and flat canals. The software reconstruction allowed a 3D high-definition preclinical analysis of the tooth anatomy. CLINICAL SIGNIFICANCE: Both digital analysis and printed models based on CBCT scans seemed fundamental to preclinically understand the abnormal endodontic anatomy.

Complications in thyroid surgery. Harmonic Scalpel, Harmonic Focus versus Conventional Hemostasis: A meta-analysis.

BACKGROUND: To evaluate the incidence of postoperative complications, hemostatic effects and safety of Total Thyroidectomy (TT) performed using the Harmonic Scalpel (HS), the Harmonic Focus (HF) or Conventional Hemostasis (CH). METHODS: The meta-analysis was performed according to PRISMA guidelines. A literature search was conducted from 2003 to 2014 and stringent criteria were required for inclusion. Thirteen studies concerning an overall population of 1458 compared HS versus CH, whilst 8 studies with 1667 patients compared HF versus CH. RESULTS: There was a significant reduction of operative time (Mean Difference [MD] = -25.49 min.; 95% CI -32.43 to -18.55), intraoperative blood loss (MD = -30.49 mL; 95% CI -53.01 to -7.97), postoperative drainage volume (MD = -12.90 mL; 95% CI -22.83 to -2.98) and postoperative pain (MD = -0.87; 95% CI -1.27 to -0.46) in patients underwent TT with HS. Regarding HF group, a significant reduction of operative time (MD = -25.99 min., 95% CI -34.56 to -17.41), length of hospital stay (MD = -0.57; 95% CI -0.97 to -0.17), transient hypocalcemia (OR = 0.56; 95% CI 0.39 to 0.81) and postoperative pain (MD = -1.33 days; 95% CI -2.49 to -0.17) resulted. CONCLUSIONS: HS TT can be a safe, useful and fast alternative to conventional TT. The newer HF can reduce the rate of hypocalcemia. Future RCTs of larger patient cohorts with more detailed data of postoperative complications, cost-effectiveness and cosmetic results, randomization procedures, intention-to-treat analyses and blinding of outcome assessors are needed to draw more meaningful conclusions.

The impact of level of education on adherence to breast and cervical cancer screening: Evidence from a systematic review and meta-analysis.

OBJECTIVE: To assess the inequalities in adherence to breast and cervical cancer screening according to educational level. METHODS: A systematic review was carried out between 2000 and 2013 by querying an electronic database using specific keywords. Studies published in English reporting an estimation of the association between level of education and adherence to breast and/or cervical cancer screening were included in the study. Two different meta-analyses were carried out for adherence to breast and cervical cancer screening, respectively: women with the highest level of education and women with the lowest level of education were compared. The level of heterogeneity was investigated and subgroup analyses were carried out. RESULTS: Of 1231 identified articles, 10 cross-sectional studies were included in the analysis. The meta-analyses showed that women with the highest level of education were more likely to have both screenings with an overall OR=1.61 (95% CI 1.36-1.91; I(2)=71%) for mammography and OR=1.96 (95% CI 1.79-2.16; I(2)=0%) for Pap test, respectively. Stratified meta-analysis for breast cancer screening included only studies that reported guidelines with target age of population ≥50 years and showed a reduction in the level of heterogeneity and an increase of 36% in the adherence (95% CI 1.19-1.55; I(2)=0%). CONCLUSIONS: This study confirms and reinforces evidence of inequalities in breast and cervical cancer screening adherence according to educational level.

Micro-Computed Tomography Evaluation of ProTaper Next and BioRace Shaping Outcomes in Maxillary First Molar Curved Canals.

INTRODUCTION: The aim of this micro-computed tomography study was to describe the shaping properties of ProGlider/ProTaper Next (PG/PTN) and ScoutRace/BioRace (SR/BR) nickel-titanium rotary systems. METHODS: Thirty maxillary first permanent molars were selected. Mesiobuccal canals were randomly assigned (n = 15) to PG/PTN or SR/BR groups. Irrigation was performed with 5% NaOCl and 10% EDTA. Specimens were scanned (voxel size, 9.1 µm) for matching volumes and surface areas and post-treatment analyses. Root canal centering ability, canal geometry enlargement, and thickness of dentinal wall at inner curvature were assessed at apical level and point of maximum curvature. Results were analyzed with 4 one-way analyses of variance. RESULTS: Canal centering ability was superior in PG/PTN (P = .006 at apical level, P = .025 at point of maximum curvature). PG/PTN demonstrated a more conservative increase of canal areas (P = .027 at apical level, P = .038 at point of maximum curvature). Centrifugal increase in canal diameters did not significantly differ between groups (P = .65 at apical level, P = .61 at point of maximum curvature). Inner dentinal wall thickness was less reduced with PG/PTN compared with SR/BR, with no statistical differences (P = .23 at point of maximum curvature, P = .89 at apical level). PG/PTN shaping taper ranged between 6% and 7%. CONCLUSIONS: Neither system produced significant shaping errors in curved canals. PG/PTN system showed better preservation of canal anatomy. PTN offset section did not influence final preparation taper.

Molecular dynamics study of the recognition of dimethylated CpG sites by MBD1 protein.

The cell is able to regulate which genes to express via chemical marks on the DNA and on the histone proteins. In all vertebrates, the modification on the DNA is methylation at position 5 of the two cytosines present in the dinucleotide sequence CpG. The information encoded by these chemical marks on the DNA is processed by a family of protein factors containing a conserved methyl-CpG binding domain (MBD). Essential to their function, the MBD proteins are able to bind DNA containing dimethylated CpG sites, whereas binding to unmethylated sites is not observed. In this paper, we perform molecular dynamics simulations to investigate the mechanism by which the mCpG binding domain of MBD1 is able to bind specifically dimethylated CpG sites. We find that the binding affinity of MBD1 to a DNA containing dimethylated CpG site is stronger by 26.4 kJ/mol relative to binding the same DNA but with an unmethylated CpG site. The contribution of each of the methyl groups to the change in free energy is very similar and additive. Therefore, this binding affinity (to a dimethylated DNA) is halved when considered relative to binding a hemimethylated DNA, a result that is also supported by experimental observations. Despite their equal contributions, the two methyl groups are recognized differently by MBD1. In one case, demethylation induces conformational changes in which the hydrophobic patch formed by the conserved residues Val20, Arg22, and Tyr34 moves away from the (methyl)cytosine, weakening the DNA-protein interactions. This is accompanied by an intrusion of a bulk water into the binding site at the protein-DNA interface. As a consequence, there is a reduction and rearrangements of the protein-DNA hydrogen bonds including a loss of a crucial hydrogen bond between Tyr34 and the (methyl)cytosine. The methylcytosine on the opposite strand is recognized by conformational changes of the surrounding conserved hydrophobic residues, Arg44 and Ser45, in which Arg44 participate in the 5mC-Arg-G triad. More specifically, the hydrogens of the methyl group form weak hydrogen bonds with the guanidino group and backbone carbonyl of the conserved Arg44, interactions that are absent when the cytosine is unmethylated. The results presented in this paper contribute to our knowledge of the different ways the chemical mark on the DNA is recognized by the epigenetic machinery.

Breast cancer risk associated with the diagnosis of a microhistological radial scar (RS): retrospective analysis in 10 years of experience.

PURPOSE: To retrospectively assess the risk of breast cancer associated with the radial scar (RS) microhistological diagnosis, also taking into consideration the percutaneous biopsy devices used, as well as the different performances of the mammographic systems (analogical, digital and tomosynthesis) in the radiological diagnosis of RS. MATERIALS AND METHODS: Between March 2002 and November 2011, 80 RSs were identified using the analogical, digital and tomosynthesis mammographic systems. Based on the microhistological examination, the patients were divided into three groups [RS without hyperplasic-proliferative lesions (HPL); RS with HPL; RS with cancer] and we assessed the risk of cancer associated with RS in the first and second group. We evaluated the mammographic features and the BI-RADS categories assigned to RSs, the biopsy devices used and the differences between the pathological examination and the microhistological diagnosis (p < 0.05). RESULTS: Based on the microhistological examination, 51/80 patients were included in the first group (9 of them not subjected to surgery), 25/80 in the second group and 4/80 in the third one. At the final histological examination, there were 7/42 (16.7%) cancers in the first group and 8/25 (32%) in the second group. The largest number of microhistological underestimation occurred in the patients who were subjected to core biopsy (15 cases) (p < 0.05). Tomosynthesis improved (p < 0.05) the identification of the RS. CONCLUSIONS: 22.3% of the RSs was associated with cancer. Given that at microhistological examination 16.7% of the RS without HPL was cancer at pathology, the surgical excision is preferred. Tomosynthesis was useful to detect parenchymal distortions.

Radiological assessment of breast density by visual classification (BI-RADS) compared to automated volumetric digital software (Quantra): implications for clinical practice.

OBJECTIVE: This study was done to assess breast density on digital mammography and digital breast tomosynthesis according to the visual Breast Imaging Reporting and Data System (BI-RADS) classification, to compare visual assessment with Quantra software for automated density measurement, and to establish the role of the software in clinical practice. MATERIALS AND METHODS: We analysed 200 digital mammograms performed in 2D and 3D modality, 100 of which positive for breast cancer and 100 negative. Radiological density was assessed with the BI-RADS classification; a Quantra density cut-off value was sought on the 2D images only to discriminate between BI-RADS categories 1-2 and BI-RADS 3-4. Breast density was correlated with age, use of hormone therapy, and increased risk of disease. RESULTS: The agreement between the 2D and 3D assessments of BI-RADS density was high (K 0.96). A cut-off value of 21% is that which allows us to best discriminate between BI-RADS categories 1-2 and 3-4. Breast density was negatively correlated to age (r = -0.44) and positively to use of hormone therapy (p = 0.0004). Quantra density was higher in breasts with cancer than in healthy breasts. CONCLUSIONS: There is no clear difference between the visual assessments of density on 2D and 3D images. Use of the automated system requires the adoption of a cut-off value (set at 21%) to effectively discriminate BI-RADS 1-2 and 3-4, and could be useful in clinical practice.

Dual base-flipping of cytosines in a CpG dinucleotide sequence.

Simultaneous flipped-out conformation of two neighboring bases on opposite strands of DNAs has been observed in several X-ray structures. It has also been detected for two cytosines on opposite strands in different contexts of CpG sites. In this paper, we study by MD simulations the dual base flipping of the two cytosines in hemi-methylated CpG site. We calculate the potential of mean force of flipping-out the unmethylated cytosine in three model systems. The first is for DNA bound to the regulatory protein UHRF1. In this case, the methyl-cytosine on the complementary strand is flipped-out into the binding pocket of the SRA domain of the protein. The other two systems are for unbound DNAs in which the methyl-cytosine is either intra-helical or extra-helical. We find that when the methyl-cytosine is flipped-out it is easier to flip-out the other (unmethylated) cytosine on the opposite strand by about 14-16kJ/mol. This lower penalty for dual-base flipping is observed for both the bound and unbound states of the DNA. Analyses of the hydrogen bond network and stacking interactions within the CpG site indicate that the lower penalty is due to stabilization of the dual-base flipped-out conformation via interactions involving the orphan guanines. The results presented in this paper suggest that the extra-helical conformation of the methyl-cytosine recognized by UHRF1 can facilitate the base-flipping process of the target cytosine to be methylated by Dnmt1.

The impact of regional co-payment and national reimbursement criteria on statins use in Italy: an interrupted time-series analysis.

BACKGROUND: Statins are among the most commonly prescribed drugs worldwide in the prevention of cardiovascular diseases and their effectiveness is largely acknowledged. The consumption of statins increased four-fold during the 2000-2010 decade in Italy and national and regional control policies were developed. Restrictions to reimbursement were fixed at the national level, whereas co-payment was introduced in some, but not all, regions. The aim of the present study is to assess the impact of such policies on the consumption of statins in Italy between 2001-2007 among outpatients. METHODS: The statin use was measured in terms of defined daily doses per 1,000 inhabitants per day (DDD/1000 inh. day) from May 2001 to December 2007. The study was conducted in 17 out of 21 regions, nine of which had implemented a co-payment policy. Time trends in consumption before and after the introduction of co-payment policies and reimbursement criteria were examined using segmented regression analysis of interrupted time-series, adjusting for seasonal components. RESULTS: The consumption of statins increased by 22.9 DDD/1000 inh. day in May 2001 to 54.7 DDD/1000 inh. day in December 2007. On average, there was a 1.7% increase in statin use each month before the national guideline changed while the increase was about 0.5% afterwards. The revision of the reimbursement criteria was associated with a significant decrease in level (coefficient = -2.80, 95% CI -3.70 to -1.90 p-value <0.001) and trend (coefficient = -0.33, 95% CI -0.37 to -0.29 p-value <0.001). The introduction of co-payment was associated with a significant change in trend of consumption so that the overall use of the drug increased by 0.04 (95% CI 0.02 to 0.07, p-value < 0.001) DDD/1000 inh. day per month in the post-intervention period, but there was no evidence of a change in level of consumption (p-value = 0.163). CONCLUSIONS: Consumption of statins in Italy increased almost three-fold during the study period. The restriction to reimbursement Interventions was associated with an immediate drop and a decrease in trend of statin use, while the regional copayment was associated with a small increase in trend of statin use.

Base-flipping propensities of unmethylated, hemimethylated, and fully methylated CpG sites.

Methylation of C5 of cytosines at CpG dinucleotide sites of the DNA is one of the most important factors regulating the expression of genes. The interactions of these CpG sites with proteins are essential for recognition and catalysis and in many cases are characterized by the flipping of either of the cytosine bases out of the DNA helix. In this paper, we present results from molecular dynamics simulations indicating that methylation of CpG sites suppresses spontaneous extra-helical conformations of either of the two cytosines. Thus, cytosines in unmethylated sites flip out easier than in hemimethylated sites and the latter flip out easier than in fully methylated sites. The different propensities for base flipping is observed not only between the cytosines that differ in their methylation states but also between the cytosines on the complementary strand. From alchemical mutation calculations, we find that methylation of one of the cytosines increases the free energy of the extra-helical conformation by 10.3-16.5 kJ/mol and this increase is additive with respect to the second methylation. Potential of mean force calculations confirm these results and reveal that cytosines in unmethylated sites favor flipping via the major-groove pathway. We perform several analyses to correlate this behavior with structural changes induced by the different methylation states of the CpG site. However, we demonstrate that the driving force for these propensities is the change in the electronic distribution around the pyrimidine ring upon methylation. In particular, unmethylated cytosine interacts more favorably (primarily via electrostatic forces) with solvent water molecules than methylated cytosine. This is observed for, both, extra-helical cytosines and intra-helical cytosines in which the cytosine on the complementary strand flips out and water molecules enter the DNA double-helix and substitute the hydrogen bonds with the orphan guanine. On the basis of these results of spontaneous base flipping, we conjecture that the mechanism for base flipping observed in complexes between hemimethylated DNAs and proteins is not likely to be passive.

Impact of regional copayment policy on selective serotonin reuptake inhibitor (SSRI) consumption and expenditure in Italy.

PURPOSE: The continuous growth of antidepressant consumption and expenditure, especially for selective serotonin reuptake inhibitors (SSRIs), has led to the adoption of several policy measures directed toward cost control in Western countries. In Italy, copayment policies have been heterogeneously introduced at a regional level as part of a strategy designed to reduce drug consumption. The aim of our study was to evaluate whether regional copayment policies have affected trends in the consumption of and expenditure for SSRIs from 2001 to 2007. METHODS: The consumption of SSRIs was measured in terms of defined daily doses per 1,000 inhabitants (DDD/1000) per day from May 2001 to December 2007. Time trends in consumption and expenditure before and after the introduction of copayment policies were examined using segmented regression analysis of interrupted time-series, adjusting for seasonal components. The study was conducted for 17 regions, nine of which had implemented a copayment policy. RESULTS: The overall consumption of SSRIs in Italy increased during the study period, from a monthly consumption of 12.85 DDD/1000 per day in May 2001 to 23.40 DDD/1000 per day in December 2007. The average monthly increase in SSRI use was 0.82 % in regions with a copayment policy versus 0.77 % in regions without a copayment policy (P = 0.329). According to the multivariable analysis, copayment was associated with a 1 % reduction in the monthly growth rate of SSRI consumption (P = 0.01). The impact of copayment on expenditure was statistically significant (P < 0.005) on both the level and the trend, even though the estimate of the effect was negligible. CONCLUSIONS: The implementation of copayment policies in Italy affected both the use and expenditure of SSRIs between 2001 and 2007 to only to a minor extent.

UHRF1 discriminates against binding to fully-methylated CpG-Sites by steric repulsion.

Cytosine methylation of CpG dinucleotide sequence is an epigenetic mark on the DNA that regulates gene expression, chromatin structure, and genome stability. Although the enzyme that catalyzes the methylation reaction after replication is Dnmt1, it was found that the protein UHRF1 is essential for maintaining DNA methylation. UHRF1 exhibits preferential binding to hemi-methylated DNA relative to both unmethylated and fully-methylated DNA strands. In this paper we report results from molecular dynamics simulations aiming to elucidate the mechanism for the discrimination of UHRF1 to bind fully-methylated DNA. From alchemical mutation free energy calculations we find that the binding affinity of fully-methylated DNA to UHRF1 is weaker by 17.9kJ/mol relative to the binding of hemi-methylated DNA. Structural analyses reveal, in agreement with the steric clash model, that a methyl group at the C5 position of the target cytosine induces a displacement of the NKR finger domain away from the DNA. As a result a net loss of, approximately, one hydrogen bond between the protein and the DNA is observed. These weakened protein-DNA interactions are located between the target cytosine and the NKR domain, as well as, between the flipped methylcytosine and the binding pocket of the SRA domain. Due to the conformational changes of the fully-methylated bound complex, water molecules intrude the protein-DNA interface and substitute the majority of the hydrogen bonds that are lost.

How to distinguish methyl-cytosine from cytosine with high fidelity.

Methylation of cytosines in the DNA is central to the epigenetic code. The patterns along the DNA formed by these chemical marks instruct the cell which proteins to express and their faithful maintenance after replication are vital to the organism's life. Although Dnmt1 is the enzyme catalyzing the methylation reaction, it was found that UHRF1 (ubiquitin-like, containing PHD and RING finger domain 1) is the protein that actually recognizes hemi-methylated CpG sites. Nevertheless, the physical mechanism driving the strikingly robust distinction between hemi-methylated and unmethylated sites is not known. In this paper, we show that the large difference in the binding affinities of UHRF1 to these sites is possible not due to the presence of the methyl group itself but is a result of the accompanying changes in the distribution of the electrons around the cytosine ring. In particular, methylation reduces the dipole moment of cytosine and, as a consequence, unmethylated DNA in its unbound state in water is more stable than hemi-methylated DNA. Furthermore, the interaction energy of hemi-methylated DNA bound to UHRF1 with its surrounding is stronger than that of unmethylated DNA. Thus, the change in the electronic structure of cytosine upon methylation destabilizes the unbound state and stabilizes the bound state rendering discrimination with high fidelity possible.

Computed micro-tomographic evaluation of glide path with nickel-titanium rotary PathFile in maxillary first molars curved canals.

INTRODUCTION: X-ray computed micro-tomography scanning allows high-resolution 3-dimensional imaging of small objects. In this study, micro-CT scanning was used to compare the ability of manual and mechanical glide path to maintain the original root canal anatomy. METHODS: Eight extracted upper first permanent molars were scanned at the TOMOLAB station at ELETTRA Synchrotron Light Laboratory in Trieste, Italy, with a microfocus cone-beam geometry system. A total of 2,400 projections on 360° have been acquired at 100 kV and 80 µA, with a focal spot size of 8 µm. Buccal root canals of each specimen (n = 16) were randomly assigned to PathFile (P) or stainless-steel K-file (K) to perform glide path at the full working length. Specimens were then microscanned at the apical level (A) and at the point of the maximum curvature level (C) for post-treatment analyses. Curvatures of root canals were classified as moderate (≤35°) or severe (≥40°). The ratio of diameter ratios (RDRs) and the ratio of cross-sectional areas (RAs) were assessed. For each level of analysis (A and C), 2 balanced 2-way factorial analyses of variance (P < .05) were performed to evaluate the significance of the instrument factor and of canal curvature factor as well as the interactions of the factors both with RDRs and RAs. RESULTS: Specimens in the K group had a mean curvature of 35.4° ± 11.5°; those in the P group had a curvature of 38° ± 9.9°. The instrument factor (P and K) was extremely significant (P < .001) for both the RDR and RA parameters, regardless of the point of analysis. CONCLUSIONS: Micro-CT scanning confirmed that NiTi rotary PathFile instruments preserve the original canal anatomy and cause less canal aberrations.

Socioeconomic disparities in the uptake of breast and cervical cancer screening in Italy: a cross sectional study.

BACKGROUND: Breast and cervical cancer screening are widely recognized as effective preventive procedures in reducing cancer mortality. The aim of this study was to evaluate the impact of socioeconomic disparities in the uptake of female screening in Italy, with a specific focus on different types of screening programs. METHODS: A cross-sectional study was conducted using data from the 2004-2005 national health interview survey. A sample of 15, 486 women aged 50-69 years for mammography and one of 35, 349 women aged 25-64 years for Pap smear were analysed. Logistic regression models were used to estimate the association between socioeconomic factors and female screening utilization. RESULTS: Education and occupation were positively associated with attendance to both screening. Women with higher levels of education were more likely to have a mammogram than those with a lower level (OR = 1.28; 95% CI = 1.10-1.49). Women of intermediate and high occupational classes were more likely to use breast cancer screening (OR = 1.77; 95% CI = 1.55-2.03, OR = 1.63; 95% CI = 1.40-1.91) compared to unemployed women. Women in the highest occupational class had a higher likelihood of cervical cancer screening compared to those in the lowest class (OR = 1.81; 95% CI = 1.63-2.01). Among women who attended screening, those with lower levels of education and lower occupational classes were more likely than more advantaged women to attend organized screening programs rather than being screened on the basis of their own initiative. CONCLUSIONS: Inequalities in the uptake of female screening widely exist in Italy. Organized screening programs may have an important role in increasing screening attendance and tackling inequalities.

Socio-economic status and prevention of cardiovascular disease in Italy: evidence from a national health survey.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death and disability in the world. Many cardiovascular risk factors can be prevented. We assessed whether socio-economic factors are associated with individual preventive behaviours in Italy. METHODS: A cross-sectional analysis of a nationally representative sample of 47,391 adults aged 40-69 years was undertaken using 2004-05 National Health Interview Survey data. Logistic regression models were developed to assess the association between socio-economic status (SES) and regular monitoring of blood pressure, cholesterol, body mass index and glycaemia. SES was estimated according to education and occupation. RESULTS: SES was significantly associated with regular monitoring of risk factors for CVD. The most educated were more likely to monitor cholesterol levels than those with less education [men odds ratio (OR) 1.64, 95% confidence interval (CI) 1.46-1.86; women OR 1.36, 95% CI 1.19-1.55]. Individuals in the highest occupational class controlled weight more frequently than those disadvantaged with an OR of 1.24 (95% CI 1.04-1.49) for men and an OR of 1.26 (95% CI 1.12-1.42) for women. CONCLUSION: Socio-economic disparities in the prevention of risk factors for CVD were clearly observed among Italian adults, generally favouring higher socio-economic groups.

Modeling the ternary complex TCR-Vbeta/CollagenII(261-273)/HLA-DR4 associated with rheumatoid arthritis.

BACKGROUND: It is known that genetic predisposition to rheumatoid arthritis (RA) is associated with the MHC class II allele HLA-DR4 and that residues 261-273 of type II collagen (huCollp261) represent an immunodominant T cell epitope restricted by the DR4 molecule. Despite recent advances in characterization of MHC and T cell receptor (TCR) contacts to this epitope, the atomic details of TCR/huCollp261/HLA-DR4 ternary complex are not known. METHODOLOGY/PRINCIPAL FINDINGS: Here we have used computational modeling to get insight into this interaction. A three-dimensional model of the TCR Vbeta domain from a DR4(+) patient affected by RA has been derived by homology modeling techniques. Subsequently, the structure of the TCR Vbeta domain in complex with huCollp261/HLA-DR4 was obtained from a docking approach in conjunction with a filtering procedure based on biochemical information. The best complex from the docking experiments was then refined by 20 ns of molecular dynamics simulation in explicit water. The predicted model is consistent with available experimental data. Our results indicate that residues 97-101 of CDR3beta are critical for recognition of huCollp261/HLA-DR4 by TCR. We also show that TCR contacts on p/MHC surface affect the conformation of the shared epitope expressed by DR alleles associated with RA susceptibility. CONCLUSIONS/SIGNIFICANCE: This work presents a three-dimensional model for the ternary complex TCR-Vbeta/collagenII(261-273)/HLA-DR4 associated with rheumatoid arthritis that can provide insights into the molecular mechanisms of self reactivity.