HIV incidence estimate combining HIV/AIDS surveillance, testing history information and HIV test to identify recent infections in Lazio, Italy

<p>Abstract</p> <p>Background</p> <p>The application of serological methods in HIV/AIDS routine surveillance systems to identify persons with recently acquired HIV infection has been proposed as a tool which may provide an accurate description of the current transmission patterns of HIV. Using the information about recent infection it is possible to estimate HIV incidence, according to the model proposed by Karon et al. in 2008, that accounts for the effect of testing practices on the number of persons detected as recently infected.</p> <p>Methods</p> <p>We used data from HIV/AIDS surveillance in the period 2004-2008 to identify newly diagnosed persons. These were classified with recent/non-recent infection on the basis of an avidity index result, or laboratory evidence of recently acquired infection (i.e., previous documented negative HIV test within 6 months; or presence of HIV RNA or p24 antigen with simultaneous negative/indeterminate HIV antibody test). Multiple imputation was used to impute missing information. The incidence estimate was obtained as the number of persons detected as recently infected divided by the estimated probability of detection. Estimates were stratified by calendar year, transmission category, gender and nationality.</p> <p>Results</p> <p>During the period considered 3,633 new HIV diagnoses were reported to the regional surveillance system. Applying the model, we estimated that in 2004-2008 there were 5,465 new infections (95%CI: 4,538-6,461); stratifying by transmission category, the estimated number of infections was 2,599 among heterosexual contacts, 2,208 among men-who-have-sex-with-men, and 763 among injecting-drug-users. In 2008 there were 952 (625-1,229) new HIV infections (incidence of 19.9 per 100,000 person-years). In 2008, for men-who-have-sex-with-men (691 per 100,000 person-years) and injecting drug users (577 per 100,000 person-years) the incidence remained comparatively high with respect to the general population, although a decreasing pattern during 2004-2008 was observed for injecting-drug-users.</p> <p>Conclusions</p> <p>These estimates suggest that the transmission of HIV infection in Lazio remains frequent and men-who-have-sex-with men and injecting-drug-users are still greatly affected although the majority of new infections occurs among heterosexual individuals.</p

Switching "on" and "off" the expression of chirality in peptide rotaxanes

The hydrogen-bond-directed synthesis, X-ray crystal structures, and optical properties of the first chiral peptide rotaxanes are reported. Collectively these systems provide the first examples of single molecular species where the expression of chirality in the form of a circular dichroism (CD) response can selectively be switched &quot;on&quot; or &quot;off&quot;, and its magnitude altered, through controlling the interactions between mechanically interlocked submolecular components. The switching is achievable both thermally and through changes in the nature of the environment. Peptido[2]rotaxanes consisting of an intrinsically achiral benzylic amide macrocycle locked onto various chiral dipeptide (Gly-L-Ala, Gly-L-Leu, Gly-L-Met, Gly-L-Phe, and Gly-L-Pro) threads exhibit strong (10-20k deg cm(2) dmol(-1)) negative induced CD (theta) values in nonpolar solvents (e.g. CHCl3), where the intramolecular hydrogen bonding between thread and macrocycle is maximized. In polar solvents (e.g., MeOH), where the intercomponent hydrogen bonding is weakened, or switched off completely, the elliptical polarization falls close to zero in some cases and can even be switched to large positive values in others. Importantly, the mechanism of generating the switchable CD response in the chiral peptide rotaxanes is also determined: a combination of semiempirical calculations and geometrical modeling using the continuous chirality measure (CCM) shows that the chirality is transmitted from the amino acid asymmetric center on the thread via the macrocycle to the C-terminal stopper of the rotaxane. This understanding could have important implications for other areas where chiral transmission from one chemical entity to another underpins a physical or chemical response, such as the seeding of supertwisted nematic liquid crystalline phases or asymmetric synthesis.</p

Cast metal core adaptation using two impression materials and intracanal techniques

Aim: This study evaluated the adaptation of cast metal cores (CMCs) using two impression materials and two intracanal impression techniques. Methods: Ten single-rooted human teeth had their root canals prepared to receive a CMC. Intracanal impressions were obtained with addition and condensation silicone materials using two types of intraradicular supports: hypodermic needle or prefabricated polycarbonate posts. Four impressions were obtained from each tooth totalizing 40 models, on which CMCs were prepared. CMC adaptation to the canal was analyzed radiographically and microscopically. The teeth were radiographed with the CMC positioned and the images were analyzed using an image-analysis software (ImageLab). In the second analysis, the teeth were sectioned longitudinally and the CMC adaptation was evaluated with a two-coordinate microscope. In both analyses, CMC adaptation to the canal was determined by calculating the percentage of the prepared canal space that was occupied by the core. Results: Statistically significant difference (2-way ANOVA - Bonferroni; p<0.05) was found between the mean values CMC adaptation obtained with the two intraradicular supports. Conclusions: The intracanal impression technique using hypodermic needle allowed a more accurate reproduction of the prepared canal space and provided significantly better CMC adaptation when the cores were obtained from addition silicone impressions

Cast metal core adaptation using two impression materials and intracanal techniques

is study evaluated the adaptation of cast metal cores (CMCs) using two impression materials and two intracanal impression techniques. Methods: Ten single-rooted human teeth had their root canals prepared to receive a CMC. Intracanal impressions were obtained with addition and condensation silicone materials using two types of intraradicular supports: hypodermic needle or prefabricated polycarbonate posts. Four impressions were obtained from each tooth totalizing 40 models, on which CMCs were prepared. CMC adaptation to the canal was analyzed radiographically and microscopically. The teeth were radiographed with the CMC positioned and the images were analyzed using an image-analysis software (ImageLab). In the second analysis, the teeth were sectioned longitudinally and the CMC adaptation was evaluated with a two-coordinate microscope. In both analyses, CMC adaptation to the canal was determined by calculating the percentage of the prepared canal space that was occupied by the core. Results: Statistically significant difference (2-way ANOVA - Bonferroni; p<0.05) was found between the mean values CMC adaptation obtained with the two intraradicular supports. Conclusions: The intracanal impression technique using hypodermic needle allowed a more accurate reproduction of the prepared canal space and provided significantly better CMC adaptation when the cores were obtained from addition silicone impressions

Hyperthermia enhances efficacy of chemotherapeutic agents in pancreatic cancer cell lines

Chemotherapy (CT) is the standard care for advanced pancreatic ductal adenocarcinoma (PDAC); however, with limited efficacy. Hyperthermia (HT) treatment has been suggested as a sensitizer to improve outcomes. However, the direct effect of the HT and CT combination is not fully understood. Therefore, we aim to assess the direct cytotoxic effect of HT in PDAC cells as monotherapy or in combination with chemotherapeutics. Different temperatures (37-, 40.5-, 41-, and 41.5 °C) and durations (6-, 12-, and 24 h) were tested in PDAC cell lines (BxPC-3, Capan-1, Capan-2, PANC-1, and MIA-PaCa-2). Different concentrations of gemcitabine, 5-fluorouracil, and cisplatin were also tested in these conditions. The impact on cell metabolic activity was determined by an MTS assay. Enhancement of chemosensitivity was assessed by a reduction in half-maximal inhibitory concentration ([Formula: see text]). HT and chemotherapeutics interactions were classified as antagonistic, additive, or synergistic using the combination index. HT inhibited cell proliferation in a cell type, temperature, and duration-dependent manner. The induction of apoptosis was seen after 6 h of HT treatment, eventually followed by secondary necrosis. The HT and CT combination led to an [Formula: see text] reduction of the tested CT. At 12 h of HT, this effect was between 25 to 90% and reached a 95% reduction at 24 h. The additive or synergistic effect was demonstrated in all cell lines and chemotherapeutics, although, again, this depended on cell type, duration, and temperature. HT is cytotoxic and enhances the therapeutic effectiveness of gemcitabine, 5-fluorouracil, and cisplatin on PDAC cells. This result was further confirmed by the decrease in the expression of RRM2, TS, and ERCC1 in BxPC-3 and Capan-2 cells. These observations warrant further study in specific subsets of PDAC patients to improve their clinical outcomes