Análisis del impacto presupuestal en Colombia de la prueba de HPV con genotipificación comparada con la citología

Introduction:

The detection of the human papillomavirus (HPV) through the combination of the HPV test and other techniques such as cytology has impacted the detection and timely treatment of lesions associated with cervical cancer.

Objective:

To estimate the budgetary impact of the strategy of early detection of HPV with DNA test genotyping with reflex cytology versus conventional cytology in women aged 30 to 65 years attending the cervical cancer screening program at a health benefit managing entity in Colombia.

Materials and methods:

Using a decision tree and a Markov model, the clinical implications and direct costs of screening, diagnosis, and treatment were estimated in a cohort of women. The analysis considered two screening cycles and their annual costs. The data on the prevalence of clinical results and the costs were taken from the health managing entity. The information on the progression, persistence, and regression of the health states were taken from the ATHENA study.

Results:

The screening scheme with the HPV test, genotyping, and reflex cytology compared to conventional cytology was cost-saving. The average cost per screening cycle with the HPV test was estimated at COP $ 129,201,363 and with cytology at COP $ 186,309,952, i.e., a saving of COP $ 57,108,589 (30.7%).

Conclusion:

The implementation of the screening strategy under evaluation suggests prospective savings derived from the early detection of health states associated with the development of cervical cancer.     

When invasion biology meets taxonomy: <Emphasis Type="Italic">Clavelina oblonga</Emphasis> (Ascidiacea) is an old invader in the Mediterranean Sea

Taxonomic issues often confound the study of invasive species, which sometimes are unrecognized as introduced in newly colonized areas. Clavelina oblonga Herdman, 1880 is an abundant ascidian species along the southeastern coast of the United States and the Caribbean Sea. It was introduced into the eastern Atlantic and Brazil decades ago. In the Mediterranean Sea, a similar species had been described as C. phlegraea Salfi 1929 and reported from southern Italy and Corsica. In the last few years a species of Clavelina has proliferated in the embayments of the Ebro Delta (NW Mediterranean), a zone of active bivalve culture industry where it has smothered mussel spat, leading to economic loss. We here report the morphological and genetic identity of this species, synonymizing the Atlantic C. oblonga and the Mediterranean C. phlegraea (the latter therefore is a synonym of the former). Thus, C. oblonga has existed in the Mediterranean for over 80 years, but was known under a different name. We also found this species in natural habitats in the Iberian Atlantic coast close to the Strait of Gibraltar, raising concerns about an ongoing expansion. In order to obtain information relevant for management, we monitored growth, reproductive cycles and settlement patterns of this ascidian on bivalve cultures in the Ebro Delta. Its biological cycles were markedly seasonal, with peak abundance and reproduction during the warmest months, followed by regression during the cold season. The settlement period was short, mostly concentrated in a single month each year. Avoidance of mussel and oyster seeding during late summer and early autumn can readily reduce the damage caused by this species.     

Discovery and optimization of orally active cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors

The synthesis, SAR, binding affinities and pharmacokinetic profiles are described for a series of cyclohexane-based prolylcarboxypeptidase (PrCP) inhibitors discovered by high throughput screening. Compounds show high levels of ex vivo target engagement in mouse plasma 20 h post oral dose.     

Effects of the new adiponectin paralogous protein CTRP-3 and of LPS on cytokine release from monocytes of patients with type 2 diabetes mellitus

Aims/Hypothesis: It was the aim to investigate the hypothesis that the new C1q/TNF-family member CTRP-3 (C1q/TNF-related protein-3) acts anti-inflammatory in human monocytes from healthy controls and patients with type 2 diabetes mellitus (T2D). Methods: Monocytes were isolated from 20 healthy controls and 30 patients with T2D. IL-6 and TNF concentrations were measured by ELISA. CTRP-3 was expressed in insect cells and used for stimulation experiments. Results: Basal IL-6 and TNF were not different in control and in T2D monocytes. LPS-stimulation (1 μg/ml) significantly (p < 0.001) increased IL-6 and TNF in the supernatants of control and in T2D monocytes to a similar extent. CTRP-3 (1 μg/ml) significantly (p = 0.03) inhibited LPS-induced IL-6 in control monocytes but not in T2D monocytes. TNF upon co-stimulation with LPS and CTRP-3 was significantly (p = 0.012) lower in control than in T2D monocytes. LPS-induced TNF concentration was significantly and positively correlated with serum total cholesterol and LDL cholesterol in T2D patients. Conclusions: CTRP-3 inhibits LPS-induced IL-6 and TNF release. This anti-inflammatory effect is lost in T2D. Serum cholesterol concentration affects the pro-inflammatory potential of LPS to induce TNF release from T2D monocytes in the presence or absence of CTRP-3. CTRP-3 might partly account for the pro-inflammatory state in T2D.     

Unusual viral ligand with alternative interactions is presented by HLA-Cw4 in human respiratory syncytial virus-infected cells

Short viral antigens bound to human major histocompatibility complex (HLA) class I molecules are presented on infected cells. Vaccine development frequently relies on synthetic peptides to identify optimal HLA class I ligands. However, when natural peptides are analyzed, more complex mixtures are found. By immunoproteomics analysis, we identify in this study a physiologically processed HLA ligand derived from the human respiratory syncytial virus matrix protein that is very different from what was expected from studies with synthetic peptides. This natural HLA-Cw4 class I ligand uses alternative interactions to the anchor motifs previously described for its presenting HLA-Cw4 class I molecule. Finally, this octameric peptide shares its C-terminal core with the H-2D(b) nonamer ligand previously identified in the mouse model. These data have implications for the identification of antiviral cytotoxic T lymphocyte responses and for vaccine development.     

Cyclooxygenase-2 deficiency leads to intestinal barrier dysfunction and increased mortality during polymicrobial sepsis

Sepsis remains the leading cause of death in critically ill patients, despite modern advances in critical care. Intestinal barrier dysfunction may lead to secondary bacterial translocation and the development of the multiple organ dysfunction syndrome during sepsis. Cyclooxygenase (COX)-2 is highly upregulated in the intestine during sepsis, and we hypothesized that it may be critical in the maintenance of intestinal epithelial barrier function during peritonitis-induced polymicrobial sepsis. COX-2(-/-) and COX-2(+/+) BALB/c mice underwent cecal ligation and puncture (CLP) or sham surgery. Mice chimeric for COX-2 were derived by bone marrow transplantation and underwent CLP. C2BBe1 cells, an intestinal epithelial cell line, were treated with the COX-2 inhibitor NS-398, PGD(2), or vehicle and stimulated with cytokines. COX-2(-/-) mice developed exaggerated bacteremia and increased mortality compared with COX-2(+/+) mice following CLP. Mice chimeric for COX-2 exhibited the recipient phenotype, suggesting that epithelial COX-2 expression in the ileum attenuates bacteremia following CLP. Absence of COX-2 significantly increased epithelial permeability of the ileum and reduced expression of the tight junction proteins zonula occludens-1, occludin, and claudin-1 in the ileum following CLP. Furthermore, PGD(2) attenuated cytokine-induced hyperpermeability and zonula occludens-1 downregulation in NS-398-treated C2BBe1 cells. Our findings reveal that absence of COX-2 is associated with enhanced intestinal epithelial permeability and leads to exaggerated bacterial translocation and increased mortality during peritonitis-induced sepsis. Taken together, our results suggest that epithelial expression of COX-2 in the ileum is a critical modulator of tight junction protein expression and intestinal barrier function during sepsis.