Characterization of TRIB2-mediated resistance to anti-cancer drugs

Dissertação de Mestrado, Oncobiologia: Mecanismos Moleculares do Cancro, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

Evaluation of antibiotic prescription for upper respiratory tract infections in the community pharmacy setting

This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License. http://creativecommons.org/licenses/by/4.0/

Association of body composition indices with insulin resistance in European adolescents: the HELENA study

Background: The different body components may contribute to the development of insulin resistance and type 2 diabetes mellitus. The aim of the present study was to examine the association of fat mass and fat free mass indices with markers of insulin resistance, independently of each other and giving, at the same time, gender-specific information in a wide cohort of European adolescents. Methods: A cross-sectional study in a school setting was conducted in 925 (430 males) adolescents (14.9 ± 1.2 years). Weight, height, anthropometric, bioimpedance and blood parameters were measured. Indices for fat mass and fat free mass, and homeostatic model assessment (HOMA) were calculated. Multiple regression analyses were performed adjusting for several confounders including fat free mass and fat mass when possible. Results: Indices of fat mass were positively associated with HOMA (all p < 0.01) after adjusting for all the confounders including fat free mass indices, in both sexes. Fat free mass indices were associated with HOMA, in both males and females, after adjusting for center, pubertal status, socioeconomic status and cardiorespiratory fitness, but the associations disappear when including fat mass indices in the adjustment's model. Conclusion: Fat mass indices derived from different methods are positively associated with insulin resistance independently of several confounders including fat free mass indices. In addition, the relationship of fat free mass with insulin resistance is influenced by the amount of fat mass in European adolescents. Nevertheless, future studies should focus not only on the role of fat mass, but also on other body components such as fat free mass because its role could vary depending of the level and distribution of fat mass.

Parental views of antibiotic use in children with upper respiratory tract infections in Jordan

Purpose: To assess the knowledge, attitudes and practices of parents towards antibiotics use for upper respiratory tract infections (URTIs) in Jordan. Methods: A cross-sectional study was carried out at 10 private outpatients’ pediatric clinics across Amman-Jordan from September to December 2013. During the study period, 1329 parents of young children who fulfilled the inclusion criteria and agreed to participate were interviewed, and completed a validated structured questionnaire. Results: A large proportion of parents (903, 68 %) believed that weather change was the main cause of acute URTIs in their children. Although 1098 (82.8 %) of parents were aware that the recurrent use of antibiotics leads to a decrease in effectiveness due to bacterial resistance, 859 (64.6 %) of the respondents reported that they would give antibiotics without prescription. Fathers (135, 40.2 %), were significantly more aware that URTIs follow its natural course without antibiotic administration compared to mothers (N = 327, 32.9 %), respectively (p = 0.005). Conclusion: There is a lack of adequate parental knowledge concerning the use and misuse of antibiotics in children in Jordan. National publicity campaign should be mounted to improve awareness. Furthermore, existing laws should be enforced to prevent parents from purchasing antibiotics over-thecounter (OTC).

Staphylococcus aureus CC398: host adaptation and emergence of methicillin resistance in livestock

UNLABELLED Since its discovery in the early 2000s, methicillin-resistant Staphylococcus aureus (MRSA) clonal complex 398 (CC398) has become a rapidly emerging cause of human infections, most often associated with livestock exposure. We applied whole-genome sequence typing to characterize a diverse collection of CC398 isolates (n = 89), including MRSA and methicillin-susceptible S. aureus (MSSA) from animals and humans spanning 19 countries and four continents. We identified 4,238 single nucleotide polymorphisms (SNPs) among the 89 core genomes. Minimal homoplasy (consistency index = 0.9591) was detected among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage. Phylogenetic analyses revealed that MSSA from humans formed the most ancestral clades. The most derived lineages were composed predominantly of livestock-associated MRSA possessing three different staphylococcal cassette chromosome mec element (SCCmec) types (IV, V, and VII-like) including nine subtypes. The human-associated isolates from the basal clades carried phages encoding human innate immune modulators that were largely missing among the livestock-associated isolates. Our results strongly suggest that livestock-associated MRSA CC398 originated in humans as MSSA. The lineage appears to have undergone a rapid radiation in conjunction with the jump from humans to livestock, where it subsequently acquired tetracycline and methicillin resistance. Further analyses are required to estimate the number of independent genetic events leading to the methicillin-resistant sublineages, but the diversity of SCCmec subtypes is suggestive of strong and diverse antimicrobial selection associated with food animal production. IMPORTANCE Modern food animal production is characterized by densely concentrated animals and routine antibiotic use, which may facilitate the emergence of novel antibiotic-resistant zoonotic pathogens. Our findings strongly support the idea that livestock-associated MRSA CC398 originated as MSSA in humans. The jump of CC398 from humans to livestock was accompanied by the loss of phage-carried human virulence genes, which likely attenuated its zoonotic potential, but it was also accompanied by the acquisition of tetracycline and methicillin resistance. Our findings exemplify a bidirectional zoonotic exchange and underscore the potential public health risks of widespread antibiotic use in food animal production.

Smoothing a Discrete Hazard Function for the Number of Patients Colonized with Methicillin-Resistance Staphylococcus Aureus in an Intensive Care Unit

A new method for estimating the time to colonization of Methicillin-resistant Staphylococcus Aureus (MRSA) patients is developed in this paper. The time to colonization of MRSA is modelled using a Bayesian smoothing approach for the hazard function. There are two prior models discussed in this paper: the first difference prior and the second difference prior. The second difference prior model gives smoother estimates of the hazard functions and, when applied to data from an intensive care unit (ICU), clearly shows increasing hazard up to day 13, then a decreasing hazard. The results clearly demonstrate that the hazard is not constant and provide a useful quantification of the effect of length of stay on the risk of MRSA colonization which provides useful insight.