Cortisol, family coping and burden in informal caregivers of addicts

This study focuses on the prospective mediation role of family coping between burden and cortisol levels in informal caregivers of addicts as well as on the feasible use of two different ways to analyse the salivary cortisol levels. Participants were 120 Portuguese informal caregivers of addicts. The cortisol samples were collected at awakening, 45 minutes later and after a 30 minute presentation of images taken from the International Affective Picture System. Family coping and caregiver burden were measured using the Portuguese versions of the Caregiver Reaction Assessment, and the Family Crisis Oriented Personal Evaluation Scale. Cortisol samples were collected in salivettes and the results were computed in order to determine the Area Under the Curve scores (AUCg, AUCi). Results found family coping to be negatively correlated with burden and AUCg levels (i.e. overall intensity) and positively correlated with either AUCg and AUCi (i.e. change over time). The mediation model revealed that family coping was a partial mediator in the relationship between the burden and AUCg levels. Therefore, Family Coping appears to be an essential variable in understanding the stress response and should be considered in further studies and interventions. In addition, the use of two different formulas for calculating cortisol levels provided important new information concerning the relationship between cortisol, burden and family coping. It seems that burden has a more profound effect on the overall intensity of the neuroendocrine response to caregiver stress and not so much on the sensitivity of the system.

Fine time scaling of purifying selection on human nonsynonymous mtDNA mutations based on the worldwide population tree and mother-child pairs

A high-resolution mtDNA phylogenetic tree allowed us to look backward in time to investigate purifying selection. Purifying selection was very strong in the last 2,500 years, continuously eliminating pathogenic mutations back until the end of the Younger Dryas (∼11,000 years ago), when a large population expansion likely relaxed selection pressure. This was preceded by a phase of stable selection until another relaxation occurred in the out-of-Africa migration. Demography and selection are closely related: expansions led to relaxation of selection and higher pathogenicity mutations significantly decreased the growth of descendants. The only detectible positive selection was the recurrence of highly pathogenic nonsynonymous mutations (m.3394T>C-m.3397A>G-m.3398T>C) at interior branches of the tree, preventing the formation of a dinucleotide STR (TATATA) in the MT-ND1 gene. At the most recent time scale in 124 mother-children transmissions, purifying selection was detectable through the loss of mtDNA variants with high predicted pathogenicity. A few haplogroup-defining sites were also heteroplasmic, agreeing with a significant propensity in 349 positions in the phylogenetic tree to revert back to the ancestral variant. This nonrandom mutation property explains the observation of heteroplasmic mutations at some haplogroup-defining sites in sequencing datasets, which may not indicate poor quality as has been claimed.

Evaluating biomaterial-and microfluidic-based 3D tumor models

Cancer is a major cause of morbidity and mortality worldwide, with a disease burden estimated to increase in the coming decades. Disease heterogeneity and limited information on cancer biology and disease mechanisms are aspects that 2D cell cultures fail to address. We review the current "state-of-the-art" in 3D Tissue Engineering (TE) models developed for and used in cancer research. Scaffold-based TE models and microfluidics, are assessed for their potential to fill the gap between 2D models and clinical application. Recent advances in combining the principles of 3D TE models and microfluidics are discussed, with a special focus on biomaterials and the most promising chip-based 3D models.

Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective

This review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85 % of all incident CC and 50 % of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country.