Efeitos cognitivos, neuropsicológicos e comportamentais da exposição a baixas concentrações de chumbo na infância

O presente trabalho consiste em uma revisão bibliográfica a respeito da exposição ao chumbo em baixas concentrações e seus efeitos em crianças. Apesar do limite tolerado de chumbo no sangue, fixado pela OMS em 10mg/dl, diversos estudos transversais e longitudinais têm apontado que doses abaixo desse limite também geram consequências negativas no desenvolvimento infantil. Na primeira infância, observa-se correlação entre exposição pré-natal ao chumbo e déficits cognitivos; e correlação inversa entre níveis correntes de chumbo no sangue e desempenho cognitivo. A exposição a baixos níveis de chumbo na primeira infância também foi associada a prejuízo no desempenho cognitivo e escolar anos depois. Exposição ao chumbo na fase escolar tem sido associada a problemas no desempenho acadêmico, na atenção e em funções neuropsicológicas diversas. Estudos recentes detectaram ligação entre baixa exposição ao chumbo e problemas de comportamento na criança. A evidência acumulada indica risco de prejuízo neuropsicológico e adaptativo em crianças expostas a baixos níveis de chumbo. Os danos são maiores em concentrações muito baixas, inferiores ao nível tolerado pela OMS, indicando a necessidade de trabalhos de prevenção.This is a literature review about low-level lead exposure and its effects on children. Although the current  World Health Organization blood level of concern stands at 10 mg/dL, numerous prospective and crosssectional studies have extended the association of blood lead and developmental impairment to lower levels of lead exposure. During early childhood, there is a positive association between prenatal lowlevel lead exposure and cognitive deficits. There is also a negative correlation between current blood lead level and cognitive performance. Low-level lead exposure in early childhood predicts cognitive and academic underachievement years later. During the school years, low-level lead exposure is concurrently associated to impairments in academic achievement, attention, and several neuropsychological functions. Recent investigations have detected a relationship between lead exposure and behavior problems in children. The evidence points to the neuropsychological and adaptive risks of low-level lead exposure during early and middle childhood and suggests that there is no safety margin at existing exposures. Harm is greater in very small concentrations, below the current WHO level of concern, thus indicating the need for prevention efforts

Periostin Responds to Mechanical Stress and Tension by Activating the MTOR Signaling Pathway

Current knowledge about Periostin biology has expanded from its recognized functions in embryogenesis and bone metabolism to its roles in tissue repair and remodeling and its clinical implications in cancer. Emerging evidence suggests that Periostin plays a critical role in the mechanism of wound healing; however, the paracrine effect of Periostin in epithelial cell biology is still poorly understood. We found that epithelial cells are capable of producing endogenous Periostin that, unlike mesenchymal cell, cannot be secreted. Epithelial cells responded to Periostin paracrine stimuli by enhancing cellular migration and proliferation and by activating the mTOR signaling pathway. Interestingly, biomechanical stimulation of epithelial cells, which simulates tension forces that occur during initial steps of tissue healing, induced Periostin production and mTOR activation. The molecular association of Periostin and mTOR signaling was further dissected by administering rapamycin, a selective pharmacological inhibitor of mTOR, and by disruption of Raptor and Rictor scaffold proteins implicated in the regulation of mTORC1 and mTORC2 complex assembly. Both strategies resulted in ablation of Periostin-induced mitogenic and migratory activity. These results indicate that Periostin-induced epithelial migration and proliferation requires mTOR signaling. Collectively, our findings identify Periostin as a mechanical stress responsive molecule that is primarily secreted by fibroblasts during wound healing and expressed endogenously in epithelial cells resulting in the control of cellular physiology through a mechanism mediated by the mTOR signaling cascade.This work was funded by the National Institutes of Health (NIH/NCI) P50-CA97248 (University of Michigan Head and Neck SPORE)

A Mycobacterium leprae Hsp65 Mutant as a Candidate for Mitigating Lupus Aggravation in Mice

Hsp60 is an abundant and highly conserved family of intracellular molecules. Increased levels of this family of proteins have been observed in the extracellular compartment in chronic inflammation. Administration of M. leprae Hsp65 [WT] in [NZBxNZW]F1 mice accelerates the Systemic Lupus Erythematosus [SLE] progression whereas the point mutated K409A Hsp65 protein delays the disease. Here, the biological effects of M. leprae Hsp65 Leader pep and K409A pep synthetic peptides, which cover residues 352–371, are presented. Peptides had immunomodulatory effects similar to that observed with their respective proteins on survival and the combined administration of K409A+Leader pep or K409A pep+WT showed that the mutant forms were able to inhibit the deleterious effect of WT on mortality, indicating the neutralizing potential of the mutant molecules in SLE progression. Molecular modeling showed that replacing Lysine by Alanine affects the electrostatic potential of the 352–371 region. The number of interactions observed for WT is much higher than for Hsp65 K409A and mouse Hsp60. The immunomodulatory effects of the point-mutated protein and peptide occurred regardless of the catalytic activity. These findings may be related to the lack of effect on survival when F1 mice were inoculated with Hsp60 or K409A pep. Our findings indicate the use of point-mutated Hsp65 molecules, such as the K409A protein and its corresponding peptide, that may minimize or delay the onset of SLE, representing a new approach to the treatment of autoimmune diseases

Profiles of Parental Burnout Around the Globe: Similarities and Differences Across 36 Countries

Parental burnout (PB) is a pervasive phenomenon. Parenting is embedded in cultural values, and previous research has shown the role of individualism in PB. In this paper, we reanalyze previously collected data to identify profiles based on the four dimensions of PB, and explore whether these profiles vary across countries’ levels of collectivistic-individualistic (COL-IND) values. Our sample comprised 16,885 individuals from 36 countries (73% women; 27% men), and we used a latent profile approach to uncover PB profiles. The findings showed five profiles: Fulfilled, Not in PB, Low risk of PB, High risk of PB and Burned out. The profiles pointed to climbing levels of PB in the total sample and in each of the three country groups (High COL/Low IND, Medium COL-IND, Low COL/High IND). Exploratory analyses revealed that distinct dimensions of PB had the most prominent roles in the climbing pattern, depending on the countries’ levels of COL/IND. In particular, we found contrast to be a hallmark dimension and an indicator of severe burnout for individualistic countries. Contrary to our predictions, emotional distance and saturation did not allow a clear differentiation across collectivistic countries. Our findings support several research avenues regarding PB measurement and intervention