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(1) Background: There is consistent evidence of the impact of early adverse experiences on mental health in adulthood, especially as a risk factor for depression. However, their influence on positive aspects of mental health such as well-being has been less extensively studied. Therefore, this study aims to investigate the effect of traumatic childhood experiences on the relationship between depression and psychological well-being in a sample of university students. (2) Methods: The Childhood Trauma Questionnaire—Short Form (CTQ-SF), the Beck Depression Inventory (BDI-IA), and Ryff's psychological well-being scale were administered to 700 Chilean university students. Several regression models were used to analyze the interaction between variables, with multivariate SEM being applied to hierarchize the relationships found. (3) Results: Emotional Neglect and Abuse stand out as the types of maltreatment with the greatest impact on mental health, associated first with a decrease in the self-acceptance dimension of psychological well-being and then with depressive symptomatology in adulthood. (4) Conclusions: Results provide evidence that early trauma has an important impact on mental health, increasing the risk of depression, however, its impact is greater on positive aspects of health, such as self-acceptance, a fundamental element in the construction of psychological well-being. [ABSTRACT FROM AUTHOR]

Individuals tend to accumulate a larger number of losses in old age than in prior stages of life, leading to major consequences for the well-being of older adults. Research has generally focused on a single type of loss, with only a handful of studies exploring the accumulation of losses in old age and examining which and how many losses are experienced, and how intense they are. The lack of instruments that reflect the diversity of the losses that individuals can sustain at this stage of life makes it difficult to accumulate knowledge in this field, since it is not possible to characterize this experience or establish associations with other significant variables. Based on a prior categorization of six types of losses, developed upon the basis of reports by older adults, we sought to construct and validate a Scale of Losses Experienced in Old Age (SLO). This scale underwent semantic validation, followed by content validation. Afterward, for the construct validation process, it was administered to a pilot sample of 249 middle-income community-dwelling older adults. The confirmatory factor analysis yielded adequate values (RMSEA = 0.060, CFI = 0.969, TLI = 0.961, SRMR = 0.075), with internal consistency also being suitable (ordinal alpha = 0.856). These values warrant recommending the use of the SLO, since it offers a view of losses in old age that is both broad and detailed, thus facilitating the production of cumulative and comparable knowledge in the field of psychogerontology while also making it possible to establish interdisciplinary connections. [ABSTRACT FROM AUTHOR]

Abstract Background The importance of in silico predictions for understanding cellular processes is now widely accepted, and a variety of algorithms useful for studying different biological features have been designed. In particular, the prediction of cis regulatory modules in non-coding human genome regions represents a major challenge for understanding gene regulation in several diseases. Recently, studies of the Wnt signaling pathway revealed a connection with neurodegenerative diseases such as Alzheimer's. In this article, we construct a classification tool that uses the transcription factor binding site motifs composition of some gene promoters to identify new Wnt/β-catenin pathway target genes potentially involved in brain diseases. Results In this study, we propose 89 new Wnt/β-catenin pathway target genes predicted in silico by using a method based on multiple Classification and Regression Tree (CART) analysis. We used as decision variables the presence of transcription factor binding site motifs in the upstream region of each gene. This prediction was validated by RT-qPCR in a sample of 9 genes. As expected, LEF1, a member of the T-cell factor/lymphoid enhancer-binding factor family (TCF/LEF1), was relevant for the classification algorithm and, remarkably, other factors related directly or indirectly to the inflammatory response and amyloidogenic processes also appeared to be relevant for the classification. Among the 89 new Wnt/β-catenin pathway targets, we found a group expressed in brain tissue that could be involved in diverse responses to neurodegenerative diseases, like Alzheimer's disease (AD). These genes represent new candidates to protect cells against amyloid β toxicity, in agreement with the proposed neuroprotective role of the Wnt signaling pathway. Conclusions Our multiple CART strategy proved to be an effective tool to identify new Wnt/β-catenin pathway targets based on the study of their regulatory regions in the human genome. In particular, several of these genes represent a new group of transcriptional dependent targets of the canonical Wnt pathway. The functions of these genes indicate that they are involved in pathophysiology related to Alzheimer's disease or other brain disorders.

Population aging is rapidly increasing in developing countries; thus, covering medical needs for breast cancer diagnosis and treatment is a priority in Latin America. We describe an approach for integrating differential expression analysis, biological pathway enrichment, in silico transcription‐binding sites and network topology, to find key genes that may be used as biomarkers or therapeutic targets. This approach is based on publicly available data from microarrays of the MCF‐7 breast cancer cell line treated with estrogen. We found significant estrogen‐responsive genes, which were used as nodes to construct networks based on protein‐protein interactions reported in the literature. Then, we conducted a topology analysis of the networks, revealing the most‐connected nodes, ie, those responsible for maintaining the network structure corresponding to genes with well‐acknowledged functions in G1/S cell cycle transition, such as cyclin‐dependent kinase 2 (CDK2), which has been proposed as a therapeutic target in classical biochemical studies. In addition, analyses of biological pathway enrichment and in silico transcription‐binding sites support the biological meaning and importance of these key genes and help to decide the best target genes. Therefore, we postulate that the integrative bioinformatics approach shown here, unlike the classical bioinformatics approach that only includes differentially expressed genes and enriched biological pathways, can be applied as an approach for finding novel biomarkers and/or therapeutic target genes for nonresponsive treatments. [ABSTRACT FROM AUTHOR]

Recent research in psychiatric genetics has led to a move away from simple diathesis-stress models to more complex models of psychopathology incorporating a focus on gene–environment interactions and epigenetics. Our increased understanding of the way biology encodes the impact of life events on organisms has also generated more sophisticated theoretical models concerning the molecular processes at the interface between “nature” and “nurture.” There is also increasing consensus that psychotherapy entails a specific type of learning in the context of an emotional relationship (i.e., the therapeutic relationship) that may also lead to epigenetic modifications across different therapeutic treatment modalities. This paper provides a systematic review of this emerging body of research. It is concluded that, although the evidence is still limited at this stage, extant research does indeed suggest that psychotherapy may be associated with epigenetic changes. Furthermore, it is argued that epigenetic studies may play a key role in the identification of biomarkers implicated in vulnerability for psychopathology, and thus may improve diagnosis and open up future research opportunities regarding the mechanism of action of psychotropic drugs as well as psychotherapy. We review evidence suggesting there may be important individual differences in susceptibility to environmental input, including psychotherapy. In addition, given that there is increasing evidence for the transgenerational transmission of epigenetic modifications in animals and humans exposed to trauma and adversity, epigenetic changes produced by psychotherapy may also potentially be passed on to the next generation, which opens up new perspective for prevention science. We conclude this paper stressing the limitations of current research and by proposing a set of recommendations for future research in this area. [ABSTRACT FROM AUTHOR]

Adherent-invasive Escherichia coli (AIEC) strains are genetically variable and virulence factors for AIEC are non-specific. FimH is the most studied pathogenicity-related protein, and there have been few studies on other proteins, such as Serine Protease Autotransporters of Enterobacteriacea (SPATEs). The goal of this study is to characterize E. coli strains isolated from patients with Crohn's disease (CD) in Chile and Spain, and identify genetic differences between strains associated with virulence markers and clonality. We characterized virulence factors and genetic variability by pulse field electrophoresis (PFGE) in 50 E. coli strains isolated from Chilean and Spanish patients with CD, and also determined which of these strains presented an AIEC phenotype. Twenty-six E. coli strains from control patients were also included. PFGE patterns were heterogeneous and we also observed a highly diverse profile of virulence genes among all E. coli strains obtained from patients with CD, including those strains defined as AIEC. Two iron transporter genes chuA, and irp2, were detected in various combinations in 68-84%of CD strains.We found that themost significant individual E. coli geneticmarker associatedwith CD E. coli strains was chuA. In addition, patho-adaptative fimHmutations were absent in some of the highly adherent and invasive strains. The fimH adhesin, the iron transporter irp2, and Class-2 SPATEs did not show a significant association with CD strains. The V27A fimH mutation was detected in the most CD strains. This study highlights the genetic variability of E. coli CD strains from two distinct geographic origins, most of them affiliated with the B2 or D E. coli phylogroups and also reveals that nearly 40% of Chilean and Spanish CD patients are colonized with E.coli with a characteristic AIEC phenotype. [ABSTRACT FROM AUTHOR]

Background: The importance of in silico predictions for understanding cellular processes is now widely accepted, and a variety of algorithms useful for studying different biological features have been designed. In particular, the prediction of cis regulatory modules in non-coding human genome regions represents a major challenge for understanding gene regulation in several diseases. Recently, studies of the Wnt signaling pathway revealed a connection with neurodegenerative diseases such as Alzheimer's. In this article, we construct a classification tool that uses the transcription factor binding site motifs composition of some gene promoters to identify new Wnt/β-catenin pathway target genes potentially involved in brain diseases. Results: In this study, we propose 89 new Wnt/β-catenin pathway target genes predicted in silico by using a method based on multiple Classification and Regression Tree (CART) analysis. We used as decision variables the presence of transcription factor binding site motifs in the upstream region of each gene. This prediction was validated by RT-qPCR in a sample of 9 genes. As expected, LEF1, a member of the T-cell factor/lymphoid enhancer-binding factor family (TCF/LEF1), was relevant for the classification algorithm and, remarkably, other factors related directly or indirectly to the inflammatory response and amyloidogenic processes also appeared to be relevant for the classification. Among the 89 new Wnt/β-catenin pathway targets, we found a group expressed in brain tissue that could be involved in diverse responses to neurodegenerative diseases, like Alzheimer's disease (AD). These genes represent new candidates to protect cells against amyloid β toxicity, in agreement with the proposed neuroprotective role of the Wnt signaling pathway. Conclusions: Our multiple CART strategy proved to be an effective tool to identify new Wnt/β-catenin pathway targets based on the study of their regulatory regions in the human genome. In particular, several of these genes represent a new group of transcriptional dependent targets of the canonical Wnt pathway. The functions of these genes indicate that they are involved in pathophysiology related to Alzheimer's disease or other brain disorders. [ABSTRACT FROM AUTHOR]

Calcium/calmodulin-dependent protein kinase IV (CaMKIV) plays a key role in the regulation of calcium-dependent gene expression. The expression of CaMKIV and the activation of CREB regulated genes are involved in memory and neuronal survival. We report here that: (a) a bioinformatic analysis of 15,476 promoters of the human genome predicted several Wnt target genes, being CaMKIV a very interesting candidate; (b) CaMKIV promoter contains TCF/LEF transcription motifs similar to those present in Wnt target genes; (c) biochemical studies indicate that lithium and the canonical ligand Wnt-3a induce CaMKIV mRNA and protein expression levels in rat hippocampal neurons as well as CaMKIV promoter activity; (d) treatment of hippocampal neurons with Wnt-3a increases the binding of β-catenin to the CaMKIV promoter: (e) In vivo activation of the Wnt signaling improve spatial memory impairment and restores the expression of CaMKIV in a mice double transgenic model for Alzheimer's disease which shows decreased levels of the kinase. We conclude that CaMKIV is regulated by the Wnt signaling pathway and that its expression could play a role in the neuroprotective function of the Wnt signaling against the Alzheimer's amyloid peptide. J. Cell. Physiol. 221: 658–667, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Objective: To assess pulmonary embolism incidence, its relationship with D-dimer levels and other possible associated factors in addition to anticoagulation and contrast medium adverse effects., Methods: A retrospective observational cohort study at a Chilean public hospital was performed. Intensive care unit mechanically ventilated COVID-19 patients older than 18 years old between March and June 2020 were included. All patients received heparin thromboprophylaxis, which was increased to the anticoagulation dose with D-dimer greater than 3µg/mL., Results: A total of 127 patients were followed up, of whom 73 underwent pulmonary computed tomography angiography (mean age, 54 ± 12 years; 49 men). Sixty-two of the 73 patients (84.9%) received full anticoagulation before computed tomography angiography. In addition, 18 of the 73 patients had pulmonary embolism (24.7%). When comparing patients with and without pulmonary embolism, no significant differences were observed in age, sex, obesity, smoking, Wells and revised Geneva scores, D-dimer or mortality. Anticoagulant use was similar in both groups. Days from the start of anticoagulation until computed tomography angiography were significantly lower in the pulmonary embolism group (p = 0.002). Three patients presented post contrast-acute kidney injury (4.1%), and one patient had major bleeding., Conclusion: Despite anticoagulation, one in four COVID-19 patients connected to mechanical ventilation and evaluated with pulmonary computed tomography angiography had pulmonary embolism. With a longer the delay in performing computed tomography angiography once empirical anticoagulation was started, significantly less pulmonary embolism was identified.

Abstract-Population aging is among the most important global transformations. Compared to European and North American countries, Chile is among the countries with the fastest growth of life expectancy at birth during recent decades. The aging of Chile's population is related to the improvement of living conditions, but also entails risks that tend to be associated with a rapid economic growth accompanied by large income inequalities and a chronic deficit of basic social benefits. The rapid demographic transition towards an aged population has unfolded in a context of poor development of public policies to tackle the opportunities and needs associated with an aging society. This article provides a brief overview of current Chilean public policy on aging, with a focus on healthy aging as defined by World Health Organization. The discussion addresses core challenges to successfully achieve healthy aging in Chile.