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Child exposure to maltreatment and neglect constitutes a significant public health problem throughout Latin American and Caribbean (LAC) countries. Although evidence-based parent training (PT) interventions constitute an empirically demonstrated alternative to prevent child maltreatment and neglect, multiple implementation barriers have prevented the large-scale dissemination of evidence-based PT interventions across LAC countries. This selective prevention study consisted of an exploratory quasi-experimental design implemented in Chile, aimed at examining the initial impact of a culturally adapted version of the evidence-based PT intervention known as GenerationPMTO©. The parenting intervention was adapted in a previous pilot study, according to a rigorous model of cultural adaptation. Based on self-reports completed by 281 caregivers, when compared to baseline measurements, significant improvements at intervention completion were observed in the majority of caregivers' parenting practices, as well as child internalizing and externalizing problematic behaviors. This study provides promising initial empirical evidence that efficacious PT interventions developed in the US can be transported to Latin American contexts, as long as they are thoroughly adapted to achieve high contextual and cultural relevance. The rates of child maltreatment across LAC countries constitute an urgent and permanent call for strongly promoting this line of prevention research., (© 2023 Family Process Institute.)

Parent training (PT) interventions constitute an empirically demonstrated alternative to promote effective parenting practices and prevent child behavioral and mental health problems. However, the dissemination of evidence-based PT interventions across Latin America remains scarce. This qualitative study had the primary objective of evaluating the level of acceptability of a culturally adapted version of the PT intervention known as GenerationPMTO © , adapted for the Chilean context. According to qualitative reports provided by 24 Chilean caregivers exposed to the culturally adapted parenting intervention, the intervention was perceived by caregivers as useful for their parenting practices, as well as contextually and culturally relevant. Current qualitative findings indicate that the culturally adapted PT intervention holds promise for larger dissemination in the Chilean context., (© 2022 American Association for Marriage and Family Therapy.)

Background: The lack of knowledge of the progression mechanisms of glioblastoma (GB), the most aggressive brain tumor, contributes to the absence of successful therapeutic strategies. Our team has recently demonstrated a crucial new role for chaperone-mediated autophagy (CMA) in pericytes (PC)-acquired immunosuppressive function, which prevents anti-tumor immune responses and facilitates GB progression. The possible impact that GB-induced CMA in PC has on other functions that might be useful for future GB prognosis/treatment, has not been explored yet. Thus, we proposed to analyze the contribution of CMA to other GB-induced changes in PC biology and determine if CMA ablation in PC is a key target mechanism for GB treatment. Methods: Studies of RNA-seq and secretome analysis were done in GB-conditioned PC with and without CMA (from knockout mice for LAMP-2A) and compared to control PC. Different therapeutic strategies in a GB mouse model were compared. Results: We found several gene expression pathways enriched in LAMP2A-KO PC and affected by GB-induced CMA in PC that correlate with our previous findings. Phagosome formation, cellular senescence, focal adhesion and the effector function to promote anti-tumor immune responses were the most affected pathways, revealing a transcriptomic profiling of specific target functions useful for future therapies. In addition, several molecules associated with tumor mechanisms and related to tumor immune responses such as gelsolin, periostin, osteopontin, lumican and vitamin D, were identified in the PC secretome dependent on GB-induced CMA. The CMA ablation in PC with GB cells showed an expected immunogenic phenotype able to phagocyte GB cells and a key strategy to develop future therapeutic strategies against GB tumor progression. A novel intravenous therapy using exofucosylated CMA-deficient PC was efficient to make PC reach the tumor niche and facilitate tumor elimination. Conclusion: Our results corroborate previous findings on the impaired immunogenic function of PC with GB-induced CMA, driving to other altered PC functions and the identifications of new target markers related to the tumor immune responses and useful for GB prognosis/therapy. Our work demonstrates CMA ablation in PC as a key target mechanism to develop a successful therapy against GB progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Molina, García-Bernal, Salinas, Rubio, Aparicio, Moraleda, Martínez and Valdor.)

KcsA, a prokaryote tetrameric potassium channel, was the first ion channel ever to be structurally solved at high resolution. This, along with the ease of its expression and purification, made KcsA an experimental system of choice to study structure-function relationships in ion channels. In fact, much of our current understanding on how the different channel families operate arises from earlier KcsA information. Being an integral membrane protein, KcsA is also an excellent model to study how lipid-protein and protein-protein interactions within membranes, modulate its activity and structure. In regard to the later, a variety of equilibrium and non-equilibrium methods have been used in a truly multidisciplinary effort to study the effects of lipids on the KcsA channel. Remarkably, both experimental and "in silico" data point to the relevance of specific lipid binding to two key arginine residues. These residues are at non-annular lipid binding sites on the protein and act as a common element to trigger many of the lipid effects on this channel. Thus, processes as different as the inactivation of channel currents or the assembly of clusters from individual KcsA channels, depend upon such lipid binding.

Purpose: Caudal-related homeobox transcription factor 2 (CDX2) has recently been proposed as a prognostic factor for gastric carcinoma. However and to the best of our knowledge, no previous report has analyzed CDX2 expression in patients with gastric adenocarcinoma receiving neoadjuvant therapy (NAT)., Patients, Materials and Methods: This is a retrospective cohort study to analyze the potential role of CDX2 expression to predict response to NAT and prognosis. This study has enrolled 57 patients receiving chemotherapy for locally advanced gastric carcinoma., Results: 59.6% of the patients were men; mean age was 64.96 years. Only 8% of the patients showed a complete response to therapy, 10% had grade 1, 28% grade 2, and 54% grade 3 regression, respectively, according to modified Ryan's criteria. On follow-up, 38.6% of the patients showed recurrence of disease (50% distant metastasis) and 28.1% eventually died of it. Twenty-three (40.4%) patients showed intense CDX2 expression. We found a statistically significant association between CDX2 expression and poor regression with NAT, but we found no association with outcome., Discussion: Our study indicates that CDX2 expression can predict lack of response to NAT. Our results have not confirmed the association with prognosis shown in previous reports., Conclusions: Despite these preliminary results, furthermore studies are necessary to define the potential use of CDX2 in gastric carcinoma.

MTX is an effective therapy for autoimmune-inflammatory diseases. The mechanisms that mediate these actions are not completely clear. It is accepted that many of these effects are mediated through the release of adenosine with the activation of the adenosine receptor A2. MTX is used as a steroid sparing agent. An improved in vitro GC cell sensitivity in GC insensitive asthma patients has been demonstrated after MTX treatment. Most GC actions are mediated by the GCR. The effect of MTX on GCRs expression has not been previously evaluated. Therefore, we evaluate if MTX regulates the expression of glucocorticoid receptors, increasing the expression of the active receptor (GCR alpha) and/or decreasing the expression of the dominant negative receptor (GCR beta). We show that MTX increases the mRNA and protein levels of GCR alpha and decreases or leaves unchanged the protein expression of the GCR beta in CEM cells in culture. This effect was also observed in other lymphocytes (Jurkat and Raji) and in PBMNC from healthy volunteers. We also show that upon MTX treatment PBMC from normal volunteers exhibit a higher sensitivity to DEX inhibition on LPS-induced TNF alpha release. To explore if these actions are mediated by adenosine through the adenosine receptor A2 we evaluate the effect of adenosine on the GCRs expression and the effect of an A2 receptor blocker (DMPX) on MTX effects on GCRs expression. Our results show that adenosine does not mimic and DMPX can enhance MTX effects on these receptors. We conclude that MTX increases the GCR alpha/GCR beta ratio of expression in lymphocytes which could mediate its previously reported effects in improving cell glucocorticoid sensitivity. These actions are not mediated by the adenosine receptor A2.

Viscotoxins are cationic proteins, isolated from different mistletoe species, that belong to the group of thionins, a group of basic cysteine-rich peptides of approximately 5 kDa. They have been shown to be cytotoxic to different types of cell, including animal, bacterial and fungal. The aim of this study was to obtain information on the cell targets and the mechanism of action of viscotoxin isoform A3 (VtA3). We describe a detailed study of viscotoxin interaction with fungal-derived model membranes, its location inside spores of Fusarium solani, as well as their induced spore death. We show that VtA3 induces the appearance of ion-channel-like activity, the generation of H2O2, and an increase in cytoplasmic free Ca2+. Moreover, we show that Ca2+ is involved in VtA3-induced spore death and increased H2O2 concentration. The data presented here strongly support the notion that the antifungal activity of VtA3 is due to membrane binding and channel formation, leading to destabilization and disruption of the plasma membrane, thereby supporting a direct role for viscotoxins in the plant defence mechanism.