Endoplasmic Reticulum Stress in Gliomas: Exploiting a Dual-Effect Dysfunction through Chemical Pharmaceutical Compounds and Natural Derivatives for Therapeutical Uses.

The endoplasmic reticulum maintains proteostasis, which can be disrupted by oxidative stress, nutrient deprivation, hypoxia, lack of ATP, and toxicity caused by xenobiotic compounds, all of which can result in the accumulation of misfolded proteins. These stressors activate the unfolded protein response (UPR), which aims to restore proteostasis and avoid cell death. However, endoplasmic response-associated degradation (ERAD) is sometimes triggered to degrade the misfolded and unassembled proteins instead. If stress persists, cells activate three sensors: PERK, IRE-1, and ATF6. Glioma cells can use these sensors to remain unresponsive to chemotherapeutic treatments. In such cases, the activation of ATF4 via PERK and some proteins via IRE-1 can promote several types of cell death. The search for new antitumor compounds that can successfully and directly induce an endoplasmic reticulum stress response ranges from ligands to oxygen-dependent metabolic pathways in the cell capable of activating cell death pathways. Herein, we discuss the importance of the ER stress mechanism in glioma and likely therapeutic targets within the UPR pathway, as well as chemicals, pharmaceutical compounds, and natural derivatives of potential use against gliomas.

Assessment of the oxidative status in mother-child couples from Seville (Spain): A prospective cohort study.

Pregnancy requires a high demand of energy, which leads to an increase of oxidative stress. The aim of this study was to assess the oxidative status in 200 couples of pregnant women-newborns at the time of delivery, for the first time, who gave birth in two University Hospitals from the province of Seville. Recruited women filled an epidemiological questionnaire with their demographic characteristics and dietary habits during pregnancy. At the time of delivery, both maternal and cord blood samples were collected. Protein oxidation, superoxide dismutase, and catalase levels were measured to assess the oxidative status of these women, together with the levels of vitamins D, B12, Zn, Se, and Cu. Our results showed a tendency for all biomarkers measured to be higher in cord blood than in maternal blood. For the correlations established between the OS markers and sociodemographic characteristics, only significant differences for carbonyl groups values were found on both maternal and cord blood, relating these higher values to the use of insecticides in the women's homes. For newborns, only a significant correlation was detected between antioxidant enzymes and the newborn's weight, specifically for superoxide dismutase activity. Additionally, the higher values obtained in cord blood might suggest metabolization, while a higher production of ROS and antioxidant enzymes might be required to maintain the balance. Measured levels for Se were similar in both maternal and cord blood, unlike Cu and Zn, where higher levels were found for maternal blood than cord blood, indicating a correlation between maternal Se values and SOD as OS biomarker. Furthermore, vitamin D levels were around the optimum values established, finding a relationship between vitamin D and new-born's height, unlike for vitamin B12 values, where a correlation with maternal food consumption characteristics was established. Overall values were inside normal ranges and consistent for our population.

Severe congenital X-linked myopathy with excessive autophagy secondary to an apparently synonymous but pathogenic novel variant.

X-linked myopathy with excessive autophagy is a rare inherited disease characterized by aberrant accumulation of autophagic vacuoles in skeletal muscle. Affected males usually show a slow progression and the heart is characteristically spared. We present four male patients from the same family with an extremely aggressive form of this disease, requiring permanent mechanical ventilation from birth. Ambulation was never achieved. Three died, one in the first hour of life, one at 7 years and one at 17 years, the last death being a consequence of heart failure. Muscle biopsy showed pathognomonic features of the disease in the 4 affected males. Genetic study found a novel synonymous variant in VMA21, c.294C>T (Gly98=). Genotyping was consistent with co-segregation with the phenotype in an X-linked recessive manner. An alteration of the normal splice pattern was confirmed by transcriptome analysis, proving that the apparently synonymous variant was the cause of this extremely severe phenotype.

On the relationship between valence and arousal in samples across the globe.

Affect is involved in many psychological phenomena, but a descriptive structure, long sought, has been elusive. Valence and arousal are fundamental, and a key question-the focus of the present study-is the relationship between them. Valence is sometimes thought to be independent of arousal, but, in some studies (representing too few societies in the world) arousal was found to vary with valence. One common finding is that arousal is lowest at neutral valence and increases with both positive and negative valence: a symmetric V-shaped relationship. In the study reported here of self-reported affect during a remembered moment (N = 8,590), we tested the valence-arousal relationship in 33 societies with 25 different languages. The two most common hypotheses in the literature-independence and a symmetric V-shaped relationship-were not supported. With data of all samples pooled, arousal increased with positive but not negative valence. Valence accounted for between 5% (Finland) and 43% (China Beijing) of the variance in arousal. Although there is evidence for a structural relationship between the two, there is also a large amount of variability in this relation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Geneva Global Hub for Education in Emergencies: A new ally for education in emergencies.

This article provides an overview of the current landscape and needs for education in emergencies, as well as challenges and opportunities in today's critical juncture, in particular with the creation of a new ally for education in emergencies: the Geneva Global Hub for Education in Emergencies. It covers the disruption of education by the Covid-19 pandemic and the associated exacerbation of child-protection risks, as well as the pandemic's impact on the realization of the right to education of displaced children and youth and those living in humanitarian crises. While there is ample recognition at the international policy level of the importance of education in emergencies, major obstacles still prevail, such as continued underfunding and the underprioritization of education in humanitarian situations. As the world faces unparalleled needs, in particular during crises, and grapples to accelerate progress toward Sustainable Development Goal 4 and meet the commitments set out in the Global Compact for Refugees, new opportunities promise to tap opportune alliances, to inspire commitment, and to boost country-level impact.

Monitoring of metals and metalloids from maternal and cord blood samples in a population from Seville (Spain).

Nowadays there is an increasing concern about exposition during prenatal stage to environmental pollutants such as metals, that make pregnant women a vulnerable group of population. Numerous studies have shown associations between the prenatal exposition to some metals and an impact on cognitive, motor and intellectual development of the child. Metals and metalloid are ubiquitous in the environment and pregnant women are exposed to them though their diet, lifestyle factors or occupational and environmental sources. One hundred of maternal and one hundred of cord blood samples were obtained at delivery from pregnant women after signing of the informed consent to determine simultaneously levels of Al, As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Se and Zn by ICP-MS. Among these metals, essential ones (Cu, Mn, Se and Zn) can have health beneficial effects at low levels, however, in high concentration are potentially toxic. On the other hand, elements such as Al, As, Cd, Hg, Pb are classified as toxic metals, no matter what its concentration was. The aim of this study was to find the potential relationships between these metals and metalloid levels, newborn's parameters, pregnancy details and the epidemiologic information obtained using a questionnaire data from the participant pregnant women from Seville (Spain). A n = 100 of participants have been enrolled, 15.6 % of the women from Virgen del Rocio Hospital were smokers during pregnancy but only 11.1 % from Virgen de Valme had the habit. Dietary habits of all participants from both hospital were quite similar in average rice, fish and canned food consumption. The characteristics of newborns were also quite similar for both hospitals. A positive correlation between maternal and cord blood was found between all metals except for Cr and Cu. The strongest correlation was found for Hg (r = 0.779, p < 0.005). Positive but weaker correlations between maternal blood and lifestyle habits were also established.

Are Anti-Prostitution Advertising Campaigns Effective? An Experimental Study.

Many governments invest public funds in communication interventions and campaigns against prostitution and sexual exploitation in an attempt to change attitudes toward prostitution and eventually decrease its consumption. Despite the considerable investment that public institutions have made in campaigns against prostitution and sexual slavery, no known empirical studies have evaluated the effectiveness of such campaigns on attitudes and behavioral change. The messages of these campaigns usually center on one of two thematic focuses: Prostituted women who suffer exploitation and male consumers of prostitution. The present study examines the impact of different anti-prostitution advertisements on attitudes among male participants (N = 155 male participants). Specifically, the experiment aims to test the differential effect of these two focuses, compared to a no-advertisement control condition, on social support for prostitution, negative and incorrect beliefs about prostitutes, and family values related to prostitution. The results show that compared with the no-advertisement control condition, advertisements focused on men who use prostitutes have a significant effect on social support toward prostitution and incorrect beliefs about prostitutes, whereas advertisements focused on female prostitutes have no effect. The results have practical implications for governments and councils regarding the efficacy of this kind of public communication campaign against prostitution consumption.

The links among relative financial scarcity, thinking style, fatalism, and well-being.

In the present research, we examined the links among relative financial scarcity, thinking style, fatalism, and well-being and their roles in predicting protective behaviors against COVID-19. Study 1 (N = 120) revealed that after an experimental manipulation to induce the perception of relative financial scarcity (versus financial abundance), people who perceived higher relative financial scarcity changed their thinking style to a more concrete mindset. In Study 2 (N = 873), the relative financial abundance-scarcity situation was measured, and the results showed that the greater the perceived relative financial scarcity was, the more concrete the mindset and the lower the sense of well-being. Importantly, we found that individuals who felt poorer but maintained an abstract thinking style reported higher well-being. Study 3 (N = 501) examined the influence of a concrete thinking style in people who perceived that their economic situation had worsened with the pandemic. The results showed that when this vulnerable population presented a more concrete mindset, they reported lower well-being, higher fatalism, and lower protective behavior against COVID-19. Thus, maintaining an abstract mindset promotes higher well-being, lower fatalism, and greater protective behaviors against COVID-19, even under economic difficulties. Because thinking style can be modified, our results encourage the development of new social intervention programs to promote an abstract mindset when people face important challenges.

Guilt Without Fault: Accidental Agency in the Era of Autonomous Vehicles.

The control principle implies that people should not feel guilt for outcomes beyond their control. Yet, the so-called 'agent and observer puzzles' in philosophy demonstrate that people waver in their commitment to the control principle when reflecting on accidental outcomes. In the context of car accidents involving conventional or autonomous vehicles (AVs), Study 1 established that judgments of responsibility are most strongly associated with expressions of guilt-over and above other negative emotions, such as sadness, remorse or anger. Studies 2 and 3 then confirmed that, while people generally endorse the control principle, and deny that occupants in an AV should feel guilt when involved in an accident, they nevertheless ascribe guilt to those same occupants. Study 3 also uncovered novel implications of the observer puzzle in the legal context: Passengers in an AV were seen as more legally liable than either passengers in a conventional vehicle, or even their drivers-especially when participants were prompted to reflect on the passengers' affective experience of guilt. Our findings document an important conflict-in the context of AV accidents-between people's prescriptive reasoning about responsibility and guilt on one hand, and their counter-normative experience of guilt on the other, with apparent implications for liability decisions.

The interplay between estrogen receptor beta and protein kinase C, a crucial collaboration for medulloblastoma cell proliferation and invasion.

Medulloblastoma (MB) is the most common and aggressive pediatric intracranial tumor. Estrogen receptor ß (ERß) expression correlates with MB development and its phosphorylation modifies its transcriptional activity in a ligand-dependent or independent manner. Using in silico tools, we have identified several residues in ERß protein as potential targets of protein kinases C (PKCs) α and δ. Using Daoy cells, we observed that PKCα and PKCδ associate with ERß and induce its phosphorylation. The activation of ERß promotes MB cells proliferation and invasion, and PKCs downregulation dysregulates these steroid receptor mediated processes. Our data suggest that these kinases may play a crucial role in the regulation of the ERß transcriptional activity. Overexpression of both PKCα and PKCδ in MB biopsies samples supports their relevance in MB progression.

Are Anti-Prostitution Advertising Campaigns Effective? An Experimental Study

Many governments invest public funds in communication interventions and campaigns against prostitution and sexual exploitation in an attempt to change attitudes toward prostitution and eventually decrease its consumption. Despite the considerable investment that public institutions have made in campaigns against prostitution and sexual slavery, no known empirical studies have evaluated the effectiveness of such campaigns on attitudes and behavioral change. The messages of these campaigns usually center on one of two thematic focuses: Prostituted women who suffer exploitation and male consumers of prostitution. The present study examines the impact of different anti-prostitution advertisements on attitudes among male participants (N = 155 male participants). Specifically, the experiment aims to test the differential effect of these two focuses, compared to a no-advertisement control condition, on social support for prostitution, negative and incorrect beliefs about prostitutes, and family values related to prostitution. The results show that compared with the no-advertisement control condition, advertisements focused on men who use prostitutes have a significant effect on social support toward prostitution and incorrect beliefs about prostitutes, whereas advertisements focused on female prostitutes have no effect. The results have practical implications for governments and councils regarding the efficacy of this kind of public communication campaign against prostitution consumption. (AU)

Nutritional Quality of the Most Consumed Varieties of Raw and Cooked Rice in Spain Submitted to an In Vitro Digestion Model.

Rice is one of the most consumed staple foods around the world and its trade is highly globalized. Increased environmental pollution generates a large amount of waste that, in many cases, is discarded close to culture fields. Some species are able to bioaccumulate toxic substances, such as metals, that could be transferred to the food chain. The main goal of this study was to evaluate the content of metallic (Al, Cd, Pb, and Cr) and metalloid elements (As) in 14 of the most consumed varieties of rice in Spain and their effects on human health. The samples were cooked, and human digestion was simulated by using a standard in vitro digestion method. Metallic and metalloid element levels were analysed by Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES), previous called microwave digestion. Both the human health risk index, Hazard Quotient, and Lifetime Cancer Risk did not show toxic values in any case. Rice with a higher non-digestible fraction showed a higher liberation of proteins and a lower glycemic index. There were no significant differences in the concentrations of metallic and metalloid elements in cooked rice or in the digestible fraction in all varieties analysed. However, Al concentrations were higher than other metals in all varieties studied due to its global distribution. No relationship has been observed between the digestibility of rice and the bioaccessibility of each metallic and metalloid element. All of the studied rice varieties are healthy food products and its daily consumption is safe. The regular monitoring of metals and As in rice consumed in Spain may contribute to improvements in the human health risk evaluation.

Differences Between the Psychological Symptoms of Health Workers and General Community After the First Wave of the COVID-19 Outbreak in Spain.

The coronavirus disease-2019 (COVID-19) has worsened the physical and mental health of the general population. Healthcare workers have a high risk of suffering a mental disorder after the first wave. In this way, psychologists, who deal with mental health issues and are considered as healthcare workers in many countries, are of interest in this context. The present study aimed to examine anxiety, depression, stress, and obsessions and compulsions across psychologists, healthcare professionals, and the general community. These variables were measured through the Depression, Anxiety, and Stress Scale (DASS-21), as well as the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), which are related to different sociodemographic variables. The study was carried out after the first wave in Spain through an online questionnaire. Structural equation modeling and a multigroup analysis were carried out across the groups and variables under study. The results suggested that; (i) healthcare workers and general community depicted similar results in anxiety and stress, as well as obsessions; (ii) the group of psychologists depicted better scores than the other groups under study; (iii) stress and anxiety did not predict compulsions in the group of psychologists; (iv) anxiety predicted obsessions for all the professions, while the relationship of this variable with stress was different for each group; and (v) invariance reached a full metric level.

Impact of Pesticide Exposure among Rural and Urban Female Population. An Overview.

Pesticides are substances that have become widely used in agriculture and the human exposure to these substances may cause adverse health outcomes. Non-occupational exposure to them can come from many sources, such as food or water. For occupational exposure, many studies have been conducted in men, as they have been mostly in charge of work related to these substances. Nonetheless, the information available concerning the exposure in women is very scarce. In addition, an important differentiation between rural and urban areas has been established, rural areas being known as the most exposed ones due to plantation fields. However, the application of higher concentrations of herbicides in small urban areas is taking a lot of importance currently as well. Regardless of gender, the conditions of exposure, and the environment, the exposure to these pesticides can have different effects on health from early life stages, resulting in different outcomes ranging from neurodevelopmental effects in newborns to different types of cancers. In this review, we discussed the toxicity of the most commonly used pesticides and the main impact on the health of the general population, focusing mainly on the effect in women from both rural and urban areas, and the different stages of development, from pregnancy or lactation to the outcomes of these exposures for their children.

High expression of Toll-like receptor 7 is a survival factor in pediatric medulloblastoma.

PURPOSE: Medulloblastoma is an embryonal brain tumor that predominantly occurs in childhood with a wide histological and molecular variability. Our aim was to investigate the expression of Toll-like receptors (TLRs), their association with the infiltration of immune cells and with the histological subgroups, and, also, with the overall survival of patients. METHODS: Fifty-six paraffin-preserved biopsies from children with medulloblastoma of the classic, desmoplastic, and anaplastic subtypes were included. Microarrays of tissues were performed, and the infiltration of T and NK cells was quantified, as well as the expression of TLR7, TLR8, and TLR9. For all statistical analyses, significance was p < 0.05. RESULTS: CD4 + and CD8 + T lymphocytes and NK cells were found infiltrating the tumor. The infiltration of NK and CD4 + cells was greater in the classic and desmoplastic subtypes than in anaplastic. We found an important expression of TLRs in all medulloblastomas, but TLR7 and TLR8 were considerably higher in classic and desmoplastic subtypes than in anaplastic. Importantly, we observed that TLR7 was a prognostic factor for survival. CONCLUSIONS: Medulloblastomas present cellular infiltration and a differential expression of TLRs depending on the histological subtype. TLR7 is a prognostic factor of survival that is dependent on treatment and age.

Association of Genetic Polymorphisms and Serum Levels of IL-6 and IL-8 with the Prognosis in Children with Neuroblastoma.

There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 (p = 0.014) and AA genotypes of rs4073 IL-8 (p = 0.002), as well as high levels of IL-6 (p = 0.009) and IL-8 (p = 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.