Reticulocyte Antioxidant Enzymes mRNA Levels versus Reticulocyte Maturity Indices in Hereditary Spherocytosis, ß-Thalassemia and Sickle Cell Disease.

The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and peroxiredoxin 2 (Prx2) are particularly important in erythroid cells. Reticulocytes and other erythroid precursors may adapt their biosynthetic mechanisms to cell defects or to changes in the bone marrow environment. Our aim was to perform a comparative study of the mRNA levels of CAT, GPX1, PRDX2 and SOD1 in reticulocytes from healthy individuals and from patients with hereditary spherocytosis (HS), sickle cell disease (SCD) and ß-thalassemia (ß-thal), and to study the association between their transcript levels and the reticulocyte maturity indices. In controls, the enzyme mRNA levels were significantly correlated with reticulocyte maturity indices for all genes except for SOD1. HS, SCD and ß-thal patients showed younger reticulocytes, with higher transcript levels of all enzymes, although with different patterns. ß-thal and HS showed similar reticulocyte maturity, with different enzyme mRNA levels; SCD and HS, with different reticulocyte maturity, presented similar enzyme mRNA levels. Our data suggest that the transcript profile for these antioxidant enzymes is not entirely related to reticulocyte maturity; it appears to also reflect adaptive mechanisms to abnormal erythropoiesis and/or to altered erythropoietic environments, leading to reticulocytes with distinct antioxidant potential according to each anemia.

Toxicity Mechanisms of Gadolinium and Gadolinium-Based Contrast Agents-A Review.

Gadolinium-based contrast agents (GBCAs) have been used for more than 30 years to improve magnetic resonance imaging, a crucial tool for medical diagnosis and treatment monitoring across multiple clinical settings. Studies have shown that exposure to GBCAs is associated with gadolinium release and tissue deposition that may cause short- and long-term toxicity in several organs, including the kidney, the main excretion organ of most GBCAs. Considering the increasing prevalence of chronic kidney disease worldwide and that most of the complications following GBCA exposure are associated with renal dysfunction, the mechanisms underlying GBCA toxicity, especially renal toxicity, are particularly important. A better understanding of the gadolinium mechanisms of toxicity may contribute to clarify the safety and/or potential risks associated with the use of GBCAs. In this work, a review of the recent literature concerning gadolinium and GBCA mechanisms of toxicity was performed.

Age-Related Changes in Clinical and Analytical Variables in Chronic Hemodialyzed Patients.

Worldwide, the number of elderly individuals receiving chronic hemodialysis is rising. The aim of our study was to evaluate several clinical and analytical biomarkers in chronically dialyzed patients and analyze how they change with age. A cross-sectional study was performed by evaluating 289 end-stage renal disease patients undergoing dialysis. We evaluated the hemogram, adipokines, the lipid profile, and several markers related to inflammation, endothelial function/fibrinolysis, nutrition, iron metabolism, and cardiac and renal fibrosis. Clinical data and dialysis efficacy parameters were obtained from all patients. The relationships between studied biomarkers and age were assessed by a statistical comparison between younger (adults with age < 65 years) and older (age ≥ 65 years) patients and by performing regression analysis. Participants presented a mean age of 68.7 years (±13.6), with 66.8% (n = 193) being classified as older. Compared to younger patients, older patients presented the following: (a) significantly lower values of diastolic blood pressure (DBP) and ultrafiltration volume; (b) lower levels of phosphorus, uric acid, creatinine, and albumin; and (c) higher circulating concentrations of tissue-type plasminogen activator (tPA), D-dimer, interleukin-6, leptin, N-terminal pro B-type natriuretic peptide, and tissue inhibitor of metalloproteinase-1. In the multiple linear regression analysis, DBP values, tPA, phosphorus, and D-dimer levels were independently associated with the age of patients (standardized betas: -0.407, 0.272, -0.230, and 0.197, respectively; p < 0.001 for all), demonstrating relevant changes in biomarkers with increasing age at cardiovascular and nutritional levels. These findings seem to result from crosstalk mechanisms between aging and chronic kidney disease.

Inhibition of erythrocyte's catalase, glutathione peroxidase or peroxiredoxin 2 - Impact on cytosol and membrane.

Catalase (CAT), glutathione peroxidase (GPx) and Prx2 (peroxiredoxin 2) are the main antioxidant enzymatic defenses of erythrocytes. They prevent and minimize oxidative injuries in red blood cell (RBC) components, which are continuously exposed to oxidative stress (OS). The crosstalk between CAT, GPx and Prx2 is still not fully disclosed, as well as why these typically cytoplasmic enzymes bind to the RBC membrane. Our aim was to understand the interplay between CAT, GPx and Prx2 in the erythrocyte's cytosol and membrane. Under specific (partial) inhibition of each enzyme and increasing H2O2-induced OS conditions, we evaluated the enzyme activities and amounts, the binding of CAT, GPx and Prx2 to RBC membrane, and biomarkers of OS, such as the reduced and oxidized glutathione levels, thiobarbituric acid reactive substances (TBARS) levels, membrane bound hemoglobin and total antioxidant status. Our results support the hypothesis that when high levels of H2O2 get within the erythrocyte, CAT is the main player in the antioxidant protection of the cell, while Prx2 and GPx have a less striking role. Moreover, we found that CAT, appears to have more importance in the antioxidant protection of cytoplasm than of the membrane components, since when the activity of CAT is disturbed, GPx and Prx2 are both activated in the cytosol and mobilized to the membrane. In more severe OS conditions, the antioxidant activity of GPx is more significant at the membrane, as we found that GPx moves from the cytosol to the membrane, probably to protect it from lipid peroxidation.

Long Pentraxin 3 as a Broader Biomarker for Multiple Risk Factors in End-Stage Renal Disease: Association with All-Cause Mortality.

Persistent inflammation in end-stage renal disease (ESRD) patients is known to underlie the progression of chronic kidney disease and to be associated with multiple risk factors including malnutrition, atherosclerosis, and cardiovascular disease (CVD). The acute-phase protein pentraxin 3 (PTX3) has a proven potential as a local inflammatory biomarker, but its clinical utility in ESRD remains unclear. Circulating levels of PTX3 and classical inflammatory mediators, including the clinical prototypical C-reactive protein (CRP), were assessed in 246 ESRD patients on dialysis and analysed in relation to the lipid profile, adipokine levels, and nutritional, cardiac, and renal fibrosis markers. Occurrence of deaths was recorded for the following year. Contrarily to the classical inflammatory markers, PTX3 levels were negatively correlated with nutritional markers and associated with a less atherogenic lipid profile. Levels of the cardiac and renal fibrosis markers and of the oxidized LDL/LDL-C ratio were found to be independent determinants of PTX3 concentration. When comparing inflammatory mediators, the increase in the PTX3 levels was the only predictor of all-cause mortality in dialysis patients in a survival model adjusted to all markers under study, other than the inflammatory ones, besides common confounding factors in dialysis. Data support the clinical applicability of PTX3 as a broader inflammatory biomarker than the classical ones, presenting a close association with inflammation, malnutrition, CVD, and renal fibrosis and a great potential to predict all-cause mortality in dialysis patients. The pleiotropic character of PTX3 may be of clinical relevance, and it could be targeted to ameliorate the high morbidity and mortality associated with ESRD.

Hepcidin and diabetes are independently related with soluble transferrin receptor levels in chronic dialysis patients.

Background: Soluble transferrin receptor (sTfR) is a biomarker of erythropoiesis, which is often impaired in dialysis patients. The aim of our study was to evaluate sTfR levels in chronically dialyzed patients and assess potential determinants of its levels. Methods: We performed a cross-sectional study by evaluating 246 end-stage renal disease patients undergoing dialysis and 32 healthy controls. Circulating levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, hepcidin, sTfR, growth differentiation factor 15 (GDF15), and traditional iron metabolism markers were measured, as well as hemogram parameters. Clinical data was obtained from all patients. Results: Compared to controls, patients presented similar values of sTfR, reticulocytes and reticulocyte production index (RPI), and significantly higher levels of IL-6, CRP, ferritin, hepcidin, TNF-α, and GDF15. Iron, transferrin, hemoglobin levels, erythrocyte count, mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) values were significantly lower in dialysis group. Within patients, sTfR values were higher in diabetic patients and were positively and significantly correlated with reticulocytes and erythrocytes, RPI, and therapeutic doses of erythropoiesis stimulating agents (ESA) and intravenous iron; and inversely and significantly correlated with circulating iron, ferritin, transferrin saturation, hepcidin, MCH, and MCHC. In multiple linear regression analysis, ESA dose, RPI, serum iron, diabetes, and hepcidin levels were independently associated with sTfR levels in dialysis patients and, thus, with erythropoiesis. Conclusion: Our data suggest that, besides RPI and ESA dose, diabetes and hepcidin are closely related to erythropoiesis in dialysis patients. The influence of diabetes on sTfR levels deserves further investigation.

Physical exercise intervention at school improved hepcidin, inflammation, and iron metabolism in overweight and obese children and adolescents.

BackgroundObesity is often associated with iron deficiency in children and adolescents. We aimed to study the effect of an 8-month physical exercise (PE) intervention on hepcidin and other markers of inflammation and on iron status in overweight/obese children and adolescents.MethodsSeventy-three overweight/obese children and adolescents participated in the 8-month-long longitudinal study. They were divided into two groups according to their participation in an after-school PE program: the PE group (n=44) and the control group (n=29). Hepcidin, interleukin (IL)-6, C-reactive protein (CRP), iron, ferritin, transferrin, and soluble transferrin receptor (sTfR) were evaluated.ResultsAt baseline, IL-6 correlated positively with hepcidin and negatively with iron and transferrin saturation, suggesting that increasing adiposity associates with increasing IL-6 and hepcidin synthesis, reducing iron availability. After 8 months, the PE group showed a decrease in BMI z-score (P=0.003), body fat mass (P=0.012), CRP (P=0.002), IL-6 (P=0.048), ferritin (P=0.013), hepcidin (P=0.040), and sTfR (P=0.010), and an increase in iron concentration (P=0.002). Moreover, the PE group, when compared with the control group, showed lower weight (P=0.026), BMI (P=0.040), waist circumference (P=0.010), and waist-to-height ratio (P=0.046).ConclusionWe showed that an 8-month-long intervention at school allowed a reduction in BMI z-score and an improvement in inflammation, reducing hepcidin levels and the disturbances in iron status.

Resilience in the face of peer victimisation and discrimination: The who, when and why in five patterns of adjustment.

Victimisation has a negative effect on psychosocial functioning. Based on the resilience theory, and with a sample of 2975 Portuguese students, the present study aims to: i) identify patterns of adjustment in the face of peer victimisation and perceptions of discrimination; ii) explore the association between the patterns of adjustment and the characteristics of participants (the who) and of the victimisation (the when and why). Cluster analysis revealed five patterns of adjustment: Unchallenged; Externally Maladjusted; Internally Maladjusted; Resilient, and At-Risk. The results suggest that there is no complete resilience in the face of social victimisation. Group differences were found regarding: i) gender, type of course, sexual orientation, ethnicity, nationality, parental educational level and religious beliefs; ii) the age at which peer victimisation was more frequent, and; iii) the motives underlying discrimination. Globally considered, peer victimisation is representative of the wider cultural environment and interventions should also target social prejudices.

Impact of a School-Based Intervention Protocol - ACORDA Project - On Adipokines in An Overweight and Obese Pediatric Population.

PURPOSE: There are few reliable studies assessing the effect of physical exercise (PE) on adipokines levels at young ages. Our objective was to study the effects of regular PE on plasma adipokines in pediatric overweight and obesity. METHOD: 117 overweight and obese children and adolescents (47% females; 10.2 years) participated in an 8-month longitudinal study divided in two groups: PE group (n = 80), engaged in an after-school PE program; control group (n = 37), with no PE program. Plasma lipids, C-reactive protein (CRP), adiponectin, resistin, leptin, IL-6, IL-1beta, TNF-alpha, insulin and glucose levels were determined. RESULTS: contrarily to the control group, the PE group presented reductions in body mass index z-score (BMIzsc) and body fat percentage that were accompanied by an improvement in lipid profile and insulin resistance, a reduction in CRP and TNF-alpha and an increase in adiponectin levels. The reductions in BMIzsc were inversely correlated with changes in adiponectin (r=-0.329, p = .003) and positively correlated with changes in percentage body fat (r = .262, p = .032), triglycerides (r = .228, p = .042) and leptin (r = .285, p = .010). CONCLUSIONS: Moderate reductions in adiposity improve proinflammatory status in obese children and adolescents. A more substantial reduction in BMIzsc was associated with a greater increment in adiponectin and reduction in leptin.

Family support in the transition to adulthood in Portugal--its effects on identity capital development, uncertainty management and psychological well-being.

In a familistic southern European society such as the Portuguese, the family has historically played a prominent role in supporting the negotiation of transition pathways into adulthood. The present study aimed at capturing (1) the relative weight of parental financial support and autonomy support in contributing to the youngsters' psychological well-being (PWB), and (2) the mediating role of identity capital and uncertainty management in this relationship. A total of 620 participants completed measures of parental support, identity capital, uncertainty management and PWB. Autonomy support was found to be the strongest predictor of PWB, both directly and indirectly through its effects on identity capital and the use of target focused uncertainty management strategies. Conversely, financial support evidenced only a minor indirect impact through the mediation of tangible identity capital. Autonomy stimulation may constitute one of the most developmentally determinant family challenges in assisting the process of coming of age in Portugal.

Modulation of human dermal microvascular endothelial cell and human gingival fibroblast behavior by micropatterned silica coating surfaces for zirconia dental implant applications.

Dental ceramic implants have shown superior esthetic behavior and the absence of induced allergic disorders when compared to titanium implants. Zirconia may become a potential candidate to be used as an alternative to titanium dental implants if surface modifications are introduced. In this work, bioactive micropatterned silica coatings were produced on zirconia substrates, using a combined methodology of sol-gel processing and soft lithography. The aim of the work was to compare the in vitro behavior of human gingival fibroblasts (HGFs) and human dermal microvascular endothelial cells (HDMECs) on three types of silica-coated zirconia surfaces: flat and micropatterned (with pillars and with parallel grooves). Our results showed that cells had a higher metabolic activity (HGF, HDMEC) and increased gene expression levels of fibroblast-specific protein-1 (FSP-1) and collagen type I (COL I) on surfaces with pillars. Nevertheless, parallel grooved surfaces were able to guide cell growth. Even capillary tube-like networks of HDMEC were oriented according to the surface geometry. Zirconia and silica with different topographies have shown to be blood compatible and silica coating reduced bacteria adhesion. All together, the results indicated that microstructured bioactive coating seems to be an efficient strategy to improve soft tissue integration on zirconia implants, protecting implants from peri-implant inflammation and improving long-term implant stabilization. This new approach of micropatterned silica coating on zirconia substrates can generate promising novel dental implants, with surfaces that provide physical cues to guide cells and enhance their behavior.

Intergenerational Solidarity During Emerging Adulthood: Associations with Psychological Distress and Satisfaction with Life in Southern Europe.

Background: Intergenerational solidarity between parents and emerging adult offspring requires more substantial attention at the present time. Changing demographic structures and transformations in family dynamics over recent decades have increased both opportunities and the need for parent-child interactions and exchanges of support and affection during emerging adulthood. Purpose: The study had two aims: first, to explore patterns in intergenerational solidarity in accordance with different sociodemographic characteristics of emerging adults; and second, to analyse associations between intergenerational solidarity and emerging adults' psychological distress and satisfaction with life. Methods: Participants were 644 emerging adult university students from Southern Europe (Spain and Portugal), aged between 18 and 29 years, who completed a self-report questionnaire designed to assess variables linked to sociodemographic aspects (gender, country of residence, sexual orientation, living status, family income), intergenerational solidarity, psychological distress and satisfaction with life. Results: The results indicated some differences in intergenerational solidarity patterns in accordance with a range of sociodemographic characteristics. They also revealed significant associations between intergenerational solidarity dimensions and emerging adults' satisfaction with life and psychological distress. Moreover, affective solidarity was found to fully mediate the relationship between associational, functional and normative solidarity and emerging adults' adjustment. In the case of conflictual solidarity, affective solidarity was found to partially mediate the relationship between this dimension of intergenerational solidarity and emerging adults' distress and to fully mediate the relationship between this same dimension and emerging adults' satisfaction with life. Conclusion: The results indicate that it is important to take sociodemographic diversity into account when exploring relationships between emerging adults and their parents. They also suggest that affective solidarity acts as a protective factor in promoting emerging adults' adjustment.

Catalase, Glutathione Peroxidase, and Peroxiredoxin 2 in Erythrocyte Cytosol and Membrane in Hereditary Spherocytosis, Sickle Cell Disease, and ß-Thalassemia.

Catalase (CAT), glutathione peroxidase (GPx), and peroxiredoxin 2 (Prx2) can counteract the deleterious effects of oxidative stress (OS). Their binding to the red blood cell (RBC) membrane has been reported in non-immune hemolytic anemias (NIHAs). Our aim was to evaluate the relationships between CAT, GPx, and Prx2, focusing on their role at the RBC membrane, in hereditary spherocytosis (HS), sickle cell disease (SCD), ß-thalassemia (ß-thal), and healthy individuals. The studies were performed in plasma and in the RBC cytosol and membrane, evaluating OS biomarkers and the enzymatic activities and/or the amounts of CAT, GPx, and Prx2. The binding of the enzymes to the membrane appears to be the primary protective mechanism against oxidative membrane injuries in healthy RBCs. In HS (unsplenectomized) and ß-thal, translocation from the cytosol to the membrane of CAT and Prx2, respectively, was observed, probably to counteract lipid peroxidation. RBCs from splenectomized HS patients showed the highest membrane-bound hemoglobin, CAT, and GPx amounts in the membrane. SCD patients presented the lowest amount of enzyme linkage, possibly due to structural changes induced by sickle hemoglobin. The OS-induced changes and antioxidant response were different between the studied NIHAs and may contribute to the different clinical patterns in these patients.

Impact of TNFRSF1B (rs3397, rs1061624 and rs1061622) and IL6 (rs1800796, rs1800797 and rs1554606) Gene Polymorphisms on Inflammatory Response in Patients with End-Stage Kidney Disease Undergoing Dialysis.

We aimed to study the impact of polymorphisms in the genes encoding interleukin-6 (IL6) and tumor necrosis factor receptor-2 (TNFR2), reported to be mortality risk predictors, in patients with end-stage kidney disease (ESKD) undergoing dialysis. TNFRSF1B (rs3397, rs1061624, and rs1061622) and IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms were studied in patients with ESKD and controls; the genotype and allele frequencies and the associations with inflammatory and erythropoiesis markers were determined; deaths were recorded throughout the following two years. The genotype and allele frequencies for the TNFRSF1B rs3397 polymorphism were different in these patients compared to those in the controls and the global and European populations, and patients with the C allele were less common. Patients with the CC genotype for TNFRSF1B rs3397 presented higher hemoglobin and erythrocyte counts and lower TNF-α levels, suggesting a more favorable inflammatory response that seems to be associated with erythropoiesis improvement. Patients with the GG genotype for TNFRSF1B rs1061622 showed lower serum ferritin levels. None of the TNFRSF1B (rs3397, rs1061624, and rs1061622) or IL6 (rs1800796, rs1800797, and rs1554606) polymorphisms had a significant impact on the all-cause mortality rate of Portuguese patients with ESKD.

Psychological Adjustment Profiles of LGBTQ+ Young Adults Residing with Their Parents during the COVID-19 Pandemic: An International Study.

The COVID-19 pandemic has been associated with poor mental health symptoms, particularly among vulnerable populations such as LGBTQ+ individuals. In the present study, we aimed to (i) identify different psychological adjustment profiles among LGBTQ+ young adults during the COVID-19 pandemic and compare LGBTQ+ young adults in relation to (ii) sociodemographic characteristics and COVID-19-related experiences and (iii) the internal and external protective resources associated with each adjustment profile. An online questionnaire was administered to 1699 LGBTQ+ young adults from six countries (Brazil, Chile, Italy, Portugal, Sweden, and the UK). A cluster analysis was conducted, and four profiles of psychological adjustment were identified: unchallenged, resilient, distressed, and at-risk. The at-risk cluster scored lowest in social support (particularly from family). The profiles of participants who experienced the highest levels of pandemic adversity (at-risk and resilient) comprised mostly South American participants, those under lockdown at the time of survey completion, those who self-identified as transgender and non-binary, and those with a plurisexual sexual orientation. Interventions should consider strategies to help young adults maintain support systems and reinforce the value of positive family relationships. Specific groups within the LGBTQ+ community that seem to be in a particularly vulnerable situation may need additional tailored support.

The Association of Leptin with Left Ventricular Hypertrophy in End-Stage Kidney Disease Patients on Dialysis.

Left ventricular hypertrophy (LVH) is a common cardiovascular complication in end-stage kidney disease (ESKD) patients. We aimed at studying the association of LVH with adiponectin and leptin levels, cardiovascular stress/injury biomarkers and nutritional status in these patients. We evaluated the LV mass (LVM) and calculated the LVM index (LVMI) in 196 ESKD patients on dialysis; the levels of hemoglobin, calcium, phosphorus, parathyroid hormone, albumin, adiponectin, leptin, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor (GDF)-15 were analyzed. ESKD patients with LVH (n = 131) presented higher NT-proBNP and GDF-15, lower hemoglobin and, after adjustment for gender, lower leptin levels compared with non-LVH patients. LVH females also showed lower leptin than the non-LVH female group. In the LVH group, LVMI presented a negative correlation with leptin and a positive correlation with NT-proBNP. Leptin emerged as an independent determinant of LVMI in both groups, and NT-proBNP in the LVH group. Low hemoglobin and leptin and increased calcium, NT-proBNP and dialysis vintage are associated with an increased risk of developing LVH. In ESKD patients on dialysis, LVH is associated with lower leptin values (especially in women), which are negatively correlated with LVMI, and with higher levels of biomarkers of myocardial stress/injury. Leptin and NT-proBNP appear as independent determinants of LVMI; dialysis vintage, hemoglobin, calcium, NT-proBNP and leptin emerged as predicting markers for LVH development. Further studies are needed to better understand the role of leptin in LVH in ESKD patients.

The Prospective Co-Parenting Relationship Scale (PCRS) for Sexual Minority and Heterosexual People: Preliminary Validation.

The coparenting relationship begins with a process of planning and negotiation about having children. Available psychological instruments have not been adapted to sexual minority people, which compromises their ecological validity. This mixed method study aimed to adapt and validate a prospective version of the Co-Parenting Relationship Scale in a Portuguese sample of sexual minority and heterosexual adults who did not have children and who were in a dyadic relationship. In study 1, cognitive interviews were used to gather participants' reflections about the original items and the role played by the family of origin and anticipated stigma in coparenting (n = 6). In study 2, using a sample of individuals from 18 to 45 years old, two Exploratory Factor Analyses (EFA) were conducted separately for sexual minority (n = 167) and heterosexual persons (n = 198), and a Confirmatory Factor Analysis (CFA) was conducted for heterosexual persons (n = 176). Results showed underscored the importance of families of origin independent of sexual orientation. Different factorial structures for sexual minority and heterosexual persons were observed. Among sexual minority persons, the role of stigma was also highlighted. Implications for practice and research are discussed.

Resilience in the face of peer victimization and perceived discrimination: The role of individual and familial factors.

BACKGROUND: Peer victimization and discrimination are two related forms of social victimization. However, the majority of studies only focus on one form or the other. This study investigates resilience in victims of both these forms of violence. OBJECTIVE: To identify individual and family level factors that foster, or hinder, resilience in the face of both peer victimization and perceived discrimination. PARTICIPANTS: In a sample of 2975 high-school students, 22% (n = 644) met the criteria for substantial social victimization. The sample's mean age was 16.5 years, 57% were girls, 19% were in vocational courses, 12% were from an ethnic minority background, and 5% were lesbian, gay, or bisexual. METHOD: A measure of resilience was created by regressing the mean levels of current mental health, self-esteem, and life satisfaction on the frequency of lifetime peer victimization and past year perceived discrimination. Regression analyses were conducted to identify correlates of resilience considering protective and vulnerability factors, including sociodemographic information, anxious personality, empathy, coping strategies, familial optimism, and the relationship with their mother and father. RESULTS: Resilience was associated with low anxious personality, four coping strategies (active, use of humor, low self-blame, low substance use), and satisfaction with the relationship with the mother. CONCLUSIONS: Resilience is related to both behavioral and meaning-making coping strategies, personality traits, and satisfaction in relationships. This study's findings can be used to tailor interventions to foster resilience in adolescents exposed to social victimization.

Cellular and Molecular Pathways Underlying the Nephrotoxicity of Gadolinium.

Mounting evidence on the short- and long-term adverse effects associated with gadolinium [Gd (III)]-based contrast agents used in magnetic resonance imaging have emerged in the past 3 decades. Safety issues arise from the release of Gd (III) from chelates and its deposition in tissues, which is exacerbated in patients with renal disease, because the kidney is the major excretion organ of most of these agents. This study aimed at unveiling the cellular and molecular mechanisms of nephrotoxicity of Gd (III), using an in vitro model of human proximal tubular cells (HK-2 cell line). Cell viability declined in a concentration- and time-dependent manner after exposure to GdCl3·6H2O. The estimated inhibitory concentrations (ICs) eliciting 1%-50% of cell death, after 24 h of exposure, ranged from 3.4 to 340.5 µM. At toxic concentrations, exposure to Gd (III) led to disruption of the oxidative status, mitochondrial dysfunction, cell death by apoptosis, switching to necrosis at higher levels, and autophagic activation. Disturbance of the lipid metabolism was already observed at low-toxicity ICs, with accumulation of lipid droplets, and upregulation of genes related to both lipogenesis and lipolysis. Gd (III)-exposure, even at the subtoxic IC01, increased the expression of modulators of various signaling pathways involved in the development and progression of renal disease, including inflammation, hypoxia, and fibrosis. Our results give new insights into the mechanisms underlying the nephrotoxic potential of Gd (III) and highlight the need to further clarify the risks versus benefits of the Gd (III)-based contrast agents currently in use.

Human Interleukin-1ß Profile and Self-Reported Pain Monitoring Using Clear Aligners with or without Acceleration Techniques: A Case Report and Investigational Study.

Introduction: There is a growing demand for more aesthetic, comfortable, and faster orthodontic treatments, and clear aligners emerged as a solution to fulfill this need. However, the effectiveness of clear aligners to treat complex malocclusions is yet contentious. The use of acceleration methods could improve the efficacy of clear aligners by stimulating cells' mechanobiology through numerous pathways, but this hypothesis is still poorly explored. Objective: We aimed to monitor the release profile of an inflammatory marker-the interleukin-1ß-and to evaluate its relationship with self-reported pain scores with and without the use of acceleration techniques during an orthodontic treatment requiring difficult tooth movements with clear aligners. Case Report. Here, we report a case of a 46-year-old female patient who presented functional and aesthetic complaints. Intraoral examination revealed a diminished overjet and overbite, rotation of teeth 45 and 24, absence of teeth 25, 35, and 36, buccolingual dislocation of tooth 21, a tendency to a Class III malocclusion, and a 2 mm left deviation of the lower midline. This study is divided into three stimulation phases: no stimulation, mechanical vibration stimulation, and photobiomodulation. Interleukin-1ß levels in gingival crevicular fluid samples from the pressure side of six selected teeth were evaluated at four time points after the orthodontic treatment onset. Pain monitoring in those teeth was performed using a visual analogue scale at the same time points. Results: Interleukin-1ß protein production peaked 24 h after treatment onset. Complex movements were associated with increased self-reported pain. Conclusion: Clear aligners show limitations in solving complex tooth movements, even when combined with acceleration. The development of customized and programmable stimulation microdevices integrated into "smart aligners," which could be designed to specifically stimulate the direction of movement and stimulation parameters and could constitute a solution to optimize the orthodontic tooth movement with clear aligners.