Batimastat Induces Cytotoxic and Cytostatic Effects in In Vitro Models of Hematological Tumors.

The role of metalloproteinases (MMPs) in hematological malignancies, like acute myeloid leukemia (AML), myelodysplastic neoplasms (MDS), and multiple myeloma (MM), is well-documented, and these pathologies remain with poor outcomes despite treatment advancements. In this study, we investigated the effects of batimastat (BB-94), an MMP inhibitor (MMPi), in single-administration and daily administration schemes in AML, MDS, and MM cell lines. We used four hematologic neoplasia cell lines: the HL-60 and NB-4 cells as AML models, the F36-P cells as an MDS model, and the H929 cells as a model of MM. We also tested batimastat toxicity in a normal human lymphocyte cell line (IMC cells). BB-94 decreases cell viability and density in a dose-, time-, administration-scheme-, and cell-line-dependent manner, with the AML cells displaying higher responses. The efficacy in inducing apoptosis and cell cycle arrests is dependent on the cell line (higher effects in AML cells), especially with lower daily doses, which may mitigate treatment toxicity. Furthermore, BB-94 activated apoptosis via caspases and ERK1/2 pathways. These findings highlight batimastat's therapeutic potential in hematological malignancies, with daily dosing emerging as a strategy to minimize adverse effects.

The Impact of Socio-Environmental, Individual, and Biological Factors on Oral Health-Related Quality of Life among Preschool Children: A Cohort Study with 3-Year Follow-Up.

This study assessed impact of socio-environmental, individual, and biological factors on the worsening and severe worsening of oral health-related quality of life (OHRQoL) among preschoolers and their families. A cohort study was conducted in Diamantina, Brazil, with 151 children between 1 and 3 years of age and their mothers, who were evaluated at baseline (2014) and re-evaluated after 3 years (2017). The children were clinically examined to assess the presence of dental caries, malocclusion, dental trauma, and enamel defects. The mothers answered the Early Childhood Oral Health Impact Scale (B-ECOHIS) and a questionnaire addressing individual characteristics of the child and socio-environmental factors. Extensive caries found in the follow-up (relative risk [RR] = 1.91; 95% confidence interval [CI] = 1.26-2.91) and failure to undergo the dental treatment recommended at baseline (RR = 2.49; 95% CI = 1.62-3.81) were associated with worsening of OHRQoL over 3 years. An increase in the number of children in the household (RR = 2.95; 95% CI = 1.06-8.25), occurrence of extensive caries in the follow-up (RR = 2.06; 95% CI = 1.05-4.07), and failure to undergo the dental treatment recommended at baseline (RR = 3.68; 95% CI = 1.96-6.89) were associated with a severe worsening of OHRQoL. In conclusion, the risk of worsening and severe worsening of OHRQoL was higher in preschoolers with extensive caries at follow-up and among those who did not undergo dental treatment. Furthermore, severe worsening of OHRQoL was also impacted by an increase in the number of children in the household.

Parthenolide Induces ROS-Mediated Apoptosis in Lymphoid Malignancies.

Lymphoid malignancies are a group of highly heterogeneous diseases frequently associated with constitutive activation of the nuclear factor kappa B (NF-κB) signaling pathway. Parthenolide is a natural compound used to treat migraines and arthritis and found to act as a potent NF-κB signaling inhibitor. This study evaluated in vitro parthenolide efficacy in lymphoid neoplasms. We assessed parthenolide metabolic activity in NCI-H929 (MM), Farage (GCB-DLBCL), Raji (BL), 697 and KOPN-8 (B-ALL), and CEM and MOLT-4 (T-ALL), by resazurin assay. Cell death, cell cycle, mitochondrial membrane potential (ΔΨmit), reactive oxygen species (ROS) and reduced glutathione (GSH) levels, activated caspase-3, FAS-ligand, and phosphorylated NF-κB p65 were evaluated using flow cytometry. CMYC, TP53, GPX1, and TXRND1 expression levels were assessed using qPCR. Our results showed that parthenolide promoted a metabolic activity decrease in all cell lines in a time-, dose-, and cell-line-dependent manner. The mechanism induced by parthenolide was demonstrated to be cell line dependent. Nonetheless, parthenolide promoted cell death by apoptosis with significant ROS increase (peroxides and superoxide anion) and GSH decrease combined with a ΔΨmit reduction across all studied cell lines. Despite the need to further understand parthenolide mechanisms, parthenolide should be considered as a possible new therapeutic approach for B- and T-lymphoid malignancies.

Monocytes in the Characterization of Pain in Palliative Patients with Severe Dementia-A Pilot Study.

In assessing and managing pain, when obtaining a self-report is impossible, therapeutic decision-making becomes more challenging. This study aimed to investigate whether monocytes and some membrane monocyte proteins, identified as a cluster of differentiation (CD), could be potential non-invasive peripheral biomarkers in identifying and characterizing pain in patients with severe dementia. We used 53 blood samples from non-oncological palliative patients, 44 patients with pain (38 of whom had dementia) and 0 without pain or dementia (controls). We evaluated the levels of monocytes and their subtypes, including classic, intermediate, and non-classic, and characterized the levels of specific phenotypic markers, namely CD11c, CD86, CD163, and CD206. We found that the relative concentrations of monocytes, particularly the percentage of classic monocytes, may be a helpful pain biomarker. Furthermore, the CD11c expression levels were significantly higher in patients with mixed pain, while CD163 and CD206 expression levels were significantly higher in patients with nociceptive pain. These findings suggest that the levels of monocytes, particularly the classic subtype, and their phenotype markers CD11c, CD163, and CD206 could serve as pain biomarkers in patients with severe dementia.

AZD-7648, a DNA-PK Inhibitor, Induces DNA Damage, Apoptosis, and Cell Cycle Arrest in Chronic and Acute Myeloid Leukemia Cells.

The non-homologous end joining pathway is vital for repairing DNA double-strand breaks (DSB), with DNA-dependent protein kinase (DNA-PK) playing a critical role. Altered DNA damage response (DDR) in chronic (CML) and acute myeloid leukemia (AML) offers potential therapeutic opportunities. We studied the therapeutic potential of AZD-7648 (DNA-PK inhibitor) in CML and AML cell lines. This study used two CML (K-562 and LAMA-84) and five AML (HEL, HL-60, KG-1, NB-4, and THP-1) cell lines. DDR gene mutations were obtained from the COSMIC database. The copy number and methylation profile were evaluated using MS-MLPA and DDR genes, and telomere length using qPCR. p53 protein expression was assessed using Western Blot, chromosomal damage through cytokinesis-block micronucleus assay, and γH2AX levels and DSB repair kinetics using flow cytometry. Cell density and viability were analyzed using trypan blue assay after treatment with AZD-7648 in concentrations ranging from 10 to 200 µM. Cell death, cell cycle distribution, and cell proliferation rate were assessed using flow cytometry. The cells displayed different DNA baseline damage, DDR gene expressions, mutations, genetic/epigenetic changes, and p53 expression. Only HEL cells displayed inefficient DSB repair. The LAMA-84, HEL, and KG-1 cells were the most sensitive to AZD-7648, whereas HL-60 and K-562 showed a lower effect on density and viability. Besides the reduction in cell proliferation, AZD-7648 induced apoptosis, cell cycle arrest, and DNA damage. In conclusion, these results suggest that AZD-7648 holds promise as a potential therapy for myeloid leukemias, however, with variations in drug sensitivity among tested cell lines, thus supporting further investigation to identify the specific factors influencing sensitivity to this DNA-PK inhibitor.

Screening for Autism Spectrum Disorders - Validation of the Portuguese Version of the Social Communication Questionnaire.

There are no assessment and screening tools for Autism Spectrum Disorders (ASD) validated for the Portuguese population. The Social Communication Questionnaire (SCQ) is an useful screening tool of ASD diagnosis. The main objectives of our study were to produce a Portuguese version of the SCQ (SCQ-PF), study its internal consistency, sensitivity and specificity in order to evaluate its validity as a screening instrument for ASD. We also wanted to study the impact of intellectual disability and verbal impairment and other mental disorders on SCQ-PF psychometric properties. The study included 211 children and adolescents, aged 4-17, divided in three groups: ASD Group (n = 96), Other Mental Disorders Group (OMD) (n = 63) and No Mental Disorders (NMD) Group (n = 52). Parents or other primary caregiver provided information on the SCQ items. The SCQ-PF score was significantly higher in the ASD group than in the other groups (p < 0.001). As to internal consistency, Cronbach's alpha was 87%. ASD subjects were distinguished from subjects without ASD (OMD and NMD Groups) and the area under the curve (AUC) was 0.897 (95% Confidence Interval: 0.852-0.943), for a cutoff of 14, which yielded the highest AUC, with values of sensitivity and specificity 0.76 and 0.93, respectively. These findings show that SCQ- PF with a cutoff of 14 is an acceptable and useful screening tool for ASD in the Portuguese population.

Alvespimycin Inhibits Heat Shock Protein 90 and Overcomes Imatinib Resistance in Chronic Myeloid Leukemia Cell Lines.

Heat shock protein 90 (HSP90) facilitates folding and stability and prevents the degradation of multiple client proteins. One of these HSP90 clients is BCR-ABL, the oncoprotein characteristic of chronic myeloid leukemia (CML) and the target of tyrosine kinase inhibitors, such as imatinib. Alvespimycin is an HSP90 inhibitor with better pharmacokinetic properties and fewer side effects than other similar drugs, but its role in overcoming imatinib resistance is not yet clarified. This work studied the therapeutic potential of alvespimycin in imatinib-sensitive (K562) and imatinib-resistant (K562-RC and K562-RD) CML cell lines. Metabolic activity was determined by the resazurin assay. Cell death, caspase activity, mitochondrial membrane potential, and cell cycle were evaluated by means of flow cytometry. Cell death was also analyzed by optical microscopy. HSPs expression levels were assessed by western blotting. Alvespimycin reduced metabolic activity in a time-, dose-, and cell line-dependent manner. Resistant cells were more sensitive to alvespimycin with an IC50 of 31 nM for K562-RC and 44 nM for K562-RD, compared to 50 nM for K562. This drug induced apoptosis via the mitochondrial pathway. In K562 cells, alvespimycin induced cell cycle arrest in G0/G1. As a marker of HSP90 inhibition, a significant increase in HSP70 expression was observed. Our results suggest that alvespimycin might be a new therapeutic approach to CML treatment, even in cases of resistance to imatinib.

Family income modifies the association between frequent sugar intake and dental caries.

AIM: The aim of this cross-sectional study was to investigate whether family income modifies associations between dental caries and sex, age, mother's education, type of preschool, sugar intake, and toothbrushing. BACKGROUND: Dental caries is a multifactorial dyanamic disease primarily mediated by biofilm and sugar. DESIGN: A randomly selected sample of 308 Brazilian preschool children aged 1-3 years underwent a clinical oral examination for the assessment of moderate/extensive dental caries using codes 3-6 of the International Caries Detection and Assessment System. Mothers were asked to fill out a form addressing the child's demographic and socioeconomic characteristics as well as the frequency of sugar intake. Statistical analysis involved descriptive statistics, the chi-squared test, and Poisson regression models. RESULTS: The prevalence of moderate/extensive dental caries was 42.5%. The adjusted model revealed that within low-income families (<2 times the monthly minimum wage), the prevalence of dental caries was higher among children with a high frequency of sugar intake (≥ twice per day) than in those with a low frequency of sugar intake (< twice a day) (RR = 1.79; CI: 1.38-2.33). In families with higher income (≥2 times the monthly wage), no significant association between sugar intake and dental caries was, however, found. CONCLUSIONS: In conclusion, monthly family income can modify the association between the high frequency of sugar intake and dental caries.

Association between child's behaviour during first dental appointment and effectiveness of dental plaque removal by caregivers.

OBJECTIVE: To evaluate the association between the behaviour of children aged 1 to 4 years during their dental appointment and the effectiveness of dental plaque removal by caregivers. METHODS: This longitudinal study with intervention had the participation of 146 children (mean age = 34.89 months), 75 of whom (51.4%) showed positive behaviour (+ and ++) and 71 (48.6%), negative behaviour (- and - -). The children were evaluated at the first dental appointment, according to the Frankl scale. They were subjected to an assessment of oral conditions, and their plaque level was recorded (Quigley-Hein Index modified by Turesky) using the Evince® device. Caregivers received oral hygiene guidance. The dental plaque assessment was performed before giving the oral hygiene guidance and 14 days later. The statistical analysis included a descriptive assessment and the Wilcoxon test (p < 0.05). RESULTS: Mean dental plaque levels dropped significantly from the first to the second assessment (p < 0.001). The sample was divided according to the child's behaviour, observing that only the group of children with positive behaviour showed significantly less dental plaque in the second assessment (p < 0.001). CONCLUSION: The positive behaviour of children aged 1 to 4 years during the first dental appointments is associated with more effective dental plaque removal by caregivers.

Impact of cancer metabolism on therapy resistance - Clinical implications.

Despite an increasing arsenal of anticancer therapies, many patients continue to have poor outcomes due to the therapeutic failures and tumor relapses. Indeed, the clinical efficacy of anticancer therapies is markedly limited by intrinsic and/or acquired resistance mechanisms that can occur in any tumor type and with any treatment. Thus, there is an urgent clinical need to implement fundamental changes in the tumor treatment paradigm by the development of new experimental strategies that can help to predict the occurrence of clinical drug resistance and to identify alternative therapeutic options. Apart from mutation-driven resistance mechanisms, tumor microenvironment (TME) conditions generate an intratumoral phenotypic heterogeneity that supports disease progression and dismal outcomes. Tumor cell metabolism is a prototypical example of dynamic, heterogeneous, and adaptive phenotypic trait, resulting from the combination of intrinsic [(epi)genetic changes, tissue of origin and differentiation dependency] and extrinsic (oxygen and nutrient availability, metabolic interactions within the TME) factors, enabling cancer cells to survive, metastasize and develop resistance to anticancer therapies. In this review, we summarize the current knowledge regarding metabolism-based mechanisms conferring adaptive resistance to chemo-, radio-and immunotherapies as well as targeted therapies. Furthermore, we report the role of TME-mediated intratumoral metabolic heterogeneity in therapy resistance and how adaptations in amino acid, glucose, and lipid metabolism support the growth of therapy-resistant cancers and/or cellular subpopulations. We also report the intricate interplay between tumor signaling and metabolic pathways in cancer cells and discuss how manipulating key metabolic enzymes and/or providing dietary changes may help to eradicate relapse-sustaining cancer cells. Finally, in the current era of personalized medicine, we describe the strategies that may be applied to implement metabolic profiling for tumor imaging, biomarker identification, selection of tailored treatments and monitoring therapy response during the clinical management of cancer patients.

Zinc Prevents DNA Damage in Normal Cells but Shows Genotoxic and Cytotoxic Effects in Acute Myeloid Leukemia Cells.

Genomic instability is prevented by the DNA damage response (DDR). Micronutrients, like zinc (Zn), are cofactors of DDR proteins, and micronutrient deficiencies have been related to increased cancer risk. Acute myeloid leukemia (AML) patients commonly present Zn deficiency. Moreover, reports point to DDR defects in AML. We studied the effects of Zn in DDR modulation in AML. Cell lines of AML (HEL) and normal human lymphocytes (IMC) were cultured in standard culture, Zn depletion, and supplementation (40 µM ZnSO4) conditions and exposed to hydrogen peroxide (H2O2) or ultraviolet (UV) radiation. Chromosomal damage, cell death, and nuclear division indexes (NDI) were assessed through cytokinesis-block micronucleus assay. The phosphorylated histone H2AX (yH2AX) expression was monitored at 0 h, 1 h, and 24 h after exposure. Expression of DDR genes was evaluated by quantitative real time polymerase chain reaction (qPCR). Zn supplementation increased the genotoxicity of H2O2 and UV radiation in AML cells, induced cytotoxic and antiproliferative effects, and led to persistent yH2AX activation. In contrast, in normal lymphocytes, supplementation decreased damage rates, while Zn depletion favored damage accumulation and impaired repair kinetics. Gene expression was not affected by Zn depletion or supplementation. Zn presented a dual role in the modulation of genome damage, preventing damage accumulation in normal cells and increasing genotoxicity and cytotoxicity in AML cells.

Genetic Variants of ABC and SLC Transporter Genes and Chronic Myeloid Leukaemia: Impact on Susceptibility and Prognosis.

Solute carrier (SLC) and ATP-binding cassette (ABC) transporters comprise a variety of proteins expressed on cell membranes responsible for intrusion or extrusion of substrates, respectively, including nutrients, xenobiotics, and chemotherapeutic agents. These transporters mediate the cellular disposition of tyrosine kinase inhibitors (TKIs), and their genetic variants could affect its function, potentially predisposing patients to chronic myeloid leukaemia (CML) and modulating treatment response. We explored the impact of genetic variability (single nucleotide variants-SNVs) of drug transporter genes (ABCB1, ABCG2, SLC22A1, and SLC22A5) on CML susceptibility, drug response, and BCR-ABL1 mutation status. We genotyped 10 SNVs by tetra-primers-AMRS-PCR in 198 CML patients and 404 controls, and assessed their role in CML susceptibility and prognosis. We identified five SNVs associated with CML predisposition, with some variants increasing disease risk, including TT genotype ABCB1 (rs1045642), and others showing a protective effect (GG genotype SLC22A5 rs274558). We also observed different haplotypes and genotypic profiles associated with CML predisposition. Relating to drug response impact, we found that CML patients with the CC genotype (rs2231142 ABCG2) had an increased risk of TKI resistance (six-fold). Additionally, CML patients carrying the CG genotype (rs683369 SLC22A1) presented a 4.54-fold higher risk of BCR-ABL1 mutations. Our results suggest that drug transporters' SNVs might be involved in CML susceptibility and TKI response, and predict the risk of BCR-ABL1 mutations, highlighting the impact that SNVs could have in therapeutic selection.

Association of the prevalence and severity of untreated traumatic dental injuries with body mass index among Brazilian preschool children.

BACKGROUND/AIM: Children with excess weight may be more predisposed to traumatic dental injuries (TDI). The aim of this study was to investigate the association between overweight/obesity and TDI presence and severity in Brazilian preschool children. MATERIAL AND METHODS: A cross-sectional study was conducted of 347 children aged three to five years. The main exposure was evaluated based on the body mass index (BMI). Socioeconomic-demographic characteristics and harmful oral habits were investigated using a questionnaire sent to the parents/guardians. Oral clinical examinations were performed to determine overjet (criteria proposed by Foster and Hamilton), and the presence and severity of TDI (criteria proposed by Andreassen). Descriptive statistics were performed. Univariate and multivariate Poisson regression analyses were conducted for each outcome. RESULTS: The prevalence of TDI in the sample was 41.5% and 16% of the children had enamel and dentin fractures. In the multivariate analysis, BMI and overjet were associated with the presence and severity of TDI (PR: 2.04 and 1.78, respectively) of TDI (PR: 2.27 and 2.24, respectively) (p < .001 for all associations). CONCLUSION: Overweight/obesity was associated with both the presence and severity of TDI in early childhood.

Association between obesity and traumatic dental injuries in pre-school children-A case-control study.

BACKGROUND/AIM: Obese children are more prone to accidents due to poorer motor skills which increase the likelihood of falls and the occurrence of traumatic dental injuries (TDIs). The aim of this study was to determine the association between overweight/obesity and TDI in pre-school children. MATERIAL AND METHODS: The case group was formed by children with TDI identified during a clinical examination (n = 262). Each pre-school child identified as a case was matched by a peer of the same age, gender and pre-school but without TDI to form the control group (n = 262). TDI was evaluated using the criteria proposed by Andreasen. The weight and height of the children were measured for the calculation of the body mass index which was plotted on the growth curve established by the World Health Organization. Socio-demographic variables were collected through questionnaires sent to the parents/guardians. Data analysis involved the determination of frequency distribution, the chi-square test and logistic regression analysis. RESULTS: The sample was composed of 253 children in each group. Among the children in the case group, 15.4% (n = 39) were overweight and 15.8% (n = 40) were obese. In the control group, 13.8% (n = 35) were overweight and 8.3% (n = 21) were obese. Children with trauma were more likely to be obese than children without trauma (OR = 2.05; 95%CI: 1.14 to 3.67; p = .016). In contrast, TDI was not associated with being overweight. A greater odds of TDI was also associated with an open bite (OR = 3.61; 95% CI: 1.64 to 7.96; p = .001) and accentuated overjet (OR = 2.19; 95% CI: 1.37 to 3.50; p = .001). CONCLUSIONS: Pre-school children with a history of dental trauma were more likely to be obese than those without a history of dental trauma whereas being overweight was not associated with TDI.

Untreated dental caries and visible plaque of mothers are not determinant for the incidence of caries in dentin among children: evidence from a 3-year prospective cohort study.

OBJECTIVES: To evaluate whether characteristics related to mother's oral health, trajectory of family income, and maternal education are associated with the incidence of caries in dentin in preschool children. MATERIALS AND METHODS: One hundred fifty-eight mothers and their children were evaluated at baseline and re-evaluated after 3 years. Sociodemographic variables, dental caries, and biofilm of the mothers and children and daily sugar intake of the children were evaluated. Poisson regression was used to evaluate what factor represents risk for the incidence of caries in dentin at four to 6 years of age. RESULTS: The risk of the incidence of caries in dentin was 54% higher in children whose mothers had a low level of education at both baseline and follow-up. Children from families with an income lower at baseline and follow-up (RR 2.49; 95% CI 1.62-3.83) and those whose families experienced a reduction in income in this period (RR 2.05; 95% CI 1.29-3.26) had a greater risk of the incidence of caries in dentin. Moreover, children who increased their daily sugar intake (RR 1.67; 95% CI 1.09-2.52), those that maintained high sugar intake (RR 1.81; 95% CI 1.14-2.87), and those with cavitated caries at baseline (RR 1.53; 95% CI 1.19-1.97) had a greater risk of the incidence of caries in dentin. CONCLUSIONS: Low mother's education, a lower family income, a reduction in family income, a high frequency of daily sugar intake, and a history of cavitated caries were risk factors for the incidence of caries in dentin. CLINICAL RELEVANCE: The results could help in the targeting of improved prevention and control strategies for dental caries.

The prevalence of malocclusion is higher in schoolchildren with signs of hyperactivity.

INTRODUCTION: Attention deficit-hyperactivity disorder is a behavioral disorder characterized by a lack of focus, impulsive behavior, and or excessive activity. This research aimed to evaluate the association between signs of attention deficit-hyperactivity disorder and malocclusion in schoolchildren. METHODS: A cross-sectional study was conducted with a representative sample of 633 children aged 7-12 years. The children were clinically examined for malocclusion using the Dental Aesthetic Index. The predominant breathing pattern was also determined. Parents answered a questionnaire addressing socioeconomic characteristics and the presence of nonnutritive sucking habits. The Swanson, Nolan, and Pelham Scale-IV was filled out by both parents and teachers to compare behavioral patterns. The children were submitted to a neuropsychological evaluation using the Raven's Colored Progressive Matrix Test. Data analysis involved the chi-square test and Poisson regression analysis. RESULTS: The prevalence of malocclusion was 42% higher among children with signs of hyperactivity reported by both parents and teachers (prevalence ratio [PR], 1.42; 95% confidence interval [CI], 1.11-1.81; P = 0.004). In the final Poisson regression model, the prevalence of malocclusion was lower among schoolchildren aged 11 and 12 years (PR, 0.62; 95% CI. 0.52-0.73; P <0.001) and higher among those who used a pacifier for at least 4 years (PR, 1.25; 95% CI, 1.02-1.54; P = 0.029) as well as those classified as mouth breathers (PR, 1.28; 95% CI, 1.09-1.51; P = 0.003). CONCLUSIONS: The prevalence of malocclusion was higher among children with signs of hyperactivity independently of age, pacifier use, and mouth breathing.

Acidic food choice among adolescents with bulimic symptomatology: a major risk factor for erosive tooth wear?

PURPOSE: Evaluate dietary habits and the presence of erosive tooth wear (ETW) among female adolescents with varying severity of bulimic symptomatology. METHODS: An explanatory study was conducted with 72 female school adolescents with bulimic symptomatology, aged 15-18 years in Southeastern Brazil. Dietary habits were evaluated through a food frequency questionnaire. Bulimic symptomatology was evaluated and classified (mild, moderate and severe) according to the Bulimic Investigatory Test of Edinburgh. ETW examinations were performed. Data analysis involved descriptive statistics, bivariate analysis, Kruskal-Wallis/Mann-Whitney tests and Poisson regression. Ethical approval and informed consents were obtained. RESULTS: The final population consisted of 62 participants. The prevalence of ETW differed among adolescents with mild, moderate and severe bulimic symptomatology (p = 0.001), corresponding to 5.9%, 8.0% and 45.0%, respectively. Adolescents with severe bulimic symptomatology presented higher daily consumption of acidic food: citric fruits (p < 0.005), diet soda (p < 0.009) and ketchup (p = 0.004). No difference related to vomiting practices was observed between groups (p = 0.060). The adjusted regression model showed that a higher prevalence of ETW was associated with self-induced vomit at least once a week (PR = 2.42, 95% CI = 1.00-5.86, p = 0.05) and higher frequencies of consumption of citric fruits (PR = 7.96, 95% CI = 1.50-42.11, p = 0.015) and diet soda (PR = 2.32, 95% CI = 1.09-4.91, p = 0.029). CONCLUSION: It was the food choices (acidic food) and not purging practices that differed among adolescents with varying severity of bulimic symptomology. Likewise, higher consumption of citric fruits was the main factor associated with higher prevalence of ETW. LEVEL OF EVIDENCE: III case-control analytic study.

Apoptosis induction and cell cycle arrest of pladienolide B in erythroleukemia cell lines.

Splicing of pre-mRNA into functional mRNA, carried out by the spliceosome, represents a crucial step in eukaryotic gene expression. Mutations and other deregulation in some of the spliceosome components have been identified in multiple pathologies, including hematological malignancies. In this context, we evaluated the therapeutic potential of a splicing inhibitor, Pladienolide B (Pla-B), in two erythroleukemia cell lines. HEL and K562 cell lines were incubated with increasing doses of Pla-B in single and daily administration. Cell viability and density were evaluated using trypan blue assay. Flow cytometry was used to evaluate cell death, cell cycle, and caspase activity. NGS analysis was performed to assess the mutational status of 4 splicing-related genes (SF3B1, U2AF1, ZRSR2 and SRSF2). Expression levels of SF3B1 and unspliced DNAJB1 were evaluated by qPCR. Pla-B significantly decreased the viability and proliferation of both cell lines in time, dose, administration schedule, and cell line-dependent manner. HEL cells were more sensible to Pla-B (IC50 = 1.5 nM) than K562 (IC50 = 25 nM), with an IC50 almost 17 times lower. Pla-B induced cell death, mainly by apoptosis, and cell cycle arrest in G0/G1 phase. No mutations were found in any of the analyzed genes, suggesting that the observed cytotoxic effect is independent of the spliceosome mutations. Splicing modulator Pla-B showed high antitumor activity against HEL and K562 cell lines, inducing apoptosis and cell cycle arrest. These data suggest that Pla-B might represent a new therapeutic approach for erythroleukemia.

Do family functioning and mothers' and children's stress increase the odds of probable sleep bruxism among schoolchildren? A case control study.

OBJECTIVE: To investigate the association between probable sleep bruxism (PSB) and associated factors in schoolchildren. MATERIALS AND METHODS: A case-control study was conducted with a representative sample of 320 schoolchildren aged 8 to 10 years. The case group (160 children with PSB) and the control group (160 children without PSB) were matched for sex and age at a proportion of 1:1. Information on audible characteristics of PSB, harmful oral habits, and socio-demographic characteristics as collected through questionnaires answered by the parents/caregivers. The family functioning of children was measured through The Family Adaptability and Cohesion Evaluation Scales (FACES III). Mothers self-administered the Lipp Stress Symptoms Inventory (LSSI) for adults to measure mothers' stress and the children filled out the Child Stress Scale (CSS) to measure the children stress. Data analysis used descriptive and logistic regression analyses (p < 0.05). RESULTS: Among the children with stress, 67.3% had PSB. Children with stress (OR = 2.22, 95% CI 1.18-4.19), those with a history of nail biting (OR = 2.22, 95% CI 1.39-3.55), and biting objects (OR = 1.77, 95% CI 1.09-2.87) were more likely to have PSB. CONCLUSION: Childhood stress and a history of nail biting or biting objects are important signs to be considered in schoolchildren with PBS. CLINICAL RELEVANCE: These results alert that the PBS might be a sign of stress and other psychological problems such as tension and anxiety related to the presence of harmful oral habits. Furthermore, the results could help in the targeting of anamnesis, improved prevention and treatment strategies for sleep bruxism which should involve an interdisciplinary approach.

The use of peracetic acid for estrogen removal from urban wastewaters: E2 as a case study.

17ß-Estradiol (E2) is a natural estrogen produced by the feminine endocrine system. It is excreted mainly through urine and feces. Exposure to E2 may affect the reproductive system of both animals and humans, especially since the removal of E2 in conventional processes and technologies present in the wastewater treatment plants is not sufficient. Chlorine is one of the most studied and used oxidant worldwide. Although there are studies that demonstrate the endocrine disrupting compounds removal like E2, its reaction with organic matter can originate by-products, namely, trihalomethanes, which are known to have high toxic potential. The main aim of the present study was to evaluate the removal of E2 (50 µg E2 L-1-maximum concentration) using peracetic acid (PAA), a seeming cleaner and innocuous alternative to chlorine. To this end, a series of jar tests were performed, using different peracetic acid concentrations (1, 5, 10, and 15 mg L-1) and contact times (10, 15, and 20 min). The results obtained showed that a peracetic acid concentration of 15 mg L-1 with a contact time of 20 min had a removal efficacy of approximately 100%. The second main goal of this study was to evaluate the ecotoxicological potential of the tested treatments on the zebrafish Danio rerio. Several oxidative stress biomarkers were evaluated, namely glutathione S-transferase, lipid peroxidation, and catalase, besides vitellogenin. Both peracetic acid and E2 caused significant increases in the oxidative stress biomarkers, although this did not lead to increased lipid peroxidation levels. In addition, peracetic acid significantly decreased the estrogenic activity of E2, as indicated by decreased vitellogenin levels. Peracetic acid demonstrated to have great potential as an alternative disinfectant for chlorine treatments, and indications for future research are discussed.