Kaempferol and Biomodified Kaempferol from Sophora japonica Extract as Potential Sources of Anti-Cancer Polyphenolics against High Grade Glioma Cell Lines.

The enzymatic hydrolysis of the extract of Sophora japonica by two glycosyl hydrolases (hesperidinase and galactosidase) was performed in order to obtain kaempferol (KPF)-enriched extract with an enhanced anticancer activity. The current study examined the effectiveness of both Sophora japonica extracts (before (KPF-BBR) and after (KPF-ABR) bioconversion reactions) in reducing cell viability and inducing apoptosis in human high-degree gliomas in vitro. Cytotoxicity was determined using an MTT assay. The effects of both compounds on the proliferation of glioma cell lines were measured using trypan blue exclusion, flow cytometry for cell cycle, wound healing (WH), and neurosphere formation assays. Cellular apoptosis was detected by DNA fragmentation and phosphatidylserine exposure. qPCR and luciferase assays evaluated NF-kB pathway inhibition. The survival rate of NG-97 and U-251 cells significantly decreased in a time- and dose-dependent manner after the addition of KPF-BBR or KPF-ABR. Thus, a 50% reduction was observed in NG-97 cells at 800 µM (KPF-BBR) and 600 µM (KPF-ABR) after 72 h. Both compounds presented an IC50 of 1800 µM for U251 after 72 h. The above IC50 values were used in all of the following analyses. Neither of the KPF presented significant inhibitory effects on the non-tumoral cells (HDFa). However, after 24 h, both extracts (KPF-BBR and KPF-ABR) significantly inhibited the migration and proliferation of NG-97 and U-251 cells. In addition, MMP-9 was downregulated in glioma cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) plus KPF-BBR and TPA+KPF-ABR compared with the TPA-treated cells. Both KPF-BBR and KPF-ABR significantly inhibited the proliferation of glioma stem cells (neurospheres) after 24 h. DNA fragmentation assays demonstrated that the apoptotic ratio of KPF-ABR-treated cell lines was significantly higher than in the control groups, especially NG-97, which is not TMZ resistant. In fact, the flow cytometric analysis indicated that KPF-BBR and KPF-ABR induced significant apoptosis in both glioma cells. In addition, both KPF induced S and G2/M cell cycle arrest in the U251 cells. The qPCR and luciferase assays showed that both KPFs downregulated TRAF6, IRAK2, IL-1ß, and TNF-α, indicating an inhibitory effect on the NF-kB pathway. Our findings suggest that both KPF-BBR and KPF-ABR can confer anti-tumoral effects on human cell glioma cells by inhibiting proliferation and inducing apoptosis, which is related to the NF-κB-mediated pathway. The KPF-enriched extract (KPF-ABR) showed an increased inhibitory effect on the cell migration and invasion, characterizing it as the best antitumor candidate.

Rectal Cancer Tissue Lipidome Differs According to Response to Neoadjuvant Therapy.

Rectal cancer (RC) is a gastrointestinal cancer with a poor prognosis. While some studies have shown metabolic reprogramming to be linked to RC development, it is difficult to define biomolecules, like lipids, that help to understand cancer progression and response to therapy. The present study investigated the relative lipid abundance in tumoral tissue associated with neoadjuvant therapy response using untargeted liquid chromatography-mass spectrometry lipidomics. Locally advanced rectal cancer (LARC) patients (n = 13), clinically staged as T3-4 were biopsied before neoadjuvant chemoradiotherapy (nCRT). Tissue samples collected before nCRT (staging) and afterwards (restaging) were analyzed to discover lipidomic differences in RC cancerous tissue from Responders (n = 7) and Non-responders (n = 6) to nCRT. The limma method was used to test differences between groups and to select relevant feature lipids from tissue samples. Simple glycosphingolipids and differences in some residues of glycerophospholipids were more abundant in the Non-responder group before and after nCRT. Oxidized glycerophospholipids were more abundant in samples of Non-responders, especially those collected after nCRT. This work identified potential lipids in tissue samples that take part in, or may explain, nCRT failure. These results could potentially provide a lipid-based explanation for nCRT response and also help in understanding the molecular basis of RC and nCRT effects on the tissue matrix.

Respiratory function of children and adolescents with osteogenesis imperfecta: respiratory muscle strength, forced vital capacity, and peak expiratory flow.

OBJECTIVE: This study aims to evaluate the respiratory function of children and adolescents with osteogenesis imperfecta (OI) followed up at a referral center. METHODS: A cross-sectional study was conducted with a non-probabilistic sample. Manovacuometry was performed with the measurement of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), and in addition, peak expiratory flow (PEF) and ventilometry were performed to measure forced vital capacity (FVC). RESULTS: In total, 23 individuals were evaluated, with a mean age of 11.6±3.4 years, 56.5% of whom were females. Regarding the classification of OI, 56.5% of the sample belonged to type IV, 30.5% to type III, and 13% to type I. The mean MIP was 64.4% of the predicted, and the mean MEP was 56.2% of the predicted. Overall, the mean PEF was 213.9 L/min, but only 140.6 L/min in the OI type III group. Median FVC was 1.9 L, corresponding to 110% of the predicted. CONCLUSIONS: Respiratory function of the study subjects was altered, with respiratory muscle strength values lower than expected in the whole sample, and peak expiratory flow was significantly reduced in the OI type III group.

Mass-Spectrometry-Based Lipidomics Discriminates Specific Changes in Lipid Classes in Healthy and Dyslipidemic Adults.

Triacylglycerols (TAGs) and cholesterol lipoprotein levels are widely used to predict cardiovascular risk and metabolic disorders. The aim of this study is to determine how the comprehensive lipidome (individual molecular lipid species) determined by mass spectrometry is correlated to the serum whole-lipidic profile of adults with different lipidemic conditions. The study included samples from 128 adults of both sexes, and they were separated into four groups according to their lipid profile: Group I-normolipidemic (TAG < 150 mg/dL, LDL-C < 160 mg/dL and HDL-c > 40 mg/dL); Group II-isolated hypertriglyceridemia (TAG ≥ 150 mg/dL); Group III-isolated hypercholesterolemia (LDL-C ≥ 160 mg/dL) and Group IV-mixed dyslipidemia. An untargeted mass spectrometry (MS)-based approach was applied to determine the lipidomic signature of 32 healthy and 96 dyslipidemic adults. Limma linear regression was used to predict the correlation of serum TAGs and cholesterol lipoprotein levels with the abundance of the identified MS-annotated lipids found in the subgroups of subjects. Serum TAG levels of dyslipidemic adults have a positive correlation with some of the MS-annotated specific TAGs and ceramides (Cer) and a negative correlation with sphingomyelins (SMs). High-density lipoprotein-cholesterol (HDL-C) levels are positively correlated with some groups of glycerophosphocholine, while low-density lipoprotein-cholesterol (LDL-C) has a positive correlation with SMs.

Enzymatic Hydrolysis of Rutin: Evaluation of Kinetic Parameters and Anti-Proliferative, Mutagenic and Anti-Mutagenic Effects.

The bioavailability of glucoside flavonoids is influenced by the nature of the sugar, glucosides being absorbed faster than rhamnoglucosides, for example. One strategy to enhance the bioavailability is enzymatic hydrolysis. In this study, some kinetic parameters of hesperidinase-mediated hydrolysis of rutin were evaluated using an UHPLC/QTOF-MSE analysis of the products of a bioconversion reaction. The resulting hydrolyzed rutins (after 4, 8 and 12 h of reaction) were submitted to anti-proliferative and Cytokinesis-Block Micronucleus (CBMN) assays in CHO-K1 cells. In the hesperidinase-mediated hydrolysis, the final concentration of quercetin-3-O-glucoside (Q3G) was directly proportional to the rutin concentration and inversely proportional to the reaction time. At an anti-proliferative concentration (2.5 µg/mL), hydrolyzed rutin derivatives did not show a mutagenic effect, except for the sample with a higher content of Q3G (after 4 h of the enzymatic hydrolysis of rutin). Moreover, the higher Q3G content in hydrolyzed rutin protected the CHO-K1 cells 92% of the time against methyl methanesulfonate-induced mutagenic damage. These results suggested that the anti-mutagenic effect of hydrolyzed rutin might be related to antioxidant and cell death induction. Presenting a good lipophilicity/hydrophilicity ratio, together with antioxidant and anti-mutagenic activities, the hesperidinase-mediated hydrolyzed rutin seemed to be a promisor raw material for the development of food supplements.

Functional status of individuals with osteogenesis imperfecta: data from a reference center

Abstract Objective: To evaluate the functional status of individuals with Osteogenesis Imperfecta (OI) followed up at a reference center in the state of Bahia. Materials and methods: This is an observational, cross-sectional, descriptive study, which evaluated individuals with OI, based on a non-probabilistic sampling. To assess motor function, the Motor Function Measure (MFM) score was used, in addition to the measurement of muscle strength using the Medical Research Council (MRC) score. Functional performance was measured using the Pediatric Assessment of Disability Inventory, Computerized Adaptive Testing (PEDI-CAT). Results: Thirty-one individuals aged between two and 18 years old were evaluated. The overall score of MFM was 74.2%, and the lowest score was found in participants with type III OI (56.3%). The median of the MRC index was 80. The mobility domain was the most affected in the PEDI-CATevaluation, with a mean T score of 23.9, (14.2 in type III OI). Conclusions: Among the evaluated individuals, functional alterations were identified, reduced global gross motor functionality and muscle strength, impacting the mobility domain, with the most relevant findings in individuals with type III OI.

Functional status of individuals with osteogenesis imperfecta: data from a reference center.

OBJECTIVE: To evaluate the functional status of individuals with Osteogenesis Imperfecta (OI) followed up at a reference center in the state of Bahia. MATERIALS AND METHODS: This is an observational, cross-sectional, descriptive study, which evaluated individuals with OI, based on a non-probabilistic sampling. To assess motor function, the Motor Function Measure (MFM) score was used, in addition to the measurement of muscle strength using the Medical Research Council (MRC) score. Functional performance was measured using the Pediatric Assessment of Disability Inventory, Computerized Adaptive Testing (PEDI-CAT). RESULTS: Thirty-one individuals aged between two and 18 years old were evaluated. The overall score of MFM was 74.2%, and the lowest score was found in participants with type III OI (56.3%). The median of the MRC index was 80. The mobility domain was the most affected in the PEDI-CAT evaluation, with a mean T score of 23.9, (14.2 in type III OI). CONCLUSIONS: Among the evaluated individuals, functional alterations were identified, reduced global gross motor functionality and muscle strength, impacting the mobility domain, with the most relevant findings in individuals with type III OI.

Altered profile of plasma phospholipids in woman with recurrent pregnancy loss and recurrent implantation failure treated with lipid emulsion therapy.

BACKGROUND: Recurrent Pregnancy Loss (RPL) and Recurrent Implantation Failure (RIF) are highly heterogeneous condition and many of the mechanisms involved still require elucidation. The aim was to analyze the lipidomic profile in plasma of women with RPL and RIF before and after receiving the Lipid Emulsion Therapy (LET) containing 10% fish oil (SMOFlipid® 20%). METHODS: This study included twenty-six women with RPL or RIF from immunological or inflammatory causes, with elevated natural killer cell levels and divided into a Pregnancy Loss or a Live Birth group according to the outcome. The women received intravenous LET and sample collecting was done before the first, third and fifth dose of LET in the pregnant women. Ultra-performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-QTOF MS) and multivariate statistical methods were performed to evaluate the profile of phospholipids present in the women's plasma. RESULTS: An increase of phosphatidylcholines (PC) 40:8 and 36:5 levels with predominance of n6 polyunsaturated fatty acids (PUFA) was observed in plasma lipids of the Pregnancy Loss Group compared to Live Birth Group. We also observed an increase in the relative abundance of n3 PUFA-PC species (42:10 and 36:6) and LysoPC 15:0 with the long term use of LET. CONCLUSION: The greater availability of n3 PUFA in plasma of the pregnant women stemming from LET use can be considered advantageous regarding the alteration of the phospholipid profile and its postulated anti-inflammatory and immunomodulatory role.

Respiratory function of children and adolescents with osteogenesis imperfecta: respiratory muscle strength, forced vital capacity, and peak expiratory flow / Função respiratória de crianças e adolescentes com osteogênese imperfeita: força muscular respiratória, capacidade vital forçada e pico de fluxo expiratório

Abstract Objective: This study aims to evaluate the respiratory function of children and adolescents with osteogenesis imperfecta (OI) followed up at a referral center. Methods: A cross-sectional study was conducted with a non-probabilistic sample. Manovacuometry was performed with the measurement of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP), and in addition, peak expiratory flow (PEF) and ventilometry were performed to measure forced vital capacity (FVC). Results: In total, 23 individuals were evaluated, with a mean age of 11.6±3.4 years, 56.5% of whom were females. Regarding the classification of OI, 56.5% of the sample belonged to type IV, 30.5% to type III, and 13% to type I. The mean MIP was 64.4% of the predicted, and the mean MEP was 56.2% of the predicted. Overall, the mean PEF was 213.9 L/min, but only 140.6 L/min in the OI type III group. Median FVC was 1.9 L, corresponding to 110% of the predicted. Conclusions: Respiratory function of the study subjects was altered, with respiratory muscle strength values lower than expected in the whole sample, and peak expiratory flow was significantly reduced in the OI type III group.

RESUMO Objetivo: Avaliar a função respiratória de crianças e adolescentes com osteogênese imperfeita (OI) acompanhados em um centro de referência. Métodos: Realizou-se um estudo de corte transversal, com amostragem não probabilística. Foi realizada manovacuometria com mensuração da pressão inspiratória máxima (PIM) e pressão expiratória máxima (PEM), além do pico de fluxo expiratório (PFE) e da ventilometria para a medida da capacidade vital forçada (CVF). Resultados: Foram avaliados 23 indivíduos, com média de idade de 11,6±3,4 anos, sendo 56,5% do sexo feminino. Com relação à classificação da OI, 56,5% da amostra pertencia ao tipo IV, 30,5% ao tipo III e 13% ao tipo I. A média de PIM foi de 64,4% do previsto, e a PEM foi de 56,2% do previsto. A média de PFE foi de 213,9 L/min, sendo 140,6 L/min no grupo de OI tipo III. A mediana da CVF foi de 1,9 L, correspondendo a 110% do previsto. Conclusões: A função respiratória dos indivíduos estudados encontrava-se alterada, com valores abaixo do esperado em toda a amostra para força muscular respiratória, além do PFE reduzido no grupo OI tipo III.

Plasma Amino Acids and Acylcarnitines Are Associated with the Female but Not Male Adolescent Swimmer's Performance: An Integration between Mass Spectrometry and Complex Network Approaches.

The main aim of this study was to compare the performance over different distances, the critical velocity (CV), and plasma acylcarnitines/amino acids of male and female adolescent swimmers. Moreover, we applied the complex network approach to identify which molecules are associated with athletes' performances. On the first day under a controlled environment, blood samples were collected after 12 h of overnight fasting. Performance trials (100, 200, 400, and 800-m) were randomly performed in the subsequent four days in a swimming pool, and CV was determined by linear distance versus time mathematical function. Metabolomic analyses were carried out on a triple quadrupole mass spectrometer performing electrospray ionization in the positive ionization mode. No difference was observed between the performance of male and female swimmers. Except for 200-m distance (p = 0.08), plasma tyrosine was positively and significantly associated with the female times during the trials (100-m, p = 0.04; 400-m, p = 0.04; 800-m, p = 0.02), and inversely associated with the CV (p = 0.02). The complex network approach showed that glycine (0.406), glutamine (0.400), arginine (0.335), free carnitine (0.355), tryptophan (0.289), and histidine (0.271) were the most influential nodes to reach tyrosine. These results revealed a thread that must be explored in further randomized/controlled designs, improving the knowledge surrounding nutrition and the performance of adolescent swimmers.

Anti-Migratory Effect of Dipotassium Glycyrrhizinate on Glioblastoma Cell Lines: Microarray Data for the Identification of Key MicroRNA Signatures.

The nuclear factor kappa B (NF-κB) pathway has been reported to be responsible for the aggressive disease phenomenon observed in glioblastoma (GBM). Dipotassium glycyrrhizinate (DPG), a dipotassium salt of glycyrrhizic acid isolated from licorice, has recently demonstrated an anti-tumoral effect on GBM cell lines U87MG and T98G through NF-κB suppression by IRAK2- and TRAF6-mediating microRNA (miR)-16 and miR-146a, respectively. Thus, the present study aimed to evaluate the expression profiles of miRNAs related to NF-κB suppression in T98G GBM cell line after DPG exposure using miRNA microarray (Affymetrix Human miRNA 4.0A), considering only predicted miRNAs as NF-κB regulator genes. Additional assays using U251 and U138MG cells were performed to validate the array results. DPG cytotoxicity was determined by (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and cellular apoptosis was quantified by DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The anti-proliferative effect was observed by cell proliferation and wound-healing assays, and the sphere formation assay examined whether DPG reduced stem cell subpopulation formation. The most over-expressed miRNAs were miR-4443 and miR-3620. The cytotoxic effect of DPG in U251 and U138MG was observed with an IC50 of 32 and 20 mM for 48 h, respectively. The IC50 of each cell line was used in all further assays. DPG treatment-induced apoptosis is observed by DNA fragmentation and increased TUNEL-positive cells. Cell proliferation and wound-healing assays showed an anti-proliferative and anti-migratory effect by DPG on the evaluated cell lines. In addition, DPG treatment led to a 100% reduction in sphere formation. The qPCR results in U251 and U138MG cells showed that DPG increased miR-4443 (2.44 vs. 1.11, p-value = 0.11; 8.27 vs. 1.25, p-value = 0.04) and miR-3620 expression (1.66 vs. 1.00, p-value = 0.03; 8.47 vs. 1.01, p-value = 0.03) and decreased CD209 (0.44 vs. 1.10, p-value = 0.03; 0.49 vs. 1.07, p-value = 0.04) and TNC (0.20 vs. 1.03, p-value = 0.001; 0.39 vs. 1.06, p-value = 0.01) mRNA levels compared to controls. Our results suggest that DPG inhibits cell viability by activating apoptosis and inhibiting cell proliferation and stem cell subpopulation formation through miR-4443 and miR-3620 upregulation. Both miRNAs are responsible for the post-transcriptional inhibition of NF-κB by CD209 and TNC modulation.

Incidência, fatores associados e impacto de complicações pulmonares no pós-operatório de cirurgia cardíaca pediátrica / Incidence, associated factors and impact of pulmonary complications in the postoperative period of pediatric cardiac surgery

Objetivo: determinar a incidência, os fatores associados e o impacto das complicações pulmonares no pós-operatório de cirurgia cardíaca pediátrica. Metodologia: estudo de coorte, prospectivo, que incluiu lactentes e crianças submetidas à cirurgia cardíaca em um hospital pediátrico, no período de novembro de 2016 a julho de 2019. Foram coletados dados dos prontuários referentes ao sexo, idade, presença de outras malformações associadas, tipo de cardiopatia, ocorrência de complicações pulmonares, tempo de ventilação mecânica (VM) e de internamento na unidade de terapia intensiva (UTI) e óbito. Resultados: a amostra foi constituída por 111 lactentes e crianças, mediana da idade de 13 meses (7-32 meses), 54,1% do sexo feminino. Quanto ao tipo de cardiopatia, 80,2% foram cianogênicas. As complicações pulmonares ocorreram em 44,1% dos casos, sendo a mais frequente a atelectasia. A mediana do tempo de VM foi 8 horas (1-48h) e 45 (40,5%) permaneceram na VM por mais de 24h. A mediana do tempo de internamento na UTI foi de 7 dias (4-12dias). Evoluíram a óbito 7 (14,3%) pacientes. Conclusão: a amostra investigada apresentou incidência elevada de complicações pulmonares no pós-operatório de cirurgia cardíaca

Objective: to determine the incidence, associated factors and impact of pulmonary complications in the postoperative period of pediatric cardiac surgery. Methodology: prospective cohort study, which included infants and children undergoing cardiac surgery in a pediatric hospital, from November 2016 to July 2019. Data were collected from medical records regarding sex, age, presence of other associated malformations, type of heart disease, occurrence of pulmonary complications, duration of mechanical ventilation (MV) and admission to the intensive care unit (ICU) stay and death. Results: the sample consisted of 111 infants and children, median age 13 months (7-32 months), 54.1% female. As for the type of heart disease, 80.2% were acyanotic. Pulmonary complications occurred in 44.1% of cases, with atelectasis being the most frequent. The median time on mechanical ventilation (MV) was 8 hours (1-48h) and 45 (40.5%) remained on MV for more than 24h. The median length of stay in the ICU was 7 days (4-12 days). 7 (14.3%) patients died. Conclusion: the investigated sample had a high incidence of pulmonary complications in the postoperative period of cardiac surgery

Serum Predose Metabolic Profiling for Prediction of Rosuvastatin Pharmacokinetic Parameters in Healthy Volunteers.

Rosuvastatin is a well-known lipid-lowering agent generally used for hypercholesterolemia treatment and coronary artery disease prevention. There is a substantial inter-individual variability in the absorption of statins usually caused by genetic polymorphisms leading to a variation in the corresponding pharmacokinetic parameters, which may affect drug therapy safety and efficacy. Therefore, the investigation of metabolic markers associated with rosuvastatin inter-individual variability is exceedingly relevant for drug therapy optimization and minimizing side effects. This work describes the application of pharmacometabolomic strategies using liquid chromatography coupled to mass spectrometry to investigate endogenous plasma metabolites capable of predicting pharmacokinetic parameters in predose samples. First, a targeted method for the determination of plasma concentration levels of rosuvastatin was validated and applied to obtain the pharmacokinetic parameters from 40 enrolled individuals; then, predose samples were analyzed using a metabolomic approach to search for associations between endogenous metabolites and the corresponding pharmacokinetic parameters. Data processing using machine learning revealed some candidates including sterols and bile acids, carboxylated metabolites, and lipids, suggesting the approach herein described as promising for personalized drug therapy.

Sensitive LC-MS/MS method for quantification of rivaroxaban in plasma: Application to pharmacokinetic studies.

Rivaroxaban is an anticoagulant (orally active direct Xa inhibitor) considered to reduce the risk of stroke and systemic embolism and treat deep vein thrombosis, pulmonary embolism, and other cardiovascular complications. Bioanalytical methods for rivaroxaban quantification in plasma are necessary for application in pharmacokinetic studies, as well as in drug therapeutic monitoring. In this work, we developed and validated a sensitive bioanalytical method using LC-MS/MS for rivaroxaban quantification in human plasma using an one-step liquid-liquid extraction. The linear concentration range was 1-600 ng/mL. The bioanalytical method was also applied to pharmacokinetic studies in healthy volunteers under fasting and fed conditions. The results demonstrated that the method is rapid, sensitive, and adequate for application in pharmacokinetic studies.

Lipid emulsion therapy in women with recurrent pregnancy loss and repeated implantation failure: The role of abnormal natural killer cell activity.

Altered immune and/or inflammatory response plays an important role in cases of recurrent pregnancy loss (RPL) and repeated implantation failure (RIF). Exacerbation of the maternal immune response through increased NK cell activity and inflammatory cytokines can cause embryo rejection leading to abortion or embryo implantation failure. Immunosuppressors or immunomodulators can help or prevent this condition. Currently, lipid emulsion therapy (LET) has emerged as a treatment for RPL and RIF in women with abnormal NK cell activity, by decreasing the exacerbated immune response of the maternal uterus and providing a more receptive environment for the embryo. However, the mechanisms by which the intralipid acts to reduce NK cell activity are still unclear. In this review, we focus on the studies that conducted LET to treat patients with RPL and RIF with abnormal NK cell activity. We find that although some authors recommend LET as an effective intervention, more studies are necessary to confirm its effectiveness in restoring NK cell activity to normal levels and to comprehend the underlying mechanisms of the lipids action in ameliorating the maternal environment and improving the pregnancy rate.

Estudo epidemiológico dos defeitos de desenvolvimento do esmalte em crianças de 2 a 4 anos de idade do município de Santa Isabel, SP / Epidemiological study of developmental enamel defects in children aged 2 to 4 years in the municipality of Santa Isabel, SP

Os distúrbios que ocorrem durante a formação do esmalte de dentes decíduos que se apresentam como Defeitos do Desenvolvimento do Esmalte (DDE) possuem importante significado clínico, pois podem causar problemas estéticos, alteração na oclusão, sensibilidade dentária e podem atuar como fator predisponente à cárie dentária, bem como ser preditor da Hipomineralização Molar - Incisivo. Estas possíveis implicações clínicas podem impactar negativamente na qualidade de vida relacionada a saúde bucal (QVRSB) das crianças com DDE. Os objetivos do presente estudo foram conhecer a prevalência e gravidade dos DDE em dentes decíduos, identificar os fatores etiológicos associados aos DDE e avaliar o impacto dos DDE na QVRSB. O estudo avaliou 336 crianças de 2 a 4 anos de idade do município de Santa Isabel, São Paulo durante a campanha nacional de vacinação. Para o diagnóstico dos DDE foi avaliada a extensão, localização, cor do defeito e o tipo de defeito, através do índice DDE modificado preconizado pela Federação Dentária Internacional. As mães ou cuidadores legais responderam a um questionário sobre variáveis sociodemográficas e condições pré, peri e pós-natal. Para avaliar o impacto dos DDE na QVRSB, foram coletados dados utilizando a versão brasileira do questionário ECOHIS. Foram realizadas análises descritivas, teste Kappa, teste qui-quadrado, teste de normalidade Kolgomorov Smirnov, teste Wilcoxon, análises não ajustadas e ajustadas de regressão de Poisson (? = 0.05). A prevalência de DDE foi 50,6%. As opacidades demarcadas (45,0%) e difusas (36,0%) de coloração branco/creme foram os defeitos mais frequentes. Molares foram os dentes mais afetados, e dentre as superfícies examinadas, as faces vestibulares foram as mais acometidas. Houve associação dos DDE com o consumo de álcool na gestação (RP 1.26; IC 95%=1.03- 1.55; p=0.022), hospitalização da criança no primeiro ano de vida por doenças infecciosas (RP=1.36; IC 95%=1.07-1.65; p=0.010) e cárie dentária (RP=1.31; IC 95%=1.03-1.65; p=0.022). Crianças que foram amamentadas por 12 meses tiveram menor risco de desenvolver DDE (RP=0.54; IC 95%=0.44-0.68; p=0.001). As opacidades de cor amarelo-marrons apresentaram maior chance de causarem impacto negativo nos domínios sintoma e limitação (p<0,05) e no domínio angústia dos pais (p<0,05). Pode-se concluir que os DDE apresentam alta prevalência e gravidade leve. Consumo de álcool durante a gravidez e hospitalização da criança por doenças infecciosas no primeiro ano de vida são fatores de risco para DDE na dentição decídua. A amamentação por um período de 12 meses é um fator de proteção ao desenvolvimento de DDE na dentição decídua. As opacidades demarcadas amarela-marrons causam impacto negativo na QVRSB de crianças de 2 a 4 anos conforme os relatos dos pais.

Potential Lipid Signatures for Diagnosis and Prognosis of Sepsis and Systemic Inflammatory Response Syndrome.

Systemic inflammatory response syndrome (SIRS) and sepsis are two conditions which are difficult to differentiate clinically and which are strongly impacted for prompt intervention. This study identified potential lipid signatures that are able to differentiate SIRS from sepsis and to predict prognosis. Forty-two patients, including 21 patients with sepsis and 21 patients with SIRS, were involved in the study. Liquid chromatography coupled to mass spectrometry and multivariate statistical methods were used to determine lipids present in patient plasma. The obtained lipid signatures revealed 355 features for the negative ion mode and 297 for the positive ion mode, which were relevant for differential diagnosis of sepsis and SIRS. These lipids were also tested as prognosis predictors. Lastly, L-octanoylcarnitine was found to be the most promising lipid signature for both the diagnosis and prognosis of critically ill patients, with accuracies of 75% for both purposes. In short, we presented the determination of lipid signatures as a potential tool for differential diagnosis of sepsis and SIRS and prognosis of these patients.

In Vivo Predictive Dissolution (IPD) for Carbamazepine Formulations: Additional Evidence Regarding a Biopredictive Dissolution Medium.

The aim of the present study was to bring additional evidence regarding a biopredictive dissolution medium containing 1% sodium lauryl sulphate (SLS) to predict the in vivo behavior of carbamazepine (CBZ) products. Twelve healthy volunteers took one immediate release (IR) dose of either test and reference formulations in a bioequivalence study (BE). Dissolution profiles were carried-out using the medium. Level A in vitro-in vivo correlations (IVIVC) were established using both one-step and two-step approaches as well as exploring the time-scaling approach to account for the differences in dissolution rate in vitro versus in vivo. A detailed step by step calculation was provided to clearly illustrate all the procedures. The results show additional evidence that the medium containing 1% SLS can be classified as a universal biopredictive dissolution tool, and that both of the approaches used to develop the IVIVC (one and two-steps) provide good in vivo predictability. Therefore, this biopredictive medium could be a highly relevant tool in Latin-American countries to ensure and check the quality of their CBZ marketed products for which BE studies were not requested by their regulatory health authorities.

In vitro - In vivo correlation in the development of oral drug formulation: A screenshot of the last two decades.

In vitro - in vivo correlation (IVIVC) allows prediction of the in vivo performance of a pharmaceutical product based on its in vitro drug release profiles and can be used to optimize formulations, set dissolution limits, reduce the number of bioequivalence studies during product development, and facilitate certain regulatory decisions. This review article aimed to assess papers published in the last two decades regarding the use of the IVIVC in the development of oral formulations, to demonstrate the scenario in this area, as well as to describe the main characteristics of the assessed studies. A systematic search of PubMed and Web of Science databases was conducted to retrieve articles reporting the use of the IVIVC in the oral formulation development in the period from 1998 to 2018. The qualified studies were abstracted regarding drug name, dosage form, BCS class, in vitro and in vivo data, level of IVIVC, number of formulations, presence of the validation and predictability. The discussion was supported by these data, which allowed to address broadly strengths and weaknesses in this area. Moreover, a large database has been described in this article containing different IVIVC models, with different substances, providing support to scientists interested in this area.

Assessing the Metabolic Impact of Ground Chia Seed in Overweight and Obese Prepubescent Children: Results of a Double-Blind Randomized Clinical Trial.

Childhood obesity is a medical condition of major public health concern. Chia seeds are used to treat certain noncommunicable diseases, and they are rich in omega-3 fatty acids, which contribute to the absorption of vitamins. A randomized double-blind clinical trial of 30 obese children was performed. The sample was composed of prepubertal 5- to 10-year-old children of both sexes with body mass indexes equal to or above the 95th percentile who were recruited through the Pediatric Department of the Faculdade de Medicina do ABC. Blood samples were drawn, the children were weighed and measured, and a 24-h dietary recall was obtained before and after the treatment. Not only were significant differences observed for fibrinogen (P = .011) but a correlation between the changes in markers and the presence of fibers was also observed for two inflammatory parameters: tumor necrosis factor-α (P = .027) and nuclear factor-κß (P = .059). These results indicate that chia seeds may have anti-inflammatory effects related to their fiber content in the context of childhood obesity.