Toxicity of REEs, Th, and U: A Biodisponibility, Cytotoxicity, and Bioaccumulation Assessment in Marine Sediment.

In this work, bioaccessibility tests for rare earth elements (REEs), Th, and U in marine sediment were carried out, in addition to complementary tests for cytotoxicity and bioaccumulation for the elements La, Ce, Eu, and Gd. The evaluation of human health risk through dermal absorption and oral ingestion was performed using the hazard quotient (HQ). According to the gastric digestion simulation (SBET), it was observed that the elements Ce and Nd exhibited higher absorption capacities in the human body (> 2 µg g-1). La and Sc presented intermediate concentrations (close to 1 µg g-1), while the remaining elements displayed concentrations below 0.5 µg g-1. In the gastrointestinal digestion extraction stage (PBET), all the elements maintained a similar absorption capacity to that observed in SBET, except for the absorption of Y which increased. The results of the bioaccumulation test conducted with fibroblast cells (L929) indicated that La and Eu had a 25% probability of intracellular accumulation. The cell viability test, with exposure to a standard REEs, Th, and U solution in 2% v v-1 HNO3 medium (until 100 µg mL-1) and an aqueous solution of La2O3, Gd(NO3)3, Ce(NO3)3, and Eu2O3 (until 1000 µg mL-1), did not demonstrate cytotoxic effects on fibroblast cells. Considering the ingestion hazard quotient (HQing) and dermal hazard quotient (HQderm) obtained, it was suggested that there is no significant risk of non-carcinogenic effects (< 1). However, they had higher HQing values compared to HQderm, indicating that REEs pose more significant risk to human health through oral ingestion absorption than dermal absorption.

Evidence for the druggability of aldosterone targets in heart failure: A bioinformatics and data science-driven decision-making approach.

BACKGROUND: Aldosterone plays a key role in the neurohormonal drive of heart failure. Systematic prioritization of drug targets using bioinformatics and database-driven decision-making can provide a competitive advantage in therapeutic R&D. This study investigated the evidence on the druggability of these aldosterone targets in heart failure. METHODS: The target disease predictability of mineralocorticoid receptors (MR) and aldosterone synthase (AS) in cardiac failure was evaluated using Open Targets target-disease association scores. The Open Targets database collections were downloaded to MongoDB and queried according to the desired aggregation level, and the results were retrieved from the Europe PMC (data type: text mining), ChEMBL (data type: drugs), Open Targets Genetics Portal (data type: genetic associations), and IMPC (data type: genetic associations) databases. The target tractability of MR and AS in the cardiovascular system was investigated by computing activity scores in a curated ChEMBL database using supervised machine learning. RESULTS: The medians of the association scores of the MR and AS groups were similar, indicating a comparable predictability of the target disease. The median of the MR activity scores group was significantly lower than that of AS, indicating that AS has higher target tractability than MR [Hodges-Lehmann difference 0.62 (95%CI 0.53-0.70, p < 0.0001]. The cumulative distributions of the overall multiplatform association scores of cardiac diseases with MR were considerably higher than with AS, indicating more advanced investigations on a wider range of disorders evaluated for MR (Kolmogorov-Smirnov D = 0.36, p = 0.0009). In curated ChEMBL, MR had a higher cumulative distribution of activity scores in experimental cardiovascular assays than AS (Kolmogorov-Smirnov D = 0.23, p < 0.0001). Documented clinical trials for MR in heart failures surfaced in database searches, none for AS. CONCLUSIONS: Although its clinical development has lagged behind that of MR, our findings indicate that AS is a promising therapeutic target for the treatment of cardiac failure. The multiplatform-integrated identification used in this study allowed us to comprehensively explore the available scientific evidence on MR and AS for heart failure therapy.

Structural Predictors of Lung Function Decline in Young Smokers with Normal Spirometry.

Rationale: Chronic obstructive pulmonary disease (COPD) due to tobacco smoking commonly presents when extensive lung damage has occurred. Objectives: We hypothesized that structural change would be detected early in the natural history of COPD and would relate to loss of lung function with time. Methods: We recruited 431 current smokers (median age, 39 yr; 16 pack-years smoked) and recorded symptoms using the COPD Assessment Test (CAT), spirometry, and quantitative thoracic computed tomography (QCT) scans at study entry. These scan results were compared with those from 67 never-smoking control subjects. Three hundred sixty-eight participants were followed every six months with measurement of postbronchodilator spirometry for a median of 32 months. The rate of FEV1 decline, adjusted for current smoking status, age, and sex, was related to the initial QCT appearances and symptoms, measured using the CAT. Measurements and Main Results: There were no material differences in demography or subjective CT appearances between the young smokers and control subjects, but 55.7% of the former had CAT scores greater than 10, and 24.2% reported chronic bronchitis. QCT assessments of disease probability-defined functional small airway disease, ground-glass opacification, bronchovascular prominence, and ratio of small blood vessel volume to total pulmonary vessel volume were increased compared with control subjects and were all associated with a faster FEV1 decline, as was a higher CAT score. Conclusions: Radiological abnormalities on CT are already established in young smokers with normal lung function and are associated with FEV1 loss independently of the impact of symptoms. Structural abnormalities are present early in the natural history of COPD and are markers of disease progression. Clinical trial registered with www.clinicaltrials.gov (NCT03480347).

Recommendations from Pediatric and Pediatric Dentistry Associations of the Americas Regarding Pacifier Use

ABSTRACT Objective: To identify online recommendations from pediatric and pediatric dentistry associations of the Americas regarding the pacifier habit. Material and Methods: A search was conducted on the associations' website (November/2021 to March/2023) to the questions: (1) Recommend using a pacifier?, (2) What care?, (3) Advantages and (4) disadvantages, (5) Ideal age, and (6) methods for habit removal. Results: Among the 36 American countries, 21 were represented on websites, social media, and official guides. The most significant portion of pediatric dentistry associations (23.81%) does not recommend the use of a pacifier if the infant is exclusively breastfeeding, and recommends avoiding the offer of a pacifier in the first days of life to facilitate the establishment of breastfeeding. Some pediatric (29.63%) associations suggested that use reduces the risk of sudden infant death syndrome. Most pediatric dentistry associations (85.71%) and some pediatric associations (22.22%) linked pacifier use to breastfeeding difficulties and the occurrence of orthodontics. Most of the 20 pediatric dentistry associations stated that the habit should be removed by a maximum of three years of age (90.48%). The most reported recommendations were behavior modification techniques and positive reinforcement. Conclusion: Most pediatric dentistry associations recommend the care and disadvantages of pacifiers and the ideal age to remove them. The few pediatric associations that provide information address indications, care, advantages and disadvantages of pacifiers, age, and methods for removing them.

Effect of oral hygiene in infants before dental eruption on Candida spp. colonization and the occurrence of oral candidiasis: A randomized clinical trial.

Background: To assess the influence of oral hygiene in infants before the primary tooth eruption on colonization by Candida spp. and the occurrence of oral candidiasis. Material and Methods: Fifty-six infants were randomly selected in their first 48 hours of life and allocated into 2 groups: Group I (Mothers were instructed to sanitize the oral cavity of the infant with gauze and filtered water once a day) and Group II (Mothers were instructed not to sanitize the oral cavity of the infant before the dental eruption). Data collection was performed one month after the birth of the infant, in their residence, including saliva collection for identification and quantification of Candida spp. Results: Colonization by Candida spp. species was found in 49.1% of the infants evaluated. There was no statistically significant difference between colonization by Candida spp. and intervention groups (p=0.947). 13.2% of the participants presented oral candidiasis during the first month of life, this prevalence was 15.4% in the control group and 11.1% in the intervention group, however, this difference was not significant (p=0.704). Conclusions: The Candida spp. colonization and the oral candidiasis occurrence, in the first month of the life of the infant, were not influenced by oral hygiene. Key words:Infants, oral hygiene, oral health, oral candidiasis.

Modeling water transport properties in carbon nanotubes: Interplay between force-field flexibility and geometrical parameters.

Modeling water and other liquids in computational simulations requires a large set of parameters. Many works have been devoted to finding new, improved water models, with almost all of them designed for bulk systems. Here, we use carbon nanotubes as a play model to investigate the effects of introducing flexibility in water force fields during molecular dynamics simulations of nanoconfined water. We explore six different models to show that viscosity, diffusion, and dipole orientation are vastly influenced by the flexibility and the family of force fields used. Particularly, we found the level of confinement (decreasing the nanotube's diameter) to increase discrepancies in the description of the dipole alignment. In smaller (10,10) nanotubes, the flexible version of the transferable intermolecular potential with three points (TIP3P/Fs) features a high directionality, while its rigid counterpart shows a more distributed dipole orientation. Both viscosity and diffusion are also extremely dependent on the force-field family, with the flexible version of the simple point charge (SPC/Fw) featuring the lower confidence interval.

Fecal microbiota transplantation in patients with metabolic syndrome and obesity: A randomized controlled trial.

BACKGROUND: Metabolic syndrome is a multifactorial disease, and the gut microbiota may play a role in its pathogenesis. Obesity, especially abdominal obesity, is associated with insulin resistance, often increasing the risk of type two diabetes mellitus, vascular endothelial dysfunction, an abnormal lipid profile, hypertension, and vascular inflammation, all of which promote the development of atherosclerotic cardiovascular disease. AIM: To evaluate the outcomes of fecal microbiota transplantation (FMT) in patients with metabolic syndrome. METHODS: This was a randomized, single-blind placebo-controlled trial comparing FMT and a sham procedure in patients with metabolic syndrome. We selected 32 female patients, who were divided into eight groups of four patients each. All of the patients were submitted to upper gastrointestinal endoscopy. In each group, two patients were randomly allocated to undergo FMT, and the other two patients received saline infusion. The patients were followed for one year after the procedures, during which time anthropometric, bioimpedance, and biochemical data were collected. The patients also had periodic consultations with a nutritionist and an endocrinologist. The primary end point was a change in the gut microbiota. RESULTS: There was evidence of a postprocedural change in microbiota composition in the patients who underwent FMT in relation to that observed in those who underwent the sham procedure. However, we found no difference between the two groups in terms of the clinical parameters evaluated. CONCLUSION: There were no significant differences in biochemical or anthropometric parameters, between the two groups evaluated. Nevertheless, there were significant postprocedural differences in the microbiota composition between the placebo group. To date, clinical outcomes related to FMT remain uncertain.

A Double-Blind, Randomized, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are a major cause of morbidity and mortality, and preventing them is a key treatment target. Long-term macrolide treatment is effective at reducing exacerbations, but there is a paucity of evidence for other antibiotic classes. Objectives: To assess whether 12-month use of doxycycline reduces the exacerbation rate in people with COPD. Methods: People with moderate to very severe COPD and an exacerbation history were recruited from three UK centers and randomized to 12 months of doxycycline 100 mg once daily or placebo. The primary study outcome was the exacerbation rate per person-year. Results: A total of 222 people were randomized. Baseline mean FEV1 was 1.35 L (SD, 0.35 L), 52.5% predicted (SD, 15.9% predicted). The median number of treated exacerbations in the year before the study was 2 (SD, 1-4). A total of 71% of patients reported two or more exacerbations, and 81% were already prescribed inhaled corticosteroids at baseline. The COPD exacerbation rate did not differ between the groups (doxycycline/placebo rate ratio [RR], 0.86; 95% confidence interval [CI], 0.67-1.10; P = 0.23). No difference was seen if only treated exacerbations or hospitalizations were considered. In preplanned subgroup analysis, doxycycline appeared to better reduce the exacerbation rate among people with severe COPD (RR, 0.36; 95% CI, 0.15-0.85; P = 0.019) and in those with an eosinophil count <300 cells/µl (RR, 0.50; 95% CI, 0.29-0.84; P = 0.01). Health status measured by St. George's Respiratory Questionnaire was 5.2 points worse in the doxycycline group at 12 months (P < 0.007). Conclusions: Doxycycline did not significantly reduce the exacerbation rate, over 12 months, in participants with COPD who exacerbated regularly, but it may have benefitted those with more severe COPD or blood eosinophil counts <300 cells/µl. Clinical trial registered with www.clinicaltrials.gov (NCT02305940).

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.

Association between asthma and oral conditions in children and adolescents: a systematic review with meta-analysis.

OBJECTIVE: To investigate the association between asthma and oral conditions in children and adolescents. MATERIAL AND METHODS: Observational studies that evaluated the association between asthma and oral conditions in children and/or adolescents were retrieved from five databases, grey literature and reference lists up to April 7th, 2022. Meta-analyses were performed, and I2 statistics were calculated. The mean difference was used as a measure of effect for continuous variables. Event frequencies were evaluated to determine odds ratios for dichotomous variables. Publication bias was investigated using Egger's test. The methodological quality (JBI) and certainty of the evidence (GRADE) were assessed. RESULTS: Forty-two studies were eligible, and sixteen were included in the meta-analysis. Mean dmft (MD: 1.11, 95%CI: 0.48-1.73), DMFT (MD: 1.01, 95% CI: 0.45-1.56), dmfs (MD: 3.62, 95%CI: 2.60-4.63) and DMFS (MD: 4.47, 95%CI: 0.98-7.96) indices were significantly higher in asthmatic children and adolescents compared to those without asthma. In the analysis of biofilm, asthmatic children and adolescents had a higher Plaque Index compared to those without asthma (MD: 0.18, 95%CI: 0.03-0.33). CONCLUSION: Asthmatic children and adolescents may be more likely to develop tooth decay and build up biofilm compared to those without asthma. It is suggested that there are no differences between asthmatic and non-asthmatic children and adolescents regarding gingivitis, developmental defects of enamel or erosive tooth wear. The certainty of the evidence was classified as 'very low'. CLINICAL RELEVANCE: Knowledge of the risks that asthma and asthma medications for oral health can assist in counselling families of children and adolescents with this condition in terms of control and prevention measures for oral problems.

Self-organizing map applied to the choice of internal standards for the determination of Cd, Pb, Sn, and platinum group elements by inductively coupled plasma mass spectrometry.

The behaviors of internal standards, according to different flow rates of the cell collision gas (He), were studied for the determination of Cd, Pb, Pd, Pt, Rh, and Sn in samples of fish and mollusks by inductively coupled plasma mass spectrometry (ICP-MS). The elements Bi, Ge, In, Sc, and Y were selected as internal standards, considering their masses and first ionization energies. Addition and recovery experiments were carried out at three concentration levels to evaluate the accuracy of the method applied for the analysis of two samples with different matrices. The results were evaluated using a self-organizing map (SOM). The best analyte/IS pairs were as follows: 114Cd+/74Ge+, 195Pt+/74Ge+, and 208Pb+/74Ge+. For 103Rh+, 106Pd+, and 120Sn+, greater accuracy was achieved without use of an internal standard. Helium gas (2.8 mL min-1) was used in the collision cell for the analytes, except for Sn, and recoveries ranged from 98 to 101% under optimal conditions. The use of SOM as an exploratory analysis tool was an effective approach for selection of the most appropriate internal standards.

Photobiomodulation Therapy on the Guided Bone Regeneration Process in Defects Filled by Biphasic Calcium Phosphate Associated with Fibrin Biopolymer.

The aim is to evaluate the effects of photobiomodulation therapy (PBMT) on the guided bone regeneration process (GBR) in defects in the calvaria of rats filled with biphasic calcium phosphate associated with fibrin biopolymer. Thirty male Wistar rats were randomly separated: BMG (n = 10), defects filled with biomaterial and covered by membrane; BFMG (n = 10), biomaterial and fibrin biopolymer covered by membrane; and BFMLG (n = 10), biomaterial and fibrin biopolymer covered by membrane and biostimulated with PBMT. The animals were euthanized at 14 and 42 days postoperatively. Microtomographically, in 42 days, there was more evident bone growth in the BFMLG, limited to the margins of the defect with permanence of the particles. Histomorphologically, an inflammatory infiltrate was observed, which regressed with the formation of mineralized bone tissue. In the quantification of bone tissue, all groups had a progressive increase in new bone tissue with a significant difference in which the BFMLG showed greater bone formation in both periods (10.12 ± 0.67 and 13.85 ± 0.54), followed by BFMG (7.35 ± 0.66 and 9.41 ± 0.84) and BMG (4.51 ± 0.44 and 7.11 ± 0.44). Picrosirius-red staining showed greater birefringence of collagen fibers in yellow-green color in the BFMLG, showing more advanced bone maturation. PBMT showed positive effects capable of improving and accelerating the guided bone regeneration process when associated with biphasic calcium phosphate and fibrin biopolymer.

The effectiveness of apple, sugar-free chewing gum, Rolly Brush® and tooth brushing in the reduction of plaque index: Crossover randomized clinical trial

Background: The implementation of the self-cleaning practice is of fundamental importance for the maintenance of oral health and to remove the human dental biofilm which is considered the main etiological factor for the development of caries and periodontal diseases. Objective: This study aimed to evaluate the use of chewing gum, Rolly Brush® and apples as forms of mechanical control and removal of the dental biofilm in the absence of brushing. Materials and Methods: Eighteen volunteers were submitted to plaque index evaluation after a period of 24 hours of no oral hygiene. Then, they would use one of the methods: chewing gum, Rolly Brush®, apple or tooth brushing, chosen by a draw, for one minute, and then, plaque index was evaluated again. This stage was repeated until all participants were submitted to all selected methods, in periods of 24 hours each. Results: Dental brushing was more effective when compared to each of the other methods applied and there was a statistically significant reduction of dental plaque index after apllying all methods of cleaning in all groups. Conclusion: Chewing gum, Rolly Brush® and apple may be used as auxiliary to dental brushing or when such method is impossible to be performed. Clinicaltrials.gov: number of protocol NCT 03.601.585.

Fundamento: A implementação da prática de autolimpeza é de fundamental importância para a manutenção da saúde bucal e remoção do biofilme dental humano que é considerado o principal fator etiológico para o desenvolvimento de cáries e doenças periodontais. Objetivo: Este estudo teve como objetivo avaliar a utilização de goma de mascar, Rolly Brush® e maçã como formas de controle mecânico e remoção do biofilme dental na ausência de escovação. Materiais e Métodos: Dezoito voluntários foram submetidos à avaliação do índice de placa após um período de 24 horas sem higiene bucal. Em seguida, utilizariam um dos métodos: goma de mascar, Rolly Brush®, ingerir uma maçã e escovar os dentes, escolhida por sorteio, por um minuto, e então, o índice de placa era novamente avaliado. Essa etapa foi repetida até que todos os participantes fossem submetidos a todos os métodos selecionados, em períodos de 24 horas cada. Resultados: A escovação dentária foi mais eficaz quando comparada a cada um dos outros métodos aplicados e houve redução estatisticamente significativa do índice de placa dentária após a aplicação do método de limpeza em todos os grupos. Conclusão: Goma de mascar, Rolly Brush® e maçã podem ser utilizados como auxiliares da escovação dentária ou quando tal método for impossível de ser realizado. Clinicaltrials.gov: Número do protocolo NCT 03.601.585.

Artificial neural network employment for element determination in Mugil cephalus by ICP OES in Pontal Bay, Brazil.

Fish are important sources of protein, making them very significant in the human diet. Although the consumption of this food is beneficial for health, it is essential that the product does not contain inorganic components above the limits recommended by the current legislation. Therefore, a method for determination of elements in fish (Mugil cephalus) samples was optimized. A simplex centroid mixture design with restriction was applied for optimization of the acid digestion of samples in an open system under reflux in order to evaluate the best ratio between the reagents HNO3, H2O2 and H2O. The results indicated that more intense analyte signals were obtained when a mixture containing 3.6 mL of HNO3 (65% v/v), 0.4 mL of H2O2 (30% v/v) and 6.0 mL of H2O was used. The accuracy of the method was assessed with a CRM of oyster tissue (NIST 1566b). The method presented relative standard deviations (RSDs) of 3.54%; 3.82%; 4.81% and 3.50% for Zn, Fe, Cu and S, respectively. The detection limits were 0.002 mg kg-1 for Cu and Zn and 0.02 mg kg-1 for Fe and S. The proposed method was applied for the determination of Zn, Fe, Cu and S in fish samples. A Kohonen Self-Organizing Map (KSOM) with K-means implementation was applied to better delimit the boundary between groups and the spatial and temporal influence on how concentrations of the chemical elements were perceived. To verify the separation, the Davies-Bouldin and Silhouette indices were used, obtaining 0.5374 and 0.8541, respectively, indicating satisfactory separation.

Targeted Retreatment of Incompletely Recovered Chronic Obstructive Pulmonary Disease Exacerbations with Ciprofloxacin. A Double-Blind, Randomized, Placebo-controlled, Multicenter, Phase III Clinical Trial.

Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are prone to nonrecovery, but there are no data about the effectiveness of retreatment for these prolonged events. We examined whether further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event.Objectives: To assess whether incompletely recovered COPD exacerbations benefit from additional treatment with ciprofloxacin, at Day 14.Methods: In a multicenter, randomized double-blind placebo-controlled trial, we studied retreatment with oral ciprofloxacin 500 mg or matched placebo twice daily for 7 days in patients with Global Initiative for Chronic Obstructive Lung Disease stage II-IV COPD and persistent symptoms and/or serum C-reactive protein ≥8 mg/L initiated 14 (±3) days after an index COPD exacerbation. The primary outcome was the time to the next exacerbation within a 90-day period.Measurements and Main Results: Among 826 patients screened at four centers, 144 eligible participants with incomplete recovery were randomized to receive ciprofloxacin (n = 72) or placebo (n = 72). Within 90 days of randomization, 57% of the patients in the ciprofloxacin group and 53% in the placebo group experienced one or more exacerbations. The median time to the next exacerbation was 32.5 days (interquartile range 13-50) in the placebo arm and 34 days (interquartile range 17-62) in the ciprofloxacin arm, which was not significantly different (adjusted hazard ratio, 1.07; 95% confidence interval, 0.68-1.68; P = 0.76). No significant differences were seen in quality-of-life scores or lung function between the treatment groups.Conclusions: In patients with persistent symptoms and/or raised C-reactive protein 14 days after a COPD exacerbation, an additional course of ciprofloxacin resulted in no additional benefit compared with placebo. This suggests that nonrecovered exacerbations are not driven by ongoing bacterial infection and may potentially be targeted with antiinflammatory therapy.Clinical trial registered with www.clinicaltrials.gov (NCT02300220).

Gut Microbiome of Children and Adolescents With Primary Sclerosing Cholangitis in Association With Ulcerative Colitis.

Few studies reported the relation of intestinal microbiome composition and diversity in pediatric patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In this cross-sectional study, we selected patients younger than 19 years old from the pediatric gastroenterology and hepatology outpatient clinic of a tertiary hospital to describe the intestinal microbiome of pediatric patients with PSC associated or not to UC. Patients were divided in PSC, PSC+UC, and UC diagnosis. A stool sample was collected from each patient (n=30) and from a healthy relative/neighbor (n=23). The microbiome composition was assessed using MiSeq (Illumina) platform. Differences in microbial composition were found between PSC and PSC+UC groups. The relative abundance of Veillonella and Megasphaera genera were increased depending on patients' age at diagnosis. Veillonella was also increased in patients who were in an active status of the disease. Both genera were positively correlated to total bilirubin and gamma-glutamyl transferase. As a conclusion, the disease, the age and the disease activity status seem to influence the intestinal microbiome, highlighting the difference of intestinal microbiome profile for patients depending on age at diagnosis. We also showed an increase of Veillonella in patients with PSC and PSC+UC, and a positive correlation of dysbiosis and higher gamma-glutamyl transferase and total bilirubin in PSC+UC patients. Our findings are promising in the diagnosis, prognosis, and future therapeutic perspectives for PSC patients.

Reflexividade sobre ações morais em adultos: um estudo fenomenológico-semiótico / Reflexivity about moral actions in adults: a semiotic phenomenological study / Reflexividad sobre acciones morales en adultos: un estudio fenomenológico-semiótico

Os fenômenos da reflexividade consciente e da moralidade são atributos exclusivos da espécie humana, com fortes indícios de indissociabilidade e de sincronia em sua história evolutiva. Com o objetivo de compreender a relação entre reflexividade e ações morais, realizou-se um estudo qualitativo, conforme os critérios da fenomenologia-semiótica, com base em entrevistas estruturadas anônimas realizadas pela internet. Participaram 363 adultos, com faixa etária entre 21 e 28 anos (35%) e 28 e 35 anos (27%), sendo 63% do sexo feminino. Os resultados revelaram um contexto temático estruturado em 18 temas e um contexto problemático composto pelos aspectos: processos de mediação e modulação das ações morais; caracterização da agência (pessoal e interna ou normativa e externa); dilemas entre padrões pessoais e sociais de ação (dissonância cognitiva); sentidos pessoais atribuídos ao agir moral (níveis deontológicos da opinião, compreendidos entre o nível ontológico e o nível estilístico). Conclui-se que a reflexividade pode exercer influência sobre as ações morais, embora nem sempre seja suficiente para motivá-las, e que uma ação intencional praticada pode exercer influência não apenas sobre a reflexividade, mas sobre o próprio self, principalmente se esta possuir conteúdo moral (ou transgressor).

The phenomena of conscious reflexivity and morality are attributes unique to the human species, with strong evidence of inseparability and synchrony in their evolutionary history. In order to understand the relationship between reflexivity and moral actions, a qualitative study was carried out, according to the criteria of phenomenology-semiotics, based on anonymous structured interviews conducted on the internet. A total of 363 adults, aged between 21 and 28 years (35%) and 28 and 35 years (27%), 63% were female. The results revealed a thematic context structured in 18 themes and a problematic context composed of the following aspects: processes of mediation and modulation of moral actions; characterization of the agency (personal and internal or normative and external); quandary between personal and social patterns of action (cognitive dissonance); personal senses attributed to moral action (deontological levels of opinion, understood between the ontological level and the stylistic level). It is concluded that reflexivity can exert an influence on moral actions, although not always enough to motivate them, and that an intentional action practiced can exert influence not only on reflexivity, but on the self, especially if it has content moral (or transgressor).

Los fenómenos de la reflexividad consciente y de la moralidad son atributos exclusivos de la especie humana, con fuertes indicios de indisociación y de sincronía en su historia evolutiva. Con el objetivo de comprender la relación entre reflexividad y acciones morales, se realizó un estudio cualitativo, conforme a los criterios de la fenomenología-semiótica, con base en entrevistas estructuradas anónimas realizadas por internet. Los resultados revelaron un contexto temático estructurado en 18 temas y un contexto problemático compuesto por los aspectos: procesos de mediación y modulación de las acciones morales; caracterización de la agencia (personal e interna o normativa y externa); dilemas entre patrones personales y sociales de acción (disonancia cognitiva); los sentidos personales atribuidos al actuar moral (niveles deontológicos de la opinión, comprendidos entre el nivel ontológico y el nivel estilístico). Se concluye que la reflexividad puede ejercer influencia sobre las acciones morales, aunque no siempre es suficiente para motivarlas, y que una acción intencional practicada puede ejercer influencia no sólo sobre la reflexividad, sino sobre el propio self, principalmente si ésta posee contenido (o transgresor).

Development of procedure for sample preparation of cashew nuts using mixture design and evaluation of nutrient profiles by Kohonen neural network.

A procedure using ICP OES for sample preparation for the determination of copper, iron and manganese in cashew nuts was developed. Constrained simplex-centroid design was applied in the optimization of the digestion in microwave oven procedure, and the results evaluated from topological maps of the Kohonen network. The best proportion evaluated for the digestion of the sample with HNO3, H2O2 and H2O was 10:45:45 (%). With optimized conditions, the detection limits were 0.63, 4.3 and 0.37 mg kg-1, and quantification 2.1, 14 and 1.2 mg kg-1 for Cu, Fe and Mg, respectively. The precision (% RSD) was 1.84, 2.31 and 2.73, for Cu, Fe and Mg, respectively. The procedure proposed had the accuracy confirmed using NIST 1568b (at 95% reliability) and was applied in the samples obtaining concentrations in the range of 10.7-19.4, 44.3-67.2 and 11.0-21.4 mg kg-1 for Cu, Fe and Mg, respectively.