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Background: Mycobacterium leprae and Mycobacterium lepromatosis are gram-positive bacterial pathogens and the causative agents of leprosy in humans across the world. The elimination of leprosy cannot be achieved by multidrug therapy alone, and highlights the need for new tools and drugs to prevent the emergence of new resistant strains., Methods: In this study, our contribution includes the prediction of vaccine targets and new putative drugs against leprosy, using reverse vaccinology and subtractive genomics. Six strains of Mycobacterium leprae and Mycobacterium lepromatosis (4 and 2 strains, respectively) were used for comparison taking Mycobacterium leprae strain TN as the reference genome. Briefly, we used a combined reverse vaccinology and subtractive genomics approach., Results: As a result, we identified 12 common putative antigenic proteins as vaccine targets and three common drug targets against Mycobacterium leprae and Mycobacterium lepromatosis. Furthermore , the docking analysis using 28 natural compounds with three drug targets was done., Conclusions: The bis-naphthoquinone compound Diospyrin (CID 308140) obtained from indigenous plant Diospyros spp . showed the most favored binding affinity against predicted drug targets, which can be a candidate therapeutic target in the future against leprosy., Competing Interests: Competing interests: The authors declare that they have no competing interests.

Objectives: To assess whether a Spanish-language text messaging program helps Latinos with diabetes better manage their disease., Methods: Spanish-speaking Latinos with type 2 diabetes and HbA1c ≥ 8% (N = 38) were recruited January 1, 2016-May 31, 2016, at a large integrated healthcare delivery system. Participants received 1-3 Spanish-language text messages about diabetes self-care per day for 3 months with an optional 3-month extension. The Wilcoxon signed-rank test for paired data was used to compare pre-post intervention HbA1c. The Wilcoxon-Mann-Whitney nonparametric test was used to compare changes in HbA1c across groups., Results: After 3 months, the median HbA1c reduction overall was 1.4 percentage points (IQR: 0.5-3.3, p < 0.01). Latinos having pre-intervention HbA1c > 10.0% had a greater reduction in median HbA1c (3.8, IQR: 0.5-5.3) compared with those having pre-intervention HbA1c ≤ 10.0% (0.9, IQR: 0.1-1.9, p < 0.05). This reduction in median HbA1c persisted after 6 months (1.3, IQR: 0.2-2.9, p < 0.01)., Conclusion: A Spanish-language text messaging program was an effective way to improve glycemic control for Latinos with type 2 diabetes., Policy Implications: Culturally and linguistically tailored text messaging programs for managing diabetes should be considered.

Congenital Zika virus (ZIKV) infection may present with a broad spectrum of clinical manifestations. Some sequelae, particularly neurodevelopmental problems, may have a later onset. We conducted a prospective cohort study of 799 high-risk pregnant women who were followed up until delivery. Eighty-three women and/or newborns were considered ZIKV exposed and/or infected. Laboratory diagnosis was made by polymerase chain reaction in the pregnant mothers and their respective newborns, as well as Dengue virus, Chikungunya virus, and ZIKV serology. Serology for toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, and syphilis infections were also performed in microcephalic newborns. The newborns included in the study were followed up until their third birthday. Developmental delay was observed in nine patients (13.2%): mild cognitive delay in three patients, speech delay in three patients, autism spectrum disorder in two patients, and severe neurological abnormalities in one microcephalic patient; sensorineural hearing loss, three patients and dysphagia, six patients. Microcephaly due to ZIKV occurred in three patients (3.6%). Clinical manifestations can appear after the first year of life in children infected/exposed to ZIKV, emphasizing the need for long-term follow-up.

Management of metastatic radioiodine refractory differentiated thyroid cancer (DTC) can be a therapeutic challenge. Generally, little is known about the paired molecular profile of the primary tumor and the metastases and whether they harbor the same genetic abnormalities. The present study compared the molecular profile of paired tumor specimens (primary tumor/metastatic sites) from patients with radioiodine refractory DTC in order to gain insight into a possible basis for resistance to radioiodine. Twelve patients with radioiodine refractory metastases were studied; median age at diagnosis of 61 years (range, 25-82). Nine patients had papillary TC (PTC), one had follicular TC (FTC), and two had Hürthle cell TC (HTC). Distant metastases were present in the lungs (n = 10), bones (n = 4), and liver (n = 1). The molecular profiling of paired tumors was performed with a panel of 592 genes for Next Generation Sequencing, RNA-sequencing, and immunohistochemistry. Digital microfluidic PCR was used to investigate TERT promoter mutations. The genetic landscape of all paired sites comprised BRAF , NRAS , HRAS , TP53 , ATM , MUTYH , POLE , and NTRK genes, including BRAF and NTRK fusions. BRAF V600E was the most common point mutation in the paired specimens (5/12). TERT promoter mutation C228T was detected in one case. PD-L1 expression at metastatic sites was highly positive (95%) for one patient with HTC. All specimens were stable for microsatellite instability testing, and the tumor mutation burden was low to intermediate. Therefore, the molecular profile of DTC primary and metastatic lesions can show heterogeneity, which may help explain some altered responses to therapeutic intervention., Competing Interests: RF is employed by Caris Life Sciences. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gomes-Lima, Shobab, Wu, Ylli, Bikas, McCoy, Feldman, Lee, Rao, Jensen, Vasko, Castro, Jonklaas, Wartofsky and Burman.)

Multifunctionalized indole derivatives were prepared by reducing azoarenes in the presence of ketones and bis(neopentylglycolato)diboron (B 2 nep 2 ) with a catalytic amount of 4,4'-bipyridyl under neutral reaction conditions, where 4,4'-bipyridyl acted as an organocatalyst to activate the B-B bond of B 2 nep 2 and form N , N '-diboryl-1,2-diarylhydrazines as key intermediates. Further reaction of N , N '-diboryl-1,2-diarylhydrazines with ketones afforded N -vinyl-1,2-diarylhydrazines, which rearranged to the corresponding indoles via the Fischer indole mechanism. This organocatalytic system was applied to diverse alkyl cyclic ketones, dialkyl, and alkyl/aryl ketones, including heteroatoms. Methyl alkyl ketones gave the corresponding 2-methyl-3-substituted indoles in a regioselective manner. This protocol allowed us to expand the preparation of indoles having high compatibility with not only electron-donating and electron-withdrawing groups but also N - and O -protecting functional groups.

Purpose: To investigate the effect of maternal dietary total antioxidant capacity (DTAC) and main food sources on the risk of preterm birth (PB) and offspring birth size., Methods: Cohort study that included 733 Brazilian mother-child pairs. Two 24 h dietary recalls were obtained during pregnancy and the usual intake was estimated through the Multiple Source Method. Data of the offspring were extracted from the national live births information system. Adjusted multivariable logistic regression models were used to investigate the relationship that energy-adjusted DTAC and food sources have with the outcomes., Results: In total, 9.7% of the children were PBs, 6.0% were born with low birth weight (LBW), 6.7% with macrosomia, 9.3% were small for gestational age (SGA) and 16.4% large for gestational age (LGA). The mean energy-adjusted DTAC ± SD was 4.7 ± 2.1 mmol. The adjusted OR (95%CI) of PB for each increasing tertile of maternal DTAC were 0.71 (0.41, 1.30) and 0.54 (0.29, 0.98), when compared with the lowest intake. For LBW, these were 0.25 (0.09, 0.65) and 0.63 (0.28, 1.41). A likelihood of lower odds for PB was found for a higher intake of fruits [0.66 (0.39, 1.09)]. Women with a higher consumption of milk were less likely to have a child with LBW [0.48 (0.23, 1.01)], and children whose mothers reported a higher intake of beans had lower odds of being born LGA [0.61 (0.39, 0.93)]., Conclusion: The data suggest that a higher intake of foods with antioxidant activity during pregnancy might reduce the chance of adverse birth outcomes.

Originated in Wuhan, China, the coronavirus 19 disease (COVID-19) has quickly spread worldwide, reaching countries that already faced other endemics and epidemics. In Brazil, such a concerning situation includes arboviruses, among which the dengue virus stands out. Here, we determined the rate of SARS-CoV-2/dengue virus co-infection in a total of 178 patients with COVID-19 symtoms admitted into a large public hospital of the Federal District of Brazil. Furthermore, we evaluated whether prior or active dengue virus infection influenced hematological, biochemical, and clinical parameters of such patients. One hundred and twelve (63%) individuals tested positive for COVID-19, of which 43 (38.4%) were co-infected with dengue virus, and 50 (44.6%) had antibodies indicative of previous dengue infection. Co-infected patients showed lower numbers of circulating lymphocytes and monocytes, higher glucose rates, and a worse pulmonary condition. Of note, prior infections with dengue virus did not influence clinical parameters, but active dengue fever resulted in higher hospitalization rate. In conclusion, amid the current complex epidemiological scenario in Brazil, our data support the notion that SARS-CoV-2 and dengue co-infection affects an important percentage of COVID-19 patients and leads to worse clinical parameters, requiring greater attention from health authorities., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: The Fricke dosimeter has been shown to be a viable option as an absorbed dose standard. This work aims to provide the dose distribution in an irradiator container during blood irradiation using Fricke dosimetry., Methods: Measurements were performed using a Gammacell Elan 3000 blood irradiator at Hemocenter in Rio de Janeiro, Brazil. A specific phantom was constructed and patented by the authors to perform these measurements. Fricke solution was prepared according to international protocols, and polyethylene bags filled with Fricke solution (n = 19) were spatially distributed within the phantom. Control bags were also submitted to the same process, except the irradiation. The irradiation time was calculated to give 25.7 Gy to the central portion of the phantom, the same dose used for blood bags., Results: Encouraging results were obtained with an overall uncertainty of 2.1% (k = 1). The obtained results were compared with the doses calculated by the physicist from Hemocenter based on parameters provided by the manufacturer. The mean dose delivered to the Fricke bag in the center of the phantom (cavity 2) was 28.7 ± 0.5 Gy, which is 12% higher than the planned dose of 25.7 Gy., Conclusions: The obtained results showed that the setup (Fricke and phantom) is able to perform dosimetry for blood irradiators. The delivered dose was higher than expected. This highlights the importance in controlling all the parameters during irradiation to ensure the correct dose for all irradiated bags., (© 2020 American Association of Physicists in Medicine.)

The field of cell therapy is leading a paradigm shift in drug development. The recent convergence of several fields, including immunology, genetics, and synthetic biology, now allows for the introduction of artificial receptors and the design of entire genetic circuitries to finely program the behavior of injected cells. A prime example of these next-generation living drugs comes in the form of T cells expressing chimeric antigen receptors (CARs), which have already demonstrated definitive evidence of therapeutic efficacy against some hematological malignancies. However, several obstacles still restrict the antitumor efficacy of and impair the widespread use of CAR-T cells. Critical challenges include limited persistence and antitumor activity in vivo, antigen escape, scarcity of suitable single markers for targeting, and therapy-related toxicity. Nevertheless, intense research activity in this field has resulted in a plethora of creative solutions to address each of these limitations. In this review, we provide a comprehensive snapshot of the current strategies used to enhance the therapeutic efficacy, applicability, and safety of genetically engineered immune cells to treat cancer.

Background: Neurogenic tumors of the larynx are rare, with few cases having been reported in the literature. Schwannomas are responsible for 0.1% of all benign tumors of the larynx. They arise in the sheaths of the peripheral, autonomic, and cranial nerves. The objective of this report is to describe a case of a bulky laryngeal schwannoma, the surgical procedure for its removal, and the long-term patient follow-up., Case Presentation: A 19-year-old Brazilian woman presented to our institution with a complaint of progressive dyspnea over the preceding year, as well as dysphonia, dysphagia for solids, and globus pharyngeus. Direct rigid laryngoscopy showed a supraglottic tumor obstructing approximately 90% of the larynx. With the symptoms progressing to severe dyspnea, an emergency tracheostomy was performed. After infusion of intravenous contrast, magnetic resonance imaging revealed a mass lesion with intense, heterogeneous contrast enhancement along the posterior wall of the hypopharynx, blocking all of the lumen and measuring 2.8 cm and 2.2 cm at its largest diameters. The image suggested a neoplastic lesion. The patient underwent open surgery for tumor resection. Her postsurgical recovery was uncomplicated. Histopathology and immunohistochemistry revealed the tumor to be a laryngeal schwannoma., Conclusion: The definitive diagnosis of laryngeal lesions can be difficult, and histopathology plays a pivotal role. Laryngeal schwannomas are rare; however, tumors can become large and may ultimately lead to airway obstruction.

The COVID-19 outbreak, caused by Sars-Cov-2, was officially declared a global pandemic in February 2020, after an unexpected increase in hospitalization and mortality. When faced with this new disease, social and physical distancing and quarantine emerged as solutions to reduce virus transmission. This article examines the quality of life (QoL) of the Brazilian population's during this period of isolation, due to the COVID-19 pandemic by analyzing; physical, psychological, social, and economic aspects. An online survey was distributed from 27 May to 14 August of 2020. A total of 1859 surveys were completed. Our results indicate that Brazilians were more affected by economic and social aspects than psychological and physical. Unemployed participants and individuals who tested positive for COVID-19 presented the lowest QoL. Females showed worst QoL scores than males, but having children did not influence the score. Higher educational level was associated with a better perception of QoL. Not following social distancing guidelines presented better scores in the psychological domain than the ones following restrict or partial social distancing rules. This study is the first to evaluate adults' QoL related to the Sars-Cov-2 pandemic in Brazil at a national level. Our data may help health authorities identify the main factors affecting the QoL of the Brazilian population, thereby orientating them to recover after the pandemic.

Objective: To evaluate the association between the use of nephrotoxic drugs and acute kidney injury in critically ill pediatric patients., Methods: This was a retrospective cohort study involving all children admitted to the intensive care unit of a pediatric hospital during a 1-year period. Acute kidney injury was defined according to the KDIGO classification. Patients with a length of hospital stay longer than 48 hours and an age between 1 month and 14 years were included. Patients with acute or chronic nephropathy, uropathy, congenital or acquired heart disease, chronic use of nephrotoxic drugs, rhabdomyolysis and tumor lysis syndrome were excluded. Patients were classified according to the use of nephrotoxic drugs during their stay at the pediatric intensive care unit., Results: The sample consisted of 226 children, of whom 37.1% used nephrotoxic drugs, 42.4% developed acute kidney injury, and 7.5% died. The following drugs, when used alone, were associated with acute kidney injury: acyclovir (p < 0.001), vancomycin (p < 0.001), furosemide (p < 0.001) and ganciclovir (p = 0.008). The concomitant use of two or more nephrotoxic drugs was characterized as an independent marker of renal dysfunction (p < 0.001). After discharge from the pediatric intensive care unit, renal function monitoring in the ward was inadequate in 19.8% of cases., Conclusion: It is necessary for intensivist physicians to have knowledge of the main nephrotoxic drugs to predict, reduce or avoid damage to their patients.

Purpose: Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy treatment planning remains a significant challenge. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study assesses the dosimetric impact attributed to differences in DIL contours generated using commonly available MRI to TRUS automated registration: rigid, semi-rigid, and deformable image registration, respectively., Methods and Materials: Ten patients, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists with expertise in TRUS-based high-dose-rate brachytherapy were asked cognitively to transfer the DIL from the mpMRI images of each patient to the TRUS image. The contours were analyzed for concordance using simultaneous truth and performance level estimation (STAPLE) algorithm. The impact of DIL contour differences due to registration variability was evaluated by comparing the STAPLE-DIL dosimetry from the reference (STAPLE) plan with that from the evaluation plans (manual and automated registration) for each patient. The dosimetric impact of the automatic registration approach was also validated using a margin expansion that normalizes the volume of the autoregistered DILs to the volumes of the STAPLE-DILs. Dose metrics including D 90 , D mean , V 150 , and V 200 to the prostate and DIL were reported. For urethra and rectum, D 10 and V 80 were reported., Results: Significant differences in DIL coverage between reference and evaluation plans were found regardless of the algorithm methodology. No statistical difference was reported in STAPLE-DIL dosimetry when manual registration was used. A margin of 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm was required to be added for rigid, semi-rigid, and deformable registration, respectively, to mitigate the difference in STAPLE-DIL coverage between the evaluation and reference plans., Conclusion: The dosimetric impact of integrating an MRI-delineated DIL into a TRUS-based brachytherapy workflow has been validated in this study. The results show that rigid, semi-rigid, and deformable registration algorithms lead to a significant undercoverage of the DIL D 90 and D mean . A margin of at least 1.5 ± 0.8 mm, 1.1 ± 0.8 mm, and 2.5 ± 1.6 mm is required to be added to the rigid, semi-rigid, and deformable DIL registration to be suitable for DIL-boosting during prostate brachytherapy., (Copyright © 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

This work is the first of a two-part study that aims to develop a computationally efficient bias correction framework to improve surface PM 2.5 forecasts in the United States. Here, an ensemble-based Kalman filter (KF) technique is developed primarily for nonrural areas with approximately 500 surface observation sites for PM 2.5 and applied to three (GEOS-Chem, WRF-Chem, and WRF-CMAQ) chemical transport model (CTM) hindcast outputs for June 2012. While all CTMs underestimate daily surface PM 2.5 mass concentration by 20-50%, KF correction is effective for improving each CTM forecast. Subsequently, two ensemble methods are formulated: (1) the arithmetic mean ensemble (AME) that equally weights each model and (2) the optimized ensemble (OPE) that calculates the individual model weights by minimizing the least-square errors. While the OPE shows superior performance than the AME, the combination of either the AME or the OPE with a KF performs better than the OPE alone, indicating the effectiveness of the KF technique. Overall, the combination of a KF with the OPE shows the best results. Lastly, the Successive Correction Method (SCM) was applied to spread the bias correction from model grids with surface PM 2.5 observations to the grids lacking ground observations by using a radius of influence of 125 km derived from surface observations, which further improves the forecast of surface PM 2.5 at the national scale. Our findings provide the foundation for the second part of this study that uses satellite-based aerosol optical depth (AOD) products to further improve the forecast of surface PM 2.5 in rural areas by performing statistical analysis of model output.

Commercial products based on Trichoderma are obtained mainly from solid-state fermentation. Submerged liquid fermentation is the most appropriate method compared to the solid medium for large-scale production of Trichoderma spp. The present study aimed to optimize the combination of key variables that influence the liquid fermentation process of Trichoderma asperelloides LQC-96 for conidial production coupled with its efficiency in the control of Sclerotinia sclerotiorum. In addition, we verified whether the optimized culture conditions can be used for the conidial production of Trichoderma erinaceum T-12 and T-18 and Trichoderma harzianum T-15. Fermentation studies were performed in shake flasks following a planned experimental design to reduce the number of tests and consumable costs. The effect of temperature, pH, photoperiod, carbon:nitrogen ratio and water activity on conidial production were assessed, which of pH was the only meaningful factor contributing to increased conidial production of T. asperelloides LQC-96. From the five variables studied initially, pH and C:N ratio were further used in the second design (rotational central composite design-RCCD). Hence, the best conditions for the production of T. asperelloides LQC-96 conidia by liquid fermentation consisted of initial pH of 3.5, C:N ratio of 200:1 at 30 °C, without glycerol, and under 24 h photoperiod. The highest conidial concentration was observed after seven days of fermentation. Under these optimal conditions, T. erinaceum T-12 and T-18, and T. harzianum T-15 were also cultivated, but only LQC-96 efficiently parasitized S. sclerotiorum, precluding sclerotium myceliogenic germination. Our findings propose optimal fermentation conditions that maximize conidial production of T. asperelloides as a potential biofungicide against S. sclerotiorum.

Purpose: The purpose of this study was to evaluate the noninferiority of Day 30 dosimetry between a machine learning-based treatment planning system for prostate low-dose-rate (LDR) brachytherapy and the conventional, manual planning technique. As a secondary objective, the impact of planning technique on clinical workflow efficiency was also evaluated., Materials and Methods: 41 consecutive patients who underwent I-125 LDR monotherapy for low- and intermediate-risk prostate cancer were accrued into this single-institution study between 2017 and 2018. Patients were 1:1 randomized to receive treatment planning using a machine learning-based prostate implant planning algorithm (PIPA system) or conventional, manual technique. Treatment plan modifications by the radiation oncologist were evaluated by computing the Dice coefficient of the prostate V 150% isodose volume between either the PIPA-or conventional-and final approved plans. Additional evaluations between groups evaluated the total planning time and dosimetric outcomes at preimplant and Day 30., Results: 21 and 20 patients were treated using the PIPA and conventional techniques, respectively. No significant differences were observed in preimplant or Day 30 prostate D 90% , V 100% , rectum V 100 , or rectum D 1cc between PIPA and conventional techniques. Although the PIPA group had a larger proportion of patients with plans requiring no modifications (Dice = 1.00), there was no significant difference between the magnitude of modifications between each arm. There was a large significant advantage in mean planning time for the PIPA arm (2.38 ± 0.96 min) compared with the conventional (43.13 ± 58.70 min) technique (p >> 0.05)., Conclusions: A machine learning-based planning workflow for prostate LDR brachytherapy has the potential to offer significant time savings and operational efficiencies, while producing noninferior postoperative dosimetry to that of expert, conventional treatment planners., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Some composite resins contain luminophorous agents in order to reproduce tooth fluorescence. The objective of this study was to compare the fluorescence spectra emitted by composite resins with those of human enamel and dentin, and their emission behaviour after a 90-day natural aging period., Material and Methods: Nine shades of the composite resins Z350XT/3M (XT), Opallis/FGM (OP) and Empress Direct/Ivoclar-Vivadent (ED) were analyzed. Five specimens (10.0 mm x 2.0mm) were fabricated for each shade. Enamel (5.0 mm x 0.30 mm) and dentin (5.0 mm x 1.0 mm) specimens were obtained from sound human third molars. Fluorescence spectra of human dentin and enamel as well as the composite specimens immediately after fabrication were measured at the excitation peaks of 375, 395 and 410 nm. To assess composite resin fluorescence intensity changes over time, measurements were conducted after 30, 60 and 90 days, at 395 nm. Differences in fluorescence intensity over time were analyzed with ANOVA and Tukey's test ( p <0.05)., Results: Fluorescence spectra baseline values of composites demonstrated no differences in intensity among the excitation peaks tested, with maximum emission found at the peak of 450 nm. Enamel and dentin spectra varied with different excitations, and the greater the excitation, the longer the wavelength in comparison to composite resins. After 90 days, XT presented an increase in fluorescence intensity, while OP and ED showed a reduction when compared with baseline values., Conclusions: Fluorescence intensity of composite resins changed during the period analyzed, with an emission behavior different from that of human enamel and dentin. The main changes occurred in the first 30 days. Key words: Composite resins, dental materials, fluorescence, fluorescence spectrometry., Competing Interests: Conflicts of interest Non declared., (Copyright: © 2020 Medicina Oral S.L.)

Background: The study evaluates children in schools that participate in the School Health Program in the Northern region of Brazil with the objective of assessing whether their schools interfered in the development of overweight/obesity and how individual and school environment variables behave according to contextual analysis., Methods: The analyses were carried out with 1036 children from 25 municipal public schools in Northern Brazil that participated in the School Health Program. We evaluated both individual characteristics and scholar environment through univariate and multivariate logistic regressions to identify which of these factors were related to overweight/obesity as well as the effect of varying such associations., Results: The considered individuals had an median age of 8 years, being 54.9% female and 27.8% presenting overweight/obesity. In multivariate logistic regression, the overweight/obesity variance in schools was 0.386 (individual variables) and 0.102 (individual and school variables), explaining 23.7% of the variation, reduction of ICC and MOR. The Akaike Information Criterion between the models was reduced and the likelihood ratio indicated better adequacy of the latter model. The investigated children had a greater chance of developing overweight/obesity when they performed 2+ sedentary activities/day, depending on school location as well as whether or not candies were sold in the school surroundings. On the other hand, a lower chance of developing overweight/obesity was identified in children that ate 5+ meals/day and practiced dance at school., Conclusion: We observed that the variables inherent to both individuals and schools favored the development of overweight/obesity in children. It is relevant that scholar curriculums incorporate healthy eating interventions and encourage body practices associated with policies that restrain the sale of ultra-processed food in schools as well as the development of intersectoral actions between education and health to control childhood obesity.

Background: Although the clinical practice guidelines recommend continuous adjustment of asthma treatment and reducing the maintenance drugs when achieving control (step-down), there are few studies of standard clinical practice aimed at collecting information on the factors that determine step-down failure., Objective: To determine the factors that determine step-down failure in standard clinical practice of patients with moderate-severe asthma controlled by a combination of inhaled glucocorticoids and long-acting beta agonists., Methods: A multicentre retrospective study included 374 patients with moderate-severe asthma controlled with inhaled glucocorticoids and long-acting beta agonists for whom the physician indicated a step-down in 2016., Results: The step-down failed in 41.7% of the patients. The following factors were related to failure: greater patient age (P=.006), presence of at least 2 comorbidities (P=.016), greater severity level (severe persistent vs. moderate persistent) (P<.001), greater age at diagnosis (>40 years) (P=.045), the higher the therapeutic step before (P=.003) and after the change (P<.001), the shorter the time of improvement/control prior to the change (P=.019), lower FEV 1 (P=.001) and a poorer Asthma Control Test score or Asthma Control Questionnaire score before the step-down (P<.001). The logistic regression analysis showed a higher probability of step-down failure in the more elderly patients (OR, 0.983; 95% CI 0.969-0.997) and those with severe asthma compared to those with moderate asthma (OR, 0.537; 95% CI 0.292-0.985), as well as an increased probability of success if the patients had the disease controlled for more than 6 months (OR, 2.253; 95% CI 1.235-4.112)., Conclusion: In standard clinical practice conditions, step-down fails in a high percentage of patients, and the suggestion is to indicate step-down when the patient has had more than 6 months of disease control., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.)

Background: The Measure of Processes of Care (MPOC) questionnaires evaluate Family-Centered Practice (FCP) in services for children with developmental disorders. The MPOC-20 and MPOC-SP are completed by parents and by rehabilitation professionals, respectively, and are widely used in several countries., Objectives: To translate and cross-culturally adapt the MPOC-20 and MPOC-SP to Brazilian Portuguese and evaluate their reliability and internal consistency., Methods: this study included translation, back-translation, cognitive interviews, testing of the pre-final versions, analysis of reliability and of internal consistency of the final versions. Respondents included parents and rehabilitation professionals from rehabilitation centers in four capital cities in Brazil., Results: Translation and cultural-adaptation procedures ensured the Brazilian versions were understandable and semantically equivalent to the original MPOC-20 and MPOC-SP. Pre-final and final versions were analyzed and vetted by the original authors. The MPOC-20 internal consistency Cronbach's alpha varied between 0.61 and 0.91 (n=107), the test-retest reliability ICC varied between 0.44 and 0.83 and the standard error of measurement varied between 0.66 and 0.85 (n=50). The MPOC-SP internal consistency Cronbach's alpha varied between 0.52 and 0.83 (n=92), the test-retest reliability ICC between 0.83 and 0.90, and the standard error of measure between 0.34 and 0.46 (n=62)., Conclusion: The Brazilian versions of the MPOC-20 and the MPOC-SP are in general stable and sufficiently reliable. They are relevant to the evaluation of FCP and provide information that can improve health services and ensure better care., (Copyright © 2019 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.)

The beneficial effect of polyphenols and magnesium(II) against oxidative stress motivated our research group to explore the antioxidant activity of phenMgIso, an aqueous soluble magnesium(II) complex containing 1,10-phenanthroline (phen) and isovanillic acid (Iso) as ligands. Combined electrospray ionization-mass spectrometry and DOSY-NMR techniques identified two complexes in methanolic solution: hexacoordinated [Mg(phen) 2 (Iso)] + and tetracoordinated [Mg(phen)(Iso)] + . The cyclic voltammogram of phenMgIso in the anodic region showed a cyclic process that interrupts the isovanillic acid degradation, probably by stabilization of the corresponding phenoxyl radical via complexation with Mg(II), which is interesting for antioxidant applications. phenMgIso competes with 2,2,6,6-tetramethylpiperidine by 1 O 2 with IC 50 ( 1 O 2 ) = 15 μg m -1 and with nitrotetrazolium blue chloride by superoxide ions (IC 50 (O 2 •- ) = 3.6 μg mL -1 ). Exposure of both zebrafish (2 mg L -1 ) and wistar male rats (3 mg kg -1 day -1 dose for 21 days) to phenMgIso does not cause mortality or visual changes compared with the respective control groups, thus phenMgIso could be considered safe under the conditions of this study. Moreover, no significant changes in comparison to both control groups were observed in the biochemical parameters on the brain-acetylcholinesterase activity, digestive tract enzyme catalase, and glutathione-S-transferase. Conversely, the performance of superoxide dismutase activity in wistar male rats increased in the presence of a complex, resulting in enhanced capacity of rats for superoxide radical enzymatic scavenging. The synergistic action of phenMgIso may be explained by the strong electrostatic interaction between Mg(II) and the O,O(phenolate) group, which makes the Iso ligand easier to oxidize and deprotonate, generating a cyclic stable species under oxidative conditions., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Background: Evidence from observational studies suggests that a greater intake of ultra-processed foods during pregnancy is associated with a higher chance of obesity, increased gestational weight gain, and neonatal adiposity. The aim of the present study is to evaluate the effectiveness of a nutritional intervention based on encouraging the consumption of unprocessed and minimally processed foods and the practice of physical activities for appropriate weight gain in overweight, adult, pregnant women. Additionally, the effect of the intervention on pregnancy outcomes, neonatal adiposity, and the child's weight and height will be investigated., Methods: This is a two-armed parallel randomized controlled trial that will be conducted at primary health units in Ribeirão Preto, SP, Brazil. Adult pregnant women who are overweight and receiving prenatal care in the public health system will be included. The women will be randomly allocated into control (standard care) or intervention groups. Those enrolled in the intervention group will participate in three individualized nutritional counselling sessions based on encouraging the consumption of unprocessed and minimally processed foods and the practice of physical activities. The recruitment of the participants will be carried out at seven health facilities over 12 months, with a sample of 300 women expected. Maternal anthropometric, sociodemographic, blood pressure, biochemical, and lifestyle data will be obtained at baseline (up to the 16th week of gestation), and during a second assessment (34th to 36th gestational week). The neonate body composition will be estimated after birth, and data on pregnancy outcomes, weight and height of children at 6, 12 and 24 months of age will be further obtained from medical records., Discussion: This will be the first randomized controlled trial to test the effectiveness of a nutritional intervention based on encouraging the consumption of unprocessed and minimally processed foods and the practice of physical activities for appropriate weight gain in adult, overweight, pregnant women. Furthermore, the effect of the intervention on pregnancy outcomes, neonatal adiposity and the child's weight and height will be evaluated., Trial Registration: Registro Brasileiro de Ensaios Clínicos (Rebec) RBR-2w9bhc July 30th 2018 (http://www.ensaiosclinicos.gov.br/rg/?q=RBR-2w9bhc+), and RBR-7yx36h June 4th 2019 (http://www.ensaiosclinicos.gov.br/rg/?q=RBR-7yx36h+0.

Purpose To determine by histomorphometric analysis whether CO2 pneumoperitoneum interferes with collagen deposition in surgical wounds in the aponeurosis of rats. Methods This experiment involved 80 male Wistar rats, randomly allocated into four groups according to pneumoperitoneum period (PRE: 30 min preoperatively; POST: 30 min postoperatively; PP: 30 min pre- and postoperatively; C: control group). CO2 pneumoperitoneum was insufflated to 5 mmHg of pressure. A laparotomy was performed; 1 cm of the left colon was then resected, and an end-to-end anastomosis was performed to simulate surgical trauma, after which the abdominal wall was closed. On postoperative days 7 or 14, a sample of the abdominal wall was collected, stained with picrosirius red and observed under polarized light in an optical microscope. The amount of collagen was estimated by computerized histomorphometric analysis. Results There were no significant differences in collagen deposition between the control and experimental groups on postoperative days 7 (p=0.720) or 14 (p=0.933). The amount of collagen increased as expected in all groups between postoperative days 7 and 14 (p=0.0003). Conclusion At 5 mmHg, CO2 pneumoperitoneum does not interfere with collagen deposition in abdominal wall surgical wounds in rats.

Objective: To verify whether early intervention focused on the family improves the cognitive, motor, and language development of children born preterm and/or at social risk in the first 3 years of life., Source of Data: Meta-analysis of clinical trials published between 2008 and 2018, in the following databases: CINAHL, MEDLINE - PubMed, MEDLINE - BVS, LILACS - BVS, IBECS - BVS, PEDro and Cochrane Reviews. Experimental studies on early interventions focused on the family, whose target groups were children born preterm and/or at social risk, with assessment of cognitive and/or motor and/or language development up to 3 years were included. The studies were rated using the PEDro Scale., Data Synthesis: Twelve studies were included from a total of 3378 articles. Early intervention focused on the family contributed to the development of the cognitive (Standardized Mean Difference - SMD=0.48, 95% CI: 0.34-0.61) and motor (SMD=0.76, 95% CI: 0.55-0.96) domains of preterm infants. Regarding cognitive development, performance improvement was observed at 12, 24 and 36 months, while in the motor domain, the effect was observed only at 12 months in preterm infants. There was no benefit of the intervention in the cognitive, motor, and language outcomes of children with the social risk factor associated to biological risk., Conclusion: Early intervention focused on the family has a positive effect on the cognition of preterm infants. The effect on motor development was lower, possibly due to the emphasis on interventions in family-child interaction. The effect of interventions on the development of children at social risk and on the language domain was inconclusive, due to the scarcity of studies in the area., (Copyright © 2019 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

The aim was to investigate the relationship between the energy contribution (E%) of foods according to the degree of industrial processing and the energy-adjusted dietary inflammatory index (E-DII) in pregnancy. Two 24-hour dietary recalls were obtained from each of the 784 pregnant women. Adjusted linear regression models allowed observing an inverse association between E-DII scores and E% from minimally processed foods β = -0.049 (95%CI -0.055- -0.042) and a direct association with the E% of ultra-processed foods β = 0.052 (95%CI 0.045-0.058), indicating a relationship between the dietary inflammatory potential and the degree of industrial processing of foods.

4,4'-Bipyridyl worked as an organocatalyst for the reduction of nitroarenes by bis(neopentylglycolato)diboron (B 2 nep 2 ), followed by hydrolysis to give the corresponding anilines. This reduction proceeded under aerobic conditions without any prepurification of substrates and reagents. We found broad functional group tolerance and compatibility for O- and N-protecting groups under the reaction conditions. The key in this catalytic system was the addition of B 2 nep 2 to 4,4'-bipyridyl to form N , N '-bis[(neopentylglycolato)boryl]-4,4'-bipyridinylidene as a deoxygenating reagent of nitroarenes.

Diaphragmatic hernias are an uncommon occurrence in the pediatric population; however, they can cause significant morbidity and mortality if the diagnosis is missed or delayed. This case discusses the radiographic and clinical exam findings of a one-year-old patient with this pathology., Competing Interests: Conflicts of Interest: By the CPC-EM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The authors disclosed none., (Copyright: © 2019 Ottoboni et al.)

The separation and preconcentration of rare earth elements (REEs) from mineral concentrates in an economically and environmentally sustainable manner are difficult tasks due to their similar physicochemical properties. Herein, a series of tetradentate phenylenedioxy diamide (PDDA) ligands were synthesized and grafted on large-pore three-dimensional KIT-6 mesoporous silica. In solid-phase extraction, the hybrid sorbents enable a size-selective separation of REEs on the basis of the bite angles of the ligands. In particular, smaller REE 3+ ions are preferentially extracted by KIT-6-1,2-PDDA, whereas light REEs with larger ionic radius are favored by KIT-6-1,3-PDDA. The exposure of bauxite residue digestion solution containing REEs as well as a number of types of competitive ions (including Th and U) to the sorbents results in selective recovery of target REEs. The possibility of regenerating the mesoporous sorbents through a simple loading-stripping-regeneration process is demonstrated over up to five cycles with no significant loss in REE extraction capacity, suggesting adequate chemical and structural stability of the new sorbent materials.

The draft Step 2 ICH S5(R3) guideline includes an exposure-based endpoint as an option for selecting the high-dose in reproductive and developmental toxicity studies. To help determine an appropriate exposure margin for embryofetal developmental toxicity testing, a retrospective analysis was undertaken to determine what threshold would have been sufficient to detect hazards to embryofetal development in rats and rabbits for 18 known and 4 presumed human teratogens. The analysis showed that using a high dose that provided at least a 6-fold exposure margin in the developmental toxicity studies would have been sufficient to detect the teratogenic hazard with relevance for humans for all these therapeutics. With regards to human risk assessment practices for developmental toxicity, the analysis showed that, after excluding lenalidomide and pomalidomide data in rats, all available AUC margins at the NOAEL for the induction of malformations or embryofetal lethality were <4-fold of the exposure at the MRHD for all 22 therapeutics. These data support the proposed general approach of increased level of concern for human risk when exposure margins of the NOAEL to the MRHD are <10-fold, reduced concern when the exposure margins are 10- to 25-fold, and minimal concern when the exposure margin is > 25-fold., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To investigate the relationship between the dietary patterns of pregnant women with maternal excessive body weight and gestational diabetes mellitus., Methods: A cross-sectional study conducted with a convenience sample of 785 adult pregnant women attended by the Unified Health System of Ribeirão Preto, state of São Paulo, between 2011 and 2012. Two 24-hour dietary recalls, corrected by the multiple source method, were employed . For the classification of the body mass index and the diagnosis of gestational diabetes mellitus, the criteria by Atalah and the World Health Organization were used, respectively. Dietary patterns were obtained by principal component analysis using the Varimax rotation method. The relationship between adherence to patterns, overweight and obesity was analyzed by multinomial logistic regression models and the relationship with gestational diabetes mellitus by adjusted unconditional logistic regression models., Results: We identified four dietary patterns: "traditional Brazilian"; "snacks"; "coffee" and "healthy". Women with a higher adherence to the "Healthy" (OR = 0.52; 95%CI 0.33-0.83) and "Brazilian Traditional" patterns (OR = 0.61; 95%CI 0.38-0.96) presented a lower chance of obesity, when compared to women with lower adherence, regardless of confounding factors. After adjustment for maternal excessive body weight, there was no association between dietary patterns and gestational diabetes mellitus., Conclusions: Among the pregnant women, greater adherence to "traditional Brazilian" and "healthy" patterns was inversely associated with obesity, but no relationship was identified with gestational diabetes mellitus after adjusting for excessive body weight. Prospective studies are recommended to investigate the relationship between dietary patterns, overweight and gestational diabetes mellitus, reducing the chance of reverse causality.

Objective: to construct collectively with nursing professionals bundle for best practices of cold chain maintenance of immunobiological agents conservation at the local level., Method: a qualitative research of convergent care type. Bundle construction was guided by the Evidence-Based Practice criterion. Data collection was carried out from October to December 2016, through five workshops, with the participation of 21 professionals from 7 vaccination rooms of a municipality of Minas Gerais State. The framework developed by Morse and Field was adopted for data analysis., Results: through bundle, care is taken regarding refrigeration equipment temperature monitoring, contingency plan performance, recyclable ice coil setting and chamber use as refrigeration equipment., Final Considerations: the chosen interventions began to guide the practice and promote a care based on safety and quality.

Background: Leishmania parasites are transmitted to vertebrate hosts by phlebotomine sandflies and, in humans, may cause tegumentary or visceral leishmaniasis. The role of PKR (dsRNA activated kinase) and Toll-like receptor 3 (TLR3) activation in the control of Leishmania infection highlights the importance of the engagement of RNA sensors, which are usually involved in the antiviral cell response, in the fate of parasitism by Leishmania. We tested the hypothesis that Phlebovirus, a subgroup of the Bunyaviridae, transmitted by sandflies, would interfere with Leishmania infection., Methodology/principal Findings: We tested two Phlebovirus isolates, Icoaraci and Pacui, from the rodents Nectomys sp. and Oryzomys sp., respectively, both natural sylvatic reservoir of Leishmania (Leishmania) amazonensis from the Amazon region. Phlebovirus coinfection with L. (L.) amazonensis in murine macrophages led to increased intracellular growth of L. (L.) amazonensis. Further studies with Icoaraci coinfection revealed the requirement of the PKR/IFN1 axis on the exacerbation of the parasite infection. L. (L.) amazonensis and Phlebovirus coinfection potentiated PKR activation and synergistically induced the expression of IFNβ and IL-10. Importantly, in vivo coinfection of C57BL/6 mice corroborated the in vitro data. The exacerbation effect of RNA virus on parasite infection may be specific because coinfection with dengue virus (DENV2) exerted the opposite effect on parasite load., Conclusions: Altogether, our data suggest that coinfections with specific RNA viruses shared by vectors or reservoirs of Leishmania may enhance and sustain the activation of host cellular RNA sensors, resulting in aggravation of the parasite infection. The present work highlights new perspectives for the investigation of antiviral pathways as important modulators of protozoan infections., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Drug interaction is an important cause of global morbidity. It is of particular importance in cancer patients since they are often in use of polypharmacy, related to interactions between the drugs and the chemotherapeutics used., Objective: To evaluate the drug interaction between chemotherapy and other drugs in cancer patients., Methods: a cross-sectional study carried out in the outpatient oncology department of a public tertiary hospital. Two hundred thirty-five patients were included, and the drugs they were using were identified. Using the MedScape and Epocrates database, we evaluated the interactions between medications and chemotherapy by defining their frequency and dividing their severity from interaction into mild, close monitoring necessity and severe., Results: 161 patients had some drug interaction. We identified 9 types of mild interactions, 23 types of interactions with close monitoring necessity, and 2 types of serious interactions. The most frequent interactions were between fluorouracil and leucovorin (32 cases) and cyclophosphamide and doxorubicin (19 cases). Serious interactions were between aspirin and pemetrexed; and leucovorin and Bactrim., Conclusion: In the present study, drug interactions were frequent, including serious interactions with a potential increase in morbidity and mortality. Thus, it is necessary for oncologists to draw up a therapeutic plan considering potential interactions between prescribed chemotherapy and current medications in use by patients.

Objective: To investigate the relationship of flavonoid intake during pregnancy with maternal excessive body weight and gestational diabetes mellitus (GDM)., Subjects and Methods: A cross-sectional study was conducted among 785 adult women in singleton pregnancies, and data were collected at the time of the oral glucose tolerance test. For the body mass index (BMI) classification according to the gestational age, the criteria of Atalah was used, and the diagnosis of GDM was based on the World Health Organization of 2014. Two 24-hour dietary recalls were obtained, and the usual intake was determined by the Multiple Source Method. Adjusted multinomial logistic regression was used to investigate the relationship of the flavonoids with overweight and obesity, and adjusted non-conditional logistic regression for the relationship of the flavonoids with GDM., Results: The mean (SD) age of the women was 28 (5) years, 32.1% were overweight, 24.6% were obese and 17.7% were diagnosed with GDM. The median (P25, P75) of total flavonoid intake was 50 (31,75) mg/day. Considering the eutrophic women as the reference, the pregnant women with a higher total flavonoid intake [OR 0.62 (95% CI 0.38; 0.96)] and anthocyanidin intake [OR 0.62 (95% CI 0.40; 0.99)] were less likely to be obese when compared to the women with lower intakes. No association of the flavonoids intake with overweight or GDM was found., Conclusion: A very low intake of flavonoids was observed. The data suggest that the intake of foods naturally rich in total flavonoids and anthocyanidin has a beneficial role regarding obesity among pregnant women.

This study aimed to investigate the relationship between food intake (considering the nature, extent, and purpose of food processing) during pregnancy and overweight, obesity, and gestational diabetes mellitus conditions. This is a cross-sectional study conducted among 785 adult women in singleton pregnancies (between 24th and 39th weeks of gestation) in Brazil. Usual food intake was estimated by the Multiple Source Method, using two 24-hour dietary recalls. The food groups of interest in this study were the unprocessed or minimally processed foods and ultra-processed foods. The World Health Organization criteria for the diagnosis of gestational diabetes mellitus and the Atalah criteria for excess weight were used. Adjusted multinomial logistic regression models were used to assess the relationship between energy contribution (%E) from foods with overweight and obesity conditions and, adjusted logistic regression models for gestational diabetes mellitus. In total, 32.1% participants were overweight, 24.6% were obese, and 17.7% of women were diagnosed with gestational diabetes mellitus . After adjustments, an inverse association between the highest tertile of %E from the intake of unprocessed or minimally processed foods and obesity was found [0.49 (0.30-0.79)]. Moreover, a positive association between the highest tertile of %E from ultra-processed food intake [3.06 (1.27-3.37)] and obesity was observed. No association between food intake (considering the nature, extent, and purpose of food processing) during pregnancy and overweight or gestational diabetes mellitus was found. The findings suggest a role of food processing in obesity but not in gestational diabetes mellitus. Further research is warranted to provide robust evidence on the relationship between the role of processed foods in obesity and gestational diabetes mellitus.

Purpose: To cross-culturally adapt and verify the measurement properties of the Brazilian version of the Motor Assessment Scale (MAS)., Methods: The process of cross-cultural adaptation followed standardized procedures. Construct validity of the MAS was investigated using Rasch analysis (n = 100), whereas inter-rater and test-retest reliabilities were evaluated using Kappa coefficients and Bland and Altman plots (n = 52)., Results: The MAS demonstrated satisfactory measurement properties. The Kappa coefficients for the inter-rater and test-retest reliabilities were 0.73 (ranging from 0.79 to 1.00) and 0.82 (ranging from 0.86 to 1.00), respectively. The Bland and Altman plots showed adequate inter-rater and test-retest agreements. No ceiling or floor effects were observed and only one item exhibited misfit to the Rasch model expectations. Item 4 "sitting to standing" exhibited marginal misfit (infit MnSq = 1.44; Zstd = 2.6), but it did not affect the unidimensionality of the scale., Conclusions: The MAS demonstrated good indicators of validity and reliability to be used for the assessment of motor function of individuals with stroke within clinical and research contexts. Implications for rehabilitation The Motor Assessment Scale is a performance-based scale for the assessment of motor function of individuals with stroke, based on a task-oriented approach. The Motor Assessment Scale has shown good clinical utility indicators dues to its quick administration, objectivity, and clinical relevance as a functional predictor. The Motor Assessment Scale showed good indicators of validity and reliability to be used within clinical and research contexts for the evaluation of motor function of individuals after stroke.

Objective: The objective of the study is to report the experience with acetaminophen in low doses as an alternative to the treatment of the ductus arteriosus of the preterm newborn., Materials and Methods: Retrospective study including preterm newborns with patent ductus arteriosus who received oral acetaminophen because treatment with indomethacin had failed or is contraindicated. A dosage consisted of a first dose of 25 mg/kg and maintenance doses of 30 mg/kg/day, for 3 to 7 days. A second cycle was administered in cases of reopening of the ductus arteriosus. The rates of ductal closure and surgery were calculated. Patients were categorized into responder and nonresponder groups for acetaminophen, and the average values of ductal diameter, weight, gestational age, and postnatal age were compared., Results: Eighty-seven preterm newborns, with a postnatal age from 3 to 27 days, with average values of ductus arteriosus equal to 2.5 ± 0.8 mm/kg, gestational age 27.2 ± 1.9 weeks, and birth weight 888.9 ± 241 g, received acetaminophen for 3 to 7 days. A second cycle was administered in 15 preterm newborns. The ductus closure rate, after one or two cycles, was 74.7%, and the recommendations for surgical closure were progressively reduced from 50% in the 1 st year to 6.2% in the past year. Lower ductal closure rate occurred in the group of newborns with the lowest average weight ( P = 0.018), the highest average ductal diameter ( P = 0.002), and the lowest average gestational age ( P = 0.09). Postnatal age at the start of acetaminophen use was shown to be irrelevant regarding the treatment ( P = 0.591)., Conclusions: Acetaminophen in low doses showed to be an effective alternative for the closure of the ductus arteriosus for preterm newborns in whom treatment with indomethacin or ibuprofen failed or was contraindicated., Competing Interests: There are no conflicts of interest.

Lactococcus lactis is a gram positive facultative anaerobe widely used in the dairy industry and human health. L. lactis subsp. lactis NCDO 2118 is a strain that exhibits anti-inflammatory and immunomodulatory properties. In this study, we applied a label-free shotgun proteomic approach to characterize and quantify the NCDO 2118 proteome in response to variations of temperature and oxygen bioavailability, which constitute the environmental conditions found by this bacterium during its passage through the host gastro-intestinal tract and in other industrial processes. From this proteomic analysis, a total of 1,284 non-redundant proteins of NCDO 2118 were characterized, which correspond to approximately 54% of its predicted proteome. Comparative proteomic analysis identified 149 and 136 proteins in anaerobic (30°C and 37°C) and non-aerated (30°C and 37°C) conditions, respectively. Our label-free proteomic analysis quantified a total of 1,239 proteins amongst which 161 proteins were statistically differentially expressed. Main differences were observed in cellular metabolism, stress response, transcription and proteins associated to cell wall. In addition, we identified six strain-specific proteins of NCDO 2118. Altogether, the results obtained in our study will help to improve the understanding about the factors related to both physiology and adaptive processes of L. lactis NCDO 2118 under changing environmental conditions.

Objective: Evidence for the combined association of the quality of dietary carbohydrates and fats during pregnancy with gestational diabetes mellitus (GDM) is scarce. The aim of this study was to identify dietary patterns during pregnancy, derived by the reduced-rank regression (RRR) model, associated with fiber density (g/1000 kcal) and the Thrombogenicity Index (TI) and to investigate their relationship with GDM., Methods: This was a cross-sectional study conducted with 785 pregnant women at gestational weeks 24 to 39. The diagnosis of GDM was based on the World Health Organization criteria. One 24-h dietary recall was obtained from all women and a second measurement from 73% of the sample, with the multiple source method used to estimate the usual diet. The patterns were determined by RRR, and the relationship with GDM was investigated using adjusted logistic regression models., Results: The mean (standard deviation) age of the women was 28 y and 17.7% had GDM. Dietary pattern 1 (high rice, beans, and vegetables, with low full-fat dairy products, biscuits, and sweets) correlated positively with fiber density and negatively with TI and was inversely associated with GDM after multiple adjustments (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.36-0.95; P = 0.03). Dietary pattern 2 (high red meats, full-fat dairy products, chocolate powder and fruits, with low chicken and margarine) correlated positively with both TI and fiber density, with no association with GDM found (OR, 1.48; 95% CI, 0.91-2.40; P = 0.11)., Conclusion: These data highlight the joint importance of the quality of dietary carbohydrates and fats in the dietary patterns of pregnant women in relation to the risk for developing GDM., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

MKRN3 mutations represent the most common genetic cause of central precocious puberty (CPP) but associations between genotype and clinical features have not been extensively explored. This systematic review and meta-analysis investigated genotype-phenotype associations and prevalence of MKRN3 mutations in CPP. The search was conducted in seven electronic databases (Cochrane, EMBASE, LILACS, LIVIVO, PubMed, Scopus, and Web of Science) for articles published until 4 September 2018. Studies evaluating MKRN3 mutations in patients with CPP were considered eligible. A total of 22 studies, studying 880 subjects with CPP, fulfilled the inclusion criteria. Eighty-nine subjects (76 girls) were identified as harboring MKRN3 mutations. Girls, compared with boys, exhibited earlier age at pubertal onset (median, 6.0 years; range, 3.0 to 7.0 vs 8.5 years; range, 5.9 to 9.0; P < 0.001), and higher basal FSH levels (median, 4.3 IU/L; range, 0.7 to 13.94 IU/L vs 2.45 IU/L; range, 0.8 to 13.70 IU/L; P = 0.003), and bone age advancement ( Δ BA; median, 2.3 years; range, -0.9 to 5.2 vs 1.2 years; range, 0.0 to 2.3; P = 0.01). Additional dysmorphisms were uncommon. A total of 14 studies evaluating 857 patients were included for quantitative analysis, with a pooled overall mutation prevalence of 9.0% (95% CI, 0.04 to 0.15). Subgroup analysis showed that prevalence estimates were higher in males, familial cases, and in non-Asian countries. In conclusion, MKRN3 mutations are associated with nonsyndromic CPP and manifest in a sex-dimorphic manner, with girls being affected earlier. They represent a common cause of CPP in western countries, especially in boys and familial cases.

Background: This study aimed to evaluate the oncological outcomes of conversion in patients undergoing resection for colon cancer., Methods: Patients with stages I-III colon adenocarcinoma operated on between 2000 and 2012 were included. Oncologic outcomes were assessed by surgical approach (laparoscopy vs. open). A secondary analysis compared patients who required conversion to open vs. laparoscopic only., Results: We identified 1196 patients that met inclusion criteria (28% laparoscopic, 72% open). Overall, 13% of laparoscopic cases were converted to open. There were no differences in 5-year overall survival (OS) (p = 0.258), disease-free survival, (DFS) (p = 0.070), cancer-specific survival (CSS) (p = 0.207), or recurrence (p = 0.216) between laparoscopy and open surgery. However, patients with conversion had a worse OS (p = 0.010) and DFS (p = 0.006) when compared to laparoscopic only., Conclusion: Conversion from laparoscopic to open surgery is a marker for worse survival outcomes. Further investigation is needed to define the underlying cause of these differences., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Children with Developmental Coordination Disorder (DCD) have difficulties performing daily activities which reflects negatively on participation, impacting their lives., Objectives: To examine the effects of the cognitive orientation to daily occupational performance Approach (CO-OP Approach) protocol on occupational performance and satisfaction of Brazilian children who have DCD; to examine whether children could transfer strategies and skills learned during CO-OP to untrained goals., Methods: A pre-post group comparison design with eight boys aged 6-10 years old. Children participated in 12 CO-OP sessions with their parents twice a week, with an extra session added to the protocol for parents´ orientation. The Canadian Occupational Performance Measure and the Performance Quality Rating Scale were used as outcome measures. The study was registered by the United States Institutes of Health at ClinicalTrials.gov (NCT03112746)., Results: Intervention resulted in higher, clinically and statistically significant, occupational performance measures according to parents, children's, and external evaluators' perspectives. All children improved occupational performance on their selected goals and five children could transfer the ability to use cognitive strategies to tasks not addressed in therapy., Conclusions: This study provides initial directions for future research to investigate the applicability and to implement CO-OP approach on pediatric settings in Brazil.

Purpose: Identifying dominant intraprostatic lesions (DILs) on transrectal ultrasound (TRUS) images during prostate high-dose-rate brachytherapy (HDR-BT) treatment planning is challenging. Multiparametric MRI (mpMRI) is the tool of choice for DIL identification; however, the geometry of the prostate on mpMRI and on the TRUS may differ significantly, requiring image registration. This study evaluates the efficacy of an in-house software for MRI-to-TRUS DIL registration (MR2US) and compares its results to rigid and B-Spline deformable registration., Methods and Materials: Ten patients with intermediate-risk prostate cancer, each with mpMRI and TRUS data sets, were included in this study. Five radiation oncologists (ROs) with expertise in TRUS-based HDR-BT were asked to cognitively contour the DIL onto the TRUS image using mpMRI as reference. The contours were analyzed for concordance using simultaneous truth and performance level estimation algorithm. Similarity indices, DIL volumes, and distance between centroid positions were measured to compare the consensus contours against the contours from ROs and the automated algorithms; registration time between all contouring methods was recorded., Results: MR2US registration had the highest dice coefficients among all patients with a mean of 0.80 ± 0.13 in comparison to rigid (0.65 ± 0.20) and B-Spline (0.51 ± 0.30). The distance between centroid positions between simultaneous truth and performance level estimation contour and MR2US, rigid, and B-Spline contours were 5 ± 2, 7 ± 5, and 18 ± 11 mm, respectively. The average registration time was significantly shorter for MR2US (11 ± 2 s) and rigid algorithm (7 ± 1 s) compared to ROs (227 ± 27 s) and B-Spline (199 ± 38 s)., Conclusions: The efficacy of integrating an MRI-delineated DIL into a TRUS-based BT workflow has been validated in this study. The MR2US software is fast and accurate enough to be used for DIL identification in prostate HDR-BT., (Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: 11β-hydroxylase deficiency accounts for 5% of congenital adrenal hyperplasia cases. Diagnosis suspiction is classically based on the association between abnormal virilization, precocious puberty, and hypertension in 46XX or 46XY subjects. We investigated two families with siblings presenting with opposed clinical features, and provided a review of the mechanisms involved in mineralocorticoid-dependent phenotypic heterogeneity., Methods: The coding region of the CYP11B1 gene of 4 patients was sequenced and familial segregation was confirmed. Clinical characterization and blood steroid profile were performed., Results: Family 1 comprised a female and a male siblings who presented in middle childhood with genital ambiguity (Prader II) and precocious puberty, respectively, associated with hypertension. In the second decade of life, the woman had three full-term pregnancies, and then evolved normotensive with no treatment over a 5-year follow up. On the other hand, her brother had hypertensive end-organ damage at age 24. In family 2, a 2.9 year-old boy presented with precocious puberty and hypertension, whereas his 21 days-old sister had genital ambiguity (Prader III) and salt wasting. A homozygous exon 4 splice site mutation was identified (IVS4ds-1G > A; c.799 G > A) in family 1, while a nonsense mutation in exon 6 (p. Q356X; c.1066 C > T) was found in family 2., Conclusion: CYP11B1 mutations were associated with highly variable phenotypes, from mild to severe virilization, and early-onset hypertension or salt wasting. Further analysis of variants in other hypertension-related genes, steroid synthesis and metabolism compensatory pathways, and/or the investigation of chimeric CYP11B genes are needed to clarify the phenotypic heterogeneity in 11β-hydroxylase deficiency.

The name of Luanna Castro Oliveira was incorrectly spelled as Luana Castro Oliveira in the original version of this article.

Competing Interests: Conflicts of Interest: By the CPC-EM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. The authors disclosed none.