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How can we reconcile religion and Enlightenment in Kant? I begin by analyzing Kant’s conception of a rational religion and the key concepts of radical evil and ethical community. I refer to many instances of overcoming evil in Kant’s work. First, I show that in the Anthropology, the cultivation of society is one possibility, while in the Idea for a Universal History, the unsociable sociability plays a role to accomplish a moral end. In Religion, on the other hand, only an ethical community can defeat evil. Since evil has its source in social relations, only a society of virtue can counteract passions. Second, I ask whether we can reconcile religious faith with rational Enlightenment or if some concepts used in Religion, such as radical evil, are only a disguise for anti-Enlightenment conceptions. Finally, I ask if it is reasonable to argue that we should keep religion as an important social practice or if it always brings a higher risk of anti-Enlightenment outcomes such as fanaticism. I analyze the case of Brazil, where the Evangelical church helped to elect a right-wing president with a very conservative and anti-Enlightenment agenda.

This paper presents a new test method able to infer - in periods of less than 7 seconds - the refrigeration capacity of a compressor used in thermal machines, which represents a time reduction of approximately 99.95% related to the standardized traditional methods. The method was developed aiming at its application on compressor manufacture lines and on 100% of the units produced. Artificial neural networks (ANNs) were used to establish a model able to infer the refrigeration capacity based on the data collected directly on the production line. The proposed method does not make use of refrigeration systems and also does not require using the compressor oil.

Anterior knee instability associated with a varus deformity is a complex condition with several treatment possibilities. Among these, anterior cruciate ligament (ACL) associated to a simultaneous valgus tibial osteotomy is a increasing indication. This simultaneous procedure adds technical issues to those related to the isolated surgeries. Thus, the osteotomy plane and location of fixation hardware shouldn?t conflict with tibial tunnel and ACL graft fixation. Authors analyze the relations between a opening tibial valgus osteotomy stabilized with a Puddu plate and ACL reconstruction with a patellar tendon graft fixated with interference screws in 10 human cadaver knees. A straight oblique tibial osteotomy starting on the medial tibial cortex and oriented laterally and proximally was performed on all knees with a 10mm opening medially and stabilized with a Puddu plate on the most posterior aspect of the medial tibia, and a tibial tunnel drilled 50° to tibial plateau. With this technique there was no intersection between tibial tunnel or interference screw and the osteotomy or the plate fixation screws.

OBJETIVO: Conhecer a prevalência de cárie e necessidades de tratamento em escolares do interior do Estado de Goiás, Brasil. MÉTODOS: A amostra foi constituída de 1.419 escolares de 6 a 12 anos de idade, de ambos os sexos, que freqüentavam 25 escolas públicas na zona urbana de 9 municípios. RESULTADOS: A percentagem de escolares livres de cárie foi muito baixa em todas as idades, sendo 4,4% aos 12 anos. O índice CPO-D variou de 0,41 aos 6 anos a 5,19 aos 12 anos. O índice ceo-d nesta faixa etária variou de 4,93 a 0,29. As necessidades de tratamento superaram as necessidades atendidas, tanto na dentição decídua quanto na permanente. CONCLUSÃO: A alta prevalência de cárie em escolares do interior de Goiás sugere a necessidade de se implantar medidas educativas e preventivas em saúde bucal que intervenham nos reais determinantes da doença na população.

OBJETIVO: Investigou-se a prevalência de cárie e necessidades de tratamento em escolares de Goiânia-GO, Brasil, que possui água fluoretada há 9 anos. METODOLOGIA: A amostra foi constituída de 1.400 escolares de 6 a 12 anos de idade que freqüentavam escolas públicas na zona urbana do município estudado. RESULTADOS: Os índices CPO-D e ceo-d encontrados no total da amostra foram 2,19 e 2,86, respectivamente, demonstrando uma redução de 57,1% em relação ao CPO-D verificado na região Centro-Oeste, em 1986. Para os escolares de 12 anos de idade, o CPO-D encontrado foi 4,59, estando acima da meta estabelecida para o ano 2.000 pela FDI/OMS. Verificou-se que a percentagem de escolares livres de cárie foi muito baixa em todas as idades, apresentando-se em torno de 11% para o total da amostra. Houve predomínio do tratamento restaurador na dentição decídua em todas as idades e na permanente a partir dos 9 anos de idade. CONCLUSÃO: A prevalência de cárie em escolares de Goiânia-GO é alta e comparável à situação verificada na maioria dos países da América Latina e nas regiões menos favorecidas de países desenvolvidos. Há necessidade de se implantar medidas educativas e preventivas em saúde bucal que intervenham nos reais determinantes da doença na população.

Sickle cell disease is an inherited chronic haemolytic anaemia whose clinical manifestations arise from the tendency of the haemoglobin to polymerize and deform red blood cells into the characteristic sickle shape (HbS), with vaso-occlusive phenomena, pain and organ damage. Sickle cell anaemia, the prototype disease, is the homozygous state and represents the most severe form of sickle cell disease. A variety of other sickle cell syndromes are a result of an interaction between HbS and certain variant haemoglobins as HbC and thalassemia. We describe the case of a 28-year-old, black man, with recurrent episodes of musculoskeletal pain. Physical examination revealed spenomegaly. Laboratory tests showed haemolytic anemia and microcytosis. The peripheral blood smear revealed frequent target cells. The high performance liquid chromatography (HPLC) detected the absence of HbA, increased HbA2 and the presence of HbS and HbC, in equal amounts. In this case, we want to draw attention to less common and non-rheumatic causes of musculoskeletal pain as well as alert to the importance of early diagnosis of sickle cell disease that can minimize and prevent many of its complications.

The Brazilian wine industry has been facing obstacles such as competition and high tax rates. Innovation is an alternative towards this scenario being it a major factor for any company's survival and growth in the market. Besides this, technological advances and access to information provide consumers with a larger number of choices and knowledge for an informed decision making. Despite differentiation efforts consumers did not obtain satisfaction. Customer interaction provides another way to generate innovation from its involvement in the production process (co-creation of value). The research was held in an awarded winery located in Bento Gonçalves (Brazil) with the objective of understanding how the process of value co-creation between Brazilian award-winning wineries and consumers influences innovation generation. It is an exploratory and qualitative study collected through in-depth interviews with a semi-structured script. The winery identifies beneficial effects in the production process resulting from interactions because it narrows the bond with the consumer creating a better understanding of the consumers as well as develop a more tailored offer regarding value. The innovations generated based on co-creation can be taken as an alternative to imposed barriers in the current Brazilian wine sector.

Dural sinus thrombosis is a rare condition and is often underdiagnosed. Because of its potentially lethal complications, it should always be considered in acute headache differential diagnosis. The authors present a report of two cases, both diagnosed on our department. They make an approach to clinical presentation, diagnosis and treatment of this disease.

Abstract Background Aromatase, the cytochrome P-450 enzyme (CYP19) responsible for estrogen biosynthesis, is an important target for the treatment of estrogen-dependent breast cancer. In fact, the use of synthetic aromatase inhibitors (AI), which induce suppression of estrogen synthesis, has shown to be an effective alternative to the classical tamoxifen for the treatment of postmenopausal patients with ER-positive breast cancer. New AIs obtained, in our laboratory, by modification of the A and D-rings of the natural substrate of aromatase, compounds 3a and 4a, showed previously to efficiently suppress aromatase activity in placental microsomes. In the present study we have investigated the effects of these compounds on cell proliferation, cell cycle progression and induction of cell death using the estrogen-dependent human breast cancer cell line stably transfected with the aromatase gene, MCF-7 aro cells. Results The new steroids inhibit hormone-dependent proliferation of MCF-7aro cells in a time and dose-dependent manner, causing cell cycle arrest in G0/G1 phase and inducing cell death with features of apoptosis and autophagic cell death. Conclusion Our in vitro studies showed that the two steroidal AIs, 3a and 4a, are potent inhibitors of breast cancer cell proliferation. Moreover, it was also shown that the antiproliferative effects of these two steroids on MCF-7aro cells are mediated by disrupting cell cycle progression, through cell cycle arrest in G0/G1 phase and induction of cell death, being the dominant mechanism autophagic cell death. Our results are important for the elucidation of the cellular effects of steroidal AIs on breast cancer.

α-Bisabolol (α-BIS) is a sesquiterpene alcohol present in chamomile essential oil [Chamomilla recutita (L.) Rauschert]. Despite its numerous pharmacological effects, its pharmacokinetics remain understudied. An analytical method capable of quantifying α-BIS in plasma is crucial to enable pharmacokinetic analysis. Presently, only one study has quantified it using mass spectrometry. Administering α-BIS requires a nanoemulsion for intravenous injection. This study aimed to develop and validate a bioanalytical method using high-performance liquid chromatography with an ultraviolet detector to quantify α-BIS in rat plasma. The method employed acetonitrile and ultrapure water (80:20, v/v) as the mobile phase, with a flow rate of 1 ml/min and concentrations ranging from 465 to 29.625 μg/ml. All US Food and Drug Administration-designated assays were successful, indicating the method's precision, accuracy, sensitivity and linearity in determining α-BIS in rat plasma. The developed nanoemulsion, assessed through dynamic light scattering analysis, the ensemble collection of particles and polydispersity index evaluation, proved safe and effective for intravenous administration. The pharmacokinetic parameters such as volume of distribution, clearance and half-life indicated that α-BIS tends to persist in the body. This study provides a foundation for further research to explore α-BIS's potential pharmaceutical applications in the future., (© 2024 John Wiley & Sons Ltd.)

The compound 6-methoxyseselin, derived from Zanthoxylum tingoassuiba , demonstrates various therapeutic properties, including vasorelaxation, antinociceptive, anti-inflammatory, and immunomodulatory effects, along with recently discovered antiasthmatic properties. This study aimed to evaluate its preclinical pharmacokinetics and pulmonary delivery in Balb/c mice. The method involved administering the compound via inhalation and intravenous routes, followed by blood sample collection for analysis using high-performance liquid chromatography with diode array detection (HPLC-DAD). The results indicated good linearity, precision, accuracy, and stability of the compound in the biological samples. Pharmacokinetic parameters such as the rate of elimination, half-life, clearance, volume of distribution, area under the curve, and mean residence time were determined for both administration routes, showing similar profiles. The lung concentrations were notably higher than the plasma concentrations, indicating significant lung penetration. These findings suggest 6-methoxyseselin as a promising candidate for new anti-asthmatic drugs, supported by its favorable pharmacokinetic profiles and high lung penetration factors. This study represents the first exploration of the pharmacokinetics and pulmonary delivery of 6-methoxyseselin in mice, highlighting its potential for further drug development.

The most adequate fixative solution for equine ovarian tissue is still to be determined as a tool to evaluate the improvement of methodological studies in assisted reproductive techniques and fertility preservation. This study aimed to evaluate a short-time ethanol 70% (ST-EtOH, 45 min) exposure as an alternative fixative compared with two classically fixatives [Carnoy's (CAR) solution and paraformaldehyde 4% (PFA)] at different fixation times (6 h, 12 h). The end points evaluated were morphology and classes of preantral follicles, follicular and stromal cell densities, and follicular and oocyte nuclear diameters in equine ovarian tissue. Ovaries (n = 6) from ovariectomized young mares were fragmented (3 × 3 × 1 mm; 20 fragments/ovary) and fixed in the tested treatments. Overall, a total of 11,661 preantral follicles were evaluated in 1444 histological slides. The ST-EtOH similarly preserved the preantral follicle morphometry and stromal cell density compared to the PFA fixative, regardless of the exposure time. Nonetheless, the CAR fixative solution had the greatest percentage of normal preantral follicles and the highest stromal cell density among all treatments. In conclusion, Carnoy's solution must be preferred compared with ST-EtOH and PFA fixatives for studies concerning the cellular morphology of equine ovarian tissue. Moreover, ST-EtOH fixative is a good alternative for equine ovarian tissue when a quick histological evaluation is required instead of more time-consuming and expensive techniques. Additional studies concerning the impact of different fixatives on the ultrastructure of cellular populations and their compatibility with IHC and molecular techniques in equine ovarian tissue are warranted., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest that would prejudice the impartiality of this scientific work., (Copyright © 2023 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Background: Granular Cell Odontogenic Fibroma (GCOF) is a rare odontogenic neoplasm reported over time with different names. The purpose of this study is to review all available data on the GCOF in the scientific literature, with a summary of all reported cases and a report of a new case., Methods: This review was conducted following the PRISMA guidelines. An electronic search was performed up to November 2022., Results: Thirty-nine studies reporting fifty-three cases were included. GCOF is a rare neoplasm among the odontogenic tumors, with a higher prevalence in women of the middle-aged and white population. This lesion occurs mostly on the posterior region of the mandible. Furthermore, based on clinical, radiographic, and histopathologic features, conservative treatment was the most reported choice with recurrence reported in two cases., Conclusion: GCOF remains controversial due to the still unsolved histogenesis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Sterilization is a fundamental step to eliminate microorganisms prior to the application of products, especially in the food and medical industries. γ-irradiation is one of the most recommended and effective methods used for sterilization, but its effect on the properties and performance of bio-based polymers is negligible. This work is aimed at evaluating the influence of γ-radiation at doses of 5, 10, 15, 25, 30, and 40 kGy on the morphology, properties, and performance of bioplastic produced from onion bulb ( Allium cepa L.), using two hydrothermal synthesis procedures. These procedures differ in whether the product is washed or not after bioplastic synthesis, and are referred to as the unwashed hydrothermally treated pulp (HTP) and washed hydrothermally treated pulp (W-HTP). The morphological analysis indicated that the film surfaces became progressively rougher and more irregular for doses above 25 kGy, which increases their hydrophobicity, especially for the W-HTP samples. In addition, the FTIR and XRD results indicated that irradiation changed the structural and chemical groups of the samples. There was an increase in the crystallinity index and a predominance of the interaction of radiation with the hydroxyl groups-more susceptible to the oxidative effect-besides the cleavage of chemical bonds depending on the γ-radiation dose. The presence of soluble carbohydrates influenced the mechanical behavior of the samples, in which HTP is more ductile than W-HTP, but γ-radiation did not cause a change in mechanical properties proportionally to the dose. For W-HTP, films there was no mutagenicity or cytotoxicity-even after γ-irradiation at higher doses. In conclusion, the properties of onion-based films varied significantly with the γ-radiation dose. The films were also affected differently by radiation, depending on their chemical composition and the change induced by washing, which influences their use in food packaging or biomedical devices.

Primary biliary cholangitis is an autoimmune disease that mostly affects women. It is uncommon in women of childbearing age and the diagnosis during pregnancy is rare and can be challenging. Described here is a case of primary biliary cholangitis first manifesting during pregnancy, with the onset of pruritus, jaundice, biochemical liver abnormalities and positive antimitochondrial antibodies. Although treatment with ursodeoxycholic acid was started at the time of diagnosis, there was a progressive worsening of cholestatic biochemical markers throughout pregnancy. In addition, fasting hyperglycemia with polyhydramnios was diagnosed, consistent with gestational diabetes. She had a spontaneous preterm delivery at 31 weeks of gestation, of a newborn who was admitted to the neonatal intensive care unit but who subsequently had no long-term sequelae of preterm delivery. A maternal postpartum flare occurred. Treatment with ursodeoxycholic acid was well tolerated during pregnancy and lactation., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Background: Segmented structures, such as bones, are typically stored as 2D contours contained on evenly spaced images (slices). Contour interpolation algorithms to turn 2D contours into a 3D surface may differ in their results, causing discrepancies in analysis. This study aimed to create an accurate and consistent algorithm for the interpolation of femur and tibial contours that can be used in computer-assisted surgical navigation systems., Methods: The implemented algorithm performs contour interpolation in a step-by-step manner, determining an optimal surface between each pair of consecutive contours. Determining such a surface is reduced to the problem of finding certain minimum-cost cycles in a directed toroidal graph. The algorithm assumes that the contours are ordered. The first step in the algorithm is the determination of branching patterns, followed by the removal of keyholes from contours, optimization of a target function based on the surface area, and mesh triangulation based on the optimization results and mesh seal., Results: The algorithm was tested on contours segmented on computed tomography images from femoral and tibial specimens; it was able to generate qualitatively good 3D meshes from the set of 2D contours for all the tested examples., Conclusion: The contour interpolation algorithm proved to be quite effective using optimization based on minimizing the area of the triangles that form the 3D surface. The algorithm can be used for the 3D reconstruction of other types of 2D cuts, but special attention must be paid with the branches, since the proposed algorithm is not designed for complex branching structures., (© 2022. The Author(s).)

This paper investigates the levels of occupational stress and work engagement among military police officers. This cross-sectional, descriptive, and analytical study was conducted with 268 police officers from the 3rd Military Police Battalion of Paraná state. We observed significant levels of occupational stress in 125 (46.7%) police officers. The main stressors were lack of career growth prospects (3.7; ±1.3); inadequate training (3.4; ±1.2); discrimination/favoritism in the work environment (3.1; ±1.4); long working hours (3.0; ±1.4); distribution of tasks (2.7; ±1.1); control type (2.7; ±1.1); gaps in disclosing information about organizational decisions (2.7; ±1.2); low valuation (2.7; ±1.2). Levels of work engagement ranged from 3.8 [medium] to 4.1 [high]. The correlation between occupational stress and work engagement was low for the dimensions of Absorption (r: -.284; p<0.001) and Overall Score (r: -0.393; p<0.001) and moderate for the dimensions Vigor (r: -0.422; p<0.001) and Dedication (r: -0.414; p<0.001). We concluded that an important number of police officers had shown occupational stress. However, they displayed good levels of work engagement and are enthusiastic, inspired, and proud of their work.

The concept of atopy was initially developed in the first quarter of the 20th century on the basis of clinical observations without any knowledge of pathogenic mechanisms. Atopy involves a collection of comorbidities that share pathogenic features, and atopic comorbidities affect outcomes of concomitant conditions rather than existing synchronously. The clinical importance of understanding the relationship of these conditions is necessary because the treatment of one condition influences the others, and the development of one leads to or precedes the development of another. Environmental influences and multigenetic predispositions result in complex relationships among the atopic conditions sharing a type 2 pathogenesis. The specialty of Allergy and Immunology is devoted to managing the comorbidities of atopy, and better understanding of their connections can improve patient care., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Objective: Assess levels of career commitment and career entrenchment among Primary Health Care workers., Methods: This Cross-sectional study addressed 393 workers using the Brazilian versions of the Career Commitment Measure (CCM) and Career Entrenchment Measure (CEM)., Results: Levels of Career commitment [75.5-77.5] were higher (p<0.001) than Career Entrenchment [66.7-69.2]. Identity levels [82.7-85.5] were higher (p<0.001) than Investment levels [60.4-65.0]. Career resilience levels [75.1-79.2] were higher (p<0.001) than Emotional costs [69.0-72.1]. Planning levels [64.2-67.1] were lower (p<0.001) than levels of limitedness of career alternatives [68.1-71.0]., Conclusion: The highest scores were obtained in Career commitment, showing the workers' identification and positive relationship with their careers, that is, these workers remain in Primary Health Care services because they identify themselves with their professions.

The purpose of this systematic review was to summarize the available data on TMJ chondrosarcomas and to perform a survival analysis of cases reported to date. This review was conducted in accordance with the PRISMA. Two authors performed an electronic search of case reports of TMJ chondrosarcoma published until August 02, 2020. Forty-seven studies reporting 53 cases were included. Chondrosarcomas of the TMJ were more prevalent in women, with a male:female ratio of 1:1.4. Survival curves were significantly associated with histological diagnosis (p = 0.004), reconstructive surgery (p = 0.024), recurrence (p < 0.001), and distant metastasis (p = 0.001). Only distant metastasis was independently associated with survival (p = 0.017). TMJ chondrosarcomas presented with low recurrence and higher survival rates than other chondrosarcomas. Synovial subtype, absence of reconstructive surgery, and presence of local recurrence or distant metastasis were associated with poorer prognosis., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The lectin of Bauhinia forficata (nBfL) is a protein able to bind reversibly to N-acetylgalactosamine, performing several functions and one of them is the antiproliferative activity in tumor cells, but its effects have not yet been evaluated in female gametes. The objective of the present study was to determine the additional effect of B. forficata recombinants lectins in the medium of maturation in vitro of bovine oocytes in expression of genes related to oxidative stress pathways. To get the proteins, the gene for this recombinant lectin (rBfL) and its truncated isoform (rtBfL) were cloned and expressed in Escherichia coli (E.coli). The oocytes obtained through follicular puncture were incubated in IVM medium for 24 h containing concentrations of 10 μg/mL, 50 μg/mL and 100 μg/mL of nBfL, rBfL and rtBfL, and a no treated group as a control. In the groups treated with the concentration of 100 μg / mL, the gene expression of genes involved in oxidative stress SOD2, CAT, GPX-1, GSR, NOS2 and apoptosis BAX, CASP3 were evaluated. The rtBfL increased the expression of the SOD2, GSR and NOS2 genes and all the tested lectins increased the expression of the CASP3 gene compared to the control group. These findings indicate that the tested concentrations of the B. forficata recombinants lectins probably influence the expression of oxidative stress genes and increase the expression of the apoptotic gene CASP3 during in vitro maturation of bovine oocytes., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Aims: The term "Food Allergy" refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders., Methods: We undertook a mixed-methods systematic review, which involved searching 11 international biomedical databases for published studies from inception to 31 December 2019. Studies were independently screened against pre-defined eligibility criteria and critically appraised by established instruments. The substantial heterogeneity of included studies precluded meta-analyses and, therefore, narrative synthesis of quantitative and qualitative data was performed., Results: We found 23 studies providing eligible primary data on symptom-specific severity of food allergic reactions, and 31 previously published symptom-severity scoring systems referred to food allergic reactions. There were seven studies which assessed quality-of-life measures in patients (and family members) with different food allergy severity and two studies that investigated the economic burden of food allergy severity. Overall, the quality and the global rating of all included studies were judged as being moderate., Conclusions: There is heterogeneity among severity scoring systems used and even outcomes considered in the context of severity of food allergy. No score has been validated. Our results will be used to inform the development of an international consensus to define the severity of food allergy., Systematic Review Registration: A protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) database with the registration number CRD42020183103 (https://www.crd.york.ac.uk/prospero/#recordDetails)., Competing Interests: The following authors declared no potential interests: Ignacio J Ansotegui; Stefania Arasi; Shahd Daher; Alessandro Fiocchi; Ulugbek Nurmatov; Stavros Petrou; Graham Roberts; Mario Sánchez-Borges; Luciana Kase Tanno; Marta Vazquez Ortiz; Gary Wing-Kin Wong. Some of the authors have professional affiliations related to the content of the systematic review as set out below: Audrey Dunn-Galvin: consultancy fee from Aimmune and DBV; Paul J Turner: grants from UK 10.13039/501100000265Medical Research Council, 10.13039/501100013342NIHR/Imperial BRC, JM Charitable Foundation and UK 10.13039/501100000354Food Standards Agency; personal fees from UK Food Standards Agency, DBV Technologies, ILSI Europe and Allergenis, non-financial support from Aimmune Therapeutics; Sayantani B Sindher: supported by 10.13039/100000002NIH grants. Involved in clinical trials with Regeneron, Aimmune Therapeutics, DBV Technologies, Adare Pharmaceuticals, Sanofi, Novartis; Ruchi Gupta: grants from The 10.13039/100000002National Institute of Health (NIH) (R21 ID # AI135705, R01 ID# AI130348, U01 ID # AI138907), Rho Inc., Stanford Sean N. Parker Center for Allergy Research, UnitedHealth Group, Thermo Fisher Scientific, Genentech, and the National Confectioners Association (NCA); is employed by Ann & Robert H. Lurie Children's Hospital of Chicago; is a Professor of Pediatrics at Northwestern University; and serves as a medical consultant/advisor for Before Brands, Kaléo Inc., Genentech, ICER, FARE, Aimmune Therapeutics, and DBV Technologies; Philippe Eigenmann: Research grants and support: Ulrich Muller Gierock Foundation, 10.13039/100011033ThermoFisher Scientific; Consultant: DBV technologies, Nesté, Danone, Novartis, Abbott; Speaking engagements: ThermoFisher Scientific, ALK, Abbott; Stock options: DBV technologies; Anna Nowak-Wegrzyn: Grant/Research/Clinical Trial Support: DBV Technologies; ITN/NIAID; 10.13039/100004324Astellas Pharmaceutical; 10.13039/100004339Sanofi-Aventis [Future therapies for food allergy]. International FPIES Association [FPIES, unpaid advisor]. Consultant/Advisory Boards: Gerber Nutrition Institute; Merck. Speaking engagements: Nestle, Thermofisher Scientific; Montserrat Fernandez-Rivas: research grants from the Spanish Government (10.13039/501100003329MINECO, ISCIII) for the project SOLMILK, ARADyAL network and PI19/01095; consultancy fees from Aimmune, DBV, Novartis, SPRIM; lecture fees from ALK, Allergy Therapeutics, Diater, GSK, HAL Allergy, Thermofisher Scientific; Brian P Vickery: Employment: Pediatric Institute of Emory University + Children's Healthcare of Atlant; Consultant/Advisor: Aimmune Therapeutics; AllerGenis, LLC; Food Allergy Research and Education (FARE); Reacta Biosciences; Grant support: NIH-NIAID; 10.13039/100006423FARE; 10.13039/100004328Genentech; Clinical investigator: Aimmune; DBV Technologies; Regeneron; Motohiro Ebisawa: lecture fees: DBV technologies and Mylan., (© 2021 The Authors.)

Background and Aims: The term "Food Allergy" refers to a complex global health problem with a wide spectrum of severity. However, a uniform definition of severe food allergy is currently missing. This systematic review is the preliminary step towards a state-of-the-art synopsis of the current evidence relating to the severity of IgE-mediated food allergy; it will inform attempts to develop a consensus to define food allergy severity by clinicians and other stakeholders., Methods: We will undertake a systematic review, which will involve searching international biomedical databases for published studies. Studies will be independently screened against pre-defined eligibility criteria and critically appraised by established instruments. Data will be descriptively and, if possible and applicable, quantitatively synthesised., Ethics and Dissemination: This study does not require any specific ethical approval since it is a systematic review. We plan to report results from this systematic review in a peer reviewed journal. These results will be used to inform the development of an international consensus to define severe food allergy. Author's potential conflicts of interest are clearly stated., Prospero Registration Number: CRD42020183103., Competing Interests: The following authors declared no potential interests: Ignacio J Ansotegui; Stefania Arasi; Shahd Daher; Alessandro Fiocchi; Ulugbek Nurmatov; Stavros Petrou; Graham Roberts; Mario Sánchez-Borges; Luciana Kase Tanno; Marta Vazquez Ortiz; Gary Wing-Kin Wong. Some of the authors have professional affiliations related to the content of the systematic review as set out below: Audrey Dunn-Galvin: consultancy fee from Aimmune and DBV; Motohiro Ebisawa: lecture fees: DBV technologies and Mylan; Philippe Eigenmann: Research grants and support: Ulrich Muller Gierock Foundation, 10.13039/100011033ThermoFisher Scientific; Consultant: DBV technologies, Nesté, Danone, Novartis, Abbott; Speaking engagements: ThermoFisher Scientific, ALK, Abbott; Stock options: DBV technologies; Montserrat Fernandez-Rivas: research grants from the Spanish Government (10.13039/501100003329MINECO, 10.13039/501100004587ISCIII) for the projectos SOLMILK, ARADyAL network and PI19/01095; consultancy fees from Aimmune, DBV, Novartis, SPRIM; lecture fees from ALK, Allergy Therapeutics, Diater, GSK, HAL Allergy, Thermofisher Scientific. Ruchi Gupta: grants from 10.13039/100000002The National Institute of Health (NIH) (R21 ID # AI135705, R01 ID# AI130348, U01 ID # AI138907), Rho Inc., Stanford Sean N. Parker Center for Allergy Research, UnitedHealth Group, 10.13039/100011033Thermo Fisher Scientific, 10.13039/100004328Genentech, and the National Confectioners Association (NCA); is employed by Ann & Robert H. Lurie Children's Hospital of Chicago; is a Professor of Pediatrics at Northwestern University; and serves as a medical consultant/advisor for Before Brands, Kaléo Inc., Genentech, ICER, FARE, Aimmune TherapeuticsAimmune Therapeutics, and DBV Technologies; Anna Nowak-Wegrzyn: Grant/Research/Clinical Trial Support: DBV Technologies; 10.13039/100000060ITN/NIAID; 10.13039/100004324Astellas Pharmaceutical; Sanofi-Aventis [Future therapies for food allergy]. International FPIES Association [FPIES, unpaid advisor]. Consultant/Advisory Boards: Gerber Nutrition Institute; Merck. Speaking engagements: Nestle, Thermofisher Scientific; Sayantani B Sindher: supported by 10.13039/100000002NIH grants. Involved in clinical trials with Regeneron, Aimmune Therapeutics, DBV Technologies, Adare Pharmaceuticals, Sanofi, Novartis; Paul J Turner: grants from UK Medical Research Council, NIHR/Imperial BRC, JM Charitable Foundation and UK Food Standards Agency; personal fees fromUK Food Standards Agency, DBV Technologies, ILSI Europe and Allergenis, non-financial support from Aimmune Therapeutics; Brian P Vickery: Employment: Pediatric Institute of Emory University + Children's Healthcare of Atlant; Consultant/Advisor: Aimmune Therapeutics; AllerGenis, LLC; Food Allergy Research and Education (FARE); Reacta Biosciences; Grant support: Immune Tolerance Network; 10.13039/100000060NIH-NIAID; 10.13039/100006423FARE; 10.13039/100004328Genentech; Clinical investigator: Aimmune; DBV Technologies; Regeneron., (© 2020 Published by Elsevier Inc. on behalf of World Allergy Organization.)

Objective: Asthma and obesity are prevalent and interrelated diseases. In the pediatric population, the effect of systemic inflammation associated to obesity, leading to inflammation of the airways, is currently controversial. Our aim was to compare inflammatory, clinical and spirometric patterns between children with asthma and obesity and those within the normal weight status range., Methods: A total of 79 boys and girls from 6 to 10 years old were selected and divided into four groups: obese asthmatics, non-obese asthmatics, obese non-asthmatics, and non-obese non-asthmatics. In addition to collecting clinical and anthropometric data, all children underwent spirometry and skin prick tests for inhalant allergens. Blood samples for measurement of cytokines and adipokines were also collected., Results: Obese asthmatics had significantly worse control of asthma than non-obese asthmatics (OR 4.9; 95%CI 1.1‒22.1), regardless of sex, physical activity and atopy. No differences in spirometry, Th1 and Th2 cytokines and adipokines levels were observed among the four groups. The prick tests were positive in 81.8 and 80% of non-obese asthmatics and obese asthmatics, respectively., Conclusions: The degree of control of asthma was significantly lower in the obese group, regardless of the findings of no differences in spirometry. Extra-pulmonary factors could be responsible for this symptomatic profile. High positivity of skin test in both groups, which is considered a good marker of atopy, shows a preponderant atopic component in the genesis of asthma, both in children with obesity and in those within the normal weight status.

Yellow fever (YF) is a re-emerging viral zoonosis caused by the Yellow Fever virus (YFV), affecting humans and non-human primates (NHP). YF is endemic in South America and Africa, being considered a burden for public health worldwide despite the availability of an effective vaccine. Acute infectious disease can progress to severe hemorrhagic conditions and has high rates of morbidity and mortality in endemic countries. In 2016, Brazil started experiencing one of the most significant YF epidemics in its history, with lots of deaths being reported in regions that were previously considered free of the disease. Here, we reviewed the historical aspects of YF in Brazil, the epidemiology of the disease, the challenges that remain in Brazil's public health context, the main lessons learned from the recent outbreaks, and our perspective for facing future YF epidemics.

Currently, testing for immunoglobulin E (IgE) sensitization is the cornerstone of diagnostic evaluation in suspected allergic conditions. This review provides a thorough and updated critical appraisal of the most frequently used diagnostic tests, both in vivo and in vitro . It discusses skin tests, challenges, and serological and cellular in vitro tests, and provides an overview of indications, advantages and disadvantages of each in conditions such as respiratory, food, venom, drug, and occupational allergy. Skin prick testing remains the first line approach in most instances; the added value of serum specific IgE to whole allergen extracts or components, as well as the role of basophil activation tests, is evaluated. Unproven, non-validated, diagnostic tests are also discussed. Throughout the review, the reader must bear in mind the relevance of differentiating between sensitization and allergy; the latter entails not only allergic sensitization, but also clinically relevant symptoms triggered by the culprit allergen., (© 2019 The Authors.)

The development of new bioactive molecules based on the molecular hybridization has been widely explored. In line with this, reliable tests should be employed to give information about the toxicology of these new molecules. In this sense, the use of in vitro tests is a valuable tool, especially the in vitro maturation of oocytes (IVM), which is an efficient resource to discover the potential toxicity of synthetic molecules. Thus, the aim of the present study was to evaluate the toxicological effects of the selenium-containing indolyl compound 3-(4-Chlorophenylselanyl)-1-methyl-1H-indole (CMI), on different quality parameters of bovine oocytes through the IVM. Different concentrations of the CMI compound (0, 25, 50, 100, 200 μM) were supplemented during the in vitro maturation process. After, the oocyte maturation rate, glutathione (GSH) levels, reactive oxygen species (ROS) levels, membrane, and mitochondrial integrity were evaluated. The results showed that the lowest concentration of CMI induced the highest GSH production (P < 0.05), an important marker of cytoplasmic quality and maturation. All treatments increased ROS production in relation to non-supplementation (P < 0.05). In addition, oocyte maturation was reduced only with the highest concentration of CMI (P < 0.05). Supplementation with CMI did not impact mitochondrial activity, integrity and cell membrane. To our knowledge, this is the first study that evaluates CMI on the oocyte in vitro maturation process. Importantly, our results did not find any toxic effect of CMI on bovine oocytes. CMI was efficient for cytoplasmic maturation by promoting an increase in the intracellular levels of glutathione., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To develop and test a beat-to-beat blood pressure monitoring device during coronary angiography, and compare it with invasive blood pressure monitoring., Methods: Twenty-eight patients with an indication for hemodynamic study were selected for this investigation, and kept in supine position. Before starting the coronary angiography, they were instructed about the use of the left radial bracelet for beat-to-beat blood pressure monitoring., Results: There was a significant difference between the time required for the catheterization laboratory team to acquire the first invasive blood pressure reading and the time to obtain the first beat-to-beat reading (11.1±5.1 and 1.5±1.8, respectively; p<0.0001). The intraclass correlation coefficients (95%CI) of systolic and diastolic blood pressures were 0.897 (0.780-0.952) and 0.876 (0.734-0.942), indicating good reproducibility., Conclusion: This study showed the process to develop a beat-to-beat blood pressure monitoring device. When compared to invasive blood pressure monitoring, there were no significant differences between the two methods. This technique may play a promising coadjuvant role when combined with invasive monitoring during coronary angiography procedures.

Background: Zika virus is an emerging arbovirus of the family Flaviviridae and genus Flavivirus that until 2007 was restricted to a few cases of mild illness in Africa and Asia., Case Presentation: We report a case of atrial fibrillation disclosed during an acute Zika virus infection in a 49-year-old man. Different biological samples were analyzed for the molecular diagnosis of Zika by real-time PCR, however only the saliva specimen was positive. The patient's wife tested positive in the serum sample, although she was an asymptomatic carrier. Moreover, a complete overview of patient's biomarkers, including cytokines, chemokines, and growth-factors levels, was analyzed and compared to gender and age matching non-infected controls, as well as other Zika infected patients, considering the 95%CI of the mean values. Elevated levels of CXCL8, CCL11, CCL2, CXCL10, IL-1β, IL-6, TNF-α, IFN-γ, IL-17, IL-1Ra, IL-4, IL-9, FGF-basic, PDGF, G-CSF, and GM-CSF were observed in the Atrial fibrillation patient, in contrast to uninfected controls. Furthermore, increased levels of CCL5, IL-1β, TNF-α, IFN-γ, IL-9, G-CSF, and GM-CSF were observed only in the atrial fibrillation patient, when compared to other Zika patients., Conclusions: To our knowledge, this is the first description of this type of cardiac disorder in Zika patients which may be considered another atypical manifestation during Zika virus infection.

The improvement of in vitro embryo production by culture media supplementation has been a potential tool to increase blastocyst quality and development. Recently, lipid-core nanocapsules (LNC), which were developed for biomedical applications as a drug-delivery system, have demonstrated beneficial effects on in vitro embryo production studies. LNCs have a core composed of sorbitan monostearate dispersed in capric/caprylic triglyceride. Based on that, we firstly investigated if LNCs supplemented during in vitro oocyte maturation had affinity to the mineral oil placed over the top of the IVM media. Also, the effects of LNC supplementation in different concentrations (0; 0.94; 4.71; 23.56; 117.80 and 589.00μg/mL) during the in vitro maturation protocol were evaluated in oocytes and blastocysts by in vitro tests. LNCs seemed not to migrate to the mineral oil overlay during the in vitro oocyte maturation. Interestingly, LNCs did not show toxic effects in the oocyte in vitro maturation rate, cumulus cells expansion and oocyte viability. The highest LNCs concentration tested (589μg/mL) generated the lowest ROS and GSH levels, and reduced apoptosis rate when compared to the control. Additionally, toxic effects in embryo development and quality were not observed. The LNC supramolecular structure demonstrated to be a promising nanocarrier to deliver molecules in oocytes and embryos, aiming the improvement of the embryo in vitro development., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Previous studies have shown that microvascular dysfunction (MD) is associated with a number of cardiovascular risk factors, including obesity. Few studies have assessed microvascular reactivity in children, and in most of these, results were confounded by the effects of puberty. Our aim was to establish whether MD is already present in obese prepubertal children., Methods: This cross-sectional study included 52 obese, 18 overweight, and 28 eutrophic children, with a mean ± standard deviation age of 7.44 ± 1.22 years. We evaluated cardiovascular risk factors and nutritive microvascular function by using nailfold dynamic videocapillaroscopy and determined functional capillary density (FCD), red blood cell velocity at resting conditions (RBCV) and at peak (RBCV max ), and time to reach peak velocity during the post-occlusive reactive hyperemic response following 1 minute ischemia., Results: On univariate analysis, differences in microvascular reactivity were not observed among the groups. Obese and overweight children had significantly higher scores than eutrophic children for the following parameters: body mass index, waist circumference, waist-to-height ratio, mean arterial pressure, homeostasis model assessment for insulin resistance, levels of insulin, leptin, glucose, triglycerides, total cholesterol, uric acid, and C-reactive protein. Multivariate analysis demonstrated the association between metabolic, anthropometric, and microvascular variables, stratified according to the degree of adiposity and body fat distribution., Conclusions: Univariate analysis did not show any difference in microvascular reactivity between groups but, by testing these variables by multivariate means, we noticed a common and direct variation between cardiovascular/metabolic risk factors and microvascular reactivity occurring early in life.

It is well known that the most important etiologies of acute pancreatitis are gallstones and alcohol consumption. Once these causes have been ruled out, especially in young adults, it is important to consider less frequent etiologic factors such as drugs, trauma, malformations, autoimmunity or systemic diseases. Other rare and less well studied causes of this pathology are infections, among which Mycoplasma pneumoniae has been reported to cause acute pancreatitis as an unusual extrapulmonary manifestation. Here, we report the case of a 21-year-old patient who had acute idiopathic pancreatitis associated with an upper respiratory tract infection. After an in-depth study, all other causes of pancreatitis were ruled out and Mycoplasma was established as the clinical etiology.

Background: Haemosporidian parasites of the genera Plasmodium and Haemoproteus can have detrimental effects on individual birds and populations. Despite recent investigations into the distribution and richness of these parasites and their vertebrate hosts, little is known about their dipteran vectors. The Neotropics has the highest diversity of mosquitoes in the world, but few studies have tried to identify vectors in this area, hampering the understanding of the ecology of avian malaria in the highly diverse Neotropical environments., Methods: Shannon traps and active collection were used to capture 27,110 mosquitoes in a Seasonally Dry Tropical Forest in southeastern Brazil, a highly endangered ecosystem., Results: We screened 17,619 mosquito abdomens from 12 different species and several unidentified specimens of Culex, grouped into 1,913 pools, for the presence of haemosporidians. Two pools (out of 459) of the mosquito Mansonia titillans and one pool (out of 29) of Mansonia pseudotitillans were positive for Plasmodium parasites, with the detection of a new parasite lineage in the former species. Detected Plasmodium lineages were distributed in three different clades within the phylogenetic tree revealing that Mansonia mosquitoes are potential vectors of genetically distant parasites. Two pools of Culex spp. (out of 43) were positive for Plasmodium gallinaceum and closely related lineages. We found a higher abundance of these putative vectors in pasture areas, but they were also distributed in areas at intermediate and late successional stages. One pool of the mosquito Psorophora discrucians (out of 173) was positive for Haemoproteus., Conclusions: The occurrence of different Plasmodium lineages in Mansonia mosquitoes indicates that this genus encompasses potential vectors of avian malaria parasites in Brazil, even though we did not find positive thoraces among the samples tested. Additional evidence is required to assign the role of Mansonia mosquitoes in avian malaria transmission and further studies will add information about evolutionary and ecological aspects of avian haemosporidia and untangle the diversity of their vectors in Brazil.

Purpose: To develop and validate a new multimedia instrument to measure health-related quality of life (HRQOL) in Portuguese-speaking patients with cancer., Methods: A mixed-methods study conducted in a large Brazilian Cancer Hospital. The instrument was developed along the following sequential phases: identification of HRQOL issues through qualitative content analysis of individual interviews, evaluation of the most important items according to the patients, review of the literature, evaluation by an expert committee, and pretesting. In sequence, an exploratory factor analysis was conducted (pilot testing, n = 149) to reduce the number of items and to define domains and scores. The psychometric properties of the IQualiV-OG-21 were measured in a large multicentre Brazilian study (n = 323). A software containing multimedia resources were developed to facilitate self-administration of IQualiV-OG-21; its feasibility and patients' preferences ("paper and pencil" vs. software) were further tested (n = 54)., Results: An exploratory factor analysis reduced the 30-item instrument to 21 items. The IQualiV-OG-21 was divided into 6 domains: emotional, physical, existential, interpersonal relationships, functional and financial. The multicentre study confirmed that it was valid and reliable. The electronic multimedia instrument was easy to complete and acceptable to patients. Regarding preferences, 61.1 % of them preferred the electronic format in comparison with the paper and pencil format., Conclusions: The IQualiV-OG-21 is a new valid and reliable multimedia HRQOL instrument that is well-understood, even by patients with low literacy skills, and can be answered quickly. It is a useful new tool that can be translated and tested in other cultures and languages.

Purpose: To evaluate the precision of both two- and three-dimensional ultrasonography in determining vertebral lesion level (the first open vertebra) in patients with spina bifida., Methods: This was a prospective longitudinal study comprising of fetuses with open spina bifida who were treated in the fetal medicine division of the department of obstetrics of Hospital das Clínicas of the Universidade de São Paulo between 2004 and 2013. Vertebral lesion level was established by using both two- and three-dimensional ultrasonography in 50 fetuses (two examiners in each method). The lesion level in the neonatal period was established by radiological assessment of the spine. All pregnancies were followed in our hospital prenatally, and delivery was scheduled to allow immediate postnatal surgical correction., Results: Two-dimensional sonography precisely estimated the spina bifida level in 53% of the cases. The estimate error was within one vertebra in 80% of the cases, in up to two vertebrae in 89%, and in up to three vertebrae in 100%, showing a good interobserver agreement. Three-dimensional ultrasonography precisely estimated the lesion level in 50% of the cases. The estimate error was within one vertebra in 82% of the cases, in up to two vertebrae in 90%, and in up to three vertebrae in 100%, also showing good interobserver agreement. Whenever an estimate error was observed, both two- and three-dimensional ultrasonography scans tended to underestimate the true lesion level (55.3% and 62% of the cases, respectively)., Conclusions: No relevant difference in diagnostic performance was observed between the two- and three-dimensional ultrasonography. The use of three-dimensional ultrasonography showed no additional benefit in diagnosing the lesion level in the fetuses with spina bifida. Errors in both methods showed a tendency to underestimate lesion level., (Thieme Publicações Ltda Rio de Janeiro, Brazil.)

Studies on the parasitology of ectoparasitic bat flies are scarce, and they are needed to identify patterns in parasitism. Hence, in the present study, we assessed community composition, prevalence, average infestation intensity, and specificity in the fly-bat associations in Brazilian tropical dry forests. In order to do that, we used the parasitological indices known as prevalence and average infestation intensity, along with an index of host specificity. We collected 1098 bat flies of 38 species. Five of the associations found are new to Brazil, 9 are new to southeastern Brazil, and 10 are new to science. Average infestation intensity varied from 1 to 9 and prevalence 0 to 100 %. In terms of specificity, 76 % of the bat flies were associated to a single host (monoxenic). These results highlight the low capacity of bat flies to survive on a not usual host especially due to an immunological incompatibility between parasites and hosts and dispersal barriers.

Objective: The aim of this study was to analyze the causes and perinatal outcome related to fetal ductus arteriosus constriction or closure at a single center over a 26-year period., Methods: This was a retrospective analysis of 45 consecutive cases of constriction (n = 41) and closure (n = 4) from 1987 through 2013. Patients were divided into Group A (maternal use of non-steroidal anti-inflammatory drugs (NSAID), n = 29), Group B (idiopathic, n = 8), and Group C (other drugs not previously described, n = 8)., Results: The median gestational age at diagnosis was 34 weeks (range, 27-38), mean systolic and diastolic velocity in the ductus arteriosus was 2.01 ± 0.66 m/s and 0.71 ± 0.46 m/s, respectively. Among the 29 cases of NSAIDs, 27.5% (8/29) have taken a single day use and 75% multiple days/doses. Right ventricular dilatation was present in 82.2% of the fetuses, tricuspid insufficiency in 86.6%, and heart failure in 22.2%. Neonatal persistent pulmonary hypertension occurred in 17.7% of the patients. Late follow-up showed all 43 survivors alive and healthy with only two deaths from unrelated causes., Conclusions: The results of this study indicate that clinically significant ductal constriction may follow maternal exposure to single doses of NSAIDs. Unknown causes or other new substances were also described, such as naphazoline, fluoxetine, isoxsuprine, caffeine and pesticides. Echocardiographic diagnosis of ductal constriction led to an active medical approach that resulted in low morbidity of this group of patients.

This work investigates, whether openEHR with its reference model, archetypes and templates is suitable for the digital representation of demographic as well as clinical data. Moreover, it elaborates openEHR as a tool for modelling Hospital Information Systems on a regional level based on a national logical infrastructure. OpenEHR is a dual model approach developed for the modelling of Hospital Information Systems enabling semantic interoperability. A holistic solution to this represents the use of dual model based Electronic Healthcare Record systems. Modelling data in the field of obstetrics is a challenge, since different regions demand locally specific information for the process of treatment. Smaller health units in developing countries like Brazil or Malaysia, which until recently handled automatable processes like the storage of sensitive patient data in paper form, start organizational reconstruction processes. This archetype proof-of-concept investigation has tried out some elements of the openEHR methodology in cooperation with a health unit in Colombo, Brazil. Two legal forms provided by the Brazilian Ministry of Health have been analyzed and classified into demographic and clinical data. LinkEHR-Ed editor was used to read, edit and create archetypes. Results show that 33 clinical and demographic concepts, which are necessary to cover data demanded by the Unified National Health System, were identified. Out of the concepts 61% were reused and 39% modified to cover domain requirements. The detailed process of reuse, modification and creation of archetypes is shown. We conclude that, although a major part of demographic and clinical patient data were already represented by existing archetypes, a significant part required major modifications. In this study openEHR proved to be a highly suitable tool in the modelling of complex health data. In combination with LinkEHR-Ed software it offers user-friendly and highly applicable tools, although the complexity built by the vast specifications requires expert networks to define generally excepted clinical models. Finally, this project has pointed out main benefits enclosing high coverage of obstetrics data on the Clinical Knowledge Manager, simple modelling, and wide network and support using openEHR. Moreover, barriers described are enclosing the allocation of clinical content to respective archetypes, as well as stagnant adaption of changes on the Clinical Knowledge Manager leading to redundant efforts in data contribution that need to be addressed in future works., (Copyright © 2015 Elsevier Inc. All rights reserved.)