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Composite materials made with synthetic fibers are extensively employed across a diverse array of engineering structures. However, from an environmental point of view, synthetic fibers do not represent the best choice, since they are not renewable and are not biodegradable as natural fibers. This study investigates the application of adhesive joints with hybrid composites, which combine natural and synthetic fibers, as potential replacements for traditional composites made solely from synthetic fibers. The main focus is on assessing the mechanical performance of these hybrid composites through end-notched flexure (ENF) tests on adhesive joints. Four different configurations of substrates were used, two with only one type of fiber (natural or synthetic) and two hybrids. Digital image correlation (DIC) analysis was conducted to provide detailed insights into the changes in displacement fields for the different configurations tested. The results indicate that adhesive joints with hybrid composites exhibit superior shear fracture energy (GIIC) compared with the joints with purely synthetic fibers. This enhancement in fracture toughness, attributed to the synergistic effects of the natural and synthetic fibers, suggests that hybrid composites could be a viable alternative, offering potential benefits in terms of sustainability and cost without compromising mechanical performance.
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Background/Objectives: The rising prevalence of musculoskeletal (MSK) conditions has not been balanced by a sufficient increase in healthcare providers. Scalability challenges are being addressed through the use of artificial intelligence (AI) in some healthcare sectors, with this showing potential to also improve MSK care. Digital care programs (DCP) generate automatically collected data, thus making them ideal candidates for AI implementation into workflows, with the potential to unlock care scalability. In this study, we aimed to assess the impact of scaling care through AI in patient outcomes, engagement, satisfaction, and adverse events. Methods: Post hoc analysis of a prospective, pre-post cohort study assessing the impact on outcomes after a 2.3-fold increase in PT-to-patient ratio, supported by the implementation of a machine learning-based tool to assist physical therapists (PTs) in patient care management. The intervention group (IG) consisted of a DCP supported by an AI tool, while the comparison group (CG) consisted of the DCP alone. The primary outcome concerned the pain response rate (reaching a minimal clinically important change of 30%). Other outcomes included mental health, program engagement, satisfaction, and the adverse event rate. Results: Similar improvements in pain response were observed, regardless of the group (response rate: 64% vs. 63%; p = 0.399). Equivalent recoveries were also reported in mental health outcomes, specifically in anxiety (p = 0.928) and depression (p = 0.187). Higher completion rates were observed in the IG (79.9% (N = 19,252) vs. CG 70.1% (N = 8489); p < 0.001). Patient engagement remained consistent in both groups, as well as high satisfaction (IG: 8.76/10, SD 1.75 vs. CG: 8.60/10, SD 1.76; p = 0.021). Intervention-related adverse events were rare and even across groups (IG: 0.58% and CG 0.69%; p = 0.231). Conclusions: The study underscores the potential of scaling MSK care that is supported by AI without compromising patient outcomes, despite the increase in PT-to-patient ratios.
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OBJECTIVE: To evaluate the impact of the state action-research project on vaccination coverage in children under two years of age in the state of Minas Gerais, according to the size of the municipalities, comparing the years 2021 and 2022. METHODS: This is a study nested within the state action-research project, a before-after community clinical trial carried out in 212 municipalities in the state of Minas Gerais. This study used secondary data on Vaccination Coverage (VC), Homogeneity of Vaccines (HVC) and Abandonment rate of multi-dose vaccines. After classifying municipalities by size and vaccination coverage rates were equitably classified, an analysis of secondary data on 12 immunobiologicals indicated for the age group in question and their abandonment rate of multi-dose vaccines was carried out. RESULTS: There was an increase in the proportion of municipalities classified as small that reached the vaccination coverage target set by the National Immunization Program (PNI) after the action-research project was carried out. There was an increase in the proportion of small municipalities classified as having a low abandonment rate for the rotavirus vaccine, in the adequate homogeneity of vaccination coverage and in the classification of risk as very low risk and low and medium risk, all with a statistically significant difference. CONCLUSION: There was an influence of municipal size on the effectiveness of the actions applied to increase vaccination coverage, explaining that proposing individualized actions for each municipality is essential to improve vaccination coverage.
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Programas de Imunização , Cobertura Vacinal , Humanos , Cobertura Vacinal/estatística & dados numéricos , Brasil , Lactente , Programas de Imunização/estatística & dados numéricos , Cidades , Vacinação/estatística & dados numéricosRESUMO
Objective: This study aimed to evaluate the cardiovascular risk of patients with post-surgical hypoparathyroidism through coronary calcium score (CACS) evaluation andcardiovascular risk calculators. Subjects and methods: Patients with post-surgical hypoparathyroidism (HG = 29) were compared to a control group (CG = 29), matched by sex and age. Demographic and clinical data were captured by a questionnaire or patient files. Both groups performed a thoracic-computed tomography to evaluate the CACS and the cardiovascular risk was calculated by two risk calculators. Results: In the HG, the supplementation of calcium varied between 500 to 2,000 mg/day and the mean calcitriol was 0.5 ± 0.29 mcg/day. The mean serum calcium and phosphorus were 8.32 ± 0.68 and 4.92 ± 0.87 mg/dL, respectively, and in the range recommended for hypoparathyroidism. The Brazilian Society of Cardiology's risk calculator showed a difference among groups, with no patient in the HG with low risk, but the CACS was similar. A positive CACS in the HG was associated with obesity and high BMI but not with calcium and/or vitamin D supplementation. Conclusion: In conclusion, patients with hypoparathyroidism did not show increased CACS, and it was not related to supplementation.
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Doença da Artéria Coronariana , Hipoparatireoidismo , Humanos , Cálcio , Hipoparatireoidismo/etiologia , BrasilRESUMO
On T cell activation, upregulation of gene expression produces the protein required for the differentiation and proliferation of effector cell populations. RAM (RNMT-Activating Mini protein/RAMAC/Fam103a1), the cofactor of the RNA cap methyltransferase RNMT (RNA guanosine N-7 cap methyltransferase), is upregulated following activation. Formation of the RNA cap protects RNA during synthesis and guides RNA processing and translation. Using conditional gene deletion, we found that Ram expression stabilizes RNMT protein in T cells and is required for its upregulation on activation. When the Ram gene is deleted in naïve T cells, there are major impacts on activation-induced RNA cap formation and gene expression. Activated T cell proliferation is dependent on increased ribosome production; in Ram knockout T cells, activation-induced expression of ribosomal protein genes and snoRNAs is most severely reduced. Consistent with these changes, Ram deletion resulted in reduced protein synthesis, and reduced growth and proliferation of CD4 T cells. Deletion of Ram results in a similar but milder phenotype to Rnmt deletion, supporting the role of RAM as a RNMT cofactor.
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Words are the primary means by which we communicate meaning and ideas, while faces provide important social cues. Studying visual illusions involving faces and words can elucidate the hierarchical processing of information as different regions of the brain are specialised for face recognition and word processing. A size illusion has previously been demonstrated for faces, whereby an inverted face is perceived as larger than the same stimulus upright. Here, two experiments replicate the face size illusion, and investigate whether the illusion is also present for individual letters (Experiment 1), and visual words and pseudowords (Experiment 2). Results confirm a robust size Illusion for faces. Letters, words and pseudowords and unfamiliar letters all show a reverse size illusion, as we previously demonstrated for human bodies. Overall, results indicate the illusion occurs in early perceptual stages upstream of semantic processing. Results are consistent with the idea of a general-purpose mechanism that encodes curvilinear shapes found in both scripts and our environment. Word and face perception rely on specialised, independent cognitive processes. The underestimation of the size of upright stimuli is specific to faces. Opposite size illusions may reflect differences in how size information is encoded and represented in stimulus-specialised neural networks, resulting in contrasting perceptual effects. Though words and faces differ visually, there is both symmetry and asymmetry in how the brain 'reads' them.
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Reconhecimento Facial , Ilusões , Humanos , Face , Encéfalo , Corpo Humano , Reconhecimento Visual de ModelosRESUMO
ABSTRACT Objective: This study aimed to evaluate the cardiovascular risk of patients with post-surgical hypoparathyroidism through coronary calcium score (CACS) evaluation and cardiovascular risk calculators. Subjects and methods: Patients with post-surgical hypoparathyroidism (HG = 29) were compared to a control group (CG = 29), matched by sex and age. Demographic and clinical data were captured by a questionnaire or patient files. Both groups performed a thoracic-computed tomography to evaluate the CACS and the cardiovascular risk was calculated by two risk calculators. Results: In the HG, the supplementation of calcium varied between 500 to 2,000 mg/day and the mean calcitriol was 0.5 ± 0.29 mcg/day. The mean serum calcium and phosphorus were 8.32 ± 0.68 and 4.92 ± 0.87 mg/dL, respectively, and in the range recommended for hypoparathyroidism. The Brazilian Society of Cardiology's risk calculator showed a difference among groups, with no patient in the HG with low risk, but the CACS was similar. A positive CACS in the HG was associated with obesity and high BMI but not with calcium and/or vitamin D supplementation. Conclusion: In conclusion, patients with hypoparathyroidism did not show increased CACS, and it was not related to supplementation.
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ABSTRACT Objective: To evaluate the impact of the state action-research project on vaccination coverage in children under two years of age in the state of Minas Gerais, according to the size of the municipalities, comparing the years 2021 and 2022. Methods: This is a study nested within the state action-research project, a before-after community clinical trial carried out in 212 municipalities in the state of Minas Gerais. This study used secondary data on Vaccination Coverage (VC), Homogeneity of Vaccines (HVC) and Abandonment rate of multi-dose vaccines. After classifying municipalities by size and vaccination coverage rates were equitably classified, an analysis of secondary data on 12 immunobiologicals indicated for the age group in question and their abandonment rate of multi-dose vaccines was carried out. Results: There was an increase in the proportion of municipalities classified as small that reached the vaccination coverage target set by the National Immunization Program (PNI) after the action-research project was carried out. There was an increase in the proportion of small municipalities classified as having a low abandonment rate for the rotavirus vaccine, in the adequate homogeneity of vaccination coverage and in the classification of risk as very low risk and low and medium risk, all with a statistically significant difference. Conclusion: There was an influence of municipal size on the effectiveness of the actions applied to increase vaccination coverage, explaining that proposing individualized actions for each municipality is essential to improve vaccination coverage.
RESUMO Objetivo: Avaliar o impacto do projeto estadual de pesquisa-ação nas coberturas vacinais em crianças menores de dois anos no estado de Minas Gerais, segundo o porte dos municípios, comparando os anos de 2021 e 2022. Métodos: Estudo aninhado ao projeto estadual de pesquisa-ação, um ensaio clínico comunitário, do tipo antes-depois, realizado em 212 municípios do estado de Minas Gerais. Utilizou-se, neste estudo, dados secundários de Cobertura Vacinal (CV), Homogeneidade das Vacinas (HCV) e Proporção de Abandono (PA). Após a classificação de municípios por porte, e as taxas de cobertura vacinal serem classificadas de maneira equânime, foi realizada uma análise de dados secundários de 12 imunobiológicos indicados para a faixa etária em questão e de suas PAs. Resultados: Observou-se aumento na proporção de municípios classificados como de pequeno porte que atingiram a meta da cobertura vacinal estabelecida pelo Programa Nacional de Imunização (PNI), após a realização do projeto de pesquisa-ação. Houve aumento na proporção de municípios de pequeno porte classificados como de baixa PA para a vacina Rotavírus, na homogeneidade adequada da CV e na classificação de risco para risco muito baixo e risco baixo e médio, todos com diferença estatisticamente significativa. Conclusão: Houve influência do porte municipal na efetividade das ações aplicadas para aumento de cobertura vacinal, explicitando que a proposição de ações individualizadas para cada município é imprescindível para melhorar a cobertura vacinal.
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OBJECTIVE: Pregnancy after bariatric surgery is a reality of the 21st century and therefore is essential that all obstetricians know how to manage it. The most prevalent nutritional deficiency is iron deficiency and, consequently, anemia. Although bariatric surgery and pregnancy are already risk factors for anemia, we evaluated in our study if there were any other risk factors and actions to improve hemoglobin levels in this population. METHODS: We performed a retrospective cohort study, and performed frequency measurements and analyzes of odds ratio, X2 and Fisher exact test to evaluate the risk factors. RESULTS: We evaluated 44 pregnancies after bariatric surgery, with an incidence of anemia of 62%, and the only identifiable risk factor for anemia was being black. As for the treatment, the iron salt used for oral supplementation did not associate with anemia risk, and in 27% of the patients, the adjustment of the oral dosage was enough for improvement in hemoglobin levels, but in 36% supplementation with intravenous iron was necessary. CONCLUSION: Being black is a risk factor for anemia. The type of iron salt does not correlate with the incidence of anemia, and for the treatment and improvement of iron dosages, it seems an effective increase in iron intake.
OBJETIVO: A gestação após cirurgia bariátrica é uma realidade do século XXI e, portanto, é de suma importância que os obstetras saibam conduzir o pré-natal dessas gestantes. A deficiência nutricional mais prevalente nessa população é a deficiência de ferro, que tem como consequência a anemia. Apesar da própria gestação e da cirurgia serem fatores de risco para anemia ferropriva, realizamos um estudo para avaliar se existem outros fatores que são de risco e quais condutas podem melhorar os níveis de hemoglobina nessa população. MéTODOS: Trata-se de um estudo de coorte retrospectiva, e foram realizadas medidas de frequência e análise odds ratio, X2, e teste de exato de Fisher para a avaliação dos fatores de risco. RESULTADOS: Foram avaliadas 44 gestações após cirurgia bariátrica com incidência de anemia de 62%, sendo que o único fator de risco identificado foi a etnia preta. O sal de ferro utilizado na reposição não se associou com o risco de anemia. Em somente 27% das gestantes o ajuste da dose oral de ferro foi suficiente para corrigir a anemia, enquanto em 36% foi necessária a suplementação com ferro endovenoso. CONCLUSãO: Ser de etnia preta foi fator de risco para anemia após cirurgia bariátrica e o tipo de sal de ferro para suplementação não se correlacionou com a incidência de anemia. Para o tratamento da anemia, somente o ajuste da dose da medicação parece ser suficiente para a resolução desta.
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Anemia Ferropriva , Anemia , Cirurgia Bariátrica , Gravidez , Feminino , Humanos , Anemia Ferropriva/etiologia , Anemia Ferropriva/complicações , Estudos Retrospectivos , Ferro/uso terapêutico , Cirurgia Bariátrica/efeitos adversos , Anemia/epidemiologia , Anemia/etiologia , Anemia/terapia , Fatores de Risco , Hemoglobinas/análiseRESUMO
Insulin (INS) resistance is often found in cancer-bearing, but its correlation with cachexia development is not completely established. This study investigated the temporal sequence of the development of INS resistance and cachexia to establish the relationship between these factors in Walker-256 tumor-bearing rats (TB rats). INS hepatic sensitivity and INS resistance-inducing factors, such as free fatty acids (FFA) and tumor necrosis factor-α (TNF-α), were also evaluated. Studies were carried out on Days 2, 5, 8, and/or 12 after inoculation of tumor cells in rats. The peripheral INS sensitivity was assessed by the INS tolerance test and the INS hepatic sensitivity in in situ liver perfusion. TB rats with 5, 8, and 12 days of tumor, but not 2 days, showed decreased peripheral INS sensitivity (INS resistance), retroperitoneal fat, and body weight, compared to healthy rats, which were more pronounced on Day 12. Gastrocnemius muscle wasting was observed only on Day 12 of tumor. The peripheral INS resistance was significantly correlated (r = -.81) with weight loss. Liver INS sensitivity of TB rats with 2 and 5 days of tumor was unchanged, compared to healthy rats. TB rats with 12 days of tumor showed increased plasma FFA and increased TNF-α in retroperitoneal fat and liver, but not in the gastrocnemius, compared to healthy rats. In conclusion, peripheral INS resistance is early, starts along with fat and weight loss and before muscle wasting, progressive, and correlated with cachexia, suggesting that it may play an important role in the pathogenesis of the cachectic process in TB rats. Therefore, early correction of INS resistance may be a therapeutic approach to prevent and treat cancer cachexia.
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Resistência à Insulina , Neoplasias , Ratos , Animais , Caquexia/etiologia , Caquexia/patologia , Insulina , Fator de Necrose Tumoral alfa , Ratos Wistar , Redução de Peso , Neoplasias/complicaçõesRESUMO
This study hypothesized the existence of cultivar-associated correlations between grape berry metabolites and its microbial residents, in Douro wine region. Integrated metabolomics with metabarcoding showed that the microbial biodiversity is not associated to berry sugar concentration, but closely connected to the profile of amino acids, flavonoids and wax compounds, which drove cultivar differentiation together with the prevalence of pathogenic fungi, yeasts and bacteria, mainly Dothideomycetes and Gammaproteobacteria. Over 7000 metabolite-microbiota correlations with ρ >|0.99| exposed a core of 15 metabolites linked to 11 microbial taxa. Serine, oxalate, cyanidin-3-O-glucoside, petunidin-3-O-glucoside, gallic acid, germanicol, sitosterol and erythrodiol correlated negatively to the abundance of most taxa, including Alternaria, Aureobasidium, Pseudopithomyces, Pseudomonas and Sphingomonas. In contrast, phenylalanine, asparagine, alanine, (epi)gallocatechin and procyanidin gallate mediated positive metabolite-OTU correlations. E. necator and A. carbonarius correlated negatively with stigmasterol and amyrin. Complex fungi-bacteria relationships ruled by Dothideomycetes and Alphaproteobacteria further suggest tight host-microbe interactions at the carposphere.
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Microbiota , Vitis , Vinho , Vitis/química , Vinho/análise , Frutas/química , Flavonoides/análise , Fungos/metabolismoRESUMO
Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in â¼ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.
Polineuropatia amiloidótica familiar associada a transtirretina (ATTRv-PN) é uma polineuropatia sensitivo-motora e autonômica hereditária autossômica dominante com mais de 130 variantes patogênicas já identificadas no gene TTR. A ATTRv-PN é uma condição genética debilitante, progressiva e que ameaça a vida, levando à morte em â¼ 10 anos se não for tratada. Nas últimas décadas, a ATTRv-PN se tornou uma neuropatia tratável. Além do transplante de fígado, iniciado em 1990, temos agora 3 medicamentos modificadores de doença aprovados em muitos países, incluindo o Brasil, e muitas outras medicações estão em desenvolvimento. O primeiro consenso brasileiro em ATTRv-PN foi realizado em Fortaleza em junho de 2017. Devido aos novos avanços nesta área nos últimos 5 anos, o Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia organizou uma segunda edição do consenso. Cada panelista ficou responsável por rever a literatura e atualizar uma parte do manuscrito. Finalmente, os 18 panelistas se reuniram virtualmente após revisão da primeira versão, discutiram cada parte do artigo e chegaram a um consenso sobre a versão final do manuscrito.
Assuntos
Neuropatias Amiloides Familiares , Polineuropatias , Humanos , Brasil , Consenso , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/genética , Neuropatias Amiloides Familiares/terapiaRESUMO
Abstract Hereditary transthyretin amyloidosis with peripheral neuropathy (ATTRv-PN) is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy with over 130 pathogenic variants identified in the TTR gene. Hereditary transthyretin amyloidosis with peripheral neuropathy is a disabling, progressive and life-threatening genetic condition that leads to death in ~ 10 years if untreated. The prospects for ATTRv-PN have changed in the last decades, as it has become a treatable neuropathy. In addition to liver transplantation, initiated in 1990, there are now at least 3 drugs approved in many countries, including Brazil, and many more are being developed. The first Brazilian consensus on ATTRv-PN was held in the city of Fortaleza, Brazil, in June 2017. Given the new advances in the area over the last 5 years, the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology organized a second edition of the consensus. Each panelist was responsible for reviewing the literature and updating a section of the previous paper. Thereafter, the 18 panelists got together virtually after careful review of the draft, discussed each section of the text, and reached a consensus for the final version of the manuscript.
Resumo Polineuropatia amiloidótica familiar associada a transtirretina (ATTRv-PN) é uma polineuropatia sensitivo-motora e autonômica hereditária autossômica dominante com mais de 130 variantes patogênicas já identificadas no gene TTR. A ATTRv-PN é uma condição genética debilitante, progressiva e que ameaça a vida, levando à morte em ~ 10 anos se não for tratada. Nas últimas décadas, a ATTRv-PN se tornou uma neuropatia tratável. Além do transplante de fígado, iniciado em 1990, temos agora 3 medicamentos modificadores de doença aprovados em muitos países, incluindo o Brasil, e muitas outras medicações estão em desenvolvimento. O primeiro consenso brasileiro em ATTRv-PN foi realizado em Fortaleza em junho de 2017. Devido aos novos avanços nesta área nos últimos 5 anos, o Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia organizou uma segunda edição do consenso. Cada panelista ficou responsável por rever a literatura e atualizar uma parte do manuscrito. Finalmente, os 18 panelistas se reuniram virtualmente após revisão da primeira versão, discutiram cada parte do artigo e chegaram a um consenso sobre a versão final do manuscrito.
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Bisphenol-A (BPA) and 17α-ethinylestradiol (EE2) are considered endocrine disrupting compounds (EDC) and they may be harmful to the normal functioning of endocrine systems of humans and animals. Moreover, the presence of these compounds in superficial and groundwater may represent serious risks, even in low concentrations like ng·L-1. The objectives of this study were to remove BPA and EE2 from solutions containing a mixture of these compounds in ultrapure water at low concentrations through reverse osmosis (RO) membrane combined with a UV/H2O2 process. Furthermore, to assess the estrogenic activity reduction after such treatments, in vitro recombinant yeast-estrogen screen (YES) assay was used. The removal efficiencies of target micropollutants increased with the increase of H2O2 dosage. For RO permeate stream, they enhanced from 91% to 96% for EE2 and from 76% to 90% for BPA while, for the concentrate stream, from 70% to 81% for EE2 and 41% to 84% for BPA as the H2O2 concentration were increased from 100 to 1000â µg·L-1. The OH radicals' generation was the dominant factor in the degradation of EDC during the UV/H2O2 treatment since the photolysis itself was not enough to degrade BPA or EE2. The estrogenic activity reduction after UV/H2O2 treatment was high, ranging from 92% to 98% for the permeate stream and from 50% to 93% for the concentrate stream. The EE2 was responsible for the whole observed estrogenic activity since BPA does not present estrogenicity, by in vitro YES assay, in the concentrations observed.
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Disruptores Endócrinos , Poluentes Químicos da Água , Animais , Humanos , Etinilestradiol/análise , Peróxido de Hidrogênio , Estrogênios , Água , Saccharomyces cerevisiae , Osmose , Poluentes Químicos da Água/análise , Disruptores Endócrinos/análiseRESUMO
Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms - overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene - can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. Conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D analogs, which may improve radiographic rickets but do not normalize growth. Complications of the conventional long-term treatment consist of hypercalcemia, hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired renal function, and potentially chronic kidney disease. Recently, burosumab, an antibody against FGF-23, was approved as a novel therapy for children and adults with X-linked hypophosphatemia and patients with tumor-induced osteomalacia. Burosumab showed good performance in different trials in children and adults. It increased and sustained the serum phosphorus levels, decreased the rickets severity and pain scores, and improved mineralization. It offers a new perspective on the treatment of chronic and disabling diseases.
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Raquitismo Hipofosfatêmico Familiar , Osteomalacia , Criança , Adulto , Humanos , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Raquitismo Hipofosfatêmico Familiar/metabolismo , Osteomalacia/tratamento farmacológico , Fatores de Crescimento de Fibroblastos , Fósforo/metabolismo , Fósforo/uso terapêutico , FosfatosRESUMO
Stress fractures (SF) represent 10%-20% of all injuries in sport medicine. An SF occurs when abnormal and repetitive loading is applied on normal bone: The body cannot adapt quickly enough, leading to microdamage and fracture. The etiology is multifactorial with numerous risk factors involved. Diagnosis of SF can be achieved by identifying intrinsic and extrinsic factors, obtaining a good history, performing a physical exam, and ordering laboratory and imaging studies (magnetic resonance imaging is the current gold standard). Relative energy deficiency in sport (RED-S) is a known risk factor. In addition, for women, it is very important know the menstrual status to identify long periods of amenorrhea in the past and the present. Early detection is important to improve the chance of symptom resolution with conservative treatment. Common presentation involves complaints of localized pain, with or without swelling, and tenderness on palpation of bony structures that begins earlier in training and progressively worsens with activity over a 2- to 3-week period. Appropriate classification of SF based on type, location, grading, and low or high risk is critical in guiding treatment strategies and influencing the time to return to sport. Stress injuries at low-risk sites are typically managed conservatively. Studies have suggested that calcium and vitamin D supplementation might be helpful. Moreover, other treatment regimens are not well established. Understanding better the pathophysiology of SFs and the potential utility of current and future bone-active therapeutics may well yield approaches that could treat SFs more effectively.
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Fraturas de Estresse , Humanos , Feminino , Fraturas de Estresse/diagnóstico , Fraturas de Estresse/etiologia , Fraturas de Estresse/terapia , Fatores de Risco , Osso e Ossos , Cálcio da Dieta , Imageamento por Ressonância Magnética/efeitos adversosRESUMO
This narrative review summarizes data on classical and nonclassical manifestations of primary hyperparathyroidism (PHPT). It is based on a rigorous literature search, inclusive of a Medline search for systematic reviews from 1940 to December 2020, coupled with a targeted search for original publications, covering four databases, from January 2013-December 2020, and relevant articles from authors' libraries. We present the most recent information, identify knowledge gaps, and suggest a research agenda. The shift in the presentation of PHPT from a predominantly symptomatic to an asymptomatic disease, with its varied manifestations, has presented several challenges. Subclinical nephrolithiasis and vertebral fractures are common in patients with asymptomatic disease. The natural history of asymptomatic PHPT with no end organ damage at diagnosis is unclear. Some observational and cross-sectional studies continue to show associations between PHPT and cardiovascular and neuropsychological abnormalities, among the different disease phenotypes. Their causal relationship is uncertain. Limited new data are available on the natural history of skeletal, renal, cardiovascular, neuropsychological, and neuromuscular manifestations and quality of life. Normocalcemic PHPT (NPHPT) is often diagnosed without the fulfillment of rigorous criteria. Randomized clinical trials have not demonstrated a consistent long-term benefit of parathyroidectomy (PTX) versus observation on nonclassical manifestations. We propose further refining the definition of asymptomatic disease, into two phenotypes: one without and one with evidence of target organ involvement, upon the standard evaluation detailed in our recommendations. Each of these phenotypes can present with or without non-classical manifestations. We propose multiple albumin-adjusted serum calcium determinations (albumin-adjusted and ionized) and exclusion of all secondary causes of high parathyroid hormone (PTH) when establishing the diagnosis of NPHPT. Refining the definition of asymptomatic disease into the phenotypes proposed will afford insights into their natural history and response to interventions. This would also pave the way for the development of evidence-based guidance and recommendations. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
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Hiperparatireoidismo Primário , Humanos , Hiperparatireoidismo Primário/complicações , Estudos Transversais , Qualidade de Vida , Revisões Sistemáticas como Assunto , Paratireoidectomia , Hormônio Paratireóideo , Cálcio , Doenças Assintomáticas , AlbuminasRESUMO
Abstract Phosphorus is one of the most abundant minerals in the human body; it is required to maintain bone integrity and mineralization, in addition to other biological processes. Phosphorus is regulated by parathyroid hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and fibroblast growth factor 23 (FGF-23) in a complex set of processes that occur in the gut, skeleton, and kidneys. Different molecular mechanisms - overproduction of FGF-23 by tumors responsible for oncogenic osteomalacia, generation of an FGF-23 mutant that is resistant to cleavage by enzymes, and impaired FGF-23 degradation due to a reduction in or loss of the PHEX gene - can lead to FGF-23-stimulating activity and the consequent waste of urinary phosphate and low levels of 1,25(OH)2D3. Conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D analogs, which may improve radiographic rickets but do not normalize growth. Complications of the conventional long-term treatment consist of hypercalcemia, hypercalciuria, nephrolithiasis, nephrocalcinosis, impaired renal function, and potentially chronic kidney disease. Recently, burosumab, an antibody against FGF-23, was approved as a novel therapy for children and adults with X-linked hypophosphatemia and patients with tumor-induced osteomalacia. Burosumab showed good performance in different trials in children and adults. It increased and sustained the serum phosphorus levels, decreased the rickets severity and pain scores, and improved mineralization. It offers a new perspective on the treatment of chronic and disabling diseases. Arch Endocrinol Metab. 2022;66(5):658-65
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ABSTRACT Stress fractures (SF) represent 10%-20% of all injuries in sport medicine. An SF occurs when abnormal and repetitive loading is applied on normal bone: The body cannot adapt quickly enough, leading to microdamage and fracture. The etiology is multifactorial with numerous risk factors involved. Diagnosis of SF can be achieved by identifying intrinsic and extrinsic factors, obtaining a good history, performing a physical exam, and ordering laboratory and imaging studies (magnetic resonance imaging is the current gold standard). Relative energy deficiency in sport (RED-S) is a known risk factor. In addition, for women, it is very important know the menstrual status to identify long periods of amenorrhea in the past and the present. Early detection is important to improve the chance of symptom resolution with conservative treatment. Common presentation involves complaints of localized pain, with or without swelling, and tenderness on palpation of bony structures that begins earlier in training and progressively worsens with activity over a 2- to 3-week period. Appropriate classification of SF based on type, location, grading, and low or high risk is critical in guiding treatment strategies and influencing the time to return to sport. Stress injuries at low-risk sites are typically managed conservatively. Studies have suggested that calcium and vitamin D supplementation might be helpful. Moreover, other treatment regimens are not well established. Understanding better the pathophysiology of SFs and the potential utility of current and future bone-active therapeutics may well yield approaches that could treat SFs more effectively.
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OBJECTIVES: Patients with type-2 diabetes mellitus (T2DM) have increased risk for bone fractures which points towards impaired bone quality. METHODS: We measured bone mineralization density distribution (BMDD) and osteocyte lacunae section (OLS) characteristics based on quantitative backscattered electron images of transiliac biopsy samples from n=26 premenopausal women with T2DM. Outcomes were compared to those from reference cohorts as well as between T2DM subgroups defined by clinical characteristics. RESULTS: Comparison to references did not reveal any differences in BMDD (all p>0.05) but a lowered OLS-density in cancellous bone in T2DM (-14.9%, p<0.001). Neither BMDD nor OLS-characteristics differed in T2DM subgroups defined by HbA1c (<7% versus >7%). The average degree of bone mineralization (CaMean) was higher (0.44 wt%Ca in T2DM, 0.30 wt%Ca in reference) and consistently the calcium concentration between the tetracycline double labels (CaYoung) was higher (0.76 wt%Ca, all p<0.001) in cancellous versus cortical bone. CONCLUSIONS: Our findings suggest that bone matrix mineralization was neither affected by the presence nor by the glycemic control of T2DM in our study cohort. The intra-individual differences between cancellous and cortical bone mineralization gave evidence for differences in the time course of the early mineralization process in these compartments in general.