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1.
Rev. osteoporos. metab. miner. (Internet) ; 15(4): 135-143, oct.-dic. 2023. tab, graf
Artigo em Inglês, Espanhol | IBECS | ID: ibc-229298

RESUMO

Objetivo: dada la repercusión que tienen las fracturas por fragilidad y sus secuelas en la vida de las mujeres con osteoporosis posmenopáusica (OPM), el objetivo de este estudio es describir y analizar su impacto en esta población. Material y métodos: se realizó una encuesta a mujeres posmenopáusicas con fractura por fragilidad en un diseño observacional transversal. Se recogieron variables sociodemográficas, impacto de la fractura (necesidad de cuidados, productividad laboral), calidad de vida relacionada con la salud (CVRS, mediante cuestionario QUALEFFO-31) y disposición a pagar (DAP) por recuperarla. Resultados: participaron 120 mujeres, promedio de edad 62 ± 7 años. Las fracturas más frecuentes fueron las de radio distal (29,9 %) y las vertebrales (21,3 %). Un 53,3 % necesitó cuidados durante su recuperación (76,5 % informales; 24,9 % formales) y un 4,2 % tuvo que ingresar en un centro/residencia sociosanitaria. De aquellas que trabajaban cuando se produjo la fractura (62,5 %), el 56 % vio su vida laboral afectada (69,3 % incapacidad temporal; 17,3 % incapacidad permanente; 10,7 % reducción de jornada; 10,7 % abandono laboral; 5,3 % permiso/excedencia; 3,6 % prejubilación). El impacto de la fractura se debió principalmente al dolor (71,7 %), dificultad para realizar actividades cotidianas (48,3 %), problemas de movilidad (46,7 %) y estado emocional (41,7 %). La mayor DAP se ofreció por recuperar la capacidad para realizar actividades cotidianas y el estado emocional. La puntuación total QUALEFFO-31 (0-100) fue 49,9 ± 10,8 (función mental: 68,3 ± 7,3; dolor: 56 ± 22,6; función física: 39,3 ± 15,5). Conclusiones: las fracturas por fragilidad tienen un alto impacto en la calidad de vida de las mujeres con OPM. Resulta fundamental poner en valor aquellos aspectos que más les preocupan para optimizar su abordaje. (AU)


Objective: Given the impact of fragility fractures and their consequences on the lives of women with postmenopausal osteoporosis (PMO), the objective of this study is to describe and analyze the impact of this kind of fractures on this population. Materials and methods: A survey was conducted among postmenopausal women with fragility fractures in a cross-sectional observational design. Sociodemographic variables, fracture impact (need for care, work productivity), and data on health-related quality of life (HRQoL, assessed using the QUALEFFO-31 questionnaire), and willingness to pay (WTP) to regain HRQoL were collected. Results: A total of 120 women participated, with a mean age of 62 ± 7 years. The most frequent fractures described were distal radius fractures (29.9 %), followed by vertebral fractures (21.3 %). A total of 53.3 % required care during their recovery (76.5 %, informal; 24.9 %, formal), and 4.2 % had to be admitted to a health care or nursing home. Among those who were working when the fracture occurred (62.5 %), 56 % had their working life affected (69.3 %, temporary disability; 17.3 %, permanent disability; 10.7 %, reduced working hours; 10.7 %, quit their jobs; 5.3 %, leave of absence; and 3.6 %, early retirement). The impact of the fracture was primarily due to pain (71.7 %), difficulty performing activities of daily living (48.3 %), mobility problems (46.7 %), and emotional state (41.7 %). The highest WTP was offered to regain the ability to perform activities of daily living and improve the emotional state. The overall QUALEFFO-31 score (0-100) was 49.9 ± 10.8 (mental function, 68.3 ± 7.3; pain, 56 ± 22.6; physical function, 39.3 ± 15.5). Conclusions: Fragility fractures play a significant role on the quality of life of women with PMO. It is of paramount importance to value the aspects that concern them the most to optimize their management. (AU)


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Fraturas por Osteoporose/classificação , Fraturas por Osteoporose/epidemiologia , Osteoporose Pós-Menopausa/complicações , Osteogênese Imperfeita , Qualidade de Vida , Custos de Cuidados de Saúde , Pós-Menopausa
2.
J Control Release ; 356: 702-713, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36931471

RESUMO

Intra-articular (IA) administration of drugs for the treatment of diseases such as rheumatoid arthritis, osteoarthritis and psoriatic arthritis is a common strategy; however, the rapid clearance from the synovial fluid restricts their effectivity due to the limited retention time. Drug Delivery Systems (DDS) are currently being developed to increase their joint retention time. This study compares the biodistribution and retention time of a senolytic peptide (PEP), with potential application in osteoarthritis disease, and this senolytic peptide encapsulated in a DDS based on a lipid nanoemulsion (PEPNE) by using positron emission tomography (PET) imaging. To this aim, the PEP was conjugated with a chelating agent (DFO) and radiolabeled with zirconium-89 (89Zr). Then, [89Zr]-PEP was encapsulated in a novel nanoemulsion formulation, composed by vitamin E, sphingomyelin, and a lipid-PEG. Afterward, healthy rats were administered with either the [89Zr]-PEP or the [89Zr]-PEP-NE via IA injection and underwent PET scans at 0.5-, 24-, 48-, 72-, 168-, 240- and 336 h post-injection. To assess the biodistribution of both radiotracers, several volume-of-interest were manually drawn in different organs of the rat body and the %ID/organ was calculated. The [89Zr]-PEP was successfully encapsulated in the NE and their physicochemical properties were minimally affected by the radiolabeling buffer. Adequate stability of both [89Zr]-PEP and [89Zr]-PEP-NE was found in synovial fluid over 72 h. Quantitative data from PET images revealed a significantly higher [89Zr]-PEP-NE retention in the injected knee than with [89Zr]-PEP in all follow-up PET scans. The [89Zr]-PEP %ID/organ values in the liver and kidney were significantly higher than those from [89Zr]-PEP-NE, which might indicate a faster elimination of the [89Zr]-PEP. Therefore, the study highlights the higher retention time on the target site of the [89Zr]-PEP-NE which may improve the therapeutic effects of the peptide. Thereby, the novel nanoemulsion formulation seems to be a successful DDS for IA injection. In addition, these results represent the first study that evaluates the distribution of a PET-guided DDS after its IA administration.


Assuntos
Desferroxamina , Senoterapia , Ratos , Animais , Distribuição Tecidual , Desferroxamina/química , Tomografia por Emissão de Pósitrons/métodos , Peptídeos , Lipídeos , Linhagem Celular Tumoral
3.
Cell Death Dis ; 13(8): 681, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931686

RESUMO

The accumulation of senescent cells is a key characteristic of aging, leading to the progression of age-related diseases such as osteoarthritis (OA). Previous data from our laboratory has demonstrated that high levels of the transmembrane protein connexin 43 (Cx43) are associated with a senescent phenotype in chondrocytes from osteoarthritic cartilage. OA has been reclassified as a musculoskeletal disease characterized by the breakdown of the articular cartilage affecting the whole joint, subchondral bone, synovium, ligaments, tendons and muscles. However, the mechanisms that contribute to the spread of pathogenic factors throughout the joint tissues are still unknown. Here, we show for the first time that small extracellular vesicles (sEVs) released by human OA-derived chondrocytes contain high levels of Cx43 and induce a senescent phenotype in targeted chondrocytes, synovial and bone cells contributing to the formation of an inflammatory and degenerative joint environment by the secretion of senescence-associated secretory associated phenotype (SASP) molecules, including IL-1ß and IL-6 and MMPs. The enrichment of Cx43 changes the protein profile and activity of the secreted sEVs. Our results indicate a dual role for sEVs containing Cx43 inducing senescence and activating cellular plasticity in target cells mediated by NF-kß and the extracellular signal-regulated kinase 1/2 (ERK1/2), inducing epithelial-to-mesenchymal transition (EMT) signalling programme and contributing to the loss of the fully differentiated phenotype. Our results demonstrated that Cx43-sEVs released by OA-derived chondrocytes spread senescence, inflammation and reprogramming factors involved in wound healing failure to neighbouring tissues, contributing to the progression of the disease among cartilage, synovium, and bone and probably from one joint to another. These results highlight the importance for future studies to consider sEVs positive for Cx43 as a new biomarker of disease progression and new target to treat OA.


Assuntos
Vesículas Extracelulares , Osteoartrite , Condrócitos/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Osteoartrite/patologia , Fenótipo
4.
J Food Sci Technol ; 58(10): 3942-3952, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34471318

RESUMO

"Queijo de Évora" is a traditional Portuguese cheese from raw ewe's milk and granted with PDO label. It is ripened traditionally in rooms with empirical control of temperature and humidity. Nowadays, almost all cheese factories use rooms with temperature and humidity control, but still a significant heterogeneity among cheeses is acknowledged due to unequal distribution of environmental conditions. This paper discusses the influence of the environmental conditions on the ripening of Queijo de Évora, including the application of computational fluid dynamics in steady state conditions. Experimental data was obtained in cheeses ripened along the traditional ripening cycle, in different locations. A significant influence of environmental conditions was observed, especially air velocity and humidity, affecting physical-chemical, microbiological and sensory characteristics. Locations with higher air velocity, presented cheeses with lower moisture content, higher mesophilic bacteria count, darker appearance and higher number of holes. Locations with higher humidity presented cheeses with lower scores on some sensorial parameters like appearance, firmness and intensity of odor. The results of computational fluid dynamics made possible the identification of areas in and around the cheese stacks were the air distribution is less than adequate or uneven, which may influence the evolution of cheese during ripening.

5.
Foods ; 10(8)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34441494

RESUMO

Traditional ewe's cheese producers face certain challenges caused by fluctuating environmental parameters inside the ripening room, which lead to lack of homogeneity in the final product. The present research discusses the application of computer fluid dynamics for simulating the distribution of environmental parameters, predicting the airflow pattern, and identifying critical areas where such parameters could cause reduced cheese quality. A new monitoring system was developed including presence sensors, temperature and humidity dataloggers, pneumatic actuators, microcontrollers, and microcomputers connected remotely for control, data visualization, and processing. The validation of the computer simulation and monitoring system was made with a batch of 40 ewe's cheeses distributed in three different zones inside a prototype ripening room and ripened for 35 days. At 35 days, a physical, chemical, and microbiological characterization of cheeses was made for evaluation of the influence of environmental conditions on cheese quality. The comparison between simulated and local measurements showed close agreement, especially concerning air velocity inside the stacks of cheese. The results of Pearson's correlation analysis and PCA concluded that temperature affected the appearance of the rind, hardness, number and area occupied by holes. Humidity affected aw and mFeret. Air velocity affected pH and the circularity of gas holes.

6.
Int J Clin Pract ; 75(10): e14550, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34145944

RESUMO

BACKGROUND: Denosumab is a monoclonal antibody approved for the treatment of postmenopausal osteoporosis. The withdrawal of denosumab produces an abrupt loss of bone mineral density and may cause multiple vertebral fractures (MVF). OBJECTIVE: The objective of this study is to study the clinical, biochemical, and densitometric characteristics in a large series of postmenopausal women who suffered MVF after denosumab withdrawal. Likewise, we try to identify those factors related to the presence of a greater number of vertebral fractures (VF). PATIENTS AND METHODS: Fifty-six patients (54 women) who suffered MVF after receiving denosumab at least for three consecutive years and abruptly suspended it. A clinical examination was carried out. Biochemical bone remodelling markers (BBRM) and bone densitometry at the lumbar spine and proximal femur were measured. VF were diagnosed by magnetic resonance imaging MRI, X-ray, or both at dorsal and lumbar spine. RESULTS: Fifty-six patients presented a total of 192 VF. 41 patients (73.2%) had not previously suffered VF. After discontinuation of the drug, a statistically significant increase in the BBRM was observed. In the multivariate analysis, only the time that denosumab was previously received was associated with the presence of a greater number of VF (P = .04). CONCLUSIONS: We present the series with the largest number of patients collected to date. 56 patients accumulated 192 new VF. After the suspension of denosumab and the production of MVF, there was an increase in the serum values of the BBRM. The time of denosumab use was the only parameter associated with a greater number of fractures.


Assuntos
Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Densidade Óssea , Conservadores da Densidade Óssea/efeitos adversos , Denosumab/efeitos adversos , Feminino , Humanos , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas da Coluna Vertebral/induzido quimicamente
7.
Artigo em Inglês | MEDLINE | ID: mdl-33809573

RESUMO

Hip fractures are an important socio-economic problem in western countries. Over the past 60 years orthogeriatric care has improved the management of older patients admitted to hospital after suffering hip fractures. Quality of care in orthogeriatric co-management units has increased, reducing adverse events during acute admission, length of stay, both in-hospital and mid-term mortality, as well as healthcare and social costs. Nevertheless, a large number of areas of controversy regarding the clinical management of older adults admitted due to hip fracture remain to be clarified. This narrative review, centered in the last 5 years, combined the search terms "hip fracture", "geriatric assessment", "second hip fracture", "surgery", "perioperative management" and "orthogeriatric care", in order to summarise the state of the art of some questions such as the optimum analgesic protocol, the best approach for treating anemia, the surgical options recommendable for each type of fracture and the efficiency of orthogeriatric co-management and functional recovery.


Assuntos
Serviços de Saúde para Idosos , Fraturas do Quadril , Idoso , Fraturas do Quadril/terapia , Hospitalização , Hospitais , Humanos , Tempo de Internação
8.
Aging (Albany NY) ; 12(16): 15882-15905, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32745074

RESUMO

Articular cartilage and synovial tissue from patients with osteoarthritis (OA) show an overactivity of connexin43 (Cx43) and accumulation of senescent cells associated with disrupted tissue regeneration and disease progression. The aim of this study was to determine the effect of oleuropein on Cx43 and cellular senescence for tissue engineering and regenerative medicine strategies for OA treatment. Oleuropein regulates Cx43 promoter activity and enhances the propensity of hMSCs to differentiate into chondrocytes and bone cells, reducing adipogenesis. This small molecule reduce Cx43 levels and decrease Twist-1 activity in osteoarthritic chondrocytes (OACs), leading to redifferentiation, restoring the synthesis of cartilage ECM components (Col2A1 and proteoglycans), and reducing the inflammatory and catabolic factors mediated by NF-kB (IL-1ß, IL-6, COX-2 and MMP-3), in addition to lowering cellular senescence in OACs, synovial and bone cells. Our in vitro results demonstrate the use of olive-derived polyphenols, such as oleuropein, as potentially effective therapeutic agents to improve chondrogenesis of hMSCs, to induce chondrocyte re-differentiation in OACs and clearing out senescent cells in joint tissues in order to prevent or stop the progression of the disease.


Assuntos
Antirreumáticos/farmacologia , Cartilagem Articular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrogênese/efeitos dos fármacos , Iridoides/farmacologia , Olea , Osteoartrite/tratamento farmacológico , Polifenóis/farmacologia , Regeneração/efeitos dos fármacos , Idoso , Antirreumáticos/isolamento & purificação , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Linhagem Celular , Microambiente Celular , Condrócitos/metabolismo , Condrócitos/patologia , Colágeno Tipo II/metabolismo , Conexina 43/genética , Conexina 43/metabolismo , Feminino , Frutas , Humanos , Glucosídeos Iridoides , Iridoides/isolamento & purificação , Masculino , NF-kappa B/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Olea/química , Osteoartrite/genética , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteogênese/efeitos dos fármacos , Polifenóis/isolamento & purificação , Transdução de Sinais , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo
9.
Lisboa; s.n; 2020.
Tese em Português | BDENF - Enfermagem | ID: biblio-1372227

RESUMO

Atualmente, considera-se viável um recém-nascido a partir das 23 semanas, no entanto, o internamento prolongado na unidade de cuidados intensivos neonatais pode prejudicar o seu neurodesenvolvimento. Tanto a manipulação excessiva como a privação do sono do recém-nascido pré-termo podem ter consequências a curto prazo e a longo prazo no seu desenvolvimento. Este relatório pretende evidenciar o desenvolvimento de competências relativas à promoção do desenvolvimento do recém-nascido pré-termo, com especial enfoque na salvaguarda do sono, assim como na prestação de cuidados de enfermagem especializados em saúde infantil e pediátrica. Este percurso de aprendizagem e desenvolvimento de competências foi baseado numa metodologia critico-reflexiva sobre e nas ações desenvolvidas nos diferentes contextos de estágio, sustentado na evidência científica e no quadro de referência da Teoria do Conforto de Kolcaba, Filosofia de Cuidados Centrados na Família e Cuidados Não Traumáticos. Destacam-se como principais atividades o desenvolvimento de uma revisão scoping sobre intervenções de enfermagem para a salvaguarda do sono do recém nascido pré-termo, uma norma de procedimento e atividades de formação em contexto de trabalho no âmbito da temática da salvaguarda do sono do recém nascido pré-termo. Pretende-se como projetos futuros em contribuir para a formação dos enfermeiros da neonatologia do meu local de trabalho, no âmbito dos cuidados neuroprotetores, mais especificamente sobre a salvaguarda do sono do recém nascido pré-termo na unidade de cuidados intensivos neonatais, assim como integrar o grupo de trabalho de neonatologia "Bem-estar do Recém-nascido" visando a implementação do procedimento sectorial elaborado durante o relatório. Pretende-se também posteriormente, publicar a revisão scoping desenvolvida durante o relatório, numa revista de enfermagem certificada.


Currently, a newborn from 23 weeks of age is considered viable, however, prolonged hospitalization in the neonatal intensive care unit can impair its neurodevelopment. Both excessive manipulation and sleep deprivation of the preterm newborn can have short-term and long-term consequences on its development. This report aims to highlight the development of competencies related to the promotion of the development of the preterm newborn, with special focus on the safeguarding of sleep, as well as on the provision of nursing care specialized in child and pediatric health. This path of learning and development of competencies was based on a critical-reflexive methodology on and on the actions developed in the different contexts of internship, supported by scientific evidence and the reference framework of Kolcaba's Comfort Theory, Philosophy of Family-Centered Care and Non-Traumatic Care. The main activities are the development of a scoping review on nursing interventions to safeguard the sleep of the preterm newborn, a standard of procedure and training activities in the work context in the context of the theme of safeguarding the sleep of the preterm newborn. It is intended as future projects to contribute to the training of neonatology nurses in my workplace, in the context of neuroprotective care, more specifically on the safeguarding of the sleep of the preterm newborn in the neonatal intensive care unit, as well as to integrate the neonatology working group "Newborn Welfare" aiming at the implementation of the sectoral procedure elaborated during the report. It is also intended later to publish the scoping review developed during the report, in a certified nursing journal.


Assuntos
Humanos , Recém-Nascido , Lactente , Enfermagem Pediátrica , Sono , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Desenvolvimento Infantil , Conforto do Paciente , Privação do Sono , Higiene do Sono
10.
Cell Death Dis ; 9(12): 1166, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518918

RESUMO

Osteoarthritis (OA), a chronic disease characterized by articular cartilage degeneration, is a leading cause of disability and pain worldwide. In OA, chondrocytes in cartilage undergo phenotypic changes and senescence, restricting cartilage regeneration and favouring disease progression. Similar to other wound-healing disorders, chondrocytes from OA patients show a chronic increase in the gap junction channel protein connexin43 (Cx43), which regulates signal transduction through the exchange of elements or recruitment/release of signalling factors. Although immature or stem-like cells are present in cartilage from OA patients, their origin and role in disease progression are unknown. In this study, we found that Cx43 acts as a positive regulator of chondrocyte-mesenchymal transition. Overactive Cx43 largely maintains the immature phenotype by increasing nuclear translocation of Twist-1 and tissue remodelling and proinflammatory agents, such as MMPs and IL-1ß, which in turn cause cellular senescence through upregulation of p53, p16INK4a and NF-κB, contributing to the senescence-associated secretory phenotype (SASP). Downregulation of either Cx43 by CRISPR/Cas9 or Cx43-mediated gap junctional intercellular communication (GJIC) by carbenoxolone treatment triggered rediferentiation of osteoarthritic chondrocytes into a more differentiated state, associated with decreased synthesis of MMPs and proinflammatory factors, and reduced senescence. We have identified causal Cx43-sensitive circuit in chondrocytes that regulates dedifferentiation, redifferentiation and senescence. We propose that chondrocytes undergo chondrocyte-mesenchymal transition where increased Cx43-mediated GJIC during OA facilitates Twist-1 nuclear translocation as a novel mechanism involved in OA progression. These findings support the use of Cx43 as an appropriate therapeutic target to halt OA progression and to promote cartilage regeneration.


Assuntos
Cartilagem Articular/imunologia , Comunicação Celular/genética , Senescência Celular/genética , Condrócitos/imunologia , Conexina 43/genética , Osteoartrite/genética , Adipócitos/efeitos dos fármacos , Adipócitos/imunologia , Adipócitos/patologia , Antígenos CD/genética , Antígenos CD/imunologia , Carbenoxolona/farmacologia , Cartilagem Articular/patologia , Estudos de Casos e Controles , Comunicação Celular/imunologia , Diferenciação Celular , Senescência Celular/imunologia , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Conexina 43/imunologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Inibidor p16 de Quinase Dependente de Ciclina/imunologia , Regulação da Expressão Gênica , Humanos , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/imunologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/patologia , NF-kappa B/genética , NF-kappa B/imunologia , Proteínas Nucleares/genética , Proteínas Nucleares/imunologia , Osteoartrite/imunologia , Osteoartrite/patologia , Cultura Primária de Células , Índice de Gravidade de Doença , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/imunologia , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/imunologia
11.
Biochim Biophys Acta Biomembr ; 1860(12): 2499-2505, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30279151

RESUMO

Cell-to-cell communication between bone, cartilage and the synovial membrane is not fully understood and it is only attributed to the diffusion of substances through the extracellular space or synovial fluid. In this study, we found for the first time that primary bone cells (BCs) including osteocytes, synovial cells (SCs) and chondrocytes (CHs) are able to establish cellular contacts and to couple through gap junction (GJ) channels with connexin43 (Cx43) being dominant. Transwell co-culture and identification by mass spectrometry revealed the exchange of essential amino acids, peptides and proteins including calnexin, calreticulin or CD44 antigen between contacting SCs, BCs and CHs. These results reveal that CHs, SCs and BCs are able to establish intercellular connections and to communicate through GJ channels, which provide a selective signalling route by the direct exchange of potent signalling molecules and metabolites.


Assuntos
Comunicação Celular , Condrócitos/metabolismo , Junções Comunicantes/metabolismo , Osteócitos/metabolismo , Aminoácidos Essenciais/metabolismo , Calnexina/metabolismo , Calreticulina/metabolismo , Células Cultivadas , Técnicas de Cocultura , Conexina 43/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/metabolismo , Transdução de Sinais , Membrana Sinovial/citologia , Membrana Sinovial/metabolismo
12.
World Neurosurg ; 117: e162-e166, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29883825

RESUMO

BACKGROUND: To date, no information about the cortical bone microstructural properties in atlas vertebrae with arcuate foramen has been reported. As a result, we aimed to test in an experimental model if there is a cortical bone thickening in an atlas vertebra which has an arcuate foramen that may play a protective role against bone fracture. METHODS: We analyzed by means of micro-computed tomography the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry atlas vertebrae with arcuate foramen and without arcuate foramen. We also reviewed a case series of 31 posterior atlas arch fractures to correlate the possible presence in the same atlas of both fracture and arcuate foramen. RESULTS: The micro-computed tomography study revealed significant differences in cortical bone thickness (P < 0.001), cortical volume (P < 0.004), and medullary volume (P = 0.013) values between the arcuate foramen vertebrae and the nonarcuate foramen vertebrae. The clinical series found no coexistence in the same vertebra of a posterior atlas arch fractures and the arcuate foramen. CONCLUSIONS: An atlas with arcuate foramen presents cortical bone thickening. This advantage in bone microarchitecture seems to contribute to a lower fracture risk compared to subjects without arcuate foramen as no coexistence in the same vertebra of a posterior atlas arch fractures and arcuate foramen was found.


Assuntos
Atlas Cervical/anatomia & histologia , Osso Cortical/anatomia & histologia , Fraturas da Coluna Vertebral/etiologia , Cadáver , Estudos de Casos e Controles , Atlas Cervical/diagnóstico por imagem , Osso Cortical/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Microtomografia por Raio-X
13.
Forensic Sci Int Genet ; 34: e7-e12, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29588179

RESUMO

Y-specific short tandem repeat (Y-STR) loci display different mutation rates and consequently are suitable for forensic, genealogical, and evolutionary studies that require different levels of timelines and resolution. Recent efforts have focused on implementing Rapidly Mutating (RM) Y-STRs to assess male specific profiles. However, due to their high mutation rate their use in kinship testing or in phylogenetic studies may be less reliable. In the present study, a novel Slowly Mutating Y-STR (SM) panel, including DYS388, DYS426, DYS461 (Y-GATA-A7.2), DYS485, DYS525, and DYS561, has been developed and evaluated in a sample set of 628 unrelated males from different worldwide populations. This panel is reproducible, sensitive, and robust for forensic applications and may be useful in conjunction with the common multiplexes, particularly in exclusion of kinship cases where minimal discrimination is reported employing the rapidly mutating Y-STR systems. Furthermore, SM Y-STR data may be of value in evolutionary studies to optimize the resolution of phylogenetic relationships generated with current Y-STR panel sets. In this study, we provide an extensive Y-STR allele and haplotype reference dataset for future applications.


Assuntos
Cromossomos Humanos Y , Genética Populacional , Repetições de Microssatélites , Taxa de Mutação , Evolução Molecular , Genética Forense , Frequência do Gene , Haplótipos , Humanos , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Grupos Raciais/genética
14.
Ageing Res Rev ; 42: 56-71, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29258883

RESUMO

Ageing processes play a major contributing role for the development of Osteoarthritis (OA). This prototypic degenerative condition of ageing is the most common form of arthritis and is accompanied by a general decline, chronic pain and mobility deficits. The disease is primarily characterized by articular cartilage degradation, followed by subchondral bone thickening, osteophyte formation, synovial inflammation and joint degeneration. In the early stages, osteoarthritic chondrocytes undergo phenotypic changes that increase cell proliferation and cluster formation and enhance the production of matrix-remodelling enzymes. In fact, chondrocytes exhibit differentiation plasticity and undergo phenotypic changes during the healing process. Current studies are focusing on unravelling whether OA is a consequence of an abnormal wound healing response. Recent investigations suggest that alterations in different proteins, such as TGF-ß/BMPs, NF-Kß, Wnt, and Cx43, or SASP factors involved in signalling pathways in wound healing response, could be directly implicated in the initiation of OA. Several findings suggest that osteoarthritic chondrocytes remain in an immature state expressing stemness-associated cell surface markers. In fact, the efficacy of new disease-modifying OA drugs that promote chondrogenic differentiation in animal models indicates that this may be a drug-sensible state. In this review, we highlight the current knowledge regarding cellular plasticity in chondrocytes and OA. A better comprehension of the mechanisms involved in these processes may enable us to understand the molecular pathways that promote abnormal repair and cartilage degradation in OA. This understanding would be advantageous in identifying novel targets and designing therapies to promote effective cartilage repair and successful joint ageing by preventing functional limitations and disability.


Assuntos
Envelhecimento/metabolismo , Cartilagem Articular/fisiologia , Diferenciação Celular/fisiologia , Plasticidade Celular/fisiologia , Osteoartrite/metabolismo , Regeneração/fisiologia , Envelhecimento/patologia , Animais , Cartilagem Articular/patologia , Proliferação de Células/fisiologia , Condrócitos/metabolismo , Condrócitos/patologia , Humanos , Osteoartrite/patologia , Transdução de Sinais/fisiologia
16.
Ann Biomed Eng ; 45(10): 2395-2408, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28639173

RESUMO

Bone fracture pattern prediction is still a challenge and an active field of research. The main goal of this article is to present a combined methodology (experimental and numerical) for femur fracture onset analysis. Experimental work includes the characterization of the mechanical properties and fracture testing on a bone simulant. The numerical work focuses on the development of a model whose material properties are provided by the characterization tests. The fracture location and the early stages of the crack propagation are modelled using the extended finite element method and the model is validated by fracture tests developed in the experimental work. It is shown that the accuracy of the numerical results strongly depends on a proper bone behaviour characterization.


Assuntos
Fraturas do Fêmur/patologia , Fraturas do Fêmur/fisiopatologia , Análise de Elementos Finitos , Modelos Biológicos , Humanos
17.
Electrophoresis ; 38(7): 1016-1021, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27987217

RESUMO

A Y-STR multiplex system has been developed with the purpose of complementing the widely used 17 Y-STR haplotyping (AmpFlSTR Y Filer® PCR Amplification kit) routinely employed in forensic and population genetic studies. This new multiplex system includes six additional STR loci (DYS576, DYS481, DYS549, DYS533, DYS570, and DYS643) to reach the 23 Y-STR of the PowerPlex® Y23 System. In addition, this kit includes the DYS456 and DYS385 loci for traceability purposes. Male samples from 625 individuals from ten worldwide populations were genotyped, including three sample sets from populations previously published with the 17 Y-STR system to expand their current data. Validation studies demonstrated good performance of the panel set in terms of concordance, sensitivity, and stability in the presence of inhibitors and artificially degraded DNA. The results obtained for haplotype diversity and discrimination capacity with this multiplex system were considerably high, providing further evidences of the suitability of this novel Y-STR system for forensic purposes. Thus, the use of this multiplex for samples previously genotyped with 17 Y-STRs will be an efficient and low-cost alternative to complete the set of 23 Y-STRs and improve allele databases for population and forensic purposes.


Assuntos
Cromossomos Humanos Y/genética , Genética Forense/métodos , Repetições de Microssatélites/genética , Reação em Cadeia da Polimerase/métodos , Genética Populacional , Humanos , Masculino , Grupos Raciais/genética
18.
J Bone Miner Res ; 32(5): 1040-1051, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28019683

RESUMO

We present final results of a study comparing teriparatide 20 µg every day (QD) with risedronate 35 mg once per week (QW) started within 2 weeks after surgery for a pertrochanteric hip fracture. Patients with BMD T-score ≤ -2.0 and 25OHD ≥9.2 ng/mL were randomized to receive 26-week double-dummy treatment plus calcium and vitamin D, followed by 52-week open-label treatment with the same assigned active drug. Primary endpoint was change from baseline in lumbar spine (LS) BMD at 78 weeks. Secondary and exploratory endpoints were change in BMD at the proximal femur, function, hip pain (Charnley score and 100 mm Visual Analog Scale [VAS]), quality of life (Short Form-36), radiology outcomes, and safety. Data were analyzed with mixed models for repeated measures (MMRM) and logistic regression. Totally, 224 patients were randomized; 171 (teriparatide: 86) contributed to the efficacy analyses (mean ± SD age: 77 ± 7.7 years, 77% females). Mean baseline LS, femoral neck (FN), and total hip (TH) T-scores were -2.16, -2.63, and -2.51, respectively. At 78 weeks, BMD increased significantly more with teriparatide compared to risedronate at the LS (+11.08% versus +6.45%; p < 0.001) and FN (+1.96% versus -1.19%; p = 0.003), with no significant between-group difference in TH BMD. Timed up-and-go (TUG) test was significantly faster with teriparatide at 6, 12, 18, and 26 weeks (differences: -3.2 to -5.9 s; p = 0.045 for overall difference). Hip pain during TUG test by 100 mm VAS was significantly lower with teriparatide at 18 weeks (adjusted difference: -11.3 mm, p = 0.033; -10.0 and -9.3 mm at 12 and 26 weeks, respectively; p = 0.079 for overall difference). Other secondary and exploratory outcomes were not different. Teriparatide group showed two new hip fractures versus seven with risedronate (p = 0.171) and more frequent hypercalcemia and hyperuricemia. In conclusion, 78-week treatment with teriparatide showed significantly greater increases in LS and FN BMD, less pain, and a faster TUG test versus risedronate. © 2016 American Society for Bone and Mineral Research.


Assuntos
Fraturas do Quadril/tratamento farmacológico , Ácido Risedrônico/administração & dosagem , Teriparatida/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Fraturas do Quadril/sangue , Fraturas do Quadril/patologia , Humanos , Estudos Prospectivos , Ácido Risedrônico/efeitos adversos , Teriparatida/efeitos adversos , Fatores de Tempo
19.
Spine J ; 17(3): 431-434, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27769752

RESUMO

BACKGROUND CONTEXT: To date, no information about the cortical bone microstructural properties in atlas vertebrae with posterior arch defects has been reported. PURPOSE: To test if there is an increased cortical bone thickening in atlases with Type A posterior atlas arch defects in an experimental model. STUDY DESIGN: Micro-computed tomography (CT) study on cadaveric atlas vertebrae. METHODS: We analyzed the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry vertebrae with a Type A atlas arch defect and normal control vertebrae. RESULTS: The micro-CT study revealed significant differences in cortical bone thickness (p=.005), cortical volume (p=.003), and medullary volume (p=.009) values between the normal and the Type A vertebrae. CONCLUSIONS: Type A congenital atlas arch defects present a cortical bone thickening that may play a protective role against atlas fractures.


Assuntos
Atlas Cervical/anormalidades , Atlas Cervical/patologia , Osso Cortical/patologia , Idoso , Cadáver , Osso Cortical/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Microtomografia por Raio-X
20.
Calcif Tissue Int ; 100(1): 29-39, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27738719

RESUMO

The purpose of this study was to estimate the burden of osteoporotic fractures beyond the hospitalization period covering up to the first year after the fracture. This was a prospective, 12-month, observational study including patients aged ≥65 years hospitalized due to a first low-trauma hip fracture, in six Spanish regions. Health resource utilization (HRU), quality of life (QoL) and autonomy were collected and total costs calculated. Four hundred and eighty seven patients (mean ± SD age 83 ± 7 years, 77 % women) were included. Twenty-two percent of patients reported a prior non-hip low-trauma fracture, 16 % were receiving osteoporotic treatment at baseline, and 3 % had densitometry performed (1.8 % T-score ≤-2.5). Sixteen percent of patients died (women 14 %; men 25 %; p = 0.0011) during the first year. Mean hospital stay was 11.8 ± 7.9 days and 95.1 % of patients underwent surgery. Other relevant HRUs were: outpatient visits in 78 % of patients (mean 9.2 ± 9.7); walking aids, 58.7 %; rehabilitation facilities, 35.5 % (28.7 ± 41.2 sessions); and formal and informal home care, 22.2 % (49.6 ± 72.2 days) and 53.4 % (77.1 ± 101.0 h), respectively. Mean direct cost was €9690 (95 % confidence interval: 9184-10,197) in women and €9019 (8079-9958) in men. Main cost drivers were: first hospitalization episode (women €7067 [73 %]; men €7196 [80 %]); outpatient visits (€1323 [14 %]; €997 [11 %]); and home care (€905 [9 %]; €767 [9 %]). QoL and autonomy showed a marked decrease during hospitalization, not entirely recovered at 12 months (p < 0.05 vs. baseline for EQ-5D, Harris hip score and modified Barthel index). In a Spanish setting, osteoporotic hip fractures incur a high societal and economic cost, mainly due to the first hospitalization HRU, but also due to subsequent outpatient visits and home care.


Assuntos
Fraturas do Quadril/terapia , Fraturas por Osteoporose/terapia , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Feminino , Custos de Cuidados de Saúde/estatística & dados numéricos , Fraturas do Quadril/economia , Hospitalização/economia , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Osteoporose/terapia , Fraturas por Osteoporose/economia , Estudos Prospectivos , Espanha
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