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1.
Encephale ; 49(6): 596-605, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36253170

RESUMO

Borderline personality disorder (BPD) is a severe and relatively prevalent psychiatric disorder, responsible for high rates of suicidal behaviors. Disturbed identity appears as at the very core of this disorder, being inter-related with all other BPD features. Notably, from a dimensional perspective on mental disorders, one should realize that it is from our usual self-representation that we live all our daily experiences. Then, if the understanding of self-concept (or identity) is impaired, all the interventions implemented to decrease the self's suffering will subsequently be impaired. The purpose of the present case study was to illustrate the nine identity diffusion categories described by Jørgensen & Bøye (2022) and how the level of identity function can be improved in a third-wave cognitive and behavioral therapy targeting progressive correct self-identification.


Assuntos
Transtorno da Personalidade Borderline , Humanos , Transtorno da Personalidade Borderline/terapia , Transtorno da Personalidade Borderline/psicologia , Terapia Comportamental , Ideação Suicida , Autoimagem
2.
Public Health ; 203: 19-22, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35016071

RESUMO

OBJECTIVES: Many African countries have reported fewer COVID-19 cases than countries elsewhere. By the end of 2020, Guinea-Bissau, West Africa, had <2500 PCR-confirmed cases corresponding to 0.1% of the ∼1.8 million national population. We assessed the prevalence of SARS-CoV-2 antibodies in urban Guinea-Bissau to help guide the pandemic response in Guinea-Bissau. STUDY DESIGN: Cross-sectional assessment of SARS-CoV-2 antibody in a cohort of staff at the Bandim Health Project. METHODS: We measured IgG antibodies using point-of-care rapid tests among 140 staff and associates at a biometric research field station in Bissau, the capital of Guinea-Bissau, during November 2020. RESULTS: Of 140 participants, 25 (18%) were IgG-positive. Among IgG-positives, 12 (48%) reported an episode of illness since the onset of the pandemic. Twenty-five (18%) participants had been PCR-tested between May and September; 7 (28%) had been PCR-positive. Four of these seven tested IgG-negative in the present study. Five participants reported that somebody had died in their house, corresponding crudely to an annual death rate of 4.5/1000 people; no death was attributed to COVID-19. Outdoor workers had a lower prevalence of IgG-positivity. CONCLUSIONS: In spite of the low official number of COVID-19 cases, our serosurvey found a high prevalence of IgG-positivity. Most IgG-positives had not been ill. The official number of PCR-confirmed COVID-19 cases has thus grossly underestimated the prevalence of COVID-19 during the pandemic. The observed overall mortality rate in households of Bandim Health Project employees was not higher than the official Guinean mortality rate of 9.6/1000 people.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Estudos Transversais , Atenção à Saúde , Guiné-Bissau/epidemiologia , Humanos
3.
Nature ; 600(7890): 621-624, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34937892

RESUMO

Magnetars are strongly magnetized, isolated neutron stars1-3 with magnetic fields up to around 1015 gauss, luminosities of approximately 1031-1036 ergs per second and rotation periods of about 0.3-12.0 s. Very energetic giant flares from galactic magnetars (peak luminosities of 1044-1047 ergs per second, lasting approximately 0.1 s) have been detected in hard X-rays and soft γ-rays4, and only one has been detected from outside our galaxy5. During such giant flares, quasi-periodic oscillations (QPOs) with low (less than 150 hertz) and high (greater than 500 hertz) frequencies have been observed6-9, but their statistical significance has been questioned10. High-frequency QPOs have been seen only during the tail phase of the flare9. Here we report the observation of two broad QPOs at approximately 2,132 hertz and 4,250 hertz in the main peak of a giant γ-ray flare11 in the direction of the NGC 253 galaxy12-17, disappearing after 3.5 milliseconds. The flare was detected on 15 April 2020 by the Atmosphere-Space Interactions Monitor instrument18,19 aboard the International Space Station, which was the only instrument that recorded the main burst phase (0.8-3.2 milliseconds) in the full energy range (50 × 103 to 40 × 106 electronvolts) without suffering from saturation effects such as deadtime and pile-up. Along with sudden spectral variations, these extremely high-frequency oscillations in the burst peak are a crucial component that will aid our understanding of magnetar giant flares.


Assuntos
Astros Celestes , Atmosfera
4.
Mater Sci Eng C Mater Biol Appl ; 121: 111800, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33579447

RESUMO

Articular cartilage is made of chondrocytes surrounded by their extracellular matrix that can both sense and respond to various mechanical stimuli. One of the most widely used in vitro model to study cartilage growth is the model of mesenchymal stromal cells-derived cartilage micropellet. However, mechanical stimulation of micropellets has never been reported probably because of their small size and imperfect round shape. The objective of the study was to develop an original custom-made device allowing both the mechanical stimulation and characterization of cartilage micropellets. The fluidic-based device was designed for the concomitant stimulation or characterization of six microspheres placed into the conical wells of a tank. In the present study, the device was validated using alginate-, collagen- and crosslinked collagen-based microspheres. Different types and ranges of pressure signals (square, sinusoidal and constant) were applied. The mechanical properties of microspheres were equivalent to those determined by a conventional compression test. Accuracy, repeatability and reproducibility of all types of pressure signals were demonstrated even though square signals were less accurate and sinusoidal signals were less reproducible than the others. The interest of this new device lies in the reliability to mechanically stimulate and characterize microspheres with diameters in the range of 900 to 1500 µm. Mechanical stimulation can be performed on six microspheres in parallel allowing the mechanical and molecular characterization of the same group of cartilage micropellets. The device will be useful to evaluate the growth of cartilage micropellets under mechanical stimuli.


Assuntos
Cartilagem Articular , Células-Tronco Mesenquimais , Condrócitos , Condrogênese , Microesferas , Reprodutibilidade dos Testes , Engenharia Tecidual
5.
J Affect Disord ; 279: 31-45, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33038698

RESUMO

BACKGROUND: Anxiety symptoms are prevalent in bipolar disorder (BD) even during periods of remission and impede treatment efficacy, prognosis and functional capacity. This highlights a pressing clinical need to identify novel effective anxiety treatments. This systematic review aimed to evaluate the evidence within the field. METHODS: Following PRISMA guidelines, we conducted a systematic search on PubMed, PsycInfo, EMBASE and Cochrane Library for randomised controlled trials (RCTs) targeting anxiety in remitted BD patients. RESULTS: We identified 10 RCTs investigating the effects of psychological or pharmacological treatments on anxiety in remitted BD patients. Two studies of transdiagnostic personalised cognitive behavioural therapy (CBT) found a treatment-related reduction in anxiety. This evidence was preliminary given small sample size and use of self-report measures in a single-blind trial design, respectively. The remaining six psychological intervention trials provided more preliminary evidence due to several methodological challenges. The two pharmacological studies found anxiolytic effects of add-on olanzapine or methylene blue to lithium treatment, respectively. Nevertheless, this evidence should be interpreted with caution given high drop-out rates and substantial side-effects that may have impeded blinding. LIMITATIONS: We did not conduct a quantitative meta-analysis. CONCLUSIONS: There is preliminary evidence for beneficial effects of modified CBT and add-on pharmacotherapy on residual anxiety in BD. Future trials should pre-screen participants for anxiety, define one clinician-rated anxiety measurement as a primary outcome, and employ intention-to-treat analysis to assess treatment effect. This will advance treatment development and enable personalised approaches to address residual anxiety in BD, which has great clinical relevance.


Assuntos
Transtorno Bipolar , Terapia Cognitivo-Comportamental , Ansiedade , Transtornos de Ansiedade/tratamento farmacológico , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Humanos , Resultado do Tratamento
6.
Sci Rep ; 10(1): 11423, 2020 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-32651456

RESUMO

Mesenchymal stem cell (MSC)-based therapy is being increasingly considered a powerful opportunity for several disorders based on MSC immunoregulatory properties. Nonetheless, MSC are versatile and plastic cells that require an efficient control of their features and functions for their optimal use in clinic. Recently, we have shown that PPARß/δ is pivotal for MSC immunoregulatory and therapeutic functions. However, the role of PPARß/δ on MSC metabolic activity and the relevance of PPARß/δ metabolic control on MSC immunosuppressive properties have never been addressed. Here, we demonstrate that PPARß/δ deficiency forces MSC metabolic adaptation increasing their glycolytic activity required for their immunoregulatory functions on Th1 and Th17 cells. Additionally, we show that the inhibition of the mitochondrial production of ATP in MSC expressing PPARß/δ, promotes their metabolic switch towards aerobic glycolysis to stably enhance their immunosuppressive capacities significantly. Altogether, these data demonstrate that PPARß/δ governs the immunoregulatory potential of MSC by dictating their metabolic reprogramming and pave the way for enhancing MSC immunoregulatory properties and counteracting their versatility.


Assuntos
Células-Tronco Mesenquimais/metabolismo , PPAR beta/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Células da Medula Óssea/citologia , Linfócitos T CD4-Positivos/citologia , Proliferação de Células , Inativação Gênica , Glicólise , Terapia de Imunossupressão , Camundongos , Oligomicinas/química , Células Th1/citologia , Células Th17/citologia
7.
Osteoarthritis Cartilage ; 28(10): 1373-1384, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659345

RESUMO

OBJECTIVE: TGFß is a key player in cartilage homeostasis and OA pathology. However, few data are available on the role of TGFß signalling in the different OA phenotypes. Here, we analysed the TGFß pathway by transcriptomic analysis in six mouse models of OA. METHOD: We have brought together seven expert laboratories in OA pathophysiology and, used inter-laboratories standard operating procedures and quality controls to increase experimental reproducibility and decrease bias. As none of the available OA models covers the complexity and heterogeneity of the human disease, we used six different murine models of knee OA: from post-traumatic/mechanical models (meniscectomy (MNX), MNX and hypergravity (HG-MNX), MNX and high fat diet (HF-MNX), MNX and seipin knock-out (SP-MNX)) to aging-related OA and inflammatory OA (collagenase-induced OA (CIOA)). Four controls (MNX-sham, young, SP-sham, CIOA-sham) were added. OsteoArthritis Research Society International (OARSI)-based scoring of femoral condyles and ribonucleic acid (RNA) extraction from tibial plateau samples were done by single operators as well as the transcriptomic analysis of the TGFß family pathway by Custom TaqMan® Array Microfluidic Cards. RESULTS: The transcriptomic analysis revealed specific gene signatures in each of the six models; however, no gene was deregulated in all six OA models. Of interest, we found that the combinatorial Gdf5-Cd36-Ltbp4 signature might discriminate distinct subgroups of OA: Cd36 upregulation is a hallmark of MNX-related OA while Gdf5 and Ltbp4 upregulation is related to MNX-induced OA and CIOA. CONCLUSION: These findings stress the OA animal model heterogeneity and the need of caution when extrapolating results from one model to another.


Assuntos
Antígenos CD36/genética , Modelos Animais de Doenças , Fator 5 de Diferenciação de Crescimento/genética , Proteínas de Ligação a TGF-beta Latente/genética , Camundongos , Osteoartrite/genética , Fator de Crescimento Transformador beta/genética , Animais , Artrite Experimental/genética , Artrite Experimental/metabolismo , Artrite Experimental/fisiopatologia , Colagenases , Dieta Hiperlipídica , Subunidades gama da Proteína de Ligação ao GTP/genética , Perfilação da Expressão Gênica , Hipergravidade , Meniscectomia , Síndrome Metabólica , Camundongos Knockout , Obesidade , Osteoartrite/metabolismo , Osteoartrite/fisiopatologia , Transcriptoma , Fator de Crescimento Transformador beta/metabolismo
8.
Mater Sci Eng C Mater Biol Appl ; 112: 110808, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32409025

RESUMO

The prevalence of diseases that affect the articular cartilage is increasing due to population ageing, but the current treatments are only palliative. One innovative approach to repair cartilage defects is tissue engineering and the use of mesenchymal stem/stromal cells (MSCs). Although the combination of MSCs with biocompatible scaffolds has been extensively investigated, no product is commercially available yet. This could be explained by the lack of mechanical stimulation during in vitro culture and the absence of proper and stable cartilage matrix formation, leading to poor integration after implantation. The objective of the present study was to investigate the biomechanical behaviour of MSC differentiation in micropellets, a well-defined 3D in vitro model of cartilage differentiation and growth, in view of tissue engineering applications. MSC micropellet chondrogenic differentiation was induced by exposure to TGFß3. At different time points during differentiation (35 days of culture), their global mechanical properties were assessed using a very sensitive compression device coupled to an identification procedure based on a finite element parametric model. Micropellets displayed both a non-linear strain-induced stiffening behaviour and a dissipative behaviour that increased from day 14 to day 29, with a maximum instantaneous Young's modulus of 179.9 ± 18.8 kPa. Moreover, chondrocyte gene expression levels were strongly correlated with the observed mechanical properties. This study indicates that cartilage micropellets display the biochemical and biomechanical characteristics required for investigating and recapitulating the different stages of cartilage development.


Assuntos
Diferenciação Celular , Condrogênese , Células-Tronco Mesenquimais/citologia , Idoso de 80 Anos ou mais , Células da Medula Óssea/citologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Condrogênese/efeitos dos fármacos , Módulo de Elasticidade , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Fatores de Transcrição SOX9/metabolismo , Engenharia Tecidual , Fator de Crescimento Transformador beta3/farmacologia
9.
Arch Orthop Trauma Surg ; 139(5): 709-716, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30840128

RESUMO

INTRODUCTION: Limited data exist on patient safety after simultaneous vs staged bilateral total knee arthroplasty (TKA) in matched groups. Hence, the aim of this study was to compare length of stay (LOS), in-hospital complications, 30-day readmissions and mortality after simultaneous and staged bilateral TKA in matched patients. PATIENTS AND METHODS: A retrospective case-control study of prospectively collected data in nine centres from February 2010 to November 2015. Propensity scores (PS) were used to match simultaneous and staged (1-6 months between stages) bilateral TKA patients with prospectively collected patient characteristics from the Lundbeck Foundation Centre for Fast-track THA and TKA Database. 30-day follow-up was acquired from the Danish Patient Registry and patient records. RESULTS: A total of 344 (47.1%) simultaneous and 386 (52.9%) staged bilateral TKA procedures were performed. PS matching was possible in 232 simultaneous and 232 staged bilateral TKA patients. LOS was median 4 days (IQR 3-5) after simultaneous and cumulated 4 days (IQR 4-6) after staged procedures. The in-hospital complication rate was 15.5% after simultaneous vs 7.3% (p = 0.004) after staged procedures. Two cases (0.9%) of venous thromboembolic events were found in each group. Eight patients (3.4%) were re-operated after simultaneous vs one patient (0.4%) after staged bilateral TKA (p = 0.037). The 30-day readmission rate was 8.6% after simultaneous vs 5.6% after staged procedures (p = 0.281). No patients died in either group. CONCLUSIONS: We found no significant differences in 30-day readmission rates and mortality between simultaneous and staged bilateral TKA, but the in-hospital complication rate and re-operation rate was higher after the simultaneous procedure calling for further matched investigations in larger cohorts.


Assuntos
Artroplastia do Joelho/métodos , Protocolos Clínicos/normas , Osteoartrite do Joelho/cirurgia , Assistência Perioperatória/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/mortalidade , Estudos de Casos e Controles , Bases de Dados Factuais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Pontuação de Propensão , Sistema de Registros , Reoperação , Estudos Retrospectivos , Fatores de Tempo
10.
Clin Microbiol Infect ; 25(4): 511.e1-511.e7, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30099133

RESUMO

OBJECTIVES: To examine the effect of a combination of probiotics on the antibody response to pneumococcal and pertussis vaccination in healthy Danish children, aged 8-14 months, at the time of starting day care. Moreover, the cytokine response to lipopolysaccharide of whole blood was assessed. METHODS: A total of 290 children were randomly allocated to receive a combination of Bifidobacterium animalis ssp. lactis and Lactobacillus rhamnosus GG daily for a 6-month intervention period, and blood samples were drawn at the start and end of the study. Specific antibody response towards Streptococcus pneumoniae serotypes and Bordetella pertussis toxin, as well as endotoxin-induced interleukin-6 (IL-6) and interferon-γ (IFN-γ) production in blood were analysed by Luminex and ELISA. RESULTS: There was no significant difference between the average individual changes from baseline to end of study in antibody concentrations for S. pneumoniae for both the probiotics (340.4% ± 11.2%) and the placebo group (382.9% ± 10.4%) (p 0.525), nor for B. pertussis toxin in the two groups (probiotics 190.1% ± 12.6% versus placebo 238.8% ± 1.1%, p 0.340). The average individual change in IL-6 concentration was significantly lower in the probiotics versus the placebo group (2.9% ± 10.3% versus 33.7% ± 9.0%, p 0.024), whereas there was no difference in IFN-γ concentration (0.0% ± 0.2% versus -0.2% ± 0.1%, p 0.279). CONCLUSIONS: The probiotic intervention did not affect the antibody response against S. pneumoniae and B. pertussis toxin in healthy Danish children.


Assuntos
Anticorpos Antibacterianos/sangue , Bordetella pertussis/imunologia , Lipopolissacarídeos/imunologia , Vacina contra Coqueluche/imunologia , Vacinas Pneumocócicas/imunologia , Probióticos/uso terapêutico , Streptococcus pneumoniae/imunologia , Vacinação , Fatores de Virulência de Bordetella/imunologia , Bifidobacterium animalis , Dinamarca , Método Duplo-Cego , Feminino , Humanos , Lactente , Interferon gama/sangue , Interleucina-6/sangue , Lacticaseibacillus rhamnosus , Masculino
11.
J Thromb Haemost ; 17(2): 250-253, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30554482

RESUMO

Venous thromboembolic events remain a concern in total hip and knee arthroplasty. Consequently, several guidelines on thromboprophylaxis have been established. However, despite similarities in methodology for evaluation of evidence, discrepancies in guideline recommendations continue to exist. Furthermore, the results of older randomized clinical trials still have significant influence despite major improvements in perioperative care. In contrast, the results of recent large cohort studies with fewer thromboembolic events are mostly used only for background data. Here we outline some of the differences between the guidelines on thromboprophylaxis from the American College of Chest Physicians, the National Institute for Health and Care Excellence and the American Academy of Orthopedic Surgeons. We discuss differences in the methodology and focus of the guidelines potentially influencing the final recommendations. Future analyses are required, including data from modern care with early mobilization and short length of stay.


Assuntos
Artroplastia de Substituição/efeitos adversos , Fibrinolíticos/administração & dosagem , Guias de Prática Clínica como Assunto , Tromboembolia Venosa/prevenção & controle , Consenso , Esquema de Medicação , Fibrinolíticos/efeitos adversos , Humanos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia
12.
Osteoarthritis Cartilage ; 27(3): 493-503, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30502449

RESUMO

OBJECTIVE: Transforming growth factor-ß (TGFß) is a major regulator of cartilage homeostasis and its deregulation has been associated with osteoarthritis (OA). Deregulation of the TGFß pathway in mesenchymal stem cells (MSCs) has been proposed to be at the onset of OA. Using a secretome analysis, we identified a member of the TGFß family, TGFß-induced protein (TGFßi or ßIGH3), expressed in MSCs and we investigated its function and regulation during OA. DESIGN: Cartilage, bone, synovium, infrapatellar fat pad and bone marrow-MSCs were isolated from patients with OA or healthy subjects. Chondrogenesis of BM-MSCs was induced by TGFß3 in micropellet culture. Expression of TGFßi was quantified by RT-qPCR, ELISA or immunohistochemistry. Role of TGFßi was investigated in gain and loss of function experiments in BM-MSCs and chondrocytes. RESULTS: TGFßi was up-regulated in early stages of chondrogenesis and its knock-down in BM-MSCs resulted in the down-regulation of mature and hypertrophic chondrocyte markers. It likely occurred through the modulation of adhesion molecules including integrin (ITG)ß1, ITGß5 and N-cadherin. We also showed that TGFßi was upregulated in vitro in a model of OA chondrocytes, and its silencing enhanced the hypertrophic marker type X collagen. In addition, TGFßi was up-regulated in bone and cartilage from OA patients while its expression was reduced in BM-MSCs. Similar findings were observed in a murine model of OA. CONCLUSIONS: Our results revealed a dual role of TGFßi during chondrogenesis and pointed its deregulation in OA joint tissues. Modulating TGFßi in BM-MSCs might be of interest in cartilage regenerative medicine.


Assuntos
Condrogênese , Células-Tronco Mesenquimais/metabolismo , Osteoartrite/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Condrócitos/metabolismo , Humanos , Camundongos , Pessoa de Meia-Idade
13.
J Thromb Haemost ; 16(12): 2471-2481, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30303610

RESUMO

Essentials The aim of deep vein thrombosis (DVT) diagnostic work-up is to maximize both safety and efficiency. We explored whether D-dimer is safe and efficient as a stand-alone test to exclude DVT. Our findings suggest it is a safe, efficient and simplified diagnostic strategy. The safety of age-adjusted D-dimer as a stand-alone test requires further investigation. SUMMARY: Background Several strategies for safely excluding deep vein thrombosis (DVT) while limiting the number of imaging tests have been explored. Objectives To determine whether D-dimer testing could safely and efficiently exclude DVT as a stand-alone test, and evaluate its performance as compared with strategies that incorporate the Wells score and age-adjusted D-dimer. Patients/Methods We included consecutive outpatients referred with suspected DVT to the Emergency Department at Østfold Hospital, Norway. STA-Liatest D-Di PLUS D-dimer was analyzed for all patients. Patients with a D-dimer level of ≥ 0.5 µg mL-1 were referred for compression ultrasonography (CUS). In patients with a D-dimer level of < 0.5 µg mL-1 , no further testing was performed and anticoagulation was withheld. Patients were followed for 3 months for venous thromboembolism (VTE). Results Of the 913 included patients, 298 (33%) had a negative D-dimer result. One hundred and seventy-three patients (18.9%) were diagnosed with DVT at baseline. One of 298 patients had DVT despite having a negative D-dimer result, resulting in a failure rate of 0.3% (95% confidence interval [CI] 0.1-1.9%). Adding the modified Wells score would have yielded a failure rate of 0.0% (95% CI 0.0-1.8%) while necessitating 87 more CUS examinations. Age-adjusted D-dimer as a stand-alone test would have necessitated 80 fewer CUS examinations than fixed D-dimer as a stand-alone test, at the cost of a failure rate of 1.6% (95% CI 0.7-3.4%). Conclusions This outcome study shows that a negative high-sensitivity D-dimer result safely excludes DVT in an outpatient population, and necessitates fewer CUS than if used in combination with Wells score. The safety of stand-alone age-adjusted D-dimer needs further assessment in prospective outcome studies.


Assuntos
Análise Química do Sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombose Venosa/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Trombose Venosa/sangue
14.
Eur J Pain ; 2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29676839

RESUMO

BACKGROUND: Persistent or increased long-term opioid consumption has previously been described following total hip- (THA) and knee arthroplasty (TKA). However, detailed information on postoperative analgesic consumption trajectories and risk factors associated with continued need of analgesics in fast-track THA and TKA is sparse. METHODS: This is a descriptive multicentre study in primary unilateral fast-track THA or TKA with prospective data on patient characteristics and information on reimbursement entitled dispensed prescriptions of paracetamol, non-steroidal anti-inflammatory drugs, opioids, anticonvulsants and antidepressants 1 month preoperatively and 1 year postoperatively. Patients were stratified according to preoperative opioid use. Postoperative analgesic consumption trajectories were stratified as increased, decreased or no use compared to the preoperative period. RESULTS: Of 8975 patients (4849 THA/4126 TKA), 33.9% had relevant reimbursed prescriptions 9-12 months postoperatively. Of 2136 (23.8%) patients with preoperative opioid use, 3.4% had unchanged opioid consumption at 9-12 months postoperatively. However, increased opioid consumption after 9-12 months occurred in 17.6 (TKA) and 10.2% (THA) compared to 9.9 and 6.3% in opioid-naive TKA and THA patients, respectively. Increased NSAID and paracetamol use was seen in 11.5 and 12.4% of all patients. Preoperative analgesic use (any), TKA, psychiatric disorder, tobacco abuse, cardiac disease and use of walking aids were associated with increased opioid consumption. CONCLUSION: Continued and increased opioid and other analgesic use occur in a clinically significant proportion of fast-track TKA and THA patients 9-12 months postoperatively, suggesting treatment failure and need for early intervention. Preoperative risk assessment may allow identification of patients in risk of increased postoperative opioid consumption. SIGNIFICANCE: We found a considerable fraction of patients with continued or increased opioid consumption 9-12 months after fast-track THA and TKA. Increase in opioid consumption was more frequent in preoperative opioid users than opioid-naive patients, but a pattern of increased analgesic consumption was present across all analgesics. Our data demonstrate a need for increased focus on long-term analgesic strategies and postoperative follow-up after THA and TKA, especially in preoperative opioid users.

15.
Anim Genet ; 49(2): 110-118, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29441627

RESUMO

Taste receptors (TASRs) and appetite and reward (AR) mechanisms influence eating behaviour, which in turn affects food intake and risk of obesity. In a previous study, we used next generation sequencing to identify potentially functional mutations in TASR and AR genes and found indications for genetic associations between identified variants and growth and fat deposition in a subgroup of animals (n = 38) from the UNIK resource pig population. This population was created for studying obesity and obesity-related diseases. In the present study we validated results from our previous study by investigating genetic associations between 24 selected single nucleotide variants in TASR and AR gene variants and 35 phenotypes describing obesity and metabolism in the entire UNIK population (n = 564). Fifteen variants showed significant association with specific obesity-related phenotypes after Bonferroni correction. Six of the 15 genes, namely SIM1, FOS, TAS2R4, TAS2R9, MCHR2 and LEPR, showed good correlation between known biological function and associated phenotype. We verified a genetic association between potentially functional variants in TASR/AR genes and growth/obesity and conclude that the combination of identification of potentially functional variants by next generation sequencing followed by targeted genotyping and association studies is a powerful and cost-effective approach for increasing the power of genetic association studies.


Assuntos
Apetite , Obesidade/veterinária , Receptores Acoplados a Proteínas G/genética , Sus scrofa/genética , Animais , Comportamento Alimentar , Frequência do Gene , Estudos de Associação Genética/veterinária , Técnicas de Genotipagem/veterinária , Sequenciamento de Nucleotídeos em Larga Escala , Obesidade/genética , Fenótipo , Polimorfismo de Nucleotídeo Único
16.
Endocr Connect ; 7(2): 334-346, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29362228

RESUMO

BACKGROUND: Several chemical UV filters/absorbers ('UV filters' hereafter) have endocrine-disrupting properties in vitro and in vivo. Exposure to these chemicals, especially during prenatal development, is of concern. OBJECTIVES: To examine maternal exposure to UV filters, associations with maternal thyroid hormone, with growth factor concentrations as well as to birth outcomes. METHODS: Prospective study of 183 pregnant women with 2nd trimester serum and urine samples available. Maternal concentrations of the chemical UV filters benzophenone-1 (BP-1) and benzophenone-3 (BP-3) in urine and 4-hydroxy-benzophenone (4-HBP) in serum were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relationships between 2nd trimester maternal concentrations of the three chemical UV filters and maternal serum concentrations of thyroid hormones and growth factors, as well as birth outcomes (weight, height, and head and abdominal circumferences) were examined. RESULTS: Positive associations between maternal serum concentrations of 4-HBP and triiodothyronine (T3), thyroxine (T4), insulin-like growth factor I (IGF-I) and its binding protein IGFBP3 were observed in mothers carrying male fetuses. Male infants of mothers in the middle 4-HBP exposure group had statistically significantly lower weight and shorter head and abdominal circumferences at birth compared to the low exposure group. CONCLUSIONS: Widespread exposure of pregnant women to chemical UV filters and the possible impact on maternal thyroid hormones and growth factors, and on fetal growth, calls for further studies on possible long-term consequences of the exposure to UV filters on fetal development and children's health.

17.
J Eur Acad Dermatol Venereol ; 32(1): 79-85, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28796916

RESUMO

BACKGROUND: More than 25% of the adult European population suffers from contact allergy, with fragrance substances recognized as one of the main causes. Since 2005, 26 fragrance contact allergens have been mandatory to label in cosmetic products within the EU if present at 10 ppm or above in leave-on and 100 ppm or above in wash-off cosmetics. OBJECTIVE: To examine exposure, based on ingredient labelling, to the 26 fragrances in a sample of 5588 fragranced cosmetic products. METHODS: The investigated products were identified through a novel, non-profit smartphone application (app), designed to provide information to consumers about chemical substances in cosmetic products. Products registered through the app between December 2015 and October 2016 were label checked according to International Nomenclature of Cosmetic Ingredients (INCI) for the presence of the 26 fragrance substances or the wording 'fragrance/parfum/aroma'. RESULTS: The largest product categories investigated were 'cream, lotion and oil' (n = 1192), 'shampoo and conditioner' (n = 968) and 'deodorants' (n = 632). Among cosmetic products labelled to contain at least one of the 26 fragrances, 85.5% and 73.9% contained at least two and at least three of the 26 fragrances, respectively. Linalool (49.5%) and limonene (48.5%) were labelled most often among all investigated products. Hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC/Lyral® ) was found in 13.5% of deodorants. Six of the 26 fragrance substances were labelled on less than one per cent of all products, including the natural extracts Evernia furfuracea (tree moss) and Evernia prunastri (oak moss). A total of 329 (5.9%) products had one or more of the 26 fragrance substances labelled but did not have 'parfum/fragrance/aroma' listed on the label. CONCLUSIONS: Consumers are widely exposed to, often multiple, well-established fragrance contact allergens through various cosmetic products intended for daily use. Several fragrance substances that are common causes of contact allergy were rarely labelled in this large sample of cosmetic products.


Assuntos
Desodorantes/química , Dermatite Alérgica de Contato/etiologia , Preparações para Cabelo/química , Aplicativos Móveis , Perfumes/análise , Creme para a Pele/química , Monoterpenos Acíclicos , Aldeídos/análise , Cicloexenos/análise , Humanos , Limoneno , Monoterpenos/análise , Perfumes/efeitos adversos , Extratos Vegetais/análise , Smartphone , Terpenos/análise
18.
Environ Int ; 110: 51-60, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29100749

RESUMO

BACKGROUND: Previous studies have demonstrated widespread exposure of humans to certain benzophenones commonly used as UV filters or UV absorbers; some of which have been demonstrated to have endocrine disrupting abilities. OBJECTIVES: To examine whether benzophenones present in pregnant women pass through the placental barrier to amniotic fluid and further to the fetal blood circulation. METHODS: A prospective study of 200 pregnant women with simultaneously collected paired samples of amniotic fluid and maternal serum and urine. In addition, unique samples of human fetal blood (n=4) obtained during cordocentesis: and cord blood (n=23) obtained at delivery, both with paired maternal samples of serum and urine collected simultaneously, were used. All biological samples were analyzed by TurboFlow-liquid chromatography - tandem mass spectrometry for seven different benzophenones. RESULTS: Benzophenone-1 (BP-1), benzophenone-3 (BP-3), 4-methyl-benzophenone (4-MBP), and 4-hydroxy-benzophenone (4-HBP) were all detectable in amniotic fluid and cord blood samples and except 4-HBP also in fetal blood; albeit at a low frequency. BP-1 and BP-3 were measured at ~10-times lower concentrations in fetal and cord blood compared to maternal serum and 1000-times lower concentration compared to maternal urine levels. Therefore BP-1 and BP-3 were only detectable in the fetal circulation in cases of high maternal exposure indicating some protection by the placental barrier. 4-MBP seems to pass into fetal and cord blood more freely with a median 1:3 ratio between cord blood and maternal serum levels. Only for BP-3, which the women seemed to be most exposed to, did the measured concentrations in maternal urine and serum correlate to concentrations measured in amniotic fluid. Thus, for BP-3, but not for the other tested benzophenones, maternal urinary levels seem to be a valid proxy for fetal exposure. CONCLUSIONS: Detectable levels of several of the investigated benzophenones in human amniotic fluid as well as in fetal and cord blood calls for further investigations of the toxicokinetic and potential endocrine disrupting properties of these compounds in order for better assessment of the risk to the developing fetus.


Assuntos
Benzofenonas/sangue , Exposição Materna/efeitos adversos , Protetores Solares/toxicidade , Adulto , Líquido Amniótico/química , Benzofenonas/urina , Cromatografia Líquida , Feminino , Sangue Fetal/química , Humanos , Gravidez , Estudos Prospectivos
19.
Br J Anaesth ; 119(2): 267-275, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28854533

RESUMO

Background: Preoperative single high-dose glucocorticoid may have early outcome benefits in total hip arthroplasty (THA) and knee arthroplasty (TKA), but long-term safety aspects have not been evaluated. Methods: From October 2013, the departments reporting to the prospective Lundbeck Foundation Database for Fast-track Hip and Knee Replacement introduced preoperative methylprednisolone (MP) 125 mg as part of a multimodal analgesic protocol in TKA. We analysed the risk of length of hospital stay (LOS) >4 days, 30 and 90 day readmissions in patients with MP vs patients having TKA before the use of MP and adjusted for comorbidity and place of surgery. An unadjusted comparison was specifically done to evaluate deep prosthetic infections. Results: Of a total of 3927 TKA procedures, 1442 received MP. Median LOS was 2 days in both groups, but the fraction with LOS >4 days was 6.0% vs 11.5% (P<0.001) in patients with MP vs those without, and with a reduced risk of LOS >4 days in adjusted analysis [odds ratio (OR) 0.51; confidence interval (CI) 0.39-0.68; P <0.001]. Readmission rates were 5.6% (CI 4.5-6.9) vs 4.4% ( P =0.095) and 7.8% vs 7.3% ( P =0.53) at 30 and 90 days with and without MP, respectively. Conclusions: In this detailed prospective cohort study, preoperative high-dose glucocorticoid administration was not associated with LOS >4 days, readmissions or infectious complications in TKA patients without contraindications.


Assuntos
Artroplastia do Joelho/efeitos adversos , Glucocorticoides/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Segurança do Paciente , Complicações Pós-Operatórias/epidemiologia , Estudos Prospectivos
20.
Water Sci Technol ; 76(5-6): 1474-1489, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28953474

RESUMO

SWINGS was a cooperation project between the European Union and India, aiming at implementing state of the art low-cost technologies for the treatment and reuse of domestic wastewater in rural areas of India. The largest wastewater treatment plant consists of a high-rate anaerobic system, followed by vertical and horizontal subsurface flow constructed wetlands with a treatment area of around 1,900 m2 and a final step consisting of solar-driven anodic oxidation (AO) and ultraviolet (UV) disinfection units allowing direct reuse of the treated water. The implementation and operation of two pilot plants in north (Aligarh Muslim University, AMU) and central India (Indira Gandhi National Tribal University, IGNTU) are shown in this study. The overall performance of AMU pilot plant during the first 7 months of operation showed organic matter removal efficiencies of 87% total suspended solids, 95% 5-day biological oxygen demand (BOD5) and 90% chemical oxygen demand, while Kjeldahl nitrogen removal reached 89%. The UV disinfection unit produces water for irrigation and toilet flushing with pathogenic indicator bacteria well below WHO guidelines. On the other hand, the AO disinfection unit implemented at IGNTU and operated for almost a year has been shown to produce an effluent of sufficient quality to be reused by the local population for agriculture and irrigation.


Assuntos
Conservação dos Recursos Naturais/métodos , Desinfecção , Luz Solar , Águas Residuárias/microbiologia , Purificação da Água/métodos , Áreas Alagadas , Agricultura , Análise da Demanda Biológica de Oxigênio , Índia , Nitrogênio/análise , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Microbiologia da Água , Poluentes Químicos da Água
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