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1.
J Dairy Sci ; 100(11): 9285-9293, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28918145

RESUMO

The objectives of this study were to (1) compare a test for serum measurement of total Ca (tCa), Mg, and P (VetTest Chemistry Analyzer, IDEXX Laboratories Inc., Westbrook, ME) to reference methods (spectrophotometric assays on a Beckman Coulter 640e automated clinical chemistry analyzer; Beckman Coulter, Brea, CA), (2) determine the relationship between ionized Ca (iCa) and reference method tCa in the immediate postpartum period, and (3) assess the relative value of these blood Ca indices as predictors of neutrophil oxidative burst activity. Samples were collected from multiparous Holstein cows (n = 33) over the first 5 d in milk. A total of 183 samples for objective 1 and 181 samples for objective 2 were available. Neutrophil oxidative burst activity was assessed once between 2 and 5 d in milk (n = 29). Linear regression demonstrated strong relationships between serum tCa, Mg, and P concentrations measured by the VetTest compared with the reference method. Bland Altman analysis indicated that the VetTest values were higher than the reference method by 0.22 mmol/L for tCa, 0.12 mmol/L for Mg, and 0.16 mmol/L for P. Compared with hypocalcemia categorized at ≤2.0 or ≤2.125 mmol/L with the reference method tCa, thresholds for the VetTest measured tCa of ≤2.23 mmol/L (sensitivity = 87%, specificity = 89%) or ≤2.30 mmol/L (sensitivity = 86%, specificity = 96%) could be used. The relationship between whole-blood iCa and reference method serum tCa differed by sampling time point after calving. Compared with identification of hypocalcemia with serum tCa measurements from the reference method (thresholds of ≤2.0 and 2.125 mmol/L), a whole-blood iCa threshold of ≤1.17 mmol/L resulted in the highest combined sensitivities (94 and 82%) and specificities (80 and 94%) at either threshold. Ionized Ca measurements were more consistently related to outcomes of neutrophil oxidative burst activity measured in vitro. The VetTest measurements of serum tCa reliably identified hypocalcemia when thresholds were adjusted to account for the bias of the test. The variation in the relationship between iCa and reference method tCa in the days following parturition suggest that these measures cannot be used interchangeably as indicators of Ca status. The more consistent associations between iCa and in vitro measures of neutrophil function, compared with tCa, indicated that this may be a more sensitive predictor of functional outcomes associated with postpartum Ca status.


Assuntos
Cálcio/sangue , Doenças dos Bovinos/metabolismo , Eletrólitos/sangue , Hipocalcemia/veterinária , Leite , Explosão Respiratória/fisiologia , Animais , Bovinos , Feminino , Hipocalcemia/metabolismo , Neutrófilos/fisiologia , Parto , Período Pós-Parto , Sensibilidade e Especificidade
2.
Herz ; 40 Suppl 2: 110-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24848864

RESUMO

The rising number of implantable devices has led to an increase in device-related workload, e.g., regular interrogation follow-up visits. Telemonitoring systems for implantable cardioverter-defibrillators (ICDs) seem to be a promising tool for reducing workload and costs, and they have the potential of optimizing patient care. However, issues such as practical functionality of ICD telemonitoring in daily routine may affect its broad implementation. The objective of this study was to evaluate potential problems during the implementation of a telemonitoring system, Medtronic CareLink™ (CL™) with respect to the installation and data transmission process. A total of 159 patients with ICDs who were equipped with the CL™ system were evaluated and followed up for 16 months regarding the success rate of the first data transmission via the telemonitoring system. In this cohort, a high rate of nontransmission of 23.9 % was observed after the 16-month follow-up. A detailed interview of these patients (no transmission) revealed that the main reasons for failed transmissions were due to the patients' loss of interest in the concept (approximately 50 %) as well as technical problems (approximately 25 %) with setting up the system. These results indicate that telemonitoring systems bear potential problems and that the evaluation of patient motivation and technical support options seems to play an important role in establishing the functionality of these systems.


Assuntos
Desfibriladores Implantáveis/estatística & dados numéricos , Análise de Falha de Equipamento/estatística & dados numéricos , Insuficiência Cardíaca/prevenção & controle , Cooperação do Paciente/estatística & dados numéricos , Consulta Remota/estatística & dados numéricos , Tecnologia de Sensoriamento Remoto/estatística & dados numéricos , Falha de Equipamento , Análise de Falha de Equipamento/métodos , Feminino , Alemanha/epidemiologia , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial/estatística & dados numéricos
3.
Perfusion ; 30(1): 17-23, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24919405

RESUMO

AIM: The aim of this study was to examine the hydrodynamic performance and gaseous microemboli (GME) activity of two centrifugal pumps for possible use in low-flow extracorporeal CO2 removal. MATERIALS & METHODS: The performance of a Rotassist 2.8 and a Rotaflow 32 centrifugal pump (Maquet Cardiopulmonary AG, Hirrlingen, Germany) was evaluated in a water-glycerine mixture-filled in vitro circuit that enabled measurement of pressures and GME at the pump inlet and pump outlet. Pressure-flow curves were acquired in a 1,000 to 5,000 rpm range while increasing drainage resistance in one series and outlet resistance in another. RESULTS: Respective minimum pump inlet and maximum pump outlet pressures were -539 mmHg and 754 mmHg for the Rotassist 2.8 and -606 mmHg and 806 mmHg for the Rotaflow 32. Maximum standard deviations on pump pressures and flow amounted to 3.0 mmHg and 0.03 L/min, respectively, regardless of pump type and drainage or outlet resistance. The GME at the pump outlet were detectable at pump inlet pressures below -156 mmHg at 0.2 L/min and 2,500 rpm for the Rotassist 2.8 and below -224 mmHg at 0.9 L/min and 3,000 rpm for the Rotaflow 32. CONCLUSION: Both the Rotassist 2.8 and Rotaflow 32 centrifugal pumps show a comparably high hydrodynamic stability, but potential GME formation with decreasing pump inlet pressures should be taken into account to ensure safe centrifugal pump-based low-flow extracorporeal CO2 removal.


Assuntos
Dióxido de Carbono/sangue , Ponte Cardiopulmonar/instrumentação , Centrifugação/instrumentação , Circulação Extracorpórea/métodos , Gases/sangue , Gases/isolamento & purificação , Circulação Extracorpórea/instrumentação , Humanos , Hidrodinâmica , Bombas de Infusão , Pressão , Segurança
4.
J Obstet Gynaecol ; 34(6): 479-81, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24786586

RESUMO

To describe the obstetric outcome in women at ages ≥ 45. A retrospective cohort study on a large existing database covering all deliveries in the Flanders region, Belgium, was performed, comparing obstetric outcomes at age 25, 35, 40 and 45 or older, for the period 2005-2010. In the period studied, 421 women gave birth at maternal age ≥ 45 vs 3,405, 15,206, 22,586 at ages 40, 35 and 25, respectively. With advancing maternal age, a significant linear increase for low birth weight (< 2,500 g) and preterm delivery (< 37, < 35 weeks and < 29 weeks), maternal hypertension and diabetes, both primary and secondary caesarean section, was noted. Between ages 40 and ≥ 45, both fetal and early neonatal death demonstrated a significant rise from 4.9/1,000 and 1.8/1,000 to 26/1,000 and 9.5/1,000, respectively. With advancing maternal age, a gradual but not statistically significant decline in the proportion of male fetuses was noted, from 51.6% at 25, to 47.2% in the oldest group. Multivariate analysis confirmed advanced maternal age to be a significant factor in low birth weight, preterm delivery, hypertension, diabetes, caesarean section and perinatal mortality. In Flanders, mothers at age 45 and older have a significantly increased risk for low birth weight, preterm delivery, hypertension, diabetes, caesarean section and perinatal mortality.


Assuntos
Idade Materna , Complicações na Gravidez/epidemiologia , Adulto , Bélgica/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Pré-Menopausa , Estudos Retrospectivos , Razão de Masculinidade
5.
Thromb Res ; 228: 21-32, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37267671

RESUMO

BACKGROUND: Idarucizumab has been approved to reverse the anticoagulant effect of dabigatran. However, there is little knowledge of the effectiveness and safety of idarucizumab in daily practice. AIMS: This systematic review and meta-analysis aims to evaluate the use, effectiveness and outcomes of idarucizumab. METHODS: A systematic literature search was performed up to September 8th 2022. Original studies including patients prescribed idarucizumab, evaluating prescription indications, prescription appropriateness, haemostatic efficacy and/or the occurrence of adverse events were eligible. Case-reports and studies performed in patients ≤18 years or in healthy volunteers were excluded. Study selection and data extraction were performed by two independent reviewers. Pooled estimates were calculated using the random-effects model, after Freeman-Tukey double-arcsine transformation. RESULTS: Thirty studies comprising 3602 patients were included. Idarucizumab was prescribed for bleeding (63.1 %, 95%CI 57.0 %-69.0 %), invasive procedures (30.5 %, 95%CI: 24.1 %-37.2 %), to enable thrombolysis (range: 2.0 %-27.3 %), dabigatran intoxication without bleeding (range: 3.6 %-7.0 %) or unspecified reasons (range: 0.4 %-18.8 %). Overall, 2.8 % (95%CI 0.5 %-6.2 %) of prescription indications were reported to be inappropriate upon post-hoc evaluation. Hemostatic effectiveness was achieved in 77.7 % (95%CI 66.7 %-87.2 %) and peri-procedural haemostasis was normal in 98.5 % (95%CI 86.6 %-100 %) of patients. The pooled incidences of all-cause mortality and thromboembolic events at any follow-up duration were 13.6 % (95%CI 9.6 %-17.9 %) and 2.0 % (95%CI 0.8 %-3.4 %), respectively. CONCLUSION: Idarucizumab was mainly prescribed in the setting of bleeding. The reported hemostatic effectiveness was good, especially perioperatively, and the incidence of thromboembolic events was low. Patients with dabigatran-associated bleeding or requiring an urgent procedure nonetheless face a high mortality risk.


Assuntos
Hemostáticos , Tromboembolia , Humanos , Dabigatrana/efeitos adversos , Antitrombinas/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico
6.
Thromb Res ; 228: 54-60, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37276718

RESUMO

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.


Assuntos
Fibrinolíticos , Neoplasias , Humanos , Fibrinolíticos/uso terapêutico , Qualidade de Vida , Neoplasias/tratamento farmacológico , Cuidados Paliativos , Morte , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Int J Obes (Lond) ; 36(10): 1346-52, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22234280

RESUMO

CONTEXT: Epidemiologically, an inverse relationship between body mass index (BMI) and sleep duration is observed. Intra-individual variance in the amount of slow wave sleep (SWS) or rapid eye movement (REM) sleep has been related to variance of metabolic and endocrine parameters, which are risk factors for the disturbance of energy balance (EB). OBJECTIVE: To investigate inter-individual relationships between EB (EB= energy intake-energy expenditure∣, MJ/24 h), SWS or REM sleep, and relevant parameters in normal-weight men during two 48 h stays in the controlled environment of a respiration chamber. SUBJECTS AND METHODS: A total of 16 men (age 23±3.7 years, BMI 23.9±1.9 kg m(-2)) stayed in the respiration chamber twice for 48 h to assure EB. Electroencephalography was used to monitor sleep (2330-0730 hrs). Hunger and fullness were scored by visual analog scales; mood was determined by State Trait Anxiety Index-state and food reward by liking and wanting. Baseline blood and salivary samples were collected before breakfast. Subjects were fed in EB, except for the last dinner, when energy intake was ad libitum. RESULTS: The subjects slept on average 441.8±49 min per night, and showed high within-subject reliability for the amount of SWS and REM sleep. Linear regression analyses showed that EB was inversely related to the amount of SWS (r=-0.43, P<0.03), and positively related to the amount of REM sleep (r=0.40, P<0.05). Relevant parameters such as hunger, reward, stress and orexigenic hormone concentrations were related to overeating, as well as to the amount of SWS and REM sleep, however, after inclusion of these parameters in a multiple regression, the amount of SWS and REM sleep did not add to the explained variance of EB, which suggests that due to their individual associations, these EB parameters are mediator variables. CONCLUSION: A positive EB due to overeating, was explained by a smaller amount of SWS and higher amount of REM sleep, mediated by hunger, fullness, State Trait Anxiety Index-state scores, glucose/insulin ratio, and ghrelin and cortisol concentrations.


Assuntos
Ansiedade/metabolismo , Ingestão de Energia , Metabolismo Energético , Fome , Hidrocortisona/metabolismo , Hiperfagia/metabolismo , Fases do Sono , Sono REM , Adolescente , Adulto , Análise de Variância , Índice de Massa Corporal , Comportamento de Escolha , Eletroencefalografia , Humanos , Masculino , Consumo de Oxigênio , Saciação , Fases do Sono/fisiologia , Adulto Jovem
8.
Clin Exp Obstet Gynecol ; 39(3): 307-9, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23157030

RESUMO

PURPOSE: To evaluate cardiotocography (CTG) alone versus CTG and ST-analysis (STAN) in daily obstetric practice in a complete region. METHODS: Prospective registration in the region of Flanders in combination with standard registration of perinatal outcome. RESULTS: Of 62,606 term deliveries registered, 57,141 (91.3%) were available for complete analysis. In 50,748 (88.8%) CTG alone and in 6,393 (11.6%) CTG+STAN was used. STAN was used significantly more in case of hypertension, diabetes and induction of labour and was associated both in univariate and multivariate analysis with significantly more secondary caesarean section for suspected foetal distress, instrumental vaginal delivery, low Apgar score and need for neonatal intensive care. There was no difference in perinatal death or asphyxia. CONCLUSION: ST-analysis versus CTG results in more caesarean sections, instrumental vaginal deliveries and neonatal intensive care. This can not be explained solely by its use in more complicated cases as in multivariate analysis including hypertension, diabetes and induction of labour ST analysis persists as a significant factor. We hypothesise that this could be explained by less well trained users not adhering to STAN-guidelines.


Assuntos
Monitorização Fetal/métodos , Monitorização Fetal/estatística & dados numéricos , Trabalho de Parto , Bélgica , Cardiotocografia , Feminino , Humanos , Hipertensão , Trabalho de Parto Induzido , Gravidez , Complicações na Gravidez , Resultado da Gravidez , Gravidez em Diabéticas , Estudos Prospectivos
9.
Internist (Berl) ; 53(2): 218-22, 2012 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-22002765

RESUMO

A 22-year-old athlete with nocturnal asymptomatic episodes of transient sinus arrest/sinoatrial block up to 7.3 s and recurrent inappropriate sinus tachycardias which had been incidentally found during Holter electrocardiography diagnostics is presented. In spite of extensive diagnostic work-up including invasive procedures like coronary angiography and electrophysiological study, no causal etiology was found. Based on the normal findings and the lack of symptoms, we decided not to implant a permanent pacemaker. After 14 months, the patient is still asymptomatic. Howerver, the 24-h Holter electrocardiography shows unchanged frequency of nocturnal transient sinus arrest episodes.


Assuntos
Eletrocardiografia Ambulatorial/métodos , Bloqueio Sinoatrial/classificação , Bloqueio Sinoatrial/diagnóstico , Adulto , Diagnóstico Diferencial , Humanos , Masculino
10.
Genes Immun ; 12(4): 310-3, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21293384

RESUMO

Mortality of pups at 8-12 weeks of age was frequently observed in Frisian Water Dogs. Blood parameters and clinical signs of newborns from three litters were monitored. Three pups from two litters showed strongly reduced levels of immunoglobulins and lymphocytes. These dogs were euthanized after first display of disease. Concurrent clinical and pathological features were consistent with a diagnosis of severe combined immunodeficiency (SCID). Defective V(D)J recombination is one of the causes of SCID in humans and animals. Eight genes involved in V(D)J recombination were investigated by segregation analysis of closely located microsatellite markers and by DNA sequence analysis. A nonsense mutation in the gene coding for V(D)J recombination factor RAG1 was identified in DNA from the cases at a position similar to that of nonsense mutations found in human SCID. It was concluded that SCID due to a mutation of RAG1 led to the high mortality.


Assuntos
Cães/genética , Proteínas de Homeodomínio/genética , Mutação , Imunodeficiência Combinada Severa/genética , Animais , Sequência de Bases , Cães/imunologia , Feminino , Masculino , Linhagem , Imunodeficiência Combinada Severa/imunologia
11.
Psychol Med ; 40(5): 807-14, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19691872

RESUMO

BACKGROUND: Individual symptoms of post-myocardial infarction (MI) depression may be differentially associated with cardiac prognosis, in which somatic/affective symptoms appear to be associated with a worse cardiovascular prognosis than cognitive/affective symptoms. These findings hold important implications for treatment but need to be replicated before conclusions regarding treatment can be drawn. We therefore examined the relationship between depressive symptom dimensions following MI and both disease severity and prospective cardiac prognosis. METHOD: Patients (n=473) were assessed on demographic and clinical variables and completed the Beck Depression Inventory (BDI) within the first week of hospital admission for acute MI. Depressive symptom dimensions were associated with baseline left ventricular ejection fraction (LVEF) and prospective cardiac death and/or recurrent MI. The average follow-up period was 2.8 years. RESULTS: Factor analysis revealed two symptom dimensions--somatic/affective and cognitive/affective--in the underlying structure of the BDI, identical to previous results. There were 49 events attributable to cardiac death (n=23) or recurrent MI (n=26). Somatic/affective (p=0.010) but not cognitive/affective (p=0.153) symptoms were associated with LVEF and cardiac death/recurrent MI. When controlling for the effects of previous MI and LVEF, somatic/affective symptoms remained significantly predictive of cardiac death/recurrent MI (hazard ratio 1.31, 95% confidence interval 1.02-1.69, p=0.038). Previous MI was also an independent predictor of cardiac death/recurrent MI. CONCLUSIONS: We confirmed that somatic/affective, rather than cognitive/affective, symptoms of depression are associated with MI severity and cardiovascular prognosis. Interventions to improve cardiovascular prognosis by treating depression should be targeted at somatic aspects of depression.


Assuntos
Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Infarto do Miocárdio/psicologia , Papel do Doente , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Países Baixos , Inventário de Personalidade/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Psicometria/estatística & dados numéricos , Recidiva , Reprodutibilidade dos Testes , Fatores de Risco , Transtornos Somatoformes/diagnóstico , Transtornos Somatoformes/psicologia , Taxa de Sobrevida , Disfunção Ventricular Esquerda/psicologia
12.
J Pregnancy ; 2020: 2793296, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33274077

RESUMO

PURPOSE: As the rate of cesarean sections (CS) continues to rise in Flanders (northern part of Belgium), it is important to understand the reasons behind this evolution and to find ways to achieve appropriate CS rates. For this analysis, we categorized CS changes between 1992 and 2016, applying the Robson 10-Group Classification System (TGCS). We also applied the TGCS to analyze the information of the only clinics where between 2008 and 2016, the absolute CS rate had fallen by more than two percent. METHODS: This paper is based on a population-based cross-sectional study. Robson's TGCS was used to analyze CS rates for the years 1992, 2000, 2008, and 2016, using the Flemish population-based birth register. RESULTS: Between 1992 and 2016, the overall CS rate increased from 11.8% in 1992 to 20.9% in 2016. The major contributors to that increase were (a) single, cephalic nulliparous women, at term in spontaneous labor (Robson group 1); (b) single, cephalic nulliparous women, at term in induced labor or CS before labor (group 2); and (c) multiparous women with single cephalic at term pregnancy with history of CS (group 5). In the subgroup of the seven clinics where the collective CS rate had decreased from 23.2% in 2008 to 19.3% in 2016, the main contributors to this decrease were Robson groups 1 and 2. CONCLUSIONS: The CS increase in Flanders between 1992 and 2016 is mainly the result of the absolute CS increase in the childbirth of nulliparous women with a single cephalic baby at term in spontaneous or induced labor and in women with a single cephalic presentation at term and a previous CS. Further research in these aforementioned groups is needed to identify the real reasons for the CS increase.


Assuntos
Cesárea/estatística & dados numéricos , Adulto , Bélgica/epidemiologia , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Trabalho de Parto , Paridade , Gravidez , Fatores de Tempo
13.
Benef Microbes ; 11(2): 101-129, 2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32073295

RESUMO

The inherent and diverse capacity of dietary fibres, nondigestible oligosaccharides (NDOs) and prebiotics to modify the gut microbiota and markedly influence health status of the host has attracted rising interest. Research and collective initiatives to determine the composition and diversity of the human gut microbiota have increased over the past decade due to great advances in high-throughput technologies, particularly the 16S ribosomal RNA (rRNA) sequencing. Here we reviewed the application of 16S rRNA-based molecular technologies, both community wide (sequencing and phylogenetic microarrays) and targeted methodologies (quantitative PCR, fluorescent in situ hybridisation) to study the effect of chicory inulin-type fructans, NDOs and specific added fibres, such as resistant starches, on the human intestinal microbiota. Overall, such technologies facilitated the monitoring of microbiota shifts due to prebiotic/fibre consumption, though there are limited community-wide sequencing studies so far. Molecular studies confirmed the selective bifidogenic effect of fructans and galactooligosaccharides (GOS) in human intervention studies. Fructans only occasionally decreased relative abundance of Bacteroidetes or stimulated other groups. The sequencing studies for various resistant starches, polydextrose and beta-glucan showed broader effects with more and different types of gut microbial species being enhanced, often including phylotypes of Ruminococcaceae. There was substantial variation in terms of magnitude of response and in individual responses to a specific fibre or NDO which may be due to numerous factors, such as initial presence and relative abundance of a microbial type, diet, genetics of the host, and intervention parameters, such as intervention duration and fibre dose. The field will clearly benefit from a more systematic approach that will support defining the impact of prebiotics and fibres on the gut microbiome, identify biomarkers that link gut microbes to health, and address the personalised response of an individual's microbiota to prebiotics and dietary fibres.


Assuntos
Dieta , Fibras na Dieta , Frutanos , Microbioma Gastrointestinal/genética , Prebióticos , Fezes/microbiologia , Humanos , Filogenia , RNA Ribossômico 16S/genética
14.
Ultrasound Med Biol ; 46(2): 445-454, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31780240

RESUMO

Ultrasound guidance is not in widespread use in prostate cancer radiotherapy workflows. This can be partially attributed to the need for image interpretation by a trained operator during ultrasound image acquisition. In this work, a one-class regressor, based on DenseNet and Gaussian processes, was implemented to automatically assess the quality of transperineal ultrasound images of the male pelvic region. The implemented deep learning approach was tested on 300 transperineal ultrasound images and it achieved a scoring accuracy of 94%, a specificity of 95% and a sensitivity of 92% with respect to the majority vote of 3 experts, which was comparable with the results of these experts. This is the first step toward a fully automatic workflow, which could potentially remove the need for ultrasound image interpretation and make real-time volumetric organ tracking in the radiotherapy environment using ultrasound more appealing.


Assuntos
Aprendizado Profundo , Pelve/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Períneo , Ultrassonografia/métodos , Ultrassonografia/normas
15.
Nat Med ; 26(2): 207-214, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31988462

RESUMO

Frameshift mutations in the DMD gene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific nucleases offers new options for restoring the DMD reading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD (DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs1, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref. 2) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51-52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca2+ handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease.


Assuntos
Distrofina/genética , Mutação da Fase de Leitura , Edição de Genes/métodos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , RNA Guia de Cinetoplastídeos/genética , Animais , Modelos Animais de Doenças , Éxons , Feminino , Regulação da Expressão Gênica , Terapia Genética , Genoma , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/terapia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Espectrometria de Massas , Músculo Esquelético/metabolismo , Músculos/metabolismo , Mioblastos/metabolismo , Miócitos Cardíacos/metabolismo , Proteoma , Suínos
16.
Phys Rev E Stat Nonlin Soft Matter Phys ; 79(2 Pt 2): 026204, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19391817

RESUMO

We analyze a large system of globally coupled phase oscillators whose natural frequencies are bimodally distributed. The dynamics of this system has been the subject of long-standing interest. In 1984 Kuramoto proposed several conjectures about its behavior; ten years later, Crawford obtained the first analytical results by means of a local center manifold calculation. Nevertheless, many questions have remained open, especially about the possibility of global bifurcations. Here we derive the system's stability diagram for the special case where the bimodal distribution consists of two equally weighted Lorentzians. Using an ansatz recently discovered by Ott and Antonsen, we show that in this case the infinite-dimensional problem reduces exactly to a flow in four dimensions. Depending on the parameters and initial conditions, the long-term dynamics evolves to one of three states: incoherence, where all the oscillators are desynchronized; partial synchrony, where a macroscopic group of phase-locked oscillators coexists with a sea of desynchronized ones; and a standing wave state, where two counter-rotating groups of phase-locked oscillators emerge. Analytical results are presented for the bifurcation boundaries between these states. Similar results are also obtained for the case in which the bimodal distribution is given by the sum of two Gaussians.

17.
Sci Immunol ; 4(34)2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-31004013

RESUMO

Bacterial dysbiosis is associated with Crohn's disease (CD), a chronic intestinal inflammatory disorder thought to result from an abnormal immune response against intestinal bacteria in genetically susceptible individuals. However, it is unclear whether dysbiosis is a cause or consequence of intestinal inflammation and whether overall dysbiosis or specific bacteria trigger the disease. Here, we show that the combined deficiency of NOD2 and phagocyte NADPH oxidase, two CD susceptibility genes, triggers early-onset spontaneous TH1-type intestinal inflammation in mice with the pathological hallmarks of CD. Disease was induced by Mucispirillum schaedleri, a Gram-negative mucus-dwelling anaerobe. NOD2 and CYBB deficiencies led to marked accumulation of Mucispirillum, which was associated with impaired neutrophil recruitment and killing of the bacterium by luminal neutrophils. Maternal immunoglobulins against Mucispirillum protected mutant mice from disease during breastfeeding. Our results indicate that a specific intestinal microbe triggers CD-like disease in the presence of impaired clearance of the bacterium by innate immunity.


Assuntos
Bactérias/imunologia , Doença de Crohn/imunologia , Disbiose/imunologia , Interações entre Hospedeiro e Microrganismos/genética , Mucosa Intestinal/imunologia , Animais , Bactérias/patogenicidade , Doença de Crohn/genética , Doença de Crohn/microbiologia , Modelos Animais de Doenças , Disbiose/genética , Disbiose/microbiologia , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Imunidade Inata/genética , Imunoglobulinas/imunologia , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Camundongos Knockout , NADPH Oxidase 2/genética , Infiltração de Neutrófilos , Neutrófilos/imunologia , Proteína Adaptadora de Sinalização NOD2/genética
18.
Facts Views Vis Obgyn ; 9(4): 189-193, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30250652

RESUMO

OBJECTIVE: This study aims to identify geographical disparities in perinatal mortality and morbidity in the province of Antwerp, Belgium. We performed a retrospective cohort study from an existing database. Data included from 1 January , 2000 to 31 December, 2009 and including all deliveries in the Province of Antwerp, Belgium. Collected outcome measures : fetal death, early and late neonatal death, preterm birth, low birth weight. Outcomes were analyzed according to postal code of the pregnant women's address. RESULTS: A total of 167.246 deliveries in sixty postal codes were analyzed and statistically significant differences (p<0.001) between postal codes for all outcome measures except for early and late neonatal death were detected. Generally postal codes tend to have either high or low prevalences for all perinatal outcomes and two postal code zones had a significantly worse perinatal outcome on all fields. Major differences in perinatal outcome exist within the well-defined area of the relatively small province of Antwerp, Belgium. CONCLUSION: Perinatal outcome is strongly influenced by maternal postal code even within a relatively affluent European region demonstrating persistent health inequalities and suggesting further research is necessary to explain these differences and create interventions to diminish inequalities.

19.
Ann Rev Mar Sci ; 8: 217-41, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26163011

RESUMO

The size of an individual organism is a key trait to characterize its physiology and feeding ecology. Size-based scaling laws may have a limited size range of validity or undergo a transition from one scaling exponent to another at some characteristic size. We collate and review data on size-based scaling laws for resource acquisition, mobility, sensory range, and progeny size for all pelagic marine life, from bacteria to whales. Further, we review and develop simple theoretical arguments for observed scaling laws and the characteristic sizes of a change or breakdown of power laws. We divide life in the ocean into seven major realms based on trophic strategy, physiology, and life history strategy. Such a categorization represents a move away from a taxonomically oriented description toward a trait-based description of life in the oceans. Finally, we discuss life forms that transgress the simple size-based rules and identify unanswered questions.


Assuntos
Bactérias/crescimento & desenvolvimento , Biologia Marinha , Baleias/crescimento & desenvolvimento , Animais , Ecossistema , Modelos Biológicos
20.
Biochim Biophys Acta ; 1425(3): 587-98, 1998 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-9838222

RESUMO

Gelatinase B (matrix metalloproteinase-9, MMP-9) contains three N-glycosylation sites and a Ser/Thr/Pro-rich type V collagen domain with repetitive attachment sites for O-linked sugars. Recombinant mouse gelatinase B was expressed in the yeast Pichia pastoris and the N-linked oligosaccharides of the truncated glycoprotein variants were analysed by in gel enzymatic release followed by mass spectrometry and normal phase HPLC. This technology, despite of the limiting amount of material, allowed the analysis of the formula of N- and O-linked sugars of the different glycoprotein variants. The 112/99- and 88-kDa gelatinase B forms each contained an oligomannose series (Man8GlcNAc2 to Man15GlcNAc2). Analysis of the hydrazine-released sugars showed that the O-linked oligosaccharides contained alpha1-2, alpha1-3 or alpha1-6 linked mannoses. These results were confirmed by lectin blot analysis of intact and glycosidase-treated enzyme variants.


Assuntos
Colagenases/química , Oligossacarídeos/química , Acetaldeído/análogos & derivados , Animais , Cromatografia Líquida de Alta Pressão , Colagenases/biossíntese , Colagenases/genética , Glicosídeo Hidrolases , Hemopexina/química , Metaloproteinase 9 da Matriz , Camundongos , Mutação , Pichia/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo , Proteínas Recombinantes/química , Análise de Sequência
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