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1.
Epilepsia ; 61 Suppl 1: S41-S46, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32378197

RESUMO

Although several validated seizure detection algorithms are available for convulsive seizures, detection of nonconvulsive seizures remains challenging. In this phase 2 study, we have validated a predefined seizure detection algorithm based on heart rate variability (HRV) using patient-specific cutoff values. The validation data set was independent from the previously published data set. Electrocardiography (ECG) was recorded using a wearable device (ePatch) in prospectively recruited patients. The diagnostic gold standard was inferred from video-EEG monitoring. Because HRV-based seizure detection is suitable only for patients with marked ictal autonomic changes, we defined responders as the patients who had a>50 beats/min ictal change in heart rate. Eleven of the 19 included patients with seizures (57.9%) fulfilled this criterion. In this group, the algorithm detected 20 of the 23 seizures (sensitivity: 87.0%). The algorithm detected all but one of the 10 recorded convulsive seizures and all of the 8 focal impaired awareness seizures, and it missed 2 of the 4 focal aware seizures. The median sensitivity per patient was 100% (in nine patients all seizures were detected). The false alarm rate was 0.9/24 h (0.22/night). Our results suggest that HRV-based seizure detection has high performance in patients with marked autonomic changes.


Assuntos
Algoritmos , Eletrocardiografia/instrumentação , Frequência Cardíaca/fisiologia , Convulsões/diagnóstico , Dispositivos Eletrônicos Vestíveis , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador , Adulto Jovem
2.
Fetal Diagn Ther ; 47(3): 228-236, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31533106

RESUMO

OBJECTIVE: The aim of this work was to investigate the association between maternal and fetal characteristics and the fetal fraction at 8-14 weeks' gestation, with emphasis on the change in the fetal fraction upon repeat sampling. METHOD: One sample for cell-free DNA (cfDNA) testing was collected at the same time as the biochemical markers for combined first trimester screening (visit 1) and another at the nuchal translucency scan (visit 2). Chromosome-selective cfDNA analysis was performed on frozen plasma. RESULTS: Overall, 321 women were included at visit 1, and 307 had a repeat blood sampling. A fetal fraction was obtained in 532 samples (238 samples with repeat fetal fraction). The fetal fraction decreased with maternal BMI (p < 0.001), was lower in Asian women (p = 0.03), and increased with ß-hCG levels (p < 0.001) and gestational age (p = 0.04). Before 10 weeks' gestation, the fetal fraction was lower (p = 0.02), as was the probability of a sufficient fetal fraction (p = 0.03) after adjustment for maternal BMI. Asian women had a higher increase in fetal fraction upon repeat sampling (p < 0.001). CONCLUSION: Before 10 weeks' gestation, the fetal fraction is significantly lower but seems to increase more rapidly compared to later gestations. Presently, combined first trimester screening with cfDNA testing should not include samples before 10 weeks' gestation.


Assuntos
Ácidos Nucleicos Livres/sangue , Primeiro Trimestre da Gravidez/sangue , Adulto , Feminino , Feto/química , Humanos , Gravidez
3.
Blood ; 129(15): 2161-2171, 2017 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-28039188

RESUMO

Wound healing requires interactions between coagulation, inflammation, angiogenesis, cellular migration, and proliferation. Healing in dermal wounds of hemophilia B mice is delayed when compared with hemostatically normal wild-type (WT) mice, with abnormal persistence of iron deposition, inflammation, and neovascularity. We observed healing following induced joint hemorrhage in WT and factor IX (FIX) knockout (FIX-/-) mice, examining also parameters previously studied in an excisional skin wound model. Hemostatically normal mice tolerated this joint bleeding challenge, cleared blood from the joint, and healed with minimal pathology, even if additional autologous blood was injected intra-articularly at the time of wounding. Following hemarthrosis, joint wound healing in hemophilia B mice was impaired and demonstrated similar abnormal histologic features as previously described in hemophilic dermal wounds. Therefore, studies of pathophysiology and therapy of hemophilic joint bleeding performed in hemostatically normal animals are not likely to accurately reflect the healing defect of hemophilia. We additionally explored the hypothesis that the use of a FIX replacement protein with extended circulating FIX activity could improve synovial and osteochondral wound healing in hemophilic mice, when compared with treatment with unmodified recombinant FIX (rFIX) in the established joint bleeding model. Significantly improved synovial wound healing and preservation of normal osteochondral architecture are achieved by extending FIX activity after hemarthrosis using glycoPEGylated FIX when compared with an equivalent dose of rFIX. These results suggest that treating joint bleeding only until hemostasis is achieved may not result in optimal joint healing, which is improved by extending factor activity.


Assuntos
Fator IX , Hemartrose , Hemofilia B , Articulações , Pele , Cicatrização , Animais , Modelos Animais de Doenças , Fator IX/genética , Fator IX/farmacologia , Hemartrose/tratamento farmacológico , Hemartrose/genética , Hemartrose/metabolismo , Hemofilia B/tratamento farmacológico , Hemofilia B/genética , Hemofilia B/metabolismo , Articulações/lesões , Articulações/metabolismo , Camundongos , Camundongos Knockout , Pele/lesões , Pele/metabolismo , Cicatrização/efeitos dos fármacos , Cicatrização/genética
4.
Epilepsia ; 60(10): 2105-2113, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31538347

RESUMO

OBJECTIVE: To assess the feasibility and accuracy of seizure detection based on heart rate variability (HRV) using a wearable electrocardiography (ECG) device. Noninvasive devices for detection of convulsive seizures (generalized tonic-clonic and focal to bilateral tonic-clonic seizures) have been validated in phase 2 and 3 studies. However, detection of nonconvulsive seizures still needs further research, since currently available methods have either low sensitivity or an extremely high false alarm rate (FAR). METHODS: In this phase 2 study, we prospectively recruited patients admitted to long-term video-EEG monitoring (LTM). ECG was recorded using a dedicated wearable device. Seizures were automatically detected using HRV parameters computed off-line, blinded to all other data. We compared the performance of 26 automated algorithms with the seizure time-points marked by experts who reviewed the LTM recording. Patients were classified as responders if >66% of their seizures were detected. RESULTS: We recruited 100 consecutive patients and analyzed 126 seizures (108 nonconvulsive and 18 convulsive) from 43 patients who had seizures during monitoring. The best-performing HRV algorithm combined a measure of sympathetic activity with a measure of how quickly HR changes occurred. The algorithm identified 53.5% of the patients with seizures as responders. Among responders, detection sensitivity was 93.1% (95% CI: 86.6%-99.6%) for all seizures and 90.5% (95% CI: 77.4%-97.3%) for nonconvulsive seizures. FAR was 1.0/24 h (0.11/night). Median seizure detection latency was 30 s. Typically, patients with prominent autonomic nervous system changes were responders: An ictal change of >50 heartbeats per minute predicted who would be responder with a positive predictive value of 87% and a negative predictive value of 90%. SIGNIFICANCE: The automated HRV algorithm, using ECG recorded with a wearable device, has high sensitivity for detecting seizures, including the nonconvulsive ones. FAR was low during the night. This approach is feasible in patients with prominent ictal autonomic changes.


Assuntos
Frequência Cardíaca/fisiologia , Convulsões/diagnóstico , Adolescente , Adulto , Idoso , Sistema Nervoso Autônomo/fisiopatologia , Criança , Pré-Escolar , Eletrocardiografia Ambulatorial , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Convulsões/fisiopatologia , Sensibilidade e Especificidade , Dispositivos Eletrônicos Vestíveis , Adulto Jovem
5.
Perfusion ; 33(2): 136-147, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28937313

RESUMO

OBJECTIVE: The postoperative systemic inflammatory response after cardiopulmonary bypass (CPB) is still an undesirable side-effect after cardiac surgery. It is most likely caused by blood contact with foreign surfaces and by the surgical trauma itself. However, the recirculation of activated shed mediastinal blood is another main cause of blood cell activation and cytokine release. Minimal invasive extracorporeal circulation (MiECC) comprises a completely closed circuit, coated surfaces and the separation of suction blood. We hypothesized that MiECC, with separated cell saved blood, would induce less of a systemic inflammatory response than MiECC with no cell-saver. The aim of this study was, therefore, to investigate the impact of cell washing shed blood from the operating field versus direct return to the ECC on the biomarkers for systemic inflammation. MATERIAL AND METHODS: In the study, patients with MiECC and cell-saver were compared with the control group, patients with MiECC and direct re-transfusion of the drawn blood shed from the surgical field. RESULTS: High amounts of TNF-α (+ 120% compared to serum blood) were found in the shed blood itself, but a significant reduction was demonstrated with the use of a cell-saver (TNF-α ng/l post-ECC 10 min: 9.5±3.5 vs. 19.7±14.5, p<0.0001). The values for procalcitonin were not significantly increased in the control group (6h: 1.07±3.4 vs. 2.15±9.55, p=0.19) and lower for C-reactive protein (CRP) (24h: 147.1±64.0 vs.134.4±52.4 p=0.28). CONCLUSION: The use of a cell-saver and the processing of shed blood as an integral part of MiECC significantly reduces the systemic cytokine load. We, therefore, recommend the integration of cell-saving devices in MiECC to reduce the perioperative inflammatory response.


Assuntos
Circulação Extracorpórea/métodos , Inflamação/sangue , Idoso , Circulação Extracorpórea/efeitos adversos , Feminino , Humanos , Masculino , Período Pós-Operatório , Estudos Prospectivos , Resultado do Tratamento
6.
Photochem Photobiol Sci ; 16(6): 985-995, 2017 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-28485745

RESUMO

The 25-hydroxy vitamin D (25(OH)D) production caused by UVB exposure is usually underestimated as the concurrent degradation of 25(OH)D is not considered. Therefore, the decrease in 25(OH)D was investigated during a 7-week period in winter when ambient UVB is negligible. Twenty-two healthy Danish individuals (113 samples) participated and had a mean and steady maximal 25(OH)D start level of 132 nmol l-1 (range of 68-216 nmol l-1) due to long-term UVB treatment prior to this study. In this group with high 25(OH)D start levels, the decrease in 25(OH)D was best described by an exponential model. This suggests a quantitatively larger elimination of 25(OH)D at high 25(OH)D start levels. A linear model (logarithm of 25(OH)D) including personal start levels as intercepts and a slope influenced by gender and the vitamin D receptor gene polymorphism rs2228570 explained 87.8% of the observed variation. The mean half-life was 89 days with a difference in half-life of 120 days between a male with rs2228570 genotype GG (59 days) and a female with rs2228570 genotype AA/AG (179 days). Thus, these two parameters explained a large part of the observed inter-individual variation of 25(OH)D. Furthermore, the decrease was analysed in two groups with medium and low 25(OH)D start levels resulting in longer half-lives of 149 days and 199 days, respectively. The longer half-lives at lower 25(OH)D levels may be caused by storage mobilisation, changed catabolism or increased intestinal absorption.


Assuntos
Polimorfismo Genético/genética , Receptores de Calcitriol/genética , Raios Ultravioleta , Vitamina D/análogos & derivados , Adulto , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Calcitriol/metabolismo , Vitamina D/análise , Vitamina D/metabolismo , Adulto Jovem
7.
Photochem Photobiol Sci ; 15(4): 536-45, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27001558

RESUMO

Vitamin D influences skeletal health as well as other aspects of human health. Even when the most obvious sources of variation such as solar UVB exposure, latitude, season, clothing habits, skin pigmentation and ethnicity are selected for, variation in the serum 25-hydroxy vitamin D (25(OH)D) response to UVB remains extensive and unexplained. Our study assessed the inter-personal variation in 25(OH)D response to UVR and the maximal obtainable 25(OH)D level in 22 healthy participants (220 samples) with similar skin pigmentation during winter with negligible ambient UVB. Participants received identical UVB doses on identical body areas until a maximal level of 25(OH)D was reached. Major inter-personal variation in both the maximal obtainable UVB-induced 25(OH)D level (range 85-216 nmol l(-1), mean 134 nmol l(-1)) and the total increase in 25(OH)D (range 3-139 nmol l(-1), mean 48 nmol l(-1)) was found. A linear model including measured 25(OH)D baselines as personal intercepts explained 54.9% of the variation. By further including personal slopes in the model, as much as 90.8% of the variation could be explained. The explained variation constituted by personal differences in slopes thus represented 35.9%. Age, vitamin D receptor gene polymorphisms, height and constitutive skin pigmentation (a skin area not exposed to UVB) explained 15.1% of this variation. Despite elimination of most known external sources of variation, our study demonstrated inter-personal variation corresponding to an observed maximal difference of 136 nmol l(-1) in the total increase of 25(OH)D and 131 nmol l(-1) in the maximal level of 25(OH)D.


Assuntos
Raios Ultravioleta , Vitamina D/análogos & derivados , Humanos , Polimorfismo Genético , Receptores de Calcitriol/genética , Estações do Ano , Vitamina D/sangue
8.
Prenat Diagn ; 36(6): 530-6, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27027563

RESUMO

OBJECTIVE: The objective of this study was to introduce non-invasive prenatal testing (NIPT) for fetal autosomal trisomies and gender in a Danish public health setting, using semi-conductor sequencing and published open source scripts for analysis. METHODS: Plasma-derived DNA from a total of 375 pregnant women (divided into three datasets) was whole-genome sequenced on the Ion Proton™ platform and analyzed using a pipeline based on WISECONDOR for fetal autosomal aneuploidy detection and SeqFF for fetal DNA fraction estimation. We furthermore validated a fetal sex determination analysis. RESULTS: The pipeline correctly detected 27/27 trisomy 21, 4/4 trisomy 18, and 3/3 trisomy 13 fetuses. Neither false negatives nor false positives (chromosomes 13, 18, and 21) were observed in our validation dataset. Fetal sex was identified correctly in all but one triploid fetus (172/173). SeqFF showed a strong correlation (R(2) = 0.72) to Y-chromosomal content of the male fetus samples. DISCUSSION: We have implemented NIPT into Danish health care using published open source scripts for autosomal aneuploidy detection and fetal DNA fraction estimation showing excellent false negative and false positive rates. SeqFF provides a good estimation of fetal DNA fraction. This coupled with an analysis of fetal sex that provides a complete NIPT workflow, which may easily be adapted for implementation in other public health laboratories. © 2016 John Wiley & Sons, Ltd.


Assuntos
Transtornos Cromossômicos/diagnóstico , DNA/sangue , Síndrome de Down/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Testes para Triagem do Soro Materno/métodos , Análise de Sequência de DNA/métodos , Trissomia/diagnóstico , Adulto , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 18 , DNA/genética , Dinamarca , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/instrumentação , Humanos , Masculino , Gravidez , Diagnóstico Pré-Natal , Saúde Pública , Semicondutores , Análise de Sequência de DNA/instrumentação , Análise para Determinação do Sexo , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18
9.
J Biomech Eng ; 138(3): 4032501, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26784124

RESUMO

The transcatheter aortic valve implantation (TAVI) valve is a bioprosthetic valve within a metal stent frame. Like traditional surgical bioprosthetic valves, the TAVI valve leaflet tissue is expected to calcify and degrade over time. However, clinical studies of TAVI valve longevity are still limited. In order to indirectly assess the longevity of TAVI valves, an estimate of the mechanical wear and tear in terms of valvular deformation and strain of the leaflets under various conditions is warranted. The aim of this study was, therefore, to develop a platform for noncontact TAVI valve deformation analysis with both high temporal and spatial resolutions based on stereophotogrammetry and digital image correlation (DIC). A left-heart pulsatile in vitro flow loop system for mounting of TAVI valves was designed. The system enabled high-resolution imaging of all three TAVI valve leaflets simultaneously for up to 2000 frames per second through two high-speed cameras allowing three-dimensional analyses. A coating technique for applying a stochastic pattern on the leaflets of the TAVI valve was developed. The technique allowed a pattern recognition software to apply frame-by-frame cross correlation based deformation measurements from which the leaflet motions and the strain fields were derived. The spatiotemporal development of a very detailed strain field was obtained with a 0.5 ms time resolution and a spatial resolution of 72 µm/pixel. Hence, a platform offering a new and enhanced supplementary experimental evaluation of tissue valves during various conditions in vitro is presented.


Assuntos
Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca , Teste de Materiais/métodos , Fenômenos Ópticos , Estresse Mecânico , Animais , Valva Aórtica/fisiologia , Bovinos , Teste de Materiais/instrumentação , Pressão , Desenho de Prótese , Fluxo Pulsátil , Análise Espaço-Temporal
10.
Blood ; 121(11): 2108-16, 2013 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-23335368

RESUMO

Frequent infusions of intravenous factor VIII (FVIII) are required to prevent bleeding associated with hemophilia A. To reduce the treatment burden, recombinant FVIII with a longer half-life was developed without changing the protein structure. FVIII-polyethylene glycol (PEG) conjugates were prepared using an enzymatic process coupling PEG (ranging from 10 to 80 kDa) selectively to a unique O-linked glycan in the FVIII B-domain. Binding to von Willebrand factor (VWF) was maintained for all conjugates. Upon cleavage by thrombin, the B-domain and the associated PEG were released, generating activated FVIII (FVIIIa) with the same primary structure and specific activity as native FVIIIa. In both FVIII- and VWF-deficient mice, the half-life was found to increase with the size of PEG. In vivo potency and efficacy of FVIII conjugated with a 40-kDa PEG (N8-GP) and unmodified FVIII were not different. N8-GP had a longer duration of effect in FVIII-deficient mouse models, approximately a twofold prolonged half-life in mice, rabbits, and cynomolgus monkeys; however, the prolongation was less pronounced in rats. Binding capacity of N8-GP on human monocyte-derived dendritic cells was reduced compared with unmodified FVIII, resulting in several-fold reduced cellular uptake. In conclusion, N8-GP has the potential to offer efficacious prevention and treatment of bleeds in hemophilia A at reduced dosing frequency.


Assuntos
Fator VIII/uso terapêutico , Hemofilia A/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Animais , Células CHO , Células Cultivadas , Cricetinae , Cricetulus , Modelos Animais de Doenças , Fator VIII/administração & dosagem , Fator VIII/metabolismo , Feminino , Glicosilação , Hemofilia A/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/metabolismo , Coelhos , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Resultado do Tratamento
11.
Int J Health Geogr ; 14: 21, 2015 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-26081106

RESUMO

BACKGROUND: Snow's work on the Broad Street map is widely known as a pioneering example of spatial epidemiology. It lacks, however, two significant attributes required in contemporary analyses of disease incidence: population at risk and the progression of the epidemic over time. Despite this has been repeatedly suggested in the literature, no systematic investigation of these two aspects was previously carried out. Using a series of historical documents, this study constructs own data to revisit Snow's study to examine the mortality rate at each street location and the space-time pattern of the cholera outbreak. METHODS: This study brings together records from a series of historical documents, and prepares own data on the estimated number of residents at each house location as well as the space-time data of the victims, and these are processed in GIS to facilitate the spatial-temporal analysis. Mortality rates and the space-time pattern in the victims' records are explored using Kernel Density Estimation and network-based Scan Statistic, a recently developed method that detects significant concentrations of records such as the date and place of victims with respect to their distance from others along the street network. The results are visualised in a map form using a GIS platform. RESULTS: Data on mortality rates and space-time distribution of the victims were collected from various sources and were successfully merged and digitised, thus allowing the production of new map outputs and new interpretation of the 1854 cholera outbreak in London, covering more cases than Snow's original report and also adding new insights into their space-time distribution. They confirmed that areas in the immediate vicinity of the Broad Street pump indeed suffered from excessively high mortality rates, which has been suspected for the past 160 years but remained unconfirmed. No distinctive pattern was found in the space-time distribution of victims' locations. CONCLUSIONS: The high mortality rates identified around the Broad Street pump are consistent with Snow's theory about cholera being transmitted through contaminated water. The absence of a clear space-time pattern also indicates the water-bourne, rather than the then popular belief of air bourne, nature of cholera. The GIS data constructed in this study has an academic value and would cater for further research on Snow's map.


Assuntos
Cólera/mortalidade , Surtos de Doenças/história , Mapeamento Geográfico , Mortalidade/tendências , Análise Espaço-Temporal , Cólera/história , História do Século XIX , Humanos , Londres/epidemiologia , Poluição da Água
12.
Proc Natl Acad Sci U S A ; 109(10): 3927-31, 2012 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-22355108

RESUMO

Tissue factor pathway inhibitor (TFPI) blocks thrombin generation via the extrinsic blood coagulation pathway. Because the severe bleeding in patients with hemophilia occurs from deficiency of intrinsic blood coagulation pathway factor VIII or IX, pharmacological agents that inactivate TFPI and, therefore, restore thrombin generation via the extrinsic pathway, are being developed for treatment of hemophilia. Murine models of combined TFPI and factor VIII deficiency were used to examine the impact of TFPI deficiency on bleeding and clotting in hemophilia. In breeding studies, Factor VIII null (F8(-/-)) did not rescue the embryonic death of TFPI null (Tfpi(-/-)) mice. Tfpi(+/-) did not alter the bleeding phenotype of F8(-/-) mice. However, total inhibition of intravascular TFPI through injection of anti-TFPI antibody mitigated tail vein bleeding. Interestingly, tail blood loss progressively decreased at doses greater than needed to totally inhibit plasma TFPI, suggesting that inhibition of a sequestered pool of TFPI released at the injury site mitigates bleeding. Because TFPI is sequestered within platelets and released following their activation, the function of platelet TFPI was examined in F8(-/-) mice lacking hematopoietic cell TFPI that was generated by fetal liver transplantation. Blood loss after tail transection significantly decreased in Tfpi(+/-);F8(-/-) mice with hematopoietic Tfpi(-/-) cells compared with Tfpi(+/-);F8(-/-) mice with Tfpi(+/+) hematopoietic cells. Additionally, following femoral vein injury, Tfpi(+/-);F8(-/-) mice with Tfpi(-/-) hematopoietic cells had increased fibrin deposition compared with identical-genotype mice with Tfpi(+/+) hematopoietic cells. These findings implicate platelet TFPI as a primary physiological regulator of bleeding in hemophilia.


Assuntos
Hemofilia A/metabolismo , Lipoproteínas/genética , Lipoproteínas/metabolismo , Animais , Coagulação Sanguínea , Modelos Animais de Doenças , Feminino , Teste de Complementação Genética , Genótipo , Células-Tronco Hematopoéticas/citologia , Hemofilia A/tratamento farmacológico , Hemofilia A/genética , Hemorragia , Fígado/embriologia , Transplante de Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fenótipo
14.
Epilepsia ; 55(7): e67-71, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24701979

RESUMO

Evidence for seizure-induced cardiac dysrhythmia leading to sudden unexpected death in epilepsy (SUDEP) has been elusive. We present a patient with focal cortical dysplasia who has had epilepsy for 19 years and was undergoing presurgical evaluation. The patient did not have any cardiologic antecedents. During long-term video-electroencephalography (EEG) monitoring, following a cluster of secondarily generalized tonic-clonic seizures (GTCS), the patient had prolonged postictal generalized EEG suppression, asystole, followed by arrhythmia, and the patient died despite cardiopulmonary resuscitation. Analysis of heart rate variability showed a marked increase in the parasympathetic activity during the period preceding the fatal seizures, compared with values measured 1 day and 7 months before, and also higher than the preictal values in a group of 10 patients with GTCS without SUDEP. The duration of the QTc interval was short (335-358 msec). This unfortunate case documented during video-EEG monitoring indicates that autonomic imbalance and seizure-induced cardiac dysrhythmias contribute to the pathomechanisms leading to SUDEP in patients at risk (short QT interval).


Assuntos
Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Morte Súbita Cardíaca/etiologia , Epilepsia/complicações , Epilepsia/fisiopatologia , Frequência Cardíaca/fisiologia , Adolescente , Adulto , Arritmias Cardíacas/diagnóstico , Criança , Epilepsia/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Nervoso Parassimpático/fisiopatologia , Convulsões/complicações , Convulsões/diagnóstico , Convulsões/fisiopatologia , Adulto Jovem
15.
J Asthma ; 51(9): 974-81, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24945942

RESUMO

OBJECTIVE: The last half-century has seen substantial changes in asthma treatment and care. We investigated whether arterial blood gas parameters in acute and non-acute asthma have changed historically. METHODS: We performed a systematic search of the literature for studies reporting P(aO2) , P(aCO2) and forced expiratory volume in 1 s, percentage of predicted (FEV1%). For each of the blood gas parameters, meta-regression analyses examined its association with four background variables: the publication year, mean FEV1%, mean age and female fraction in the respective studies. RESULTS: After screening, we included 43 articles comprising 61 datasets published between 1967 and 2013. In studies of habitual-state asthma, mean P(aO2) was positively associated with the publication year (p = 0.001) and negatively with mean age (p < 0.01). Mean P(aCO2) showed a positive association with publication year (p = 0.001) and a negative association with female fraction (p < 0.05). In acute asthma studies, blood gas levels were unassociated with publication year and mean age, mean P(aO2) was positively associated with FEV1% (p < 0.05) whereas mean P(aCO2) showed a negative association with FEV1% (p < 0.05) for studies with mean FEV1% <40. In neither acute nor habitual-state studies was mean arterial pH associated with any of the predictor variables. CONCLUSIONS: In studies of habitual-state asthma, mean reported P(aO2) and P(aCO2) levels were found to have increased since 1967. In acute asthma studies, mean P(aO2) and P(aCO2) were associated with mean FEV1% but not with either publication year or patient age.


Assuntos
Asma/sangue , Doença Aguda , Gasometria , Volume Expiratório Forçado , Humanos , Troca Gasosa Pulmonar , Análise de Regressão
16.
BMC Dermatol ; 14: 8, 2014 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-24762088

RESUMO

BACKGROUND: Micro RNAs (miRs) have emerged as key regulators during oncogenesis. They have been found to regulate cell proliferation, differentiation, and apoptosis. Mir-125b has been identified as an oncomir in various forms of tumours, but we have previously proposed that miR-125b is a suppressor of lymph node metastasis in cutaneous malignant melanoma. Our goal was therefore to further examine this theory. METHODS: We used in-situ-hybridization to visualise miR-125b expression in primary tumours and in lymph node metastasis. Then using a miRVector plasmid containing a miR-125b-1 insert we transfected melanoma cell line Mel-Juso and then investigated the effect of the presence of a stable overexpression of miR-125b on growth by western blotting, flow cytometry and ß-galactosidase staining. The tumourogenicity of the transfected cells was tested using a murine model and the tumours were further examined with in-situ-hybridization. RESULTS: In primary human tumours and in lymph node metastases increased expression of miR-125b was found in single, large tumour cells with abundant cytoplasm. A stable overexpression of miR-125b in human melanoma cell line Mel-Juso resulted in a G0/G1 cell cycle block and emergence of large cells expressing senescence markers: senescence-associated beta-galactosidase, p21, p27 and p53. Mel-Juso cells overexpressing miR-125b were tumourigenic in mice, but the tumours exhibited higher level of cell senescence and decreased expression of proliferation markers, cyclin D1 and Ki67 than the control tumours. CONCLUSIONS: Our results confirm the theory that miR-125b functions as a tumour supressor in cutaneous malignant melanoma by regulating cellular senescence, which is one of the central mechanisms protecting against the development and progression of malignant melanoma.


Assuntos
Senescência Celular , Melanoma/metabolismo , Melanoma/patologia , MicroRNAs/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Proliferação de Células , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Melanoma/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Neoplasias Cutâneas , Transfecção , Regulação para Cima , Adulto Jovem , Melanoma Maligno Cutâneo
17.
Sci Rep ; 14(1): 3238, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331948

RESUMO

Far-UVC light in the wavelength range of 200-230 nm has attracted renewed interest because of its safety for human exposure and effectiveness in inactivating pathogens. Here we present a compact solid-state far-UVC laser source based on second-harmonic generation (SHG) using a low-cost commercially-available blue laser diode pump. Leveraging the high intensity of light in a nanophotonic waveguide and heterogeneous integration, our approach achieves Cherenkov phase-matching across a bonded interface consisting of a silicon nitride (SiN) waveguide and a beta barium borate (BBO) nonlinear crystal. Through systematic investigations of waveguide dimensions and pump power, we analyze the dependencies of Cherenkov emission angle, conversion efficiency, and output power. Experimental results confirm the feasibility of generating far-UVC, paving the way for mass production in a compact form factor. This solid-state far-UVC laser source shows significant potential for applications in human-safe disinfection, non-line-of-sight free-space communication, and deep-UV Raman spectroscopy.

18.
Sci Rep ; 14(1): 1864, 2024 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-38253772

RESUMO

The left atrium (LA) hemodynamic indices hold prognostic value in various cardiac diseases and disorders. To understand the mechanisms of these conditions and to assess the performance of cardiac devices and interventions, in vitro models can be used to replicate the complex physiological interplay between the pulmonary veins, LA, and left ventricle. In this study, a comprehensive and adaptable in vitro model was created. The model includes a flexible LA made from silicone and allows distinct control over the systolic and diastolic functions of both the LA and left ventricle. The LA was mechanically matched with porcine LAs through expansion tests. Fluid dynamic measures were validated against the literature and pulmonary venous flows recorded on five healthy individuals using magnetic resonance flow imaging. Furthermore, the fluid dynamic measures were also used to construct LA pressure-volume loops. The in vitro pressure and flow recordings expressed a high resemblance to physiological waveforms. By decreasing the compliance of the LA, the model behaved realistically, elevating the a- and v-wave peaks of the LA pressure from 12 to 19 mmHg and 22 to 26 mmHg, respectively, while reducing the S/D ratio of the pulmonary venous flowrate from 1.5 to 0.3. This model provides a realistic platform and framework for developing and evaluating left heart procedures and interventions.


Assuntos
Apêndice Atrial , Cardiopatias , Humanos , Animais , Suínos , Hidrodinâmica , Átrios do Coração/diagnóstico por imagem , Ventrículos do Coração
19.
Physiol Meas ; 45(5)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38729184

RESUMO

Objective. Pressure-volume loop analysis, traditionally performed by invasive pressure and volume measurements, is the optimal method for assessing ventricular function, while cardiac magnetic resonance (CMR) imaging is the gold standard for ventricular volume estimation. The aim of this study was to investigate the agreement between the assessment of end-systolic elastance (Ees) assessed with combined CMR and simultaneous pressure catheter measurements compared with admittance catheters in a porcine model.Approach. Seven healthy pigs underwent admittance-based pressure-volume loop evaluation followed by a second assessment with CMR during simultaneous pressure measurements.Main results. Admittance overestimated end-diastolic volume for both the left ventricle (LV) and the right ventricle (RV) compared with CMR. Further, there was an underestimation of RV end-systolic volume with admittance. For the RV, however, Ees was systematically higher when assessed with CMR plus simultaneous pressure measurements compared with admittance whereas there was no systematic difference in Ees but large differences between admittance and CMR-based methods for the LV.Significance. LV and RV Ees can be obtained from both admittance and CMR based techniques. There were discrepancies in volume estimates between admittance and CMR based methods, especially for the RV. RV Ees was higher when estimated by CMR with simultaneous pressure measurements compared with admittance.


Assuntos
Imageamento por Ressonância Magnética , Animais , Suínos , Pressão Sanguínea/fisiologia , Ventrículos do Coração/diagnóstico por imagem , Modelos Animais
20.
Acta Obstet Gynecol Scand ; 92(9): 1070-8, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23730731

RESUMO

OBJECTIVE: Electrohysterographic assessment of the propagation velocity of uterine depolarization has been introduced as a promising predictor of preterm labor. Therefore, the objectives of this study were to characterize the uterine electrohysterographic signals during labor and to determine the propagation velocity and propagation direction of electrohysterographic signals. DESIGN: Descriptive study. SETTING: Department of Obstetrics and Gynecology, Aarhus University Hospital, Denmark. POPULATION: Eight women in active labor at term. METHODS: Electrohysterograms (three channels) were recorded using surface electrodes placed abdominally along the vertical median axis with an inter-electrode distance of 6.5-11.2 cm. In total, 89 contractions were analyzed. RESULTS: Electrohysterographic characteristics: The duration of the contractions was 61.0 ± 18.0 s (mean ± SD). The median frequency of the power spectrum density was 0.51 (0.44; 0.51) Hz (median; 10th; 90th percentile). The greatest signal magnitude was obtained by the electrode in the centermost position. The propagation velocity: 2.15 (0.66; 13.8) cm/s in the upper part and 1.53 (0.58; 6.7) cm/s in the lower part of the uterus. Propagation direction: Both downward (58%) and upward (42%) propagation of the electrohysterographic signals occurred. Moreover, downward and upward propagations were recorded simultaneously in the upper and lower part of the uterus, suggesting a multidirectional propagation pattern. CONCLUSIONS: Labor contractions, expressed by electrohysterographic signals, propagate both in the downward and upward direction, a phenomenon that must be taken into account when determining the propagation velocity for preterm labor diagnostics.


Assuntos
Eletrodiagnóstico/métodos , Trabalho de Parto/fisiologia , Contração Uterina/fisiologia , Adulto , Feminino , Humanos , Gravidez , Processamento de Sinais Assistido por Computador
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