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1.
Int J Legal Med ; 138(3): 839-847, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38231204

RESUMO

The evaluation of a morphine concentration in postmortem blood is routine for a forensic toxicologist. We here report three fatal cases where we found high morphine concentrations with 7.96, 4.30, and 5.82 mg/l in femoral blood that have to be estimated as unusually high. All these individuals died due to severe burn injuries and obtained morphine in the context of their palliative care in the last hours of their lives. According to the autopsy results, the cause of death in case 1 was burn disease with burns of about 90% of the body surface area (BSA), case 2 burn trauma, and case 3 burn shock. Besides morphine, propofol, fentanyl, sufentanil, midazolam, diazepam, lorazepam, cefazolin, and rocuronium were detected in femoral blood. The findings fitted well with the detailed clinical documentation. Further evidence of therapeutic concentrations of quetiapine, duloxetine, and melperone could be matched to preexisting medication of the individuals. Physiologically based pharmacokinetic modelling (PBPK) was applied, developed for the intravenous administration of morphine, to find an explanation for the high morphine concentrations in femoral blood. Quantification of morphine in body fluids and tissue was performed to calculate morphine tissue concentration ratios to the morphine concentration in femoral blood. The presented cases show that pharmacokinetic simulations can reflect decreased renal clearance and decreased hepatic metabolism in general. However, this prediction is not sufficient to explain the high morphine concentrations in femoral blood measured here. It can be assumed that burn shock in particular leads to altered pharmacokinetics, namely decreased distribution of morphine.


Assuntos
Queimaduras , Propofol , Humanos , Morfina/farmacocinética , Cuidados Paliativos , Diazepam , Queimaduras/metabolismo
2.
J Immunol ; 208(3): 571-581, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34965962

RESUMO

IDO2 is one of two closely related tryptophan catabolizing enzymes induced under inflammatory conditions. In contrast to the immunoregulatory role defined for IDO1 in cancer models, IDO2 has a proinflammatory function in models of autoimmunity and contact hypersensitivity. In humans, two common single-nucleotide polymorphisms have been identified that severely impair IDO2 enzymatic function, such that <25% of individuals express IDO2 with full catalytic potential. This, together with IDO2's relatively weak enzymatic activity, suggests that IDO2 may have a role outside of its function in tryptophan catabolism. To determine whether the enzymatic activity of IDO2 is required for its proinflammatory function, we used newly generated catalytically inactive IDO2 knock-in mice together with established models of contact hypersensitivity and autoimmune arthritis. Contact hypersensitivity was attenuated in catalytically inactive IDO2 knock-in mice. In contrast, induction of autoimmune arthritis was unaffected by the absence of IDO2 enzymatic activity. In pursuing this nonenzymatic IDO2 function, we identified GAPDH, Runx1, RANbp10, and Mgea5 as IDO2-binding proteins that do not interact with IDO1, implicating them as potential mediators of IDO2-specific function. Taken together, our findings identify a novel function for IDO2, independent of its tryptophan catabolizing activity, and suggest that this nonenzymatic function could involve multiple signaling pathways. These data show that the enzymatic activity of IDO2 is required only for some inflammatory immune responses and provide, to our knowledge, the first evidence of a nonenzymatic role for IDO2 in mediating autoimmune disease.


Assuntos
Artrite/imunologia , Autoimunidade/imunologia , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Animais , Antígenos de Neoplasias/metabolismo , Linhagem Celular , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Técnicas de Introdução de Genes , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Células HEK293 , Humanos , Inflamação/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Polimorfismo de Nucleotídeo Único/genética
3.
Sensors (Basel) ; 24(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38339459

RESUMO

Mobile fitness applications provide the opportunity to show users real-time feedback on their current fitness activity. For such applications, it is essential to accurately track the user's current fitness activity using available mobile sensors, such as inertial measurement units (IMUs). Convolutional neural networks (CNNs) have been shown to produce strong results in different time series classification tasks, including the recognition of daily living activities. However, fitness activities can present unique challenges to the human activity recognition task (HAR), including greater similarity between individual activities and fewer available data for model training. In this paper, we evaluate the applicability of CNNs to the fitness activity recognition task (FAR) using IMU data and determine the impact of input data size and sensor count on performance. For this purpose, we adapted three existing CNN architectures to the FAR task and designed a fourth CNN variant, which we call the scaling fully convolutional network (Scaling-FCN). We designed a preprocessing pipeline and recorded a running exercise data set with 20 participants, in which we evaluated the respective recognition performances of the four networks, comparing them with three traditional machine learning (ML) methods commonly used in HAR. Although CNN architectures achieve at least 94% test accuracy in all scenarios, two traditional ML architectures surpass them in the default scenario, with support vector machines (SVMs) achieving 99.00 ± 0.34% test accuracy. The removal of all sensors except one foot sensor reduced the performance of traditional ML architectures but improved the performance of CNN architectures on our data set, with our Scaling-FCN reaching the highest accuracy of 99.86 ± 0.11% on the test set. Our results suggest that CNNs are generally well suited for fitness activity recognition, and noticeable performance improvements can be achieved if sensors are dropped selectively, although traditional ML architectures can still compete with or even surpass CNNs when favorable input data are utilized.


Assuntos
Aprendizado de Máquina , Redes Neurais de Computação , Humanos , Fatores de Tempo , Exercício Físico , Atividades Humanas
4.
Prostate ; 83(1): 56-63, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36073730

RESUMO

BACKGROUND: To investigate the clinical implications of magnetic resonance imaging (MRI) negative prostate cancer (PCa) in a cohort of men undergoing transperineal prostate biopsy. METHODS: We included all men without prior diagnosis of PCa undergoing transperineal template saturation ± fusion-guided targeted biopsy of the prostate between November 2014 and March 2018. Before biopsy, all patients underwent MRI and biopsies were performed irrespective of imaging results. Baseline characteristics, imaging, biopsy results, and follow-up information were retrieved from the patient charts. Patients were classified as either MRI negative (Prostate Imaging Reporting and Data System [PIRADS] ≤ 2) or positive (PIRADS ≥ 3). ISUP grade group 1 was defined as clinically nonsignificant (nsPCa) and ≥2 as clinically significant PCa (csPCa). Primary outcome was the individual therapeutic decision after diagnosis of PCa stratified according to MRI visibility. Secondary outcomes were the sensitivity and specificity of MRI, and the urooncological outcomes after radical prostatectomy (RP). RESULTS: From 515 patients undergoing prostate biopsy, 171 (33.2%) patients had a negative and 344 (66.8%) a positive MRI. Pathology review stratified for MRI negative and positive cases revealed nsPCa in 27 (15.8%) and 32 (9.3%) and csPCa in 26 (15.2%) and 194 (56.4%) of the patients, respectively. The rate of active treatment in the MRI negative was lower compared with the MRI positive cohort (12.3% vs. 53.2%; odd ratio [OR] = 0.12; p < 0.001). While men with negative MRI were more likely to undergo active surveillance (AS) than MRI positive patients (18.1% vs. 10.8%; OR = 1.84; p = 0.027), they rarely underwent RP (6.4% vs. 40.7%, OR = 0.10; p < 0.001). Logistic regression revealed that a negative MRI was independently protective for active treatment (OR = 0.32, p = 0.014). The specificity, sensitivity, negative, and positive predictive value of MRI for detection of csPCa were 49.2%, 88.2%, 56.4%, and 84.8%, respectively. The rate of adverse clinicopathological outcome features (pT3/4, ISUP ≥4, or prostate-specific antigen [PSA]-persistence) following RP was 4.7% for men with MRI negative compared to 17.4% for men with MRI positive PCa (OR = 3.1, p = 0.19). CONCLUSION: Only few men with MRI negative PCa need active cancer treatment at the time of diagnosis, while the majority opts for AS. Omitting prostate biopsies and performing a follow-up MRI may be a safe alternative to reduce the number of unnecessary interventions.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/cirurgia , Neoplasias da Próstata/diagnóstico por imagem , Imageamento por Ressonância Magnética
5.
J Perinat Med ; 51(5): 634-640, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-36441559

RESUMO

OBJECTIVES: To compare short term variation (STV) and phase rectified signal averaging (PRSA) and their association with fetal outcome in early onset fetal growth restriction (FGR). METHODS: Data were used from a retrospective cohort study of women who were admitted for FGR and/or pre-eclampsia and who were delivered by pre-labor Cesarean section or had a fetal death before 32 weeks' gestation. Computerized cardiotocography (cCTG) registrations of the 5 days before delivery or fetal death were used for calculation of STV and PRSA. PRSA was expressed as the average acceleration capacity (AAC) and average deceleration capacity (ADC). FHR decelerations were classified visually as absent, 1-2 per hour or recurrent. Abnormality of STV and of PRSA was either analyzed as a single parameter or in combination with recurrent decelerations. Endpoints were defined as composite adverse condition at birth consisting of fetal death, low Apgar score, low umbilical pH, the need for resuscitation after birth and as major neonatal morbidity or neonatal death. RESULTS: Included were 367 pregnancies of which 20 resulted in fetal death. An abnormal cCTG with either recurrent decelerations and/or low STV or recurrent decelerations and/or low PRSA were similarly associated with composite adverse condition at birth (n=99), but neither with major neonatal morbidity. CONCLUSIONS: PRSA and STV have similar efficacy for measuring fetal heart rate variation in early onset FGR. An increased risk of a composite adverse condition at birth is indicated by a low value of either parameter and/or the presence of recurrent decelerations.


Assuntos
Cesárea , Retardo do Crescimento Fetal , Recém-Nascido , Gravidez , Humanos , Feminino , Retardo do Crescimento Fetal/diagnóstico , Estudos Retrospectivos , Cardiotocografia/métodos , Morte Fetal , Frequência Cardíaca Fetal/fisiologia
6.
Eur Arch Otorhinolaryngol ; 280(7): 3171-3176, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36707432

RESUMO

PURPOSE: Different techniques are used to fix crimp and CliP® Piston stapes prostheses to the long process of the incus (LPI). The CliP® Piston provides a stiff connection in contrast to the static bended loop of the crimp prosthesis, which imitates the physiological incudostapedial joint (ISJ) and thereby potentially leads to different hearing outcome. METHODS: In a retrospective single-center study of German-speaking one hundred and ninety patients who underwent stapes surgery CliP® Piston or crimp prostheses between the years of 2016 and 2019 by the same surgeon and in the same setting. Pre- and postoperative bone- (BC) and air-conduction (AC) pure-tone thresholds, pre- and postoperative air-bone gap (ABG) for 0.5, 1, 1.5, 2, 3, 4 kHz and the surgery time were examined. RESULTS: The postoperative bone conduction thresholds were significantly lower in the frequencies between 0.5 and 3 kHz and the mean ABG was < 10 dB in most cases independent of the prosthesis used. Crimp prosthesis showed a significantly better closure of the ABG at 0.5 kHz. CONCLUSIONS: The audiological outcome after stapes surgery is dependent on the type of prosthesis used, as reflected by the frequency-specific air-bone gap. The better ABG closure with the crimp prosthesis might be the result of the connection to the LPI imitating the physiological ISJ. The crimp prosthesis may be the better choice if use of hearing aids is expected postoperatively.


Assuntos
Prótese Ossicular , Otosclerose , Cirurgia do Estribo , Humanos , Estudos Retrospectivos , Implantação de Prótese , Cirurgia do Estribo/métodos , Audição , Estribo , Condução Óssea , Resultado do Tratamento , Otosclerose/cirurgia
7.
HNO ; 71(2): 100-105, 2023 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-36469098

RESUMO

SCIENTIFIC BACKGROUND: Speech audiometry measurements under the influence of background noise are a fundamental part of evaluating the outcome of hearing care. As yet far, there are no recommendations for selecting a suitable method for adaptive speech audiometry measurements in background noise in cochlear implant (CI) care, so either the choice the adaptive level change of the speech signal (S) with constant noise (N) or the adaptive level change of N with constant S. OBJECTIVES: Do the measurement results of the monaural speechrecognition threshold in noise (SRT) with the Oldenburg Sentence Test (OLSA) depend on the choice of level control? MATERIAL AND METHODS: A total of 50 series of measurements with OLSA in noise and the Freiburg speech intelligibility test in quiet (FBE) on middle-aged CI patients from clinical routine. RESULTS: There is no significant difference in the measurement results with different level controls when the SRT is less than 5 [Formula: see text]. Below 55 % monosyllabic intelligibility in quiet, the SRT in noise becomes greater than 5 [Formula: see text]. CONCLUSION: From a clinical, audiological and methodological point of view, it is advisable to carry out the adaptive monaural speech intelligibility measurement with a constant speech signal at 65 [Formula: see text].


Assuntos
Implante Coclear , Implantes Cocleares , Percepção da Fala , Pessoa de Meia-Idade , Humanos , Ruído/efeitos adversos , Audiometria da Fala , Inteligibilidade da Fala
8.
Diabetes Obes Metab ; 24(5): 849-858, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34984802

RESUMO

AIMS: To investigate the seroconversion following first and second COVID-19 vaccination in people with type 1 and type 2 diabetes in relation to glycaemic control prior to vaccination and to analyse the response in comparison to individuals without diabetes. MATERIALS AND METHODS: This prospective, multicentre cohort study analysed people with type 1 and type 2 diabetes and a glycated haemoglobin level ≤58 mmol/mol (7.5%) or >58 mmol/mol (7.5%), respectively, and healthy controls. Roche's Elecsys anti-SARS-CoV-2 S immunoassay targeting the receptor-binding domain was used to quantify anti-spike protein antibodies 7 to 14 days after the first and 14 to 21 days after the second vaccination. RESULTS: A total of 86 healthy controls were enrolled in the study, as well as 161 participants with diabetes, of whom 150 (75 with type 1 diabetes and 75 with type 2 diabetes) were eligible for the analysis. After the first vaccination, only 52.7% of participants in the type 1 diabetes group and 48.0% of those in the type 2 diabetes group showed antibody levels above the cut-off for positivity. Antibody levels after the second vaccination were similar in participants with type 1 diabetes, participants with type 2 diabetes and healthy controls after adjusting for age, sex and multiple testing (P > 0.05). Age (r = -0.45, P < 0.001) and glomerular filtration rate (r = 0.28, P = 0.001) were significantly associated with antibody response. CONCLUSIONS: Anti-SARS-CoV-2 S receptor-binding domain antibody levels after the second vaccination were comparable in healthy controls and in participants with type 1 and type 2 diabetes, irrespective of glycaemic control. Age and renal function correlated significantly with the extent of antibody levels.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Estudos de Coortes , Diabetes Mellitus Tipo 2/complicações , Humanos , Imunidade Humoral , Estudos Prospectivos , Vacinação
9.
Heart Vessels ; 37(7): 1195-1202, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35034171

RESUMO

High-sensitive troponin T (hs-TnT) is increasingly used for prognostication in patients with acute heart failure (AHF). However, uncertainty exists whether hs-TnT shows comparable prognostic performance in patients with heart failure and different classes of left ventricular ejection fraction (LV-EF). The aim of the present study was to assess the prognostic value of hs-TnT for the prediction of 30-day mortality depending on the presence of HF with preserved ejection fraction (HFpEF), HF with mid-range LV-EF (HFmrEF) and HF with reduced LV-EF (HFrEF) in patients with acutely decompensated HF. Patients admitted to our institution due to AHF were retrospectively included. Clinical information was gathered from electronic and paper-based patient charts. Patients with myocardial infarction were excluded. A total of 847 patients were enrolled into the present study. A significant association was found between HF groups and hs-TnT (regression coefficient -0.018 for HFpEF vs. HFmrEF/HFrEF; p = 0.02). The area under the curve (AUC) of hs-TnT for the prediction of 30-mortality was significantly lower in patients with HFpEF (AUC 0.61) than those with HFmrEF (AUC 0.80; p = 0.01) and HFrEF (AUC 0.73; p = 0.04). Hs-TnT was not independently associated with 30-day outcome in the HFpEF group (OR 1.48 [95%-CI 0.89-2.46]; p = 0.13) in contrast to the HFmrEF group (OR 4.53 [95%-CI 1.85-11.1]; p < 0.001) and HFrEF group (OR 2.58 [95%-CI 1.57-4.23]; p < 0.001). Prognostic accuracy of hs-TnT in patients hospitalized for AHF regarding 30-day mortality is significantly lower in patients with HFpEF compared to those with HFmrEF and HFrEF.


Assuntos
Insuficiência Cardíaca , Troponina T , Função Ventricular Esquerda , Insuficiência Cardíaca/mortalidade , Humanos , Prognóstico , Estudos Retrospectivos , Volume Sistólico , Troponina T/análise
10.
Heart Vessels ; 37(1): 69-76, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34152442

RESUMO

High-sensitive troponin T (hs-TnT) is increasingly used for clinical outcome prediction in patients with acute heart failure (AHF). However, there is an ongoing debate regarding the potential impact of renal function on the prognostic accuracy of hs-TnT in this setting. The aim of the present study was to assess the prognostic value of hs-TnT within 6 h of admission for the prediction of 30-day mortality depending on renal function in patients with AHF. Patients admitted to our institution due to AHF were retrospectively included. Clinical information was gathered from electronic and paper-based patient charts. Patients with myocardial infarction were excluded. A total of 971 patients were enrolled in the present study. A negative correlation between estimated glomerular filtration rate (eGFR) and hsTnT was identified (Pearson r = - 0.16; p < 0.001) and eGFR was the only variable to be independently associated with hsTnT. The area under the curve (AUC) of hs-TnT for the prediction of 30-mortality was significantly higher in patients with an eGFR ≥ 45 ml/min (AUC 0.74) compared to those with an eGFR < 45 ml/min (AUC 0.63; p = 0.049). Sensitivity and specificity of the Youden Index derived optimal cut-off for hs-TnT was higher in patients with an eGFR ≥ 45 ml/min (40 ng/l: sensitivity 73%, specificity 71%) compared to patients with an eGFR < 45 ml/min (55 ng/l: sensitivity 63%, specificity 62%). Prognostic accuracy of hs-TnT in patients hospitalized for AHF regarding 30-day mortality is significantly lower in patients with reduced renal function.


Assuntos
Insuficiência Cardíaca , Rim , Troponina T/análise , Biomarcadores , Taxa de Filtração Glomerular , Insuficiência Cardíaca/diagnóstico , Humanos , Rim/fisiologia , Prognóstico , Estudos Retrospectivos
11.
Eur Arch Otorhinolaryngol ; 279(10): 4667-4675, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34874465

RESUMO

PURPOSE: The Vibrant Soundbridge (VSB) was introduced in 1996, and the fourth generation of the audio processor recently released. This clinical study evaluates the audiological performance and subjective satisfaction of the new SAMBA 2 audio processor compared to its predecessor, SAMBA. METHOD: Fifteen VSB users tested both audio processors for approximately 3 weeks. Air conduction and bone conduction thresholds and unaided and aided sound field thresholds were measured with both devices. Speech performance in quiet (Freiburg monosyllables) and noise (OLSA) was evaluated as well as subjective listening effort (ACALES) and questionnaire outcomes (SSQ12 and APSQ). In addition, data from 16 subjects with normal hearing were gathered on sound field tests and ACALES. RESULTS: Both audio processors showed substantial improvement compared to the unaided condition. The SAMBA and SAMBA 2 had comparable performance in sound filed thresholds, while the SAMBA 2 was significantly better in speech in quiet, speech in noise, reduced listening effort, and improved subjective satisfaction compared with the SAMBA. CONCLUSION: The SAMBA 2 audio processor, compared to its predecessor SAMBA, offers improved performance throughout the parameters investigated in this study. Patients with a VSB implant would benefit from an upgrade to SAMBA 2.


Assuntos
Auxiliares de Audição , Prótese Ossicular , Percepção da Fala , Condução Óssea , Audição , Humanos
12.
J Emerg Med ; 62(3): 359-367, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35065860

RESUMO

BACKGROUND: The differentiation of myocardial infarction (MI) in the setting of acute heart failure (AHF) can be challenging because the majority of patients presenting with AHF show elevations of high-sensitive troponin (hs-Tn). Fast identification of MI is crucial to perform timely coronary angiography and to improve clinical outcome. OBJECTIVES: The aim of the present study was to assess the diagnostic accuracy of different levels of hs-Tn for the identification of type 1 MI in patients with AHF. METHODS: This was a retrospective single-center analysis of admitted AHF patients with documentation of high-sensitive troponin T (hs-TnT). RESULTS: A total of 649 patients were enrolled into the present study. Of them, 18% had type 1 MI, 7% had type 2 MI, 69% had myocardial injury, and 6% had no myocardial injury. The area under the curve of hs-TnT for the prediction of type 1 MI was 0.70. Sensitivity and specificity of the hs-TnT 99th percentile upper reference limit (URL) for type 1 MI was 100% and 8%, respectively. The Youden index derived cut-off of hs-TnT was 50 ng/L, showing a sensitivity and specificity for type 1 MI of 63% and 68%, respectively. No significant difference regarding 30-day mortality was found depending on the presence of type 1 MI (odds ratio 1.86; 95% confidence interval 0.91-3.81). CONCLUSIONS: Hs-TnT-based identification of type 1 MI in patients with AHF requires higher cut-offs compared with the 99th percentile URL used in overall acute coronary syndrome populations. However, the adjusted cut-off provided only moderate sensitivity and specificity.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Biomarcadores , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Humanos , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Estudos Retrospectivos , Troponina , Troponina T
13.
Anal Chem ; 93(6): 3112-3121, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33534544

RESUMO

Point-of-care (PoC) tests are practical and effective diagnostic solutions for major clinical problems, ranging from the monitoring of a pandemic to recurrent or simple measurements. Although, in recent years, a great improvement in the analytical performance of such sensors has been observed, there is still a major issue that has not been properly solved: the ability to perform adequate sample treatments. The main reason is that normally sample treatments require complicated or long procedures not adequate for deployment at the PoC. In response, a sensing platform, called paper-based electrophoretic bioassay (PEB), that combines the key characteristics of a lateral flow assay (LFA) with the sample treatment capabilities of electrophoresis is developed. In particular, the ability of PEB to separate different types of particles and to detect human antibodies in untreated spiked whole blood is demonstrated. Finally, to make the platform suitable for PoC, PEB is coupled with a smartphone that controls the electrophoresis and reads the optical signal generated. It is believed that the PEB platform represents a much-needed solution for the detection of low target concentrations in complex media, solving one of the major limitations of LFA and opening opportunities for point-of-care sensors.


Assuntos
Técnicas Biossensoriais , Smartphone , Bioensaio , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos
14.
Virol J ; 18(1): 169, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404450

RESUMO

BACKGROUND: Transmission of all known pathogenic orthohantaviruses (family Hantaviridae) usually occurs via inhalation of aerosols contaminated with viral particles derived from infected rodents and organ manifestation of infections is characterized by lung and kidney involvement. Orthohantaviruses found in Eurasia cause hemorrhagic fever with renal syndrome (HFRS) and New World orthohantaviruses cause hantavirus cardiopulmonary syndrome (HCPS). However, cases of infection with Old World orthohantaviruses with severe pulmonary manifestations have also been observed. Therefore, human airway cells may represent initial targets for orthohantavirus infection and may also play a role in the pathogenesis of infections with Eurasian orthohantaviruses. METHODS: We analyzed the permissiveness of primary endothelial cells of the human pulmonary microvasculature and of primary human epithelial cells derived from bronchi, bronchioles and alveoli for Old World orthohantavirus Puumala virus (PUUV) in vitro. In addition, we examined the expression of orthohantaviral receptors in these cell types. To minimize donor-specific effects, cells from two different donors were tested for each cell type. RESULTS: Productive infection with PUUV was observed for endothelial cells of the microvasculature and for the three tested epithelial cell types derived from different sites of the respiratory tract. Interestingly, infection and particle release were also detected in bronchial and bronchiolar epithelial cells although expression of the orthohantaviral receptor integrin ß3 was not detectable in these cell types. In addition, replication kinetics and viral release demonstrate enormous donor-specific variations. CONCLUSIONS: The human respiratory epithelium is among the first targets of orthohantaviral infection and may contribute to virus replication, dissemination and pathogenesis of HFRS-causing orthohantaviruses. Differences in initial pulmonary infection due to donor-specific factors may play a role in the observed broad variance of severity and symptoms of orthohantavirus disease in patients. The absence of detectable levels of integrin αVß3 surface expression on bronchial and small airway epithelial cells indicates an alternate mode of orthohantaviral entry in these cells that is independent from integrin ß3.


Assuntos
Células Endoteliais/virologia , Virus Puumala , Replicação Viral , Febre Hemorrágica com Síndrome Renal , Humanos , Integrinas , Cultura Primária de Células , Virus Puumala/fisiologia , Sistema Respiratório/citologia , Sistema Respiratório/virologia
15.
World J Urol ; 39(6): 2029-2035, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32929626

RESUMO

PURPOSE: To assess the effects of a new ejaculation-sparing thulium laser enucleation of the prostate (ES-ThuLEP) technique on sexual functions and micturition, in patients with lower urinary tract symptoms secondary to benign prostatic hyperplasia (BPH) and to evaluate how the surgical technique of ES-ThuLEP can lead to ejaculation preservation. METHODS: A prospective study was carried out between January 2015 and January 2018 on patients with surgical indication for BPH, who wished to preserve ejaculation. The patients were treated with ES-ThuLEP and were evaluated before and 3 and 6 months after surgery. Three validated questionnaires (ICIQ-MLUTSsex, IIEF-5 and IPSS) were used to assess changes in ejaculation, erectile function and urinary symptoms. Uroflowmetry (Qmax and Qavg), post-void residual volume and voided volume were also evaluated, to assess micturition improvement. Patients with moderate to severe erectile dysfunction were excluded. Statistical analysis was performed with the Student's t test, Chi-square test and logistic regression analysis. RESULTS: Two hundred and eighty three patients were enrolled. Ejaculation was spared in 203 and 219 patients at 3 and 6 months after surgery. No significant differences were observed between erectile function before and after surgery: baseline IIEF-5 = 16.2 ± 4.47 vs 16.7 ± 2.9 (p = 0.419) and 17.7 ± 3.2 (p = 0.410) at 3 and 6 months. Significant improvement in urinary symptoms was achieved: baseline IPSS = 19.4 ± 7.24 vs 5.8 ± 4.3 (p = 0.032) and 3.9 ± 4.1 (p = 0.029) at 3 and 6 months. CONCLUSION: ES-ThuLEP effectively preserved ejaculation in over two thirds of the patients without compromising micturition improvement or erectile function. ES-ThuLEP could be a valid treatment option for BPH in young and sexually active men.


Assuntos
Ejaculação , Terapia a Laser/métodos , Sintomas do Trato Urinário Inferior/cirurgia , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Túlio/uso terapêutico , Idoso , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Hiperplasia Prostática/complicações , Resultado do Tratamento
16.
World J Urol ; 39(7): 2375-2382, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32997262

RESUMO

PURPOSE: To compare intra and perioperative parameters between HoLEP and ThuLEP in the treatment of benign prostatic hyperplasia and to evaluate clinical and functional outcomes of the two procedures with a 12-month follow-up. METHODS: A prospective randomized study was performed on 236 consecutive patients who underwent ThuLEP (n = 115), or HoLEP (n = 121) in three different centers. Intra and perioperative parameters were analyzed: operative time, enucleated tissue weight, irrigation volume, blood loss, catheterization time, hospital stay and complications. Patients were evaluated preoperatively and 3 and 12 months postoperatively with the international prostate symptom score (IPSS), the quality of life (QoL) score, post-void residual volume (PVR), PSA and maximum flow rate (Qmax). RESULTS: Preoperative variables in each study arm did not show any significant difference. Compared to HoLEP, ThuLEP showed similar operative time (63.69 vs 71.66 min, p = 0.245), enucleated tissue weight (48.84 vs 51.13 g, p = 0.321), catheterization time (1.9 vs 2.0 days, p = 0.450) and hospital stay (2.2 vs 2.8 days, p = 0.216), but resulted in less haemoglobin decrease (0.45 vs 2.77 g/dL, p = 0.005). HoLEP presented a significantly higher number of patients with postoperative acute urinary retention and stress incontinence. No significant differences were found in PSA, Qmax, PVR, IPSS and QoL score during follow-up. CONCLUSION: ThuLEP and HoLEP both relieved lower urinary tract symptoms equally, with high efficacy and safety. ThuLEP detemined reduced blood loss and early postoperative complications. Catheterization time, enucleated tissue, hospital stay, operative time and follow-up parameters did not show any significant difference.


Assuntos
Lasers de Estado Sólido/uso terapêutico , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Túlio/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Europace ; 23(5): 789-796, 2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-33276379

RESUMO

AIMS: Present society is constantly ageing and elderly frequently suffer from conditions that are difficult and/or costly to treat if detected late. Effective screening of the elderly is therefore needed so that those requiring detailed clinical work-up are identified early. We present a prospective validation of a screening strategy based on a Polyscore of seven predominantly autonomic, non-invasive risk markers. METHODS AND RESULTS: Within a population-based survey in Germany (INVADE study), participants aged ≥60 years were enrolled between August 2013 and February 2015. Seven prospectively defined Polyscore components were obtained during 30-min continuous recordings of electrocardiogram, blood pressure, and respiration. Out of 1956 subjects, 168 were excluded due to atrial fibrillation, implanted pacemaker, or unsuitable recordings. All-cause mortality over a median 4-year follow-up was prospectively defined as the primary endpoint. The Polyscore divided the investigated population (n = 1788, median age: 72 years, females: 58%) into three predefined groups with low (n = 1405, 78.6%), intermediate (n = 326, 18.2%), and high risk (n = 57, 3.2%). During the follow-up, 82 (4.6%) participants died. Mortality in the Polyscore-defined risk groups was 3.4%, 7.4%, and 17.5%, respectively (P < 0.0001). The Polyscore-based mortality prediction was independent of Framingham score, diabetes, chronic kidney disease, and major stroke and/or myocardial infarction history. It was particularly effective in those aged <75 years (n = 1145). CONCLUSION: The Polyscore-based mortality risk assessment from short-term non-invasive recordings is effective in the elderly general population, especially those aged 60-74 years. Implementation of a comprehensive Polyscore screening of this age group is proposed to advance preventive medical care.


Assuntos
Infarto do Miocárdio , Acidente Vascular Cerebral , Idoso , Sistema Nervoso Autônomo , Feminino , Humanos , Estudos Prospectivos , Medição de Risco , Fatores de Risco
18.
Microsc Microanal ; 27(1): 129-139, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33303043

RESUMO

One of the primary uses for transmission electron microscopy (TEM) is to measure diffraction pattern images in order to determine a crystal structure and orientation. In nanobeam electron diffraction (NBED), we scan a moderately converged electron probe over the sample to acquire thousands or even millions of sequential diffraction images, a technique that is especially appropriate for polycrystalline samples. However, due to the large Ewald sphere of TEM, excitation of Bragg peaks can be extremely sensitive to sample tilt, varying strongly for even a few degrees of sample tilt for crystalline samples. In this paper, we present multibeam electron diffraction (MBED), where multiple probe-forming apertures are used to create multiple scanning transmission electron microscopy (STEM) probes, all of which interact with the sample simultaneously. We detail designs for MBED experiments, and a method for using a focused ion beam to produce MBED apertures. We show the efficacy of the MBED technique for crystalline orientation mapping using both simulations and proof-of-principle experiments. We also show how the angular information in MBED can be used to perform 3D tomographic reconstruction of samples without needing to tilt or scan the sample multiple times. Finally, we also discuss future opportunities for the MBED method.

19.
Eur Arch Otorhinolaryngol ; 278(7): 2277-2288, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32880736

RESUMO

PURPOSE: Evaluating the effectiveness of intraoperative auditory brainstem responses (ABRs) to stimulation by the Vibrant Soundbridge (VSB) active middle ear implant for quantifying the implant's floating mass transducer (FMT) coupling quality. METHODS: In a diagnostic multicentric study, patients (> 18 years) who received a VSB with different coupling modalities were included. Pre- and postoperative bone conduction thresholds, intraoperative VSB-evoked ABR thresholds (VSB-ABR) using a modified audio processor programmed to preoperative bone conduction thresholds, postoperative vibrogram thresholds, and postoperative VSB-ABR thresholds were measured. Coupling quality was calculated from the difference between the pure tone average at 1000, 2000, and 4000 Hz (3PTA) vibrogram and postoperative 3PTA bone conduction thresholds. RESULTS: Twenty-three patients (13 males, 10 females, mean age 56.6 (± 12.5) years) were included in the study. Intraoperative VSB-ABR response thresholds could be obtained in all except one patient where the threshold was > 30 dB nHL. Postoperatively, an insufficient coupling of 36.7 dB was confirmed in this patient. In a Bland-Altman analysis of the intraoperative VSB-ABRs and coupling quality, the limits of agreement exceeded ± 10 dB, i.e., the maximum allowed difference considered as not clinically important but the variation was within the general precision of auditory brainstem responses to predict behavioral thresholds. Five outliers were identified. In two patients, the postoperative VSB-ABR thresholds were in agreement with the coupling quality, indicating a change of coupling before the postoperative testing. CONCLUSION: The response thresholds recorded in this set-up have the potential to predict the VSB coupling quality and optimize postoperative audiological results.


Assuntos
Perda Auditiva Condutiva-Neurossensorial Mista , Prótese Ossicular , Limiar Auditivo , Condução Óssea , Potenciais Evocados Auditivos do Tronco Encefálico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transdutores
20.
Int J Audiol ; 60(7): 507-513, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33124508

RESUMO

OBJECTIVE: The goal of this study was the evaluation of a synthetic version of the Digits-in-Noise (DiN) in participants with normal hearing. Additionally, the basis characteristics of the DiN in CI recipients were investigated. DESIGN AND STUDY SAMPLE: Twenty participants with normal hearing and 21 CI recipients with a Nucleus®-System ran two to three adaptive and up to five fixed measurements. Afterwards the discrimination function was measured with fixed signal-to-noise ratios. RESULTS: All subjects were able to perform the DiN within three minutes per test run. The median speech reception threshold (SRT) for the NH was -8.1 dBSNR, with a median steepness of 23%/dBSNR. The median absolute test-retest difference in the NH group was 0.4 dB (range: 0 to 1.5 dB). In the CI group, the SRTs range from -6.6 to +12.4 dBSNR with a median test-retest difference of 0.4 dB (range: 0 to 6.1 dB). CONCLUSION: The synthetic DiN is a valuable complement of the audiometric test battery in CI recipients. The excellent applicability is also particularly helpful in poor performing CI recipients. With its small time exposure, it is a time- and cost-saving test, which could also be used at home via app to check the individual hearing success.


Assuntos
Implantes Cocleares , Percepção da Fala , Audiometria , Testes Auditivos , Humanos , Ruído/efeitos adversos , Razão Sinal-Ruído , Teste do Limiar de Recepção da Fala
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