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OBJECTIVE: The aim of this study was to determine whether the differences in insertion gains from the first fit to generic prescriptions of hearing aids can predict the self-reported hearing aid (HA) outcomes for first-time and experienced HA users. DESIGN: This was a prospective observational study. STUDY SAMPLE: The study included 885 first-time and 330 experienced HA users with a valid real-ear measurement on both ears and answers to the abbreviated version of the Speech, Spatial, and Quality of Hearing (SSQ12) and the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaires. RESULTS: K-means clustering of gain differences between individual real-ear insertion gain to three generic gain prescriptions (NAL-NL2, NAL-RP, and one-third gain rules) was performed. The gain difference at higher frequencies generally differentiated the clusters. The experienced users in the cluster with fittings closest to NAL-NL2 and NAL-RP prescription were found to exhibit a higher IOI-HA Factor 1 score (representing the overall benefit of the hearing aid use). The gain differences to generic prescription did not affect other self-reported outcomes for first-time and experienced HA users. CONCLUSION: The experienced HA users with minimal gain deviations from generic prescriptions reported better self-perceived benefits than users with larger deviations. However, this was not apparent in first-time users.
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Auxiliares de Audição , Perda Auditiva Neurossensorial , Humanos , Autorrelato , Perda Auditiva Neurossensorial/reabilitação , Prescrições , Medidas de Resultados Relatados pelo PacienteRESUMO
OBJECTIVE: To investigate the effect of hearing aid (HA) intervention on long-term health-related quality of life (HRQoL) changes in first-time and experienced HA users using the 15D questionnaire. Secondly, the study explored the relationship between clinical parameters and changes in 15D scores. DESIGN: A prospective observational study. STUDY SAMPLE: The study population included 1562 patients (1113 first-time and 449 experienced HA users) referred for HA rehabilitation. All patients responded to the 15D at baseline, two months after HA fitting, and at long-term follow-up (698 ± 298 d). RESULTS: Among both first-time and experienced HA users, significant improvements in hearing-dimension (15D-3) score were observed at two-month follow-up which sustained at long-term follow-up. 15D total scores significantly decreased at long-term follow-up. Self-reported hearing abilities, word recognition scores, and HA use time were significantly and positively correlated to increased 15D. CONCLUSIONS: Both groups of HA users reported improved hearing-related QoL after HA treatment which sustained at long-term follow-up but the improvement in total 15D total score did not sustain for either group. The results suggest that HA intervention positively affects hearing-related QoL among older adults with hearing loss, and the findings support the use of 15D as a tool for the evaluation of HA treatment effects.
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OBJECTIVE: The speech intelligibility index (SII) is used to quantify the audibility of the speech. This study examined the relationship between self-reported hearing aid (HA) outcomes and the difference in aided SII (SIIA) calculated from the initial fit (IF) gain and that prescribed as per the second generation of National Acoustic Laboratory Non-Linear (NAL-NL2). DESIGN: A prospective observational study. STUDY SAMPLE: The study included 718 first-time and 253 experienced HA users. All users had a valid real-ear measurement (REM) at three input levels (55, 65 and 80 dB SPL). RESULTS: The gain provided by IF was lower than NAL-NL2 at 55 and 65 dB SPL. IF gain exhibited reduced compression than NAL-NL2 as input levels increased from 55 to 80 dB SPL. On average, the SIIA provided by IF was significantly lower than that for NAL-NL2 at all input levels. The difference in SIIA between IF and NAL-NL2 at 80 dB SPL input level with 0 dB signal-to-noise ratio (SNR) turned out to be a predictor for self-reported outcome for first-time HA users. CONCLUSION: The study suggests that an SIIA close to that provided by NAL-NL2 at high input levels would be preferred to obtain a better self-reported outcome. .
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OBJECTIVE: To investigate the effects of previous occupational noise exposure in older adults with hearing loss on (1) audiometric configuration and acoustic reflex (AR) thresholds and (2) self-reported hearing abilities and hearing aid (HA) effectiveness. DESIGN: A prospective observational study. STUDY SAMPLE: The study included 1176 adults (≥60 years) with bilateral sensorineural hearing loss. Pure-tone audiometry, AR thresholds, and responses to the abbreviated version of the Speech, Spatial, and Qualities of Hearing Scale (SSQ12) and the International Outcome Inventory for Hearing Aids (IOI-HA) questionnaire were obtained, along with information about previous occupational noise exposure. RESULTS: Greater occupational noise exposure was associated with a higher prevalence of steeply sloping audiograms in men and women and a 0.32 (95% CI: -0.57; -0.06) scale points lower mean SSQ12 total score among noise-exposed men. AR thresholds did not show a significant relation to noise-exposure status, but hearing thresholds at a given frequency were related to elevated AR thresholds at the same frequency. CONCLUSIONS: A noise exposure history is linked to steeper audiograms in older adults with hearing loss as well as to poorer self-reported hearing abilities in noise-exposed men. More attention to older adults with previous noise exposure is warranted in hearing rehabilitation.
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To use regeneratively active cells for cell therapeutic applications, the cells must be isolated from their resident tissues. Different isolation procedures subject these cells to varying degrees of mechanical strain, which can affect the yield of cell number and viability. Knowledge of cell volumetric mass density is important for experimental and numerical optimization of these procedures. Although methods for measuring cell volumetric mass density already exist, they either consume much time and cell material or require a special setup. Therefore, we developed a user-friendly method that is based on the use of readily available instrumentation. The newly developed method is predicated on the linear relationship between the volumetric mass density of the cell suspension and the volumetric mass density, number, and diameter of the cells in the suspension. We used this method to determine the volumetric mass density of mesenchymal stem cells (MSCs) and compared it to results from the established density centrifugation.
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Mesenchymal stem/stromal cells (MSC) are capable of progenitor cell fraction renewal or tissue-specific differentiation. These properties are maintained during in vitro cultivation, making them an interesting model system for testing biological and pharmacological compounds. Cell cultivation in 2D is commonly used to study cellular responses, but the 2D environment does not reflect the structural situation of most cell types. Therefore, 3D culture systems have been developed to provide a more accurate physiological environment in terms of cell-cell interactions. Since knowledge about the effects of 3D culture on specific differentiation processes is limited, we studied the effects on osteogenic differentiation and the release of factors affecting bone metabolism for up to 35 days and compared them with the effects in 2D culture. We demonstrated that the selected 3D model allowed the rapid and reliable formation of spheroids that were stable over several weeks and both accelerated and enhanced osteogenic differentiation compared with the 2D culture. Thus, our experiments provide new insights into the effects of cell arrangement of MSC in 2D and 3D. However, due to the different culture dimensions, various detection methods had to be chosen, which in principle limits the explanatory power of the comparison between 2D and 3D cultures.
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PURPOSE: This study was aimed at understanding the effect of time taken to adapt to the new hearing aids (HAs) and the timeline of HA adjustments performed over more than a year of rehabilitation on self-reported HA outcomes. METHOD: A self-report of the time it took to get accustomed to the new HAs and adjustment of the HAs during a year of rehabilitation collected from 690 HA users using a nonstandardized questionnaire were analyzed. The abbreviated version of the Speech, Spatial, and Quality of Hearing questionnaire and the International Outcome Inventory for Hearing Aids were used as the self-reported HA outcome. RESULT: Out of 690 participants, 442 (64%) got accustomed to HAs within 2 months. Ninety-one participants (13%) did not get accustomed to the HAs at all, out of which 74 (81%) were first-time HA users. Eighty-four participants (12%) did not receive any HA adjustments after their initial fitting, and 49 (7%) had their HAs adjusted four or more times during the 1 year of rehabilitation. Three hundred ninety (57%) participants got their HA adjusted only at the 2-month follow-up visit, showing the intent to adjust given an opportunity. The stepwise multiple linear regression results showed the significant impact of getting accustomed to the HA and having HA adjusted at multiple instances on the self-reported HA outcomes. CONCLUSION: This study showed the importance of getting accustomed to the HA and having a minimal number of adjustments to have a better long-term self-reported HA outcome.
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Auxiliares de Audição , Humanos , Adulto , Idioma , Inquéritos e Questionários , Autorrelato , DinamarcaRESUMO
To provide clinical guidance in hearing aid prescription for older adults with presbycusis, we investigated differences in self-reported hearing abilities and hearing aid effectiveness for premium or basic hearing aid users. Secondly, as an explorative analysis, we investigated if differences in gain prescription verified with real-ear measurements explain differences in self-reported outcomes. The study was designed as a randomized controlled trial in which the patients were blinded towards the purpose of the study. In total, 190 first-time hearing aid users (>60 years of age) with symmetric bilateral presbycusis were fitted with either a premium or basic hearing aid. The randomization was stratified on age, sex, and word recognition score. Two outcome questionnaires were distributed: the International Outcome Inventory for Hearing Aids (IOI-HA) and the short form of the Speech, Spatial, and Qualities of Hearing Scale (SSQ-12). In addition, insertion gains were calculated from real-ear measurements at first-fit for all fitted hearing aids. Premium hearing aid users reported 0.7 (95%CI: 0.2; 1.1) scale points higher total SSQ-12 score per item and 0.8 (95%CI: 0.2; 1.4) scale points higher speech score per item, as well as 0.6 (95%CI: 0.2; 1.1) scale points higher qualities score compared to basic-feature hearing aid users. No significant differences in reported hearing aid effectiveness were found using the IOI-HA. Differences in the prescribed gain at 1 and 2 kHz were observed between premium and basic hearing aids within each company. Premium-feature devices yielded slightly better self-reported hearing abilities than basic-feature devices, but a statistically significant difference was only found in three out of seven outcome variables, and the effect was small. The generalizability of the study is limited to community-dwelling older adults with presbycusis. Thus, further research is needed for understanding the potential effects of hearing aid technology for other populations. Hearing care providers should continue to insist on research to support the choice of more costly premium technologies when prescribing hearing aids for older adults with presbycusis. Clinical Trial Registration: https://register.clinicaltrials.gov/, identifier NCT04539847.
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The retrospective reporting of users' hearing aid (HA) usage can provide insight into individualized HA usage patterns. Understanding these HA usage patterns can help to provide a tailored solution to meet the usage needs of HA users. This study aims to understand the HA usage pattern in daily-life situations from self-reported data and to examine its relationship to self-reported outcomes. A total of 1537 participants who responded to questions related to situations where they always took off or put on the HAs were included in the study. A latent class analysis was performed to stratify the HA users according to their HA usage pattern. The results showed distinct usage patterns in the latent classes derived for both scenarios. The demographics, socio-economic indicators, hearing loss, and user-related factors were found to impact HA usage. The results showed that the HA users who reported using the HAs all the time (regular users) had better self-reported HA outcomes than situational users, situational non-users, and non-users. The study explained the underlying distinct HA usage pattern from self-reported questionnaires using latent class analysis. The results emphasized the importance of regular use of HAs for a better self-reported HA outcome.
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Mesenchymal stem/stromal cells (MSC) are capable of renewing the progenitor cell fraction or differentiating in a tissue-specific manner. Adipogenic differentiation of adipose-tissue-derived MSC (adMSC) is important in various pathological processes. Adipocytes and their progenitors are metabolically active and secrete molecules (adipokines) that have both pro- and anti-inflammatory properties. Cell culturing in 2D is commonly used to study cellular responses, but the 2D environment does not reflect the structural situation for most cell types. Therefore, 3D culture systems have been developed to create an environment considered more physiological. Since knowledge about the effects of 3D cultivation on adipogenic differentiation is limited, we investigated its effects on adipogenic differentiation and adipokine release of adMSC (up to 28 days) and compared these with the effects in 2D. We demonstrated that cultivation conditions are crucial for cell behavior: in both 2D and 3D culture, adipogenic differentiation occurred only after specific stimulation. While the size and structure of adipogenically stimulated 3D spheroids remained stable during the experiment, the unstimulated spheroids showed signs of disintegration. Adipokine release was dependent on culture dimensionality; we found upregulated adiponectin and downregulated pro-inflammatory factors. Our findings are relevant for cell therapeutic applications of adMSC in complex, three-dimensionally arranged tissues.
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Adipogenia , Células-Tronco Mesenquimais , Adipócitos , Adipocinas/metabolismo , Diferenciação Celular , Células-Tronco Mesenquimais/metabolismoRESUMO
BACKGROUND: Heart disease and atrial fibrillation are the leading causes of death worldwide. Patient morbidity and mortality associated with cardiovascular disease can be reduced by more accurate and continuous diagnostic and therapeutic tools provided by cardiovascular implantable electronic devices (CIEDs). OBJECTIVES: Long-term operation of CIEDs continues to be a challenge due to limited battery life and the associated risk of device failure. To overcome this issue, new approaches for autonomous battery supply are being investigated. RESULTS: Here, the state of the art in CIED power supply is presented and an overview of current strategies for autonomous power supply in the cardiovascular field is given, using the body as a sustainable energy source. Finally, future challenges and potentials as well as advanced features for CIEDs are discussed. CONCLUSION: CIEDs need to fulfil more requirements for diagnostic and telemetric functions, which leads to higher energy requirements. Ongoing miniaturization and improved sensor technologies will help in the development of new devices.
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Fibrilação Atrial , Desfibriladores Implantáveis , Cardiopatias , Marca-Passo Artificial , Fibrilação Atrial/terapia , Previsões , Cardiopatias/terapia , HumanosRESUMO
The relation between degree of sensorineural hearing loss and maximum speech identification scores (PBmax) is commonly used in audiological diagnosis and rehabilitation. It is important to consider the relation between the degree of hearing loss and the lower boundary of PBmax, as the PBmax varies largely between subjects at a given degree of hearing loss. The present study determines the lower boundary by estimating the lower limit of the one-tailed 95% confidence limit (CL) for a Dantale I, word list, in a large group of young and older subjects with primarily sensorineural hearing loss. PBmax scores were measured using Dantale I, at 30 dB above the speech reception threshold or at the most comfortable level from 1,961 subjects with a wide range of pure-tone averages. A nonlinear quantile regression approach was applied to determine the lower boundary (95% CL) of PBmax scores. At a specific pure-tone average, if the measured PBmax is poorer than the lower boundary (95% CL) of PBmax, it may be considered disproportionately poor.
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Perda Auditiva Neurossensorial , Perda Auditiva , Percepção da Fala , Audiometria de Tons Puros , Audiometria da Fala , Perda Auditiva Neurossensorial/diagnóstico , Humanos , FalaRESUMO
BACKGROUND: Percutaneous coronary intervention is among the most common therapeutic interventions in cardiology. This procedure may, however, be associated with a rare, though life-threatening complication: acute coronary perforation (CP). CP is primarily treated using covered stents, which are made of bare metal stents with a polytetrafluoroethylene (PTFE) or polyurethane coating. These stents' major limitations include higher rates of thrombus formation and restenosis. Hence, there is a still unmet need for new stents regarding their design and composition. Or, to test new covered stent designs, the rabbit iliac artery has become the best-established animal model. This study sought to present a preclinical animal approach designed to test covered stents that are utilized following vessel perforation. METHODS: The animal experiments were performed using New Zealand white rabbits, each weighting 3.5-4.5 kg. The animal models described herein relied on the three most common clinical causes for CP, such as guidewire-induced, balloon catheter bursting, and device oversizing. Moreover, the sealing capacity of covered stent grafts was assessed for each of these models by means of angiography. RESULTS: We herein report a rabbit iliac artery perforation model using three different types of vessel perforation that closely mimic the clinical setting, such as guidewire-induced, balloon catheter rupture, and device oversizing. Using the same rabbit iliac perforation model, we additionally assessed the sealing capacity of a covered stent graft for each model. CONCLUSIONS: The novel rabbit iliac artery perforation models, as described in this report, represent promising animal testing approaches. While their setting is very similar to the real-life context encountered in humans, all three models are based on an animal model that is ideally suited for evaluating the sealing capacity and performance of new medical devices for humans.
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Doença das Coronárias/terapia , Modelos Animais de Doenças , Traumatismos Cardíacos/prevenção & controle , Intervenção Coronária Percutânea/efeitos adversos , Stents , Animais , Traumatismos Cardíacos/etiologia , CoelhosRESUMO
Vitamin D is critical for calcium homeostasis. Following cutaneous synthesis or ingestion, vitamin D is metabolized to 25(OH)D and then to the active form 1,25(OH)2D. Low serum vitamin D levels are common in the general population and cause a decline in calcium absorption, leading to low serum levels of ionized calcium, which in turn trigger the release of parathyroid hormone, promoting skeletal resorption and, eventually, bone loss or osteomalacia. Vitamin D deficiency is generally defined as a serum 25(OH)D concentration <25-37 nmol/l (<10-15 ng/ml), but the definition of the milder state of vitamin D insufficiency is controversial. Three recent meta-analyses concluded that vitamin D must be administered in combination with calcium in order to substantially reduce the risk of nonvertebral fracture in adults over the age of 50 years. Fracture protection is optimal when patient adherence to medication exceeds 80% and vitamin D doses exceed 700 IU/day. In addition to disordered calcium homeostasis, low vitamin D levels might have effects on cell proliferation and differentiation and immune function. Randomized, double-blind, placebo-controlled trials are needed to clarify whether vitamin D supplementation is beneficial in cancer, autoimmune disease and infection. This Review focuses on the pathophysiology, clinical correlates, evaluation and treatment of hypovitaminosis D.
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Fenômenos Fisiológicos Musculoesqueléticos , Deficiência de Vitamina D/fisiopatologia , Vitamina D/fisiologia , Cálcio da Dieta/administração & dosagem , Suplementos Nutricionais , Humanos , Vitamina D/administração & dosagem , Vitamina D/sangue , Vitamina D/metabolismo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
BACKGROUND: The regeneration of tissue defects at the interface between soft and hard tissue, eg, in the periodontium, poses a challenge due to the divergent tissue requirements. A class of biomaterials that may support the regeneration at the soft-to-hard tissue interface are self-assembling peptides (SAPs), as their physicochemical and mechanical properties can be rationally designed to meet tissue requirements. MATERIALS AND METHODS: In this work, we investigated the effect of two single-component and two complementary ß-sheet forming SAP systems on their hydrogel properties such as nanofibrillar architecture, surface charge, and protein adsorption as well as their influence on cell adhesion, morphology, growth, and differentiation. RESULTS: We showed that these four 11-amino acid SAP (P11-SAP) hydrogels possessed physico-chemical characteristics dependent on their amino acid composition that allowed variabilities in nanofibrillar network architecture, surface charge, and protein adsorption (eg, the single-component systems demonstrated an ~30% higher porosity and an almost 2-fold higher protein adsorption compared with the complementary systems). Cytocompatibility studies revealed similar results for cells cultured on the four P11-SAP hydrogels compared with cells on standard cell culture surfaces. The single-component P11-SAP systems showed a 1.7-fold increase in cell adhesion and cellular growth compared with the complementary P11-SAP systems. Moreover, significantly enhanced osteogenic differentiation of human calvarial osteoblasts was detected for the single-component P11-SAP system hydrogels compared with standard cell cultures. CONCLUSION: Thus, single-component system P11-SAP hydrogels can be assessed as suitable scaffolds for periodontal regeneration therapy, as they provide adjustable, extracellular matrix-mimetic nanofibrillar architecture and favorable cellular interaction with periodontal cells.
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Aminoácidos/química , Hidrogéis/química , Nanofibras/química , Osteoblastos/citologia , Osteogênese , Fragmentos de Peptídeos/química , Periodonto/citologia , Adesão Celular , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Matriz Extracelular , Humanos , Técnicas In Vitro , Células-Tronco Neurais/citologia , Células-Tronco Neurais/fisiologia , Osteoblastos/fisiologia , Periodonto/fisiologiaRESUMO
Kawasaki Disease is a small-to-medium-vessel vasculitis that preferentially affects children. Kawasaki Disease can occur in adults, but the presentation may differ from that observed in children. Typical findings in both adults and children include fever, conjunctivitis, pharyngitis, and skin erythema progressing to a desquamating rash on the palms and soles. Adults more frequently present with cervical adenopathy (93% of adults vs. 15% of children), hepatitis (65% vs. 10%), and arthralgia (61% vs. 24-38%). In contrast, adults are less frequently affected by meningitis (10% vs. 34%), thrombocytosis (55% vs. 100%), and coronary artery aneurysms (5% vs. 18-25%). We report a case of acute Kawasaki Disease in a 24-year-old man who presented with rash, fever, and arthritis. He was successfully treated with high-dose aspirin and intravenous immunoglobulin (IVIG). Our case highlights the importance of considering Kawasaki Disease in adults presenting with symptoms commonly encountered in a general medical practice.
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Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/fisiopatologia , Doença Aguda , Adulto , Aspirina/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológicoRESUMO
OBJECTIVE: Pediatric cardiac arrest carries a poor prognosis. Basic life support improves survival. Studies on pediatric basic life support (PBLS) training are sparse. The aim of our study was to investigate the effect of self-training in PBLS. PARTICIPANTS AND METHODS: We conducted a prospective controlled trial enrolling nurses from pediatric and maternity wards (n=29 in each group). Self-training, including a manikin and access to a web-based video on PBLS, was compared with a 2-h instructor-led course. Two weeks after training, all participants were tested in a mock scenario of pediatric cardiac arrest. Fifteen parameters equivalent to the steps in the PBLS algorithm - for example, effective ventilations, effective chest compressions, calling for help, and correct sequence of actions, were evaluated and rated dichotomously (1=approved or 0=not approved). RESULTS: No difference was observed in the baseline demographics between the self-training group and the instructor-led group. The participants in the self-training group accessed the website 2±1.5 times (mean±SD) and spent 41±25 min on the site. There was no significant difference between the two groups in the overall average score (10.5 in the self-training group vs. 10.0 in the instructor-led group, P=0.51) or in any of the 15 parameters. After the study, all participants felt that they had improved their skills and felt capable of performing PBLS. CONCLUSION: Self-training is not statistically different to instructor-led training in teaching PBLS. Self-evaluated confidence improved, but showed no difference between groups. PBLS may be disseminated through self-training.
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Reanimação Cardiopulmonar/educação , Enfermagem em Emergência/educação , Adulto , Criança , Avaliação Educacional , Feminino , Parada Cardíaca/terapia , Humanos , Manequins , EnsinoRESUMO
OBJECTIVE: To study if the public is able to recognise and understand the International Liaison Committee on Resuscitation (ILCOR) sign for automated external defibrillators (AEDs), and to explore how national resuscitation councils have adopted the sign. METHODS: A survey was conducted among travellers in an international airport serving 21 million passengers annually. Participants were asked to state the meaning of six international safety signs, one of which was the ILCOR AED sign. Also, all national resuscitation councils forming ILCOR were contacted to determine whether they recommend the ILCOR AED sign and the existence of national legislation regarding AED signage. RESULTS: In total, 493 travellers (42 nationalities) were included. Correct identification of the ILCOR AED sign was achieved by 39% (95% CI 35% to 43%). Information on AED signage was obtained from 41 of 44 (93%) national resuscitation councils; 26 councils (63%) recommended the use of the ILCOR AED sign. In two countries, the ILCOR AED sign was mandatory by law. CONCLUSIONS: There is limited public recognition and understanding of the ILCOR AED sign. The ILCOR AED sign is not unanimously recommended by national resuscitation councils worldwide. Initiatives promoting public awareness of AEDs are warranted.
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Aeroportos , Compreensão , Cardioversão Elétrica/instrumentação , Conhecimentos, Atitudes e Prática em Saúde , Diretórios de Sinalização e Localização , Parada Cardíaca Extra-Hospitalar/terapia , Reconhecimento Psicológico , Ressuscitação/instrumentação , Viagem , Adolescente , Adulto , Conscientização , Criança , Estudos Transversais , Desfibriladores , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Hypertension is a major risk factor for development of atherosclerotic cardiovascular disease (ASCVD). Although lowering blood pressure with antihypertensive drugs reduces the increased risk of ASCVD, residual increased risk still remains, suggesting that hypertension may cause chronic changes that promote atherosclerosis. Thus, we tested the hypothesis that hypertension increases the susceptibility to atherosclerosis in mice even after a period of re-established normotension. METHODS: We used the 2-kidney, 1-clip (2K1C) technique to induce angiotensin-driven renovascular hypertension, and overexpression of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene to cause severe hypercholesterolemia and atherosclerosis. RESULTS: First, we performed 2K1C (n = 8) or sham surgery (n = 9) in PCSK9 transgenic mice before they were fed a high fat diet for 14 weeks. As expected, 2K1C did not affect cholesterol levels, but induced cardiac hypertrophy and significantly increased the atherosclerotic lesion area compared to sham mice (1.8 fold, p < 0.01). Next, we performed 2K1C (n = 13) or sham surgery (n = 14) in wild-type mice but removed the clipped/sham-operated kidney after 10 weeks to eliminate hypertension, and subsequently induced hypercholesterolemia by way of adeno-associated virus-mediated hepatic gene transfer of PCSK9 combined with high-fat diet. After 14 weeks of hypercholesterolemia, atherosclerotic lesion areas were not significantly different in mice with or without prior 2K1C hypertension (0.95 fold, p = 0.35). CONCLUSION: Renovascular hypertension in mice does not induce pro-atherogenic changes that persist beyond the hypertensive phase. These results indicate that hypertension only promotes atherogenesis when coinciding temporally with hypercholesterolemia.
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Aterosclerose/complicações , Hipercolesterolemia/complicações , Hipertensão Renovascular/complicações , Animais , Aterosclerose/diagnóstico , Aterosclerose/patologia , Aterosclerose/fisiopatologia , Pressão Sanguínea , Dieta Hiperlipídica , Modelos Animais de Doenças , Técnicas de Transferência de Genes , Humanos , Hipercolesterolemia/patologia , Hipertensão Renovascular/patologia , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fatores de Risco , Sístole , Resultado do TratamentoRESUMO
The presence and expression of sopB, sopD1, sopE1, and avrA genes encoding virulence associated effector proteins were studied comparatively in 405 Salmonella enterica strains. They belong to different serovars and clonal types (genotypes, phage types) and originated from different clinical (systemic infection, focal enteritis, enterocolitis) and epidemic sources (epidemics, sporadic cases). The sopB and sopD1 determinants were commonly prevalent, but sopE1 and avrA genes only in 55% and 80%, respectively. A correlation of this pattern of absence and presence of the respective genes to the epidemic and clinical origin could not be detected. In contrast, the expression of the respective genes appeared differently: SopB and SopE1 proteins are well produced, but SopD1 and AvrA proteins only rarely under the applied standard culture conditions. However, using a range of different environmental signals (temperature, pH, cations, etc.) some of the S. enterica nonproducer strains (e. g., S. Agona, S. Bovismorbificans, S. Virchow, etc.) begin to produce AvrA and SopD1. They turned now into an expression profile which was found typically for the epidemic strains of S. Typhimurium and S. Enteritidis. Also S. enterica strains from systemic infections could be characterized by their strong SopB and SopE1 expression while SopD1 and AvrA proteins were missing. Although it is premature to outline generally a correlation of these expression profiles and the clinical and epidemiological potency of Salmonellae, the reported results allow a first understanding how a fine tuning of their virulence will take place.