RESUMO
Epitranscriptomic events such as adenosine-to-inosine (A-to-I) RNA editing by ADAR can recode mRNAs to translate novel proteins. Editing of the mRNA that encodes actin crosslinking protein Filamin A (FLNA) mediates a Q-to-R transition in the interactive C-terminal region. While FLNA editing is conserved among vertebrates, its physiological function remains unclear. Here, we show that cardiovascular tissues in humans and mice show massive editing and that FLNA RNA is the most prominent substrate. Patient-derived RNA-Seq data demonstrate a significant drop in FLNA editing associated with cardiovascular diseases. Using mice with only impaired FLNA editing, we observed increased vascular contraction and diastolic hypertension accompanied by increased myosin light chain phosphorylation, arterial remodeling, and left ventricular wall thickening, which eventually causes cardiac remodeling and reduced systolic output. These results demonstrate a causal relationship between RNA editing and the development of cardiovascular disease indicating that a single epitranscriptomic RNA modification can maintain cardiovascular health.
Assuntos
Pressão Sanguínea , Filaminas/metabolismo , Hipertensão/metabolismo , Contração Muscular , Miocárdio/metabolismo , Edição de RNA , Precursores de RNA/metabolismo , Remodelação Vascular , Animais , Filaminas/genética , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Hipertensão/genética , Hipertensão/patologia , Camundongos , Miocárdio/patologia , Precursores de RNA/genética , Análise de Sequência de RNARESUMO
OBJECTIVE: To examine whether parenteral nutrition using a mixed lipid emulsion containing fish oil improves the neurodevelopmental outcomes of extremely low birth weight infants. STUDY DESIGN: The study is a secondary outcome analysis of a double-blind randomized trial of 230 extremely low birth weight infants performed at a single level IV neonatal care unit (Medical University Vienna; June 2012 to June 2015). Participants received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil, or a soybean oil-based lipid emulsion for parenteral nutrition. Neurodevelopment of study participants was assessed at 12 and 24 months corrected age (August 2013 to October 2017) using the Bayley Scales of Infant-Toddler Development, third edition. RESULTS: At discharge, 206 of the 230 study participants were eligible. At 12 and 24 months corrected age, 174 of 206 (85%) and 164 of 206 (80%) infants were evaluated. At 12 months, there was no significant difference in cognitive (mixed lipid: median, 95 [IQR, 85-101]; soybean oil: median, 95 [IQR, 85-100]; P = .71), language (mixed lipid: median, 86 [IQR, 77-94], soybean oil: median, 89 [IQR, 79-94]; P = .48), or motor scores (mixed lipid: median, 88 [IQR, 76-94], soybean oil: median, 88 [IQR, 79-94]; P = .69). At 24 months, there was again no significant difference in cognitive (mixed lipid: median, 95 [IQR, 80-105], soybean oil: median, 95 [IQR, 90-105]; P = .17), language (mixed lipid: median, 89 [IQR, 75-97], soybean oil 89 [IQR, 77-100]; P = .54), and motor scores (mixed lipid: median, 94 [IQR, 82-103], soybean oil: median, 94 [IQR, 85-103]; P = .53). CONCLUSIONS: Parenteral nutrition using a mixed lipid emulsion containing fish oil did not improve neurodevelopment of extremely low birth weight infants at 12 and 24 months corrected age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585935.
Assuntos
Emulsões Gordurosas Intravenosas/uso terapêutico , Óleos de Peixe/uso terapêutico , Transtornos do Neurodesenvolvimento/prevenção & controle , Nutrição Parenteral , Método Duplo-Cego , Feminino , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Azeite de Oliva/uso terapêutico , Óleo de Soja/uso terapêutico , Triglicerídeos/uso terapêuticoRESUMO
PURPOSE: The impact of peripheral retinal lesions (PL) visualized with ultra-wide-field imaging on diabetic retinopathy (DR) remains unclear. The purpose of this study was to assess the presence of PL and their association with macular microvasculopathy, metabolic dysfunction, and neurodegeneration in patients with Type II diabetes and early retinal disease. METHODS: Forty-five degree color fundus (Topcon) and 200° ultra-wide-field images (Optos) were assessed for the presence and severity of DR. Lesions anterior to the 45° were considered peripheral. The foveal avascular zone area, perimeter and acircularity index, and foveal full-retina and parafoveal superficial/deep complex vessel density were evaluated with RTVue optical coherence tomography angiography. Vessel oxygen saturation was measured with oximetry. Peripapillary retinal nerve fiber and individual macular retinal layer thicknesses were measured with Spectralis optical coherence tomography. RESULTS: Among the 161 eyes (80 left eyes) of 81 patients (34 female), 64 (39.8%) showed higher levels of DR on ultra-wide-field than on 45° fundus images (P < 0.0001). PL were identified in 97 eyes (60.3%) and in 59 among 115 eyes without central signs of DR. No significant correlation to biomarkers of central microvascular disease (foveal avascular zone/vessel density variables), oxygen saturation, and retinal layer thickness was found. CONCLUSION: Ultra-wide-field imaging helps to detect more eyes with early DR due to the detection of PL, which appear independently of biomarkers of macular microvascular impairment, metabolic function, and neuropathy in eyes without central signs of DR. These results suggest that the evaluation of the retinal periphery may become crucial in DR screening if PL are proven to influence disease outcomes.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Retinopatia Diabética/diagnóstico , Oxigênio/sangue , Degeneração Retiniana/diagnóstico , Vasos Retinianos/fisiopatologia , Adulto , Idoso , Retinopatia Diabética/fisiopatologia , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Oximetria , Degeneração Retiniana/fisiopatologia , Tomografia de Coerência ÓpticaRESUMO
PURPOSE: To quantify morphologic photoreceptor integrity during anti-vascular endothelial growth factor (anti-VEGF) therapy of neovascular age-related macular degeneration and correlate these findings with disease morphology and function. METHODS: This presents a post hoc analysis on spectral-domain optical coherence tomography data of 185 patients, acquired at baseline, Month 3, and Month 12 in a multicenter, prospective trial. Loss of the ellipsoid zone (EZ) was manually quantified in all optical coherence tomography volumes. Intraretinal cystoid fluid, subretinal fluid (SRF), and pigment epithelial detachments were automatically segmented in the full volumes using validated deep learning methods. Spatiotemporal correlation of fluid markers with EZ integrity as well as bivariate analysis between EZ integrity and best-corrected visual acuity was performed. RESULTS: At baseline, EZ integrity was predominantly impaired in the fovea, showing progressive recovery during anti-vascular endothelial growth factor therapy. Topographic analysis at baseline revealed EZ integrity to be more likely intact in areas with SRF and vice versa. Moreover, we observed a correlation between EZ integrity and resolution of SRF. Foveal EZ integrity correlated with best-corrected visual acuity at all timepoints. CONCLUSION: Improvement of EZ integrity during anti-VEGF therapy of neovascular age-related macular degeneration occurred predominantly in the fovea. Photoreceptor integrity correlated with best-corrected visual acuity. Ellipsoid zone integrity was preserved in areas of SRF and showed deterioration upon SRF resolution.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Células Fotorreceptoras de Vertebrados/patologia , Doenças Retinianas/diagnóstico por imagem , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Neovascularização de Coroide/fisiopatologia , Feminino , Angiofluoresceinografia , Humanos , Processamento de Imagem Assistida por Computador , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ranibizumab/uso terapêutico , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual , Degeneração Macular Exsudativa/fisiopatologiaRESUMO
Knowledge about the variable course of the perforating arteries near the body of the femur is essential during surgical procedures (e.g., percutaneous cerclage wiring, plate osteosynthesis, Ilizarov technique). Our aims were to determine the number of perforating arteries, and to identify safe zones along the body of the femur within which perforating arteries are unlikely to pass toward the back of the thigh. The number of perforating arteries was determined in both legs of 100 formalin-fixed anatomic specimens of both sexes. The level of passage of perforating arteries near the body of the femur was measured in reference to a line from the anterior superior iliac spine to the medial femoral condyle. In each leg, two to seven perforating arteries were present. In 64% of legs, at least one artery divided into two to four branches before entering the back of the thigh. Thus, the total number of branches passing near the body of the femur varied between two to nine. Perforating arteries passed to the back of the thigh at every level between 14.0 and 36.5 cm from the anterior superior iliac spine (16-39% of the leg length). Within this distance, no safe zones along the body of the femur could be identified. The present study shows the high variability regarding number and course of the perforating arteries. Surgeons can be faced with an artery at every level on the posteromedial aspect of the body of the femur between 14.0 and 36.5 cm distally to the anterior superior iliac spine. Clin. Anat. 33:507-515, 2020. © 2019 Wiley Periodicals, Inc.
Assuntos
Artéria Femoral/anatomia & histologia , Fêmur/irrigação sanguínea , Coxa da Perna/irrigação sanguínea , Idoso de 80 Anos ou mais , Cadáver , Dissecação , Humanos , MasculinoRESUMO
OBJECTIVES: To examine whether a mixed lipid emulsion reduces the incidence of parenteral nutrition associated cholestasis (PNAC) in extremely low birth weight (ELBW, <1000 g) infants. STUDY DESIGN: This double-blind randomized trial of 230 ELBW infants (June 2012-October 2015) was performed at a single level IV neonatal intensive care unit. Patients received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil-(intervention) or a soybean oil-based lipid emulsion (control) for parenteral nutrition. The primary outcome measure was PNAC (conjugated bilirubin >1.5 mg/dL [25 µmol/L] at 2 consecutive measurements). The study was powered to detect a reduction of PNAC from 25% to 10%. RESULTS: Reasons for noneligibility of 274 infants screened were refusal to participate (n = 16), death (n = 10), withdrawal of treatment (n = 5), higher order multiples (n = 9), and parents not available for consent (n = 4). Intention to treat analysis was carried out in 223 infants (7 infants excluded after randomization). Parenteral nutrition associated cholestasis was 11 of 110 (10.1%) in the intervention and 18 of 113 (15.9%) in the control group (P = .20). Multivariable analyses showed no statistically significant difference in the intention to treat (aOR 0.428, 95% CI 0.155-1.187; P = .10) or per protocol population (aOR 0.457, 95% CI 0.155-1.347; P = .16). There was no statistically significant effect on any other neonatal morbidity. CONCLUSIONS: The incidence of parenteral nutrition associated cholestasis was not significantly reduced using a mixed lipid emulsion in ELBW infants. TRIAL REGISTRATION: ClinicalTrials.govNCT01585935.
Assuntos
Colestase/prevenção & controle , Óleos de Peixe/uso terapêutico , Azeite de Oliva/uso terapêutico , Nutrição Parenteral/efeitos adversos , Óleo de Soja/uso terapêutico , Triglicerídeos/uso terapêutico , Colestase/etiologia , Método Duplo-Cego , Emulsões , Feminino , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , MasculinoRESUMO
BACKGROUND AND STUDY AIM: The European guidelines for quality assurance in colorectal cancer screening and diagnosis contain postpolypectomy surveillance recommendations. They recommend follow-up intervals depending on the findings at index colonoscopy, and divide patients into a low-, intermediate- or high-risk group.âThe aim of this study was to assess the adherence of Austrian endoscopists to the European guidelines and to determine whether sending a reminder letter resulted in better adherence. METHODS: A single reminder letter containing the guidelines was sent to all endoscopists who participated in the Certificate of Quality for Screening Colonoscopy program in Austria. Adherence was assessed before and after the letter had been sent. Factors associated with adherence were investigated. RESULTS: We found poor baseline adherence to the guidelines. After the reminder letter, the adherence slightly improved in the low-risk group, but did not change in the intermediate-risk or high-risk groups. An adenoma detection rate of at least 20â% was associated with higher adherence rates. Generally, internists and hospitals showed better adherence compared with surgeons and private practices, respectively, both before and after the reminder letter. CONCLUSION: A single reminder letter was not enough to improve the poor adherence to the European postpolypectomy surveillance guidelines. Thus, future studies are required to identify and eliminate all factors responsible for nonadherence to postpolypectomy guidelines in order to reach the goal of a safe, effective, and cost-effective colorectal cancer prevention tool in the near future.
Assuntos
Colonoscopia/normas , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/normas , Fidelidade a Diretrizes , Programas de Rastreamento/métodos , Idoso , Áustria/epidemiologia , Neoplasias Colorretais/epidemiologia , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
PURPOSE: Reduced thickness of the ganglion cell inner plexiform layer indicates diabetic neurodegeneration and can be assessed by spectral domain optical coherence tomography. The authors investigated the comparability of ganglion cell inner plexiform layer measurements from two spectral domain optical coherence tomography devices in patients with diabetic macular edema (DME). METHODS: Analysis of optical coherence tomography data sets of eyes with and fellow eyes without DME. Macular cube scans of sufficient signal strength on Cirrus (Carl Zeiss Meditec) were compared with correlating scans on Spectralis (Heidelberg Engineering, Germany) being acquired within 1 hour. RESULTS: Eighty-one equivalent data sets for 20 eyes with DME (20 patients; 6 female) and 33 for 9 fellow eyes without DME (9 patients; 2 female) were included from each device. In DME eyes, mean ganglion cell inner plexiform layer thicknesses were 62.5 ± 20.4 µm on Cirrus and 91.2 ± 9.3 µm on Spectralis. Ganglion cell inner plexiform layer was significantly thicker on Spectralis analyzing eyes with and without signs of DME (P < 0.001). The ganglion cell inner plexiform layer variance (54.2%) related to device differences decreased to 34.8% in eyes without DME. CONCLUSION: Ganglion cell inner plexiform layer data from different devices vary considerably and cannot be used interchangeably. As spectral domain optical coherence tomography is indispensable for identifying ganglion cell loss associated with diabetic neurodegeneration, clinicians should be aware of the difference when monitoring patients.
Assuntos
Retinopatia Diabética/patologia , Edema Macular/patologia , Células Ganglionares da Retina/patologia , Tomografia de Coerência Óptica/métodos , Idoso , Retinopatia Diabética/diagnóstico por imagem , Feminino , Humanos , Edema Macular/diagnóstico por imagem , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Angiogenesis, the formation of new blood vessels, is an essential process under physiological and pathological conditions. METHOD: Here, we improved the directed in vivo angiogenesis assay (DIVAA®) test, which is based on the usage of small Matrigel-filled tubes that are implanted into mice subcutaneously for a period of up to 15 days. The subsequent ex vivo assessment of neoangiogenesis within the silicon tubes is then achieved by fluorometry. RESULTS: We showed that the immunohistochemical quantification of the ingrowth of endothelial cells, based on CD31, was superior to the fluorometric quantification advised in the manufacturer's instructions. We optimised the explantation procedure, ensuring the complete recovery of the ingrown vessels. Using this modified protocol, we investigated the effect of the length of stay of the implanted tubes as well as of the concentration of the growth factors VEGF and FGF on the assay. CONCLUSION: Our improved protocol offered an effective and reliable alternative to the original assay, which is expected to facilitate in vivo research on angiogenesis and, thus, might drive the development of novel therapeutic agents.
Assuntos
Indutores da Angiogênese/administração & dosagem , Bioensaio/métodos , Colágeno/administração & dosagem , Células Endoteliais/efeitos dos fármacos , Imuno-Histoquímica , Laminina/administração & dosagem , Neovascularização Fisiológica/efeitos dos fármacos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Proteoglicanas/administração & dosagem , Tela Subcutânea/irrigação sanguínea , Animais , Biomarcadores/metabolismo , Combinação de Medicamentos , Células Endoteliais/metabolismo , Fluorometria , Processamento de Imagem Assistida por Computador , Camundongos Endogâmicos C57BL , Reprodutibilidade dos Testes , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/administração & dosagemRESUMO
INTRODUCTION: Epilepsy is one of the most common neurological diseases and has many detrimental effects on the patients' well-being as well as sleep quality. The aim of this study was to assess the subjective quality of sleep and influencing factors on subjective sleep quality in patients with partial epilepsy using a combined retrospective and prospective study design. METHODS: We conducted a combined retrospective and prospective study in patients with partial epilepsy and analyzed subjective ratings of sleep quality in 32 patients (17 female, 15 male; mean age: 40.41 ± 12.67 years, range: 20-64) with partial epilepsy (mean duration of epilepsy diagnosis: 18.31 ± 13.26 years) and 32 healthy gender-matched and age-matched controls. All patients filled out a seizure diary for 90 days, which included the number, duration, and type (partial vs. secondary generalized) of epileptic seizures and intake of antiepileptic and sleep medications. At baseline, all participants completed the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Beck's Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). Poor sleepers were defined by a PSQI score of ≥ 5. RESULTS: Twenty-three patients (72%) reported 15.17 ± 25.54 seizures in the previous three months, and nine (28%) patients reported being seizure-free. During the 90-day diary period, twenty-two patients (69%) documented a total of 319 epileptic seizures, while ten patients (31%) reported that they were seizure-free. The mean PSQI score of all patients was 4.88 ± 2.92 (range: 1-14) and the mean ESS score was 5.25 ± 2.98 (range: 0-10). The mean PSQI score of the control group was 3.25 ± 1.57 (range: 1-6), and their mean ESS score was 6.72 ± 3.48 (range: 0-14). The comparison of the two groups showed a significantly higher PSQI score in the patient group (t = 2.778, p = 0.008), but no statistically significant difference regarding their ESS score (t = -1.811, p = 0.075). Sixteen (50%) patients were poor sleepers. Good sleepers showed a significantly lower PSQI (2.69 ± 1.08 vs. 7.06 ± 2.49; p < 0.001) and BDI scores (2.38 ± 2.50 vs. 9.63 ± 7.63; p < 0.002) than poor sleepers. Linear regression analysis showed that the BDI score was the significant predictor for the PSQI score (estimate: 0.2019; p = 0.00819) and for the ESS score (estimate: 0.2251; p = 0.0321). CONCLUSION: In patients with partial epilepsy, a higher depression score was the best predictor for a poor subjective sleep quality and increased daytime sleepiness.
Assuntos
Depressão/diagnóstico , Epilepsias Parciais/complicações , Transtornos do Sono-Vigília/psicologia , Sono , Adolescente , Adulto , Depressão/psicologia , Epilepsias Parciais/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Fases do Sono , Transtornos do Sono-Vigília/complicações , Adulto JovemRESUMO
BACKGROUND: The assessment of mobility is important in the acute care setting. Existing tests suffer from limitations. The aim of the study was to examine the inter-rater reliability, the validity, the sensitivity to change, and the internal consistency of an ICF based scale. METHODS: In a prospective study inpatients in the acute care setting with restricted mobility aged above 50 years assigned to rehabilitative treatment were included. Assessment of subscales of the Functional Independence Measure (FIM) and the ICF based Basic Mobility Scale (BMS) were performed at admission and before discharge. Furthermore pain, length of stay in hospital, and post-discharge residential status were recorded. Inter-rater reliability, criterion-concurrent validity, sensitivity to change, and internal consistency were calculated. Furthermore, floor and ceiling effects were determined. RESULTS: One hundred twenty-five patients (79 women/46 men) were included. The BMS showed an excellent inter-rater reliability for the total BMS (ICC BMS: 0.85 (95 % CI: 0.81-0.88). The criterion-concurrent validity was high to excellent (Spearman correlation coefficient: -0.91 in correlation to FIM) and the internal consistency was good (Cronbach's alpha 0.88). The BMS proved to be sensitive to improvements in mobility (Wilcoxon's signed rank test: p < 0.0001; The effect size for the BMS was 1.075 and the standardized response mean 1.10. At admission, the BMS was less vulnerable to floor effects. CONCLUSIONS: The BMS may be used as a reliable and valid tool for the assessment of mobility in the acute care setting. It is easy to apply, sensitive to change during the hospital stay and not vulnerable to floor and ceiling effects.
Assuntos
Avaliação da Deficiência , Serviços Médicos de Emergência/normas , Hospitalização , Limitação da Mobilidade , Doenças Musculoesqueléticas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/fisiopatologia , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Immunoadsorption (IAS) and therapeutic plasma exchange (TPE) are considered safe although fibrinogen is removed. To date no comparison of fibrinogen reduction and associated risk of bleeding in apheresis exists. METHODS: Retrospective analysis of TPE, three IAS adsorbers, and combined TPE/IAS regarding fibrinogen reduction and bleeding incidence in 67 patients (1,032 treatments). RESULTS: TPE and TPE/IAS reduced fibrinogen by 64 ± 11% and 58 ± 9%, leading to concentrations <100 mg/dl in 20 and 17% of treatments, respectively. IAS decreased fibrinogen less than TPE (26 ± 6%, p < 0.0001), resulting in fibrinogen concentrations <100 mg/dl in 1% of treatments. The processed volume correlated with reduction in TPE (r = 0.64, p < 0.01), but not in IAS. Bleeding occurred in 1.3% (IAS), 2.3% (TPE) and 3.1% (TPE/IAS) of treatments. CONCLUSION: Hypofibrinogenemia occurs in 20% of patients after TPE and TPE/IAS, but rarely after IAS. IAS removes fibrinogen independently of volume processed. Overall, bleeding is rare in apheresis.
Assuntos
Fibrinogênio/isolamento & purificação , Hemorragia/prevenção & controle , Técnicas de Imunoadsorção/instrumentação , Troca Plasmática/instrumentação , Plasmaferese/instrumentação , Adulto , Feminino , Hemorragia/etiologia , Humanos , Técnicas de Imunoadsorção/efeitos adversos , Imunoadsorventes/química , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Esclerose Múltipla/terapia , Miastenia Gravis/patologia , Miastenia Gravis/terapia , Troca Plasmática/efeitos adversos , Troca Plasmática/métodos , Plasmaferese/efeitos adversos , Plasmaferese/métodos , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/patologia , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/terapia , Estudos RetrospectivosAssuntos
Janus Quinase 2/antagonistas & inibidores , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Proteínas de Neoplasias/antagonistas & inibidores , Células-Tronco Neoplásicas/enzimologia , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Feminino , Humanos , Janus Quinase 2/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas/patologiaRESUMO
Recent studies suggest that the combination of caffeine-containing drinks together with alcohol might reduce the subjective feelings of alcohol intoxication-the so-called "masking effect". In this study, we aimed to review the effects of alcohol in combination with caffeine or energy drink with special focus on the "masking effect". Fifty-two healthy male volunteers were analysed concerning breath alcohol concentration and subjective sensations of intoxication using a 18 item Visual Analogue Scale in a randomised, double-blinded, controlled, four treatments cross-over trial after consumption of (A) placebo, (B) alcohol (vodka 37.5% at a dose of 46.5 g ethanol), (C) alcohol in combination with caffeine at a dose of 80 mg (equivalent to one 250 ml can of energy drink) and (D) alcohol in combination with energy drink at a dose of 250 ml (one can). Primary variables were headache, weakness, salivation and motor coordination. Out of four primary variables, weakness and motor coordination showed a statistically significant difference between alcohol and non-alcohol group, out of 14 secondary variables, five more variables (dizziness, alterations in sight, alterations in walking, agitation and alterations in speech) also showed significant differences due mainly to contrasts with the non-alcohol group. In none of these end points, could a statistically significant effect be found for the additional ingestion of energy drink or caffeine on the subjective feelings of alcohol intoxication. This within-subjects study does not confirm the presence of a "masking effect" when combining caffeine or energy drink with alcohol.
Assuntos
Intoxicação Alcoólica/psicologia , Álcoois/efeitos adversos , Cafeína/efeitos adversos , Bebidas Energéticas/efeitos adversos , Adulto , Álcoois/administração & dosagem , Cafeína/administração & dosagem , Voluntários Saudáveis , Humanos , Masculino , Adulto JovemRESUMO
AIM: To prospectively monitor subclinical changes in capillary perfusion and retinal layer thickness in patients with type 2 diabetes and early diabetic retinal disease over 2 years. METHODS: In this longitudinal study we performed biannual retinal vascular imaging using optical coherence tomography angiography (RTVue) to analyse the foveal avascular zone (FAZ) area, perimeter, acircularity index (AI) and parafoveal superficial/deep vessel density (VD). Spectral-domain optical coherence tomography (Spectralis) was used to measure the thickness of nine macular layers and the peripapillary nerve fibre layer. RESULTS: Among 117 eyes (58 left) of 59 patients (21 female), 105 had no diabetic retinopathy (DR), 6 mild and 6 moderate non-proliferative DR at baseline. We found DR progression in 13 eyes at year 2. The FAZ area (+0.008±0.002 mm2/year, p<0.0001), perimeter (+0.036±0.010 mm/year, p=0.006) and AI (+0.005±0.002/year, p=0.0280) increased significantly. A pronounced decrease was found in the superficial (-1.425±0.290%/year, p<0.0001) but not the deep VD. Inner neuroretinal loss was confined to the ganglion cell (-0.539±0.150 µm/year, p=0.0004) and the inner plexiform layer (-0.361±0.127 µm/year, p=0.0045). In the outer retina, we observed a statistically significant decrease in thickness in the outer plexiform, photoreceptor layer and pigment epithelium of -0.921±0.161 µm/year, -0.325±0.139 µm/year and -0.385±0.084 µm/year, respectively. CONCLUSION: Subclinical signs of microangiopathy and neurodegeneration appear in parallel and are highly progressive even in the earliest stages of diabetic retinal disease. Trial registration number EudraCT20156000239634.
Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Retinopatia Diabética/diagnóstico , Feminino , Angiofluoresceinografia/métodos , Humanos , Estudos Longitudinais , Masculino , Perfusão , Vasos Retinianos/diagnóstico por imagem , Tomografia de Coerência Óptica/métodosRESUMO
BACKGROUND/AIMS: Optical coherence tomography (OCT) is commonly used to diagnose and assess diabetic macular oedema (DME). Swept-source OCT (SS-OCT) promises improved imaging depth and more independence from media opacities. Heidelberg Spectralis full-depth imaging (FDI) combines details at different depths to one representation. The aim of this study was to determine the comparability of the imaging methods concerning DME ultrastructure. METHODS: Two graders assessed the presence of typical DME phenomena in eyes with centre-involving DME on Topcon Atlantis SS-OCT and Heidelberg Spectralis FDI spectral-domain OCT (SD-OCT) B-scans. Retinal layer segmentation was corrected and choroidal layers were manually segmented. Graders measured cyst and subretinal fluid (SRF) diameters and counted hyper-reflective foci (HRF). Findings were recorded and statistically analysed. RESULTS: Statistically significant systematic biases (Spectralis-Atlantis) were found for the HRF count (outside the central mm, -6.39, p=0.0338), chorioretinal thickness (central mm: -35.45 µm, p=0.00034), choroidal thickness (central mm: -60.97 µm, p=0.00004) and Sattler's layer thickness (-42.69 µm, p=0.0001). Intergrader agreement was excellent or very good for posterior vitreous detachment, vitreomacular attachment (central mm) and SRF presence in both devices. Manually delineated Sattler's layer thickness showed an intraclass correlation of 0.85 with FDI SD-OCT but 0.26 with SS-OCT (p=0.003). CONCLUSION: Prominent aspects such as cysts in the outer nuclear layer and SRF can be identified with comparable confidence, while a significant systematic bias underlies chorioretinal, choroidal and Sattler's layer thickness and HRF count. Specialists should use the same device at every examination during longitudinal clinical consideration or cross-sectional evaluation of these ultrastructural biomarkers.
Assuntos
Corioide/ultraestrutura , Retinopatia Diabética/diagnóstico , Macula Lutea/ultraestrutura , Edema Macular/diagnóstico , Tomografia de Coerência Óptica/métodos , Idoso , Estudos Transversais , Retinopatia Diabética/complicações , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
Clinical tests assessing olfactory performance have become indispensable for diagnosing olfactory dysfunction. As time and personnel resources are limited, it would be advantageous to have shorter protocols focusing on singular aspects of olfactory performance, such as odor identification. However, such a unidimensional approach is often inconclusive and needs further tests (and tools). Hence, new testing methods with high levels of sensitivity, specificity, and reproducibility are required for clinical practice. Here, we developed a Sniffin' Sticks odor mixture identification test method (SSomix), with emphasis on resource efficiency and simplicity of administration. SSomix consists of mixtures of two and three odors applied onto a piece of paper using 11 out of 16 items from the original Sniffin' Sticks identification test kit. A total of 66 healthy subjects and 22 patients with olfactory dysfunction were included in the study. SSomix showed good to excellent test-retest reliability and validity. The area under the receiver operating characteristics curves indicated good diagnostic accuracy in identifying patients with reduced and severely impaired olfactory function. SSomix was a suitable downsizing of the original kit, especially regarding resource efficiency.
Assuntos
Transtornos do Olfato/diagnóstico , Olfato , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas e Procedimentos Diagnósticos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Odorantes/análise , Transtornos do Olfato/fisiopatologia , Limiar Sensorial , Adulto JovemRESUMO
OBJECTIVE: The current study assesses the feasibility of in vitro practice of percutaneous puncture techniques in a pulsatile flow-model. DESIGN: Prospective, controlled, randomized study. SETTING: The percutaneous access to endovascular aortic repair is considered safe, but success rates may be dependent on surgeon experience with the technique. PARTICIPANTS: Fourteen vascular surgery trainees and consultants were enrolled and randomized to a study or control group with both groups receiving instructions by a tutor on how to perform ultrasound guided percutaneous puncture and closure using a suture-mediated closure device. The study group received additional hands-on training on a pulsatile flowmodel of the groin and the performance of both groups was then graded. Study group participants were timed during and after their training on the model. RESULTS: The study group achieved higher overall grading than the control group on a 5-point scale with higher scores indicating a better performance (mean overall scores 4.0 ± 0.7 versus 2.8 ± 1.0, respectively; pâ¯=â¯0.03). Experienced participants (more than 20 punctures performed before the study) achieved higher overall scores than trainees (3.8 ± 0.4 versus 2.5 ± 0.8, respectively; pâ¯=â¯0.01). Five participants in the study group could deploy and close the ProGlide closure device correctly without the help of a tutor while being graded (71% in the study versus 0% in the control group; pâ¯=â¯0.02). Study group participants improved their overall score from 3.2 ± 0.9 to 4.0 ± 0.7 during training (pâ¯=â¯0.02). Time needed to complete the puncture and closure reduced from 456 seconds on average before, to 302 seconds after training (p < 0.001). CONCLUSIONS: Study group participants could improve their overall score while working on the simulator. More experienced participants performed better during the simulation, which may indicate the model to be life-like and a potential skills assessment tool. Simulation training may be a valuable adjunct to traditional forms of training when teaching an endovascular technique but is limited by its reliance on simulators and demo devices.