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Carolina Cisneros,1 Rocío Magdalena Díaz-Campos,2 Núria Marina,3 Carlos Melero,2 Alicia Padilla,4 Silvia Pascual,5 Celia Pinedo,6 Andrea Trisán7 On behalf of the DUMA Study Group 1Service of Pneumology, Hospital Universitario de La Princesa, 2Service of Pneumology, Hospital Universitario 12 de Octubre, Madrid, 3Asthma Unit, Laboratorio de Exploración Funcional, Department of Pneumology, Hospital Universitario Cruces, BioCruces, Barakaldo, Bizkaia, 4Agencia Sanitaria Costal de Sol, Marbella, Málaga, 5Service of Pneumology, Hospital de Galdakao, Bizkaia, 6Service of Pneumology, Hospital Clínico San Carlos, 7Service of Pneumology, Hospital Universitario Puerta de Hierro, Madrid, Spain Abstract: This paper, developed by consensus of staff physicians of accredited asthma units for the management of severe asthma, presents information on the process and requirements for already-existing asthma units to achieve official accreditation by the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Three levels of specialized asthma care have been established based on available resources, which include specialized units for highly complex asthma, specialized asthma units, and basic asthma units. Regardless of the level of accreditation obtained, the distinction of “excellence” could be granted when more requirements in the areas of provision of care, technical and human resources, training in asthma, and teaching and research activities were met at each level. The Spanish experience in the process of accreditation of specialized asthma units, particularly for the care of patients with difficult-to-control asthma, may be applicable to other health care settings. Keywords: asthma unit, severe asthma, uncontrolled asthma, asthma treatment

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OBJECTIVE:: To determine the point prevalence of pulmonary hypertension (PH) and its relationship with respiratory disturbances in obese patients living at moderate altitude. SUBJECTS:: A total of 57 obese patients comprised the final sample and consisted of 34 women and 23 men, with a mean age of 42.7±12.1?ys and a mean body mass index (BMI) 47.1±10.6?kg/m2 (range from 30.1 to 76.1). The mean living altitude was 2248.7?m, range 2100-2400?m above sea level. MEASUREMENTS:: Doppler echocardiography, pulmonary function tests, arterial blood gas analysis, and polysomnography were performed. RESULTS:: Data showed that 96.5% of the studied sample had daytime PH defined as calculated systolic pulmonary artery pressure (PSAP) >30?mmHg (mean PSAP=50, s.d.=13?mmHg). The severity of diurnal PH was found to be related to the presence of alveolar hypoventilation and BMI. The main risk factor for severity of diurnal PH was hypoventilation with a significant odds ratio (OR) 7.96, 95% CI 1.35-46.84, BMI was (OR 1.12, 95% CI 1.02-1.25) and apnea/hypopnea index was not a predictor of pulmonary hypertension severity (OR 0.99, 95% CI 0.97-1.02). CONCLUSION:: We concluded that prevalence of diurnal PH is high in obese patients living at moderate altitude, and that hypoventilation is the main risk factor associated with the severity of pulmonary hypertension.International Journal of Obesity (2004) 28, 1174-1180. doi:10.1038/sj.ijo.0802726 Published online 29 June 2004 [ABSTRACT FROM AUTHOR]

The detection of clustered microcalcifications can help the radiologist to detect early breast cancer. Microcalcifications exhibit some important characteristics, such as small size and high luminosity. Use of a computer-aided diagnosis (CAD) method can prevent them being overlooked. In this report, a multiresolution analysis is performed based on a multilevel wavelet transformation. Decomposition produces sub-band images which become visible only as details of the different scales. Thereafter, all the images will be combined in a final image, in order to obtain an image that contains all the interest details at the scale where microcalcifications tend to appear. Once the image, called detail image, is obtained, it is necessary to determine which details correspond with microcalcifications. Statistical analysis of the histogram permits classification of the zones likely to contain microcalcifications. Applying this statistical techniques over the whole image and representing the results in a two-dimensional map, clustered microcalcification regions are clearly distinguishable. Copyright © 2000 by W.B. Saunders Company [ABSTRACT FROM AUTHOR]

Background: Biologic therapies play a crucial role in the treatment of severe asthma. Tezepelumab, a human monoclonal antibody (mAb), inhibits thymic stromal lymphopoietin, a pivotal factor in the pathophysiology of asthma. Although randomized clinical trials have demonstrated the efficacy of Tezepelumab, evidence gaps remain in real-world scenarios., Objective: We sought investigate Tezepelumab's response in a clinical setting, focusing on patients who previously failed to other asthma mAbs., Methods: Real-life study with severe uncontrolled asthma patients despite mAb treatment, requiring a switch to Tezepelumab. Follow-up was done four to six months after initiation of Tezepelumab. The primary endpoint was to evaluate the response in patients with poor response or intolerance to other mAbs., Results: Nine patients were followed up during 7 months. Patients were predominantly middle-aged females with eosinophilic or eosinophilic-allergic phenotypes. Patients had a median failure rate of 2 mAbs (IQR 2-3), with an uncontrolled asthma (median of 2 severe exacerbations the previous year, airflow obstruction and 78% corticosteroid dependence). Tezepelumab demonstrated after 4 to 6 months of treatment reduce corticosteroid dependence (complete withdrawal in 2/7 patients), no exacerbations in 6/9, symptoms control improvement (Asthma Control Test score improved in 5/9) and modulate lung function (improving in 3/9 patients). These findings align with clinical trial results, suggesting Tezepelumab's potential in real-world settings., Conclusion: In real-world scenarios, despite the study's limitations, our results underscore Tezepelumab's promise as a therapeutic option for uncontrolled severe asthma, and may be useful for non-responders to other mAbs. Further studies are needed to corroborate these findings.

Introduction: The multiple forced expiratory maneuvers that must be performed during methacholine test require a high degree of collaboration and can lead to fatigue. However, impulse oscillometry (IOS) is a noninvasive test, quick and easy to perform, that does not require effort-dependent maneuvers. Objectives: The primary endpoint was to evaluate the relationship between IOS and spirometry during the methacholine test. The secondary endpoint was to study the predictive value of baseline IOS in the development of bronchial hyperreactivity. Methods: Observational, prospective, cross-sectional study, with recruitment of consecutive patients from the pulmonology department with clinical suspicion of bronchial asthma with negative bronchodilator test and normal FeNO. Results: Twenty-five patients were included, with a mean age of 49 ± 18 years. Thirteen patients (52%) had a positive methacholine test. The correlation between IOS indices and FEV1 was significant ( p < 0.05) in all cases. The indices with the highest predictive power were R5-20 and AX. The optimal cutoff points were an increase of greater than 32.96% in R5, greater than 120.83% for X5, an increase of 30.30 [kPa l-1s-1] in R5-20, and an increase of 1.01 [kPa l-1] for AX. Baseline oscillometry demonstrated a strong predictive value in the development of bronchial hyperreactivity, with a sensitivity of 61.5% and a specificity of 91.7%, using the cut-off point of 160.0% for R5. Conclusions: IOS may be a valuable alternative to forced spirometry in detecting bronchial hyperreactivity during the methacholine test, showing a good correlation between both tests.

Purpose: Bariatric surgery (BS) has several potential metabolic benefits. However, little is known about its impact on changes in the inflammatory potential of diet and its effect on inflammatory and metabolic markers. This study aimed to assess the short-term beneficial effects of BS on dietary inflammatory potential and inflammatory and metabolic markers., Materials and Methods: Participants (n = 20) were evaluated 3 months before and after BS. Body mass, body mass index, anthropometric measurements, fat mass, fat-free mass, visceral fat, skeletal muscle mass, basal metabolic rate, serum lipids, HOMA-IR, QUICKI and inflammatory markers, including leptin, adiponectin, adiponectin/leptin ratio and plasminogen activator inhibitor-1 (PAI-1), were evaluated. Diet data were collected using a 3-day diet record and the dietary inflammatory index (DII®) and energy-adjusted dietary inflammatory index (E-DII TM ) scores were computed., Results: There was a reduction in DII® (2.56 vs 2.13) and E-DII TM (2.18 vs 0.45) indicating an improvement in inflammatory nutritional profile. Moreover, there were increases in the adiponectin/leptin ratio (0.08 vs 0.21) and QUICKI scores (0.31 vs 0.37), and reductions in leptin (36.66 vs 11.41 ng/ml) and HOMA-IR scores (3.93 vs 1.50). There were also improvements in body composition and anthropometric parameters., Conclusions: BS promotes changes in metabolic profile, inflammatory state and food intake and these modifications appeared to be associated with improvements in diet-related inflammation, an increase in the adiponectin/leptin ratio and a reduction in leptin. These results contribute to knowledge on the contribution bariatric surgery can make to the treatment of obesity and the reduction of related comorbidities., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In recent years, advances in knowledge of molecular mechanisms involved in asthma have changed uncontrolled severe asthma (USA) treatment, with the appearance of biological treatment. USA is a heterogeneous entity with different endotypes and phenotypes. Nowadays, the biological drugs approved with asthma indication are omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. Tezepelumab is approved by the Food and Drug Administration (FDA) in the United States and, recently, by the European Medicines Agency (EMA). All these biological drugs have shown their efficacy in clinical trials, especially in reducing exacerbations, improving asthma control, quality of life, pulmonary function, and withdrawing systemic corticosteroids or at least reducing their daily dose, with some differences between them. Except for mepolizumab and reslizumab, biological drugs have different targets and thus different therapeutic indications should be expected; however, in some patients, more than one drug could be indicated, making the election more difficult. Because there are no direct comparisons between biological drugs, some biomarkers are used to choose between them, but they are not unbeatable. In this article, an algorithm to choose the first biological drug in a specific patient is proposed based on different study results and patient' characteristics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 López-Viña, Díaz Campos, Trisán Alonso and Melero Moreno.)

Although biologics have demonstrated to be effective in T2-high asthma patients, there is little experience with these drugs in asthma-COPD overlap (ACO). The aim of this study was to compare the effectiveness of biologics in these two conditions. We included 318 patients (24 ACO and 297 asthma) treated with monoclonal antibodies and followed for at least 12 months. Omalizumab was the most frequently employed biologic agent both in patients with ACO and asthma. Asthma control test (ACT) scores after at least 12 months of biologic therapy were not significantly different between groups. The percentage of patients with ≥1 exacerbation and ≥1 corticosteroid burst was significantly higher in ACO patients (70.8 vs 27.3 and 83.3% vs 37.5%, respectively), whereas the percentage of "controlled" patients (with no exacerbations, no need for corticosteroids and ACT ≥ 20) was significantly lower (16.7% vs 39.7%). In conclusion, this report suggests that patients with ACO treated with biologics reach worse outcomes than asthma patients., Competing Interests: Dr. Pérez de Llano reports grants, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from GSK, grants and personal fees from TEVA, personal fees and non-financial support from Novartis, personal fees and non-financial support from Chiesi, personal fees from Sanofi, personal fees from Menarini, personal fees from Leo-Pharma, personal fees from GEBRO, personal fees from GILEAD, grants and personal fees from Esteve, personal fees from ROVI, personal fees from MSD, personal fees from TECHDOW PHARMA, non-financial support from FAES, outside the submitted work. Dr. Dacal Rivas reports personal fees and non-financial support from Esteve, personal fees and non-financial support from Boehringer-Ingelheim, non-financial support from GSK, non-financial support from Novartis, non-financial support from TEVA, non-financial support from Chiesi, non-financial support from Ferrer, outside the submitted work. Dr. Marina Malanda reports payment for lectures including Service on speakers bureaus, payment for development of educational presentations and travel/accommodations/meeting expenses, outside the submitted work. Dr. Plaza Moral reports grants and personal fees from AstraZeneca, personal fees from Boehringer-Ingelheim, personal fees from GSK, personal fees from Merck, grants and personal fees from Chiesi, personal fees from Novartis, grants from Menarini, personal fees from Sanofi, outside the submitted work. Dr. Gullón has nothing to disclose. Dr. Muñoz Esquerre reports grants, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from GSK, personal fees and non-financial support from TEVA, personal fees and non-financial support from Novartis, personal fees and non-financial support from Chiesi, personal fees and non-financial support from Sanofi, personal fees and non-financial support from Menarini, personal fees from Ferrer, personal fees and non-financial support from FAES PHARMA, personal fees and non-financial support from MUNDIPHARMA, personal fees and non-financial support from ORIONPHARMA, personal fees and non-financial support from ALK ABELLÓ, outside the submitted work. Dr. García-Moguel reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Sanofi, GSK, Chiesi, Orionpharma, Leti, Stallergenes, Allergy therapeutics; payment for expert testimony from AstraZeneca, Sanofi and GSK, support for attending meetings and/or travel from Novartis, Allergy therapeutics, Stallergenes Greer and TEVA; participation on a data safety monitoring board or advisory board from GSK, AstraZeneca and Sanofi; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from AstraZeneca; receipt of equipment, materials, drugs, medical writing, gifts or other services from GSK. Dr. Díaz Campos reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GSK, Pfizer and Novartis; payment for expert testimony from GSK, AstraZeneca; support for attending meetings and/or travel from Chiesi, Menarini; Participation on a Data Safety Monitoring Board or Advisory Board from TEVA, GSK. Dr. Martinez-Moragón, declares that in the last three years received honoraria for speaking at sponsored meetings from AstraZeneca, Boehringer-Ingelheim, Chiesi, GlaxoSmithKline, Sanofi, Novartis, TEVA and ALK; and as a consultant for AstraZeneca, Boehringer-Ingelheim and GlaxoSmithKline. Dr. Harbenau Mena reports payment for expert testimony from GSK, AstraZeneca, Sanofi and Novartis. Dr. Cosio reports personal fees from AstraZeneca, grants and personal fees from Boehringer-Ingelheim, grants and personal fees from Novartis, grants and personal fees from Chiesi, personal fees from Sanofi, grants from Menarini, personal fees from Esteve, grants and personal fees from GSK, outside the submitted work. Dr. Padilla-Galo reports grants, personal fees and non-financial support from Astra-Zeneca, personal fees and non-financial support from GSK, TEVA, Chiesi and Novartis, and personal fees from ALK, Sanofi, Mundipharma and Bial, outside the submitted work. Dr. Cisneros reports grants, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from GSK, grants and personal fees from TEVA, personal fees and non-financial support from Novartis, personal fees and non-financial support from Chiesi, Pfizer, Mundipharma, personal fees from Sanofi, personal fees from Menarini, grants and personal fees from Esteve, personal fees from ROVI, personal fees from MSD, personal fees from TECHDOW PHARMA, non-financial support from FAES, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2022 Pérez de Llano et al.)

Neural-immune interactions are related to the synapse plasticity and other dynamic processes in the nervous system. The absence or dysfunction of cellular/molecular elements from the immune system lead to impairments in the central and peripheral nervous system with behavior consequences such as cognitive, sensory, and locomotor deficits as well as social disabilities and anxiety disturbances. Cellular interactions between immune cells such as macrophages, microglia, and neutrophils with glial or neuronal cells have been of increasing interest over the last years. However, little is known about the role of immune-derived soluble factors in the context of homeostasis of the nervous system. Leukotrienes (LTs) are lipid mediators derived from the oxidation of arachidonic acid by 5-lipoxygenase (5-LO), and are classically involved in inflammation, allergies, and asthma. Here, we demonstrated that adult mice lacking 5-LO (5-LO -/- ) showed motor deficits in rotarod test and increased repetitive behavior (marble burying test). These behavioral changes are accompanied by increased levels of synapse proteins (PSD95 and synaptophysin) at the motor cortex and hippocampus, but not with BDNF alterations. No changes in microglial cell density or morphology were seen in the brains of 5-LO -/- mice. Furthermore, expression of fractalkine receptor CX3CR1 was increased and of its ligand CX3CL1 was decreased in the cortex of 5-LO -/- mice. Here we provide evidence for the involvement of 5-LO products structuring synapses network with motor behavior consequences. We suggest that the absence of 5-LO products lead to modified microglial/neuron interaction, reducing microglial pruning., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To investigate the effects of an interdisciplinary intervention on biomarkers of inflammation and their relationship with fibroblast growth factor 21 (FGF21) concentrations in women with overweight and obesity., Methods: Thirty-one women were enrolled in a 12-week interdisciplinary weight loss program delivered by a team comprising an endocrinologist, nutritionist and exercise physiologist. Body composition; anthropometric measures; metabolic and inflammatory markers including adiponectin, leptin, and atrial natriuretic peptide (ANP) were assessed at baseline and post-therapy. The homeostasis model assessment of insulin resistance (HOMA-IR) and the homeostasis model assessment of adiponectin (HOMA-AD) were calculated. The participants were divided into two groups: those with increased FGF21, and those with decreased FGF21., Results: The sample comprised women aged 32 ± 5 years with a body mass index of 33.64 ± 3.49 kg/m 2 . Body weight, waist circumference and leptin concentration were decreased in the whole sample after therapy. However, only the group with an increase in FGF21 concentration presented significant improvements in adiponectin concentration and adiponectin/leptin ratio. Moreover, although there was a reduction of leptin in both groups, it was greater in the increased FGF21 groups. There was a reduction in ANP in the decreased FGF21 group., Conclusion: Changes in FGF21 concentrations were different among the women participating in the weight loss program, with some having increased levels and some reduced levels. Furthermore, improvements in adiponectin and the adiponectin/leptin ratio were found only in the group with increased FGF21 concentration.

Background: The knee osteoarthritis (OA) is a joint disease characterized by degradation of articular cartilage that leads to chronic inflammation. Exercise programs and photobiomodulation (PBM) are capable of modulating the inflammatory process of minimizing functional disability related to knee OA. However, their association on the concentration of biomarkers related to OA development has not been studied yet. The aim of the present study is to investigate the effects of PBM (via cluster) with a physical exercise program in functional capacity, serum inflammatory and cartilage degradation biomarkers in patients with knee OA., Methods: Forty-two patients were randomly allocated in 3 groups: ESP: exercise + sham PBM; EAP: exercise + PBM and CG: control group. Six patients were excluded before finished the experimental period. The analyzed outcomes in baseline and 8-week were: the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) and the evaluation of serum biomarkers concentration (IL-1β, IL-6, IL-8, IL-10 e TNF-α, and CTX-II)., Results: An increase in the functional capacity was observed in the WOMAC total score for both treated groups (p < 0.001) and ESP presents a lower value compared to CG (p < 0.05) the 8-week post-treatment. In addition, there was a significant increase in IL-10 concentration of EAP (p < 0.05) and higher value compared to CG (p < 0.001) the 8-week post-treatment. Moreover, an increase in IL-1β concentration was observed for CG (p < 0.05). No other difference was observed comparing the other groups., Conclusion: Our data suggest that the physical exercise therapy could be a strategy for increasing functional capacity and in association with PBM for increasing IL-10 levels in OA knee individuals., Trial Registration: ReBEC (RBR-7t6nzr)., (© 2021. The Author(s).)

The thermodynamic properties and band gap energies were evaluated for six ortho- and peri-fused polycyclic aromatic hydrocarbons (PAHs): triphenylene; benzo[ a ]pyrene; benzo[ e ]pyrene; perylene; benzo[ ghi ]perylene; coronene. The standard molar enthalpies of formation in the crystalline state and the standard molar enthalpies of sublimation were measured by high precision combustion calorimetry and Knudsen effusion methodology, respectively. The combination of the molar enthalpies of formation in the crystalline state with the respective enthalpies of sublimation was used to evaluate the energetics of the progressive peri-fusion of the aromatic moieties from triphenylene to coronene aiming to investigate the hypothetical superaromaticity character of coronene. The linear trend of the enthalpy of formation in crystalline and gaseous phases in the series (from benzo[ e ]pyrene to coronene) is an irrefutable indication of a non-superaromaticity character of coronene. High accurate thermodynamic properties of sublimation (volatility, enthalpy, and entropy of sublimation) were derived by the measurement of vapor pressures as a function of temperature, using a Knudsen/quartz crystal effusion methodology. Furthermore, the π-electronic conjugation of these compounds was explored by evaluation of the optical band gaps along with this series of compounds. The morphology of perylene, benzo[ ghi ]perylene, and coronene thin films, deposited by physical vapor deposition onto transparent conductive oxide substrates (ITO and FTO), was used to analyze the nucleation and growth mechanisms. The morphologies observed were found to be related to the cohesive energy and entropy of the bulk.

Tau is a microtubule-associated protein (MAP) responsible for controlling the stabilization of microtubules in neurons. Tau function is regulated by phosphorylation. However, in some neurological diseases Tau becomes aberrantly hyperphosphorylated, which contributes to the pathogenesis of neurological diseases, known as tauopathies. Western blotting (WB) has been widely employed to determine Tau levels in neurological disease models. However, Tau quantification by WB should be interpreted with care, as this approach has been recognized as prone to produce artifactual results if not properly performed. In the present study, our goal was to evaluate the influence of a freeze-and-thaw cycle, a common procedure preceding WB, to the integrity of Tau in brain homogenates from rats, 3xTg-AD mice and human samples. Homogenates were prepared in ice-cold RIPA buffer supplemented with protease/phosphatase inhibitors. Immediately after centrifugation, an aliquot of the extracts was analyzed via WB to quantify total and phosphorylated Tau levels. The remaining aliquots of the same extracts were stored for at least 2 weeks at either -20 or -80°C and then subjected to WB. Extracts from rodent brains submitted to freeze-and-thaw presented a ∼25 kDa fragment immunoreactive to anti-Tau antibodies. An in-gel digestion followed by mass spectrometry (MS) analysis in excised bands revealed this ∼25 kDa species corresponds to a Tau fragment. Freeze-and-thaw-induced Tau proteolysis was detected even when extracts were stored at -80°C. This phenomenon was not observed in human samples at any storage condition tested. Based on these findings, we strongly recommend the use of fresh extracts of brain samples in molecular analysis of Tau levels in rodents., (© 2021 The Author(s).)

The accumulation of amyloid protein aggregates in tissues is the basis for the onset of diseases known as amyloidoses. Intriguingly, many amyloidoses impact the central nervous system (CNS) and usually are devastating diseases. It is increasingly apparent that neurotoxic soluble oligomers formed by amyloidogenic proteins are the primary molecular drivers of these diseases, making them lucrative diagnostic and therapeutic targets. One promising diagnostic/therapeutic strategy has been the development of antibody fragments against amyloid oligomers. Antibody fragments, such as fragment antigen-binding (Fab), scFv (single chain variable fragments), and VHH (heavy chain variable domain or single-domain antibodies) are an alternative to full-length IgGs as diagnostics and therapeutics for a variety of diseases, mainly because of their increased tissue penetration (lower MW compared to IgG), decreased inflammatory potential (lack of Fc domain), and facile production (low structural complexity). Furthermore, through the use of in vitro-based ligand selection, it has been possible to identify antibody fragments presenting marked conformational selectivity. In this review, we summarize significant reports on antibody fragments selective for oligomers associated with prevalent CNS amyloidoses. We discuss promising results obtained using antibody fragments as both diagnostic and therapeutic agents against these diseases. In addition, the use of antibody fragments, particularly scFv and VHH, in the isolation of unique oligomeric assemblies is discussed as a strategy to unravel conformational moieties responsible for neurotoxicity. We envision that advances in this field may lead to the development of novel oligomer-selective antibody fragments with superior selectivity and, hopefully, good clinical outcomes.

In this study, a homogeneous thin film growth of pentacene onto indium tin oxide (ITO) coated glass surfaces is explored using a high-resolution and reproducible vapor deposition methodology. Moreover, vacuum thermal evaporation of ionic liquids (ILs) ([C 2 C 1 im][NTf 2 ] and [C 2 C 1 im][OTF]) onto ITO, gold/palladium (AuPd) and pentacene surfaces were performed. A greater wettability behavior of ILs is observed for surfaces containing AuPd. Sequential and simultaneous depositions of ILs and pentacene were explored. Simultaneous depositions lead to the formation of nanocomposites films, consisting of IL micro- and nanodroplets covered by pentacene layers. Plasma surface treatment was used to induce the ILs droplets coalescence and explore the dynamics and phase separation of the nanocomposites. The [C 2 C 1 im][OTF] droplets were found to be completely covered with pentacene, which suggests a great affinity between cation-anion pairs and the aromatic moiety. Pentacene films and their nanocomposites with ILs exhibit a typical optical band gap of E gap =1.77 eV, indicating that the nanocomposite phase domains are large enough to behavior as the bulk., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Introduction: Robotic-Assisted Radical Prostatectomy (RARP) has largely replaced the open technique worldwide as the first surgical modality for prostate cancer. We aim at describing the experience of RARP at a high-volume single cancer center, proposing a modified technique of nerve-sparing prostatectomy and comparing functional outcomes throughout our experience. Materials and Methods: We retrospectively reviewed 1088 patients divided into group 1 (operated from May 2013 to November 2014), submitted to the standard transperitoneal robotic technique, and group 2 (operated from December 2014 to December 2017), submitted to extraperitoneal RARP with complete anterior peri-prostatic preservation technique and a clipless approach (no use of clips and cautious use of bipolar energy). We constructed a retrospective 1:2 matched-pair analysis considering age, body mass index, D'Amico risk classification, and American Society of Anesthesiologists classification as matching criteria. Univariate and multivariate Cox logistic regression analysis were used to identify predictors related to recovery of continence and erectile function. Results: Groups were comparable by clinical and demographic variables. There was no significant difference in overall continence rate. Mean time for continence recovery was 6.6 months in group 1 and 5.8 months in group 2. Erectile function recovery, with or without drugs, in 12 months was described in 53.5% in group 1 and 75% in group 2. Potency recovery was significantly earlier in group 2. Conclusions: In our experience, extraperitoneal RARP with complete anterior peri-prostatic preservation and a clipless approach is a feasible and reproducible technique. It demonstrated improved erectile function recovery and similar continence results. Prospective multicenter studies are needed to validate these results.

Purpose: To evaluate the effect of a zinc chloride (ZnCl2) solution (2% wt), incorporated into a two-step etch-and-rinse adhesive system (AS), on microtensile bond strength (µTBS) to caries-affected dentin (CAD)., Methods: First, the degree of conversion (DC) of the AS with and without the ZnCl2 solution was evaluated by Fourier transform infrared spectroscopy (FTIR). Second, beam-shaped samples (7 mm × 2 mm × 1 mm) were prepared with the AS containing the ZnCl2 solution to perform flexural strength (FS) tests. For µTBS testing purposes, CAD surfaces were etched with phosphoric acid and randomly divided into three groups (n=10) : ZnCl2- AS with ZnCl2; NT (no treatment)- AS without ZnCl2; and CHX - pretreatment with 2% chlorhexidine solution. AS (Adper Single Bond 2) was applied according to the manufacturer's instructions, and resin composite restorations were built up. After 24 hours, the resin-dentin blocks were sectioned into specimens (0.8 mm2), and then subjected to micro;TBS testing immediately following, or after 6 or 12 months of water storage (WS). The adhesive interface was evaluated by scanning electron microscope. Both µTBS and FS tests were performed using a universal testing machine ( 0.5 mm/minute). FS and DC data were submitted to the Student t-test, and µTBS data were subjected to two-way ANOVA and Tukey's test (α= 0.05)., Results: DC was not affected by ZnCl2 incorporation into AS (P= 0.2527). Higher FS values were obtained in the group with ZnCl2 added to AS. Regarding µTBS, the mean of the NT group was statistically higher than that of the ZnCl2 or the CHX groups (P< 0.001(, regardless of WS, but the latter groups did not differ from each other. µTBS at 24 hours was statistically superior to that of 6 and 12 months of WS (P< 0.001)., Competing Interests: The authors declared no conflict of interest., (Copyright©American Journal of Dentistry.)

Objective: To compare the results of the standard urotherapy alone and associated with pelvic floor muscle training alone, and in combination with oxybutynin in treatment of nonmonosymptomatic nocturnal enuresis., Methods: A total of 38 children aged 5 to 10 years were randomized into three groups: Group I (n=12) that was submitted to standard urotherapy; Group II (n=15), standard urotherapy associated with pelvic floor muscle training; and Group III (n=11), standard urotherapy associated with pelvic floor muscle training and oxybutynin; the treatment lasted 12 weeks. The assessment tools used were playful bladder diary, and a 48-hour bladder diary, before and after treatment. After 2 years, patients were assessed by telephone using a standardized questionnaire., Results: The data of children from the three groups were homogeneous at baseline. After 12-week treatment, all children showed improved symptoms and signs of nonmonosymptomatic nocturnal enuresis, but the differences were not significant among the groups. After 2 years, the three groups showed maintenance of treatment results, but no differences among them., Conclusion: All treatment modalities were effective regarding improved enuresis and lower urinary tract symptoms, but the sample was not large enough to show differences among groups.

Investigations suggest the benefits of low-level laser therapy (LLLT) to improve noninvasive body contouring treatments, inflammation, insulin resistance and to reduce body fat. However, the mechanism for such potential effects in association with exercise training (ET) and possible implications in browning adiposity processes remains unclear. Forty-nine obese women were involved, aged between 20 and 40 years with a body mass index (BMI) of 30-40 kg/m 2 . The volunteers were divided into Phototherapy (808 nm) and SHAM groups. Interventions consisted of exercise training and phototherapy applications post exercise for 4 months, with three sessions/week. Body composition, lipid profile, insulin resistance, atrial natriuretic peptide (ANP), WNT5 signaling, interleukin-6 (IL-6), and fibroblast growth factor-21 (FGF-21) were measured. Improvements in body mass, BMI, body fat mass, lean mass, visceral fat, waist circumference, insulin, HOMA-IR, total cholesterol, LDL-cholesterol, triglycerides, and ANP in both groups were demonstrated. Only the Phototherapy group showed a reduction in interleukin-6 and an increase in WNT5 signaling. In addition, it was possible to observe a higher magnitude change for the fat mass, insulin, HOMA-IR, and FGF-21 variables in the Phototherapy group. In the present investigation, it was demonstrated that exercise training associated with LLLT promotes an improvement in body composition and inflammatory processes as previously demonstrated. The Phototherapy group especially presented positive modifications of WNT5 signaling, FGF-21, and ANP, possible biomarkers associated with browning adiposity processes. This suggests that this kind of intervention promotes results applicable in clinical practice to control obesity and related comorbidities.

Objective: To determine the frequency of the performance of mammography with preventive purpose of the screening of breast cancer in Spanish women, the evolution between the years 2006-2014, the sociodemographic profile of the women who undergo the mammography and to analyze the factors that influence in their adhesion., Design: Transversal study., Sites: Spain., Participants: A total of 53.628 women over 15 years old that are surveyed in the National Health Survey in Spain 2006 and 2011/12 and the European Health Survey in Spain 2009 and 2014., Measurements: The following variables were used: mammography, frequency of mammography performance and the reason for the realization, as well as sociodemographic variables. Social class was obtained from the last occupation of the main family supporter. A logistic regression analysis was performed with sociodemographic variables., Results: The prevalence of mammography has been increasing from 2006 to 2014, and also for the reason that the participants had received a letter, they were telephoned or offered in their Health Center to undergo this test. There are significant differences in the performance of mammography in the different autonomous communities., Conclusions: Performing mammography has increased significantly from 2006 to 2014, although there are still differences between autonomous communities, with Ceuta and Melilla being the least percentage of performed mammography. The factors that are related to greater performed mammography are: higher educational level, higher social class, married civil status, Spanish nationality and age., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Objective: Leptin is an adipokine released mainly by adipose tissue, with many functions including regulation of energy balance. However, little is known about the effect of LEPR polymorphism on orexigenic and anorexigenic neuropeptides. Thus, the aim of the present study is to verify the influence of LEPR polymorphism (rs2767485) on serum orexigenic (NPY, MCH and AgRP) and anorexigenic (Leptin and α-MSH) neuropeptides levels among obese adolescents submitted to 1year of multicomponent weight loss therapy., Methods: Seventy-six adolescents with obesity were enrolled in 1year of weight loss therapy including clinical, nutritional, psychological and exercise-related. Blood samples were collected to analyze neuropeptides (NPY, MCH, AgRP and leptin) and LEPR genotyping. Visceral fat was measured by ultrasound and body composition was measured by plethysmography. The parameters were measured at baseline and after one year. Adolescents were grouped according to genotype (TT or CT+CC group). Effect of the weight loss therapy was analyzed through ANOVA and Wilcox, according to normality. Statistic value was set at <0.05., Results: C-allele carriers have the orexigenic neuropeptides (NPY, AgRP and MCH) levels statistically higher when compared with TT group, at baseline. Furthermore, TT group seems to respond better to the therapy by a greater delta on BMI. Indeed, the data suggest a concomitant increased of AgRP levels in CT+CC genotypes, after weight loss therapy., Conclusion: Both groups responded to the weight loss intervention, however wildtypes (TT) appear to respond to the intervention most optimally with C carries, where post intervention reduction in BMI was significantly greater in wildtypes. The leptin receptor polymorphism seems to affect neuroendocrine regulation of energy balance among adolescents with obesity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

During 2014-2016, we conducted mosquito-based Zika virus surveillance in Rio de Janeiro, Brazil. Results suggest that Zika virus was probably introduced into the area during May-November 2013 via multiple in-country sources. Furthermore, our results strengthen the hypothesis that Zika virus in the Americas originated in Brazil during October 2012-May 2013.

Mayaro virus (MAYV) is an arthropod-borne virus and a member of the family Togaviridae, genus Alphavirus. Its infection leads to an acute illness accompanied by long-lasting arthralgia. To date, there are no antiviral drugs or vaccines against infection with MAYV and resources for the prevention or treatment of other alphaviruses are very limited. MAYV has served as a model to study the antiviral potential of several substances on alphavirus replication. In this work we evaluated the antiviral effect of seven new derivatives of thieno[2,3-b]pyridine against MAYV replication in a mammalian cell line. All derivatives were able to reduce viral production effectively at concentrations that were non-toxic for Vero cells. Molecular modeling assays predicted low toxicity risk and good oral bioavailability of the substances in humans. One of the molecules, selected for further study, demonstrated a strong anti-MAYV effect at early stages of replication, as it protected pre-treated cells and also during the late stages, affecting virus morphogenesis. This study is the first to demonstrate the antiviral effect of thienopyridine derivatives on MAYV replication in vitro, suggesting the potential application of these substances as antiviral molecules against alphaviruses. Additional in vivo research will be needed to expand the putative therapeutic applications.

Background: Homeostasis Model Assessment-Adiponectin (HOMA-AD) is suggesting a new biomarker of insulin resistance in obese population. In this way, the purpose of this study was to investigate the effects of different kinds of exercise in the sensitive index predictor of insulin resistance., Methods: A total of 148 obese adolescents were enrolled in the program. They aged 15-19 y, with Body Mass Index (BMI) ≥P95th and were submitted to 1 year of interdisciplinary weight loss therapy, randomized in two groups, aerobic training (AT) (N.=51) and aerobic plus resistance training (N.=97). Blood samples were collected to analyze adiponectin, glucose and insulin concentrations. The insulin resistance was measured by HOMA-AD and Homeostasis Model Assessment Insulin Resistance Index (HOMA-IR)., Results: Both kinds of exercise training promoted a decrease in body mass, body mass index, fat mass, visceral and subcutaneous fat. However, only aerobic plus resistance training was effective to reduce HOMA-AD, insulin and glucose concentration; and increase insulin sensibility and adiponectin concentration., Conclusions: The aerobic plus resistance training was more effective than AT alone to improve the HOMA-AD, suggesting clinical application on obesity, diabetes, atherosclerosis and metabolic syndrome control in the pediatric population.

Introduction: The main purpose of the present study was to investigate whether I/D polymorphism of the ACE gene might affect metabolic changes related to the metabolic syndrome through a long-term interdisciplinary therapy in obese adolescents., Methods: In total, 125 obese adolescents who entered the interdisciplinary obesity programme were assigned to the following two subgroups: metabolic syndrome or non-metabolic syndrome. They were evaluated at baseline and after 1 year. Genomic DNA was extracted from circulating leukocytes., Results: Subjects with the II genotype in the non-metabolic syndrome group were only to increase their fat-free mass after therapy. Regarding lipid profile, subjects with ID and DD genotypes from both groups reduced their low-density lipoprotein cholesterol levels significantly. The metabolic parameters from the ID and DD genotypes of the non-metabolic syndrome group showed a significantly improved insulin response., Conclusion: In the present study, we showed that the ACE polymorphism was able to influence the fat-free mass in the I-carry allele in the non-metabolic syndrome group positively. In addition, the I-carry allele was able to improve the insulin resistance of the metabolic syndrome group significantly. These results suggest that the ACE I/D genotypes can influence, in different ways, the specific parameters of metabolism among obese adolescents submitted for long-term interdisciplinary therapy.

Klebsiella pneumoniae is a pathogen frequently associated with antibiotic-resistant nosocomial infections. Here, we describe the genome of KP-Rio/2015, a novel phage of K. pneumoniae belonging to the family Podoviridae., (Copyright © 2016 Meira et al.)

Objective: This study aimed to identify cutoff points for detecting hypertriglyceridemic waist phenotype (HTWP) in adolescents and to investigate the association of the HTWP with insulin resistance (IR) and metabolic syndrome components., Methods: A multicentric cross-sectional study of 861 adolescents (10-19 years of age, 504 girls) was conducted. Pubertal stage, anthropometric, and laboratory parameters were assessed. IR was assessed by Homeostasis Model Assessment for Insulin Resistance (HOMA1-IR) index and hyperglycemic clamp (n = 80). HTWP was defined by the presence of increased plasma triglycerides (TGs) and increased waist circumference (WC) according to cutoff points obtained in ROC curve analysis given the HOMA1-IR index as a reference method., Results: Cutoffs for WC and TGs, with a higher sum of sensitivity (S) and specificity (E), were, respectively: >84 cm (S:65.1%, E:71.9%) and >87 mg/dL (S:65.1%, E:73.4%) in pubertal girls; >88.5 cm (S:80.2%, E:60.2%) and >78 mg/dL (S:60.5%, E:53.2%) in postpubertal girls; >94 cm (S:73.1%, E:83.1%) and >79 mg/dL (S:61.5%, E:60.2%) in pubertal boys; and >99 cm (S:81.3%, E:78.7%) and >86 mg/dL in postpubertal boys (S:68.1%, E:60.7%). HTWP frequency was 27.5%. In the phenotype presence, after adjustment for age and pubertal stage, blood pressure and fasting glucose levels were elevated and high-density lipoprotein cholesterol was lower (p < 0.001). Adolescents with the HTWP showed more IR, evaluated both by the HOMA1-IR and by the clamp test (p < 0.003)., Conclusion: The findings suggest HTWP as an IR status in adolescents. Cutoff point standardization for gender and pubertal stage, combined with the ease of application of the method, may allow their use for screening adolescents who would most benefit from lifestyle changes.

The purpose of the present study was to evaluate if interdisciplinary therapy can influence the cardiometabolic and serum free fatty acid profile. The second aim was to evaluate if there is an association between serum free fatty acids, inflammation and cardiometabolic biomarkers in obese adolescents with and without metabolic syndrome submitted to a long-term interdisciplinary therapy. The study involved 108 postpuberty obese adolescents, who were divided according to metabolic syndrome (MetS) diagnosis: MetS (n=32) and Non-MetS (n=76). The interdisciplinary therapy consisted of a 1-year period of nutrition, psychology, physical exercise and clinical support. After therapy, both groups improved metabolic, inflammatory (leptin, adiponectin, leptin/adiponectin ratio, adiponectin/leptin ratio and C-reactive protein) and cardiometabolic profile (PAI-1 and ICAM). Metabolic syndrome prevalence reduced from 28.70% to 12.96%. Both groups reduced myristic acid (C14:0) and increased docosahexaenoic acid (DHA, C22:6n3), heneicosapentaenoic acid (HPA, C21:5n3) and arachidonic acid (C20:4n6). After adjustment for metabolic syndrome and the number of metabolic syndrome parameters, multiple regression analysis showed that changes in VCAM and PAI-1 were negatively associated with changes in cis-linoleic acid (C18:2n6c). Additionally, changes in trans-linoleic acid (C18:2n6t) were also positively associated with these biomarkers. Moreover, leptin and leptin/adiponectin ratio were negatively associated with changes in docosapentaenoic acid (DPA, C22:5n3) and stearidonic acid (SDA, C18:4n3). Adiponectin/leptin ratio was positively associated with docosapentaenoic acid (DPA, C22:5n3). Changes in adiponectin were positively correlated with changes in omega 3, such as heneicosapentaenoic acid (HPA, C21:5n3) and docosapentaenoic acid (DPA, C22:5n3). Results support that interdisciplinary therapy can control inflammatory and cardiometabolic profile in obese adolescents. Moreover, serum fatty acids can be influenced by lifestyle changes and are able to modulate these biomarkers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The ageing of the population is a reality in our society nowadays. The aging process changes increase the probability that health problems occur. This fact involves that the needs of care demanded by the population increase too. The care for the elderly generally are provided in home environments, where often, the primary caregiver is another old person. In this sense, must be taken into account that this stage of life, the old age, although there has been important improvements in the quality of life and in the resolution of health problems, presents certain limitations refers to physical and mental declines that affect to the functional capacity of elderly caregivers. For this reason, it is necessary to carry out a comprehensive geriatric assessment to identify unresolved needs and establish care strategies required to attend their demands for care.

Very few data exist on the management of adult patients diagnosed with primary immune thrombocytopenia (ITP). The objectives of this study were to describe the diagnostic and treatment patterns for ITP and to compare the findings to recent ITP guidelines. We retrospectively analyzed the medical records of adult ITP patients diagnosed with primary ITP between January 2011 and June 2012 and examined whether management strategies were consistent or not with eight recent guideline-recommended practices. Overall, median age at the diagnosis of the disease (n = 101) was 58 years and median platelet count 12 × 10(9)/L with 75.2 % of patients having symptoms of ITP. The study perceived two major shortcomings in the diagnostic approach: (1) failure to perform peripheral blood film examination in 22.8 % of patients, a test that is mandatory by all guidelines, and (2) ordinary bone marrow assessment in more than half of the patients at diagnosis (50.5 %), a test not routinely recommended by guidelines. Low appropriateness in therapeutic management of patients included (1) unjustified use of intravenous immunoglobulin in the absence of bleeding in 54.8 % of patients and (2) splenectomy not being deferred until 6-12 months from diagnosis (median 161 days). Data also reflect a trend towards the early use of thrombopoietin receptor agonists in the treatment of patients who are refractory to any first-line therapy. We have recognized important areas of inapropriateness in the diagnostic and therapeutic management of adult ITP patients. Compliance with established guidelines should be encouraged in order to improve patient outcomes.

Home accidents are more common in the elderly and they can have serious consequences to the injured person's health. At home, chances to suffer accidents of any type are higher, because it's the place where old people spend most of their daily time. It is important to point out that a high percentage of domestic accidents could be easily avoided by taking some simple cautions. The main aim of this paper is to know how we can prevent most common domestic accidents in the aged population: falls, burnings, poisonings and fire prevention.

Burn injuries are tissue injuries originated as a result of a physical or chemical trauma. They can cause from a mild skin affectation to the total destruction of the affected tissues, depending on various levels of severity. Moreover, if the affected body surface is very large, patient life can seriously be compromised. In this chapter, the intention is to clarify the nursing care for the affected area, once patient's life risk is stabilized and controlled. This care should be based on an adequate approach to local handling of burn injuries, after their severity and prognosis have been stated. To do this, it will be used the standardized nursing language NNN, referring to Nursing Diagnosis NANDA (North American Nursing Diagnosis Association), Nursing Outcomes Classification (NOC) and Nursing Interventions Classification (NIC). This taxonomy is very useful to describe the Nursing clinical practice of burns care because it can easily be used by nurses participating in the care of this type of patients. Nursing plans using the NNN taxonomy can be designed using existing software applications.

Objective: To assess the relationship between the degree of waist circumference (WC) and nonalcoholic fatty liver disease (NAFLD) in obese adolescents of both genders, analyzed according to quartiles of WC., Methods: Cross-sectional study that involved 247 obese adolescents aged 12-19 years. Mean values of the nutritional parameters and serum analyses were compared with the groups using the independent t-test. Pearson correlation coefficient was used to determine the relationship of the parameters studied. Chi-square test for trend was used to determine the relationship between the prevalence of the NAFLD and WC quartile by gender., Results: NAFLD were presented in 60% of the study participants. Obese adolescents in the 3rd and 4th quartiles of WC presented higher prevalence of NAFLD when compared with that in the 1st quartile in both genders. The NAFLD patients had significantly higher values for body weight, BMI (body mass index), BAZ-score (BMI-for-age z-scores), total fat (% and kg), WC, visceral fat, insulin, insulin resistance index (HOMA-IR), aspartate aminotransferase and alanine aminotransferase, when compared with non-NAFLD obese adolescents., Conclusions: The results presented here suggest that an increase in WC can reliably predict the risk of NAFLD in obese adolescents. This is a low cost and easy-to-use tool that can help in screening in adolescents., (Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.)

Myxofibrosarcoma is recognized as a malignant neoplasm of fibroblastic origin with increased prevalence in the elderly, presenting as nodules or tumors that may extend to the dermis and skeletal muscle, preferably in the lower limbs. Histologically it is characterized by a proliferation of spindle cells in a myxoid stroma. Myxofibrosarcoma has a high potential for local recurrence and metastasis, mainly when it presents a high or intermediate histological grade. We report the case of an eighty-four year old patient with a difficult diagnosis of a highly aggressive tumor.

We studied the mechanisms involved in the human corpora cavernosa (HCC) relaxation induced by a new metal-based nitric oxide (NO) donor, the ruthenium complex cis-[Ru(bpy)2Imn(NO)](+3) (FOR0811). FOR0811 produced relaxation in phenylephrine (PE)-precontracted HCC with a maximal response that achieved 112.9 ± 10.6%. There was no difference between the maximal relaxation induced by FOR0811 when compared with sodium nitroprusside (SNP) (106.8 ± 7.3%), BAY41-2272 (107.6 ± 4.1%) or vardenafil (103.4 ± 3.8%), however, FOR0811 was less potent than SNP and vardenafil. L-N(G)-nitroarginine methyl ester (L-NAME), a NO synthase inhibitor, had no effect in the concentration-response curve elicited by FOR0811. 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a heme-site inhibitor of soluble guanylyl cyclase (sGC) was able to either block or reverse the relaxation induced by FOR0811. On the other hand, the relaxation induced by FOR0811 was not affected by glibenclamide, a blocker of ATP-sensitive potassium channels. FOR0811 (10 μM) was able to increase cyclic guanosine monophosphate (cGMP) levels in corpora cavernosa strips. FOR0811 completely relaxes HCC by a sGC-cGMP-dependent mechanism and can be a lead compound in the development of new stable NO donors.