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BACKGROUND: Immunoglobulin A (IgA) nephropathy is a disorder of the immune system affecting kidney function, and genome-wide association studies (GWAS) have defined numerous loci with associated variation, all implicating components of innate or adaptive immunity. Among these, single nucleotide polymorphisms (SNPs) in a region including the multiallelic copy number variation (CNV) of DEFA1A3 are associated with IgA nephropathy in both European and Asian populations. At present, the precise factors underlying the observed associations at DEFA1A3 have not been defined, although the key alleles differ between Asian and European populations, and multiple independent factors may be involved even within a single population. METHODS: In this study, we measured DEFA1A3 copy number in UK family trios with an offspring affected by IgA nephropathy, used the population distributions of joint SNP-CNV haplotypes to infer the likely segregation in trios, and applied transmission disequilibrium tests (TDT) to examine joint SNP-CNV haplotypes for over- or undertransmission into affected offspring from heterozygous parents. RESULTS AND CONCLUSIONS: We observed overtransmission of 3-copy class 2 haplotypes (raw p = 0.029) and some evidence for under-transmission of 3-copy class 1 haplotypes (raw p = 0.051), although these apparent effects were not statistically significant after correction for testing of multiple haplotypes.
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Glomerulonefrite por IGA , alfa-Defensinas , Humanos , Haplótipos , Variações do Número de Cópias de DNA , Polimorfismo de Nucleotídeo Único , alfa-Defensinas/genética , Estudo de Associação Genômica Ampla , Glomerulonefrite por IGA/genética , Suscetibilidade a Doenças , Predisposição Genética para Doença , Peptídeos Cíclicos/genéticaRESUMO
Deferoxamine mesylate (DFO) is an FDA-approved, hexadentate iron chelator routinely used to alleviate systemic iron burden in thalassemia major and sickle cell patients. Iron accumulation in these disease states results from the repeated blood transfusions required to manage these conditions. Iron accumulation has also been implicated in the pathogenesis of Alzheimer's disease (AD), Parkinson's disease (PD), and secondary injury following intracerebral hemorrhage (ICH). Chelation of brain iron is thus a promising therapeutic strategy for improving behavioral outcomes and slowing neurodegeneration in the aforementioned disease states, though the effectiveness of DFO treatment is limited on several accounts. Systemically administered DFO results in nonspecific toxicity at high doses, and the drug's short half-life leads to low patient compliance. Mixed reports of DFO's ability to cross the blood-brain barrier (BBB) also appear in literature. These limitations necessitate novel DFO formulations prior to the drug's widespread use in managing neurodegeneration. Herein, we discuss the various dosing regimens and formulations employed in intranasal (IN) or systemic DFO treatment, as well as the physiological and behavioral outcomes observed in animal models of AD, PD, and ICH. The clinical progress of chelation therapy with DFO in managing neurodegeneration is also evaluated. Finally, the elimination of intranasally administered particles via the glymphatic system and efflux transporters is discussed. Abundant preclinical evidence suggests that intranasal DFO treatment improves memory retention and behavioral outcome in rodent models of AD, PD, and ICH. Several other biochemical and physiological metrics, such as tau phosphorylation, the survival of tyrosine hydroxylase-positive neurons, and infarct volume, are also positively affected by intranasal DFO treatment. However, dosing regimens are inconsistent across studies, and little is known about brain DFO concentration following treatment. Systemic DFO treatment yields similar results, and some complex formulations have been developed to improve permeability across the BBB. However, despite the success in preclinical models, clinical translation is limited with most clinical evidence investigating DFO treatment in ICH patients, where high-dose treatment has proven dangerous and dosing regimens are not consistent across studies. DFO is a strong drug candidate for managing neurodegeneration in the aging population, but before it can be routinely implemented as a therapeutic agent, dosing regimens must be standardized, and brain DFO content following drug administration must be understood and controlled via novel formulations.
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Doença de Alzheimer/tratamento farmacológico , Hemorragia Cerebral/tratamento farmacológico , Desferroxamina/administração & dosagem , Portadores de Fármacos/química , Doença de Parkinson/tratamento farmacológico , Sideróforos/administração & dosagem , Administração Intranasal , Doença de Alzheimer/patologia , Animais , Disponibilidade Biológica , Barreira Hematoencefálica/metabolismo , Encéfalo/citologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/patologia , Desferroxamina/farmacocinética , Modelos Animais de Doenças , Meia-Vida , Humanos , Injeções Intramusculares , Injeções Intraventriculares , Injeções Espinhais , Injeções Subcutâneas , Ferro/metabolismo , Adesão à Medicação , Nanopartículas/química , Mucosa Nasal/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Doença de Parkinson/patologia , Permeabilidade , Sideróforos/farmacocinética , Distribuição TecidualRESUMO
OBJECTIVE: Operator skills are essential for thoracic ultrasound (TUS) to ensure diagnostic accuracy. Immersive virtual reality (IVR) has shown potential within medical education but never for assessment of TUS skills. This study was aimed at developing an IVR test for assessing TUS skills, gathering validity evidence and establishing a pass/fail score. METHODS: An expert panel developed a test based on the TUS protocol by the European Respiratory Society (ERS), including a tutorial and two clinical cases (pleural effusion and interstitial syndrome), using an IVR platform (VitaSim, Odense, Denmark). Four anterior, four lateral and six posterior zones were available for examination and decision of diagnosis. Each correct examination equaled one point. The contrasting groups' method was used to set a pass/fail score. RESULTS: Data were collected during the 2022 ERS Congress. We included 13 novices (N, experience: 0 TUS), 22 intermediates (I, 1-50 TUS) and 11 experienced clinicians (E, >50 TUS). Cronbach's α was 0.86. The total mean point scores in case 1 (C1) were (N) 5.0 ± 2.7, (I) 7.3 ± 2.4 and (E) 8.7 ± 1.3, and the scores in case 2 (C2) were (N) 4.5 ± 1.8, (I) 6.7 ± 2.3 and (E) 8.5 ± 2.1. Significant differences were found between N and I for C1 (p = 0.007) and C2 (p = 0.02), I and E for C1 (p = 0.04) and C2 (p = 0.019) and N and E for C1 (p < 0.001) and C2 (p < 0.001). The pass/fail score was 7 points in each case. CONCLUSION: We established an IVR test that can distinguish between operators with different TUS skills. This enables a standardized, objective and evidence-based approach to assessment of TUS skills.
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Educação Médica , Realidade Virtual , Competência Clínica , Reprodutibilidade dos Testes , UltrassonografiaRESUMO
This article provides a brief overview of the Adult Cystic Fibrosis Conference (#ACFMilan2023) programme, which will be held on 1-2 December 2023, in Milan (Italy) and online. https://bit.ly/3sKpN6p.
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Thoracic ultrasound has developed into an integral part of the respiratory physician's diagnostic and therapeutic toolbox, with high diagnostic accuracy for many diseases causing acute or chronic respiratory symptoms. However, it is vitally important that the operator has received the appropriate education and training to ensure a systematic and thorough examination, correct image interpretation, and that they then have the appropriate skills to integrate all the findings for patient benefit. In this review, we present the new European Respiratory Society thoracic ultrasound training programme, including a discussion of curriculum development, its implementation, and trainee evaluation. This programme enables participants to gain competence in thoracic ultrasound through structured, evidence-based training with robustly validated assessments and certification. The training programme consists of three components: an online, theoretical part (part 1), which is accessible all year; a practical course (part 2), with four courses held each year (two online courses and two on-site courses); and an examination (part 3) comprising an objective structured clinical examination (OSCE), which is hosted each year at the European Respiratory Society Congress.
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This article provides an overview of the reasons to attend the 2023 ERS Congress, including a summary of the ECM session and the NEXT programme. https://bit.ly/46ghP4g.
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The continuous and ongoing coronavirus disease 2019 (COVID-19) pandemic has highly affected pulmonologists and pulmonology residents worldwide. To identify where additional work and resources must be focused, it is important to explore on what parameters the pulmonologists and residents are challenged. We present the results of a society-led survey on pulmonologists' and pulmonology residents' work and clinical life during the pandemic. A total of 579 pulmonologists and pulmonology residents completed the survey (5.9% of the European Respiratory Society's physician members) and most respondents answered that they have had sufficient training on how to handle patients with COVID-19 (e.g. how to handle patients to prevent virus spread). However, more than a third of the respondents (n=210, 36.3%) had performed procedures they did not feel competent in due to the pandemic and, for example, relocation to COVID-19 units. We must strive for investment in research on medical education and potentially simulation-based training in technical procedures to ensure competence and decrease the insecurity about new procedures, especially in the setting of worldwide pandemics or acute critical situations.
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An overview of what to expect from the European Respiratory Society (ERS) International Congress 2022, including the top picks of the International Congress Programme Committee and a summary of the Early Career Member session. https://bit.ly/3tNTlgY.
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In 2005, the European Respiratory Society (ERS) launched a project to harmonise education and training and to address the heterogeneity of respiratory health training across Europe. Since then, various educational activities have been developed for different target audiences. This article will describe the overall methodology and the projects developed over the years, detailing their objectives and target audiences. Moving forward, ERS strives to provide a structure for the continuing professional development of respiratory physicians.
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This article provides a brief description of the Early Career Member session and guidance on how to get the most out of the European Respiratory Society (ERS) International Congress 2021, to help attendees plan their Congress in advance. https://bit.ly/3dBNrYC.
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This study was carried out aiming to evaluate the repellent and acaricidal activity of major ingredient compounds from coconut oil including their methyl ester derivatives and catnip oil against nymphs and larvae of Amblyomma sculptum. Repellent candidates, coconut oil free fatty acids (coconut FFA mainly C12, C10 and C8 acid); lauric acid (C12 acid); capric acid (C10 acid); methyl laurate; methyl caprate and 10 % each of C12, C10 and C8 acid (1:1:1) in lavender oil formulation (CFA in lavender formula) and catnip oil (Nepeta cataria), were screened using a Petri dish bioassay to assess repellency. Catnip oil, methyl caprate, methyl laurate, and CFA in lavender formulation repelled ticks strongly (P < 0.05) at almost all times evaluated, with an average of 77.8-100% repellency. Some candidate repellents with consistent strong repellence observed were selected for further evaluation, with coconut CFA in lavender formula showing a repellency lasted up to 7 days, while those of catnip oil and methyl caprate were active for 4 and 3 days, respectively. For the acaricide test, five concentrations (2.5; 5; 10; 15 and 20 mg/mL) were evaluated using the larval packet test. Only CFA in lavender formula and two methyl esters showed acaricidal activity, with methyl laurate presenting the strongest toxicity at 15 mg/mL concentration, which was effective against more than 93 % of the tested larvae. Catnip oil caused no mortality of A. scultptum larvae in all concentrations tested.
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Acaricidas , Repelentes de Insetos , Nepeta , Acaricidas/farmacologia , Amblyomma , Animais , Óleo de Coco , Repelentes de Insetos/farmacologia , Ácidos LáuricosRESUMO
Volumetric muscle loss necessitates novel tissue engineering strategies for skeletal muscle repair, which have traditionally involved cells and extracellular matrix-mimicking scaffolds and have thus far been unable to successfully restore physiologically relevant function. However, the incorporation of various nanomaterial additives with unique physicochemical properties into scaffolds has recently been explored as a means of fabricating constructs that are responsive to electrical, magnetic, and photothermal stimulation. Herein, several classes of nanomaterials that are used to mediate external stimulation to tissue engineered skeletal muscle are reviewed and the impact of these stimuli-responsive biomaterials on cell growth and differentiation and in vivo muscle repair is discussed. The degradation kinetics and biocompatibilities of these nanomaterial additives are also briefly examined and their potential for incorporation into clinically translatable skeletal muscle tissue engineering strategies is considered. Overall, these nanomaterial additives have proven efficacious and incorporation in tissue engineering scaffolds has resulted in enhanced functional skeletal muscle regeneration.
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A reflection on @EuroRespSoc education, a learning pathway for the future: better practice, better physicians, better patients http://bit.ly/2XHmr3J.
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The @EuroRespSoc launches a new thoracic oncology continuous professional development programme http://bit.ly/31ShuTp.
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The ERS International Congress educational forum brings together experts to advance respiratory medicine http://ow.ly/hP9k30kz6ZM.
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ERS has developed a syllabus for postgraduate training in respiratory infections to guide programme designers http://ow.ly/xJ0R30m8CYB.
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ERS launches structured EBUS training programme http://ow.ly/br5P302vhh3.