1,721,065 research outputs found
Efficacy of augmentation therapy for emphysema associated with α1-antitrypsin deficiency: Enough is enough
No full textRare variants in alpha 1 antitrypsin deficiency: a systematic literature review
No full textBackground: Alpha 1 Antitrypsin Deficiency (AATD) is a largely underrecognized genetic condition characterized by low Alpha 1 Antitrypsin (AAT) serum levels, resulting from variations in SERPINA1. Many individuals affected by AATD are thought to be undiagnosed, leading to poor patient outcomes. The Z (c.1096G > A; p.Glu366Lys) and S (c.863A > T; p.Glu288Val) deficiency variants are the most frequently found variants in AATD, with the Z variant present in most individuals diagnosed with AATD. However, there are many other less frequent variants known to contribute to lung and/or liver disease in AATD. To identify the most common rare variants associated with AATD, we conducted a systematic literature review with the aim of assessing AATD variation patterns across the world. Methods: A systematic literature search was performed to identify published studies reporting AATD/SERPINA1 variants. Study eligibility was assessed for the potential to contain relevant information, with quality assessment and data extraction performed on studies meeting all eligibility criteria. AATD variants were grouped by variant type and linked to the geographical region identified from the reporting article. Results: Of the 4945 articles identified by the search string, 864 contained useful information for this study. Most articles came from the United States, followed by the United Kingdom, Germany, Spain, and Italy. Collectively, the articles identified a total of 7631 rare variants and 216 types of rare variant across 80 counties. The F (c.739C > T; p.Arg247Cys) variant was identified 1,281 times and was the most reported known rare variant worldwide, followed by the I (c.187C > T; p.Arg63Cys) variant. Worldwide, there were 1492 Null/rare variants that were unidentified at the time of source article publication and 75 rare novel variants reported only once. Conclusion: AATD goes far beyond the Z and S variants, suggesting there may be widespread underdiagnosis of patients with the condition. Each geographical region has its own distinctive variety of AATD variants and, therefore, comprehensive testing is needed to fully understand the true number and type of variants that exist. Comprehensive testing is also needed to ensure accurate diagnosis, optimize treatment strategies, and improve outcomes for patients with AATD
Diagnosis and treatment of pulmonarydisease in alfa-1-antitrypsin deficiency: A statement of European Respiratory Society
No full textAlpfa-1-antitrypsin deficiency (AATD) is the most common hereditary disorder in adults. It is associated with an increased risk of developing pulmonary emphysema and liver disease. The lung injury in AATD is closely associated with smoking, but progressive lung disease could occur even in never-smokers. A number of individuals with AATD remain undiagnosed and therefore do not receive appropriate care and treatment. The most recent international document on AATD was the joint statement of the American Thoracic Society and the European Respiratory Society published in 2003. Thereafter, there has been a continuous development of novel, more accurate and less expensive genetic diagnostic methods. Furthermore, new outcome parameters have been developed and validated for use in clinical trials and a new series of observational and randomized clinical trials have provided more evidence concerning the efficacy and safety of augmentation therapy, the only specific treatment available for the pulmonary disease associated with AATD. As AATD is a rare disease, it is important to createnational and international registries and to collect information prospectively about the natural history of the disease. Management of AATD patients must be supervised by national or regional expert centres and inequalities in access to therapies across Europe should be addressed
Sanger and Next-Generation Sequencing of AAT
No full text: Sequencing of DNA is normally the final procedure carried out to determine the actual pathogenic variants when the techniques used for genotyping are unable to provide complete identification of both AAT alleles. Gene sequencing of complete SERPINA1 gene by using the Sanger method or next-generation sequencing (NGS) is crucial to enable correct diagnosis in patients with alpha1-antitrypsin deficiency caused by uncommon AAT variants.This protocol explains how to correctly sequence SERPINA1 gene both with Sanger method and NGS
Mesenchymal stem/stromal cell secretome for lung regeneration: The long way through “pharmaceuticalization” for the best formulation.
No full textPulmonary acute and chronic diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis and pulmonary hypertension, are considered to be major health issues worldwide. Cellular therapies with Mesenchymal Stem Cells (MSCs) offer a new therapeutic approach for chronic and acute lung diseases related to their anti-inflammatory, immunomodulatory, regenerative, pro-angiogenic and anti-fibrotic properties. Such therapeutic effects can be attributed to MSC-secretome, made of free soluble proteins and extracellular vesicles (EVs). This review summarizes the recent findings related to the efficacy and safety of MSC-derived products in pre-clinical models of lung diseases, pointing out the biologically active substances contained into MSC-secretome and their mechanisms involved in tissue regeneration. A perspective view is then provided about the missing steps required for the secretome “pharmaceuticalization” into a high quality, safe and effective medicinal product, as well as the formulation strategies required for EV non-invasive route of administration, such as inhalation
What is the knowledge on alpha-1 antitrypsin deficiency among Italian pulmonologists?
No full textIntroduction. Alpha-1 antitrypsin Deficiency (AATD) is a genetic disorder conferring increased risk of developing lung and liver disease. Its prevalence in Italy is not clearly ascertained but certainly there is a great discrepancy between expected and observed cases. Knowledge of a disease is a pre-condition to diagnose it. Aim of the present study was to ascertain the status of the knowledge on AATD among Italian Pulmonologists. Materials and methods. An electronic Survey on AATD was designed. The Survey was repeatedly electronically sent to 250 Heads of Pulmonary Departments in Italy between September and December 2011. It comprised a general and a specific part on AATD, including eight questions. Questions were focused on clinical characteristics, prevalence, diagnosis and treatment of pulmonary manifestations. For each question three answers were available, only one was correct. Results. Only 21.5% of pulmonologists participated to the Survey. The majority of participants gave a correct answer to questions regarding: clinical manifestations, % of subject with COPD affected by AATD, how to diagnose AATD, patients at risk of AATD to be tested for it, differences between treatment of COPD without vs. with AATD, indications to replacement therapy (RT) with exogenous AAT, GOLD stage in which RT is more effective, while the majority of participants thought that AATD in Europe is much rarer (1/20.000) than what is estimated to be (1/5.000). Discussion. The data show that Italian pulmonologists are aware of AATD and are knowledgeable about this condition. However, the response rate was low questioning the representativeness of the examined sample. In addition the majority of participant believe that AATD in Italy is much rarer than what expected from available genetic epidemiology data
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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