Pulmonary exacerbations in patients with primary ciliary dyskinesia: an expert consensus definition for use in clinical trials

Pulmonary exacerbations; Primary ciliary dyskinesia; DefinitionEmpitjorament pulmonar; Discinèsia ciliar primària; DefinicióEmpeoramiento pulmonar; Discinesia ciliar primaria; DefiniciónPulmonary exacerbations are a cause of significant morbidity in patients with primary ciliary dyskinesia (PCD) and are frequently used as an outcome measure in clinical research into chronic lung diseases. So far, there has been no consensus on the definition of pulmonary exacerbations in PCD. 30 multidisciplinary experts and patients developed a consensus definition for children and adults with PCD. Following a systematic review, the panel used a modified Delphi process with a combination of face-to-face meetings and e-surveys to develop a definition that can be used in research settings for children and adults with PCD. A pulmonary exacerbation was defined by the presence of three or more of the following seven items: 1) increased cough, 2) change in sputum volume and/or colour, 3) increased shortness of breath perceived by the patient or parent, 4) decision to start or change antibiotic treatment because of perceived pulmonary symptoms, 5) malaise, tiredness, fatigue or lethargy, 6) new or increased haemoptysis, and 7) temperature >38°C. The consensus panel proposed that the definition should be used for future clinical trials. The definition should be validated and the usability assessed during these studies

CiliarMove: new software for evaluating ciliary beat frequency helps find novel mutations by a Portuguese multidisciplinary team on primary ciliary dyskinesia

This study was supported by the Fundação para a Ciência e a Tecnologia (PTDC/BEXBID/1411/ 2014 research grant). S.S. Lopes was funded by FCT Investigator IF/00951/2012, by NOVA Medical School and by FCT CEEC-IND 2018. P. Sampaio was funded by the PhD fellowship FCT: SFRH/BD/111611/2015. M. Roxo-Rosa was funded by the UID/Multi/04462/2013-LISBOA-01-0145-FEDER-007344 grant (iNOVA4Health). C.M. Quintão was funded by Fundação para a Ciência e Tecnologia (UID/FIS/04559/2013). S.S. Lopes participates in and acknowledge financial support from the COST Action BEAT-PCD (BM1407). S.S. Lopes received funding from project LysoCil funded by the European Union Horizon 2020 research and innovation under grant agreement No 811087. Funding information for this article has been deposited with the Crossref Funder Registry.Evaluation of ciliary beat frequency (CBF) performed by high-speed videomicroscopy analysis (HVMA) is one of the techniques required for the correct diagnosis of primary ciliary dyskinesia (PCD). Currently, due to lack of open-source software, this technique is widely performed by visually counting the ciliary beatings per a given time-window. Our aim was to generate open-source, fast and intuitive software for evaluating CBF, validated in Portuguese PCD patients and healthy volunteers. Nasal brushings collected from 17 adult healthy volunteers and 34 PCD-referred subjects were recorded using HVMA. Evaluation of CBF was compared by two different methodologies: the new semi-automated computer software CiliarMove and the manual observation method using slow-motion movies. Clinical history, nasal nitric oxide and transmission electron microscopy were performed for diagnosis of PCD in the patient group. Genetic analysis was performed in a subset (n=8) of suspected PCD patients. The correlation coefficient between the two methods was R-2=0.9895. The interval of CBF values obtained from the healthy control group (n=17) was 6.18-9.17 Hz at 25 degrees C. In the PCD-excluded group (n=16), CBF ranged from 6.84 to 10.93 Hz and in the PCD group (n=18), CBF ranged from 0 to 14.30 Hz. We offer an automated open-source programme named CiliarMove, validated by the manual observation method in a healthy volunteer control group, a PCD-excluded group and a PCD-confirmed group. In our hands, comparisons between CBF intervals alone could discern between healthy and PCD groups in 78% of the cases.publishersversionpublishe

Randomized, direct comparison study of Saccharomyces boulardii CNCM I-745 versus multi-strained Bacillus clausii probiotics for the treatment of pediatric acute gastroenteritis

Background: The choice of an appropriate probiotic for pediatric acute gastroenteritis (PAGE) can be confusing. Our aim was to compare the efficacy and safety of 2 probiotics (Saccharomyces boulardii CNCM I-745 vs a 4-strain mixture of Bacillus clausii O/C, SIN, N/R, T) for the treatment of PAGE. Methods: A 2-arm parallel, randomized trial recruited children (6 months to 5 years old) with mild-moderate acute diarrhea, from 8 centers in Argentina. A total of 317 children were enrolled and blindly randomized to 5 days of either S boulardii CNCM I-745 (n = 159) or a 4-strain mixture of B clausii (n = 158), then followed for 7 days post-probiotic treatment. A stool sample was collected at inclusion for pathogen identification. The primary outcome was duration of diarrhea defined as the time from enrollment to the last loose stool followed by the first 24-hour period with stool consistency improvement. Secondary outcomes included frequency of loose stools/day, severity of diarrhea, number reporting no diarrhea at Day 6, time-to-first formed stool, recurrence of diarrhea by study end (Day 12) and safety outcomes. Results: Three hundred twelve (98%) children completed the study. S boulardii CNCM I-745 showed a significant reduction (P =.04) in the mean duration of diarrhea (64.6 hours, 95% confidence interval [CI] 56.5-72.8) compared to those given B clausii (78.0 hours, 95% CI 69.9-86.1). Both probiotics showed improvement in secondary outcomes and were well-tolerated. Conclusion: In this study, S boulardii CNCM I-745 demonstrated better efficacy than B clausii mix for reducing the duration of pediatric acute diarrhea.Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Carosella, Mabel V.. No especifíca;Fil: Ceballos, Ana. Instituto Médico Río Cuarto; ArgentinaFil: D'Andrea, Ulises. Instituto Médico Río Cuarto; ArgentinaFil: Jofre, Sandra M.. No especifíca;Fil: Marotta, Carolina. No especifíca;Fil: Mugeri, Domingo. No especifíca;Fil: Sabbaj, Liliana. No especifíca;Fil: Soto, Adriana. No especifíca;Fil: Josse, Constant. No especifíca;Fil: Montestruc, Francois. No especifíca;Fil: McFarland, Lynne V.. No especifíca

Letramento digital no ensino médio: diálogos com os desafios da escola na sociedade tecnológica

Na cibercultura (LÉVY, 1999), o indivíduo precisa desenvolver estratégias para acessar, localizar, selecionar e avaliar criticamente a informação disponibilizada no ciberespaço, além de conhecer as normas que regem a comunicação mediada por computador. Nesse contexto, o letramento digital configurase como conceito amplamente (re)visitado, percebendo-se as relações dos sujeitos com “as práticas letradas mediadas por computadores e outros dispositivos eletrônicos” (BUZATO, 2003, p. 03). Dos livros impressos às telas dos computadores, leitores e autores (re)descobrem seus papéis no mundo digital. Novas competências são postas para educadores e educandos, visto que os processos de ensino-aprendizagem são redimensionados em função das mediações tecnológicas que surgem a partir do acesso às mídias digitais. Pretende-se investigar as práticas de letramento digital de alunos do ensino médio, tendo em vista a necessidade de a escola reavaliar planejamentos e ações didáticas, no sentido de contribuir para a formação crítica de leitores e produtores de textos. Como aportes teóricos foram utilizadas as abordagens de Coscarelli (2005); Soares (2002); Buzato(2003-2007); Rojo (2007); Lima e Araújo (2011); Marcuschi e Xavier (2004), em relação aos conceitos de letramento digital. A pesquisa é fruto do projeto Letramento digital: redes sociais e gêneros digitais na motivação nas práticas de leitura e escrita na escola, que participa do Programa Institucional de Iniciação à Docência (PIBID) do curso de Licenciatura em Letras/ UFRPE

Los orígenes de un nuevo gen de diseño de alas de mariposa dentro de una familia de reguladores conservados del ciclo celular

A major challenge in evolutionary biology is to understand the origins of novel structures. The wing patterns of butterflies and moths are derived phenotypes unique to the Lepidoptera. Here we identify a gene that we name poikilomousa (poik), which regulates colour pattern switches in the mimetic Heliconius butterflies. Strong associations between phenotypic variation and DNA sequence variation are seen in three different Heliconius species, in addition to associations between gene expression and colour pattern. Colour pattern variants are also associated with differences in splicing of poik transcripts. poik is a member of the conserved fizzy family of cell cycle regulators. It belongs to a faster evolving subfamily, the closest functionally characterised orthologue being the cortex gene in Drosophila, a female germ-line specific protein involved in meiosis. poik appears to have adopted a novel function in the Lepidoptera and become a major target for natural selection acting on colour and pattern variation in this group

Correlação entre a qualidade de vida e a classificação funcional em pacientes com insuficiência cardíaca congestiva em internamento hospitalar

Sendo um dos principais problemas de saúde pública, a Insuficiência Cardíaca Congestiva (ICC) acaba resultando em prejuízo progressivo da capacidade funcional ao portador, o que contribui para a elevada morbi-mortalidade destes. O objetivo deste estudo foi correlacionar a qualidade de vida através do LIhFE (Minnesota Living With Heart Failure Questionnaire) com a classificação funcional – CF do NYHA (New York Heart Association) de pacientes com ICC em internamento hospitalar. Foram entrevistados 24 pacientes de ambos os sexos, média de idade de 55 anos, em internamento hospitalar na Santa Casa de Misericórdia de Maceió. Foi aplicado o Questionário LIhFE-Minnesota, possuindo 21 questões que avaliam as dimensões Física e Emocional, sendo também realizada a classificação CF –NYHA em classe I, Classe II, Classe III e Classe IV de acordo com os sintomas de fadiga, dispnéia e intensidade do esforço físico. Analisando-se os resultados, verificaram-se correlação positiva para a CF-NYHA e a dimensão física (p = 0,05). Foram comparados os escores do LIhFE-Minnesota com as dimensões física (p=0,0005) e emocional (p=0,0008). Desta forma conclui-se que a correlação da classificação funcional foi evidente para o dimensão física do LIhFE – Minnesota, porém não encontramos evidências da correlação entre a qualidade de vida e a classificação funcional

Quality standards for managing children and adolescents with bronchiectasis: an international consensus

The global burden of bronchiectasis in children and adolescents is being recognised increasingly. However, marked inequity exists between, and within, settings and countries for resources and standards of care afforded to children and adolescents with bronchiectasis compared with those with other chronic lung diseases. The European Respiratory Society (ERS) clinical practice guideline for the management of bronchiectasis in children and adolescents was published recently. Here we present an international consensus of quality standards of care for children and adolescents with bronchiectasis based upon this guideline. The panel used a standardised approach that included a Delphi process with 201 respondents from the parents and patients’ survey, and 299 physicians (across 54 countries) who care for children and adolescents with bronchiectasis. The seven quality standards of care statements developed by the panel address the current absence of quality standards for clinical care related to paediatric bronchiectasis. These internationally derived, clinician-, parent-and patient-informed, consensus-based quality standards statements can be used by parents and patients to access and advocate for quality care for their children and themselves, respectively. They can also be used by healthcare professionals to advocate for their patients, and by health services as a monitoring tool, to help optimise health outcomes.</p

Correlação entre o fast-track (desmame precoce) e as complicações pulmonares no pós-operatório de revascularização do miocárdio em um hospital de Maceió

Os métodos para revascularização do miocárdio (RM) têm evoluído rapidamente nos últimos anos. Novos procedimentos estão sendo desenvolvidos, visando à diminuição de complicações pulmonares, a permanência hospitalar e os altos custos desses procedimentos, como também melhorar a qualidade de vida. A utilização do programa fast-track, quando a extubação traqueal ocorre em até oito horas de pós-operatório, está relacionada a essa diminuição de complicações pulmonares. Objetivo: Correlacionar o fast-track com as complicações pulmonares no pós-operatório de revascularização do miocárdio no Hospital do Coração de Alagoas. Materiais e Métodos: Estudo Prospectivo Quantitativo Descritivo com uma a amostra não probabilística por conveniência de acordo com o número de pacientes coronariopatas internos no Hospital do Coração de Alagoas. Resultados: Observou-se que a doença coronariana foi mais comum no sexo masculino, com 68,2%, e 31,8% no sexo feminino, que os fatores de riscos que mais contribuíram para as complicações pulmonares foram Hipertensão Arterial Sistêmica seguida de Sedentarismo, e a Correlação entre o tempo de permanência no hospital e as complicações pulmonares, que obteve índice de relevância signifi cativa. Conclusão: Podemos afi rmar que o programa de agilização fast-track reduz as complicações pulmonares nos pacientes submetidos à cirurgia de revascularização do miocárdio

Clinical utility of NGS diagnosis and disease stratification in a multiethnic primary ciliary dyskinesia cohort

Background Primary ciliary dyskinesia (PCD), a genetically heterogeneous condition enriched in some consanguineous populations, results from recessive mutations affecting cilia biogenesis and motility. Currently, diagnosis requires multiple expert tests.Methods The diagnostic utility of multigene panel next-generation sequencing (NGS) was evaluated in 161 unrelated families from multiple population ancestries.Results Most (82%) families had affected individuals with biallelic or hemizygous (75%) or single (7%) pathogenic causal alleles in known PCD genes. Loss-of-function alleles dominate (73% frameshift, stop-gain, splice site), most (58%) being homozygous, even in non-consanguineous families. Although 57% (88) of the total 155 diagnostic disease variants were novel, recurrent mutations and mutated genes were detected. These differed markedly between white European (52% of families carry DNAH5 or DNAH11 mutations), Arab (42% of families carry CCDC39 or CCDC40 mutations) and South Asian (single LRRC6 or CCDC103 mutations carried in 36% of families) patients, revealing a striking genetic stratification according to population of origin in PCD. Genetics facilitated successful diagnosis of 81% of families with normal or inconclusive ultrastructure and 67% missing prior ultrastructure results.Conclusions This study shows the added value of high-throughput targeted NGS in expediting PCD diagnosis. Therefore, there is potential significant patient benefit in wider and/or earlier implementation of genetic screening

Intracranial Aneurysm Classifier Using Phenotypic Factors: An International Pooled Analysis

Intracranial aneurysms (IAs) are usually asymptomatic with a low risk of rupture, but consequences of aneurysmal subarachnoid hemorrhage (aSAH) are severe. Identifying IAs at risk of rupture has important clinical and socio-economic consequences. The goal of this study was to assess the effect of patient and IA characteristics on the likelihood of IA being diagnosed incidentally versus ruptured. Patients were recruited at 21 international centers. Seven phenotypic patient characteristics and three IA characteristics were recorded. The analyzed cohort included 7992 patients. Multivariate analysis demonstrated that: (1) IA location is the strongest factor associated with IA rupture status at diagnosis; (2) Risk factor awareness (hypertension, smoking) increases the likelihood of being diagnosed with unruptured IA; (3) Patients with ruptured IAs in high-risk locations tend to be older, and their IAs are smaller; (4) Smokers with ruptured IAs tend to be younger, and their IAs are larger; (5) Female patients with ruptured IAs tend to be older, and their IAs are smaller; (6) IA size and age at rupture correlate. The assessment of associations regarding patient and IA characteristics with IA rupture allows us to refine IA disease models and provide data to develop risk instruments for clinicians to support personalized decision-making