CFTR Expression Analysis in Human Nasal Epithelial Cells by Flow Cytometry

Rationale: Unbiased approaches that study aberrant protein expression in primary airway epithelial cells at single cell level may profoundly improve diagnosis and understanding of airway diseases. We here present a flow cytometric procedure to study CFTR expression in human primary nasal epithelial cells from patients with Cystic Fibrosis (CF). Our novel approach may be important in monitoring of therapeutic responses, and better understanding of CF disease at the molecular level. Objectives: Validation of a panel of CFTR-directed monoclonal antibodies for flow cytometry and CFTR expression analysis in nasal epithelial cells from healthy controls and CF patients. Methods: We analyzed CFTR expression in primary nasal epithelial cells at single cell level using flow cytometry. Nasal cells were stained for pan-Cytokeratin, E cadherin, and CD45 (to discriminate epithelial cells and leukocytes) in combination with intracellular staining of CFTR. Healthy individuals and CF patients were compared. Measurements and Main Results: We observed various cellular populations present in nasal brushings that expressed CFTR protein at different levels. Our data indicated that CF patients homozygous for F508del express varying levels of CFTR protein in nasal epithelial cells, although at a lower level than healthy controls. Conclusion: CFTR protein is expressed in CF patients harboring F508del mutations but at lower levels than in healthy controls. Multicolor flow cytometry of nasal cells is a relatively simple procedure to analyze the composition of cellula

Modified Chrispin-Norman chest radiography score for cystic fibrosis: observer agreement and correlation with lung function

Contains fulltext : 96114.pdf ( ) (Closed access)OBJECTIVE: To test observer agreement and two strategies for possible improvement (consensus meeting and reference images) for the modified Chrispin-Norman score for children with cystic fibrosis (CF). METHODS: Before and after a consensus meeting and after developing reference images three observers scored sets of 25 chest radiographs from children with CF. Observer agreement was tested for line, ring, mottled and large soft shadows, for overinflation and for the composite modified Chrispin-Norman score. Correlation with lung function was assessed. RESULTS: Before the consensus meeting agreement between observers 1 and 2 was moderate-good, but with observer 3 agreement was poor-fair. Scores correlated significantly with spirometry for observers 1 and 2 (-0.72<R<-0.42, P < 0.05), but not for observer 3. Agreement with observer 3 improved after the consensus meeting. Reference images improved agreement for overinflation and mottled and large shadows and correlation with lung function, but agreement for the modified Chrispin-Norman score did not improve further. CONCLUSION: Consensus meetings and reference images improve among-observer agreement for the modified Chrispin-Norman score, but good agreement was not achieved among all observers for the modified Chrispin-Norman score and for bronchial line and ring shadows

Chondrodysplasia, enchondromas and a chest deformity causing severe pulmonary morbidity in a boy with a PTHLH duplication:A case report

Parathyroid hormone-like hormone (PTHLH) plays an important role in bone formation. Several skeletal dysplasias have been described that are associated with disruption of PTHLH functioning. Here we report on a new patient with a 898 Kb duplication on chromosome 12p11.22 including the PTHLH gene. The boy has multiple skeletal abnormalities including chondrodysplasia, lesions radiographically resembling enchondromas and posterior rib deformities leading to a severe chest deformity. Severe pulmonary symptoms were thought to be caused by limited mobility and secondary sputum evacuation problems due to the chest deformity. Imaging studies during follow-up revealed progression of the number of skeletal lesions over time. This case extends the phenotypic spectrum associated with copy number variation of PTHLH

Sex differences associated with adverse drug reactions resulting in hospital admissions

Background Adverse drug events, including adverse drug reactions (ADRs), are responsible for approximately 5% of unplanned hospital admissions: a major health concern. Women are 1.5-1.7 times more likely to develop ADRs. The main objective was to identify sex differences in the types and number of ADRs leading to hospital admission. Methods ADR-related hospital admissions between 2005 and 2017 were identified from the PHARMO Database Network using hospital discharge diagnoses. Patients aged >= 16 years with a drug possibly responsible for the ADR and dispensed within 3 months before admission were included. Age-adjusted odds ratios (OR) with 95% CIs for drug-ADR combinations for women versus men were calculated. Results A total of 18,469 ADR-related hospital admissions involving women (0.35% of all women admitted) and 14,678 admissions involving men (0.35% of all men admitted) were included. Most substantial differences were seen in ADRs due to anticoagulants and diuretics. Anticoagulants showed a lower risk of admission with persistent haematuria (ORadj 0.31; 95%CI 0.21, 0.45) haemoptysis (ORadj 0.47, 95%CI 0.30,0.74) and subdural haemorrhage (ORadj 0.61; 95%CI 0.42,0.88) in women than in men and a higher risk of rectal bleeding in women (ORadj 1.48; 95%CI 1.04,2.11). Also, there was a higher risk of admission in women using thiazide diuretics causing hypokalaemia (ORadj 3.03; 95%CI 1.58, 5.79) and hyponatraemia (ORadj 3.33, 95%CI 2.31, 4.81) than in men. Conclusions There are sex-related differences in the risk of hospital admission in specific drug-ADR combinations. The most substantial differences were due to anticoagulants and diuretics.Peer reviewe

Hermansky-Pudlak syndrome type 2 manifests with fibrosing lung disease early in childhood

Background: Hermansky-Pudlak syndrome (HPS), a hereditary multisystem disorder with oculocutaneous albinism, may be caused by mutations in one of at least 10 separate genes. The HPS-2 subtype is distinguished by the presence of neutropenia and knowledge of its pulmonary phenotype in children is scarce. Methods: Six children with genetically proven HPS-2 presented to the chILD-EU register between 2009 and 2017; the data were collected systematically and imaging studies were scored blinded. Results: Pulmonary symptoms including dyspnea, coughing, need for oxygen, and clubbing started 3.3 years before the diagnosis was made at the mean age of 8.83 years (range 2-15). All children had recurrent pulmonary infections, 3 had a spontaneous pneumothorax, and 4 developed scoliosis. The frequency of pulmonary complaints increased over time. The leading radiographic pattern was ground-glass opacities with a rapid increase in reticular pattern and traction bronchiectasis between initial and follow-up Computer tomography (CT) in all subjects. Honeycombing and cysts were newly detectable in 3 patients. Half of the patients received a lung biopsy for diagnosis; histological patterns were cellular non-specific interstitial pneumonia, usual interstitial pneumonia-like, and desquamative interstitial pneumonia. Conclusions: HPS-2 is characterized by a rapidly fibrosing lung disease during early childhood. Effective treatments are required

Maternal morbidity in the first year after childbirth in Mombasa Kenya; a needs assessment

<p>Abstract</p> <p>Background</p> <p>In sub-Saharan Africa, few services specifically address the needs of women in the first year after childbirth. By assessing the health status of women in this period, key interventions to improve maternal health could be identified. There is an underutilised opportunity to include these interventions within the package of services provided for woman-child pairs attending child-health clinics.</p> <p>Methods</p> <p>This needs assessment entailed a cross-sectional survey with 500 women attending a child-health clinic at the provincial hospital in Mombasa, Kenya. A structured questionnaire, clinical examination, and collection of blood, urine, cervical swabs and Pap smear were done. Women's health care needs were compared between the early (four weeks to two months after childbirth), middle (two to six months) and late periods (six to twelve months) since childbirth.</p> <p>Results</p> <p>More than one third of women had an unmet need for contraception (39%, 187/475). Compared with other time intervals, women in the late period had more general health symptoms such as abdominal pain, fever and depression, but fewer urinary or breast problems. Over 50% of women in each period had anaemia (Hb <11 g/l; 265/489), with even higher levels of anaemia in those who had a caesarean section or had not received iron supplementation during pregnancy. Bacterial vaginosis was present in 32% (141/447) of women, while 1% (5/495) had syphilis, 8% (35/454) <it>Trichomonas vaginalis </it>and 11% (54/496) HIV infection.</p> <p>Conclusion</p> <p>Throughout the first year after childbirth, women had high levels of morbidity. Interface with health workers at child health clinics should be used for treatment of anaemia, screening and treatment of reproductive tract infections, and provision of family planning counselling and contraception. Providing these services during visits to child health clinics, which have high coverage both early and late in the year after childbirth, could make an important contribution towards improving women's health.</p

Reliability of orthostatic beat-to-beat blood pressure tests: implications for population and clinical studies

Objective: To assess the test–retest reliability of orthostatic beat-to-beat blood pressure responses to active standing and related clinical definitions of orthostatic hypotension. Methods: A random sample of community-dwelling older adults from the pan-European Survey of Health, Ageing and Retirement in Europe, Ireland underwent a health assessment that mimicked that of the Irish Longitudinal Study on Ageing. An active stand test was performed using continuous blood pressure measurements. Participants attended a repeat assessment 4–12 weeks after the initial measurement. A mixed-effects regression model estimated the reliability and minimum detectable change while controlling for fixed observer and time of day effects. Results: A total of 125 individuals underwent repeat assessment (mean age 66.2 ± 7.5 years; 55.6% female). Mean time between visits was 84.3 ± 23.3 days. There was no significant mean difference in heart rate or blood pressure recovery variables between the first and repeat assessments. Minimum detectable change was noted for changes from resting values in systolic blood pressure (26.4 mmHg) and diastolic blood pressure (13.7 mmHg) at 110 s and for changes in heart rate (10.9 bpm) from resting values at 30 s after standing. Intra-class correlation values ranged from 0.47 for nadir values to 0.80 for heart rate and systolic blood pressure values measured 110 s after standing. Conclusion: Continuous orthostatic beat-to-beat blood pressure and related clinical definitions show low to moderate reliability and substantial natural variation over a 4–12-week period. Understanding variation in measures is essential for study design or estimating the effects of orthostatic hypotension, while clinically it can be used when evaluating longer term treatment effects

GISualization: visualized integration of multiple types of data for knowledge co-production

Urban planning deals with multiple layers of information stemming from concurrent activities and stakeholders intervening in urban development. For a better management of complexity more comprehensiveness and data integration are needed. This study develops an adaptive and iterative mixed-method approach for knowledge production in urban transformation processes. Specific research questions relate to data integration from different sources and facilitation of co-production of knowledge beyond triangulation. A new multi-layer framework, GISualization, has been developed in the context of a research project exploring compact city qualities. The framework is structured through five data layers, representing different methods for data collection and different grades of complexity, richness and interpretation: basic statistics; advanced statistics; exogenous quali-quantitative descriptions; exogenous qualitative descriptions; and endogenous qualitative descriptions. Thus, data stem from both quantitative and qualitative sources. Our study has proven that GISualization is a methodological framework that enables analysis and visualization of complex data in a rich format. The approach is closely related to analytical eclecticism and abductivity. It embodies a collaborative communication platform that provides a language to navigate between heterogeneous data, information and methods. The GISualization framework opens up for broader stakeholder involvement and community participation extending research into the domain of transdisciplinary knowledge production