Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry.

Rationale: Postbronchodilator spirometry is used for the diagnosis of chronic obstructive pulmonary disease. However, prebronchodilator reference values are used for spirometry interpretation. Objectives: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or postbronchodilator reference values generated within SCAPIS (Swedish CArdioPulmonary bioImage Study) when interpreting postbronchodilator spirometry in a general population. Methods: SCAPIS reference values for postbronchodilator and prebronchodilator spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or postbronchodilator reference values, with respiratory burden in the SCAPIS general population (28,851 individuals). Measurements and Main Results: Bronchodilation resulted in higher predicted medians and lower limits of normal (LLNs) for FEV1/FVC ratios. The prevalence of postbronchodilator FEV1/FVC ratio lower than the prebronchodilator LLN was 4.8%, and that of postbronchodilator FEV1/FVC lower than the postbronchodilator LLN was 9.9%, for the general population. An additional 5.1% were identified as having an abnormal postbronchodilator FEV1/FVC ratio, and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%; P < 0.001), and self-reported physician-diagnosed chronic obstructive pulmonary disease (2.8% vs. 0.5%, P < 0.001) than subjects with a postbronchodilator FEV1/FVC ratio greater than the LLN for both pre- and postbronchodilation. Conclusions: Pre- and postbronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of postbronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using postbronchodilator reference values when interpreting postbronchodilator spirometry might enable the identification of individuals with mild disease and be clinically relevant.

Control of release in active packaging/coating for food products; approaches, mechanisms, profiles, and modeling.

Antimicrobial or antioxidant active packaging (AP) is an emerging technology in which a bioactive antimicrobial or antioxidant agent is incorporated into the packaging material to protect the contained product during its shelf life from deterioration. The important issue in AP is making a balance between the deterioration rate of the food product and the controlled release of the bioactive agent. So, the AP fabrication should be designed in such a way that fulfills this goal. Modeling the controlled release is an effective way to avoid trial and error and time-consuming experimental runs and predict the release behavior of bioactive agents in different polymeric matrices and food/food simulants. To review the release of bioactive compounds from AP, in the first part of this review we present an introductory explanation regarding the release controlling approaches in AP. Then the release mechanisms are explained which are very important in defining the appropriate modeling approach and also the interpretation of the modeling results. Different release profiles that might be observed in different packaging systems are also introduced. Finally, different modeling approaches including empirical and mechanistic techniques are covered and the recent literature regarding the utilization of such approaches to help design new AP is thoroughly studied.

Interaction between ß-glucans and gut microbiota: a comprehensive review.

Gut microbiota (GMB) in humans plays a crucial role in health and diseases. Diet can regulate the composition and function of GMB which are associated with different human diseases. Dietary fibers can induce different health benefits through stimulation of beneficial GMB. ß-glucans (BGs) as dietary fibers have gained much interest due to their various functional properties. They can have therapeutic roles on gut health based on modulation of GMB, intestinal fermentation, production of different metabolites, and so on. There is an increasing interest in food industries in commercial application of BG as a bioactive substance into food formulations. The aim of this review is considering the metabolizing of BGs by GMB, effects of BGs on the variation of GMB population, influence of BGs on the gut infections, prebiotic effects of BGs in the gut, in vivo and in vitro fermentation of BGs and effects of processing on BG fermentability.

Femtosecond laser irradiation as a novel method for nanosheet growth and defect generation in g-C3N4.

Among the many recently developed photo-catalytic materials, graphitic carbon nitride (g-C3N4) shows great promise as a catalytic material for water splitting, hydrogen generation, and related catalytic applications. Herein, synthesized bulk g-C3N4is simply irradiated under a 35 fs pulse at mixed photon energies (800 nm and its second harmonic). g-C3N4was synthesized from melamine following a facile thermal polymerization procedure. The prepared material was introduced, in an aqueous environment, to the femtosecond laser for various lengths of time. The treated material demonstrates a significant increase in surface area, relative to the untreated samples, indicating that irradiation is a successful method for exfoliation. The subsequent characterization reveals that the mixed irradiation process drives significant defect generation and sheet growth, which is not seen under 800 nm irradiation. Extended mixed irradiation results in 4 nm thick nanosheets with lateral dimensions 4× that of the bulk material. The treated material shows improved dye absorption/removal. This novel method of defect generation and nanosheet growth shows great potential as a g-C3N4pre-treatment method for co-catalytic applications. Herein it is shown that femtosecond laser irradiation drives exfoliation beyond 100 nm particle sizes, and sheet-like morphologies under extended irradiation, which must be taken into account when using this method to improve material performance.

Rumen-protected glucose hastens uterine involution and increases numbers of ovarian follicles in early post-partum dairy cows.

The primary objectives were to investigate the effects of feeding a new rumen-protected glucose (RPG) on uterine involution and ovarian follicular dynamics in recently calved dairy cattle. From 4 to 30 days after calving, 16 Holsteins (first to third lactation, mean parity 1.75) were randomly assigned to be fed either a basal diet top-dressed with either 600 g RPG (RPG group) or 600 g of the coating material and glucose (CONT group). Based on transrectal ultrasonography, conducted every 3 days starting 20 days after calving, the interval from calving to complete uterine involution was shorter in RPG versus CONT (27.1 vs. 30.4 days, p < .01). Furthermore, based on transrectal ultrasonography conducted every 2 days, cattle fed RPG had smaller (3.0-4.9 mm) ovarian follicles (2.96 vs. 0.9, p < .001) and more total follicles (5.26 vs. 2.85, p < .01). Feeding RPG had increased serum insulin concentrations (4.59 ± 0.54 vs. 3.13 ± 0.57, p < .05), but had no significant effects on serum glucose concentrations, dry matter intake or milk yield. In conclusion, we inferred that cattle fed RPG had increased glucose turnover that was responsible for higher insulin concentrations, faster uterine involution, and more ovarian follicles.

Mucins 3A and 3B Are Expressed in the Epithelium of Human Large Airway.

Aberrant mucus secretion is a hallmark of chronic obstructive pulmonary disease (COPD). Expression of the membrane-tethered mucins 3A and 3B (MUC3A, MUC3B) in human lung is largely unknown. In this observational cross-sectional study, we recruited subjects 45-65 years old from the general population of Stockholm, Sweden, during the years 2007-2011. Bronchial mucosal biopsies, bronchial brushings, and bronchoalveolar lavage fluid (BALF) were retrieved from COPD patients (n = 38), healthy never-smokers (n = 40), and smokers with normal lung function (n = 40). Protein expression of MUC3A and MUC3B in bronchial mucosal biopsies was assessed by immunohistochemical staining. In a subgroup of subjects (n = 28), MUC3A and MUC3B mRNAs were quantified in bronchial brushings using microarray. Non-parametric tests were used to perform correlation and group comparison analyses. A value of p < 0.05 was considered statistically significant. MUC3A and MUC3B immunohistochemical expression was localized to ciliated cells. MUC3B was also expressed in basal cells. MUC3A and MUC3B immunohistochemical expression was equal in all study groups but subjects with emphysema had higher MUC3A expression, compared to those without emphysema. Smokers had higher mRNA levels of MUC3A and MUC3B than non-smokers. MUC3A and MUC3B mRNA were higher in male subjects and correlated negatively with expiratory air flows. MUC3B mRNA correlated positively with total cell concentration and macrophage percentage, and negatively with CD4/CD8 T cell ratio in BALF. We concluded that MUC3A and MUC3B in large airways may be a marker of disease or may play a role in the pathophysiology of airway obstruction.

Exploring the impact of the United States-based accreditation council for pharmacy education certification on pharmacy education outside the United States.

Introduction: The Accreditation Council for Pharmacy Education (ACPE) offers certification for interested pharmacy programs outside the United States. This study aimed to explore the reported impact of this certification on the quality of pharmacy education among ACPE-certified pharmacy programs outside the US. Methods: This cross-sectional study was based on highly structured, standardized interviews. A predetermined questionnaire was designed to include both quantitative and qualitative items, which assessed participants' thoughts on the impact of ACPE certification on the quality of pharmacy education as well as programmatic and student learning outcomes. A total of 15 pharmacy colleges and schools outside the US have received the ACPE certification as of July 2020. After IRB approval, these programs were invited to participate in online live interviews, which were scheduled from May to July 2020 via Zoom®, and lasted approximately 45 min each. Results: Administrators from 13 programs participated in this study (87% respondent rate). The majority of these international pharmacy programs reported that the ACPE certification had promoted the quality of pharmacy education at their institutions. However, there were different views on how the ACPE certification has affected the operation of these international pharmacy programs. There was little or no impact of the certification on financial resources, such as salaries and development funds. Conclusion: Despite being confined to little or no change in certain areas of their programs, all the interviewees believed the ACPE certification had an overall positive impact on the quality of their programs, particularly in the area of assessment, preceptor quality and development, improving teaching and learning methods in both didactic and experiential curricula, and developing an inclusive feedback system to receive input from various stakeholders.

Secretory anti-citrullinated protein antibodies in serum associate with lung involvement in early rheumatoid arthritis.

OBJECTIVE: A 'mucosal connection' in RA presently attracts increasing attention. We recently described the occurrence of secretory antibodies to citrullinated protein (SC-ACPA) in sera from patients with recent-onset RA. The current study was performed to evaluate possible associations between serum levels of secretory ACPA and signs of lung involvement in patients with early, untreated RA. METHODS: One hundred and forty-two RA patients were included as part of the 'LUng Investigation in newly diagnosed RA' study. One hundred and six patients were examined with high-resolution CT (HRCT) and 20 patients underwent bronchoscopy, where bronchial biopsies and bronchoalveolar lavage fluid (BALF) samples were obtained. SC-ACPA in serum and BALF were detected by an enzyme-linked immunoassay. Antibody levels were related to smoking history, pulmonary function, HRCT, BALF cell counts and findings in bronchial biopsies. RESULTS: SC-ACPA occurred in 16% of the serum samples and in 35% of the BALF samples. SC-ACPA levels in serum correlated with SC-ACPA levels in BALF (σ = 0.50, P = 0.027) and were higher among patients with HRCT parenchymal lung abnormalities (P = 0.022) or bronchiectasis (P = 0.042). Also, ever smoking was more frequent among serum SC-ACPA-positive patients (91% vs 67%, P = 0.023), and the SC-ACPA levels correlated with the number of pack-years (σ=0.20, P = 0.020). CONCLUSION: In early, untreated RA, serum levels of SC-ACPA reflect lung involvement in terms of local ACPA levels, smoking and lung abnormalities on HRCT. These findings strengthen the link between mucosal ACPA responses and the lungs in RA.

Smoking-associated increase in mucins 1 and 4 in human airways.

RATIONALE: Smoking-related chronic obstructive pulmonary disease (COPD) is associated with dysregulated production of mucus. Mucins (MUC) are important both for mucus secretion and epithelial defense. We have examined the distribution of MUC1 and MUC4 in the airway epithelial cells of never-smokers and smokers with and without COPD. METHODS: Mucosal biopsies and bronchial wash samples were obtained by bronchoscopy from age- and sex-matched COPD-patients (n = 38; GOLD I-II/A-B), healthy never-smokers (n = 40) and current smokers with normal lung function (n = 40) from the Karolinska COSMIC cohort (NCT02627872). Cell-specific expressions of MUC1, MUC4 and regulating factors, i.e., epithelial growth factor receptor (EGFR) 1 and 2, were analyzed by immunohistochemistry. Soluble MUC1 was measured by quantitative immunodetection on slot blot. RESULTS: The levels of cell-bound MUC1 expression in basal cells and in soluble MUC1 in bronchial wash were increased in smokers, regardless of airway obstruction. Patients with chronic bronchitis had higher MUC1 expression. The expression of MUC4 in cells with goblet cell phenotype was increased in smokers. The expression of EGFR2, but not that of EGFR1, was higher in never-smokers than in smokers. CONCLUSIONS: Smoking history and the presence of chronic bronchitis, regardless of airway obstruction, affect both cellular and soluble MUC1 in human airways. Therefore, MUC1 may be a novel marker for smoking- associated airway disease.

Evaluation of the risk factors associated with emergency department boarding: A retrospective cross-sectional study.

PURPOSE: Boarding is a common problem in the emergency department (ED) and is associated with poor health care and outcome. Imam Khomeini Hospital is the main healthcare center in Urmia, a metropolis in the northwest of Iran. Due to the overcrowding and high patient load, we aim to characterize the rate, cause and consequence of boarding in the ED of this center. METHODS: All medical records of patients who presented to the ED of Imam Khomeini Hospital from August 1, 2017 to August 1, 2018 were retrospectively analyzed. Patients with uncompleted records were excluded. Boarding was defined as the inability to transfer the admitted ED patients to a downstream ward in ≥2 h after the admission order. Demographic data, boarding rate, mortality and triage levels (1-5) assessed by emergency severity index were collected and analyzed. The first present time of patients was classified into 4 ranges as 0:00-5:59, 6:00-11:59, 12:00-17:59 and 18:00-23:59. Descriptive, parametric and non-parametric statistical tests were performed and the risk of boarding was determined by Pearson Chi-square test. RESULTS: Demographic data analysis showed that 941 (58.5%) male and 667 (41.5%) female, altogether 1608 patients were included in this study. Five patients (0.3%) died. The distribution of patients with the triage levels 1-5 was respectively 79 (4.9%), 1150 (71.5%), 374 (23.3%), 4 (0.2%) and 0 (0%). Most patients were of level 2. Only 75 (4.7%) patients required intensive care. The majority of patients (84.2%) were presented at weekdays. The maximum patient load was observed between 12:00-17:59. Of the 1608 patients, 340 (21.1%) experienced boarding within a mean admission time of 13.70 h. Among the 340-boarded patients, 20.1% belonged to surgery, 12.1% to orthopedics, 10.9% to neurosurgery and 10.3% to neurology. The boarding rate was higher in females, patients requiring intensive care and those with low triage levels. Compared with the non-boarded, the boarded patients had a higher mean age. CONCLUSION: The boarding rate is higher in the older and female patients. Moreover, boarding is dependent on the downstream ward sections: patients requiring surgical management experience the maximum boarding rate.

Long-term smoking alters abundance of over half of the proteome in bronchoalveolar lavage cell in smokers with normal spirometry, with effects on molecular pathways associated with COPD.

BACKGROUND: Smoking represents a significant risk factor for many chronic inflammatory diseases, including chronic obstructive pulmonary disease (COPD). METHODS: To identify dysregulation of specific proteins and pathways in bronchoalveolar lavage (BAL) cells associated with smoking, isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun proteomics analyses were performed on BAL cells from healthy never-smokers and smokers with normal lung function from the Karolinska COSMIC cohort. Multivariate statistical modeling, multivariate correlations with clinical data, and pathway enrichment analysis were performed. RESULTS: Smoking exerted a significant impact on the BAL cell proteome, with more than 500 proteins representing 15 molecular pathways altered due to smoking. The majority of these alterations occurred in a gender-independent manner. The phagosomal- and leukocyte trans endothelial migration (LTM) pathways significantly correlated with FEV1/FVC as well as the percentage of CD8+ T-cells and CD8+CD69+ T-cells in smokers. The correlations to clinical parameters in healthy never-smokers were minor. CONCLUSION: The significant correlations of proteins in the phagosome- and LTM pathways with activated cytotoxic T-cells (CD69+) and the level of airway obstruction (FEV1/FVC) in smokers, both hallmarks of COPD, suggests that these two pathways may play a role in the molecular events preceding the development of COPD in susceptible smokers. Both pathways were found to be further dysregulated in COPD patients from the same cohort, thereby providing further support to this hypothesis. Given that not all smokers develop COPD in spite of decades of smoking, it is also plausible that some of the molecular pathways associated with response to smoking exert protective mechanisms to smoking-related pathologies in resilient individuals. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02627872 ; Retrospectively registered on December 9, 2015.

Proteomic profiling of lung immune cells reveals dysregulation of phagocytotic pathways in female-dominated molecular COPD phenotype.

BACKGROUND: Smoking is the main risk factor for chronic obstructive pulmonary disease (COPD). Women with COPD who smoke experienced a higher risk of hospitalization and worse decline of lung function. Yet the mechanisms of these gender-related differences in clinical presentations in COPD remain unknown. The aim of our study is to identify proteins and molecular pathways associated with COPD pathogenesis, with emphasis on elucidating molecular gender difference. METHOD: We employed shotgun isobaric tags for relative and absolute quantitation (iTRAQ) proteome analyses of bronchoalveolar lavage (BAL) cells from smokers with normal lung function (n = 25) and early stage COPD patients (n = 18). Multivariate modeling, pathway enrichment analysis, and correlation with clinical characteristics were performed to identify specific proteins and pathways of interest. RESULTS: More pronounced alterations both at the protein- and pathway- levels were observed in female COPD patients, involving dysregulation of the FcγR-mediated phagocytosis-lysosomal axis and increase in oxidative stress. Alterations in pathways of the phagocytosis-lysosomal axis associated with a female-dominated COPD phenotype correlated well with specific clinical features: FcγR-mediated phagocytosis correlated with FEV1/FVC, the lysosomal pathway correlated with CT < -950 Hounsfield Units (HU), and regulation of actin cytoskeleton correlated with FEV1 and FEV1/FVC in female COPD patients. Alterations observed in the corresponding male cohort were minor. CONCLUSION: The identified molecular pathways suggest dysregulation of several phagocytosis-related pathways in BAL cells in female COPD patients, with correlation to both the level of obstruction (FEV1/FVC) and disease severity (FEV1) as well as emphysema (CT < -950 HU) in women. TRIAL REGISTRATION: No.: NCT02627872 , retrospectively registered on December 9, 2015.

Differences in regional air trapping in current smokers with normal spirometry.

We investigated regional air trapping on computed tomography in current smokers with normal spirometry. It was hypothesised that presence of regional air trapping may indicate a specific manifestation of smoking-related changes.40 current smokers, 40 patients with chronic obstructive pulmonary disease (COPD), and 40 healthy never- smokers underwent computed tomography scans. Regional air trapping was assessed on end-expiratory scans and emphysema, micronodules and bronchial wall thickening on inspiratory scans. The ratio of expiratory and inspiratory mean lung attenuation (E/I) was calculated as a measure of static (fixed) air trapping.Regional air trapping was present in 63% of current smokers, in 45% of never smokers and in 8% of COPD patients (p<0.001). Current smokers with and without regional air trapping had E/I ratio of 0.81 and 0.91, respectively (p<0.001). Forced expiratory volume in 1 s (FEV1) was significantly higher and emphysema less frequent in current smokers with regional air trapping.Current smokers with regional air trapping had higher FEV1 and less emphysema on computed tomography. In contrast, current smokers without regional air trapping resembled COPD. Our results highlight heterogeneity among smokers with normal spirometry and may contribute to early detection of smoking related structural changes in the lungs.

Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality; however, the role of inflammatory mediators in its pathobiology remains unclear. The aim of this study was to investigate the influence of gender in COPD on lipid mediator levels.Bronchoalveolar lavage fluid (BALF) and serum were obtained from healthy never-smokers, smokers and COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage I-II/A-B) (n=114). 94 lipid mediators derived from the cytochrome-P450, lipoxygenase, and cyclooxygenase pathways were analysed by liquid chromatography-mass spectrometry.Multivariate modelling identified a 9-lipid panel in BALF that classified female smokers with COPD from healthy female smokers (p=6×10(-6)). No differences were observed for the corresponding male population (p=1.0). These findings were replicated in an independent cohort with 92% accuracy (p=0.005). The strongest drivers were the cytochrome P450-derived epoxide products of linoleic acid (leukotoxins) and their corresponding soluble epoxide hydrolase (sEH)-derived products (leukotoxin-diols). These species correlated with lung function (r=0.87; p=0.0009) and mRNA levels of enzymes putatively involved in their biosynthesis (r=0.96; p=0.003). Leukotoxin levels correlated with goblet cell abundance (r=0.72; p=0.028).These findings suggest a mechanism by which goblet cell-associated cytochrome-P450 and sEH activity produce elevated leukotoxin-diol levels, which play a putative role in the clinical manifestations of COPD in a female-dominated disease sub-phenotype.

Signs of immune activation and local inflammation are present in the bronchial tissue of patients with untreated early rheumatoid arthritis.

OBJECTIVES: Events in the lungs might contribute to generation of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). We investigated if signs of immune activation are present in bronchial biopsies and bronchoalveolar lavage (BAL) of patients with early-untreated RA without clinical signs of lung involvement. METHODS: Twenty-four patients with RA with symptom duration <1 year and naïve to disease-modifying antirheumatic drugs were subjected to bronchoscopy where BAL and mucosal bronchial biopsies were retrieved. For comparison, 15 bronchial biopsies and 79 BAL samples from healthy volunteers were available. Histological examination was performed to evaluate lymphocyte infiltration, presence of immune cells (T and B cells, plasma cells, dendritic cells and macrophages) and immune activation markers. Cell composition of BAL samples was analysed by differential counting and T cell subsets by flow cytometry. RESULTS: Lymphocyte infiltration was more frequently found in ACPA-positive patients (50%) as compared with ACPA-negative patients (17%) and controls (13%). Germinal centres, B cells and plasma cells were only found in ACPA-positive patients. The frequency of T cells in bronchial biopsies of patients with ACPA-positive RA was positively associated with expression of immune activation markers. BAL samples of patients with ACPA-positive, but not ACPA-negative, RA had significantly higher relative numbers of lymphocytes and expressed higher levels of activation markers compared with controls. CONCLUSIONS: Signs of immune cell accumulation and activation are present both in the bronchial tissue and in BAL of untreated patients with early RA without concomitant lung disease, strengthening the role of the lung compartment as an important player in ACPA-positive RA.

Analysis of superiorly projecting anterior communicating artery aneurysms: anatomy, techniques, and outcome. A proposed classification system.

Superiorly projecting (SP) anterior communicating artery (AComA) aneurysms are typically described as a homogenous group. Clinically and microsurgically, these aneurysms vary in multiple important characteristics. We propose a microsurgical classification system for these complex aneurysms and review its implications regarding presentation, microsurgical techniques, and outcome. This retrospective analysis reviews patients undergoing clipping of SP AComA aneurysms (2005-2013). The classification system is based on the virtual plane created by the A2 segments and its relationship to the aneurysm. Aneurysm type was assessed by intraoperative images and videos. Type 1 is defined by bisection of the dome by the virtual plane. Type 2 is defined by dome projection posterior to this plane. Sagittal rotation of the plane defines type 3. We analyzed clinical presentation, morphology, angiographic characteristics, operative technique, and outcome relative to the classification types. There were 44 SP AComA aneurysms. 3D angiographic images predicted classification type in 83%. Type 1 presented more often with SAH (95.5%, p = 0.0046). There was no statistically significant difference between the types regarding patient demographics or aneurysm characteristics. In type 2, fenestrated clips were used frequently (87.5% p= 0.0016), and there was higher rate of intraoperative rupture (37.5%). Although there was no statistically significant difference between the types in respect to HH grade upon presentation, patients with type 2 aneurysms experienced higher rates of poor GOS (50%). The proposed classification system for SP AComA aneurysms has implications regarding surgical planning, micro-dissection, clipping, and outcome. Type 2 aneurysms carry significant surgical risk.

A fatal case of JC virus meningitis presenting with hydrocephalus in a human immunodeficiency virus-seronegative patient.

JC virus (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy, JCV granule cell neuronopathy, and JCV encephalopathy. Whether JCV can also cause meningitis has not yet been demonstrated. We report a case of aseptic meningitis resulting in symptomatic hydrocephalus in a human immunodeficiency virus-seronegative patient. Brain imaging showed enlargement of ventricles but no parenchymal lesion. She had a very high JC viral load in the cerebrospinal fluid (CSF) and developed progressive cognitive dysfunction despite ventricular drainage. She was diagnosed with pancytopenia and passed away after 5.5 months. Postmortem examination revealed productive JCV infection of leptomeningeal and choroid plexus cells, and limited parenchymal involvement. Sequencing of JCV CSF strain showed an archetype-like regulatory region. Further studies of the role of JCV in aseptic meningitis and in idiopathic hydrocephalus are warranted.

Lung density on high resolution computer tomography (HRCT) reflects degree of inflammation in smokers.

BACKGROUND: Smokers have increased cell concentration in the lower respiratory tract indicating a chronic inflammatory state, which in some individuals may lead to development of chronic obstructive pulmonary disease (COPD). Computer tomography (CT) imaging provides means of quantifying pulmonary structure and early signs of disease. We investigated whether lung density on high resolution CT differs between smokers and never-smokers and if this were associated to intensity of inflammation. METHODS: Forty smoking volunteers with normal pulmonary function, 40 healthy never-smokers and 40 patients with COPD of GOLD stage I-II, were included. Mean lung attenuation and percentage of pixels in the lung with attenuation between -750 and -900 HU (percentage higher density spectrum (%HDS)) were calculated on inspiratory CT-scans. Markers of systemic inflammation in blood and cell counts in bronchoalveolar lavage (BAL) fluid were recorded. RESULTS: Lung density expressed as %HDS was increased in smokers (44.0 ± 5.8%) compared to both never-smokers (38.3 ± 5.8%) and patients with COPD (39.1 ± 5.8%), (p < 0.001, for both). Females had denser lungs than males, which was dependent on body height. Cell concentration in BAL were correlated to lung density in smokers (r = 0.50, p < 0.001). CONCLUSIONS: Lung density on CT is associated with cell concentration in BAL in smokers and may mirror an inflammatory response in the lung. Gender difference in lung density is dependent on height. In COPD with emphysema, loss of lung tissue may counterbalance the expected increase in density due to inflammation. The findings may help to interpret high resolution CT in the context of smoking and gender and highlight the heterogeneity of structural changes in COPD.

Current endovascular treatment options for central retinal arterial occlusion: a review.

Central retinal artery occlusion, although relatively rare, is an ophthalmological emergency. If left untreated, complete blindness will ensue. Conventional therapies have not significantly improved outcomes compared with the natural history of the disease. Several case series of more recent endovascular approaches, such as intraarterial fibrinolysis, report successful outcomes. Still other studies regarding intraarterial fibrinolysis do not demonstrate any significantly better outcomes, with some even indicating increased complication rates. Therefore, the authors present a review of the current endovascular treatment options for central retinal artery occlusion.

Gender differences in the bronchoalveolar lavage cell proteome of patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide and is increasing, primarily among women. Underdiagnosis is common, and because of the heterogeneous disease characteristics, molecular markers of specific disease phenotypes and more efficacious treatment regimens are urgently needed. OBJECTIVE: In this study the soluble proteome of bronchoalveolar lavage cells, primarily consisting of macrophages, was investigated with the aim of identifying phenotypic differences in early disease development. METHODS: Two-dimensional difference gel electrophoresis was used for relative quantification of protein levels, and multivariate modeling was applied to identify proteins of interest that were subsequently identified by means of liquid chromatography-mass spectrometry. RESULTS: Significant gender differences were unveiled, with numerous alterations in the bronchoalveolar lavage cell proteome occurring in female but not male patients with COPD. Specifically, a subset of 19 proteins provided classification of female healthy smokers from female patients with COPD with 78% predictive power. Subsequent pathway analyses linked the observed alterations to downregulation of the lysosomal pathway and upregulation of the oxidative phosphorylation pathway, possibly linking dysregulation of macroautophagy to a female-dominated COPD disease phenotype. CONCLUSION: This investigation makes an important contribution to the elucidation of putative molecular mechanisms underlying gender-based differences in the pathophysiology of COPD, linking alterations of specific molecular pathways to previously observed gender differences in clinical COPD phenotypes. Furthermore, these results stress the importance of the gender-specific search for biomarkers, diagnosis, and treatment in COPD.