Expression of MUC5AC and MUC5B mucins in normal and cystic fibrosis lung

AbstractHypersecretion of airway mucus is a characteristic feature of chronic airway diseases like cystic fibrosis (CF) and leads via impairment of the muco-ciliary clearance and bacterial superinfection to respiratory failure. The major components of the mucus matrix forming family of mucins in the airways are MUC5AC and MUC5B. To investigate the expression of these glycoproteins in CF, immunohistochemistry was carried out on trachea, bronchi and peripheral lung obtained from CF patients and compared to normal lung tissues. MUC5AC immunohistochemistry demonstrated signals in goblet cells of the epithelial lining. Also, goblet cells inside glandular secretory ducts revealed MUC5AC-positive staining. In comparison to those from normal subjects, CF sections were characterized by inflammatory changes and goblet cell hyperplasia, resulting in increased numbers of MUC5AC-positive cells. Immunohistochemical staining for MUC5B showed abundant staining of submucosal glands and epithelial goblet cells. Inside the glands, the immunoreactivity was restricted to glandular mucous cells. MUC5AC and MUC5B are expressed in the same histological pattern in CF compared to normal tissues with an increase of MUC5AC-positive cells due to goblet cell hyper- and metaplasia

In Vitro Structural and Functional Evaluation of Gold Nanoparticles Conjugated Antibiotics

Bactericidal efficacy of gold nanoparticles conjugated with ampicillin, streptomycin and kanamycin were evaluated. Gold nanoparticles (Gnps) were conjugated with the antibiotics during the synthesis of nanoparticles utilizing the combined reducing property of antibiotics and sodium borohydride. The conjugation of nanoparticles was confirmed by dynamic light scattering (DLS) and electron microscopic (EM) studies. Such Gnps conjugated antibiotics showed greater bactericidal activity in standard agar well diffusion assay. The minimal inhibitory concentration (MIC) values of all the three antibiotics along with their Gnps conjugated forms were determined in three bacterial strains,Escherichia coli DH5α,Micrococcus luteusandStaphylococcus aureus. Among them, streptomycin and kanamycin showed significant reduction in MIC values in their Gnps conjugated form whereas; Gnps conjugated ampicillin showed slight decrement in the MIC value compared to its free form. On the other hand, all of them showed more heat stability in their Gnps conjugated forms. Thus, our findings indicated that Gnps conjugated antibiotics are more efficient and might have significant therapeutic implications

Editorial: Experimental models of asthma

Since 2002, a workshop entitled "Asthma in animal models" has been held once a year in Hannover, Germany. It is organized by the Fraunhofer Institute of Toxicology and Experimental Medicine in collaboration with the collaborative research centre "Sonderforschungsbereich" 587, "Immune reactions of the lung in infection and allergy" (Hannover Medical School). The aim of these meetings is an intense scientific exchange between researchers and clinicians coming from academic or industrial background. Over the years the topics within the extensive field of asthma and COPD have ranged from methodological aspects to the influence of infections and environmental factors up to perspectives in the development of new therapeutic strategies

Hausärztliche Versorgung in Deutschland – Gleicher Zugang für alle?

Hintergrund Ein gleichmäßiger Zugang zu hausärztlicher Versorgung spielt eine wesentliche Rolle bei der medizinischen Versorgung in Deutschland und ist daher Ziel der ambulanten Bedarfsplanung. Ziel der Arbeit Mit der vorliegenden Arbeit sollen räumliche Aspekte des Zugangs zur hausärztlichen Versorgung untersucht und mit den Zielen der aktuellen Bedarfsplanung verglichen werden. Material und Methoden Der räumliche Zugang zur hausärztlichen Versorgung wurde auf Basis der „integrated Floating Catchment Area“-Methodik unter Einsatz eines geografischen Informationssystems auf Ebene von Quadratkilometer-Zellen (Hektarzellen für Großstädte) gemessen („Zugangsindex“). Ergebnisse Die Analyse von 649 Millionen generierten Datensätzen zeigte erhebliche geografische Variationen des Zugangs: 4,7 % der Gesamtbevölkerung leben in Gebieten mit signifikant niedrigerem hausärztlichen Zugang (z-Wert = –3,4) während 48,0 % in einem Gebiet mit signifikant höherem hausärztlichen Zugang leben (z-Wert = 9,7). Der durchschnittliche Zugangsindex lag bei 0,14 (SD = 0,15) und war umso höher, je urbaner das Gebiet (r = 0,64; p < 0,001) und je geringer der Grad der regionalen Deprivation war (r = –0,37; p < 0,001). Innerhalb der Bedarfsplanungsregionen variierte der Zugangsindex um durchschnittlich Δ = 0,23 (SD = 0,19) und korrelierte nicht mit dem hausärztlichen Versorgungsgrad (r = –0,04; p = 0,28). Diskussion Bezüglich des Zugangs zu hausärztlicher Versorgung bestehen in Deutschland Stadt-Land-Disparitäten sowie soziale Ungleichheit im Sinne regionaler Deprivation. Aus diesem Grund sollte die Bedarfsplanung zukünftig räumliche Aspekte des Zugangs wie Erreichbarkeit und Verfügbarkeit stärker berücksichtigen

Einrichtung einer umweltzone und ihre wirksamkeit auf die PM10-feinstaubkonzentration - Eine pilotanalyse am beispiel München (Introduction of a low-emission zone and the effect on air pollutant concentration of particulate matter (PM10) - A pilot study in Munich)

Since the introduction of low emission zones in Germany in 2008 the question of their efficiency has been debated. In this pilot study, measurement data collected before and after the introduction of the low emission zone in Munich (October 2007 until January 2008 vs. October 2008 until Januar 2009) were analysed on the basis of matched quadruples. Applying previously described methods (Morfeld et al. 2011), continuously measured half-hour fine dust concentration data (PM10) - simultaneously determined at an index station situated inside the low emission zone and a reference station outside of the zone - were contrasted and analysed (difference score method in the two-period case). Meteorological parameters (height of the inversion base, amount of precipitation, wind velocity) as well as baseline data of index and reference stations were taken into account as covariates in regression analyses. The statistical approach was successfully validated in an analysis of simulated data. 26438 quadrupels could be matched for analysis. Averages of PM10 concentration values before (after) introducing the low emission zone were 33.9 μg/m3 (39.0 μg/m3) at 5 index stations and 24.6 μg/m3 (30.5 μg/m3) at 2 reference stations. Taking covariates into account, an additive model estimated the change in concentration associated to the introduction of the low emission zone as +0.017 μg/m3 (0.95-CI: -0.33 μg/m3, +0.37 μg/m3), a multiplicative model estimated the relative effect as -0.5% (0.95-CI: -0.12%, +0.30%). The results of this study differ relevantly from the findings of an earlier investigation by Cyrys et al. (2009) who analyzed the same data. This analysis does not prove the effectiveness of Munich's low emission zone. This study also points out that the methodological approach is crucial for a scientifically reliable evaluation of the efficacy of low emission zones. Strict rules need to be followed in order to prevent from misinterpretations

Spatial accessibility of general inpatient care in Germany: An analysis of surgery, internal medicine and neurology.

Improving spatial accessibility to hospitals is a major task for health care systems which can be facilitated using recent methodological improvements of spatial accessibility measures. We used the integrated floating catchment area (iFCA) method to analyze spatial accessibility of general inpatient care (internal medicine, surgery and neurology) on national level in Germany determining an accessibility index (AI) by integrating distances, hospital beds and morbidity data. The analysis of 358 million distances between hospitals and population locations revealed clusters of lower accessibility indices in areas in north east Germany. There was a correlation of urbanity and accessibility up to r = 0.31 (p < 0.001). Furthermore, 10% of the population lived in areas with significant clusters of low spatial accessibility for internal medicine and surgery (neurology: 20%). The analysis revealed the highest accessibility for heart failure (AI = 7.33) and the lowest accessibility for stroke (AI = 0.69). The method applied proofed to reveal important aspects of spatial accessibility i.e. geographic variations that need to be addressed. However, for the majority of the German population, accessibility of general inpatient care was either high or at least not significantly low, which suggests rather adequate allocation of hospital resources for most parts of Germany

Prediction of hospital visits for the general inpatient care using floating catchment area methods: A reconceptualization of spatial accessibility.

Background The adequate allocation of inpatient care resources requires assumptions about the need for health care and how this need will be met. However, in current practice, these assumptions are often based on outdated methods (e.g. Hill-Burton Formula). This study evaluated floating catchment area (FCA) methods, which have been applied as measures of spatial accessibility, focusing on their ability to predict the need for health care in the inpatient sector in Germany. Methods We tested three FCA methods (enhanced (E2SFCA), modified (M2SFCA) and integrated (iFCA)) for their accuracy in predicting hospital visits regarding six medical diagnoses (atrial flutter/fibrillation, heart failure, femoral fracture, gonarthrosis, stroke, and epilepsy) on national level in Germany. We further used the closest provider approach for benchmark purposes. The predicted visits were compared with the actual visits for all six diagnoses using a correlation analysis and a maximum error from the actual visits of +/- 5%, +/- 10% and +/- 15%. Results The analysis of 229 million distances between hospitals and population locations revealed a high and significant correlation of predicted with actual visits for all three FCA methods across all six diagnoses up to rho = 0.79 (p < 0.001). Overall, all FCA methods showed a substantially higher correlation with actual hospital visits compared to the closest provider approach (up to rho = 0.51; p < 0.001). Allowing a 5% error of the absolute values, the analysis revealed up to 13.4% correctly predicted hospital visits using the FCA methods (15% error: up to 32.5% correctly predicted hospital). Finally, the potential of the FCA methods could be revealed by using the actual hospital visits as the measure of hospital attractiveness, which returned very strong correlations with the actual hospital visits up to rho = 0.99 (p < 0.001). Conclusion We were able to demonstrate the impact of FCA measures regarding the prediction of hospital visits in non-emergency settings, and their superiority over commonly used methods (i.e. closest provider). However, hospital beds were inadequate as the measure of hospital attractiveness resulting in low accuracy of predicted hospital visits. More reliable measures must be integrated within the proposed methods. Still, this study strengthens the possibilities of FCA methods in health care planning beyond their original application in measuring spatial accessibility

Accessibility of general and specialized obstetric care providers in Germany and England: An analysis of location and neonatal outcome.

BACKGROUND: Health care accessibility is known to differ geographically. With this study we focused on analysing accessibility of general and specialized obstetric units in England and Germany with regard to urbanity, area deprivation and neonatal outcome using routine data. METHODS: We used a floating catchment area method to measure obstetric care accessibility, the degree of urbanization (DEGURBA) to measure urbanity and the index of multiple deprivation to measure area deprivation. RESULTS: Accessibility of general obstetric units was significantly higher in Germany compared to England (accessibility index of 16.2 vs. 11.6; p < 0.001), whereas accessibility of specialized obstetric units was higher in England (accessibility index for highest level of care of 0.235 vs. 0.002; p < 0.001). We further demonstrated higher obstetric accessibility for people living in less deprived areas in Germany (r = - 0.31; p < 0.001) whereas no correlation was present in England. There were also urban-rural disparities present, with higher accessibility in urban areas in both countries (r = 0.37-0.39; p < 0.001). The analysis did not show that accessibility affected neonatal outcomes. Finally, our computer generated model for obstetric care provider demand in terms of birth counts showed a very strong correlation with actual birth counts at obstetric units (r = 0.91-0.95; p < 0.001). CONCLUSION: In Germany the focus of obstetric care seemed to be put on general obstetric units leading to higher accessibility compared to England. Regarding specialized obstetric care the focus in Germany was put on high level units whereas in England obstetric care seems to be more balanced between the different levels of care with larger units on average leading to higher accessibility

Access to intensive care in 14 European countries: A spatial analysis of intensive care need and capacity in the light of COVID-19.

Purpose The coronavirus disease 2019 (COVID-19) poses major challenges to health-care systems worldwide. This pandemic demonstrates the importance of timely access to intensive care and, therefore, this study aims to explore the accessibility of intensive care beds in 14 European countries and its impact on the COVID-19 case fatality ratio (CFR). Methods We examined access to intensive care beds by deriving (1) a regional ratio of intensive care beds to 100,000 population capita (accessibility index, AI) and (2) the distance to the closest intensive care unit. The cross-sectional analysis was performed at a 5-by-5 km spatial resolution and results were summarized nationally for 14 European countries. The relationship between AI and CFR was analyzed at the regional level. Results We found national-level differences in the levels of access to intensive care beds. The AI was highest in Germany (AI = 35.3), followed by Estonia (AI = 33.5) and Austria (AI = 26.4), and lowest in Sweden (AI = 5) and Denmark (AI = 6.4). The average travel distance to the closest hospital was highest in Croatia (25.3 min by car) and lowest in Luxembourg (9.1 min). Subnational results illustrate that capacity was associated with population density and national-level inventories. The correlation analysis revealed a negative correlation of ICU accessibility and COVID-19 CFR (r = - 0.57;p < 0.001). Conclusion Geographical access to intensive care beds varies significantly across European countries and low ICU accessibility was associated with a higher proportion of COVID-19 deaths to cases (CFR). Important differences in access are due to the sizes of national resource inventories and the distribution of health-care facilities relative to the human population. Our findings provide a resource for officials planning public health responses beyond the current COVID-19 pandemic, such as identifying potential locations suitable for temporary facilities or establishing logistical plans for moving severely ill patients to facilities with available beds