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Background: Despite advancements in treatment and early diagnosis, people with lung cancer are not living as long as those with other cancers. The more common symptoms of lung cancer, such as breathlessness, fatigue, and depression, can be alleviated by improving patients' physical functioning. Therefore, good symptom management and improved health-related quality of life (HRQoL) are priorities in this patient group. However, current health care services have limited capacity to provide this support. One way to address this issue of health care resources is to empower patients to self-manage their condition using eHealth technologies., Objective: The purpose of this review was to identify and assess available research on technologies that support persons with lung cancer to improve or maintain their physical functioning, HRQoL, or both., Methods: Six databases-PubMed, Web of Science, CINAHL, MEDLINE, SPORTDiscus, and PsycINFO-were searched from January 1, 1990, to April 30, 2023. Studies were suitable for inclusion if the participants included people with lung cancer aged >18 years who had been exposed to a physical activity, exercise, or training intervention that was delivered via an electronic or web-based application with or without a comparator. Furthermore, the study had to report on the impact of the intervention on physical functioning and HRQoL. Studies that focused on telemedicine without a digital intervention were excluded. The Grading of Recommendations Assessment, Development, and Evaluation system was used to assess the quality of the included papers. Due to the heterogeneity of the studies, a narrative synthesis was undertaken., Results: This review is reported in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 794 papers were initially identified through our search, of which, after screening, 8 (1%) were confirmed suitable for inclusion in the review. As 2 (25%) of the 8 papers reported on different stages of the same study, we included only 7 studies in our analysis. The studies were undertaken between 2010 and 2018 across multiple countries and aimed to develop a technology and test its feasibility or acceptance. The 7 technologies identified included web-based applications, mobile apps, and gaming consoles. The studies demonstrated impact on walking distance, muscle strength, balance, dyspnea symptoms, and cancer-related fatigue. HRQoL scores also showed improvement., Conclusions: The findings indicate that eHealth technologies can positively impact physical functioning and well-being for people with lung cancer, but there are limited studies that demonstrate the impact of these digital interventions over longer periods. None of the studies reported on the implementation or adoption of a mobile health or eHealth intervention in routine clinical practice, highlighting the need for further research in this area., Trial Registration: PROSPERO CRD42023414094; https://tinyurl.com/39hhbwyx., (©Suriya Kirkpatrick, Zoe Davey, Peter Richard Wright, Catherine Henshall. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 26.07.2024.)

The free-living thermophilic amoeba Naegleria fowleri ( N. fowleri ) causes the highly fatal disease primary amoebic meningoencephalitis. The environmental conditions that are favorable to the growth and proliferation of N. fowleri are not well-defined, especially in northern regions of the United States. In this study, we used culture-based methods and multiple molecular approaches to detect and analyze N. fowleri and other Naegleria spp. in water, sediment, and biofilm samples from five hot spring sites in Grand Teton National Park, Wyoming, U.S.A. These results provide the first detections of N. fowleri in Grand Teton National Park and provide new insights into the distribution of pathogenic N. fowleri and other nonpathogenic Naegleria spp. in natural thermal water systems in northern latitudes., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Introduction: Rapid treatment of acute ischemic stroke (AIS) depends on sufficient staffing which differs between Stroke Centers and Stroke Units in Switzerland. We studied the effect of admission time on performance measures of AIS treatment and related temporal trends over time., Patients and Methods: We compared treatment rates, door-to-image-time, door-to-needle-time, and door-to-groin-puncture-time in stroke patients admitted during office hours (Monday-Friday 8:00-17:59) and non-office hours at all certified Stroke Centers and Stroke Units in Switzerland, as well as secular trends thereof between 2014 and 2019, using data from the Swiss Stroke Registry. Secondary outcomes were modified Rankin Scale and mortality at 3 months., Results: Data were eligible for analysis in 31,788 (90.2%) of 35,261 patients. Treatment rates for IVT/EVT were higher during non-office hours compared with office hours in Stroke Centers (40.8 vs 36.5%) and Stroke Units (21.8 vs 18.5%). Door-to-image-time and door-to-needle-time increased significantly during non-office hours. Median (IQR) door-to-groin-puncture-time at Stroke Centers was longer during non-office hours compared to office hours (84 (59-116) vs 95 (66-130) minutes). Admission during non-office hours was independently associated with worse functional outcome (1.11 [95%CI: 1.04-1.18]) and increased mortality (1.13 [95%CI: 1.01-1.27]). From 2014 to 2019, median door-to-groin-puncture-time improved and the treatment rate for wake-up strokes increased., Discussion and Conclusion: Despite differences in staffing, patient admission during non-office hours delayed IVT to a similar, modest degree at Stroke Centers and Stroke Units. A larger delay of EVT was observed during non-office hours, but Stroke Centers sped up delivery of EVT over time. Patients admitted during non-office hours had worse functional outcomes, which was not explained by treatment delays., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: VLA, SAS, PRW, MP, TK, AvH, TM, EC, SS, RS, JV, JN, LS, SR, MS, MLM, BR, GS report no conflicting interests. GMDM has received support from the Swiss National Science Foundation; Spezialprogramm Nachwuchsförderung Klinische Forschung, University of Basel; Science Funds of the University Hospital Basel; Swiss Heart Foundation; Bangerter-Rhyner-Stiftung; Swisslife Jubiläumsstiftung for Medical Research; Swiss Neurological Society; Fondazione Dr Ettore Balli; De Quervain research grant; Thermo-Fisher-GmbH; consultant honoraria by Bayer; speaker honoraria by Medtronic and BMS/Pfizer. HG has received research support from the Swiss National Science Foundation, advisory board honoraria from Daiichi-Sankyo and funding for travel from BMS/Pfizer. STE has received funding for travel or speaker honoraria from Bayer Boehringer-Ingelheim, and Daiichi-Sankyo. He has served on scientific advisory boards for Bayer, Boehringer-Ingelheim, BMS/Pfizer, MindMaze, the editorial board of Stroke. He has received an educational grant from Pfizer and research support from the Science Funds of the University Hospital Basel, the University Basel, the Swiss Heart Foundation and the Swiss National Science Foundation. KN received speaker’s fees from Abbott. MA received Speaker honoraria from Bayer, Boehringer-Ingelheim, and Covidien; Scientific advisory board honoraria from Amgen, Bayer, Boehringer-Ingelheim, BMS, Pfizer, Covidien, Daichy Sankyo and Nestlé Health Science. Research grants from the Swiss Heart Foundation and the Swiss National Science Foundation. UF has received research support from the Swiss National Science Foundation, the Swiss Heart Foundation and Medtronic; he is a consultant for Medtronic, Stryker, and CSL-Behring. PM received speaker honoraria from Medtronic, Stryker. Consultant for Medtronic, Cerenovus, Phenox, Microvention, research grants from the Swiss Heart Foundation, Siemens and iSchemview. MG reports grants from Bangerter-Rhyner-Foundation. JK reports grants from the Swiss Stroke Society and the Swiss Academy of Medical Sciences/Bangerter Foundation. PM has received has received through his institution research grants from the Swiss National Science Foundation, the Swiss Heart Foundation and the ERISTA program (Pfizer/BMS); consulting fees from Medtronic. All this support goes to his institution for stroke education and research. CWC has received modest honoraria for scientific advisory board from Bayer, Boehringer-Ingelheim and iSchemaview; Research grants from the Swiss Heart Foundation. MB has received honoraria for travel from Bayer and for participation in advisory board from AstraZeneca. GK has received modest honoraria for travel and advisory board from Bayer, Medtronic, Alexion, Bial, Boehringer-Ingelheim and Zambon, a research grant from the Swiss Heart Foundation, Swiss Parkinson Foundation, Swiss National Science Foundation. ARL has received modest honoraria for travel and advisory board from Bayer, Moleac and Amgen and research grants from the P&K Pühringer-Foundation. SW received research funds by the Swiss National Science Foundation, the UZH Clinical research priority program (CRPP) stroke, the Swiss Heart foundation, Boehringer-Ingelheim, speakers honorarium from Amgen and a consultancy fee from Bayer. NP has received research funding from the Swiss Heart Foundation and the Swiss National Science Foundation, speaker honoraria from Vifor; served on advisory boards for Bayer, Boehringer-Ingelheim, BMS/Pfizer, Daiichi-Sankyo and AstraZeneca. FM has received research support from the Swiss Heart Foundation and has not received any honoria from industry 2017. CBe received modest honoraria for travel and advisory board from Novartis and Bayer. CBo reports travel and speaker honoraria from Amgen, Bayer, Biogen, Boehringer-Ingelheim, Bristol-Myers-Squibb, Lilly, Merck, Novartis, Pfizer, Roche, Servier, Sanofi, TEVA. LHB has received grants from the Swiss National Science Foundation, the University of Basel, the Swiss Heart Foundation, and the “Stiftung zur Förderung der gastroenterologischen und allgemeinen klinischen Forschung sowie der medizinischen Bildauswertung.” Unrestricted research grant from AstraZeneca, consultancy or advisory board fees or speaker’s honoraria from Amgen, Bayer, Bristol-Myers-Squibb, Claret Medical, and InnovHeart, and travel grants from AstraZeneca and Bayer., (© European Stroke Organisation 2022.)

Background and Purpose: Breast cancer can be a major challenge for affected women. Knowledge of the physical function, symptoms of cancer-related fatigue, anxiety, and depression based on the cancer treatment may help to guide adequate support., Methods: For this prospective observational study, we collected data from seventy-nine women with a mean age 54.6 ± 9.5 years prior to the onset of breast cancer treatment (T0) and after (T1/T2). Handgrip strength test (HGS), six-minute walk test (6MWT), the phase angle (PhA), the hospital anxiety and depression scale (HADS), and functional assessment of chronic illness therapy-fatigue (FACIT-F) were used to collect data from four treatment subgroups SC, surgery + chemotherapy; SCR, surgery + chemotherapy + radiation therapy; SR, surgery + radiation therapy; and S, surgery., Results: A mixed ANOVA revealed a significant interaction between time and group for PhA, F = 8.55, p < 0.01; HGS, F = 3.59, p < 0.01; 6MWT, F = 4.47, p < 0.01; and FACIT-F, F = 2.77, p < 0.05 with most pronounced deterioration seen in group SCR (PhA 4.8°; HGS 27.5 kg, 6MWT 453.4 m, FACIT-F 33.8 points). HADS data displayed moderate anxiety and depression predominantly after treatment., Conclusion: Our study showed that the extent of change in physical function, symptoms of fatigue, anxiety, and depression depends on the treatment conditions. The potentially higher risk of impaired function due to the prevalence of values below a critical threshold requires early initiated multidisciplinary support., (© 2022. The Author(s).)

Background: Endovascular treatment in large artery occlusion stroke reduces disability. However, the impact of anesthesia type on clinical outcomes remains uncertain., Methods: We compared consecutive patients in the Swiss Stroke Registry with anterior circulation stroke receiving endovascular treatment with or without general anesthesia (GA). The primary outcome was disability on the modified Rankin Scale after 3 months, analyzed with ordered logistic regression. Secondary outcomes included dependency or death (modified Rankin Scale score ≥ 3), National Institutes of Health Stroke Scale after 24 hours, symptomatic intracranial hemorrhage with ≥ 4 points worsening on National Institutes of Health Stroke Scale within 7 days, and mortality. Coarsened exact matching and propensity score matching were performed to adjust for indication bias., Results: One thousand two hundred eighty-four patients (GA: n=851, non-GA: n=433) from 8 Stroke Centers were included. Patients treated with GA had higher modified Rankin Scale scores after 3 months than patients treated without GA, in the unmatched (odds ratio [OR], 1.75 [1.42-2.16]; P <0.001), the coarsened exact matching (n=332-524, using multiple imputations of missing values; OR, 1.60 [1.08-2.36]; P =0.020), and the propensity score matching analysis (n=568; OR, 1.61 [1.20-2.15]; P =0.001). In the coarsened exact matching analysis, there were no significant differences in National Institutes of Health Stroke Scale after 1 day (estimated coefficient 2.61 [0.59-4.64]), symptomatic intracranial hemorrhage (OR, 1.06 [0.30-3.75]), dependency or death (OR, 1.42 [0.91-2.23]), or mortality (OR, 1.65 [0.94-2.89]). In the propensity score matching analysis, National Institutes of Health Stroke Scale after 24 hours (estimated coefficient, 3.40 [1.76-5.04]), dependency or death (OR, 1.49 [1.07-2.07]), and mortality (OR, 1.65 [1.11-2.45]) were higher in the GA group, whereas symptomatic intracranial hemorrhage did not differ significantly (OR, 1.77 [0.73-4.29])., Conclusions: This large study showed worse functional outcome after endovascular treatment of anterior circulation stroke with GA than without GA in a real-world setting. This finding appears to be independent of known differences in patient characteristics between groups.

Background and Purpose: In Switzerland, the COVID-19 incidence during the first pandemic wave was high. Our aim was to assess the association of the outbreak with acute stroke care in Switzerland in spring 2020., Methods: This was a retrospective analysis based on the Swiss Stroke Registry, which includes consecutive patients with acute cerebrovascular events admitted to Swiss Stroke Units and Stroke Centers. A linear model was fitted to the weekly admission from 2018 and 2019 and was used to quantify deviations from the expected weekly admissions from 13 March to 26 April 2020 (the "lockdown period"). Characteristics and 3-month outcome of patients admitted during the lockdown period were compared with patients admitted during the same calendar period of 2018 and 2019., Results: In all, 28,310 patients admitted between 1 January 2018 and 26 April 2020 were included. Of these, 4491 (15.9%) were admitted in the periods March 13-April 26 of the years 2018-2020. During the lockdown in 2020, the weekly admissions dropped by up to 22% compared to rates expected from 2018 and 2019. During three consecutive weeks, weekly admissions fell below the 5% quantile (likelihood 0.38%). The proportion of intracerebral hemorrhage amongst all registered admissions increased from 7.1% to 9.3% (p = 0.006), and numerically less severe strokes were observed (median National Institutes of Health Stroke Scale from 3 to 2, p = 0.07)., Conclusions: Admissions and clinical severity of acute cerebrovascular events decreased substantially during the lockdown in Switzerland. Delivery and quality of acute stroke care were maintained., (© 2021 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Breast cancer can be a significant challenge for those affected. Knowledge of physical function, social-emotional challenges, and perceived cognitive function based on the cancer treatment regimens may help to inform adequate support., Methods: For this prospective observational pilot study, we collected data of seventy-nine women (mean age 54.6 ± 9.5 years) before (T0) and after (T1) initial breast cancer treatment. Functional Assessment of Cancer Therapy-Breast (FACT-B) and Functional Assessment of Cancer Therapy-Cognitive-Function (FACT-Cog) were used to collect data of four treatment subgroups: SCR = Surgery + Chemotherapy + Radiation Therapy; SC = Surgery + Chemotherapy; SR = Surgery + Radiation Therapy; S = Surgery. A mixed ANOVA and posthoc analysis (Tukey, Games-Howell) were used to detect interactions (group by time) and the main effect. A repeated-measures ANOVA displayed individual group differences (time)., Results: Significant interaction showed more deterioration was experienced with SC and SCR than SR and S for FACT-B (p < 0.01) and FACT-Cog (p < 0.001). The longitudinal comparison between T0 and T1 indicated a significant group main effect on all subscales (p < 0.001) except for Emotional Well-Being. Significant reductions (p < 0.05) in FACT-B, (- 19%); FACT-Cog, (- 21%) with most pronounced effect in Physical Well-Being (- 30%), Functional Well-Being (- 20%), Breast Cancer Subscale (- 20%), Perceived Cognitive Impairments (- 18%) and Impact of Cognitive Impairments on Quality of Life (- 39%) were detected for SCR., Conclusion: Our study showed that the extent of change in health-related quality of life (HRQoL) and perceived cognitive function (PCF) depends on the treatment regimen. Multidisciplinary support initiated early in breast cancer therapy is needed, especially for women undergoing combined cancer treatment. Routine assessment of patient-reported outcomes (PROs) in oncology practice may increase the transparency of patients' perceived circumstances, leading to personalized and optimized acute and survivorship care., (© 2022. The Author(s).)

Context: Correction of hyponatremia might represent an additional treatment for improving stroke patients' clinical outcomes., Objective: Admission hyponatremia is associated with worse clinical outcome in stroke patients, but whether normalization of hyponatremia improves outcome is unknown. We investigated whether normalization of hyponatremia affects patients' disability, mortality, and stroke recurrence within 3 months; length of hospitalization; and discharge destination., Design: This was a registry-based analysis of data collected between January 2016 and December 2018. We linked data from Swiss Stroke Registry (SSR) with electronic patients' records for extracting sodium values., Setting: We analyzed data of hospitalized patients treated at University Hospital of Basel., Patients: Stroke patients whose data and informed consent were available., Main Outcome Measure: Modified Rankin Scale (mRS) score at 3 months. The tested hypothesis was formulated after SSR data collection but before linkage with electronic patients' records., Results: Of 1995 patients, 144 (7.2%) had hyponatremia on admission; 102 (70.8%) reached normonatremia, and 42 (29.2%) remained hyponatremic at discharge. An increase of initial sodium was associated with better functional outcome at 3 months (odds ratio [OR] 0.94; 95% CI, 0.90-0.99, for a shift to higher mRS per 1 mmol/L sodium increase). Compared with normonatremic patients, patients who remained hyponatremic at discharge had a worse functional outcome at 3 months (odds ratio 2.46; 95% CI, 1.20-5.03, for a shift to higher mRS). No effect was found on mortality, recurrence, or length of hospitalization., Conclusions: In hospitalized acute stroke patients, persistent hyponatremia is associated with worse functional outcome. Whether active correction of hyponatremia improves outcome remains to be determined in prospective studies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Among 400 Aspergillus species from respiratory samples in Switzerland, Aspergillus fumigatus was the most frequent species. Non- fumigatus Aspergillus spp were more prevalent among solid organ transplant recipients and after azole exposure. Azole resistance was detected in 4 A fumigatus isolates, 3 of them with the "environmental" mutation TR 34 /L98H in the cyp51A gene., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Knowledge of clinically established factors of physical function such as body composition, bioelectrical phase angle (PhA) and handgrip strength (HGS) with mortality predictive and health-related relevance is limited in prostate cancer survivors (PCS). Therefore, the aim of this study was to characterise and compare body composition data of PCS with extensive reference data as well as to analyse PhA and HGS and the prevalence of critical prognostic values at an early stage of cancer survivorship., Methods: One hundred and forty-eight PCS were examined at the start (T1) and end (T2) of a 3-week hospitalised urooncological rehabilitation, which began median 28 days after acute cancer therapy. Examinations included a bioimpedance analysis and HGS test. Comparison of body composition between PCS and reference data was performed using bioimpedance vector analysis (BIVA)., Results: BIVA of the whole PCS group showed abnormal physiology with a cachectic state and a state of overhydration/oedema, without significant changes between T1 and T2. The age- and BMI-stratified subgroup analysis showed that PCS aged 60 years and older had this abnormal pattern compared to the reference population. HGS (T1: 38.7 ± 8.9 vs T2: 40.8 ± 9.4, kg), but not PhA (T1/T2: 5.2 ± 0.7, °), changed significantly between T1 and T2. Values below a critical threshold reflecting a potentially higher risk of mortality and impaired function were found for PhA in 20% (T1) and 22% (T2) of PCS and in 41% (T1) and 29% (T2) for HGS., Conclusions: BIVA pattern and the prevalence of critically low HGS and PhA values illustrate the necessity for intensive continuation of rehabilitation and survivorship care especially in these 'at risk' cases. The routine assessment of body composition, PhA and HGS offer the opportunity to conduct a risk stratification for PCS and could help personalising and optimising treatment in rehabilitation and ongoing survivorship care., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Aims: In this study, we aimed to investigate whether body composition analysis (BCA) derived from bioelectrical impedance vector analysis (BIVA) could be used to monitor the hydration status of patients with acute heart failure (AHF) during intensified diuretic therapy., Methods and Results: This observational, single-centre study involved a novel, validated eight-electrode segmental body composition analyser to perform BCA derived from BIVA with an alternating current of 100 μA at frequencies of 5, 7.5, 50, and 75 kHz. The BCA-derived and BIVA-derived parameters were estimated and compared with daily body weight measurements in hospitalized patients with AHF. A total of 867 BCA and BIVA assessments were conducted in 142 patients (56.3% men; age 76.8 ± 10.7 years). Daily changes in total body water (TBW) and extracellular water (ECW) were significantly associated with changes in body weight in 62.2% and 89.1% of all measurements, respectively (range, ±1 kg). Repeated measures correlation coefficients between weight loss and TBW loss resulted with rho 0.43, P < 0.01, confidence interval (CI) [0.36, 0.50] and rho 0.71, P > 0.01, CI [0.67, 0.75] for ECW loss. Between the first and last assessments, the mean weight loss was -2.5 kg, compared with the -2.6 L mean TBW loss and -1.7 L mean ECW loss. BIVA revealed an increase in mean Resistance R and mean Reactance X c across all frequencies, with the subsequent reduction in body fluid (including corresponding body weight) between the first and last assessments., Conclusions: Body composition analysis derived from BIVA with a focus on ECW is a promising approach to detect changes in hydration status in patients undergoing intensified diuretic therapy. Defining personalized BIVA reference values using bioelectrical impedance devices is a promising approach to monitor hydration status., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Autonomous water sampling technologies may help to overcome the human resource challenges of monitoring biological threats to rivers over long time periods and across large geographic areas. The Monterey Bay Aquarium Research Institute has pioneered a robotic Environmental Sample Processor (ESP) that overcomes some of the constraints associated with traditional sampling since it can automate water sample filtration and preservation of the captured material. The ESP was originally developed for marine environment applications. Here we evaluated whether the ESP can provide reliable, timely information on environmental (e)DNA detections of human and fish pathogens and introduced fishes at U.S. Geological Survey streamgage sites in freshwater rivers. We compared eDNA collected via ESP at high frequency (e.g., every 3 h) with manual eDNA collections collected at lower frequency (e.g., weekly). We found that water samples filtered and preserved by ESPs successfully detected the DNA of human pathogens, fish pathogens and introduced fishes. Both ESP and manually collected samples provided similar information about target DNA presence. We suggest that the greatest current benefit of the ESP is the cost savings of high frequency, bio-surveillance at remote or hard to access sites. The full potential of robotic technologies like the ESP will be realized when they can more easily execute in situ analyses of water samples and rapidly transmit results to decision-makers.

As the key enzyme of bacterial nitrogen assimilation, glutamine synthetase (GS) is tightly regulated. In cyanobacteria, GS activity is controlled by the interaction with inactivating protein factors IF7 and IF17 encoded by the genes gifA and gifB, respectively. We show that a glutamine-binding aptamer within the gifB 5' UTR of Synechocystis sp. PCC 6803 is critical for the expression of IF17. Binding of glutamine induced structural re-arrangements in this RNA element leading to enhanced protein synthesis in vivo and characterizing it as a riboswitch. Mutagenesis showed the riboswitch mechanism to contribute at least as much to the control of gene expression as the promoter-mediated transcriptional regulation. We suggest this and a structurally related but distinct element, to be designated type 1 and type 2 glutamine riboswitches. Extended biocomputational searches revealed that glutamine riboswitches are exclusively but frequently found in cyanobacterial genomes, where they are primarily associated with gifB homologs. Hence, this RNA-based sensing mechanism is common in cyanobacteria and establishes a regulatory feedback loop that couples the IF17-mediated GS inactivation to the intracellular glutamine levels. Together with the previously described sRNA NsiR4, these results show that non-coding RNA is an indispensable component in the control of nitrogen assimilation in cyanobacteria.

The Freiburg RNA tools webserver is a well established online resource for RNA-focused research. It provides a unified user interface and comprehensive result visualization for efficient command line tools. The webserver includes RNA-RNA interaction prediction (IntaRNA, CopraRNA, metaMIR), sRNA homology search (GLASSgo), sequence-structure alignments (LocARNA, MARNA, CARNA, ExpaRNA), CRISPR repeat classification (CRISPRmap), sequence design (antaRNA, INFO-RNA, SECISDesign), structure aberration evaluation of point mutations (RaSE), and RNA/protein-family models visualization (CMV), and other methods. Open education resources offer interactive visualizations of RNA structure and RNA-RNA interaction prediction as well as basic and advanced sequence alignment algorithms. The services are freely available at http://rna.informatik.uni-freiburg.de.

Many years of research in RNA biology have soundly established the importance of RNA-based regulation far beyond most early traditional presumptions. Importantly, the advances in "wet" laboratory techniques have produced unprecedented amounts of data that require efficient and precise computational analysis schemes and algorithms. Hence, many in silico methods that attempt topological and functional classification of novel putative RNA-based regulators are available. In this review, we technically outline thermodynamics-based standard RNA secondary structure and RNA-RNA interaction prediction approaches that have proven valuable to the RNA research community in the past and present. For these, we highlight their usability with a special focus on prokaryotic organisms and also briefly mention recent advances in whole-genome interactomics and how this may influence the field of predictive RNA research.

To maintain genome integrity, organisms employ DNA damage response, the underlying principles of which are conserved from bacteria to humans. The bacterial small RNA OxyS of Escherichia coli is induced upon oxidative stress and has been implicated in protecting cells from DNA damage; however, the mechanism by which OxyS confers genome stability remained unknown. Here, we revealed an OxyS-induced molecular checkpoint relay, leading to temporary cell cycle arrest to allow damage repair. By repressing the expression of the essential transcription termination factor nusG , OxyS enables read-through transcription into a cryptic prophage encoding kilR The KilR protein interferes with the function of the major cell division protein FtsZ, thus imposing growth arrest. This transient growth inhibition facilitates DNA damage repair, enabling cellular recovery, thereby increasing viability following stress. The OxyS-mediated growth arrest represents a novel tier of defense, introducing a new regulatory concept into bacterial stress response., (© 2017 The Authors. Published under the terms of the CC BY 4.0 license.)

Computational methods can often facilitate the functional characterization of individual sRNAs and furthermore allow high-throughput analysis on large numbers of sRNA candidates. This chapter outlines a potential workflow for computational sRNA analyses and describes in detail methods for homolog detection, target prediction, and functional characterization based on enrichment analysis. The cyanobacterial sRNA IsaR1 is used as a specific example. All methods are available as webservers and easily accessible for nonexpert users.

The IntaRNA algorithm enables fast and accurate prediction of RNA-RNA hybrids by incorporating seed constraints and interaction site accessibility. Here, we introduce IntaRNAv2, which enables enhanced parameterization as well as fully customizable control over the prediction modes and output formats. Based on up to date benchmark data, the enhanced predictive quality is shown and further improvements due to more restrictive seed constraints are highlighted. The extended web interface provides visualizations of the new minimal energy profiles for RNA-RNA interactions. These allow a detailed investigation of interaction alternatives and can reveal potential interaction site multiplicity. IntaRNAv2 is freely available (source and binary), and distributed via the conda package manager. Furthermore, it has been included into the Galaxy workflow framework and its already established web interface enables ad hoc usage., (© The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.)

CLIP-seq experiments are currently the most important means for determining the binding sites of RNA binding proteins on a genome-wide level. The computational analysis can be divided into three steps. In the first pre-processing stage, raw reads have to be trimmed and mapped to the genome. This step has to be specifically adapted for each CLIP-seq protocol. The next step is peak calling, which is required to remove unspecific signals and to determine bona fide protein binding sites on target RNAs. Here, both protocol-specific approaches as well as generic peak callers are available. Despite some peak callers being more widely used, each peak caller has its specific assets and drawbacks, and it might be advantageous to compare the results of several methods. Although peak calling is often the final step in many CLIP-seq publications, an important follow-up task is the determination of binding models from CLIP-seq data. This is central because CLIP-seq experiments are highly dependent on the transcriptional state of the cell in which the experiment was performed. Thus, relying solely on binding sites determined by CLIP-seq from different cells or conditions can lead to a high false negative rate. This shortcoming can, however, be circumvented by applying models that predict additional putative binding sites., (Copyright © 2017. Published by Elsevier Inc.)

Background: While NGS allows rapid global detection of transcripts, it remains difficult to distinguish ncRNAs from short mRNAs. To detect potentially translated RNAs, we developed an improved protocol for bacterial ribosomal footprinting (RIBOseq). This allowed distinguishing ncRNA from mRNA in EHEC. A high ratio of ribosomal footprints per transcript (ribosomal coverage value, RCV) is expected to indicate a translated RNA, while a low RCV should point to a non-translated RNA., Results: Based on their low RCV, 150 novel non-translated EHEC transcripts were identified as putative ncRNAs, representing both antisense and intergenic transcripts, 74 of which had expressed homologs in E. coli MG1655. Bioinformatics analysis predicted statistically significant target regulons for 15 of the intergenic transcripts; experimental analysis revealed 4-fold or higher differential expression of 46 novel ncRNA in different growth media. Out of 329 annotated EHEC ncRNAs, 52 showed an RCV similar to protein-coding genes, of those, 16 had RIBOseq patterns matching annotated genes in other enterobacteriaceae, and 11 seem to possess a Shine-Dalgarno sequence, suggesting that such ncRNAs may encode small proteins instead of being solely non-coding. To support that the RIBOseq signals are reflecting translation, we tested the ribosomal-footprint covered ORF of ryhB and found a phenotype for the encoded peptide in iron-limiting condition., Conclusion: Determination of the RCV is a useful approach for a rapid first-step differentiation between bacterial ncRNAs and small mRNAs. Further, many known ncRNAs may encode proteins as well.

Photorhabdus luminescens maintains a symbiotic relationship with the nematodes Heterorhabditis bacteriophora and together they infect and kill insect larvae. To maintain this symbiotic relationship, the bacteria must produce an array of secondary metabolites to assist in the development and replication of nematodes. The regulatory mechanisms surrounding production of these compounds are mostly unknown. The global post-transcriptional regulator, Hfq, is widespread in bacteria and performs many functions, one of which is the facilitation of sRNA binding to target mRNAs, with recent research thoroughly exploring its various pleiotropic effects. Here we generate and characterize an hfq deletion mutant and show that in the absence of hfq, the bacteria are no longer able to maintain a healthy symbiosis with nematodes due to the abolishment of the production of all known secondary metabolites. RNAseq led us to produce a second deletion of a known repressor, HexA, in the same strain, which restored both metabolite production and symbiosis., (© 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Antioxidant activity of symbiotic organisms known as lichens is an intriguing field of research because of its strong contribution to their ability to withstand extremes of physical and biological stress (e.g. desiccation, temperature, UV radiation and microbial infection). We present a comparative study on the antioxidant activities of 76 Icelandic and 41 Hawaiian lichen samples assessed employing the DPPH- and FRAP-based antioxidant assays. Utilizing this unprecedented sample size, we show that while highest individual sample activity is present in the Icelandic dataset, the overall antioxidant activity is higher for lichens found in Hawaii. Furthermore, we report that lichens from the genus Peltigera that have been described as strong antioxidant producers in studies on Chinese, Russian and Turkish lichens also show high antioxidant activities in both Icelandic and Hawaiian lichen samples. Finally, we show that opportunistic sampling of lichens in both Iceland and Hawaii will yield high numbers of lichen species that exclusively include green algae as photobiont., (© 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.)

The molecular roles of many RNA-binding proteins in bacterial post-transcriptional gene regulation are not well understood. Approaches combining in vivo UV crosslinking with RNA deep sequencing (CLIP-seq) have begun to revolutionize the transcriptome-wide mapping of eukaryotic RNA-binding protein target sites. We have applied CLIP-seq to chart the target landscape of two major bacterial post-transcriptional regulators, Hfq and CsrA, in the model pathogen Salmonella Typhimurium. By detecting binding sites at single-nucleotide resolution, we identify RNA preferences and structural constraints of Hfq and CsrA during their interactions with hundreds of cellular transcripts. This reveals 3'-located Rho-independent terminators as a universal motif involved in Hfq-RNA interactions. Additionally, Hfq preferentially binds 5' to sRNA-target sites in mRNAs, and 3' to seed sequences in sRNAs, reflecting a simple logic in how Hfq facilitates sRNA-mRNA interactions. Importantly, global knowledge of Hfq sites significantly improves sRNA-target predictions. CsrA binds AUGGA sequences in apical loops and targets many Salmonella virulence mRNAs. Overall, our generic CLIP-seq approach will bring new insights into post-transcriptional gene regulation by RNA-binding proteins in diverse bacterial species., (© 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Mechanisms adjusting replication initiation and cell cycle progression in response to environmental conditions are crucial for microbial survival. Functional characterization of the trans-encoded small non-coding RNA (trans-sRNA) EcpR1 in the plant-symbiotic alpha-proteobacterium Sinorhizobium meliloti revealed a role of this class of riboregulators in modulation of cell cycle regulation. EcpR1 is broadly conserved in at least five families of the Rhizobiales and is predicted to form a stable structure with two defined stem-loop domains. In S. meliloti, this trans-sRNA is encoded downstream of the divK-pleD operon. ecpR1 belongs to the stringent response regulon, and its expression was induced by various stress factors and in stationary phase. Induced EcpR1 overproduction led to cell elongation and increased DNA content, while deletion of ecpR1 resulted in reduced competitiveness. Computationally predicted EcpR1 targets were enriched with cell cycle-related mRNAs. Post-transcriptional repression of the cell cycle key regulatory genes gcrA and dnaA mediated by mRNA base-pairing with the strongly conserved loop 1 of EcpR1 was experimentally confirmed by two-plasmid differential gene expression assays and compensatory changes in sRNA and mRNA. Evidence is presented for EcpR1 promoting RNase E-dependent degradation of the dnaA mRNA. We propose that EcpR1 contributes to modulation of cell cycle regulation under detrimental conditions.

CopraRNA (Comparative prediction algorithm for small RNA targets) is the most recent asset to the Freiburg RNA Tools webserver. It incorporates and extends the functionality of the existing tool IntaRNA (Interacting RNAs) in order to predict targets, interaction domains and consequently the regulatory networks of bacterial small RNA molecules. The CopraRNA prediction results are accompanied by extensive postprocessing methods such as functional enrichment analysis and visualization of interacting regions. Here, we introduce the functionality of the CopraRNA and IntaRNA webservers and give detailed explanations on their postprocessing functionalities. Both tools are freely accessible at http://rna.informatik.uni-freiburg.de., (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Histone acetyl transferases (HATs) play distinct roles in many cellular processes and are frequently misregulated in cancers. Here, we study the regulatory potential of MYST1-(MOF)-containing MSL and NSL complexes in mouse embryonic stem cells (ESCs) and neuronal progenitors. We find that both complexes influence transcription by targeting promoters and TSS-distal enhancers. In contrast to flies, the MSL complex is not exclusively enriched on the X chromosome, yet it is crucial for mammalian X chromosome regulation as it specifically regulates Tsix, the major repressor of Xist lncRNA. MSL depletion leads to decreased Tsix expression, reduced REX1 recruitment, and consequently, enhanced accumulation of Xist and variable numbers of inactivated X chromosomes during early differentiation. The NSL complex provides additional, Tsix-independent repression of Xist by maintaining pluripotency. MSL and NSL complexes therefore act synergistically by using distinct pathways to ensure a fail-safe mechanism for the repression of X inactivation in ESCs.DOI: http://dx.doi.org/10.7554/eLife.02024.001., (Copyright © 2014, Chelmicki et al.)

Objectives: This study evaluates whether the recently described lateral mortise (LM) approach to therapeutic ankle injections can also be used to inject the ankle prior to magnetic resonance arthrography (MRA) without impairing the evaluation of the anterior talofibular ligament (ATFL)., Materials and Methods: An IRB-approved, retrospective review of ankle MRAs performed using the LM approach between April 2009 and April 2011 was conducted. The MRAs were independently evaluated by three musculoskeletal radiologists for: ATFL assessment (well assessed, limited or unable to assess), amount of fluid in the anterolateral soft tissues (none to large), and capsular distention (underdistended to overdistended). Patient age, gender, fluoroscopy time, injection location, degree of ankle arthritis, and ankle joint narrowing on radiographs were recorded. Statistical analysis was performed using exact binomial confidence limits., Results: Fifteen MRAs were successfully performed on 13 patients (mean age: 27 years, 11 male, 2 female). Mean fluoroscopic time was 39 s (range 9–108) and mean volume injected was 7 mL (range 5–9 mL). The ATFL was well assessed on all MRAs. A moderate to large amount of fluid was noted in the anterolateral soft tissues on 5 out of 15 MRAs. No ankle joints were underdistended, but 3 out of 15 were overdistended., Conclusion: Since the ATFL is inferior to the location used for the LM injection, the interpretation of the ankle MRA, specifically ATFL evaluation, was not compromised in any patient. Therefore, the LM approach can be used as an alternative to the anteromedial approach for ankle MRA without sacrificing diagnostic quality.

The small RNA AbcR1 regulates the expression of ABC transporters in the plant pathogen Agrobacterium tumefaciens, the plant symbiont Sinorhizobium meliloti, and the human pathogen Brucella abortus. A combination of proteomic and bioinformatic approaches suggested dozens of AbcR1 targets in A. tumefaciens. Several of these newly discovered targets are involved in the uptake of amino acids, their derivatives, and sugars. Among the latter is the periplasmic sugar-binding protein ChvE, a component of the virulence signal transduction system. We examined 16 targets and their interaction with AbcR1 in close detail. In addition to the previously described mRNA interaction site of AbcR1 (M1), the CopraRNA program predicted a second functional module (M2) as target-binding site. Both M1 and M2 contain single-stranded anti-SD motifs. Using mutated AbcR1 variants, we systematically tested by band shift experiments, which sRNA region is responsible for mRNA binding and gene regulation. On the target site, we find that AbcR1 interacts with some mRNAs in the translation initiation region and with others far into their coding sequence. Our data show that AbcR1 is a versatile master regulator of nutrient uptake systems in A. tumefaciens and related bacteria.

Small RNAs (sRNAs) constitute a large and heterogeneous class of bacterial gene expression regulators. Much like eukaryotic microRNAs, these sRNAs typically target multiple mRNAs through short seed pairing, thereby acting as global posttranscriptional regulators. In some bacteria, evidence for hundreds to possibly more than 1,000 different sRNAs has been obtained by transcriptome sequencing. However, the experimental identification of possible targets and, therefore, their confirmation as functional regulators of gene expression has remained laborious. Here, we present a strategy that integrates phylogenetic information to predict sRNA targets at the genomic scale and reconstructs regulatory networks upon functional enrichment and network analysis (CopraRNA, for Comparative Prediction Algorithm for sRNA Targets). Furthermore, CopraRNA precisely predicts the sRNA domains for target recognition and interaction. When applied to several model sRNAs, CopraRNA revealed additional targets and functions for the sRNAs CyaR, FnrS, RybB, RyhB, SgrS, and Spot42. Moreover, the mRNAs gdhA, lrp, marA, nagZ, ptsI, sdhA, and yobF-cspC were suggested as regulatory hubs targeted by up to seven different sRNAs. The verification of many previously undetected targets by CopraRNA, even for extensively investigated sRNAs, demonstrates its advantages and shows that CopraRNA-based analyses can compete with experimental target prediction approaches. A Web interface allows high-confidence target prediction and efficient classification of bacterial sRNAs.

Marine myxobacteria (Enhygromyxa, Plesiocystis, Pseudoenhygromyxa, Haliangium) are phylogenetically distant from their terrestrial counterparts. Salimabromide is the first natural product from the Plesiocystis/Enhygromyxa clade of obligatory marine myxobacteria. Salimabromide has a new tetracyclic carbon skeleton, comprising a brominated benzene ring, a furano lactone residue, and a cyclohexane ring, bridged by a seven-membered cyclic moiety. The absolute configuration was deduced from experimental and calculated CD data. Salimabromide revealed antibiotic activity towards Arthrobacter cristallopoietes., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: The purpose of this study was to evaluate the lateral mortise approach for performing therapeutic ankle injections., Materials and Methods: Fluoroscopically guided ankle joint injections performed from November 2009 through June 2011 using the lateral ankle mortise approach were retrospectively reviewed. Data recorded included age, sex, fluoroscopic time, person performing the procedure, injection location, and preprocedure and postprocedure pain levels. Radiographs were reviewed for arthritis on a modified Kellgren-Lawrence scale, and the degree of anterior tibiotalar and lateral mortise narrowing was graded from none to severe. Univariate and multivariate statistical analyses were performed., Results: Fifty-three injections were performed on 46 patients (mean age, 50.2 years; mean fluoroscopic time, 44.3 ± 47.3 seconds). Fifty injections in 44 patients were successful with the lateral mortise approach. The degrees of arthritis and anterior tibiotalar joint narrowing were moderate in 22.6% and 20.8% of cases and severe in 39.6% and 32.1% of cases. Lateral mortise narrowing was moderate in 9.4% and severe in 1.9% of cases. Average pre-procedure and postprocedure pain levels were 5.3/10 ± 2.4/10 and 1.7/10 ± 2.3/10. Multivariate analysis showed that increased fluoroscopic time was associated with moderate to severe lateral mortise narrowing (p = 0.011) but that arthritis score (p = 0.811) and degree of anterior tibiotalar joint narrowing (p = 0.416) were not. Pain reduction was associated with a higher preinjection pain score (p ≤ 0.001)., Conclusion: The lateral mortise approach is an effective alternative to the anterior medial approach for performing therapeutic ankle injections. It is especially useful when moderate to severe ankle arthritis or anterior tibiotalar joint narrowing is present.

Marine algae are known to contain a wide variety of bioactive compounds, many of which have commercial applications in pharmaceutical, medical, cosmetic, nutraceutical, food and agricultural industries. Natural antioxidants, found in many algae, are important bioactive compounds that play an important role against various diseases and ageing processes through protection of cells from oxidative damage. In this respect, relatively little is known about the bioactivity of Hawaiian algae that could be a potential natural source of such antioxidants. The total antioxidant activity of organic extracts of 37 algal samples, comprising of 30 species of Hawaiian algae from 27 different genera was determined. The activity was determined by employing the FRAP (Ferric Reducing Antioxidant Power) assays. Of the algae tested, the extract of Turbinaria ornata was found to be the most active. Bioassay-guided fractionation of this extract led to the isolation of a variety of different carotenoids as the active principles. The major bioactive antioxidant compound was identified as the carotenoid fucoxanthin. These results show, for the first time, that numerous Hawaiian algae exhibit significant antioxidant activity, a property that could lead to their application in one of many useful healthcare or related products as well as in chemoprevention of a variety of diseases including cancer.

Fusing complex data from two disparate sources has been demonstrated to improve the accuracy in quantifying active ingredients in mixtures of pharmaceutical powders. A four-component simplex-centroid design was used to prepare blended powder mixtures of acetaminophen, caffeine, aspirin and ibuprofen. The blends were analyzed by Fourier transform infra-red spectroscopy (FTIR) and powder X-ray diffraction (PXRD). The FTIR and PXRD data were preprocessed and combined using two different data fusion methods: fusion of preprocessed data (FPD) and fusion of principal component scores (FPCS). A partial least square (PLS) model built on the FPD did not improve the root mean square error of prediction. However, a PLS model built on the FPCS yielded better accuracy prediction than PLS models built on individual FTIR and PXRD data sets. The improvement in prediction accuracy of the FPCS may be attributed to the removal of noise and data reduction associated with using PCA as a preprocessing tool. The present approach demonstrates the usefulness of data fusion for the information management of large data sets from disparate sources., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We live and work in a multicultural world and need to be knowledgeable about culture and how it affects the quality of care given to patients. Although people of the non-dominant culture may have knowledge of the English language, many have limited English proficiency (LEP), a topic of great importance for the ophthalmic patient in the healthcare setting where populations grow increasingly diverse. Knowing how to communicate effectively with patients includes an understanding oflanguage. Because of the need for accuracy in ophthalmic surgical treatment, it is critical for ophthalmic caregivers to learn the skills necessary to communicate proficiently with their patients in order to assure a positive outcome in patient care. To achieve this goal, ophthalmic healthcare providers need to realize that accessing medical interpreter services is a necessary component of providing culturally sensitive patient care.

Elevated concentrations of naturally occurring Cd have been found mainly in the bauxitic soils of central Jamaica at levels up to 100-1,000 times higher than typical worldwide averages. Some food crops cultivated on these soils absorb significant amounts of Cd. Autopsy studies of kidney Cd concentrations confirm elevated human exposure, and some long-term residents in central Jamaica exceed the general population average by a factor of two. Diet studies have ascertained that a population in central Jamaica is at risk of being exposed to Cd levels in excess of the Provisional Tolerable Weekly Intake (PTWI) set by the WHO of 7 μgCd/kg bodyweight/week, and the EU TWI of 2.5 μgCd/kg bodyweight/week. Elevated levels of urine cadmium (U-Cd) and beta-2 microglobulin (β2-MG) concentrations were confirmed with a strong correlation between soil Cd and the U-Cd. Also, higher β2-MG concentrations (>200μg/g creatinine) were found in the population with U-Cd concentrations greater than 2.5μg/L. While this identification is often taken to indicate impairment in the reabsorption capacity of the renal tubules leading to renal disease, there is no evidence in the mortality records of enhanced deaths in central Jamaica compared with the general population resulting from renal disease or diabetes related complications. The highest median age of death in the island is found in Manchester, the parish with the highest average Cd concentration. While we have identified a possible Cd linked renal dysfunction, significant indications of morbidity are not present in the general population.

In conclusion, the welfare of the child is of paramount importance in the detection and treatment ofretinoblastoma. It is important for the parents to feel comfortable with the care their child is receiving since they are facing a lengthy course of therapy. Consequently, the family will require the support of the entire ambulatory surgical daycare team for years to come.

The present work describes (a) the identification and characterization of an impurity, 2,4,5,7-tetrabromo-6-hydroxy-9-(2,3,4,5-tetrachlorophenyl)-3H-xanthen-3-one (BCPX), in the color additives D&C Red Nos. 27 and 28 (phloxine B) and (b) the determination of the extent and level of BCPX contamination in certified lots of these colors. For these purposes, BCPX (a compound not previously reported in the literature) was synthetically prepared. Test portions from 42 certified lots of D&C Red Nos. 27, 28 and 27 lakes were analyzed for BCPX using an HPLC method that included gradient elution and UV-vis photodiode array detection. Those lots were submitted for certification by both domestic (six) and foreign (six) manufacturers during the past 4 years. Of the test portions analyzed, 32 (76.2%) contained BCPX in amounts ranging from 0.01 to 3.21%. The remaining 10 test portions (23.8%) contained no detectable BCPX or less than 0.008%, which is the limit of quantification for the present method. The analyses revealed substantial differences in the level of BCPX across different manufacturers. The wide range of BCPX levels found in the analyzed lots suggests that the presence of BCPX in D&C Red Nos. 27 and 28 may be avoided or significantly reduced during the manufacturing process.

Background: Training therapy with its manifold effects should be part of a modern and multi modular treatment of the COPD. Because of the specific symptoms (e. g. muscle atrophy, dyspnea, low testosterone levels) and the deconditioning of these patients, a resistance training might meet the demands of a COPD-exercise-therapy rather than an endurance training. The aim of this research project was to evaluate the efficiency of a hypertrophic maximal strength training on various COPD relevant parameters., Methods: 28 patients with moderate to severe COPD (m12/f16) were randomized and divided in a treatment and a control group. The patients in the treatment group underwent a resistance training (hypertrophic maximal strength training) for 12 weeks, initially two times, then three times a week., Results: Considering the results of the daily Peak-Flow-Measurement, there was no significant change in both groups, but a trend towards an improvement could be found in the treatment group. There was no difference in the change of FEV 1. The performance on the ergo cycle showed a highly significant improvement (p < 0.001) in the treatment group of 18.7 % (21.9 Watt). The results of the SGRQ showed a significant improvement (p < 0.05) of the HRQL in the treatment group. A change of the HRQL in the control group was not found., Conclusions: These data support the hypotheses that a short term high intensity strength training programme is suitable to improve performance measures of patients with moderate to severe COPD and it might also improve pulmonary function. The conclusion can be drawn, that this kind of resistance training can be prefered as COPD-specific training therapy and offers new treatment perspectives.

Despite numerous advantages, fluidized bed adsorption is limited in commercial applications due to a poor understanding of the relationships between mass transfer, hydrodynamics, and adsorption. To obtain a better understanding of these parameters, we used two commercially available resins to compare the adsorption of lysozyme as a function of bed expansion and bulk-phase viscosity using frontal analysis. Under static conditions adsorption was well represented by a Langmuir isotherm. Dynamic capacities at breakthrough were measured and normalized relative to the equilibrium capacity of each resin to facilitate direct comparison of resin performance under each condition. To quantify the impact of resin characteristics in expanded bed adsorption, we carried out a comparison of mass-transfer effects using a macroporous resin, Streamline SP, and a hyper-diffusive resin, S-HyperD LS. Both resins are designed for fluidized bed adsorption of proteins. In this study the results of frontal analysis showed that breakthrough was due to mass-transfer limitations of the adsorbing particles at expansions of 2 times the settled bed height. At expansions of 3 and 4 times the settled bed height, axial dispersion increased significantly; however mass-transfer limitations were still the dominant mechanistic feature contributing to early breakthrough at reduced dynamic capacity. Adsorption capacity under all conditions in this study was poorer for the macroporous resin than for the hyper-diffusive resin due to intraparticle mass-transfer limitations.

In this study, solid-phase adsorption by macroporous and hyper-diffusive resins was investigated in a batch uptake adsorption system to quantify solid-phase diffusion rates as a function of bulk phase viscosity. The performance of chromatographic resins used for adsorption of proteins is dependent on several factors including solid and liquid-phase diffusivity, boundary layer mass transfer, and intraparticle mass transfer effects. Understanding these effects is critical to process development and optimization of both packed and fluidized bed adsorption systems. The macroporous resin used here was Streamline SP, and the hyper-diffusive resin was S-HyperD LS. Both have been frequently used in fluidized bed adsorption of proteins; however, factors that affect uptake rates of these media are not well quantified. Adsorption isotherms were well represented by an empirical fit of a Langmuir isotherm. Solid-phase diffusion coefficients obtained from simulations were in agreement with other models for macroporous and hyper-diffusive particles. S-HyperD LS in the buffer system had the highest uptake rate, but increased bulk phase viscosity decreased the rate by approximately 50%. Increases in bulk phase viscosity increased film mass transfer effects, and uptake was observed to be a strong function of the film mass transfer coefficient. Uptake by Streamline SP particles was slower than S-HyperD in buffer, due to a greater degree of intraparticle mass transfer resistance. The effect of increased film mass transfer resistance coupled with intraparticle mass transfer resistances at an increased bulk phase viscosity resulted in a decrease of 80% in the uptake rate by Streamline SP relative to S-HyperD.