Electroosmotic flow reversal outside glass nanopores.

We report observations of a striking reversal in the direction of electroosmotic flow (EOF) outside a conical glass nanopore as a function of salt concentration. At high ionic strengths (>100 mM), we observe EOF in the expected direction as predicted by classical electrokinetic theory, while at low salt concentrations (<1 mM) the direction of the flow is reversed. The critical crossover salt concentration depends on the pore diameter. Finite-element simulations indicate a competition between the EOF generated from the inner and outer walls of the pore, which drives flows in opposite directions. We have developed a simple analytical model which reveals that, as the salt concentration is reduced, the flow rates inside the pore are geometrically constrained, whereas there is no such limit for flows outside the pore. This model captures all of the essential physics of the system and explains the observed data, highlighting the key role the external environment plays in determining the overall electroosmotic behavior

A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study

SummaryBackground The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan. Methods On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control. Findings Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation. Interpretation Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto. Funding The Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG)

Pulmonary hypertension associated with chronic lung diseases

In 2015, the international guidelines for diagnosis and treatment of pulmonary hypertension (PH) were updated. Group 3 of the current classification includes PH associated with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), other pulmonary diseases with restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, chronic exposure to high altitude, and developmental lung diseases [1]. PH associated with COPD and ILD is common but difficult to manage, as no long-term randomised controlled trial (RCT) has been conducted with specific pulmonary arterial hypertension (PAH) drugs in PH associated with COPD, and the one recent RCT in PH associated with ILD had to be stopped early due to a possible increased risk of death and side effects in the treatment group. Specific treatment may thus be harmful and may worsen gas exchange as a result of possible recruitment of less oxygenised areas, i.e. by increasing ventilation-perfusion mismatch. Management of PH patients with chronic lung diseases requires careful evaluation and understanding of pathophysiological mechanisms. Interestingly, mediators in PAH and in fibrotic lung disease show some overlaps. Several drugs effective in PAH have been evaluated for anti-fibrotic treatment in ILD, but until today without consistent success. While new drugs with anti-fibrotic effects are now accessible, a specific evidence-based treatment for PH in ILD or COPD with or without emphysema is not yet available

Electrocardiographic alterations by pneumothorax: a case-control study with review of the literature

BACKGROUND: Numerous ECG alterations due to pneumothorax have been reported. The objective of the study was to establish the presence of ECG changes associated with pneumothorax in the literature, and in a cohort of patients with proven pneumothorax compared with age- and sex-matched healthy controls. METHODS: A systematic review for ECG alterations associated with pneumothorax was performed. We then reviewed our hospital database for patients with pneumothorax and identified all patients with an ECG available at this time. The retrieved ECG alterations in the systematic review were identified in our pneumothorax patients and compared with a healthy sex- and age-matched control group. Accordingly, we calculated sensitivity and specificity for all alterations. RESULTS: Seventeen ECG alterations were found and defined from the systematic review. Our pneumothorax cohort consisted of 82 pneumothorax patients and 82 control patients. Specificity was mostly more than 90%, but sensitivities were low. Phasic R voltage (pneumothorax group 25.6% vs control group 1.2%), T-wave inversion (31.7% vs 2.4%), prolonged QTc (11.0% vs 2.4%), right axis deviation (14.6% vs 3.6%) and QRS voltage ratio in aVF/I >2 (41.5% vs 22.0%) were significantly more frequent in pneumothorax patients compared with controls. CONCLUSION: The sensitivity of published ECG signs in predicting pneumothorax in our cohort was low, which means that ECG findings are an unsuitable tool for pneumothorax screening. However, presence of these ECG signs might raise a suspicion of pneumothorax in patients presenting with dyspnoea, or unclear chest discomfort

Oxidative stress in hypobaric hypoxia and influence on vessel-tone modifying mediators

Increased pulmonary artery pressure is a well-known phenomenon of hypoxia and is seen in patients with chronic pulmonary diseases, and also in mountaineers on high altitude expedition. Different mediators are known to regulate pulmonary artery vessel tone. However, exact mechanisms are not fully understood and a multimodal process consisting of a whole panel of mediators is supposed to cause pulmonary artery vasoconstriction. We hypothesized that increased hypoxemia is associated with an increase in vasoconstrictive mediators and decrease of vasodilatators leading to a vasoconstrictive net effect. Furthermore, we suggested oxidative stress being partly involved in changement of these parameters. Oxygen saturation (Sao2) and clinical parameters were assessed in 34 volunteers before and during a Swiss research expedition to Mount Muztagh Ata (7549 m) in Western China. Blood samples were taken at four different sites up to an altitude of 6865 m. A mass spectrometry-based targeted metabolomic platform was used to detect multiple parameters, and revealed functional impairment of enzymes that require oxidation-sensitive cofactors. Specifically, the tetrahydrobiopterin (BH4)-dependent enzyme nitric oxide synthase (NOS) showed significantly lower activities (citrulline-to-arginine ratio decreased from baseline median 0.21 to 0.14 at 6265 m), indicating lower NO availability resulting in less vasodilatative activity. Correspondingly, an increase in systemic oxidative stress was found with a significant increase of the percentage of methionine sulfoxide from a median 6% under normoxic condition to a median level of 30% (p<0.001) in camp 1 at 5533 m. Furthermore, significant increase in vasoconstrictive mediators (e.g., tryptophan, serotonin, and peroxidation-sensitive lipids) were found. During ascent up to 6865 m, significant altitude-dependent changes in multiple vessel-tone modifying mediators with excess in vasoconstrictive metabolites could be demonstrated. These changes, as well as highly significant increase in systemic oxidative stress, may be predictive for increase in acute mountain sickness score and changes in Sao2

Health Preference Measures in Patients with Obstructive Sleep Apnea Syndrome Undergoing Continuous Positive Airway Pressure Therapy: Data from a Randomized Trial

Background: In patients with obstructive sleep apnea syndrome (OSAS), the preference-based, health-related quality of life in terms of utility has not been extensively studied. Objective: To address this point, we compared the performance of different instruments assessing utility in patients with OSAS undergoing continuous positive airway pressure (CPAP) therapy. Materials and Methods: Data of 208 patients with OSAS (28 women, mean ± SE age 54.4 ± 0.7 years, apnea-hypopnea index (AHI) 51.9 ± 1.8/h, Epworth sleepiness score 13.4 ± 0.2) participating in a randomized trial of different CPAP modalities over 2 years were analyzed. Evaluations included sleep studies, Epworth sleepiness scale, and several utility instruments that measure subjective health preference on a scale ranging from 1 (most preferred and perfect health) to 0 (least preferred and very poor health). Results: After 2 years of CPAP therapy, the mean ± SE AHI was 6.7 ± 1.5/h and Epworth score 7.9 ± 0.4, both p < 0.001 versus baseline. Baseline utilities and changes (95% confidence interval) after 2 years of CPAP therapy were EuroQol 5-dimensions 0.79 ± 0.01, 0.02 (0.00–0.05, p = 0.064); short-form 6-dimension medical outcome questionnaire 0.72 ± 0.01, 0.06 (0.04–0.08, p < 0.001); Euro-thermometer visual analog scale 0.70 ± 0.01, 0.09 (0.07–0.12, p < 0.001); time trade-off 0.82 ± 0.01, 0.03 (0.01–0.06, p = 0.002); and standard gamble 0.82 ± 0.01, −0.01 (−0.03 to 0.02, p = 0.712). Conclusion: The short-form 6-dimensions questionnaire, the Euro-thermometer, and the time trade-off instruments reflected the major clinical improvements in OSAS, while the EuroQoL 5-dimensions and standard gamble tests were not sensitive to CPAP effects. These results indicate that the evaluation of utility of a treatment for OSAS depends critically on the instrument used, which is important from an individual and societal perspective