Discovery of the Principal Cystic Fibrosis Mutation (F508del) in Ancient DNA from Iron Age Europeans

The most common, life-threatening autosomal recessive disease of Europeans and Euro-Americans, cystic fibrosis (CF), occurs predominately in patients with the F508del mutation.1 Although F508del is currently detectable as a single allele in 1/30-1/40 Europeans2-4 and Euro-Americans,5 it has not been determined what heterozygote selective advantage(s) might account for its relatively high prevalence. Indirect evidence6 suggests that this mutation was present in Brittany at least 3000 years ago, but no direct analyses of ancient DNA have been reported to identify F508del and clarify its frequency in prehistoric inhabitants of Europe. Here we show that F508del was present in 3 of 32 Iron Age inhabitants of Austria from whom DNA could be recovered from molar teeth using procedures that fulfill authenticity criteria.7 Because these individuals, who were buried in cemeteries along the Danube river, were shown by radiocarbon dating of isolated bone collagen to have lived there during 544-255 BC, this indicates that the F508del mutation is definitely more than 2000 years old and that CF (the disease) was present among them. More generally, the apparent enrichment of this Iron Age population in F508del suggests an evolutionary advantage in their environment that can be investigated by interdisciplinary strategies of paleoepidemiology

Making A Difference

Volunteering at the ANA meant helping new Americans feel welcome in a new place. It meant helping people feel capable at new things, make connections, and feel like they belong. We assisted them to become leaders of tomorrow. By lending a helping hand to a family, we were embraced by the sharing of two totally different yet very similar cultures. They taught us, we taught the

Effect of a patient engagement tool on positive airway pressure adherence: analysis of a German healthcare provider database

Objective/background: This study investigated the addition of a real-time feedback patient engagement tool on positive airway pressure (PAP) adherence when added to a proactive telemedicine strategy. Patients/methods: Data from a German healthcare provider (ResMed Healthcare Germany) were retrospectively analyzed. Patients who first started PAP therapy between 1 September 2009 and 30 April 2014, and were managed using telemedicine (AirView™; proactive care) or telemedicine + patient engagement tool (AirView™ + myAir™; patient engagement) were eligible. Patient demographics, therapy start date, sleep- disordered breathing indices, device usage hours, and therapy termination rate were obtained and compared between the two groups. Results: The first 500 patients managed by telemedicine-guided care and a patient engagement tool were matched with 500 patients managed by telemedicine-guided care only. The proportion of nights with device usage ≥4 h was 77 ± 25% in the patient engagement group versus 63 ± 32% in the proactive care group (p < 0.001). Therapy termination occurred less often in the patient engagement group (p < 0.001). The apnea-hypopnea index was similar in the two groups, but leak was significantly lower in the patient engagement versus proactive care group (2.7 ± 4.0 vs 4.1 ± 5.3 L/min; p < 0.001). Conclusions: Addition of a patient engagement tool to telemonitoring-guided proactive care was associated with higher device usage and lower leak. This suggests that addition of an engagement tool may help improve PAP therapy adherence and reduce mask leak

Determining the prevalence and predictors of sleep disordered breathing in patients with chronic heart failure: rationale and design of the SCHLA-HF registry

BACKGROUND: The objective of the SCHLA-HF registry is to investigate the prevalence of sleep-disordered breathing (SDB) in patients with chronic heart failure with reduced left ventricular systolic function (HF-REF) and to determine predictors of SDB in such patients. METHODS: Cardiologists in private practices and in hospitals in Germany are asked to document patients with HF-REF into the prospective SCHLA-HF registry if they meet predefined inclusion and exclusion criteria. Screening was started in October 2007 and enrolment was completed at the end of May 2013. After enrolment in the registry, patients are screened for SDB. SDB screening is mainly undertaken using the validated 2-channel ApneaLink™ device (nasal flow and pulse oximetry; ResMed Ltd., Sydney, Australia). Patients with a significant number of apneas and hypopneas per hour recording time (AHI ≥15/h) and/or clinical symptoms suspicious of SDB will be referred to a cooperating sleep clinic for an attended in-lab polysomnography with certified scoring where the definite diagnosis and, if applicable, the differentiation between obstructive and central sleep apnea will be made. Suggested treatment will be documented. DISCUSSION: Registries play an important role in facilitating advances in the understanding and management of cardiovascular disease. The SCHLA-HF registry will provide consistent data on a large group of patients with HF-REF that will help to answer questions on the prevalence, risk factors, gender differences and stability of SDB in these patients by cross-sectional analyses. Further insight into the development of SDB will be gained by extension of the registry to include longitudinal data

Adaptive servo-ventilation for central sleep apnea in heart failure

Background Central sleep apnea is associated with poor prognosis and death in patients with heart failure. Adaptive servo-ventilation is a therapy that uses a noninvasive ventilator to treat central sleep apnea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure. We investigated the effects of adaptive servo-ventilation in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea. Methods We randomly assigned 1325 patients with a left ventricular ejection fraction of 45% or less, an apnea–hypopnea index (AHI) of 15 or more events (occurrences of apnea or hypopnea) per hour, and a predominance of central events to receive guideline-based medical treatment with adaptive servo-ventilation or guideline-based medical treatment alone (control). The primary end point in the time-to-event analysis was the first event of death from any cause, lifesaving cardiovascular intervention (cardiac transplantation, implantation of a ventricular assist device, resuscitation after sudden cardiac arrest, or appropriate lifesaving shock), or unplanned hospitalization for worsening heart failure. Results In the adaptive servo-ventilation group, the mean AHI at 12 months was 6.6 events per hour. The incidence of the primary end point did not differ significantly between the adaptive servo-ventilation group and the control group (54.1% and 50.8%, respectively; hazard ratio, 1.13; 95% confidence interval [CI], 0.97 to 1.31; P=0.10). All-cause mortality and cardiovascular mortality were significantly higher in the adaptive servo-ventilation group than in the control group (hazard ratio for death from any cause, 1.28; 95% CI, 1.06 to 1.55; P=0.01; and hazard ratio for cardiovascular death, 1.34; 95% CI, 1.09 to 1.65; P=0.006). Conclusions Adaptive servo-ventilation had no significant effect on the primary end point in patients who had heart failure with reduced ejection fraction and predominantly central sleep apnea, but all-cause and cardiovascular mortality were both increased with this therapy. (Funded by ResMed and others; SERVE-HF ClinicalTrials.gov number, NCT00733343. opens in new tab.

Cardiovascular risk in patients with alpha-1-antitrypsin deficiency

Background: Alpha-1-antitrypsin deficiency (AATD) is a rare inherited condition caused by mutations of the SERPINA1 gene that is associated with the development of a COPD like lung disease. The comorbidities in patients with AATD-related lung diseases are not well defined. The aim of this study was to analyze the clinical phenotype of AATD patients within the German COPD cohort study COSYCONET (“COPD and SYstemic consequences-COmorbidities NETwork”) cohort focusing on the distribution of comorbidities. Method and results: The data from 2645 COSYCONET patients, including 139 AATD patients (110 with and 29 without augmentation therapy), were analyzed by descriptive statistics and regression analyses. We found significantly lower prevalence of cardiovascular comorbidities in AATD patients as compared to non-AATD COPD patients. After correction for age, pack years, body mass index, and sex, the differences were still significant for coronary artery disease (p = 0.002) and the prevalence of peripheral artery disease as determined by an ankle-brachial-index <= 0.9 (p = 0.035). Also the distribution of other comorbidities such as bronchiectasis differed between AATD and non-deficient COPD. Conclusion: AATD is associated with a lower prevalence of cardiovascular disease, the underlying mechanisms need further investigation

Verticalization of bacterial biofilms

Biofilms are communities of bacteria adhered to surfaces. Recently, biofilms of rod-shaped bacteria were observed at single-cell resolution and shown to develop from a disordered, two-dimensional layer of founder cells into a three-dimensional structure with a vertically-aligned core. Here, we elucidate the physical mechanism underpinning this transition using a combination of agent-based and continuum modeling. We find that verticalization proceeds through a series of localized mechanical instabilities on the cellular scale. For short cells, these instabilities are primarily triggered by cell division, whereas long cells are more likely to be peeled off the surface by nearby vertical cells, creating an "inverse domino effect". The interplay between cell growth and cell verticalization gives rise to an exotic mechanical state in which the effective surface pressure becomes constant throughout the growing core of the biofilm surface layer. This dynamical isobaricity determines the expansion speed of a biofilm cluster and thereby governs how cells access the third dimension. In particular, theory predicts that a longer average cell length yields more rapidly expanding, flatter biofilms. We experimentally show that such changes in biofilm development occur by exploiting chemicals that modulate cell length.Comment: Main text 10 pages, 4 figures; Supplementary Information 35 pages, 15 figure

Effectiveness of a 3-weeks hospital-based outpatient high intensity pulmonary strength and endurance training program for patients with advanced chronic obstructive pulmonary disease (COPD)

Die Trainingstherapie hat sich als wichtige evidenzbasierte Maßnahme im Management der mittelschweren bis schweren chronisch obstruktiven Lungenerkrankung (COPD) nach Leitlinie der „Globalen Initiative für chronisch obstruktive Lungenerkrankungen“ (GOLD) etabliert. Körperliches Training wird als zentraler Bestandteil der multimodalen Therapie eingestuft. Die eingesetzten Trainingskonzepte unterscheiden sich insbesondere bezüglich Trainingsintensität und Trainingsdauer. In dieser Studie wurden die Effekte einer 3-wöchigen Trainingstherapie bei Patienten mit COPD im GOLD-Stadium II bis IV im Vergleich zum Lungensport von gleicher Dauer analysiert. Es handelte sich um ein Parallelgruppendesign mit jeweils 20 Patienten im Alter von 66 Jahren in der Trainingsgruppe und von 63 Jahren in der Lungensportgruppe. In der Trainingsgruppe erfolge eine multimodale Trainingstherapie unter Einschluss eines submaximal dosierten Kraft-/ Ausdauertrainings an jeweils 3 Tagen der Woche in 3 aufeinander folgenden Wochen. In der Kontrollgruppe nahmen die Patienten einmal wöchentlich an den Aktivitäten einer Lungensportgruppe teil. Als Erfolgsparameter wurden Spirometrie, Bodyplethysmographie, Transferfaktor für Kohlenmonoxyd, 6-Minuten Gehstrecke und Fragebögen zur generellen „Short-Form-36“ (SF36) und zur krankheitsspezifischen Lebensqualität „Chronic Respiratory Questionnaire“ (CRQ) sowie Blutuntersuchungen „C-reaktives Protein“ (CRP) und „B-derived Natriuretic Peptide“ (BNP) eingesetzt. In beiden Gruppen haben alle 20 Patienten das komplette Programm absolviert. Die Trainingsgruppe erreichte eine klinisch relevante Zunahme der 6-Minuten Gehstrecke von 431m auf 476m (p<0,001), während die Kontrollgruppe keine relevante Verbesserung der Gehstrecke erreichte (465 auf 482m; p=n.s.). Im SF36 fanden sich in der Trainingsgruppe signifikante Verbesserungen der psychischen (p<0,04) und körperlichen (p<0,01) Summenscores im Verlauf von 3 Wochen. Außerdem besserte sich die krankheitsspezifische Lebensqualität bezüglich des Summenscores (p=0,01) und in den Domänen Atemnot (0,02), Krankheitsbewältigung (p<0,03) und Stimmungslage (p=0,0001) des CRQ-Fragebogens. Die Studie zeigt, dass bei Patienten mit stabiler COPD im GOLD-Stadium II-IV auch nach medikamentöser Optimierung durch Trainingstherapie eine weitere Verbesserung erreicht werden kann. Im Vergleich zum Lungensport waren die Verbesserungen durch Trainingstherapie statistisch signifikant und auch klinisch relevant. Gebessert fanden sich Belastungskapazität, belastungsinduzierte Atemnot und mehrere Parameter der generellen und krankheitsspezifischen Lebensqualität. Diese Studie belegt außerdem, dass selbst Patienten mit schwerstgadiger COPD im GOLD-Stadium IV in ambulanten Trainingsprogrammen unter physiothera-peutischer Überwachung effektiv trainiert werden können.Background: Exercise training is widely promoted as a key component in pulmonary rehabilitation for patients with chronic obstructive pulmonary disease (COPD). This study aimed to assess the effects of a 3-week hospital-based outpatient high intensity strength and endurance training program (TG) on exercise capacity, lung function and quality of life. Methods: We did a randomized, prospective, parallel-group controlled study in 40 patients with COPD (12 men and 28 women; mean age 64.7 years; FEV1 44.79% of predicted). Twenty patients were enrolled in a TG program consisting of strength- (ergometer) and endurance training, 3 times a week, for 90 minutes, and 20 patients received a conventional lung sport program (LS) once a week. The following outcome parameters were assessed in weekly intervals: spirometry and bodybox data, exercise capacity (6MWD), and quality of life (SF36, CRQ). Results: Neither lung function data nor breathlessness scores on the Borg-scale changed significantly. Exercise tolerance as assessed by the 6MWD increased significantly from 431m to 476m (p<0.001) in the TG group. There was an improvement of the mental summary score from 23.8 to 24.3 (p<0.04) and of the physical summary score from 24.1 to 24.7 p<0.01) in the SF36 questionnaire. In addition, the CRQ domains dyspnea (p=0.03), emotion (p=0.0001) and mastery (p=0.03) improved significantly. The CRQ summary score improved from 18.0 to 19.9 (p=0.01). In the control group (LS) there was no significant change in exercise capacity or quality of life. Conclusion: Even in patients with advanced COPD a 3-weeks hospital-based outpatient high intensity strength and endurance training program results in improvements of exercise tolerance and quality of life without changes in lung function

Effect of the Heat Flux Density on the Evaporation Rate of a Distilled Water Drop

This paper presents the experimental dependence of the evaporation rate of a nondeaerated distilled water drop from the heat flux density on the surfaces of non-ferrous metals (copper and brass). A drop was placed on a heated substrate by electronic dosing device. To obtain drop profile we use a shadow optical system; drop symmetry was controlled by a high-speed video camera. It was found that the evaporation rate of a drop on a copper substrate is greater than on a brass. The evaporation rate increases intensively with raising volume of a drop. Calculated values of the heat flux density and the corresponding evaporation rates are presented in this work. The evaporation rate is found to increase intensively on the brass substrate with raising the heat flux density