There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a ...variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se. To explore this hypothesis, we developed a highly specific ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels correlated strongly with age, revealing much lower concentrations in older (avg. 58.1 years) compared to younger (avg. 27.6 years) individuals. This difference between the age groups was enhanced after acidification of the plasmas (p<0.0001), possibly reflecting a decrease of alpha-synuclein-antibody complexes or chaperone activity in older individuals. Our results support the concept that alpha-synuclein homeostasis may be impaired early on, possibly due to disturbance of the proteostasis network, a key component of healthy aging. Thus, alpha-synuclein may be a novel biomarker of aging, a factor that should be considered when analyzing its presence in biological specimens.
The etiology of sleep bruxism in obstructive sleep apnea (OSA) patients is not yet fully clarified. This prospective clinical study aimed to investigate the connection between probable sleep bruxism, ...electromyographic muscle tone, and respiratory sleep patterns recorded during polysomnography.
106 patients with OSA (74 males, 31 females, mean age: 56.1 ± 11.4 years) were divided into two groups (sleep bruxism: SB; no sleep bruxism: NSB). Probable SB were based on the AASM criteria: self-report of clenching/grinding, orofacial symptoms upon awakening, abnormal tooth wear and hypertrophy of the masseter muscle. Both groups underwent clinical examination for painful muscle symptoms aligned with Temporomandibular Disorders Diagnostic Criteria (DC/TMD), such as myalgia, myofascial pain, and headache attributed to temporomandibular disorder. Additionally, non-complaint positive muscle palpation and orofacial-related limitations (Jaw Functional Limited Scale-20: JFLS-20) were assessed. A one-night polysomnography with electromyographic masseter muscle tone (EMG) measurement was performed. Descriptive data, inter-group comparisons and multivariate logistic regression were calculated.
OSA patients had a 37.1% prevalence of SB. EMG muscle tone (N1-N3, REM; P = 0.001) and the number of hypopneas (P = 0.042) were significantly higher in the sleep bruxism group. While measures like apnea-hypopnea-index (AHI), respiratory-disturbance-index (RDI), apnea index (AI), hypopnea-index (HI), number of arousals, and heart rate (1/min) were elevated in sleep bruxers, the differences were not statistically significant. There was no difference in sleep efficiency (SE; P = 0.403). Non-complaint masseter muscle palpation (61.5%; P = 0.015) and myalgia (41%; P = 0.010) were significant higher in SB patients. Multivariate logistic regression showed a significant contribution of EMG muscle tone and JFLS-20 to bruxism risk.
Increased EMG muscle tone and orofacial limitations can predict sleep bruxism in OSA patients. Besides, SB patients suffer more from sleep disorder breathing. Thus, sleep bruxism seems to be not only an oral health related problem in obstructive apnea. Consequently, interdisciplinary interventions are crucial for effectively treating these patients.
The study was approved by the Ethics Committee of Philipps-University Marburg (reg. no. 13/22-2022) and registered at the "German Clinical Trial Register, DRKS" (DRKS0002959).
The eruption of the Eyjafjallajökull volcano, Iceland, in April and May 2010 caused unprecedented disruptions of European air traffic showing that timely monitoring of volcanic ash and SO2 dispersion ...as well as the corresponding plume heights are important for aviation safety. This paper describes the observations of SO2 and BrO columns in the eruption plume and the determination of the SO2 plume height using the GOME‐2 satellite instrument. During the eruptive period in May 2010, SO2 total columns of up to ∼20 DU and BrO columns of ∼7.7 × 1013 molec/cm2 were detected. The BrO/SO2 ratio estimated from the GOME‐2 observations of the Eyjafjallajökull eruption varies from 1.1 × 10−4 to 2.1 × 10−4. The SO2 plume heights estimated from the GOME‐2 observations on 5 May range from 8–13 km and mostly agree within 1–3 km with visual observations, radar data and modeling results. Furthermore, the GOME‐2 SO2 observations are compared with in situ measurements of the DLR Falcon aircraft on 17 and 18 May 2010 and with Brewer instruments at Valentia, Ireland and Hohenpeissenberg, Germany. The SO2 columns derived from the Falcon profile measurements range from 0.6–4.7 DU and the comparison with the GOME‐2 measurements shows a good agreement, mainly within 1 DU. The Brewer observations at Hohenpeissenberg also agree well with the GOME‐2 measurements with a daily average SO2 column of ∼1.3 DU during the overpass of the SO2 cloud on 18 May, whereas the Brewer instrument at Valentia shows up to 50% higher SO2 columns (∼8 DU) on 11 May.
Key Points
SO2 and BrO in the eruption plume of Eyjafjallajokull using GOME‐2
Direct retreival of the SO2 plume height from GOME‐2 measurements
Comparison of GOME‐2 data with model simulations, Falcon and Brewer observations
Abstract
STUDY QUESTION
In oocytes of advanced maternal age (AMA) women, what are the mechanisms leading to aneuploidy and what is the association of aneuploidy with embryo development?
SUMMARY ...ANSWER
Known chromosome segregation errors such as precocious separation of sister chromatids explained 90.4% of abnormal chromosome copy numbers in polar bodies (PBs), underlying impaired embryo development.
WHAT IS KNOWN ALREADY
Meiotic chromosomal aneuploidies in oocytes correlate with AMA (>35 years) and can affect over half of oocytes in this age group. This underlies the rationale for PB biopsy as a form of early preimplantation genetic testing for aneuploidy (PGT-A), as performed in the ‘ESHRE STudy into the Evaluation of oocyte Euploidy by Microarray analysis’ (ESTEEM) randomized controlled trial (RCT). So far, chromosome analysis of oocytes and PBs has shown that precocious separation of sister chromatids (PSSC), Meiosis II (MII) non-disjunction (ND), and reverse segregation (RS) are the main mechanisms leading to aneuploidy in oocytes.
STUDY DESIGN, SIZE, DURATION
Data were sourced from the ESTEEM study, a multicentre RCT from seven European centres to assess the clinical utility of PGT-A on PBs using array comparative genomic hybridization (aCGH) in patients of AMA (36–40 years). This included data on the chromosome complement in PB pairs (PGT-A group), and on embryo morphology in a subset of embryos, up to Day 6 post-insemination, from both the intervention (PB biopsy and PGT-A) and control groups.
PARTICIPANTS/MATERIALS, SETTING, METHODS
ESTEEM recruited 396 AMA patients: 205 in the intervention group and 191 in the control group. Complete genetic data from 693 PB pairs were analysed. Additionally, the morphology from 1034 embryos generated from fertilized oocytes (two pronuclei) in the PB biopsy group and 1082 in the control group were used for statistical analysis.
MAIN RESULTS AND THE ROLE OF CHANCE
Overall, 461/693 PB pairs showed abnormal segregation in 1162/10 810 chromosomes. The main observed abnormal segregations were compatible with PSSC in Meiosis I (MI) (n = 568/1162; 48.9%), ND of chromatids in MII or RS (n = 417/1162; 35.9%), and less frequently ND in MI (n = 65/1162; 5.6%). For 112 chromosomes (112/1162; 9.6%), we observed a chromosome copy number in the first PB (PB1) and second PB (PB2) that is not explained by any of the known mechanisms causing aneuploidy in oocytes. We observed that embryos in the PGT-A arm of the RCT did not have a significantly different morphology between 2 and 6 days post-insemination compared to the control group, indicating that PB biopsy did not affect embryo quality. Following age-adjusted multilevel mixed-effect ordinal logistic regression models performed for each embryo evaluation day, aneuploidy was associated with a decrease in embryo quality on Day 3 (adjusted odds ratio (aOR) 0.62, 95% CI 0.43–0.90), Day 4 (aOR 0.15, 95% CI 0.06–0.39), and Day 5 (aOR 0.28, 95% CI 0.14–0.58).
LIMITATIONS, REASON FOR CAUTION
RS cannot be distinguished from normal segregation or MII ND using aCGH. The observed segregations were based on the detected copy number of PB1 and PB2 only and were not confirmed by the analysis of embryos. The embryo morphology assessment was static and single observer.
WIDER IMPLICATIONS OF THE FINDINGS
Our finding of frequent unexplained chromosome copy numbers in PBs indicates that our knowledge of the mechanisms causing aneuploidy in oocytes is incomplete. It challenges the dogma that aneuploidy in oocytes is exclusively caused by mis-segregation of chromosomes during MI and MII.
STUDY FUNDING/COMPETING INTEREST(S)
Data were mined from a study funded by ESHRE. Illumina provided microarrays and other consumables necessary for aCGH testing of PBs. None of the authors have competing interests.
TRIAL REGISTRATION NUMBER
Data were mined from the ESTEEM study (ClinicalTrials.gov Identifier NCT01532284).
Introduction: In clinical practice, wheezing and coughing represent a worsening of the respiratory situation of COPD patients and should be monitored long-term during and after an Acute Exacerbation ...of COPD (AECOPD) to observe the therapy. We investigated if overnight monitoring of wheezing and coughing is feasible during AECOPD and whether automatic long--term monitoring enables an objective assessment during and after an AECOPD. Methods: In 14 patients (age: 56-80 years) with pre-existing COPD (stages B-D) nighttime wheezing and coughing events were monitored for a period of three weeks. The portable LEOSoundR monitor recorded three nights into AECOPD (nights 1, 3 and 6) during the hospital stay, and the 20th night post-AECOPD ambulatory. Before each recording the subjective symptom severity was assessed by a COPD Assessment Test (CAT) and a Modified British Medical Research Council (MMRC) dyspnoea index questionnaire. Results: In all 14 patients, lung sounds were recorded in good quality during each of the 4 recording nights. Wheezing ranged between 5% and 90% (79-539.5 minutes) of the recording time on the first night. All patients showed some coughs, in four patients coughing was particularly pronounced and largely receding over the total investigation period. As group, the percentages of wheezing and the number of coughs did not show significant differences between the four recording times. The CAT scores (p<0.001) declined over the course of investigation period, suggesting a subjective improvement of symptoms. Conclusion: The observational study showed that standardized long-term recording can be performed in high-quality during acute COPD exacerbation as it does not require the patient's cooperation. The good-quality data of coughs and wheezing were analyzed qualitatively and quantitatively. The long-term presentation of respiratory symptoms during an AECOPD offers the opportunity to evaluate factors that influence exacerbations and therapeutic approaches. Keywords: COPD, wheezing, cough, long term monitoring of respiratory sounds, CAT, exacerbation
This review presents updated information on small airways in the pathogenesis of chronic obstructive respiratory diseases. The lungs have a branching structure, segmentally divided from trachea down ...to the alveoli (generations 1 - 23). Airways can be divided into a conducting (generations 1 - 16) and a respiratory zone (generations 17 - 23). Conducting zone is mainly for air transportation, respiratory zone for gas exchange. Increasing attention has been directed to the role of small airways in chronic obstructive respiratory diseases. The small conducting airways < 2 mm in diameter are the major site of airway inflammation and obstruction in COPD. It has been shown that the last generation of small conducting airways, the terminal bronchioles, are significantly destroyed in patients with very severe COPD. At what stage in the development of COPD the loss of small airways occurs is not exactly known. The small airways represent the most important target for deposition of inhaled therapeutic particles. Currently there is no gold standard for detecting small airway dysfunction. Techniques such as spirometry and body plethysmography can provide information on air trapping. High-resolution CT enables the diagnosis of pulmonary emphysema and diseases of the large airways. Only micro-CT imaging offers the option to describe microstructure of terminal bronchioles. Impulse oscillometry, gas washout techniques and analysis of exhaled nitric oxide are diagnostic tools which have to be validated for diagnosis and treatment response of small airway diseases.
Pulmonary emphysema is characterised by irreversible destruction and enlargement of alveolar structure distal to terminal bronchioles. Small conducting airways < 2 mm in diameter are the major site ...of chronic airway inflammation and obstruction in COPD patients. 80 - 90 % of the last generation of small conducting airways, the terminal bronchioles, are destroyed in patients with very severe COPD. Recent data showing, that small airways disease is also a pathological feature in patients with COPD GOLD stage 1 and 2. Although 40 % of terminal and 60 % of transitional bronchioles were destroyed, there was no sign for emphysema. Only a significant loss of terminal and respiratory bronchioles seems to be able to induce pulmonary emphysema and respiratory symptoms.
Medication management of asthma is based on level of asthma control. GINA defined criteria for asthma control include asking about daytime symptoms, limitation of activity, nocturnal ...symptoms/awakenings and need for reliever treatment. Effective asthma control is necessary for preventing exacerbations and worsening of lung function. Standardized and validated questionnaires such as asthma control test (ACT) help to assess the level of asthma control. Asthma control is classified as controlled, partially controlled or uncontrolled. Multicenter studies like REALISE and AIRE give health care professionals information about effectiveness and adherence to medication over nearly 15 years. Asthma is still poorly controlled in more than 50 % of patients despite the availability of very effective drugs. Low adherence to the treatment, fear of systemic side effects related to long term treatment with inhaled corticosteroids, inadequate knowledge of the disease may be responsible factors for bad asthma control. Optimized tools for disease management and intensified education are necessary for therapeutic success.
Natural self-reactive antibodies in the peripheral blood may play a considerable role in the control of potentially toxic proteins that may otherwise accumulate in the aging brain. The significance ...of serum antibodies reactive against α-synuclein is not well known. We explored serum IgG levels to monomeric α-synuclein in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) with a novel and validated highly sensitive ELISA assay. Antibody levels revealed stark differences in patients compared to healthy subjects and were dependent on diagnosis, disease duration and age. Anti-α-synuclein IgG levels were increased in both patient groups, but in early DLB to a much greater extent than in AD. Increased antibody levels were most evident in younger patients, while with advanced age relatively low levels were observed, similar to healthy individuals, exhibiting stable antibody levels independent of age. Our data show the presence of differentially altered IgG levels against α-synuclein in DLB and AD, which may relate to a disturbed α-synuclein homeostasis triggered by the disease process. These observations may foster the development of novel, possibly preclinical biomarkers and immunotherapeutic strategies that target α-synuclein in neurodegenerative disease.
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