The blue supergiant Sher 25 revisited in the Gaia era

Aims. The evolutionary status of the blue supergiant Sher 25 and its membership to the massive cluster NGC 3603 are investigated. Methods. A hybrid non-LTE (local thermodynamic equilibrium) spectrum synthesis approach is employed to analyse a high-resolution optical spectrum of Sher 25 and five similar early B-type comparison stars in order to derive atmospheric parameters and elemental abundances. Fundamental stellar parameters are determined by considering stellar evolution tracks, Gaia Data Release 3 (DR3) data and complementary distance information. Interstellar reddening and the reddening law along the sight line towards Sher 25 are constrained employing UV photometry for the first time in addition to optical and infrared data. The distance to NGC 3603 is reevaluated based on Gaia DR3 data of the innermost cluster O-stars. Results. The spectroscopic distance derived from the quantitative analysis implies that Sher 25 lies in the foreground of NGC 3603, which is found to have a distance of $d_\mathrm{NGC 3603}$ = 6250$\pm$150 pc. A cluster membership is also excluded as the hourglass nebula is unaffected by the vigorous stellar winds of the cluster stars and from the different excitation signatures of the hourglass nebula and the nebula around NGC 3603. Sher 25 turns out to have a luminosity of log L/L$_\odot$ = 5.48$\pm$0.14, equivalent to that of a $\sim$27 $M_\odot$ supergiant in a single-star scenario, which is about half of the mass assumed so far, bringing it much closer in its characteristics to Sk-69{\deg}202, the progenitor of SN 1987A. Sher 25 is significantly older than NGC 3603. Further arguments for a binary (merger) evolutionary scenario of Sher 25 are discussed.Comment: 27 pages, 22 figures, Accepted for publication in Astronomy & Astrophysics, Data: https://doi.org/10.5281/zenodo.823015

Long-term persistence with evolocumab treatment and sustained reductions in LDL-cholesterol levels over 30 months: final results from the European observational HEYMANS study

BACKGROUND AND AIMS: Variability in low-density lipoprotein-cholesterol (LDL-C) level control at a population level is associated with poor cardiovascular outcomes. Limited data exist on LDL-C level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. Using data from the HEYMANS registry, this analysis aimed to assess evolocumab persistence and discontinuation over 30 months of evolocumab treatment and to evaluate at a population level the variability in LDL-C level reductions during the study period. METHODS: HEYMANS was a prospective registry of adults initiating evolocumab in routine clinical practice in 12 European countries. Data were collected for up to and including 6 months before evolocumab initiation and up to 30 months after. Evolocumab discontinuation was analysed for two time periods: 0-12 months and 12-30 months. RESULTS: In total, 1951 patients were included in the study. The median reduction in LDL-C levels was 58% within 3 months after evolocumab initiation; this reduction was maintained over 30 months. More than 90% of patients continued receiving evolocumab at 12 months and 30 months of follow-up. Of patients with an LDL-C level measurement during follow-up, approximately 85% achieved a ≥30% reduction from baseline at each follow-up visit and approximately 60% achieved a ≥50% reduction. CONCLUSIONS: Evolocumab therapy was associated with sustained LDL-C level reductions up to 30 months, and persistence with evolocumab remained high, both at 12 and 30 months. Expanding the use of monoclonal antibodies such as evolocumab could provide improvements in LDL-C level control at a population level in European clinical practice

The potential use of spectral electromyographic fatigue as a screening and outcome monitoring tool of sarcopenic back muscle alterations

Background: To examine whether or not median frequency surface electromyographic (MF-EMG) back muscle fatigue monitoring would be able to identify alterations in back muscle function in elderly muscles, if a protocol was used that allowed optimum standardization of the processes underlying electromyographic fatigue, and whether these tests were reliable from day to day. Methods: A total of 42 older (21 females; 67 (±10.5) years old) and 44 younger persons (19 females; 33 (±10) years) performed maximum isometric back extensions which were followed by one 30 s lasting 80% submaximum extension. Participants were seated on a dynamometer with their trunks 30° anteflexed, and they repeated all tests after 1-2 days and 6 weeks. SEMG was recorded bilaterally from the L1 (iliocostalis lumborum), L2 (longissimus), and L5 (multifidus) recording sites. Outcome variables included maximum back extension torque, initial MF-EMG (IMF-EMG), MF-EMG slope declines, and individual MF-EMG muscular imbalance scores. Two-factorial ANOVAs served to examine the age and gender-specific effects, and models from Generalizability Theory (G-Theory) were used for assessing retest-reliability. Results: Maximum back extension moment was non-significantly smaller in elders. IMF-EMG was overall higher in elders, with significant differences at the L5 recordings sites. In the elderly, MF-EMG fatigue declines were significantly smaller in L5, in the recording with the most negative slope, or if the slope of all electrodes was considered. Retest reliability was unanimous in young and older persons. ICC-type measurements from G-Theory of both the IMF and the fatigue slopes ranged from 0.7 to 0.85. Absolute SEM values were found clinically acceptable for the IMF-EMG, but relatively high for the fatigue slope declines. Conclusions: The MF-EMG fatigue method is able to elucidate alterations of aging back muscles. This method, thus, might be suggested as a potential biomarker to objectively identify persons at risk for sarcopenia. Considering the clinical relevance of the IMF-EMG relative to the MF-EMG slope declines, spectral EMG may also be used as an outcome monitoring tool in elderly populations

Bariatric surgery prevents carotid wall thickness progression.

BACKGROUND Bariatric surgery is a treatment option for patients with severe obesity and improves parameters of cardiovascular and/or metabolic disease. Carotid intima media thickness (C-IMT) is a surrogate measure of subclinical atherosclerosis. Previous studies showed short to mid-term arrest and even regression of C‑IMT progression following bariatric surgery. We aimed to investigate the long-term effect of weight loss on C‑IMT progression 10 years after bariatric surgery in comparison to a population-based control cohort. METHODS In total, 21 eligible patients were examined preoperatively, at 5 and 10 years after bariatric surgery. Anthropometric parameters, plasma triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), insulin, and glucose were assessed at all three study visits. C‑IMT was measured via B‑mode scans of the common carotid artery. C‑IMT progression was measured in an age-matched and BMI-matched cohort selected from the population-based Bruneck study to compare with changes in C‑IMT progression after bariatric surgery. RESULTS C‑IMT remained stable over the 10-year observation period after bariatric surgery. The control cohort showed a significant C‑IMT progression over 10 years. The difference in C‑IMT progression over 10 years was significant (p < 0.01) between both cohorts. CONCLUSION Weight loss induced by bariatric surgery halts the natural progression of C‑IMT over a 10-year observation period

Age and gender related neuromuscular pattern during trunk flexion-extension in chronic low back pain patients

Background: The root mean square surface electromyographic activity of lumbar extensor muscles during dynamic trunk flexion and extension from standing has repeatedly been recommended to objectively assess muscle function in chronic low back pain patients. However, literature addressing older patients is sparse. This cross sectional study sought to examine differences in neuromuscular activation between age groups (>60 versus 40-60 versus <40 years) and sexes during a standardized trunk flexion-extension task. Methods: A total of 216 patients (62 older, 84 middle-aged, 70 younger) performed maximum trunk extensions followed by trunk flexion extension testing thereby holding static positions at standing, half, and full trunk flexion. The lumbar extensor muscle activity and 3d-accelerometric signals intended to monitor hip and trunk position angles were recorded from the L5 (multifidus) and T4 (semispinalis thoracis) levels. Permutation ANOVA with bootstrapped confidence intervals were performed to examine for age and gender related differences. Ridge-regressions investigated the impact of physical-functional and psychological variables to the half flexion relaxation ratio (i.e. muscle activity at the half divided by that in maximum flexion position). Results: Maximum back extension torque was slightly but significantly higher in youngest compared to oldest patients if male and females were pooled. Normalized RMS-SEMG revealed highest lumbar extensor muscle activity at standing in the oldest and the female groups. Patients over 60 years showed lowest activity changes from standing to half (increments) and from half to the maximum flexion position (decrements) leading to a significantly lower half flexion relaxation ratio compared to the youngest patients. These oldest patients demonstrated the highest hip and lowest lumbothoracic changes of position angles. Females had higher regional hip and gross trunk ranges of movement compared to males. Lumbothoracic flexion and the muscle activity at standing had a significant impact on the half flexion relaxation ratio. Conclusions: The neuromuscular activation pattern and the kinematics in this trunk flexion-extension task involving static half flexion position changed according to age and sex. The test has a good potential to discriminate between impaired and unimpaired neuromuscular regulation of back extensors in cLBP patients, thereby allowing the design of more individualized exercise programs. Electronic supplementary material The online version of this article (doi:10.1186/s12984-016-0121-1) contains supplementary material, which is available to authorized users

Evidence based medicine in physical medicine and rehabilitation (English version)

In the last twenty years the term “Evidence Based Medicine (EBM)” has spread into all areas of medicine and is often used for decision-making in the medical and public health sector. It is also used to verify the significance and/or the effectiveness of different therapies. The definition of EBM is to use the physician’s individual expertise, the patient’s needs and the best external evidence for each individual patient. Today, however, the term EBM is often wrongly used as a synonym for best “external evidence”. This leads not only to a misuse of evidence based medicine but suggests a fundamental misunderstanding of the model which was created by Gordon Guyatt, David Sackett and Archibald Cochrane. This problem becomes even greater the more social insurance institutions, public healthcare providers and politicians use external evidence alone as a main guideline for financing therapies in physical medicine and general rehabilitation without taking into account the physician’s expertise and the patient’s needs.The wrong interpretation of EBM can lead to the following problems: well established clinical therapies are either questioned or not granted and are therefore withheld from patients (for example physical pain management). Absence of evidence for individual therapy methods does not prove their ineffectiveness! In this short statement the significance of EBM in physical medicine and general rehabilitation will be analysed and discussed

Low-density lipoprotein cholesterol levels exceed the recommended European threshold for PCSK9i initiation: lessons from the HEYMANS study

Aims To describe the characteristics of patients receiving evolocumab in clinical practice across 12 European countries and simulate the association between low-density lipoprotein cholesterol (LDL-C) reduction and cardiovascular (CV) risk reduction. ......................................................................................................................................................................................... Methods and results The characteristics of hyperlipidaemic patients at initiation of evolocumab and treatment patterns study—HEYMANS (n = 1952) is a prospective registry of patients ≥18 years old who initiated evolocumab from 1 August 2015 onwards. Mean (standard deviation) age was 60 (10.8), 85% had a prior CV event, 45% were diagnosed with familial hypercholesterolaemia (FH), and 60% had statin intolerance. At evolocumab initiation, 43% were receiving any statin, 16% were receiving ezetimibe without statin, and 41% received no background lipid-lowering therapy (LLT), with LDL-C levels reflecting local proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) reimbursement criteria. Median LDL-C decreased from 3.98 to 1.63 mmol/L within 3 months of evolocumab initiation and was maintained over 24 months. Overall, 58% achieved risk-based 2019 European Society of Cardiology/European Atherosclerosis Society LDL-C goals but that proportion was higher (68%) in patients receiving background LLT compared with those not receiving background LLT (44%). In patients with atherosclerotic cardiovascular disease without FH, the simulated relative CV risk reduction associated with evolocumab treatment was 34% (25–44%). ......................................................................................................................................................................................... Conclusion Across Europe, LDL-C levels at evolocumab initiation were three times higher than recommended thresholds for PCSK9i initiation, reflecting disparities between implementation and guidelines. More patients attained risk-based LDLC goals when receiving evolocumab in combination with LLT vs. those not receiving combination therapy. Population health could be improved and LDL-C goals better attained if LDL-C thresholds for PCSK9i reimbursement were lowered, enabling more patients to receive combination therapy when neede

Metabolic recovery after weight loss surgery is reflected in serum microRNAs.

Funder: Ministerio de Educación, Cultura y Deporte - SpainFunder: Fondation Leducq; FundRef: http://dx.doi.org/10.13039/501100001674Funder: Marie Skłodowska-Curie Innovative Training Network TRAIN-HEARTFunder: National Institute of Health ResearchINTRODUCTION: Bariatric surgery offers the most effective treatment for obesity, ameliorating or even reverting associated metabolic disorders, such as type 2 diabetes. We sought to determine the effects of bariatric surgery on circulating microRNAs (miRNAs) that have been implicated in the metabolic cross talk between the liver and adipose tissue. RESEARCH DESIGN AND METHODS: We measured 30 miRNAs in 155 morbidly obese patients and 47 controls and defined associations between miRNAs and metabolic parameters. Patients were followed up for 12 months after bariatric surgery. Key findings were replicated in a separate cohort of bariatric surgery patients with up to 18 months of follow-up. RESULTS: Higher circulating levels of liver-related miRNAs, such as miR-122, miR-885-5 p or miR-192 were observed in morbidly obese patients. The levels of these miRNAs were positively correlated with body mass index, percentage fat mass, blood glucose levels and liver transaminases. Elevated levels of circulating liver-derived miRNAs were reversed to levels of non-obese controls within 3 months after bariatric surgery. In contrast, putative adipose tissue-derived miRNAs remained unchanged (miR-99b) or increased (miR-221, miR-222) after bariatric surgery, suggesting a minor contribution of white adipose tissue to circulating miRNA levels. Circulating levels of liver-derived miRNAs normalized along with the endocrine and metabolic recovery of bariatric surgery, independent of the fat percentage reduction. CONCLUSIONS: Since liver miRNAs play a crucial role in the regulation of hepatic biochemical processes, future studies are warranted to assess whether they may serve as determinants or mediators of metabolic risk in morbidly obese patients

Isometric force production parameters during normal and experimental low back pain conditions

BACKGROUND: The control of force and its between-trial variability are often taken as critical determinants of motor performance. Subjects performed isometric trunk flexion and extension forces without and with experiment pain to examine if pain yields changes in the control of trunk forces. The objective of this study is to determine if experimental low back pain modifies trunk isometric force production. METHODS: Ten control subjects participated in this study. They were required to exert 50 and 75% of their isometric maximal trunk flexion and extension torque. In a learning phase preceding the non painful and painful trials, visual and verbal feedbacks were provided. Then, subjects were asked to perform 10 trials without any feedback. Time to peak torque, time to peak torque variability, peak torque variability as well as constant and absolute error in peak torque were calculated. Time to peak and peak dF/dt were computed to determine if the first peak of dF/dt could predict the peak torque achieved. RESULTS: Absolute and constant errors were higher in the presence of a painful electrical stimulation. Furthermore, peak torque variability for the higher level of force was increased with in the presence of experimental pain. The linear regressions between peak dF/dt, time to peak dF/dt and peak torque were similar for both conditions. Experimental low back pain yielded increased absolute and constant errors as well as a greater peak torque variability for the higher levels of force. The control strategy, however, remained the same between the non painful and painful condition. Cutaneous pain affects some isometric force production parameters but modifications of motor control strategies are not implemented spontaneously. CONCLUSIONS: It is hypothesized that adaptation of motor strategies to low back pain is implemented gradually over time. This would enable LBP patients to perform their daily tasks with presumably less pain and more accuracy

Complement protein C1q interacts with DC-SIGN via its globular domain, and thus may interfere with HIV-1 transmission

Dendritic Cells (DCs) are the most potent antigen presenting cells capable of priming naïve T cells. Its C-type lectin receptor, DC-SIGN, regulates a wide range of immune functions. Along with its role in HIV-1 pathogenesis through complement opsonization of the virus, DC-SIGN has recently emerged as an adaptor for complement protein C1q on the surface of immature DCs via a trimeric complex involving gC1qR, a receptor for the globular domain of C1q. Here, we have examined the nature of interaction between C1q and DC-SIGN in terms of domain localization, and implications of C1q-DC-SIGN-gC1qR complex formation on HIV-1 transmission. We first expressed and purified recombinant extracellular domains of DC-SIGN and its homologue SIGN-R as tetramers comprising of the entire extra cellular domain including the α-helical neck region, and monomers comprising of the carbohydrate recognition domain only. Direct binding studies revealed that both DC-SIGN and SIGN-R were able to bind independently to the recombinant globular head modules ghA, ghB and ghC, with ghB being the preferential binder. C1q appeared to interact with DC-SIGN or SIGN-R in a manner similar to IgG. Mutational analysis using single amino acid substitutions within the globular head modules showed that TyrB175 and LysB136 38 were critical for the C1q-DC-SIGN/SIGN-R interaction. Competitive studies revealed that gC1qR and ghB shared overlapping binding sites on DC-SIGN, implying that HIV- 1 transmission by DCs could be modulated due to the interplay of gC1qR-C1q with DC-SIGN. Since C1q, gC1qR and DC-SIGN can individually bind HIV-1, we examined how C1q and gC1qR modulated HIV-1-DC-SIGN interaction in an infection assay. Here, we report, for the first time, that C1q suppressed DC-SIGN-mediated transfer of HIV-1 to activated PBMCs, although the globular head modules did not. The protective effect of C1q was negated by the addition of gC1qR. In fact, gC1qR enhanced DC-SIGN-mediated HIV-1 transfer, suggesting its role in HIV-1 pathogenesis. Our results highlight the consequences of multiple innate immune pattern recognition molecules forming a complex that can modify their functions in a way which may be advantageous for the pathogen