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Abstract The seismic‐electromagnetic phenomenon entails the generation of transient electromagnetic signals, which can be observed both simultaneously (co‐seismic) and preceding (pre‐seismic) a seismic wave arrival. Following the most accredited hypothesis, these signals are mainly due to electrokinetic effects, generated on microscopic scale in porous media containing electrolytic fluids. Thus, the seismic‐electromagnetic signals are expected to be suitable for the detection and tracking of crustal fluids. Despite the growing interest in this phenomenon, there is a lack of freely available observational database of earthquake‐related electromagnetic signals recorded at co‐located seismic and magnetotelluric stations. To fill this gap, we set up two multicomponent monitoring stations in two seismically active areas of Southern Italy: the Gargano Promontory and the High Agri Valley. This work is both aimed to systematically analyse earthquake‐generated seismic‐electromagnetic recordings and to make the collected database accessible to the scientific community.

We present a seismic catalog (Bindi et al., 2024, https://doi.org/10.5880/GFZ.2.6.2023.010) including energy magnitude Me estimated from P waves recorded at teleseismic distances in the range 20°≤Δ≤98° and for depths shorter than 80 km. The catalog is built starting from the event catalog disseminated by GEOFON (GEOFOrschungsNetz), considering 6349 earthquakes with moment magnitude Mw≥5 occurring between 2011 and 2023. Magnitudes are computed using 1 031 396 freely available waveforms archived in EIDA (European Integrated Data Archive) and IRIS (Incorporated Research Institutions for Seismology) repositories, retrieved through the standard International Federation of Digital Seismograph Networks (FDSN) web services (https://www.fdsn.org/webservices/, last access: March 2024). A reduced, high-quality catalog for events with Mw≥5.8 and from which stations and events with only few recordings were removed forms the basis of a detailed analysis of the residuals of individual station measurements, which are decomposed into station- and event-specific terms and a term accounting for remaining variability. The derived Me values are compared to Mw computed by GEOFON and with the Me values calculated by IRIS. Software and tools developed for downloading and processing waveforms for bulk analysis and an add-on for SeisComP for real-time assessment of Me in a monitoring context are also provided alongside the catalog. The SeisComP add-on has been part of the GEOFON routine processing since December 2021 to compute and disseminate Me for major events via the existing services.

ObjectivesThis analysis characterized changes in weight in participants with obstructive sleep apnea (OSA) or narcolepsy treated with solriamfetol (Sunosi™) 37.5 (OSA only), 75, 150, or 300 mg/d.MethodsIn two 12-week, randomized, placebo-controlled trials and one 1-year open-label extension study, changes in weight were evaluated from baseline to end of study (week 12 or week 40 of the open-label extension [after up to 52 weeks of solriamfetol treatment]) in participants with OSA or narcolepsy.ResultsAfter 12 weeks of solriamfetol treatment, median percent change in weight from baseline across all solriamfetol doses was -0.84%, compared with 0.54% for placebo, in participants with OSA; and -0.07%, compared with 3.08% for placebo, in participants with narcolepsy. After up to 52 weeks of solriamfetol treatment, overall median percent change in weight from baseline was -1.76%, which showed a dose-dependent pattern (75 mg, 0.57%; 150 mg, -1.2%; 300 mg, -2.5%). Results were similar in subgroups of participants with OSA or narcolepsy, with overall median percent changes in weight of -2.2% and -1.1%, respectively. After up to 52 weeks of solriamfetol treatment, the percentage of participants with weight loss ≥5% relative to baseline was 25.7% overall and increased in a dose-dependent manner (75 mg, 4.5%; 150 mg, 17.3%; 300 mg, 32.4%). Results were similar among subgroups of participants with OSA or narcolepsy, with 26.4% and 24.2% of participants experiencing weight loss ≥5%, respectively. No weight-related treatment-emergent adverse events were serious.ConclusionsSolriamfetol treatment was associated with decreases in body weight in a dose-related manner.

IntroductionThis study investigates the interplay between body composition, dietary patterns, and physical activity across genders, focusing on gender-specific differences in food preferences and eating behaviors. Understanding these interactions is crucial for developing targeted nutritional and lifestyle interventions.MethodsA cross-sectional study was conducted with 1,333 participants (58.7% female, 41.3% male), aged 18–65 years. Participants were categorized into tertiles based on their fat mass to fat-free mass (FM-to-FFM) ratio. Data on dietary choices, eating behaviors, and physical activity were collected and analyzed to identify gender-specific trends.ResultsSignificant gender-specific differences were observed in food preferences and eating behaviors. Males experienced greater hunger in the late afternoon, while females felt more hunger in the morning. Males showed a preference for processed and red meats, whereas females preferred cooked vegetables. Eating behaviors such as meal skipping, uncontrolled eating, nocturnal eating, and taste preferences (sweet or salty) varied distinctly between FM-to-FFM tertiles and genders. Higher FM-to-FFM ratios correlated with lower physical activity levels, particularly in strength training and general sports engagement.DiscussionThese findings highlight the complex interactions between body composition, dietary habits, and lifestyle factors, emphasizing gender-specific differences. The results suggest that body composition and BMI significantly impact health-related behaviors, necessitating tailored interventions to address these differences and promote healthier lifestyles.

Approximate computing is a technique that sacrifices the accuracy of the result for an advantage in terms of power, area, and speed. It is useful for error-tolerant applications such as image and video processing. Many approximate arithmetic circuits can be devised using approximate versions of the basic binary full adder that simply adds three bits to generate carry and sum. Therefore, the approximate full adder has been the subject of extensive investigation in recent years. In this paper we present a comprehensive analysis of approximate full adders, by synthesizing in a FinFET 14 nm technology the whole set of possible designs, achievable by modifying one or more entries of the full adder truth-table. Our exhaustive analysis shows that only a few out of the many thousands of synthesized circuits perform reasonably well as approximate full adders. Our analysis re-discovers the approximate full adders already proposed in the literature and identifies some new ones. Examples of using the newly discovered approximate full adders in typical error resilient applications are provided, showing the performance and the usefulness of approximate arithmetic circuit designs in the real-world.

The European Integrated Data Archive (EIDA) is a data service within Observatories and Research Facilities for European Seismology (ORFEUS) which distributes seismological waveform data across, presently, 12 federated data centres, so-called EIDA nodes. EIDA is also integrated into the European Research Infrastructure EPOS (European Plate Observing System). The increasing need of quantifying the scientific impact of such Research Infrastructures at all levels of operations has led EIDA to develop a unified system able to provide global indicators for data delivery across all EIDA nodes. To achieve this goal, EIDA implemented a system where the numbers are collected and aggregated by each EIDA node and ingested in a centralised database, accessible through an online API. The successful implementation of the system stems from carefully identifying the relevant indicators for well-defined groups of users. The implementation combines simplicity and robustness whilst respecting the distributed design of EIDA. The architecture and implementation choices may be of interest to other multi-site data distribution research infrastructures that face the challenge of providing meaningful key performance indicators.

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (SOST and RUNX2) and advanced glycation end-products (AGEs) were impaired in T2D. We investigated Wnt signaling regulation and its association with AGEs accumulation and bone strength in T2D from bone tissue of 15 T2D and 21 non-diabetic postmenopausal women undergoing hip arthroplasty. Bone histomorphometry revealed a trend of low mineralized volume in T2D (T2D 0.249% [0.156–0.366]) vs non-diabetic subjects 0.352% [0.269–0.454]; p=0.053, as well as reduced bone strength (T2D 21.60 MPa [13.46–30.10] vs non-diabetic subjects 76.24 MPa [26.81–132.9]; p=0.002). We also showed that gene expression of Wnt agonists LEF-1 (p=0.0136) and WNT10B (p=0.0302) were lower in T2D. Conversely, gene expression of WNT5A (p=0.0232), SOST (p

Abstract The present white paper concerns the indications and recommendations of the SciSpacE Science Community to make progress in filling the gaps of knowledge that prevent us from answering the question: “How Do Gravity Alterations Affect Animal and Human Systems at a Cellular/Tissue Level?” This is one of the five major scientific issues of the ESA roadmap “Biology in Space and Analogue Environments”. Despite the many studies conducted so far on spaceflight adaptation mechanisms and related pathophysiological alterations observed in astronauts, we are not yet able to elaborate a synthetic integrated model of the many changes occurring at different system and functional levels. Consequently, it is difficult to develop credible models for predicting long-term consequences of human adaptation to the space environment, as well as to implement medical support plans for long-term missions and a strategy for preventing the possible health risks due to prolonged exposure to spaceflight beyond the low Earth orbit (LEO). The research activities suggested by the scientific community have the aim to overcome these problems by striving to connect biological and physiological aspects in a more holistic view of space adaptation effects.

Study objectivesSolriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved in the United States and European Union for excessive daytime sleepiness in adults with narcolepsy (75-150 mg/day) or obstructive sleep apnea (OSA; 37.5-150 mg/day). In 12-week studies, solriamfetol was associated with improvements in quality of life in participants with narcolepsy or OSA. These analyses evaluated the long-term effects of solriamfetol on quality of life.MethodsParticipants with narcolepsy or OSA who completed previous solriamfetol studies were eligible. A 2-week titration was followed by a maintenance phase ≤ 50 weeks (stable doses: 75, 150, or 300 mg/day). Quality of life assessments included Functional Outcomes of Sleep Questionnaire short version, Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, and 36-Item Short Form Health Survey version 2. Mean (standard deviation) changes from baseline to end of study were evaluated. Data were summarized descriptively. Adverse events were assessed.ResultsSafety population comprised 643 participants (417 OSA, 226 narcolepsy). Solriamfetol improved Functional Outcomes of Sleep Questionnaire short version Total scores (mean change [standard deviation], 3.7 [3.0]) and 36-Item Short Form Health Survey version 2 Physical and Mental Component Summary scores (3.1 [6.9] and 4.3 [8.4], respectively); improvements were sustained throughout treatment. On Work Productivity and Activity Impairment Questionnaire: Specific Health Problem, solriamfetol reduced (improved) % presenteeism, % overall work impairment, and % activity impairment by a minimum of 25%. Common adverse events (≥ 5%): headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, decreased appetite, and upper respiratory tract infection.ConclusionsLong-term solriamfetol treatment was associated with clinically meaningful, sustained improvements in functional status, work productivity, and quality of life for up to 52 weeks. Adverse events were similar between narcolepsy and OSA.Clinical trial registrationRegistry: ClinicalTrials.gov; Name: A Long-Term Safety Study of JZP-110 in the Treatment of Excessive Sleepiness in Subjects with Narcolepsy or OSA; Identifier: NCT02348632; URL: https://clinicaltrials.gov/ct2/show/NCT02348632.CitationWeaver TE, Pepin J-L, Schwab R, et al. Long-term effects of solriamfetol on quality of life and work productivity in participants with excessive daytime sleepiness associated with narcolepsy or obstructive sleep apnea. J Clin Sleep Med. 2021;17(10):1995-2007.

Abstract A major aim in the study of crustal fluids is the development of automatic methodologies for monitoring deep‐source, non‐volcanic gas emissions’ spatio‐temporal evolution. Crustal fluids play a significant role in the generation of large earthquakes and the characterization of their emissions on the surface can be essential for better understanding crustal processes generating earthquakes. We investigate seismic tremors recorded over 4 days in 2019 at the Mefite d’Ansanto (southern Apennines, Italy) that is located at the northern end of the fault system that generated the Mw 6.9 1980 Irpinia Earthquake. The Mefite d’Ansanto is hypothesized to be the largest natural, non‐volcanic, CO2‐rich gas emission on Earth. The seismic tremor is studied by employing a dense temporary seismic network and an automated detection algorithm based on non‐parametric statistics of the recorded signal amplitudes. We extracted signal characteristics (RMS amplitude and statistical moments of amplitudes both in time and frequency domains) for use in the subsequent supervised machine‐learning classification of the target tremor and accidently detected anthropogenic and background noise. The data set is used for the training and optimization of station‐based KNN (k‐Nearest‐Neighbors) binary classifiers obtaining good classification performances with a median overall accuracy across all stations of 92.8%. The classified tremor displayed common features at all stations: variable duration (16 s to 30–40 min), broad peak frequency (4–20 Hz) with varying amplitudes, and two types of signals: (a) long‐duration, high‐amplitude tremor and (b) pulsating tremor. Higher tremor amplitudes recorded at stations closer to local bubbling and pressurized vents suggest multiple local tremor sources.

IntroductionFood preferences are influenced by various factors, such as culture, age, and gender. The relationship between food tastes, meal preferences, and eating habits has been studied extensively in recent years; however, research on gender differences in these fields still needs to be addressed. The aim of this study was to investigate gender differences in food preferences and eating habits through self-administered questionnaires in a large Italian population sample.MethodsThe online survey included questions on food tastes, meal preferences, eating habits, and sport involvement.ResultsThe results of the study underline significant gender-specific dietary tendencies among the 2198 participants (1314 females and 884 males, average age 41.1 ± 12.7 yrs). The majority of subjects were in the annual income range between €20,000 and €40,000. Our analysis reveals significant gender differences in dietary preferences and eating habits. Men prefer red and processed meat, with significantly higher consumption rates than women. Women, on the other hand, show a greater inclination towards vegetables, whole grains, tofu, and high-cocoa-content dark chocolate, aligning with healthier food choices. The study also found differences in eating behaviors, including the frequency of meals, snacking habits, and hunger patterns: women tend to eat more frequently and report higher levels of hunger in the morning, while men tend to skip snacks. Furthermore, differences extend to eating contexts, such as the speed of eating, eating out, and eating alone, with men more likely to eat quickly and dine out. Episodes of uncontrolled eating without hunger also differ, with women reporting these behaviors more frequently than men. In addition, the analysis of sports preferences showed distinct patterns, with a lower percentage of women playing sports and those who do play sports preferring endurance and strength training, while men prefer strength training and endurance sports.DiscussionThese findings elucidate the complex interplay of biological, cultural, and gender-based factors in shaping dietary preferences and eating behaviors. In particular, our study reveals that gender dynamics significantly influence food choice and eating habits: women tend to choose healthier foods and eat regular meals, while men show preferences for specific tastes and meal-related behaviors. This analysis underscores the nuanced differences between male and female dietary patterns, influenced not only by inherent biological factors such as genetics and hormonal responses but also by societal norms and cultural contexts. Taken together, our results highlight the importance of integrating different perspectives, thus providing valuable insights into the development of public health strategies and tailored nutrition interventions aimed at chronic disease prevention.

The causes and metabolic consequences of lipohypertrophy (LH) from incorrect insulin injection techniques have been well-known for a long time and are the subject of countless publications. However, only some researchers propose structured research modalities for LH and programs to teach patients how to prevent them and minimize their effects, thus contributing to complete rehabilitation. Experts and scientific societies have produced consensus documents and recommendations to spread the culture of LH and its complications among clinicians. However, they should go deeper into LH detection methods. This short article analyzes the recent literature on the best way to explore and find more or less evident LH lesions by using a structured and validated clinical methodology to benefit the many clinicians without access to technological equipment such as ultrasonography. This text also aims to bring awareness that since the last published recommendations on injection techniques, new needles for insulin injection, more technologically advanced and suitable for specific populations, have come to market but still need a thorough evaluation.

Study objectivesTo evaluate long-term safety and maintenance of efficacy of solriamfetol treatment for excessive daytime sleepiness in narcolepsy and obstructive sleep apnea (OSA).MethodsParticipants with narcolepsy or OSA who completed a prior solriamfetol study were eligible. A 2-week titration period was followed by a maintenance phase (up to 50 weeks). Efficacy was assessed by Epworth Sleepiness Scale (ESS) and Patient and Clinical Global Impression of Change (PGI-C and CGI-C, respectively). After approximately 6 months of treatment, a subgroup entered a 2-week placebo-controlled randomized withdrawal (RW) phase. Change in ESS from beginning to end of the RW phase was the primary endpoint; PGI-C and CGI-C were secondary endpoints. Safety was assessed throughout the study.ResultsIn the maintenance phase, solriamfetol-treated participants demonstrated clinically meaningful improvements on ESS, PGI-C, and CGI-C. In the RW phase, least squares mean change on ESS was 1.6 in participants continuing solriamfetol versus 5.3 in participants switched to placebo (p < .0001). For both secondary endpoints, higher percentages of participants receiving placebo were reported as worse at the end of the RW phase versus solriamfetol (p < .0001). Common treatment-emergent adverse events (TEAEs) with solriamfetol were headache, nausea, nasopharyngitis, insomnia, dry mouth, anxiety, decreased appetite, and upper respiratory tract infection; 27 (4.2%) participants experienced at least one serious TEAE, and 61 (9.5%) withdrew because of TEAEs.ConclusionsThis study demonstrated long-term maintenance of efficacy of solriamfetol under open-label and double-blind, placebo-controlled conditions. Safety profile of solriamfetol was consistent with previous 12-week studies; no new safety concerns were identified.Trial registrationNCT02348632.

The number of adult individuals with insulin-treated diabetes mellitus (DM) is steadily increasing worldwide. The main local complications of insulin injection are lipohypertrophies (LHs), i.e., subcutaneous nodules consisting of aggregates of macro-adipocytes and fibrin. These nodules result from errors repeatedly made by patients while injecting insulin. Despite being very common, LH lesions/nodules due to incorrect insulin injection techniques are often flat and hardly visible and thus require thorough deep palpation examination and ultrasonography (US) for detection. Identifying LHs is crucial, especially in elderly and frail subjects, because they may eventually result in poor diabetes control due to associated unpredictable insulin release patterns. Raising awareness of the adequate detection of LHs and their clinical consequences is crucial and urgent. A call to action is required on this topic at all levels of undergraduate and postgraduate education.

This cross-sectional study analyses differences in dietary habits, taste preferences, variety of protein sources and body composition (BC) profiles among individuals following omnivorous, flexitarian, lacto-ovo-vegetarian and pescatarian diets. Furthermore, it assesses the correlations between these dietary patterns and various sports, classified by exercise intensity, in relation to BC parameters. The study analysed the eating habits and BC data of 1342 participants aged 18–65 years, classified into four diet groups based on their 7-day food diaries and questionnaire responses. Our analysis revealed gender- and age-related differences in weekly food consumption and protein source variety, with men generally consuming more meat, processed meat and fish than women, especially in younger age groups. Differences in dairy and soy consumption were also noted between age groups, while legume and soy preferences showed no gender disparity across all ages. Among non-sporting individuals, vegetarians exhibited lower fat mass (FM%) compared to other diets, while among athletes, vegetarians and pescatarians in in endurance and strength sports, respectively, displayed lower FM%, with flexitarians and omnivores in endurance sports showing higher FM%. Non-athletic omnivores and vegetarians demonstrated a greater proportion of body protein, while among athletes, those engaged in strength training exhibited a higher body protein content across all dietary groups compared to those in endurance training. Among non-athletic groups, vegetarians exhibited the lowest FM/FFM (fat mass/fat-free mass) ratio, while among athletes, vegetarians in endurance sports and participants in strength training across other diets showed lower FM/FFM ratios. The results emphasise the complex interaction between diet, BC and lifestyle choices, revealing how different combinations of diet and sport are associated with optimised BC.

Fundamentals of Macroscopic Chemical Analysis is a newly developed foundation-level course that integrates concepts from traditional physical and analytical chemistry courses. The course was designed to serve majors in chemistry, biochemistry, and biology as well as pre-health professional students. The main goal of this course is to develop the ideas of energy, stability, and direction of changes for chemical systems. Students develop the idea of free energy through thermodynamic laws and apply the concept of free energy to develop the quantitative picture of selected physical and chemical equilibrium systems.

Immune checkpoint inhibitors (ICIs) has revolutionized the treatment of different advanced solid tumors, but most patients develop severe immune-related adverse events (irAEs). Although a bi-directional crosstalk between bone and immune systems is widely described, the effect of ICIs on the skeleton is poorly investigated. Here, we analyze the changes in plasma levels of type I collagen C-terminal telopeptide (CTX-I) and N-terminal propeptide of type I procollagen (PINP), reference makers of bone turnover, in patients treated with ICIs and their association with clinical outcome.A series of 44 patients affected by advanced non-small cell lung cancer or renal cell carcinoma, without bone metastases, and treated with ICIs as monotherapy were enrolled. CTX-I and PINP plasma levels were assessed at baseline and after 3 months of ICIs treatment by ELISA kits.A significant increase of CTX-I with a concomitant decreasing trend towards the reduction of PINP was observed after 3 months of treatment. Intriguingly, CTX-I increase was associated with poor prognosis in terms of treatment response and survival. These data suggest a direct relationship between ICIs treatment, increased osteoclast activity and potential fracture risk.Overall, this study reveals that ICIs may act as triggers for skeletal events, and if confirmed in larger prospective studies, it would identify a new class of skeletal-related irAEs.

Abstract Pompe disease is a metabolic myopathy due to acid alpha‐glucosidase deficiency. In addition to glycogen storage, secondary dysregulation of cellular functions, such as autophagy and oxidative stress, contributes to the disease pathophysiology. We have tested whether oxidative stress impacts on enzyme replacement therapy with recombinant human alpha‐glucosidase (rhGAA), currently the standard of care for Pompe disease patients, and whether correction of oxidative stress may be beneficial for rhGAA therapy. We found elevated oxidative stress levels in tissues from the Pompe disease murine model and in patients’ cells. In cells, stress levels inversely correlated with the ability of rhGAA to correct the enzymatic deficiency. Antioxidants (N‐acetylcysteine, idebenone, resveratrol, edaravone) improved alpha‐glucosidase activity in rhGAA‐treated cells, enhanced enzyme processing, and improved mannose‐6‐phosphate receptor localization. When co‐administered with rhGAA, antioxidants improved alpha‐glucosidase activity in tissues from the Pompe disease mouse model. These results indicate that oxidative stress impacts on the efficacy of enzyme replacement therapy in Pompe disease and that manipulation of secondary abnormalities may represent a strategy to improve the efficacy of therapies for this disorder.

Hilary C Strollo,1 Seyed M Nouraie,1 Karin F Hoth,2 Craig M Riley,3 Chad Karoleski,1 Yingze Zhang,1 Nicola A Hanania,4 Russell P Bowler,5,6 Jessica Bon,1 Frank C Sciurba1 1University of Pittsburgh Medical Center, Department of Medicine, Department of Pulmonary Allergy and Critical Care Medicine, Pittsburgh, PA, USA; 2University of Iowa Carver College of Medicine, Department of Psychiatry, Iowa City, IA, USA; 3Chester County Hospital, University of Pennsylvania Health System, West Chester, PA, USA; 4Baylor College of Medicine, Department of Pulmonary, Critical Care and Sleep Medicine, Houston, TX, USA; 5National Jewish Health, Department of Medicine, Denver, CO, USA; 6University of Colorado School of Medicine, Denver, CO, USACorrespondence: Hilary C StrolloUniversity of Pittsburgh Medical Center, Department of Medicine, Department of Pulmonary Allergy and Critical Care Medicine, NW 628 UPMC Montefiore, 3459 Fifth Avenue, Pittsburgh, PA, 15213, USATel +1 412-692-2210Fax +1 412-692-4842Email strolloh2@upmc.eduRationale: Depression is a prevalent comorbidity of chronic obstructive pulmonary disease (COPD) that, along with COPD, has been associated with inflammation. An association between inflammation and depression in COPD has not been validated in a large COPD cohort.Methods: Individuals from the University of Pittsburgh SCCOR cohort and the COPDGene cohort with tobacco use history and airway obstruction (FEV1/FVC < 0.7) were evaluated using the Beck Depression Inventory II (BDI-II) and the Hospital Anxiety and Depression Scale (HADS), respectively. Participants completed symptom-related questionnaires and plasma IL-6 measurements. T-test, Fisher’s Exact tests and logistic regression were used for statistical analysis.Results: The SCCOR cohort included 220 obstructed participants: 44% female and 21.4% with elevated depressive symptoms. GOLD staging distribution was predominantly stage I and II. The COPDGene cohort included 745 obstructed participants: 44% female and 13.0% with elevated depressive symptoms. GOLD distribution was predominantly stage II and III. In the SCCOR cohort, correlation between IL-6 and depressive symptoms trended toward significance (p= 0.08). Multivariable modeling adjusted for FEV1, age, gender and medical comorbidities showed a significant association (OR = 1.70, 95% CI = 1.08– 2.69). IL-6 was significantly associated with elevated depressive symptoms in COPDGene in both univariate (p=0.001) and multivariable modeling (OR = 1.52, 95% CI =1.13– 2.04).Conclusion: Elevated plasma IL-6 levels are associated with depressive symptoms in individuals with COPD independent of airflow limitation and comorbid risk factors for depression. Our results suggest that systemic inflammation may play a significant and possibly bidirectional role in depression associated with COPD.Keywords: IL-6, depression, beck depression inventory, BDI, HADS, TNF-a, CRP, SCCOR, COPDGene

Background: Among international cardiologists it is unclear whether equipoise exists regarding the benefit of diagnosing and managing obstructive sleep apnea (OSA) to improve atrial fibrillation (AF) outcomes and whether clinical practice and equipoise are linked. Methods: Between January 2019 and June 2020 we distributed a web-based 12-question survey regarding OSA and AF management to practicing cardiologists in 16 countries. Results: The United States, Japan, Sweden, and Turkey accounted for two-thirds of responses. 863 cardiologists responded; half were general cardiologists, a quarter electrophysiologists. Responses regarding treating OSA with CPAP to improve AF endpoints were mixed. 33% of respondents referred AF patients for OSA screening. OSA was diagnosed in 48% of referred patients and continuous positive airway pressure (CPAP) was prescribed for 59% of them. Nearly 70% of respondents believed randomized controlled trials (RCTs) of OSA treatment in AF patients were necessary and indicated willingness to contribute to such trials. Conclusions: There was no clinical equipoise among surveyed cardiologists; a majority expressed certainty that combined OSA and AF treatment is superior to AF treatment alone for improving AF outcomes. However, a minority of surveyed cardiologists referred AF patients for OSA testing, and while half of screened AF patients had OSA, CPAP was prescribed in little more than half of them, reflecting the view that better clinical trial evidence is needed to support this practice. Our results underscore the need for larger, multi-national prospective studies of OSA treatment and AF outcomes to inform more uniform society guideline recommendations.

BACKGROUND: Insomnia is common in primary care medical practices. Although behavioral treatments for insomnia are safe, efficacious, and recommended in practice guidelines, they are not widely-available, and their effects on comorbid medical conditions remain uncertain. We are conducting a pragmatic clinical trial to test the efficacy of two cognitive behavioral treatments for insomnia (Brief Behavioral Treatment for Insomnia (BBTI) and Sleep Healthy Using the Internet (SHUTi)) versus an enhanced usual care condition (EUC). METHODS/DESIGN: The study is a three-arm, parallel group, randomized controlled trial. Participants include 625 adults with hypertension and insomnia, recruited via electronic health records from primary care practices affiliated with a large academic medical center. After screening and baseline assessments, participants are randomized to treatment. BBTI is delivered individually with a live therapist via web-interface/telehealth sessions, while SHUTi is a self-guided, automated, interactive, web-based form of cognitive behavioral therapy for insomnia. Participants in EUC receive an individualized sleep report, educational resources, and an online educational video. Treatment outcomes are measured at 9 weeks, 6 months, and 12 months. The primary outcome is patient-reported sleep disturbances. Secondary outcomes include other self-reported sleep measures, home blood pressure, body mass index, quality of life, health functioning, healthcare utilization, and side effects. DISCUSSION: This randomized clinical trial compares two efficacious insomnia interventions to EUC, and provides a cost-effective and efficient examination of their similarities and differences. The pragmatic orientation of this trial may impact sleep treatment delivery in real world clinical settings and advance the dissemination and implementation of behavioral sleep interventions. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT02508129 ; Date Registered: July 21, 2015).

BackgroundSleep difficulties are commonly reported by patients with asthma; however, the prevalence of insomnia and its association with disease burden and well-being is unknown. We aimed to determine the prevalence of insomnia, defined as combined sleep-specific complaints with associated daytime symptoms, among a large sample of adults with asthma, and to compare well-being, asthma control, and asthma-related health care utilization in individuals with asthma and insomnia and those without insomnia.MethodsBaseline data from adults with physician-confirmed asthma enrolled in the Severe Asthma Research Program III was used for analyses (N = 714). Participants completed the Insomnia Severity Index (ISI), Asthma Control Test, Asthma Quality of Life Questionnaire, and Hospital Anxiety and Depression Scale.ResultsInsomnia (ISI ≥ 10) was identified in 263 participants (37%). Presence of insomnia was associated with higher levels of depression and anxiety symptoms and poorer quality of life. Those with insomnia had a 2.4-fold increased risk for having not well-controlled asthma and a 1.5-fold increased risk for asthma-related health care utilization in the past year compared with those without insomnia.ConclusionsInsomnia is highly prevalent in asthma and is associated with adverse outcomes. Further studies are needed to gain a better understanding of the interaction between insomnia and asthma control.

Oxidative stress, a key mediator of cardiovascular disease, metabolic alterations, and cancer, is independently associated with menopause and obesity. Yet, among postmenopausal women, the correlation between obesity and oxidative stress is poorly examined. Thus, in this study, we compared oxidative stress states in postmenopausal women with or without obesity. Body composition was assessed via DXA, while lipid peroxidation and total hydroperoxides were measured in patient’s serum samples via thiobarbituric-acid-reactive substances (TBARS) and derivate-reactive oxygen metabolites (d-ROMs) assays, respectively. Accordingly, 31 postmenopausal women were enrolled: 12 with obesity and 19 of normal weight (mean (SD) age 71.0 (5.7) years). Doubled levels of serum markers of oxidative stress were observed in women with obesity in women with obesity compared to those of normal weight (H2O2: 32.35 (7.3) vs. 18.80 (3.4) mg H2O2/dL; malondialdehyde (MDA): 429.6 (138.1) vs. 155.9 (82.4) mM in women with or without obesity, respectively; p < 0.0001 for both). Correlation analysis showed that both markers of oxidative stress increased with an increasing body mass index (BMI), visceral fat mass, and trunk fat percentage, but not with fasting glucose levels. In conclusion, obesity and visceral fat are associated with a greater increase in oxidative stress in postmenopausal women, possibly increasing cardiometabolic and cancer risks.

According to a traditional view, logical validity consists in nec- essary truth preservation. Such an account has been argued to carry an apparent commitment to a unique property of truth to be preserved from premises to conclusion. Recent discussions, however, have concluded that if the metaphor of truth preservation is carefully unpacked, no need for a unique property is there. All is needed is that certain structural rela- tions among instantiations of truth properties hold. Against this view, we argue that a unique general truth property is indeed required by logical validity. We first show that the unpacking should be correctly understood since it imposes constraints on the concept and the properties of truth. We then demonstrate that, under such constraints, a general property is not imposed by truth preservation but by another feature of validity: its uniformity. Finally, some options that could be attempted to resist this result are discussed, showing that (strong) truth pluralism and deflationism are affected in different ways. [ABSTRACT FROM AUTHOR]

Pompe disease is an inherited metabolic disorder due to the deficiency of the lysosomal acid α-glucosidase (GAA). The only approved treatment is enzyme replacement therapy with the recombinant enzyme (rhGAA). Further approaches like pharmacological chaperone therapy, based on the stabilising effect induced by small molecules on the target enzyme, could be a promising strategy. However, most known chaperones could be limited by their potential inhibitory effects on patient’s enzymes. Here we report on the discovery of novel chaperones for rhGAA, L- and D-carnitine, and the related compound acetyl-D-carnitine. These drugs stabilise the enzyme at pH and temperature without inhibiting the activity and acted synergistically with active-site directed pharmacological chaperones. Remarkably, they enhanced by 4-fold the acid α-glucosidase activity in fibroblasts from three Pompe patients with added rhGAA. This synergistic effect of L-carnitine and rhGAA has the potential to be translated into improved therapeutic efficacy of ERT in Pompe disease.

Introduction: Metabolic syndrome (MetS) is increasingly common in adults as well as in children and adolescents. However, preventing and treating MetS is one of the most pressing challenges for public health services worldwide. At present, the only approved treatments for MetS are dietary changes and physical activity, which are associated with a high rate of non-compliance. On the contrary, no drugs are licensed to treat metabolic syndrome, although a number of drugs are used to treat individual metabolic abnormalities, which increases the risk of adverse events, particularly in children. Policaptil Gel Retard® (PGR), an oral macromolecule complex based on polysaccharides, has been demonstrated to significantly reduce body weight, peak blood glucose (BG) levels, insulin levels, and lipid levels, providing an interesting non-pharmacological therapeutic option for MetS-associated metabolic abnormalities, especially in younger patients.Aims: To review available studies on the use of PGR in children, adolescents, or adults with obesity or metabolic syndrome.Methods: A systematic search of electronic databases for PGR and MetS. A total of six studies were identified and included.Results: Across four randomized clinical studies and one retrospective clinical study including a total of 359 obese children and adolescents with or without MetS and 157 overweight/obese adults with or without MetS and/or T2DM, a single dose of PGR resulted in a reduction in appetite and postprandial triglyceride levels in younger patients and peak postprandial BG levels in adults. Decreased lipid levels were observed in adults following a normocaloric diet who received PGR for 30 days. As a long-term treatment, in combination with a low-glycemic index diet with or without metformin, PGR resulted in reduced body mass index and waist circumference, improved insulin sensitivity with reduction of glucose-metabolism abnormalities, increased insulin reserve and, finally, an improved circulating lipid profile, regardless of age. No safety issues were reported.Conclusion: Policaptil Gel Retard® is an effective and safe non-pharmacological approach to improve the treatment of MetS-associated cardiovascular risk factors in children, adolescents, and adults.