Little is known about the effects of subzero temperatures on the formation
of secondary organic aerosol (SOA) from α-pinene. In the current
work, ozone-initiated oxidation of α-pinene at initial
...concentrations of 10 and 50 ppb, respectively, is performed at
temperatures of 20, 0, and −15 ∘C in
the Aarhus University Research on Aerosol (AURA) smog chamber during the Aarhus Chamber Campaign on Highly Oxygenated
Organic Molecules and Aerosols (ACCHA). Herein, we show how temperature influences the
formation and chemical composition of α-pinene-derived SOA with a
specific focus on the formation of organic acids and dimer esters. With
respect to particle formation, the results show significant increase in
particle-formation rates, particle number concentrations, and particle mass
concentrations at low temperatures. In particular, the number concentrations
of sub-10 nm particles were significantly increased at the lower 0 and −15 ∘C temperatures. Temperature also affects
the chemical composition of formed SOA. Here, detailed offline chemical
analyses show that organic acids contribute from 15 % to 30 % by mass,
with highest contributions observed at the lowest temperatures, indicative
of enhanced condensation of these semivolatile species. In comparison, a
total of 30 identified dimer esters were seen to contribute between 4 % and 11 % to the total SOA mass. No significant differences in the chemical
composition (i.e. organic acids and dimer esters) of the α-pinene-derived SOA particles are observed between experiments performed at
10 and 50 ppb initial α-pinene concentrations, thus suggesting a
higher influence of reaction temperature compared to that of α-pinene loading on the SOA chemical composition. Interestingly, the effect
of temperature on the formation of dimer esters differs between the
individual species. The formation of less oxidized dimer esters – with
oxygen-to-carbon ratio (O:C)<0.4 – is shown to increase at low
temperatures, while the formation of the more oxidized species (O:C>0.4) is suppressed, consequently resulting in
temperature-modulated composition of the α-pinene-derived SOA.
Temperature ramping experiments exposing α-pinene-derived SOA to
changing temperatures (heating and cooling) reveal that the chemical
composition of the SOA with respect to dimer esters is governed almost
solely by the temperature at which oxidization started and is insusceptible to
subsequent changes in temperature. Similarly, the resulting SOA mass
concentrations were found to be more influenced by the initial α-pinene oxidation temperatures, thus suggesting that the formation
conditions to a large extent govern the type of SOA formed, rather than the
conditions to which the SOA is later exposed. For the first time, we discuss the relation between the identified dimer
ester and the highly oxygenated organic molecules (HOMs) measured by
chemical ionization–atmospheric pressure interface–time-of-flight mass spectrometer (CI-APi-ToF) during the ACCHA experiments. We propose
that, although very different in chemical structures and O:C ratios, many
dimer esters and HOMs may be linked through similar RO2 reaction
pathways and that dimer esters and HOMs merely represent two different
fates of the RO2 radicals.
This study aimed to develop a method using computer vision techniques to accurately detect and delineate the proximal femur in radiographs of Legg–Calvé–Perthes disease (LCPD) patients. Currently, ...evaluating femoral head deformity, a crucial predictor of LCPD outcomes, relies on unreliable categorical and qualitative classifications. To address this limitation, we employed the pretrained object detection model YOLOv5 to detect the proximal femur on over 2000 radiographs, including images of shoulders and chests, to enhance robustness and generalizability. Subsequently, we utilized the U‐Net convolutional neural network architecture for image segmentation of the proximal femur in more than 800 manually annotated images of stage IV LCPD. The results demonstrate outstanding performance, with the object detection model achieving high accuracy (mean average precision of 0.99) and the segmentation model attaining an accuracy score of 91%, dice coefficient of 0.75, and binary IoU score of 0.85 on the held‐out test set. The proposed fully automatic proximal femur detection and segmentation system offers a promising approach to accurately detect and delineate the proximal femoral bone contour in radiographic images, which is essential for further image analysis in LCPD patients. Clinical significance: This study highlights the potential of computer vision techniques for enhancing the reliability of Legg–Calvé–Perthes disease staging and outcome prediction.
The receptor of advanced glycation end products (RAGE) and its ligands are linked to the pathogenesis of coronary artery disease (CAD), and circulating soluble receptor of advanced glycation end ...products (sRAGE), reflecting the RAGE activity, is suggested as a potential biomarker. Elevated sRAGE levels are reported in relation to acute ischemia and this review focuses on the role of sRAGE as a biomarker for the acute coronary syndrome (ACS). The current studies demonstrated that sRAGE levels are elevated in relation to ACS, however during a very narrow time period, indicating that the time of sampling needs attention. Interestingly, activation of RAGE may influence the pathogenesis and reflection in sRAGE levels in acute and stable CAD differently.
Background
Combined withdrawal and early preventive medication was the most effective treatment for medication overuse headache (MOH) within the first 6 months in a previous study, but results from a ...longer follow‐up period are lacking.
Objective
(1) To measure the efficacy at 1 year of three different treatment approaches to MOH; (2) to compare withdrawal and early preventives (W+P), preventives with potential withdrawal therapy after 6 months (P+pW), and withdrawal with delayed potential preventives (W+pP); and (3) to identify predictors of chronic headache after 1 year.
Methods
Patients with MOH and migraine and/or tension‐type headache were randomly assigned to one of the three outpatient treatments. Headache calendar and questionnaires were filled out. Primary outcome was a reduction in headache days/month after 1 year.
Results
Of 120 patients, 96 completed 1‐year follow‐up, and all were included in our analyses. Overall headache days/month were reduced from 24.6 (23.4–25.8) to 15.0 (13.0–17.0) (p < 0.0001), and only 11/96 patients (11%) relapsed. Reduction in monthly headache days was 10.3 days (95% CI: 6.7–13.9) in the W+P group, 10.8 days (95% CI: 7.6–14) in the P+pW group, and 7.9 days (95% CI: 5.1–10.7) in the W+pP group. No significant differences in treatment effect were seen between the three groups (p = 0.377). After 1 year, 39/96 (41%) had chronic headache. Predictors of chronic headache after 1 year were higher headache frequency (aOR 1.19; 1.09–1.31), more days with acute medication (aOR 1.11; 1.03–1.19), higher pain intensity (aOR 1.04; 1.01–1.08), and depression (aOR 4.7; 1.38–18.95), whereas higher self‐rated health (aOR 0.61; 0.36–0.97) and high caffeine consumption (aOR 0.40; 0.16–0.96) were predictors of a lower risk of chronic headache. No adverse events were reported.
Conclusions
All treatment strategies proved effective in treating MOH with a low relapse rate. The W+P strategy leads to the fastest effect, confirming earlier treatment recommendations. Identification of predictors for chronic headache may help identify more complex patients.
Migraine is a highly prevalent and disabling neurological disease. Excessive use of acute medications can lead to medication-overuse headache (MOH), occurring when a patient experiences an increasing ...number of headache and migraine days, despite taking greater amounts of acute medication. To treat MOH, a preventive migraine treatment and/or withdrawal of the overused medication(s) are advised. Brief Educational Intervention (BEI) has been shown to be an effective tool with promising results for MOH. Here, we report the design of a clinical trial that aims to evaluate the efficacy of eptinezumab, an anti-calcitonin gene-related peptide preventive migraine treatment, as an add-on to BEI for treatment of MOH in those with chronic migraine.
RESOLUTION will be a phase 4, multi-national, randomized, double-blind, placebo-controlled study. This study will enroll approximately 570 participants with dual diagnoses of chronic migraine and MOH. Eligible patients will be randomly allocated to one of two treatment groups, BEI and eptinezumab (100 mg;
= 285) or BEI and placebo (
= 285), in a 1:1 ratio. The primary endpoint is the change from baseline in monthly migraine days over weeks 1-4. Secondary and exploratory endpoints will assess monthly migraine days over weeks 1-12, MOH remission, transition from chronic to episodic migraine, health-related quality of life, work productivity, and the safety and tolerability of eptinezumab in this patient population.
This study will be conducted in accordance with good clinical practice. All patients will be fully informed about the study, including the risks and benefits of participation, and all participants will provide informed consent for participation in the trial and dissemination of results.
Background
Dependence‐like behaviour may complicate withdrawal and increase risk of relapse of medication overuse headache (MOH). The most effective treatment for reducing dependence‐like behaviour ...is unknown.
Objectives
To compare patient‐reported outcomes among three treatment strategies for MOH. The primary outcome was change in Severity of Dependence Scale (SDS) score from baseline to 6 months.
Methods
Patients with MOH were randomized to (1) withdrawal combined with preventive medication from start (W+P), (2) preventive medication without withdrawal (P), or (3) withdrawal with optional preventive medication 2 months after withdrawal (W). At baseline, 2, and 6 months, patients filled out SDS (used for measurements of dependence‐like behaviour and treatment feasibility), Headache Under‐Response of Treatment (HURT) and WHO Quality of Life BREF questionnaires.
Results
Out of 120 patients with MOH, 100 completed the 6‐month follow‐up and filled out questionnaires. The W+P arm was the most effective in treating MOH. After 6 months, the SDS score was reduced by 3.69 (95% CI 3.23–4.49) in the W+P arm, by 3.19 (95% CI 2.43–3.96) in the W arm, and by 1.65 (95% CI 0.96–2.33) in the P arm (p = 0.04). At baseline and after 2 months, the P arm was considered the most feasible treatment, but at 6‐month follow‐up, there was no difference in feasibility score, change in HURT score, or quality of life.
Conclusions
Dependence‐like behaviour was reduced most in the two withdrawal arms. Withdrawal combined with preventive medication is recommended for the treatment of MOH.
Significance
Withdrawal combined with preventive medication from start is the treatment strategy that reduces dependence‐like behaviour the most in MOH patients. Patients initially considered preventive treatment without withdrawal as the most feasible treatment. However, no difference in feasibility between the three arms was found at 6‐month follow‐up. Withdrawal combined with preventive medication is recommended for treatment of MOH.
This work investigates the individual and combined effects of temperature and volatile organic compound precursor concentrations on the chemical composition of particles formed in the dark ozonolysis ...of α-pinene. All experiments were conducted in a 5 m3 Teflon chamber at an initial ozone concentration of 100 ppb and initial α-pinene concentrations of 10 and 50 ppb, respectively; at constant temperatures of 20, 0, or −15 ∘C; and at changing temperatures (ramps) from −15 to 20 and from 20 to −15 ∘C. The chemical composition of the particles was probed using a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). A four-factor solution of a positive matrix factorization (PMF) analysis of the combined HR-ToF-AMS data is presented. The PMF analysis and the elemental composition analysis of individual experiments show that secondary organic aerosol particles with the highest oxidation level are formed from the lowest initial α-pinene concentration (10 ppb) and at the highest temperature (20 ∘C). A higher initial α-pinene concentration (50 ppb) and/or lower temperature (0 or −15 ∘C) results in a lower oxidation level of the molecules contained in the particles. With respect to the carbon oxidation state, particles formed at 0 ∘C are more comparable to particles formed at −15 ∘C than to those formed at 20 ∘C. A remarkable observation is that changes in temperature during particle formation result in only minor changes in the elemental composition of the particles. Thus, the temperature at which aerosol particle formation is induced seems to be a critical parameter for the particle elemental composition. Comparison of the HR-ToF-AMS-derived estimates of the content of organic acids in the particles based on m/z 44 in the mass spectra show good agreement with results from off-line molecular analysis of particle filter samples collected from the same experiments. Higher temperatures are associated with a decrease in the absolute mass concentrations of organic acids (R-COOH) and organic acid functionalities (-COOH), while the organic acid functionalities account for an increasing fraction of the measured particle mass.
Background
Many people suffering from migraine combine pharmacological and non-pharmacological treatments. The purpose of this systematic review is to provide an updated guideline for some widely ...used non-pharmacological treatment options for migraine.
Methods
We conducted a systematic literature review of randomized studies of adults with migraine treated with manual joint mobilisation techniques, supervised physical activity, psychological treatment, acupuncture and patient education. The main outcomes measured were days with headache and quality of life. Recommendations were formulated based on the Grade of Recommendation, Assessment, Development and Evaluation (GRADE) approach including patient preferences based on expert opinion and questionnaire data.
Results
The overall level of certainty of the evidence was low to very low. Manual therapy techniques and psychological treatment did not change the studied outcomes. Supervised physical activity might have a positive impact on quality of life, acupuncture on headache frequency, intensity, quality of life and the use of attack-medicine. Patient education might improve self-rated health and quality of life and increase the number of well-informed patients.
Conclusion
Based on observed effects, the lack of serious adverse events, and patients’ preferences, we make weak recommendations for considering the investigated interventions as a supplement to standard treatment.
Protocol registration: Prospero CRD42020220132.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of diabetic kidney disease. The actions of AGEs are mediated both through a non-receptor mediated pathway and through ...specific receptors for AGEs (e.g. RAGE). To explore a potentially specific role for RAGE in renal changes in type 1 diabetes, we examined the renal effects of a neutralising murine RAGE-antibody (ab) in streptozotocin (STZ)-diabetic mice, a model of type 1 diabetes. One group of STZ-diabetic mice was treated for two months with the RAGE-ab, while another STZ-diabetic group was treated for the same period with an irrelevant immunoglobulin G (IgG). Two groups of non-diabetic NMRI mice were treated with either RAGE-ab or isotype-matched IgG for two months. Placebo-treated STZ-diabetic mice showed an increase in kidney weight, glomerular volume, basement membrane thickness (BMT), urinary albumin excretion (UAE) and creatinine clearance (CrCl), when compared with non-diabetic controls. In RAGE-ab-treated STZ-diabetic mice, the increase in kidney weight and UAE was reduced, while the increase in CrCl was abolished. RAGE-ab administration in NMRI mice caused a reduction in liver weight and an increase in BMT. Renal messenger RNA (mRNA) for connective tissue growth factor and collagen IVα1 was increased in placebo-treated diabetic animals. RAGE-ab treatment had no impact on the expression of these factors. The renal effects of RAGE-ab administration in STZ-diabetic mice were seen without impact on body weight, blood glucose or food consumption. In conclusion, the present data support the hypothesis that RAGE is an important pathogenic factor in the renal changes in an animal model of type 1 diabetes.
Low-grade inflammation has been associated with cardiovascular disease (CVD) and chronic heart failure (CHF). The aim of the present study was to investigate the potential usefulness of the ...inflammatory protein calprotectin as a biomarker in CHF.
Plasma calprotectin was measured in 193 CHF patients with left ventricular function <45% and in 100 healthy controls at baseline. Patients with CHF were followed for a median period of 2.6 years according to mortality.
The levels of plasma calprotectin were significantly increased in the CHF patients compared to the control group (P < 0.01), primarily due to elevated levels in the patients with New York Heart Association (NYHA) class III and IV. Furthermore, plasma calprotectin was a superior biomarker of high NYHA classes than other parameters reflecting CHF severity, OR 2.2 (1.1-4.3) (P = 0.019). After the follow-up period, 46 patients had died. Plasma calprotectin levels did not predict mortality in CHF patients.
Plasma calprotectin is increased in CHF patients, indicating that inflammatory activity is upregulated in CHF and may be associated with the severity of CHF.
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