Magnetic Field Properties inside the Jet of Mrk 421: Multiwavelength Polarimetry Including the Imaging X-ray Polarimetry Explorer

We conducted a polarimetry campaign from radio to X-ray wavelengths of the high-synchrotron-peak (HSP) blazar Mrk 421, including Imaging X-ray Polarimetry Explorer (IXPE) measurements on 2022 December 6-8. We detected X-ray polarization of Mrk 421 with a degree of $\Pi_{\rm X}$=14$\pm$1$\%$ and an electric-vector position angle $\psi_{\rm X}$=107$\pm$3$^{\circ}$ in the 2-8 keV band. From the time variability analysis, we find a significant episodic variation in $\psi_{\rm X}$. During 7 months from the first IXPE pointing of Mrk 421 in 2022 May, $\psi_{\rm X}$ varied across the range of 0$^{\circ}$ to 180$^{\circ}$, while $\Pi_{\rm X}$ maintained similar values within $\sim$10-15$\%$. Furthermore, a swing in $\psi_{\rm X}$ in 2022 June was accompanied by simultaneous spectral variations. The results of the multiwavelength polarimetry show that the X-ray polarization degree was generally $\sim$2-3 times greater than that at longer wavelengths, while the polarization angle fluctuated. Additionally, based on radio, infrared, and optical polarimetry, we find that rotation of $\psi$ occurred in the opposite direction with respect to the rotation of $\psi_{\rm X}$ over longer timescales at similar epochs. The polarization behavior observed across multiple wavelengths is consistent with previous IXPE findings for HSP blazars. This result favors the energy-stratified shock model developed to explain variable emission in relativistic jets. The accompanying spectral variation during the $\psi_{\rm X}$ rotation can be explained by a fluctuation in the physical conditions, e.g., in the energy distribution of relativistic electrons. The opposite rotation direction of $\psi$ between the X-ray and longer-wavelength polarization accentuates the conclusion that the X-ray emitting region is spatially separated from that at longer wavelengths.Comment: 17 pages, 13 figures, 4 tables; Accepted for publication in A&

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

A Repeated Cross-Sectional Pilot Study of Physical Activity, Levels of Depression and Anxiety during the COVID-19 Pandemic in Young Greek Adults

Regular physical activity (PA) and, more specifically, exercise, is associated with lower levels of stress, depression, and anxiety. The aim of this repeated cross-sectional pilot study was to investigate the impact of participating in PA on the mental health of young adults in Greece during the COVID-19 pandemic. The study was carried out during two quarantine periods: Survey I on 5 May 2020, and Survey II on 30 April 2021. The Hamilton Anxiety (HAM-A) and Beck Depression Inventory-II (BDI-II) scales and the level of PA were used to assess a sample of individuals aged between 18 and 26 years old. In 2020 and 2021, a total of 268 (33.9% males) and 380 (37.1% females) subjects participated in the studies, respectively. According to the findings, the vast majority of the participants in both samples reported that they are physically active (p = 0.86), while they consider exercise as a significant health factor (p = 0.10). Moreover, anxiety levels statistically significant increased (p = 0.001), while depression levels remained relatively stable with a slight increase of approximately (p > 0.05). Additionally, in both surveys, individuals who engaged in a PA program exhibited reduced levels of depression and anxiety (p = 0.001). Also, gender appears to influence anxiety and depression levels, while a lack of exercise exacerbates these measures in both genders when compared to physically active individuals. Concludingly, it is crucial for public health strategies to include interventions that promote safe PA in the event of future lockdowns or similar emergencies

Prevalence of Diabetes and Its Association with Atherosclerotic Cardiovascular Disease Risk in Patients with Familial Hypercholesterolemia: An Analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH)

Familial hypercholesterolemia (FH) and type 2 diabetes mellitus (T2DM) are both associated with a high risk of atherosclerotic cardiovascular disease (ASCVD). Little is known about the prevalence of T2DM and its association with ASCVD risk in FH patients. This was a cross-sectional analysis from the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH) including adults with FH (n = 1719, mean age 51.3 ± 14.6 years). Of FH patients, 7.2% had a diagnosis of T2DM. The prevalence of ASCVD, coronary artery disease (CAD), and stroke was higher among subjects with T2DM compared with those without (55.3% vs. 23.3%, 48.8% vs. 20.7%, 8.3% vs. 2.7%, respectively, p p = 0.004]. FH patients with T2DM were more likely to have undergone coronary revascularization than those without (14.2% vs. 4.5% for coronary artery bypass graft, and 23.9% vs. 11.5% for percutaneous coronary intervention, p < 0.001). T2DM is associated with an increased risk for prevalent ASCVD in subjects with FH. This may have implications for risk stratification and treatment intensity in these patients

LDL cholesterol target achievement in heterozygous familial hypercholesterolemia patients according to 2019 ESC/EAS lipid guidelines: Implications for newer lipid-lowering treatments

Background: The 2019 European guidelines (ESC/EAS) for the treatment of dyslipidaemias recommend more aggressive targets for low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia (FH). Current lipid-lowering treatment is often inadequate to achieve these targets. Methods: Data from the HELLAS-FH registry were analysed to assess achievement of LDL-C targets in adults with FH based on the 2019 ESC/EAS guidelines. In patients who had not achieved LDL-C target, the maximally reduced LDL-C value was calculated after theoretical switch to rosuvastatin/ezetimibe 40/10 mg/day. The percentage of patients who remained candidates for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) was then calculated. Results: Patients (n = 1694, mean age 50.8 +/- 14.7 years) had LDL-C levels 242 +/- 71 mg/dL (6.3 +/- 1.8 mmol/L) at diagnosis. Most treated patients were receiving statins (97.5%) and about half were on additional ezetimibe (47.5%). Based on the 2019 ESC/EAS guidelines the percentage of patients achieving LDL-C goals was only 2.7%. Following theoretical up titration to rosuvastatin/ezetimibe 40/10 mg, LDL-C target achievement rate would increase to 5.9%. In this scenario, most patients (55.9%) would be eligible for PCSK9i treatment. Following theoretical administration of a PCSK9i, LDL-C target achievement rate would rise to 57.6%. However, 42.4% of patients would still be eligible for further LDL-C lowering treatment. Conclusions: Most FH patients do not reach new LDL-C targets even if on maximum intensity statin/ezetimibe treatment. In this case, more than half of FH patients are candidates for PCSK9i therapy and a considerable proportion may still require additional LDL-C lowering