Cardiac magnetic resonance in histologically proven eosinophilic myocarditis.

BACKGROUND: Eosinophilic myocarditis (EM) is a life-threatening acute heart disease. Cardiac magnetic resonance (CMR) excels in the assessment of myocardial diseases but CMR studies of EM are limited. We aimed to describe CMR findings in histologically proven EM. METHODS: Patients with histologically proven EM seen at an academic center from 2000 through 2020 were identified. Of the 28 patients ascertained, 15 had undergone CMR for diagnosis and constitute our study cohort. RESULTS: The patients, aged 51 ± 17 years, presented with fever (53%), dyspnea (47%), chest pain (53%), heart block (20%), and blood eosinophilia (60%). On CMR, all 15 patients had myocardial edema with 10 of them (67%) having abnormally high left ventricular (LV) mass as well. LV ejection fraction measured < 50% in 11 patients (73%) and < 30% in 2 (13%), but only 6 (40%) had dilated LV size. Eight patients (53%) had pericardial effusion. LV late gadolinium enhancement (LGE) was found in all but one patient (13/14; 93%). LGE was always multifocal and subendocardial but could involve any myocardial layer. Patients with necrotizing EM by histopathology (n = 6) had higher LGE mass (32.1 ± 16.6% vs 14.5 ± 7.7%, p = 0.050) and more LV segments with LGE (15 ± 2 vs 9 ± 3 out of 17, p = 0.003) than patients (n = 9) without myocyte necrosis. Two patients had LV thrombosis accompanying widespread subendocardial LGE. CONCLUSIONS: In EM, CMR shows myocardial edema and LGE that is typically subendocardial but can involve any myocardial layer. The left ventricle is often non-dilated with moderate-to-severe systolic dysfunction. Pericardial effusion is common. Necrotizing EM presents with extensive myocardial LGE on CMR.

Building shape-focused pharmacophore models for effective docking screening.

The performance of molecular docking can be improved by comparing the shape similarity of the flexibly sampled poses against the target proteins' inverted binding cavities. The effectiveness of these pseudo-ligands or negative image-based models in docking rescoring is boosted further by performing enrichment-driven optimization. Here, we introduce a novel shape-focused pharmacophore modeling algorithm O-LAP that generates a new class of cavity-filling models by clumping together overlapping atomic content via pairwise distance graph clustering. Top-ranked poses of flexibly docked active ligands were used as the modeling input and multiple alternative clustering settings were benchmark-tested thoroughly with five demanding drug targets using random training/test divisions. In docking rescoring, the O-LAP modeling typically improved massively on the default docking enrichment; furthermore, the results indicate that the clustered models work well in rigid docking. The C+ +/Qt5-based algorithm O-LAP is released under the GNU General Public License v3.0 via GitHub ( https://github.com/jvlehtonen/overlap-toolkit ). SCIENTIFIC CONTRIBUTION: This study introduces O-LAP, a C++/Qt5-based graph clustering software for generating new type of shape-focused pharmacophore models. In the O-LAP modeling, the target protein cavity is filled with flexibly docked active ligands, the overlapping ligand atoms are clustered, and the shape/electrostatic potential of the resulting model is compared against the flexibly sampled molecular docking poses. The O-LAP modeling is shown to ensure high enrichment in both docking rescoring and rigid docking based on comprehensive benchmark-testing.

Phylogenetic relationships and systematics of tapeworms of the family Davaineidae (Cestoda, Cyclophyllidea), with emphasis on species in rodents.

The present study aims at clarifying the poorly known phylogenetic relationships and systematics of cestodes of the family Davaineidae Braun, 1900 (Cyclophyllidea), primarily the genus Raillietina Fuhrmann, 1920 and of the subfamily Inermicapsiferinae (Anoplocephalidae) from mammals (mostly rodents, 31 new isolates) and birds (eight new isolates). Phylogenetic analyses are based on sequences of the large subunit ribosomal RNA gene (28S) and mitochondrial NADH dehydrogenase subunit 1 gene (nad1). The main phylogenetic pattern emerging from the present analysis is the presence of three independent lineages within the main clade of the subfamily Davaineinae, one of which is almost entirely confined to species from rodents and the other two show a mixture of species from birds and mammals. It is suggested that the major diversification of the main clade took place in birds, possibly in galliforms. The subsequent diversification included repeated host shifts from birds to mammals and to other birds, and from rodents to other mammals, showing that colonisation of new host lineages has been the main driver in the diversification of davaineine cestodes. It is also shown that all isolates of Inermicapsifer Janicki, 1910, mainly from rodents, form a monophyletic group positioned among Raillietina spp. in the "rodent lineage", indicating that the genus Inermicapsifer is a member of the family Davaineidae. This means that the subfamily Inermicapsiferinae and the family Inermicapsiferidae should be treated as synonyms of the Davaineidae, specifically the subfamily Davaineinae. Three additional genera generally included in the Inermicapsiferinae, i.e. Metacapsifer Spasskii, 1951, Pericapsifer Spasskii, 1951 and Thysanotaenia Beddard, 1911, are also assigned here to the Davaineidae (subfamily Davaineinae). Raillietina spp. were present in all three main lineages and appeared as multiple independent sublineages from bird and mammalian hosts, verifying the non-monophyly of the genus Raillietina and suggesting a presence of multiple new species and genera.

Mental health after the COVID-19 pandemic among Finnish youth: a repeated, cross-sectional, population-based study.

BACKGROUND: High levels of mental health problems among young people were reported during the COVID-19 pandemic, but studies of the post-pandemic period are scarce. We assessed mental health problems among Finnish youth before, during, and after the COVID-19 pandemic using nationwide population-based samples. Our aim was to examine in which direction the heightened levels of adolescent mental health problems have developed after the pandemic. METHODS: In this national, repeated cross-sectional, population-based study in Finland, we recruited students at lower and upper secondary level (aged 13-20 years) who were taking part in the Finnish School Health Promotion (SHP) survey in 2015-23 (119 681-158 897 participants per round). The SHP is based on total sampling and conducted biennially between March and May. Self-reports covered the seven-item Generalized Anxiety Disorder Scale; the two-item Patient Health Questionnaire for depression; the Mini Social Phobia Inventory for social anxiety; the Short Warwick-Edinburgh Mental Wellbeing Scale for mental wellbeing; loneliness; the Sick, Control, One Stone, Fat, Food measure for disordered eating; and suicidality (suicidal ideation, deliberate self-harm, and suicide attempts). Scales were dichotomised using validated cutoffs. Presence of any and comorbid mental health problems was assessed. Logistic (for dichotomised outcomes) and linear (for Short Warwick-Edinburgh Mental Wellbeing Scale) mixed effects models were used to analyse the effect of survey year on mental health, controlling for sociodemographic background factors and stratified by gender and school level. Cisgender and transgender youth were compared. FINDINGS: Between 2015 and 2023, the SHP study recruited 722 488 students (371 634 [51·6%] girls and 348 857 [48·4%] boys) with a mean age of 15·8 years (SD 1·3) who were either in the eighth and ninth grades of comprehensive school or the first and second years of general and vocational upper secondary schools in Finland. The proportion of participants with generalised anxiety, depression, and social anxiety symptoms above the cutoff increased from pre-COVID-19 levels to 2021 and remained at these higher levels in 2023 among all study groups. Among girls in lower secondary education, prevalence of generalised anxiety, depression, and social anxiety symptoms increased from 2021 to 2023, as did social anxiety among girls in upper secondary education. Among boys, the proportion with social anxiety symptoms decreased between 2021 and 2023. Mental wellbeing scores decreased in all groups between 2021 and 2023, and disordered eating increased in girls, and in boys in lower secondary education. Suicidality increased in girls but not in boys. Loneliness was the only measure to show improvement in all groups from 2021 to 2023. In 2023, 55 895 (72·6%) of 76 994 girls and 22 718 (32·8%) of 69 205 boys reported at least one mental health problem, and 37 250 (48·4%) girls and 9442 (13·6%) boys reported comorbid mental health problems. Among both transfeminine and transmasculine youth, the prevalence of generalised anxiety and depression symptoms decreased from 2021 to 2023, but compared with cisgender youth, the proportions were significantly higher throughout. INTERPRETATION: The effects of the COVID-19 pandemic on youth mental health could be long lasting. In this study, the substantial change for the better among transgender youth was a positive exception. Providing adequate support and treatment for young people with poor mental health is essential, but solutions to the mental health crisis need to address a wider societal perspective and should be developed in partnership with young people. FUNDING: NordForsk, Research Council of Finland. TRANSLATIONS: For the Finnish and Swedish translations of the abstract see Supplementary Materials section.

30-Year Trends in the Incidence, Characteristics, and Outcome of Cardiac Sarcoidosis in a Nationwide Cohort.

Background: Cardiac sarcoidosis (CS) is a rare but potentially fatal inflammatory cardiomyopathy. Objectives: The authors studied temporal changes in the incidence, characteristics, and outcome of CS. Methods: A retrospective analysis was made of a 30-year nationwide cohort of CS. Results: The cohort comprised 511 patients with a median age of 52 years and female preponderance (69%). Altogether 77, 166, and 268 cases of CS were diagnosed in years 1988 to 2009, 2010 to 2014, and 2015 to 2019, respectively; the 5-year count of 2015 to 2019 was 134-fold the count of 1990 to 1994 (268/2) and 18-fold the count of 2000 to 2004 (268/15). Prior to 2010, compared with the later periods, CS presented more often with ventricular tachycardia/fibrillation (prevalence 36% vs 19% in 2010-2014 and 11% in 2015-2019, P < 0.001), left ventricular ejection fraction <50% (49%, 35%, and 31%; P = 0.010), and elevation of natriuretic peptides (87%, 57%, and 49%; P < 0.001). On magnetic resonance imaging, late gadolinium enhancement involved a median of 15% (IQR: 11%-22%) of left ventricular mass in studies of 1988 to 2009 (n = 16), 15% (IQR: 9%-22%) in studies of 2010 to 2014 (n = 87), and 11% (IQR: 5%-19%) in studies of 2015 to 2019 (n = 150) (P = 0.031). The respective 5-year incidences of the composite of death, heart transplantation, left ventricular-assisted device implantation, or ventricular tachyarrhythmia were 40% (95% CI: 29%-51%), 32% (95% CI: 25%-39%), and 23% (95% CI: 16%-30%) (P = 0.002). The prognostic trend disappeared after adjustment for differences in the presenting phenotype. Conclusions: Diagnoses of incident CS have increased exponentially in Finland. Concurrently, the phenotype has turned milder and prognosis better, suggesting detection of CS at an earlier stage of its course.