Left ventricular clefts - incidental finding or pathologic sign of Wilson's disease?

Background: Wilson’s disease is an inherited autosomal recessive multi-systemic disorder characterized by reduced excretion and consequently excessive accumulation of copper in different organs, such as the heart. Results: In a prospective controlled trial, which is the largest to date, we evaluated 61 patients with Wilson’s disease, age- and sex-matched to 61 healthy patients, for cardiac manifestation using cardiac magnetic resonance imaging. Patients were under stable disease and had no signs of heart failure at the time of examination. We detected a left ventricular cleft, an invagination penetrating more than 50% wall thickness of the adjoining compact myocardium in diastole, in 20% of the patients (12 out of 61) compared to 5% among control patients (3 out of 61, p = 0.013). No correlation between the incidence of cleft and a certain genotype of Wilson’s disease was found. All described cases were incidental findings and none of the patients showed other signs of cardiac involvement. Conclusions: To conclude, the results of this study suggests that the increased occurrence of left ventricular clefts is due to Wilson’s disease. Large studies with a long observation period are needed for further evaluation

Attosecond imaging of photo-induced dynamics in molecules using time-resolved photoelectron momentum microscopy

We explore the novel capabilities offered by attosecond extreme ultraviolet and x-ray pulses that can be now generated by free-electron lasers and high-harmonics generation sources for probing photon-induced electron dynamics in molecules. We theoretically analyze how spatial and temporal dependence of charge migration in a pentacene molecule can be followed by means of time-resolved photoelectron microscopy on the attosecond time scale. Performing the analysis, we accurately take into account that an attosecond probe pulse leads to considerable spectral broadening. We demonstrate that the excited-state dynamics of a neutral pentacene molecule in the real space map onto unique features of photoelectron momentum maps.Comment: Accepted to Phys. Rev.

A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans.Juliana Garcia, Vera Marisa Costa, Ricardo Dinis-Oliveira and Ricardo Silvestre thank FCT-Foundation for Science and Technology-for their PhD grant (SFRH/BD/74979/2010), Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/110001/2015) and Investigator grants (IF/01147/2013) and (IF/00021/2014), respectively. This work was supported by the Fundacao para a Ciencia e Tecnologia (FCT) - project PTDC/DTPFTO/4973/2014 - and the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundacao para a Ciencia e Tecnologia) through project Pest-C/EQB/LA0006/2013

Reliability and construct validity of the "Questionnaire on attitudes towards inclusion for teachers" (EFI-L) in a sample of pre-service teachers and non-students

Ziel der vorliegenden Studie ist eine Erweiterung der psychometrischen Wissensbasis zum „Einstellungsfragebogen zu Inklusion für Lehrkräfte“ (EFI-L). Die Daten wurden im Rahmen einer Studie zu Einstellungen zur Inklusion von Schüler*innen mit Körperbehinderungen erhoben. Untersucht wurden als zentrale Gütekriterien die Reliabilität und faktorielle Validität in drei Teilstichproben: 216 Studierende des Lehramts Sonderpädagogik und 149 Studierende sonstiger Lehramtsstudiengänge bearbeiteten den EFI-L vollständig, bei 157 Berufstätigen wurde eine Kurzform mit den Skalen Fachliche Förderung und Soziale Inklusion eingesetzt. Außerdem wurden zur Prüfung der Validität auch Zusammenhänge mit der Qualität persönlicher Erfahrungen in inklusiven Settings geprüft und ob sich die gemessenen Einstellungen in den Teilstichproben unterscheiden, wobei für Studierende der Sonderpädagogik die positivsten Einstellungen zu Inklusion erwartet wurden. Die Reliabilitätsschätzungen (interne Konsistenz) ergaben in allen Teilstichproben befriedigende Werte. Konfirmatorische Faktorenanalysen zeigten weder für das 3-faktorielle Modell der Studierenden noch für eine 2-faktorielle Form bei Berufstätigen eine überzeugende Passung. In Gruppenvergleichen fanden sich die höchsten Werte bei Studierenden der Sonderpädagogik. Die erlebte Qualität von persönlichen Erfahrungen mit inklusiven Bildungsangeboten korrelierte positiv mit den Skalen des EFI-L. (DIPF/Orig.)The aim of the present study is to expand the psychometric knowledge base on the „Questionnaire on Attitudes towards Inclusion for Teachers” (EFI-L). The data were collected in the context of a study on attitudes towards inclusion of students with physical disabilities. Reliability and factorial validity were investigated as central quality criteria in three subsamples: 216 pre-service teachers in special education and 149 pre-service teachers in other teacher education programs completed the complete EFI-L, and a short form with the scales Promoting academic competencies and Social Inclusion was used for157 professionals. Furthermore, in terms of placing the EFI-L in a nomological network, the attitudes measured were expected to be related to the quality of personal experiences in inclusive settings and to differ across the subsamples, with special education students expected to have the most positive attitudes toward inclusion. Reliability estimates (internal consistency) yielded satisfactory values in all subsamples. Confirmatory factor analyses showed no convincing fit for either the 3-factorial model among students and the 2-factorial model among professionals. In group comparisons, the highest values were found among students of special education. The perceived quality of personal experiences with inclusion correlated positively with the scales of the EFI-L. (DIPF/Orig.

Lesion Extent Negatively Impacts Intellectual Skills in Pediatric Focal Epilepsy

BACKGROUND Cognitive development in children and adolescents with focal lesional epilepsy is determined by the underlying epileptogenic lesion, in addition to epilepsy itself. However, the impact of lesion-related variables on intelligence quotient (IQ) and developmental quotient (DQ) remains largely unexplored. Here, we aimed to determine the effect of lesion-related predictors and their relation with epilepsy-related predictors of intellectual functioning. METHODS We retrospectively analyzed data from children with focal lesional epilepsy who underwent standardized cognitive evaluation yielding IQ/DQ in our institution. RESULTS We included 50 consecutive patients aged 0.5 to 17.5 years (mean, 9.3; S.D., 4.9) at cognitive assessment. Epilepsy duration was 0 to 15.5 years (mean, 3.8; S.D., 4.1). Of the total cohort, 30 (60%) patients had unilobar lesions, seven (14%) multilobar, 10 (20%) hemispheric, and three (6%) bilateral. Etiology was congenital in 32 (64%) cases, acquired in 14 (28%), and progressive in four (8%). For patients with unilobar lesions, the mean IQ/DQ was 97.1 ± 15.7, for multilobar 98.9 ± 20.2, for hemispheric 76.1 ± 20.5, and for bilateral 76.3 ± 4.5. Larger lesion extent, earlier epilepsy onset, and longer epilepsy duration correlated with lower IQ/DQ in the univariate analysis, whereas only lesion extent and epilepsy duration contributed significantly to the explanatory model in the multivariable analysis. CONCLUSIONS The present study demonstrates that lesion extent and epilepsy duration are important risk factors for intellectual impairment in pediatric patients with focal lesional epilepsy. These findings are useful for family counseling and the early consideration of interventions that may limit the duration of epilepsy

Alterations of lipid metabolism in Wilson disease

<p>Abstract</p> <p>Introduction</p> <p>Wilson disease (WD) is an inherited disorder of human copper metabolism, characterised by accumulation of copper predominantly in the liver and brain, leading to severe hepatic and neurological disease. Interesting findings in animal models of WD (Atp7b^-/-and LEC rats) showed altered lipid metabolism with a decrease in the amount of triglycerides and cholesterol in the serum. However, serum lipid profile has not been investigated in large human WD patient cohorts to date.</p> <p>Patients and Methods</p> <p>This cohort study involved 251 patients examined at the Heidelberg and Dresden (Germany) University Hospitals. Patients were analysed on routine follow-up examinations for serum lipid profile, including triglycerides, cholesterol, high density lipoprotein (HDL) and low density lipoprotein (LDL). Data on these parameters at time of diagnosis were retrieved by chart review where available. For statistical testing, patients were subgrouped by sex, manifestation (hepatic, neurological, mixed and asymptomatic) and treatment (D-penicillamine, trientine, zinc or combination).</p> <p>Results</p> <p>A significant difference in total serum cholesterol was found in patients with hepatic symptoms, which diminished under therapy. No alterations were observed for HDL, LDL and triglycerides.</p> <p>Conclusion</p> <p>Contradictory to previous reports using WD animal models (Atp7b^-/-and LEC rats), the most obvious alteration in our cohort was a lower serum cholesterol level in hepatic-affected patients, which might be related to liver injury. Our data suggested unimpaired cholesterol metabolism in Wilson disease under therapy, independent of the applied medical treatment.</p

Transcriptomes of <i>Trypanosoma brucei</i> rhodesiense from sleeping sickness patients, rodents and culture:Effects of strain, growth conditions and RNA preparation methods

All of our current knowledge of African trypanosome metabolism is based on results from trypanosomes grown in culture or in rodents. Drugs against sleeping sickness must however treat trypanosomes in humans. We here compare the transcriptomes of Trypanosoma brucei rhodesiense from the blood and cerebrospinal fluid of human patients with those of trypanosomes from culture and rodents. The data were aligned and analysed using new user-friendly applications designed for Kinetoplastid RNA-Seq data. The transcriptomes of trypanosomes from human blood and cerebrospinal fluid did not predict major metabolic differences that might affect drug susceptibility. Usefully, there were relatively few differences between the transcriptomes of trypanosomes from patients and those of similar trypanosomes grown in rats. Transcriptomes of monomorphic laboratory-adapted parasites grown in in vitro culture closely resembled those of the human parasites, but some differences were seen. In poly(A)-selected mRNA transcriptomes, mRNAs encoding some protein kinases and RNA-binding proteins were under-represented relative to mRNA that had not been poly(A) selected; further investigation revealed that the selection tends to result in loss of longer mRNAs

Utilization frequency and patient-reported effectiveness of symptomatic therapies in post-COVID syndrome

Background To date there is no causal treatment for post-COVID syndrome, leaving symptomatic treatments as the primary recourse. However, the practical implementation and effectiveness of these interventions remain underexplored. This study aimed to investigate the utilization frequency of symptomatic therapies and patient-reported effectiveness across various treatment modalities at a German post-COVID center. Methods As the baseline investigation we conducted a single-cohort retrospective study to analyze the frequency of symptomatic therapies among post-COVID patients who attended the post-COVID center of the University Hospital of Erlangen, between December 2022 to July 2023. Additionally, we administered a follow-up at least 3 months after the initial presentation, using a questionnaire to assess patient-reported improvements in post-COVID symptoms associated with the symptomatic therapies received. Results Our study included 200 patients (mean age: 44.6 ± 12.6 years; 69.0% women; mean duration since acute infection: 15.3 ± 8.3 months). Pharmacotherapy was the predominant symptomatic treatment (79.5%), with psychotropic drugs (32.5%) and analgesics (31.5%) being the most frequently prescribed. Over half of the patients (55.5%) utilized vitamins and nutritional supplements. Hospital admission rates to acute care occurred in 35.5% of cases; 33.0% underwent inpatient rehabilitation and 31.0% pursued outpatient psychotherapy. Cardiologists (76.5%), pulmonologists (67.5%), and neurologists (65.5%) were the most consulted specialists. Therapies involving medical devices were infrequently employed (12.0%). In a follow-up questionnaire (response rate: 82.5%, 6.3 ± 2.2 months post-baseline), beta-blockers were the most effective pharmacological intervention with 31.5% of patients reporting strong to very strong symptom improvement, followed by antibiotics (29.6%). Furthermore, 33.0% of the patients perceived plasmapheresis to strongly alleviate symptoms. Only a small proportion of the sample attributed a strong or very strong symptom improvement to outpatient psychotherapy (11.0%). Conclusion This study provides initial insights into symptomatic therapy utilization and patient-reported symptom improvement in post-COVID syndrome. Further research into symptoms clusters and interdisciplinary collaboration are warranted to comprehensively address the multifaceted physical and psychological symptomatology. Trial registration The study was registered at the German Clinical Trials Register (DRKS-ID: DRKS00033621) on March 20, 2024.Open Access funding enabled and organized by Projekt DEAL.Universitätsklinikum Erlangen (8546

Quorum sensing in African Trypanosomes

Many microbial eukaryotes exhibit cell-cell communication to co-ordinate group behaviours as a strategy to exploit a changed environment, adapt to adverse conditions or regulate developmental responses. Although best characterised in bacteria, eukaryotic microbes have also been revealed to cooperate to optimise their survival or dissemination. An excellent model for these processes are African trypanosomes, protozoa responsible for important human and animal disease in sub Saharan Africa. These unicellular parasites use density sensing in their mammalian host to prepare for transmission. Recently, the signal and signal transduction pathway underlying this activity have been elucidated, revealing that the parasite exploits oligopeptide signals generated by released peptidases to monitor cell density and so generate transmission stages. Here we review the evidence for this elegant quorum sensing mechanism and its parallels with similar mechanisms in other microbial systems. We also discuss its implications for disease spread in the context of coinfections involving different trypanosome species

Three-Month Follow-Up of the Post-COVID Syndrome after Admission to a Specialised Post-COVID Centre—A Prospective Study Focusing on Mental Health with Patient Reported Outcome Measures (PROMs) †

Background and objective: The impairments and duration of PASC (post-acute sequelae of COVID-19) symptoms in mental health have, to date, not been comprehensively examined. Our objective is to provide longitudinal data on the mental health of Post-COVID patients and to identify risk and protective factors associated with a severe or prolonged course. Methods: The mental health of 265 Post-COVID patients of the outpatient Post-COVID centre of the University Hospital Erlangen was assessed 17.1 (T0) and 22.5 months after infection (T1). An online survey with validated questionnaires for Post-COVID symptoms (Post-COVID Syndrome Score), depression (Patient Health Questionnaire-9), somatic symptoms (Patient Health Questionnaire-15), anxiety (Generalized Anxiety Disorder-7), fatigue (Fatigue Severity Scale) and Post-Exertional Malaise (PEM) (DePaul Post-Exertional Malaise Screening) was conducted in the home environment. Results: In total, 80% of patients experienced severe PASC at follow-up. Clinically relevant symptoms of depression, persistent somatic symptoms, anxiety and fatigue were reported by 55.8%, 72.5%, 18.9% and 89.4% of patients, respectively. Depressive, anxiety and somatic symptom severity decreased significantly over time; fatigue and PEM remained at an unchanged high level. The risk factor for higher depression scores was older age; prior psychiatric illness treated with psychotherapy was associated with more severe depressive, somatic, anxiety and PASC symptoms. PEM symptoms were significantly associated with longer duration between acute infection and initial presentation in the Post-COVID centre. Conclusions: Our findings align with previous research, claiming severe mental health symptoms in PASC syndrome, lasting for months after infection. In-depth assessment of risk and protective factors for the mental health implications of PASC is needed for the planning of health services and disease prevention.This research received no external funding