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Persistent poor psychosocial functioning, which is associated with impairments in cognition, is one of the main barriers to recovery in schizophrenia. Although cognitive remediation therapy (CRT) has shown general efficacy in improving cognition and functioning, simultaneously focusing on social cognition and social behavioural processes may increase its efficacy. In a multicenter, rater-blinded, randomized controlled trial, schizophrenia patients (N=177) were assigned to six months of either Integrated Social Cognitive and Behavioral Skills Therapy (ISST) or, as an active control intervention, Neurocognitive Remediation Therapy (NCRT). The primary endpoint was all-cause discontinuation (ACD) over the 12-month study period. Secondary endpoints were cognition, psychosocial functioning and quality of life, and clinical symptoms. ACD was not significantly different between the ISST and NCRT groups (43.3% vs 34.5%, respectively). More improvement was seen in social cognition (Pictures of Facial Affect; d=0.83) in the ISST group and in neurocognition (subscores of the Auditory Verbal Learning Test; d=0.29-0.40) in the NCRT group. Level of functioning, quality of life, and clinical symptoms significantly improved in both groups, with no significant between-group differences. Both therapies differentially improved measures of the cognitive domains they were designed for. Moreover, they both improved social functioning with high effect sizes (d=0.8-1.0), underlining the important role of CRT in recovery-oriented schizophrenia treatment. However, the absence of a third group without an active intervention limits the interpretability of the results.

Objectives: Pregnancies in women with Fontan circulation are on the rise, and they are known to imply high maternal and fetal complication rates. The altered hemodynamic profile of univentricular circulation affects placental development and function. This study describes placental sonomorphologic appearance and Doppler examinations and correlates these to histopathologic findings and pregnancy outcomes in women with Fontan circulation. Methods: A single-center retrospective analysis of pregnancies in women with Fontan circulation was conducted between 2018 and 2023. Maternal characteristics and obstetric and neonatal outcomes were recorded. Serial ultrasound examinations including placental sonomorphologic appearance and Doppler studies were assessed. Macroscopic and histopathologic findings of the placentas were reviewed. Results: Six live births from six women with Fontan physiology were available for analysis. Prematurity occurred in 83% (5/6 cases) and fetal growth restriction and bleeding events in 66% (4/6 cases) each. All but one placenta showed similar sonomorphologic abnormalities starting during the late second trimester, such as thickened globular shape, inhomogeneous echotexture, and hypoechoic lakes, resulting in a jelly-like appearance. Uteroplacental blood flow indices were within normal range in all women. The corresponding histopathologic findings were non-specific and consisted of intervillous and subchorionic fibrin deposition, villous atrophy, hypoplasia, or fibrosis. Conclusions: Obstetric and perinatal complication rates in pregnancies of women with Fontan circulation are high. Thus, predictors are urgently needed. Our results suggest that serial ultrasound examinations with increased awareness of the placental appearance and its development, linked to the Doppler sonographic results of the uteroplacental and fetomaternal circulation, may be suitable for the early identification of cases prone to complications.

Spreading depolarizations (SD) contribute to lesion progression after experimental focal cerebral ischemia while such correlation has never been shown in stroke patients. In this prospective, diagnostic study, we investigate the association of SDs and secondary infarct progression after malignant hemispheric stroke. SDs were continuously monitored for 3–9 days with electrocorticography after decompressive hemicraniectomy for malignant hemispheric stroke. To ensure valid detection and analysis of SDs, a threshold based on the electrocorticographic baseline activity was calculated to identify valid electrocorticographic recordings. Subsequently SD characteristics were analyzed in association to infarct progression based on serial MRI. Overall, 62 patients with a mean stroke volume of 289.6 ± 68 cm3 were included. Valid electrocorticographic recordings were found in 44/62 patients with a mean recording duration of 139.6 ± 26.5 hours and 52.5 ± 39.5 SDs per patient. Infarct progression of more than 5% was found in 21/44 patients. While the number of SDs was similar between patients with and without infarct progression, the SD-induced depression duration per day was significantly longer in patients with infarct progression (593.8 vs. 314.1 minutes; *p = 0.046). Therefore, infarct progression is associated with a prolonged SD-induced depression duration. Real-time analysis of electrocorticographic recordings may identify secondary stroke progression and help implementing targeted management strategies.

For adolescents, DSM-5 differentiates anorexia nervosa (AN) and atypical AN with the 5th BMI-centile-for-age. We hypothesized that the diagnostic weight cut-off yields (i) lower weight loss in atypical AN and (ii) discrepant premorbid BMI distributions between the two disorders. Prior studies demonstrate that premorbid BMI predicts admission BMI and weight loss in patients with AN. We explore these relationships in atypical AN. Based on admission BMI-centile < or ≥5th, participants included 411 female adolescent inpatients with AN and 49 with atypical AN from our registry study. Regression analysis and t-tests statistically addressed our hypotheses and exploratory correlation analyses compared interrelationships between weight loss, admission BMI, and premorbid BMI in both disorders. Weight loss in atypical AN was 5.6 kg lower than in AN upon adjustment for admission age, admission height, premorbid weight and duration of illness. Premorbid BMI-standard deviation scores differed by almost one between both disorders. Premorbid BMI and weight loss were strongly correlated in both AN and atypical AN. Whereas the weight cut-off induces discrepancies in premorbid weight and adjusted weight loss, AN and atypical AN overall share strong weight-specific interrelationships that merit etiological consideration. Epidemiological and genetic associations between AN and low body weight may reflect a skewed premorbid BMI distribution. In combination with prior findings for similar psychological and medical characteristics in AN and atypical AN, our findings support a homogenous illness conceptualization. We propose that diagnostic subcategorization based on premorbid BMI, rather than admission BMI, may improve clinical validity. Because body weights of patients with AN must drop below the 5th BMI-centile per DSM-5, they will inherently require greater weight loss than their counterparts with atypical AN of the same sex, age, height and premorbid weight. Indeed, patients with atypical AN had a 5.6 kg lower weight loss after controlling for these variables. In comparison to the reference population, we found a lower and higher mean premorbid weight in patients with AN and atypical AN, respectively. Considering previous psychological and medical comparisons showing little differences between AN and atypical AN, we view a single disorder as the most parsimonious explanation. Etiological models need to particularly account for the strong relationship between weight loss and premorbid body weight.

Abstract. The loess–palaeosol sequence and intercalated Palaeolithic find layers at the former brickyard of Rheindahlen are matters of ongoing scientific dispute. The age of different palaeosols and loess layers, hence their correlation with the global climate cycles, and the timing of repeated Neanderthal occupations have been hotly debated. These disagreements should be solved because the exceptional sedimentary and Palaeolithic sequences at Rheindahlen provide a unique opportunity to study diachronic changes in Neanderthal behaviour within the context of past climate change. We thus revisited one of the key loess sections of the Rheindahlen site to improve our understanding of loess formation processes and provide a more reliable chronostratigraphic framework for the sequence. High-resolution grain size analyses and micromorphology show that the Erkelenz Soil and the Rheindahlen Soil are characterized by more strongly developed Bt horizons than the modern soil. While these soils represent interglacial phases, the lowermost palaeosol likely formed during an interstadial and has been overprinted by weak clay illuviation during the formation of the Rheindahlen Soil. Sedimentary features of prolonged frost characterize loess and palaeosols below the modern soil and give indirect evidence for a Holocene age of the uppermost part of the sequence. Our luminescence dating approach corroborates this correlation and adds several Last Glacial deposition ages for the upper metres of the sequence. Previous correlation of this part of the sedimentary sequence with the penultimate glacial is thus rejected, whereas placing the Middle Palaeolithic inventories A3, B1, and B2 into the Last Glacial is confirmed. Luminescence measurements for the parental loess of the Erkelenz Soil and for loess layers below did not provide reliable ages probably related to signal saturation. The age of this part of the sequence thus remains open, hence the timing of human occupation testified by Palaeolithic inventories B3, B4/5, C1, and D1. The new findings provide an improved base for stratigraphic correlation of the Rheindahlen loess sequence and for investigating diachronic change in Neanderthal behaviour against the background of past climate change.

Clinical high risk for psychosis (CHR-P) offers a window of opportunity for early intervention and recent trials have shown promising results for the use of N-acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention (IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of CHR-P patients. In this double-blind, randomized, controlled multicenter trial, a 2 × 2 factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI compared to psychological stress management (PSM). The primary endpoint was the transition to psychosis or deterioration of CHR-P symptoms after 18 months. While insufficient recruitment led to early trial termination, a total of 48 participants were included in the study. Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI + NAC: 72.7 ± 13.4%, PSM + NAC: 72.7 ± 13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ± 15.3%, PSM + PLC: 39.0 ± 17.4%). However, a log-rank chi-square test in Kaplan-Meier analysis revealed no significant difference of survival probability for NAC vs control (point hazard ratio: 0.879, 95% CI 0.281-2.756) or IPPI vs control (point hazard ratio: 0.827, 95% CI 0.295-2.314). The number of adverse events (AE) did not differ significantly between the four groups. The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P compared to controls could not be statistically validated in this trial. However, results indicate a consistent pattern that warrants further testing of NAC as a promising and well-tolerated intervention for CHR patients in future trials with adequate statistical power.

Pharmacotherapy with drugs like naltrexone or acamprosate is a well-evaluated element in the treatment of alcohol dependence (AD). However, in many countries, these medications are rarely administered. The objective of the present study was to identify from patients' perspective factors that prevent the initiation and compliance with pharmacological treatment of AD. Patients from inpatient alcohol withdrawal treatment underwent a standardized interview. Questions included socio-demographic data, history of AD, treatment history, knowledge and personal experience regarding pharmacotherapy of AD, and personal views about the causes of AD. Three hundred patients (mean age 47.3 years, 27.7% female, mean duration of AD 8.9 years, 67% with a history of previous inpatient withdrawal treatment) were included. The majority of patients (58.7%) already knew drugs for the pharmacotherapy of AD. Thirty percent had ever used such medications, most often acamprosate. Except for disulfiram, pharmacotherapy of AD had lasted only a few weeks, on average. Medication usually had been applied without additional psychotherapy. No severe side effects were reported. Patients had often stopped pharmacotherapy on their own, when assuming they had reached stable abstinence. Openness to start pharmacotherapy for AD was currently stated by 67% of the total sample. In multiple logistic regression, openness was predicted by having a concept of AD as a medical disease and by a shorter duration of AD. To improve the administration of pharmacotherapy for AD implementation strategies should be systematically developed and evaluated with a focus on the concept of AD as a medical disease.