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BackgroundThe Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score".MethodsThe COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed.ResultsFrom >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex.ConclusionsCOH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.

Background The mental health benefits of cannabidiol (CBD) are promising but can be inconsistent, in part due to challenges in defining an individual’s effective dosage. In schizophrenia, alterations in anandamide (AEA) concentrations, an endocannabinoid (eCB) agonist of the eCB system, reflect positively on treatment with CBD. Here, we expanded this assessment to include eCBs alongside AEA congeners, comparing phytocannabinoids and dosage in a clinical setting.Methods Liquid chromatography-tandem mass spectrometry quantified changes in serum levels of AEA, 2-arachidonoylglycerol (2-AG), alongside AEA-related compounds oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which were attained from two independent, parallel-designed, clinical trials investigating single, oral CBD (600 or 800 mg), delta-9-tetrahydrocannabinol (Δ9-THC, 10 or 20 mg) and combination administration (CBD|800 mg+Δ9-THC|20 mg) in healthy volunteers (HVs, n=75). Concentrations were measured at baseline (t=0), 65 and 160 min post administration.Results CBD-led increases in AEA (1.6-fold), OEA and PEA (1.4-fold) were observed following a single 800 mg (pcorr

Summary: Both mental health and mental illness unfold in complex and unpredictable ways. Novel artificial intelligence approaches from the area of dynamical systems reconstruction can characterize such dynamics and help understand the underlying brain mechanisms, which can also be used as potential biomarkers. However, applying deep learning to model dynamical systems at the individual level must overcome numerous computational challenges to be reproducible and clinically useful. In this study, we performed an extensive analysis of these challenges using generative modeling of brain dynamics from fMRI data as an example and demonstrated their impact on classifying patients with schizophrenia and major depression. This study highlights the tendency of deep learning models to identify functionally unique solutions during parameter optimization, which severely impacts the reproducibility of downstream predictions. We hope this study guides the future development of individual-level generative models and similar machine learning approaches aimed at identifying reproducible biomarkers of mental illness.

IntroductionBrachycephalic obstructive airway syndrome (BOAS) is a common condition in brachycephalic dogs, with Pugs (PG) and French Bulldogs (FB) appearing to be particularly typically affected. Objective and easy-to-perform tests are necessary to detect the disease at an early stage and to exclude dogs affected by BOAS from breeding.MethodsThe present study investigated the extent to which vital signs and salivary cortisol concentrations can be used to distinguish between healthy and BOAS-affected dogs in a standardized fitness test. A total of 57 PG, 56 FB and 27 meso- and dolichocephalic dogs were studied as control group (CG). In addition to vital signs, salivary cortisol concentrations were measured before and after the exercise test.ResultsIt emerged that non-brachycephalic dogs showed a higher fitness level than brachycephalic dogs. The PG recovered significantly slower than the FB after the exercise test. In unaffected PG, cortisol levels rose significantly after the test and then fell again, in unaffected FB they fell significantly during the test. Unexpectedly, cortisol levels remained constant in BOAS affected dogs of both breeds.DiscussionA possible explanation could be a disturbance of the pituitary–hypothalamic–adrenal axis, which could be due to the chronic stress of affected animals. This would have to be clarified in further studies. In conclusion, a submaximal fitness test may be a useful method to identify dogs suffering from BOAS as it is imperative to prevent the breeding and reproduction of affected dogs.

Abstract Background Mammary adenocarcinomas are one of the most common tumour diseases in bitches. The relationship between oxidative stress and the degree of malignancy of the tumour has not been sufficiently researched in veterinary medicine. Objectives The main objective was to investigate the potential role of MDA as a practice‐relevant biomarker for the assessment of systemic oxidative stress and to determine whether this parameter can indicate the malignancy grade of a mammary adenocarcinoma. Methods In the present pilot study, MDA plasma concentrations were analysed in 55 bitches with (n = 28) and without (n027) malignant adenocarcinomas of the mammary gland using two different measurement methods and the relationship to tumour size was investigated. Results The mean MDA concentration measured by enzyme‐linked immunosorbent assay (ELISA) was 289 ng/mL (range 365–634 ng/mL) in dogs with grade 1 adenocarcinoma (n = 13), 288.5 ng/mL (range 85–752 ng/mL) in dogs with grade 2 adenocarcinoma (n = 10), 332 ng/mL (range 239–947 ng/mL) in dogs with grade 3 (n = 5) adenocarcinoma and 293 ng/mL (range 175–549 ng/mL) in dogs without a mammary tumour (n = 27). When MDA was measured by HPLC, the average MDA concentration in the study group (n = 11) was 0.24 µmol/L (range 0.16–0.37) and that of the control group (n = 15) was 0.27 µmol/L (range 0.16–1.62). Thus, there were no significant differences between the study group with malignant adenocarcinomas and the control group in both examination methods (p > 0.05). Furthermore, there was no correlation between the MDA concentrations and the approximate volume of the mammary tumour. Conclusion The results highlight the challenges of providing a prognosis for the malignancy of a mammary adenocarcinoma based on MDA concentrations in plasma using ELISA or HPLC. As a result, histopathological examination remains the gold standard for diagnosing and differentiating adenocarcinomas of the mammary gland.

Declarative memory retrieval is thought to involve reinstatement of neuronal activity patterns elicited and encoded during a prior learning episode. Furthermore, it is suggested that two mechanisms operate during reinstatement, dependent on task demands: individual memory items can be reactivated simultaneously as a clustered occurrence or, alternatively, replayed sequentially as temporally separate instances. In the current study, participants learned associations between images that were embedded in a directed graph network and retained this information over a brief 8 min consolidation period. During a subsequent cued recall session, participants retrieved the learned information while undergoing magnetoencephalographic recording. Using a trained stimulus decoder, we found evidence for clustered reactivation of learned material. Reactivation strength of individual items during clustered reactivation decreased as a function of increasing graph distance, an ordering present solely for successful retrieval but not for retrieval failure. In line with previous research, we found evidence that sequential replay was dependent on retrieval performance and was most evident in low performers. The results provide evidence for distinct performance-dependent retrieval mechanisms, with graded clustered reactivation emerging as a plausible mechanism to search within abstract cognitive maps.

IntroductionThe cat represents an important model in order to investigate basic physiological knowledge of salivary secretion as well as pharmacokinetics of active substances.ObjectiveThe aim of the study was to review in which diagnostic application areas saliva testing is routinely used and in which areas it could be further explored in the future.Materials and methodsLiterature relevant to the research question was collected in March 2022 using the Pubmed database.ResultsThe diagnosis of infectious diseases in cat saliva is one of the most important fields of application. Saliva diagnostics may also indicate dental diseases, allergies or kidney and other metabolic diseases. Sexual and stress hormones can also be measured in cat saliva. A number of clinically relevant allergens in cat saliva that may cause allergies in humans has been investigated and described, in addition to infectious agents that can be transmitted from cats to humans.ConclusionsSaliva testing in cats can be useful in many areas, including the detection of infectious diseases, allergies and dental disease. However, it is far from being used to its full potential within veterinary medicine.

Abstract Background Suicidality, ranging from passive suicidal thoughts to suicide attempt, is common in major depressive disorder (MDD). However, relatively little is known about patient, illness and treatment characteristics in those with co-occurring MDD and suicidality, including the timing of and factors associated with the offset, continuation or reemergence of suicidality. Here, we present the background, rationale, design and hypotheses of the Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression (OASIS-D) study, an investigator-initiated, observational study, funded by Janssen-Cilag GmbH. Methods/Results OASIS-D is an eight-site, six-month, cohort study of patients aged 18-75 hospitalized with MDD. Divided into three sub-studies and patient populations (PPs), OASIS-D will (i) systematically characterize approximately 4500 consecutively hospitalized patients with any form of unipolar depressive episode (PP1), (ii) evaluate the validity of the clinical diagnosis of moderate or severe unipolar depressive episode with the Mini-International Neuropsychiatric Interview (M.I.N.I.) and present suicidality (at least passive suicidal thoughts) present ≥ 48 h after admission with the Sheehan-Suicide Tracking Scale (S-STS), assessing also predictors of the diagnostic concordance/discordance of MDD in around 500 inpatients (PP2), and (iii) characterize and prospectively follow for 6 months 315 inpatients with a research-verified moderate or severe unipolar depressive episode and at least passive suicidal thoughts ≥ 48 h after admission, evaluating treatment and illness/response patterns at baseline, hospital discharge, 3 and 6 months. Exploratory objectives will describe the association between the number of days with suicidality and utilization of outpatient and inpatient care services, and structured assessments of factors influencing the risk of self-injurious behavior without suicidal intent, and of continuous, intermittent or remitted suicidality during the 6-month observation period. Conclusion Despite their frequency and clinical relevance, relatively little is known about patient and treatment characteristics of individuals with MDD and suicidality, including factors moderating and mediating the outcome of both MDD and suicidality. Results of the OASIS-D study are hoped to improve the understanding of the frequency, correlates and 6-month naturalistic treatment and outcome trajectories of different levels of suicidality in hospitalized adults with MDD and suicidality. Trial registration NCT04404309 [ClinicalTrials.gov]

In recent years several studies established the diagnostic value of anti-Müllerian hormone (AMH) in companion animals. However, less is known about physiological AMH concentrations in young individuals highlighting the necessity to apply the diagnostic findings to this group. The aim of this study was to determine the AMH values of healthy male and female dogs between the age of 8 and 48 weeks, tomcats under 8 weeks and up to 48 weeks of age and queens between 2 to 12 weeks of age. In total, 96 blood samples were collected. Anti-Müllerian hormone was measured in all samples and testosterone was measured in the oldest age group of the males in both species. The hormones were analyzed using a human based chemiluminescence immune assay. Overall, AMH concentrations were higher in males than in females (p < 0.001). According to the AMH concentration there was no difference in males, but queens had significant higher AMH concentrations than bitches (p < 0.001). AMH remained high in males up to week 24 and decreased significantly thereafter (tomcats: p = 0.015; male dogs: p = 0.013), which correlated with an increase in testosterone levels for male dogs only. In bitches, AMH remained below the detection limit until the week 16 and slightly increased subsequently. In queens, AMH was detectable from the beginning with a significant increase in the older age group (p = 0.003). Half of the cats in the older age group even approached the chemiluminescence immune assay’s upper limit. The results show that female cats secrete AMH much earlier than female dogs in which AMH secretion begins just shortly before the start of the puberty. In the male animals, the decrease in AMH concentration around puberty was similar in dogs and cats, but a correlation with the increase of testosterone was only observed in dogs. Further research is required to determine the origin of the high AMH concentrations in female kittens and the lack of correlation between testosterone and AMH concentrations in male kittens.

Abstract Background Climate change is one of the greatest threats to health that societies face and can adversely affect mental health. Given the current lack of a European consensus paper on the interplay between climate change and mental health, we signal a need for a pan-European position paper about this topic, written by stakeholders working in mental health care. Methods On behalf of the European Psychiatric Association (EPA), we give recommendations to make mental health care, research, and education more sustainable based on a narrative review of the literature. Results Examples of sustainable mental healthcare comprise preventive strategies, interdisciplinary collaborations, evidence-based patient care, addressing social determinants of mental health, maintaining health services during extreme weather events, optimising use of resources, and sustainable facility management. In mental health research, sustainable strategies include investigating the impact of climate change on mental health, promoting research on climate change interventions, strengthening the evidence base for mental health-care recommendations, evaluating the allocation of research funding, and establishing evidence-based definitions and clinical approaches for emerging issues such as ‘eco-distress’. Regarding mental health education, planetary health, which refers to human health and how it is intertwined with ecosystems, may be integrated into educational courses. Conclusions The EPA is committed to combat climate change as the latter poses a threat to the future of mental health care. The current EPA position paper on climate change and mental health may be of interest to a diverse readership of stakeholders, including clinicians, researchers, educators, patients, and policymakers.

BackgroundSevere and complex angular limb deformities in dogs require accurate morphological assessment using diagnostic imaging to achieve successful orthopedic surgery. Computed tomography (CT) is commonly used to overcome projection errors in two-dimensional angular measurements of dog hindlimb alignment. Three-dimensional volume rendering (VR) techniques permit virtual positioning and variable projection, but the final CT-image that defines the projection plane for angular measurements remains two-dimensional.ObjectiveWe wanted to develop a true three-dimensional open-source technique to measure the alignments of the hind limbs of dogs in CT scanners.MethodsWe developed an open-source 3D Slicer plug-in, to perform angular measurements using vector calculations in three-dimensional space. In 113 CT-scans of canine pelvic limbs, femoral torsion, femoral varus, femorotibial rotation, tibial torsion, tibial varus and tibiotalar rotation angles were calculated and compared to an already validated technique using VoXim®.ResultsReference points were identified and measurements were possible in the 113 acquisitions. The greatest difference between the two techniques was 1.4° at only one tibial torsion angle. Mean values for all Bland-Altman plots did not show significant differences and were less than 0.07° for all comparisons.DiscussionBased on these results we considered angular measurements of canine hind limb alignment in CT scans using the 3D Slicer extension program sufficiently accurate for clinical orthopedic and surgical purposes in veterinary medicine.ConclusionWith our open-source 3D Slicer extension software, we provide a free accessible tool for veterinary orthopedic surgeons and thus we hope to improve angular measurements in CT-scans of canine hind limb deformities through true three-dimensionality.

Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

Bone substitutes are ideally biocompatible, osteoconductive, degradable and defect-specific and provide mechanical stability. Magnesium phosphate cements (MPCs) offer high initial stability and faster degradation compared to the well-researched calcium phosphate cements (CPCs). Calcium magnesium phosphate cements (CMPCs) should combine the properties of both and have so far shown promising results. The present study aimed to investigate and compare the degradation and osseointegration behavior of 3D powder-printed wedges of CMPC and MPC in vivo. The wedges were post-treated with phosphoric acid (CMPC) and diammonium hydrogen phosphate (MPC) and implanted in a partially loaded defect model in the proximal rabbit tibia. The evaluation included clinical, in vivo µ-CT and X-ray examinations, histology, energy dispersive X-ray analysis (EDX) and scanning electron microscopy (SEM) for up to 30 weeks. SEM analysis revealed a zone of unreacted material in the MPC, indicating the need to optimize the manufacturing and post-treatment process. However, all materials showed excellent biocompatibility and mechanical stability. After 24 weeks, they were almost completely degraded. The slower degradation rate of the CMPC corresponded more favorably to the bone growth rate compared to the MPC. Due to the promising results of the CMPC in this study, it should be further investigated, for example in defect models with higher load.