The manifestation of affective symptoms in multiple sclerosis and discussion of the currently available diagnostic assessment tools.

INTRODUCTION In addition to physical and cognitive symptoms, patients with multiple sclerosis (MS) have an increased risk of experiencing mental health problems. METHODS This narrative review provides an overview of the appearance and epidemiology of affective symptoms in MS such as depression, anxiety, bipolar disorder, euphoria, and pseudobulbar affect. Furthermore, the association between affective symptoms and quality of life and the currently used diagnostic instruments for assessing these symptoms are considered whereby relevant studies published between 2009 and 2021 were included in the review. RESULTS Patients with mild and moderate disability more frequently reported severe problems with depression and anxiety than severe mobility problems. Apart from the occurrence of depression, little is known about the association of other affective symptoms such as anxiety, bipolar disorder, euphoria, and pseudobulbar affect and subsyndromal symptoms, which fail to meet the diagnostic criteria but are nevertheless a significant source of distress. Although there are a few recommendations in the research to perform routine screenings for diagnosable affective disorders, a standardized diagnostic procedure to assess subsyndromal symptoms is still lacking. As the applied measurements are diverse and show low accuracy to detect these symptoms, patients who experience affective symptoms are less likely to be identified. DISCUSSION In addition to the consideration of definite psychiatric diagnoses, there is an unmet need for a common definition and assessment of disease-related affective symptoms in MS. Future studies should focus on the improvement and standardization of a common diagnostic procedure for subsyndromal affective symptoms in MS to enable integrated and optimal care for patients

Globally invariant metabolism but density-diversity mismatch in springtails.

Soil life supports the functioning and biodiversity of terrestrial ecosystems. Springtails (Collembola) are among the most abundant soil arthropods regulating soil fertility and flow of energy through above- and belowground food webs. However, the global distribution of springtail diversity and density, and how these relate to energy fluxes remains unknown. Here, using a global dataset representing 2470 sites, we estimate the total soil springtail biomass at 27.5 megatons carbon, which is threefold higher than wild terrestrial vertebrates, and record peak densities up to 2 million individuals per square meter in the tundra. Despite a 20-fold biomass difference between the tundra and the tropics, springtail energy use (community metabolism) remains similar across the latitudinal gradient, owing to the changes in temperature with latitude. Neither springtail density nor community metabolism is predicted by local species richness, which is high in the tropics, but comparably high in some temperate forests and even tundra. Changes in springtail activity may emerge from latitudinal gradients in temperature, predation and resource limitation in soil communities. Contrasting relationships of biomass, diversity and activity of springtail communities with temperature suggest that climate warming will alter fundamental soil biodiversity metrics in different directions, potentially restructuring terrestrial food webs and affecting soil functioning

Global fine-resolution data on springtail abundance and community structure

Springtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.</p

Global fine-resolution data on springtail abundance and community structure

CODE AVAILABILITY : Programming R code is openly available together with the database from Figshare.SUPPLEMENTARY MATERIAL 1 : Template for data collectionSUPPLEMENTARY MATERIAL 2 : Data Descriptor WorksheetSpringtails (Collembola) inhabit soils from the Arctic to the Antarctic and comprise an estimated ~32% of all terrestrial arthropods on Earth. Here, we present a global, spatially-explicit database on springtail communities that includes 249,912 occurrences from 44,999 samples and 2,990 sites. These data are mainly raw sample-level records at the species level collected predominantly from private archives of the authors that were quality-controlled and taxonomically-standardised. Despite covering all continents, most of the sample-level data come from the European continent (82.5% of all samples) and represent four habitats: woodlands (57.4%), grasslands (14.0%), agrosystems (13.7%) and scrublands (9.0%). We included sampling by soil layers, and across seasons and years, representing temporal and spatial within-site variation in springtail communities. We also provided data use and sharing guidelines and R code to facilitate the use of the database by other researchers. This data paper describes a static version of the database at the publication date, but the database will be further expanded to include underrepresented regions and linked with trait data.Open Access funding enabled and organized by Projekt DEAL.http://www.nature.com/sdatahj2024Plant Production and Soil ScienceSDG-15:Life on lan

Non-pharmacological randomized intervention trial for the management of neuropsychological symptoms in outpatients with progressive multiple sclerosis.

PURPOSE Despite typically more pronounced cognitive and mental health issues in progressive disease courses of multiple sclerosis (PMS), rehabilitation research in this subgroup is rare. The efficacy of two non-pharmacological interventions with positive results from prior investigations was therefore examined in PMS specifically. METHODS Persons with PMS (pwPMS) received either computerized cognitive training (BrainStim), standardized cognitive-behavioral group sessions (Metacognitive Training [MaTiMS]), or a combination of both in an ambulatory setting. Neuropsychological assessment was conducted before and after the four-week intervention. RESULTS 37 participants (13 with primary/24 with secondary PMS, meanage = 52.87, SDage = 7.11, meanEDSS = 4.02, SDEDSS = 1.35) entered analyses. The BrainStim group improved in immediate and delayed verbal memory, recognition, verbal working memory, and perceived cognitive deficits while experiencing increased anxiety post-intervention. MaTiMS participants reported high program satisfaction and less cognitive difficulties at retest. The Combination group performed better in immediate and delayed verbal memory, and in information processing speed after training. Descriptive data further indicated positive effects on anxiety and depression in the MaTiMS and Combination group. CONCLUSIONS While objective cognitive performance improved when explicitly trained, psychoeducative sessions contributed to subjective mental health. The combination of both approaches is thus suggested, considering the specific needs of pwPMS treated in an ambulatory setting

Klinische Umsetzbarkeit der kognitiven Screeningbatterie BICAMS bei Patienten mit Multipler Sklerose: Ergebnisse der Machbarkeitsstudie in Deutschland

Hintergrund: Patienten mit Multipler Sklerose (MS) leiden in 40-70 % der Fälle unter kognitiven Störungen. Der kognitive Status gilt erwiesenermaßen als Prädiktor für Berufsfähigkeit und frühzeitige Berentung. Eine regelmäßige Erfassung der kognitiven Leistungsfähigkeit ist somit dringend indiziert. Zielsetzung: Die deutsche Fassung der international empfohlenen BICAMS (Brief International Cognitive Assessment for Multiple Sclerosis)-Batterie wurde auf Praktikabilität in der klinischen Routine neurologischer Praxen in Deutschland multizentrisch überprüft. Material und Methoden: Medizinische Fachangestellte (MFAs) wurden hinsichtlich der Durchführung und Auswertung von BICAMS geschult. Alle ausgewerteten Testbögen wurden von unabhängigen neuropsychologischen Experten überprüft. Ergebnisse: Insgesamt 1606 BICAMS-Datensätze wurden in 65 Zentren erhoben. Von diesen konnten 1573 analysiert werden. 49,7 % der erhobenen Datensätze wurden inklusive aller Auswerteschritte korrekt durchgeführt. Bei den anderen 50,3 % fanden sich Durchführungs-, Auswerte- oder Transformationsfehler. Nach Bereinigung der Stichprobe durch fehlerbehaftete Fälle ergaben sich Werte der Interrater-Reliabilität pro Testverfahren in Höhe von ICC &amp;gt;= 0,953. Diskussion: Grundsätzlich ist BICAMS für den Einsatz im klinischen Alltag sehr zu empfehlen. Es bleibt allerdings zu betonen, dass obgleich die Interrater-Reliabilität für die final bereinigte Stichprobe sehr hoch war, im Gesamtdatensatz 50,3 % Durchführungs-, Auswerte- oder Transformationsfehler gefunden wurden. Daraus lässt sich die Notwendigkeit ableiten, nicht-psychologisches Personal noch eingehender in der Anwendung und Auswertung von BICAMS durch Experten zu schulen und zu supervidieren

Supporting brain health in multiple sclerosis: exploring the potential of neuroeducation combined with practical mindfulness exercises in the management of neuropsychological symptoms.

OBJECTIVE We aimed at examining the effects of a known metacognitive training in MS (MaTiMS) and its modification with an additional neuroeducational module and mindfulness-based exercises (MaTiMS-modified) on neuropsychiatric and cognitive outcomes in people with progressive multiple sclerosis (pwpMS). Exploratively, we investigated whether the modification may show an additional benefit. METHODS Both interventions were administered in small groups of ambulatory patients. Neuropsychological testing before and after the 3- to 4-week intervention phase comprised patient reported outcomes and cognitive tests. After 3, 6 and 12 months, participants completed online surveys. Analysis of change scores (between baseline and retest) with t-tests (Mann-Whitney U and Wilcoxon tests, respectively) and mixed ANCOVAs with repeated measures for comparison of both interventions were conducted. RESULTS A total of 65 pwpMS turned to a final sample of 50 (n = 15 excluded due to drop-outs, occurrence of relapse or steroid treatment). Change scores within MaTiMS revealed no significant effect on the PDQ-20 total score and only a significant effect on the subscale retrospective memory lasting 3 months with a moderate effect size. In contrast, MaTiMS-modified revealed a highly significant change in PDQ-20 total compared to baseline and significant improvements with small to moderate effect sizes on all PDQ-20 subscales (lasting until 3 months), in self-efficacy, stress, visuo-spatial working memory (moderate effect sizes), and fatigue (small effect size). While no interaction effect between time and group could be revealed, a significant main effect for time was found in PDQ-20 total. CONCLUSION Both MaTiMS and MaTiMS-modified positively affected perceived cognitive deficits. However, our data speak in favor of additional benefits by adding neuroeducational and mindfulness-based exercises thus being valuable methods to support brain health including self-efficacy, perceived stress, and fatigue, even in patients with a chronic and progressive brain disease

Suspected penicillin allergy: risk assessment using an algorithm as an antibiotic stewardship project

&lt;jats:title&gt;Summary&lt;/jats:title&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Background&lt;/jats:title&gt; &lt;jats:p&gt;Beta-lactam antibiotics (BLA) are the treatment of choice for a large number of bacterial infections. Putative BLA allergies are often reported by patients, but rarely confirmed. Many patients do not receive BLA due to suspected allergy. There is no systematic approach to risk stratification in the case of a history of suspected BLA allergy.&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Methods&lt;/jats:title&gt; &lt;jats:p&gt;Using the available stratification programs and taking current guidelines into account, an algorithm for risk stratification, including recommendations on the use of antibiotics in cases of compellingly indicated BLA despite suspected BLA allergy, was formulated by the authors for their maximum care university hospital.&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Results&lt;/jats:title&gt; &lt;jats:p&gt;The hospital is in great need of recommendations on how to deal with BLA allergies. Patient-reported information in the history forms the basis for classifying the reactions into four risk categories: (1) BLA allergy excluded, (2) benign delayed reaction, (3) immediate reaction, and (4) severe cutaneous and extracutaneous drug reaction. Recommendations strictly depend on this classification and range from use of full-dose BLA or use of BLA under certain conditions (e.g., two-stage dose escalation, non-cross-reactive BLA only) to prohibiting all BLA and the use of alternative non-BLA. In case of suspected immediate or delayed allergic reactions, there is an additional recommendation regarding subsequent allergy testing during a symptom-free interval.&lt;/jats:p&gt; &lt;/jats:sec&gt;&lt;jats:sec&gt; &lt;jats:title&gt;Conclusion&lt;/jats:title&gt; &lt;jats:p&gt;Triage of patients with suspected BLA is urgently required. While allergy testing, including provocation testing, represents the most reliable solution, this is not feasible in all patients due to the high prevalence of BLA allergies. The risk stratification algorithm developed for the authors’ hospital represents a tool suitable to making a contribution to rational antibiotic therapy.&lt;/jats:p&gt; &lt;/jats:sec&gt

The transcriptional coactivator and histone acetyltransferase CBP regulates neural precursor cell development and migration

Abstract CREB (cyclic AMP response element binding protein) binding protein (CBP, CREBBP) is a ubiquitously expressed transcription coactivator with intrinsic histone acetyltransferase (KAT) activity. Germline mutations within the CBP gene are known to cause Rubinstein-Taybi syndrome (RSTS), a developmental disorder characterized by intellectual disability, specific facial features and physical anomalies. Here, we investigate mechanisms of CBP function during brain development in order to elucidate morphological and functional mechanisms underlying the development of RSTS. Due to the embryonic lethality of conventional CBP knockout mice, we employed a tissue specific knockout mouse model (hGFAP-cre::CBPFl/Fl, mutant mouse) to achieve a homozygous deletion of CBP in neural precursor cells of the central nervous system. Our findings suggest that CBP plays a central role in brain size regulation, correct neural cell differentiation and neural precursor cell migration. We provide evidence that CBP is both important for stem cell viability within the ventricular germinal zone during embryonic development and for unhindered establishment of adult neurogenesis. Prominent histological findings in adult animals include a significantly smaller hippocampus with fewer neural stem cells. In the subventricular zone, we observe large cell aggregations at the beginning of the rostral migratory stream due to a migration deficit caused by impaired attraction from the CBP-deficient olfactory bulb. The cerebral cortex of mutant mice is characterized by a shorter dendrite length, a diminished spine number, and a relatively decreased number of mature spines as well as a reduced number of synapses. In conclusion, we provide evidence that CBP is important for neurogenesis, shaping neuronal morphology, neural connectivity and that it is involved in neuronal cell migration. These findings may help to understand the molecular basis of intellectual disability in RSTS patients and may be employed to establish treatment options to improve patients’ quality of life

Opposing Effects of CREBBP Mutations Govern the Phenotype of Rubinstein-Taybi Syndrome and Adult SHH Medulloblastoma

Recurrent mutations in chromatin modifiers are specifically prevalent in adolescent or adult patients with Sonic hedgehog-associated medulloblastoma (SHH MB). Here, we report that mutations in the acetyltransferase CREBBP have opposing effects during the development of the cerebellum, the primary site of origin of SHH MB. Our data reveal that loss of Crebbp in cerebellar granule neuron progenitors (GNPs) during embryonic development of mice compromises GNP development, in part by downregulation of brain-derived neurotrophic factor (Bdnf). Interestingly, concomitant cerebellar hypoplasia was also observed in patients with Rubinstein-Taybi syndrome, a congenital disorder caused by germline mutations of CREBBP. By contrast, loss of Crebbp in GNPs during postnatal development synergizes with oncogenic activation of SHH signaling to drive MB growth, thereby explaining the enrichment of somatic CREBBP mutations in SHH MB of adult patients. Together, our data provide insights into time-sensitive consequences of CREBBP mutations and corresponding associations with human diseases