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Alterations of perfusion and functional connectivity of the cingulate motor area are associated with psychomotor retardation in major depressive disorder
No full textPsychomotor retardation, characterized by slowing of speech, thoughts, and a decrease of movements, is frequent in patients with major depressive disorder (MDD). However, its neurobiological correlates are still poorly understood. This study aimed to explore if cerebral blood flow (CBF) and resting state functional connectivity (rs-FC) of the motor network are altered in patients with MDD and if these changes are associated with psychomotor retardation. Thirty-six right-handed patients with depression and 19 right-handed healthy controls (HC) that did not differ regarding age and sex underwent arterial spin labelling (ASL) and resting-state functional MRI (rs-fMRI) scans. Psychomotor retardation was assessed with the motoric items of the core assessment of psychomotor change (CORE) questionnaire. Patients with MDD had more pronounced psychomotor retardation scores than HC. Patients with MDD had reduced CBF in bilateral cingulate motor area (CMA) and increased resting-state functional connectivity (rs-FC) between the cluster in the CMA and a cluster localized in bilateral supplementary motor areas (SMA). Furthermore, increased rs-FC between the CMA and the left SMA was associated with more pronounced psychomotor retardation. Our results suggest that reduced perfusion of the CMA and increased rs-FC between the CMA and the SMA are associated with psychomotor retardation in patients with depression
The effect of climate at origin on Douglas-fir growth, leaf traits and embolism resistance along a rainfall gradient in Central Europe
No full textKey message
In Douglas-fir grown in Central Europe, growth and specific leaf area differed between coastal and interior provenances but little intra-specific variability was found for the Huber value and xylem safety.
Abstract
In Central Europe, the economically most important timber species for roundwood production, Norway spruce, has been severely affected by recent global change-type drought events. Due to its large spatial distribution, Douglas-fir (Pseudotsuga menziesii) is considered for conversion to climate-resilient forests. Specifically, provenances from moister coastal and drier and colder interior regions might differ in drought tolerance traits. Here, we characterized aboveground biomass increment as well as leaf morphological and plant hydraulic traits in mature trees of 28 Douglas-fir provenances from three climate-at-origin groups across a climatic gradient in Central Europe, covering a precipitation range of 542 mm yr−1. Irrespective of the gradient, the northern interior provenances had a 5.4 kg yr−1 lower aboveground biomass increment than the two coastal groups, accompanied by a 13% smaller specific leaf area. On the other hand, the Huber value, embolism resistance (P50) and leaf carbon isotope signature (δ13C) as proxy for long-term intrinsic water use efficiency did not differ between climate-origin groups. Across the gradient and within a climate-origin-group, no effect of climatic aridity on any of the traits covered was observed. Especially P50 showed very little intra-specific variability, and our observed mean of −3.5 MPa is in the same range as P50-values for Douglas-fir recently reported from Europe. Our results for Douglas-fir support that xylem safety is a rather conservative and evolutionary canalized trait in conifers, while the Huber value revealed less plasticity as expected. Future studies are needed to test whether slower-growing interior provenances with thicker and smaller needles might be more drought tolerant and thus better suited for cultivation in the future climate of Central Europe although xylem safety does not differ
Cytokine-mediated inhibition of Staphylococcus aureus adherence and invasion into nonphagocytic cells
No full textStaphylococcus aureus is a major pathogen responsible for a wide range of infections, from minor skin diseases to life-threatening conditions, such as sepsis and pneumonia. Its ability to invade nonphagocytic cells, evading the immune system and persisting intracellularly complicates the treatment and contributes to recurrent infections. In this study, we investigated the role of cytokines in inhibiting S. aureus adherence and invasion into nonphagocytic human cells. Monomac-6 cells were stimulated with heat-killed S. aureus (HKSA) to produce a cytokine cocktail, which was used to treat various human cell lines, including HEK293, A549, HaCaT, and HT29. Our results demonstrate that cytokines significantly reduced S. aureus adherence and invasion into HEK293, HaCaT, and HT29 cells by altering the expression of key host cell receptors for S. aureus adhesins and invasion, such as integrins and heat shock proteins. These effects of cytokines were mediated via JAK-STAT pathway as tofacitinib supplementation, a JAK inhibitor, reversed the effects of cytokine cocktail. However, these effects were not observed in A549 cells, most likely due to their ability to actively internalize pathogens. These findings suggest that cytokines provide a crucial line of defense against the ability of S. aureus to invade nonphagocytic cells by modulating the expression of host cells receptors
Conserving saproxylic flagship species by complementing 150 years of natural history with citizen science data—the case of the stag beetles (Lucanidae, Coleoptera) of Portugal
No full textThe use of flagship species in conservation, such as the European Stag Beetle (Lucanus cervus), can positively affect the conservation of other taxonomic or functionally related species. This is especially true for taxonomic groups where the knowledge regarding their distribution and ecology is generally limited, as is the case of insects. This work represents the most accurate and up-to-date publication on the distribution, ecology and environmental niche of the four lucanids found in Portugal. Moreover, it unravels how citizen science initiatives can positively impact conservation planning for flagship species and their taxonomic and functionally related species. Compared to non-citizen science sources, citizen science data increased the known distribution area for all four species (1.6 to 7.2 fold) and confirmed most of the current known species distribution (50.0% to 95.5%). It also expanded the known environmental niche breadth for all species (1.1 to 4.2 fold) and the species suitable modelled habitat (1.1 to 2.1 fold) with very good model performances (AUC > 0.8 and TSS > 0.6). Our results suggest that to improve the conservation of these species, it is paramount to value native forests in Portugal. Management actions to accomplish this might include preserving current native forests and small natural features (such as large old trees) throughout the landscape while simultaneously increasing native forest development. In addition, climate change will affect the species' distribution since all are highly susceptible to specific (bio-)climatic conditions that are expected to change in the next decades. These findings not only enhance our understanding of these species' current distribution but also pave the way for targeted and integrative conservation efforts throughout the country, especially in areas where the (now assessed) ecological niche requirements and habitat availability (either in terms of landscape composition or structure) are met. Guidelines and priorities are discussed on how to implement conservation measures in Portugal following the recently approved European Nature Restoration Law
The baseline examinations of the German National Cohort (NAKO): recruitment protocol, response, and weighting
No full textThe German National Cohort (NAKO) is the largest population-based epidemiologic cohort study in Germany and investigates the causes of the most common chronic diseases. Between 2014 and 2019, a total of 1.3 million residents aged 20–69 years from 16 German regions were randomly selected from the general population and invited to participate following a highly standardized recruitment protocol. The overall response was 15.6% and differed considerably across study centers (7.6–30.7%). Females were more likely to participate than males (17.5% vs. 14.1%) and participation increased with age (10.2% in age group “ 60 years”). Across all study regions, response was highest in rural areas (22.3%), followed by towns and suburbs (17.2%), and was lowest in cities (14.5%). Compared with the general population in the respective study regions, participants with low and medium education are underrepresented in the NAKO sample, while highly educated participants are overrepresented. Participants with non-German nationality and with a migration background are also underrepresented. Participants living in single households are underrepresented, while participants from larger households (2 or more persons) are overrepresented compared to the general population. Survey weights are made available to researchers along with the study data that account for the sampling design and adjust for differences in the distribution of age, sex, nationality (German vs. non-German), migration status, education, and household size
Patient Number and Treatment Patterns in Cytomegalovirus Viremia and Disease Following Solid Organ and Hematopoietic Stem Cell Transplantation in Germany: Results of a Delphi Consensus Study
No full textIntroduction
Management of cytomegalovirus (CMV) viremia/disease in transplant recipients may be complicated by toxicities and resistance to conventional antivirals, adding to the overall healthcare burden. Despite advances in analyzing real-world data in current years, little is known about refractory and resistant CMV. This study therefore aimed to characterize treatment patterns and patient numbers with special focus on refractory and resistant CMV.
Methods
Two classical three-round Delphi consensus panels with German clinical experts in CMV following solid organ transplantations (SOT) and hematopoietic stem cell transplantations (HSCT) were held between October and December 2021 using online questionnaires. Consensus was defined as agreement of 75% of participants.
Results
Following SOT, experts agreed that on average 65% of SOT patients are not affected by CMV at all, while 35% of patients experience CMV viremia or disease. Of SOT patients treated with antiviral therapies, experts agreed that 90% respond to their first-line treatment and 10% do not. For HSCT, experts agreed that 62% of patients experience no CMV, while 38% of patients are diagnosed with either CMV viremia or CMV disease. It was further estimated that 23% HSCT patients receiving antiviral treatment do not respond to their first-line CMV treatment. Experts reached consensus on the reasons for non-response, suggesting that among non-responders, 55% were intolerant, while 45% of non-responders were refractory/resistant to first-line treatment.
Conclusion
Based on the current incidence of transplantations in Germany, experts estimated that 103 SOT and 225 HSCT patients need second-line CMV treatment annually
Comparison of two methods for decoding honeybee waggle dances
No full textHoneybees communicate the locations of profitable resources using waggle dances. Researchers have used two manual dance decoding methods to infer the spatial foraging patterns of the bees. The ‘waggle run method’ infers foraging distance from waggle duration, representing the actual distance signal of the bees, and the ‘circuit method’ infers foraging distance from the duration of complete dance circuits, including both waggle and return phases. The circuit method enables decoding dances by real-time observation and is likely quicker, but it might give inaccurate distance estimates due to variations in the return phases. Here, we decoded 200 natural waggle dances from four Apis mellifera colonies using both methods to test how well inferences about foraging locations would match and compared the time required for dance decoding. We found a high linear correlation between foraging distances inferred from waggle duration and circuit duration (R2, 0.793). However, the circuit method systematically overestimated foraging distances by about 86 m. Both methods provided similar results with respect to relative differences in spatial foraging patterns between the four test colonies. Decoding the dances using the circuit method was three to four times faster than the waggle run method (2 versus 7.3 min per dance). We conclude that the circuit method can be used for many research questions that require manual dance decoding to minimize time costs. However, when aiming to maximize the accuracy of inferred foraging locations, systematic errors of the circuit method should be accounted for, or the waggle run method should be used
Infants < 90 days of age with late-onset sepsis display disturbances of the microbiome-immunity interplay
No full textObjective
We hypothesized that previously healthy infants < 90 days of age with late-onset sepsis (LOS) have disturbances of the gut microbiome with yet undefined specific immunological patterns.
Methods
We performed a prospective single-center convenience sample study between January 2019 and July 2021 in a case-control design. Routine diagnostics included conventional cultures (blood, cerebrospinal fluid, urine), PCRs and inflammatory markers in infants aged < 90 days with clinical LOS. We additionally analyzed blood lymphocyte subsets including CD4 + CD25 + forkhead box protein (FoxP3)+ Tregs and performed 16 S rRNA sequencing of stool samples, both compared to age-matched healthy controls. Results were adjusted for potential confounders that may influence microbial composition.
Results
51 infants with fever and clinical LOS were enrolled. Bacterial sepsis was diagnosed in n = 24 (47.1%) and viral infection in n = 13 (25.5%) infants, whereas in 14 (27.3%) infants the cause of fever remained undetermined. When compared to healthy controls, the gut microbiome of LOS infants at disease onset was characterized by a shift in community composition, specifically, decreased abundance of B. longum and an increase of Bacteroidia spp. Intriguingly, the abundance of B. longum negatively correlated with the frequency of blood CD4-positive cells in healthy controls but not in infants with LOS. At one year of age, we observed microbiome differences in infants with history of LOS when compared to healthy controls, such as an increased gut microbial diversity.
Conclusion
Our data suggest potential signatures of the microbiome-immunity interplay in infants with LOS, which should be investigated further as possible targets for prevention
Non-invasive prediction of atrial cardiomyopathy characterized by multipolar high-density contact mapping
No full textIntroduction
Atrial cardiomyopathy (AC) establishes links between atrial fibrillation (AF), left atrial (LA) mechanical dysfunction, structural remodeling, and thromboembolic events. Early diagnosis of AC may impact AF treatment and stroke risk prevention. Modern endocardial contact-mapping provides high-resolution electro-anatomical (EA) maps of the LA, thus allowing to display the myocardial substrate based on impaired signal amplitude and to characterize AC. Correlation of invasively assessed AC using a novel, multipolar mapping catheter (OCTARAY™, Biosense Webster, limited market release) and LA echocardiographic parameters could form the basis for a set of echo parameters for non-invasive prediction of AC.
Methods
We retrospectively identified 50 adult patients who underwent primary pulmonary vein isolation (PVI) for paroxysmal or persistent AF between 08/22 and 05/23 fulfilling the selection criteria: (i) EA mapping with a novel multipolar mapping catheter (Octaray®); (ii) acquisition of voltage maps in sinus rhythm (SR) with ≥ 5000 points/map; and (iii) transthoracic echocardiography acquired in SR ≤ 48 h before PVI. Exclusion criterion was previous LA ablation. We generated EA maps with two sets of upper voltage thresholds (0.2–0.5 mV and 0.2–1.0 mV) and assessed total LA low voltage area (LVA). As LVA thresholds for the classification of AC are not yet established, an unsupervised machine learning cluster analysis was performed using a Gaussian mixture model (GMM), and two groups of patients with mild and severe AC were identified. Based on these two groups, we selected echo parameters for further analysis by applying the Boruta algorithm. The predictive capacity of the selected parameters was evaluated using a support vector machine.
Results
The mean age of the studied sample (n = 50) was 63 ± 11 years, 62% were men, 64% showed persistent AF, median CHA2DS2-VASc score was 2 (quartiles 1, 3), and NT-proBNP was 190 (71, 391) pg/ml. A median of 5771 (5217, 6988) points/map were acquired. GMM yielded clusters of mild AC (n = 28) and severe AC (n = 22). Median LVA was 0.6 cm2 (< 0.5 mV) resp. 4.1 cm2 (< 1.0 mV) in group mild AC and 6.9 cm2 (< 0.5 mV) resp. 27.2 cm2 (< 1.0 mV) in group severe AC. Several echocardiographic parameters differed between the groups of mild and severe AC: dynamic LA parameters (end diastolic LA reservoir strain: 24.5% (22, 29) vs 15% (12, 19), p < 0.001; LA reservoir strain at atrial contraction: 22% (19, 25) vs 15% (11, 18), p < 0.001, end diastolic LA contraction strain: 13% (8, 15) vs 7.5% (3, 13), p < 0.01) as well as LA end-systolic volume index to a´ ratio (LAVI/a′: 297 (231,365) vs 510 (326,781), p < 0.01). Consistent distribution of NT-proBNP (mild AC: 125 (48,189) pg/ml, severe AC: 408 (254,557) pg/ml, p < 0.0001) and CHA2DS2-VASc score (mild AC: 1 (1–2), severe AC: 3 (3–4), p < 0.0001) served as proof of concept. Applying the selected echocardiographic parameters, the machine learning algorithm correctly identified both subgroups with a mean AUC of 0.9 (95% CI 0.83–0.99). At 12 months, AF recurrence rate was 10.7% in mild AC and 40.9% in severe AC (p < 0.05).
Conclusion
Among patients qualifying for PVI, machine learning analysis of high-resolution LA maps allowed to identify subgroups with mild and severe AC avoiding the use of arbitrary LVA thresholds. The subgroups were predicted non-invasively with good accuracy using a machine learning approach that incorporated a set of echocardiographic markers. This data could advance the clinical triage of patients with AF
Gantry-free cone-beam CT arthrography for diagnosis of scapholunate ligament injuries: accelerating the preoperative work-up in acute wrist trauma
No full textObjective
Combining fluoroscopy and high-resolution cone-beam CT (CBCT) in a multipurpose scanner without a conventional gantry holds the potential for time-saving in musculoskeletal interventions. This study investigated the performance of gantry-free CBCT arthrography in patients with suspected scapholunate ligament (SLL) tears.
Materials and methods
Fifty-five patients (29 men, 46.0 ± 15.3 years) who underwent preoperative gantry-free CBCT arthrography between June 2021 and March 2024 were analyzed retrospectively. Three radiologists assessed CBCT arthrograms for tears of the palmar and dorsal SLL segments. Surgical reports served as the reference standard for calculating indicators of diagnostic accuracy. Interreader agreement was tested by computing Krippendorff α. Radiation dose and examination time were recorded.
Results
Tears of the palmar and dorsal SLL segment were recorded in 25 (45%) and 6 patients (11%), respectively. CBCT arthrography facilitated good sensitivity (range for all readers: 84–92%) and excellent specificity (93–97%) in the assessment of the palmar SLL. For the dorsal SLL, sensitivity (83–100%) and specificity (96–98%) were even higher. Substantial agreement was determined for both the palmar (α = 0.83, 95% CI: 0.74–0.90) and dorsal SLL (0.84, 0.70–0.95). The mean volume CT dose index for CBCT arthrography was 3.2 ± 1.4 mGy. Not requiring patient repositioning, the median time between fluoroscopy-guided contrast injection and CBCT was 3:05 min (2:31–3:50 min).
Conclusion
Gantry-free CBCT arthrography allows for excellent accuracy in the preoperative diagnosis of SLL tears with low radiation dose. The ability to alternate between fluoroscopy and CBCT without repositioning facilitates a “one-stop-shop” approach with short examination time