Randomized Controlled Trial of Individualized Arousal-Biofeedback for children and adolescents with Disruptive Behavior Disorders (DBD)

Background: Disruptive behavior disorders (including conduct disorder (CD) and oppositional defiant disorder (ODD)) are common childhood and adolescent psychiatric conditions often linked to altered arousal. The recommended first-line treatment is multi-modal therapy and includes psychosocial and behavioral interventions. Their modest effect sizes along with clinically and biologically heterogeneous phenotypes, emphasize the need for innovative personalized treatment targeting impaired functions such as arousal dysregulation. Methods: A total of 37 children aged 8-14 years diagnosed with ODD/CD were randomized to 20 sessions of individualized arousal biofeedback using skin conductance levels (SCL-BF) or active treatment as usual (TAU) including psychoeducation and cognitive-behavioral elements. The primary outcome was the change in parents´ ratings of aggressive behavior measured by the Modified Overt Aggression Scale. Secondary outcome measures were subscales from the Child Behavior Checklist, the Inventory of Callous-Unemotional traits and the Reactive-Proactive Aggression Questionnaire. Results: The SCL-BF treatment was neither superior nor inferior to the active TAU. Both groups showed reduced aggression after treatment with small effects for the primary outcome and large effects for some secondary outcomes. Importantly, successful learning of SCL self-regulation was related to reduced aggression at post-assessment. Conclusions: Individualized SCL-BF was not inferior to active TAU for any treatment outcome with improvements in aggression. Further, participants were on average able to self-regulate their SCL, and those who best learned self-regulation showed the highest clinical improvement, pointing to specificity of SCL-BF regulation for improving aggression. Further studies with larger samples and improved methods, for example by developing BF for mobile use in ecologically more valid settings are warranted

A genetic investigation of sex bias in the prevalence of attention-deficit/hyperactivity disorder

Background Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. Methods We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish populationregister data (N=77,905 cases, N=1,874,637 population controls). Results Genetic correlation analyses using two methods suggested near complete sharing of common variant effects across sexes, with rg estimates close to 1. Analyses of population data, however, indicated that females with ADHD may be at especially high risk of certain comorbid developmental conditions (i.e. autism spectrum disorder and congenital malformations), potentially indicating some clinical and etiological heterogeneity. Polygenic risk score (PRS) analysis did not support a higher burden of ADHD common risk variants in female cases (OR=1.02 [0.98-1.06], p=0.28). In contrast, epidemiological sibling analyses revealed that the siblings of females with ADHD are at higher familial risk of ADHD than siblings of affected males (OR=1.14, [95% CI: 1.11-1.18], p=1.5E-15). Conclusions Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity, based on epidemiological analyses. However, molecular genetic analyses suggest that autosomal common variants largely do not explain the sex bias in ADHD prevalence

The Effectiveness of Leech Therapy in Chronic Low Back Pain - A Randomised Controlled Trial

Hintergrund: Zur Blutegeltherapie liegen bereits Wirksamkeitsnachweise bei einzelnen chronischen muskuloskelettalen Schmerzsyndromen vor. Klinische Studien zu Rückenschmerzen fehlen bislang. Empirisch werden Blutegel bei dieser Indikation häufig eingesetzt. Wir entschieden uns daher, eine erste randomisierte Studie zur Blutegeltherapie bei chronischem unterem Rückenschmerz durchzuführen. Methoden: Patienten mit chronischem unterem Rückenschmerz wurden nach Randomisierung einer einmaligen lokalen Therapie mit 4-7 Blutegeln oder einer Bewegungstherapiegruppe unter Leitung eines Physiotherapeuten (1 h/Woche, über 4 Wochen) zugeführt. Der Studienbeobachtungszeitraum betrug 8 Wochen mit Messzeitpunkten Baseline sowie nach 28 und 56 Tagen. Primärer Zielparameter war die Veränderung des durchschnittlichen Rückenschmerzes (100-mm-VAS) nach 28 Tagen. Sekundäre Zielparameter waren Veränderungen der Funktionseinschrän-kungen (Roland-Morris Disability Scale, Funktionsfragebogen Hannover), Lebens-qualität (SF-36), Schmerzwahrnehmung (SES), Depressivität (CES-D) und der Schmerzmittelverbrauch (Fragebögen/Tagebuch) und die Erwartungshaltung. Ergebnisse: In die Studie wurden insgesamt 44 Patienten eingeschlossen. Davon wurden n=25 (59,3±7,0 Jahre) der Interventionsgruppe und n=19 (56,5±7,8 Jahre) der Kontrollgruppe durch Randomisation zugeordnet. Der mittlere Rückenschmerz (100-mm-VAS) sank von prätherapeutisch 61,2±15,6 mm auf 33,1±22,4 mm am Tag 28 in der Blutegelgruppe (n=25), bzw. von 61,6±14,8 mm auf 59,8±16,7 mm in der Bewegungstherapiegruppe (n=19) (Gruppendifferenz -25,2 mm [95 % KI -41,0;-9,5; p=0,0018]). Der Gruppenunterschied in der 100-mm-VAS Schmerz nach 56 Tagen war statistisch nicht signifikant (−23,6 mm 95 % KI [−37,1; –10,2; p=0.056]). Signifikante Effekte zugunsten der Blutegelgruppe zeigten sich auch zu beiden Zeitpunkten (Tag 28/56) bei der körperlichen Einschränkung und Funktion sowie der körperlichen Lebensqualität. Die psychische Lebensqualität verbesserte sich in beiden Gruppen gleichermaßen. In der Blutegelgruppe war die Erwartungshaltung höher, beeinflusste aber die Ergebnisse bei Berücksichtigung als Kovariate nicht signifikant Schlussfolgerung: Eine einmalige Behandlung mit Blutegeln ist symptomatisch effektiv gegenüber einer moderaten Bewegungstherapie bezüglich kurzfristiger Verringerung der Schmerzstärke (4 Wochen), sowie Funktion und Lebensqualität im kurz- und mittelfristigen Zeitraum (4 bzw. 8 Wochen). Die Blutegeltherapie er-scheint damit als eine mögliche ergänzende wirksame Methode in der Behandlung chronischer unterer Rückenschmerzen.Background: Leech therapy has demonstrated its effectiveness in different musculoskeletal pain syndromes, but not in low back pain. Empirically, leeches are frequently used for that indication. Thus, we decided to conduct the first study to assess the effectiveness of leech therapy in chronic low back pain. Methods: Patients suffering from chronic low back pain were randomized to either receive once a local therapy with 4-7 leeches or movement or a complex physiotherapy led by a physiotherapist (1h/w over 4 w). The study period was set up with 8 w. Visits to assess outcome were conducted at baseline, resp. 28, resp. 56 days thereafter. Primary outcome was change in mean back pain (100-mm-VAS) after 28 days. Secondary outcome were change in disability due to back pain (Roland-Morris disability scale and Funktionsfragebogen Hannover), quality of life (SF-36), depression (CED-D), and consumption of pain medication by diary. Results: 44 patients were included, n=25 (age 59.3±7.0 y) allocated to the interventional group and n=19 (56.5±7.8 y) to the control group. Mean back pain in the leech group was reduced from 61.2±15.6 mm at baseline to 33.1±22.4 mm on day 28 (n=25) and from 61.6±14.8 mm to 59.8±16.7 mm in the physiotherapy group (n=19) (group difference -25.2 mm [95 % CI -41.0;-9.5; p=0.0018]). We also found significant changes favoring leech therapy at both post-treatment visits (days 28, resp. 56) for physical disability as well as physical quality of life. Psychological quality of life improved simultaneously in both groups. Patients’ expectation was higher in the leech group but this did not alter the results significantly when used as a co-variate. Conclusion: A single treatment with leeches is symptomatically more effective when compared to moderate exercise for short-term (4 w) reduction of pain and for short-term (4w) as well as midterm (8w) improvements of quality of life. Leech therapy could be considered as a potential additional method in treating chronic low back pain

Intra- and interrater reliabilities and a method comparison of 2D and 3D techniques in cadavers to determine sacroiliac screw loosening

Abstract Sacroiliac (SI) screw loosening may indicate persistent instability, non-union and contribute to pain. Yet, there is no reliable objective measurement technique to detect and monitor SI screw loosening. In 9 cadaveric pelvises one of two SI screw was turned back approximately 20 mm and subsequently assessed by optical measurement, fluoroscopy and a 3D scan using an image intensifier. CTs were segmented and a contour-based registration of the 3D models and the fluoroscopies was performed to measure SI backing out (X-ray module). Three independent observers performed measurements with three repetitions. Deviation of the measurement techniques to the 3D scan, intra- and interrater reliabilities and method equivalence to the 3D scan were assessed. The X-ray module and two fluoroscopic measurement techniques yielded a difference less than 5 mm compared to the 3D scan and equivalence to the 3D scan. Intrarater reliability was for two observers and almost all techniques very good. Three fluoroscopic measurement techniques and optical measurements displayed a very good interrater reliability. The 3D scan and X-ray module yielded the most precise values for SI screw loosening but only the fluoroscopic measurement of the inlet lateral loosening displayed a good reliability and equivalence to the 3D scan

Comparing Binaural Pre-processing Strategies I

In a collaborative research project, several monaural and binaural noise reduction algorithms have been comprehensively evaluated. In this article, eight selected noise reduction algorithms were assessed using instrumental measures, with a focus on the instrumental evaluation of speech intelligibility. Four distinct, reverberant scenarios were created to reflect everyday listening situations: a stationary speech-shaped noise, a multitalker babble noise, a single interfering talker, and a realistic cafeteria noise. Three instrumental measures were employed to assess predicted speech intelligibility and predicted sound quality: the intelligibility-weighted signal-to-noise ratio, the short-time objective intelligibility measure, and the perceptual evaluation of speech quality. The results show substantial improvements in predicted speech intelligibility as well as sound quality for the proposed algorithms. The evaluated coherence-based noise reduction algorithm was able to provide improvements in predicted audio signal quality. For the tested single-channel noise reduction algorithm, improvements in intelligibility-weighted signal-to-noise ratio were observed in all but the nonstationary cafeteria ambient noise scenario. Binaural minimum variance distortionless response beamforming algorithms performed particularly well in all noise scenarios

Binding of CD40L to Mac-1's i-domain involves the EQLKKSKTL motif and mediates leukocyte recruitment and atherosclerosis-but does not affect immunity and thrombosis in mice

Rationale: CD40L figures prominently in chronic inflammatory diseases such as atherosclerosis. However, since CD40L potently regulates immune function and hemostasis by interaction with CD40 receptor and the platelet integrin GPIIb/IIIa, its global inhibition compromises host defense and generated thromboembolic complications in clinical trials. We recently reported that CD40L mediates atherogenesis independently of CD40 and proposed Mac-1 as an alternate receptor. Objective: Here, we molecularly characterized the CD40L-Mac-1 interaction and tested whether its selective inhibition by a small peptide modulates inflammation and atherogenesis in vivo. Methods and Results: CD40L concentration-dependently bound to Mac-1 I-domain in solid phase binding assays, and a high-affinity interaction was revealed by surface-plasmon-resonance analysis. We identified the motif EQLKKSKTL, an exposed loop between the α1 helix and the β-sheet B, on Mac-1 as binding site for CD40L. A linear peptide mimicking this sequence, M7, specifically inhibited the interaction of CD40L and Mac-1. A cyclisized version optimized for in vivo use, cM7, decreased peritoneal inflammation and inflammatory cell recruitment in vivo. Finally, LDLr -/- mice treated with intraperitoneal injections of cM7 developed smaller, less inflamed atherosclerotic lesions featuring characteristics of stability. However, cM7 did not interfere with CD40L-CD40 binding in vitro and CD40L-GPIIb/IIIa-mediated thrombus formation in vivo. Conclusions: We present the novel finding that CD40L binds to the EQLKKSKTL motif on Mac-1 mediating leukocyte recruitment and atherogenesis. Specific inhibition of CD40L-Mac-1 binding may represent an attractive anti-inflammatory treatment strategy for atherosclerosis and other inflammatory conditions, potentially avoiding the unwanted immunologic and thrombotic effects of global inhibition of CD40L.Fil: Wolf, Dennis. Albert-Ludwigs-Universität Freiburg; Alemania. Baker IDI Heart and Diabetes Institute; AustraliaFil: Hohmann, Jan David. Baker IDI Heart and Diabetes Institute; AustraliaFil: Wiedemann, Ansgar. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Bledzka, Kamila. Cleveland Clinic. Department of Molecular Cardiology; Estados UnidosFil: Blankenbach, Hermann. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Marchini, Timoteo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Bioquímica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de Bioquímica y Medicina Molecular; Argentina. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Gutte, Katharina. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Zeschky, Katharina. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Bassler, Nicole. Baker IDI Heart and Diabetes Institute; AustraliaFil: Hoppe, Natalie. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Rodriguez, Alexandra Ortiz. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Herr, Nadine. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Hilgendorf, Ingo. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Stachon, Peter. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Willecke, Florian. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Duerschmied, Daniel. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: von zur Muhlen, Constantin. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Soloviev, Dmitry A.. Cleveland Clinic. Department of Molecular Cardiology; Estados UnidosFil: Zhang, Li. University of Maryland; Estados UnidosFil: Bode, Christoph. Albert-Ludwigs-Universität Freiburg; AlemaniaFil: Plow, Edward F.. Cleveland Clinic. Department of Molecular Cardiology; Estados UnidosFil: Libby, Peter. Harvard Medical School; Estados UnidosFil: Peter, Karlheinz. Baker IDI Heart and Diabetes Institute; AustraliaFil: Zirlik, Andreas. Albert-Ludwigs-Universität Freiburg; Alemani

A ligand-specific blockade of the integrin Mac-1 selectively targets pathologic inflammation while maintaining protective host-defense

Integrin-based therapeutics could block inflammatory processes but they also impair host defence, limiting their usefulness. Here the authors report an anti-Mac1 antibody that blocks its interaction with pro-inflammatory ligand CD40L but not other ligands, and show that it can protect against sepsis in mice

Interdisciplinary Geo-ecological Research across Time Scales in the Northeast German Lowland Observatory (TERENO-NE)

The Northeast German Lowland Observatory (TERENO-NE) was established to investigate the regional impact of climate and land use change. TERENO-NE focuses on the Northeast German lowlands, for which a high vulnerability has been determined due to increasing temperatures and decreasing amounts of precipitation projected for the coming decades. To facilitate in-depth evaluations of the effects of climate and land use changes and to separate the effects of natural and anthropogenic drivers in the region, six sites were chosen for comprehensive monitoring. In addition, at selected sites, geoarchives were used to substantially extend the instrumental records back in time. It is this combination of diverse disciplines working across different time scales that makes the observatory TERENO-NE a unique observation platform. We provide information about the general characteristics of the observatory and its six monitoring sites and present examples of interdisciplinary research activities at some of these sites. We also illustrate how monitoring improves process understanding, how remote sensing techniques are fine-tuned by the most comprehensive ground-truthing site DEMMIN, how soil erosion dynamics have evolved, how greenhouse gas monitoring of rewetted peatlands can reveal unexpected mechanisms, and how proxy data provides a long-term perspective of current ongoing changes