A comparison of two models of ADHD: state regulation versus delay aversion

“Attention Deficit/Hyperactivity Disorder” (ADHD), in het Nederlands “aandachtstekortstoornis met hyperactiviteit”, is één van de meest voorkomende psychiatrische stoornissen. ADHD is een ontwikkelingsstoornis die gekenmerkt wordt door ernstige en persisterende symptomen van onoplettendheid, impulsiviteit en/of hyperactiviteit; en leidt tot significante beperkingen in beroepsmatig, schools of sociaal functioneren (Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR), American Psychiatric Association, 2000). Tot op heden is de etiologie van ADHD nog niet volledig begrepen en bestaan er verschillende neuropsychologische theorieën ter verklaring van de symptomen van ADHD. Lange tijd werd verondersteld dat de symptomen van ADHD het gevolg zijn van een primair tekort in executief functioneren zoals inhibitie, planning, werkgeheugen en “set shifting” (voor een overzicht: zie Barkley, 1997; Castellanos & Tannock, 2002). Recent onderzoek heeft echter aangetoond dat executieve verklaringsmodellen onvoldoende de symptomen van ADHD kunnen verklaren (Willcutt et al., 2005). Bovendien suggereren recentere neuropsychologische theorieën dat tekortkomingen in executief functioneren bij kinderen met ADHD niet statisch zijn; het al dan niet optreden van zwakkere prestaties zou namelijk afhangen van de situationele en motivationele context. Huidig proefschrift focust op twee vooraanstaande neuropsychologische modellen die het dynamische karakter van ADHD benadrukken en in het bijzonder de rol van contextuele factoren: het toestandsregulatiemodel (State Regulation Deficit model (SRD); van der Meere, 2002) en het “Delay Aversion” model (DAv; Sonuga-Barke, Wiersema, van der Meere, & Roeyers, 2010). Het toestandsregulatiemodel stelt dat prestaties afhankelijk zijn van energetische processen zoals arousal, activatie en effort (Sanders, 1983). Volgens dit model hebben kinderen met ADHD moeilijkheden met het aanpassen van hun energetische interne toestand aan de veranderende eisen uit de omgeving (van der Meere, 2002). Onderzoek heeft aangetoond dat omgevingsfactoren, zoals het manipuleren van de snelheid waarmee informatie wordt aangeboden tijdens een taak, een invloed heeft op de interne toestand. Meer concreet zou een snelle stimulusaanbieding leiden tot een overactieve toestand en een trage stimulusaanbieding tot een onderactieve toestand. Kinderen met ADHD zouden er niet in slagen om deze sub-optimale toestanden te reguleren, namelijk een onderactieve toestand op te krikken en een overactieve toestand te temperen, waardoor ze zwakke prestaties behalen. Het toestandsregulatiemodel veronderstelt aldus een omgekeerde U relatie tussen de interne toestand en taakprestaties. Aangezien kinderen met ADHD problemen hebben met het reguleren van hun interne toestand, zou deze omgekeerde U functie bij hen uitdrukkelijker tot uiting komen in vergelijking met typisch ontwikkelende kinderen. Onderzoek waarbij de snelheid van stimulusaanbieding werd gemanipuleerd, ondersteunt de voorspellingen van het toestandsregulatiemodel (voor een overzicht zie: Sergant, 2005; van der Meere 2002; Sonuga-Barke et al., 2010). Het “Delay Aversion model” stelt dat prestaties van kinderen met ADHD hoofdzakelijk worden beïnvloed door intolerantie voor uitstel. Kinderen met ADHD zouden zwakker presteren dan typisch ontwikkelende kinderen in uitgestelde situaties. Volgens dit model is het primair tekort dat aan de grondslag ligt van de symptomen van ADHD een verstoorde codering van toekomstige beloningen. Na verloop van tijd zou dit primaire tekort leiden tot het ontwikkelen van negatief affect ten aanzien van situaties waar men moet wachten (Sonuga-Barke et al., 2010). Onderzoek ondersteunt de voorspellingen van dit model. Meer bepaald stelde men vast dat kinderen met ADHD een sterke voorkeur hebben voor kleine onmiddellijke beloningen boven grotere uitgestelde beloningen. Bovendien lijken kinderen met ADHD gefrustreerd te zijn wanneer een wachttijd extern wordt opgelegd (Marco et al., 2009)

Evaluation of atrial electromechanical conduction delay in case of hemodynamically insignificant rheumatic heart disease: A tissue Doppler study

Background: Atrial electromechanical delay (AEMD) that reflects delayed conduction may show us the clinical reflection of pathological changes in the atria. The main objective of the present study is to investigate AEMD in patients who had previous rheumatic carditis but without hemodynamically significant valvular disease. Methods: A total of 40 patients, previously diagnosed as rheumatic carditis but without significant valvular stenosis/regurgitation and atrial enlargement; and 39 age- and-sex matched controls were enrolled for the present study. Parameters of AEMD (lateral mitral annulus electromechanical delay, septal mitral annulus electromechanical delay and lateral tricuspid annulus electromechanical delay) were measured with tissue Doppler echocardiography and left intra-atrial and inter-atrial conduction times were calculated accordingly. A 24h ambulatory Holter monitoring was used in both groups to detect atrial fibrillation episodes and quantify atrial extrasystoles. Results: Parameters of AEMD, including left intra-atrial and inter-atrial conduction times of subjects in the study group were longer compared to the control group (23.7 ± 7.0 vs. 18.3 ± 6.2). Conclusions: Increased AEMD is observed in patients with previous rheumatic carditis and no significant valvular stenosis/regurgitation and atrial enlargement, which may partly explain the increased incidence of atrial fibrillation observed in these patients

Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients

Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment

Technical Aspects and Clinical Limitations of Sperm DNA Fragmentation Testing in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

PURPOSE: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. MATERIALS AND METHODS: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. RESULTS: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). CONCLUSIONS: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Technical aspects and clinical limitations of sperm DNA fragmentation testing in male infertility: A global survey, current guidelines, and expert recommendations

Purpose Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice. Materials and Methods Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured. Results The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%). Conclusions This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial