The acute effects of aerobic exercise on sleep in patients with unipolar depression: a randomized controlled trial

Study ObjectivesInsomnia increases the risk of negative disease trajectory, relapse, and suicide in patients with depression. We aimed at investigating the effects of a single bout of aerobic exercise, performed after 02:00 pm, on the subsequent night’s sleep in patients with depression.MethodsThe study was designed as a two-arm parallel-group, randomized, outcome assessor-blinded, controlled, superiority trial. Patients between 18 and 65 years of age with a primary diagnosis of unipolar depression were included. The intervention was a single 30-minute bout of moderate aerobic exercise. The control group sat and read for 30 minutes. The primary outcome was sleep efficiency measured by polysomnography. Secondary outcomes were other polysomnographic variables, subjective sleep quality, daytime sleepiness, mood states, and adverse events.ResultsNinety-two patients were randomized to the exercise (N = 46) or control group (N = 46). There were no clinically relevant differences at baseline. Intent-to-treat analysis ANCOVA of follow-up sleep efficiency, adjusted for baseline levels and minimization factors, did not detect a significant effect of the allocation (β = −0.93, p = 0.59). There was no evidence for significant differences between both groups in any other objective or subjective sleep outcomes, daytime sleepiness, or adverse events. The intervention had an immediate positive effect on mood states, including depressiveness (β = −0.40, p = 0.003).ConclusionsThis is the first trial to study the effects of a single bout of aerobic exercise on sleep in patients with depression to the best of our knowledge. Aerobic exercise had no effect on sleep efficiency but had a strong beneficial effect on mood and did not increase adverse outcomes. These results add to the growing body of evidence that, contrary to sleep hygiene recommendations, exercise after 02:00 pm is not detrimental for sleep.Clinical Trial RegistrationClinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03673397. Protocol registered on September 17, 2018.     

Vergleichende klinische Untersuchungen mit psychologischen Tests

Ohne Zusammenfassung     

Inactivation of a non-enveloped RNA virus by artificial ribonucleases: honey bees and acute bee paralysis virus as a new experimental model for in vivo antiviral activity assessment

RNA-containing viruses represent a global threat to the health and wellbeing of humans and animals. Hence, the discovery of new approaches for the design of novel vaccines and antiviral compounds attains high attention. Here we describe the potential of artificial ribonucleases (aRNases), low molecular weight compounds capable to cleave phosphodiester bonds in RNA under mild conditions, to act as antiviral compounds via destroying the genome of non-enveloped RNA viruses, and the potential of utilizing honey bee larvae and adult bees (Apis mellifera) as a novel experimental system for the screening of new antiviral compounds. Pre-incubation of an Acute bee paralysis virus (ABPV) suspension with aRNases D3-12, K-D-1 or Dp12F6 in a concentration-dependent manner increased the survival rate of bee larvae and adult bees subsequently infected with these preparations, whereas incubation of the virus with aRNases ABL3C3 or L2-3 had no effect at all. The results of RT-PCR analysis of viral RNA isolated from aRNase-treated virus particles confirmed that virus inactivation occurs via degradation of viral genomic RNA: dose-dependent inactivation of ABPV correlates well with the cleavage of viral RNA. Electron microscopy analysis revealed that the morphology of ABPV particles inactivated by aRNases remains unaffected as compared to control virus preparations. Altogether the obtained results clearly demonstrate the potential of aRNases as a new virus inactivation agents and bee larvae/ABPV as a new in vivo system for the screening of antiviral compounds.     

Die übertragbarkeit der Tuberkulinhautempfindlichkeit von Kindern auf Meerschweinchen durch Cantharidenblasensedimente

Zusammenfassung In zwei Untersuchungsreihen wird über die Möglichkeit einer experimentellen Übertragung der Tuberkulinhautempfindlichkeit von Kindern auf Meerschweinchen durch gewaschenes Cantharidenblasensediment berichtet. Das Sediment wurde vor der Übertragung 12 Std mit Alttuberkulin Koch in der Verdünnung 5:1 bei 38° gehalten.Das in gleicher Weise verarbeitete Cantharidenblasensediment tuberkulinnegativer Kinder übertrug die Tuberkulinhautempfindlichkeit, nichtAn Hand einer dritten Untersuchungsreihe wird die Möglichkeit einer cellulären Fixierung des Tuberkulins an das Chantharidenblasensediment tuberkulinnegativer Kinder besprochen.     

Branchiostoma floridae has separate healing and sealing enzymes for 5′-phosphate RNA ligation

Animal cells have two tRNA splicing pathways: (i) a 5′-P ligation mechanism, where the 5′-phosphate of the 3′ tRNA half becomes the junction phosphate of the new phosphodiester linkage, and (ii) a 3′-P ligation process, in which the 3′-phosphate of the 5′ tRNA half turns into the junction phosphate. Although both activities are known to exist in animals, in almost three decades of investigation, neither of the two RNA ligases has been identified. Here we describe a gene from the chordate Branchiostoma floridae that encodes an RNA ligase (Bf RNL) with a strict requirement for RNA substrates with a 2′-phosphate terminus for the ligation of RNAs with 5′-phosphate and 3′-hydroxyl ends. Unlike the yeast and plant tRNA ligases involved in tRNA splicing, Bf RNL lacks healing activities and requires the action of a polynucleotide kinase (PNK) and a cyclic phosphodiesterase (CDPase) in trans. The activities of these two enzymes were identified in a single B. floridae protein (Bf PNK/CPDase). The combined activities of Bf RNL and Bf PNK/CPDase are sufficient for the joining of tRNA splicing intermediates in vitro, and for the functional complementation of a tRNA ligase-deficient Saccharomyces cerevisiae strain in vivo. Hence, these two proteins constitute the 5′-P RNA ligation pathway in an animal organism.Archaeal and eukaryal cells have ubiquitous intron-containing tRNA precursors, and their correct processing to mature tRNA is essential for viability. The first step in tRNA maturation is the removal of introns by the tRNA splicing endonuclease (1) generating the linear intron and two tRNA halves with 2′,3′-cyclic phosphate and 5′-hydroxyl termini (Fig. 1A, Top). Different strategies are used to subsequently join the tRNA halves together. A 3′-P ligation pathway exists in archaea and in animals (2, 3). Fungi, plants, and—as a second pathway—animals employ a more complex reaction that requires GTP and ATP to generate the crucial 5′-phosphate involved in a 5′-P ligation process (Fig. 1). The multifunctional yeast (class I) and plant (class II) tRNA ligases combine three enzymatic activities in a single polypeptide (Fig. 1B): an adenylyltransferase, a polynucleotide kinase (PNK), and a cyclic phosphodiesterase (CPDase) (4). These RNA ligases perform both “healing” and “sealing” steps (5) during ligation (Fig. 1A). The 2′,3′-cyclic phosphate at the 3′-end of the 5′ tRNA half is hydrolyzed by the CPDase to generate a 2′-phosphate and 3′-OH (gray box). Then the 5′-OH group of the 3′ tRNA half is phosphorylated by the GTP-dependent PNK (yellow box). In a third step, the ligase protein is adenylylated and the AMP is transferred to the 5′-phosphate of the 3′ tRNA half followed by the formation of the 2′-phosphomonoester-3′,5′-phosphodiester bond and the release of AMP. Finally, the 2′-phosphate at the splice junction is removed by a nicotinamide-adenine dinucleotide-dependent phosphotransferase (4, 6–11). This enzyme cascade is called the 5′-P (yeast-type) RNA ligation pathway.Open in a separate windowFig. 1.Schematic representation of 5′-P ligation proteins with their corresponding enzymatic activities. (A) Cleavage of an intron-containing pre-tRNA by the tRNA splicing endonuclease produces a 5′-tRNA half with a 2′,3′-cyclophosphate (Top, in gray) and a 3′-half with a 5′-hydroxyl (Top, in yellow) (1). The 5′-half gets modified by a 2′,3′-cyclic-3′-phosphodiesterase activity resulting in a tRNA half with a 2′-phosphate-3′-hydroxyl (Middle Left). The 5′-hydroxyl of the 3′-half gets phosphorylated by a polynucleotide kinase (Middle Right). An RNA ligase module can now connect (seal) these modified (healed) tRNA halves in an ATP-dependent reaction producing a 2′-phosphomonoester-3′,5′-phosphodiester bond (4). (B) According to their sequence conservation the 5′-P ligation enzymes can be divided into four different classes. Class I (including all fungi, trypanosome, and Tetrahymena tRNA ligases) and class II (including the tRNA ligases of vascular plants) 5′-P ligation enzymes contain the three intrinsic activities on one polypeptide, and share a sequence conservation only in between their corresponding class. The newly identified class III (this study) localize the RNA ligase and the bifunctional polynucleotide kinase/cyclic phosphodiesterase on two separate proteins which together are sufficient for tRNA ligation in vitro and in vivo. The class III system also encodes an additional RNA polynucleotide kinase (Clp1). In the class IV system, the RNA ligase has not yet been identified, but the healing enzymes of the human Clp1 kinase and of the rat CPDase which no longer exhibit polynucleotide kinase activity have been characterized.A PNK and an RNA ligase activity involved in the maturation of mammalian pre-tRNAs was reported almost 30 y ago (12). Subsequently this reaction was shown to yield a 2′-phosphomonoester-3′,5′-phosphodiester bond at the splice junction (13). Recently, the human PNK (hClp1) was purified and shown to be associated with the tRNA splicing endonuclease and responsible for the phosphorylation of the 5′-OH ends of 3′ tRNA halves (14). The data suggest that hClp1 plays a catalytic role in the 5′-P ligation pathway in animal cells (13) (Fig. 1B). These data are in line with the finding that hClp1 expression in Saccharomyces cerevisiae complements mutations in the essential PNK module of yeast tRNA ligase (15). It is also known that mammalian 2′,3′-cyclic nucleotide phosphodiesterase (CNP) is able to complement mutations in the CPDase domain of the yeast tRNA ligase (16). Thus, if CNP and hClp1 were genuine components of the animal 5′-P ligation pathway, then all enzymatic activities including the RNA ligase would be encoded by separate genes, and all would act in concert. Clearly, this is in contrast to the trifunctional yeast and plant enzymes.Here we provide evidence that the chordate Branchiostoma floridae harbors (i) an RNA ligase with the same substrate specificity as fungal and plant tRNA ligases, (ii) a cyclic phosphodiesterase protein with CPDase and PNK activity, and (iii) a Clp1 protein with polynucleotide kinase activity. The bifunctional PNK/CPDase protein in concert with the ligase protein catalyzes the 5′-P RNA ligation pathway in vitro and in vivo.     

Vergleichende klinische Untersuchungen mit psychologischen Tests

Zusammenfassung Vergleichende statistische Untersuchungen mit dem Draw a man-Test Goodenoughs und dem Mann-Zeichen-Test Zilers bei 201 Kindern, von denen in 164 Fällen elektrencephalographische Befunde vorliegen, zeigten signifikante Unterschiede in den Zeichnungen menschlicher Figuren von Kindern ohne pathologische EEG-Befunde gegenüber Kindern mit elektrencephalographisch nachweisbarer Hirnschädigung. Die kombinierte Anwendung beider Tests in der klinischen Diagnostik kann deshalb empfohlen werden.     

Infection of honey bees with acute bee paralysis virus does not trigger humoral or cellular immune responses

We have studied the responses of honey bees at different life stages (Apis mellifera) to controlled infection with acute bee paralysis virus and have identified the haemolymph of infected larvae and adult worker bees as the compartment where massive propagation of ABPV occurs. Insects respond with a broad spectrum of induced innate immune reactions to bacterial infections, whereas defence mechanisms based on RNA interference play a major role in antiviral immunity. In this study, we have determined that honey bee larvae and adult workers do not produce a humoral immune reaction upon artificial infection with ABPV, in contrast to control individuals challenged with Escherichia coli. ABPV-infected bees produced neither elevated levels of specific antimicrobial peptides (AMPs), such as hymenoptaecin and defensin, nor any general antimicrobial activity, as revealed by inhibition-zone assays. Additionally, adult bees did not generate melanised nodules upon ABPV infection, an important cellular immune function activated by bacteria and viruses in some insects. Challenge of bees with both ABPV and E. coli showed that innate humoral and cellular immune reactions are induced in mixed infections, albeit at a reduced level.     

Der Roboter —statistische Auswertung von 1000 Mann-Zeichnungen

Zusammenfassung 1000 Mann-Zeichnungen von 317 hirngesunden, 338 hirngeschädigten Kindern und 345 Kindern mit klinisch und psychologisch für Hirnschäden verdächtigen Befunden lassen differentialdiagnostisch verwertbare signifikante Unterschiede erkennen. Die hirngesunden Kindern eigene plastische Zeichnung eines Mannes wird teilweise oder völlig bei der Hälfte der Zeichnungen hirngeschädigter Kinder vermißt, an ihre Stelle tritt die Darstellung drei- oder viereckiger Körperteile. Solche Zeichnungen nennen wir Roboter oder Teil-Roboter. Eine Betrachtung dieser Roboter zeigt, daß häufiger die langen Linien von Rumpf, Armen und Beinen nicht plastisch gezeichnet werden als die Details (Kopf, Hals und anderes Zubehör). Daraus wird geschlossen, daß besonders die Formwiedergabe infolge motorischer Unsicherheit beeinträchtigt ist, und daß dieser Mangel durch Zeichnung vieler Details kompensiert werden soll. Damit ließe sich die aus der Literatur für den Mann-Zeichen-Test bekannte Vereinfachung und Vernachlässigung von Proportionen und Linienführung bei Neigung zu überaltersdurchschnittlicher Wiedergabe von Details erklären.Herrn Professor Dr. G. Joppich zum 65. Geburtstag gewidmet.     

Vergleichende klinische Untersuchungen mit psychologischen tests

Zusammenfassung Mit dem von Bender eingeführten und für gesunde Kinder standardisierten Visual Motor Gestalt-Test wurden unter Anwendung einer eigenen Berechnungsmethodik vergleichende Untersuchungen an 186 Kindern, von denen in 143 Fällen ein elektrencephalographischer Befund vorliegt, durchgeführt. In Übereinstimmung mit den Literaturangaben ließen sich durch statistische Berechnung Unterschiede in den Testergebnissen von Kindern mit pathologischen EEG-Befunden gegenüber Kindern ohne elektrencephalographisch nachweisbare Hirnschädigung sichern.