Die Wirkung einer frühen Antibiotikatherapie auf die Besiedlung mit potenziell pathogenen Erregern bei Frühgeborenen mit einem Gestationsalter <32 Schwangerschaftswochen

Hintergrund: Infektionen sind eine der wichtigsten Komplikationen bei Frühgeborenen. Daher erhalten bis zu 80% der Frühgeborenen Antibiotika in der ersten Lebenswoche. Antibiotika erhöhen aber auch das Auftreten von Komplikationen wie der BPD, der NEC, der LOS oder dem Tod. Wahrscheinlich liegen dem Veränderungen des Mikrobioms durch die Antibiotikatherapie zugrunde. Seit 2013 erfolgt auf neonatologischen Intensivstationen in Deutschland ein wöchentliches Kolonisations-Screening auf multiresistente Erreger und Erreger mit erhöhtem epidemischem Potential. Ziel dieser Arbeit war es, den Einfluss einer frühen Antibiotikatherapie in der ersten Lebenswoche auf die Kolonisation mit ppE zu untersuchen und weitere Einflussfaktoren für eine solche Besiedlung zu beschreiben. Methoden: Es erfolgte eine retrospektive, multizentrische Analyse von klinischen und mikrobiologischen Daten von 1543 Frühgeborenen mit einem Gestationsalter von unter 32 Schwangerschaftswochen die in drei deutschen neonatologischen Zentren (Tübingen, Bonn, Stuttgart) zwischen 2014 und 2019 geboren worden waren. Dabei wurden jedoch nur Frühgeborene berücksichtigt, die bis zum 35. Lebenstag überlebt hatten. Die Daten wurden mittels SPSS 26.0 (IBM, München, Germany) zunächst deskriptiv und mittels T-Test und Chi-Quadrat-Test analysiert. Im Anschluss daran erfolgte dann eine binäre logistische Regressionsanalyse mit möglichen Einflussfaktoren auf die Besiedlung mit ppE. Analog wurde die Untersuchung des Einflusses der Dauer und des Beginns einer Antibiotikatherapie durchgeführt. Ergebnisse: Von den 1543 im Auswertezeitraum in den teilnehmenden Zentren geborenen Frühgeborenen unter 32 SSW überlebten 1407 (91,2%) bis zum 35. Lebenstag und wurden in den Auswertungen berücksichtigt. Es erhielten 911/1407 (64,7%) der Frühgeborenen mit Gestationsalter <32 SSW und 428/480 (89,2%) der Frühgeborenen mit Gestationsalter <28 SSW in der ersten Lebenswoche Antibiotika. Bei 547/1407(38.9%) wurde ein ppE im Kolonissationsscreening nachgewiesen. Die Antibiotikatherapie in der ersten Lebenswoche hatte keinen Einfluss auf den Nachweis ppE. Einzig das Zentrum der Behandlung war unabhängig mit dem Nachweis von ppE assoziiert. Entgegen den Erwartungen ging eine kurze Antibiotikatherapie (1-2 Tage) im Vergleich zu längerer Therapiedauer mit einem erhöhten Risiko für die Besiedlung mit Erregern mit erhöhtem epidemischem Potential einher. Schlussfolgerung: In dieser Studie konnte kein Zusammenhang zwischen einer frühen Antibiotikatherapie und dem Nachweis von ppE bei Frühgeborenen gefunden werden. Überraschenderweise erhöhte eine kurze Antibiotikatherapie (1-2 Tage) das Risiko einer Besiedlung mit Erregern mit hohem epidemischem Potential. Es sind weitere Studien nötig, um die Bedeutung einer Besiedlung mit ppE besser bewerten zu können

6-Hydroxydopamine lesion of the rat prefrontal cortex impairs motor initiation but not motor execution

We examined the effects of bilateral 6-hydroxydopamine (6-OHDA) lesions of the medial prefrontal cortex (PFC) in rats on motor initiation and execution in a simple reaction time task. Reaction times (RT) and movement times (MT) were measured in trained rats on four preand postoperative days. Animals with 6-OHDA lesions were selectively impaired on motor initiation as measured by a significant increase in RT on each postoperative day. Motor execution was intact postoperatively, since MT was not altered. Neurochemical analysis revealed a significant depletion of prefrontal dopamine (DA) and noradrenaline (NA) in lesioned animals. It was concluded that DA and, to a lesser extent, NA in the rat PFC were involved in monitoring RT performance

The Determinants Of Human Wellbeing In Professional Activities

The article discusses the issue of person's attitude towards success in his professional activities, which are the value of human labor and his wellbeing in professioanl activity. Personal attitude and substantial components of socio-psychological factors of attitude development provides the field of welfare of the employee. It focuses on the implementation of efficient technologies of formation attitude towards success in the process of training and retraining. The object of the research was the OJSC Evrazruda candidate pool members studying at the Evraz Siberia Regional Staff Training Center, as well as a group of experts (engineer, metallurgists). The techniques of V. K. Gerbachevsky, V. V. Stolin, S. R. Panteleyev, H. J. Eysenck, M. Rokeach, N. M. Peysakhov and J. Rotter were used in the research. The study showed the interconnection of a person's attitude with the dominant features of the component structure of motivational, volitional and self-consciousness factors. They are the determinants of wellbeing and quality of life in professional activity

Risk factors in critical illness myopathy during the early course of critical illness: a prospective observational study

INTRODUCTION: Non-excitable muscle membrane indicates critical illness myopathy (CIM) during early critical illness. We investigated predisposing risk factors for non-excitable muscle membrane at onset of critical illness. METHODS: We performed sequential measurements of muscle membrane excitability after direct muscle stimulation (dmCMAP) in 40 intensive care unit (ICU) patients selected upon a simplified acute physiology (SAPS-II) score >OR= 20 on 3 successive days within 1 week after ICU admission. We then investigated predisposing risk factors, including the insulin-like growth factor (IGF)-system, inflammatory, metabolic and hemodynamic parameters, as well as suspected medical treatment prior to first occurrence of abnormal dmCMAP. Nonparametric analysis of two-factorial longitudinal data and multivariate analysis were used for statistical analysis. RESULTS: 22 patients showed abnormal muscle membrane excitability during direct muscle stimulation within 7 (5 to 9.25) days after ICU admission. Significant risk factors for the development of impaired muscle membrane excitability in univariate analysis included inflammation, disease severity, catecholamine and sedation requirements, as well as IGF binding protein-1 (IGFBP-I), but did not include either adjunctive hydrocortisone treatment in septic shock, nor administration of neuromuscular blocking agents or aminoglycosides. In multivariate Cox regression analysis, interleukin-6 remained the significant risk factor for the development of impaired muscle membrane excitability (HR 1.006, 95%-CI (1.002 to 1.011), P = 0.002). CONCLUSIONS: Systemic inflammation during early critical illness was found to be the main risk factor for development of CIM during early critical illness. Inflammation-induced impairment of growth-factor mediated insulin sensitivity may be involved in the development of CIM

Puzzled by GRB 060218

We study the optical-UV/X-ray spectral energy distribution of GRB 060218 during the prompt phase and during what seems to be the afterglow phase. The results are puzzling, since if the opt-UV and the X-ray emission belong to a single backbody (BB), then its luminosity is too large, and this BB cannot be interpreted as the signature of the shock breakout of the supernova. There are also serious problems in associating the emission expected by the supernova shock breakout with either the opt-UV or the X-ray emission. In the former case we derive too small ejecta velocities; in the latter case, on the contrary, the required velocity is too large, corresponding to the large radius of a BB required to peak close to the UV band. We then present what we think is the most conservative alternative explanation, namely a synchrotron spectrum, self-absorbed in the opt-UV and extending up to the X-ray band, where we observe the emission of the most energetic electrons, which are responsible for the exponential roll-over of the spectrum. The obtained fit can explain the entire spectrum except the BB observed in the X-rays, which must be a separate component. The puzzling feature of this interpretation is that the same model is required to explain the spectrum also at later times, up to 1e5 s, because the opt-UV emission remains constant in shape and also (approximately) in normalisation. In this case the observed X-ray flux is produced by self-Compton emission. Thus the prompt emission phase should last for ~1e5 s or more. Finally, we show that the BB observed in X-rays, up to 7000 seconds, can be photospheric emission from the cocoon or stellar material, energized by the GRB jet at radii comparable to the stellar radius (i.e. 1e10-1e11 cm), not very far from where this material becomes transparent (e.g. 1e12 cm).Comment: revised version accepted for publication in MNRAS (Letters

Sex Differences in the Effects of Acute and Chronic Stress and Recovery after Long-Term Stress on Stress-Related Brain Regions of Rats

Studies show that sex plays a role in stress-related depression, with women experiencing a higher vulnerability to its effect. Two major targets of antidepressants are brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element–binding protein (CREB). The aim of this study was to investigate the levels of CREB, phosphorylation of CREB (pCREB), and BDNF in stress-related brain regions of male and female rats after stress and recovery. CREB and pCREB levels were examined in CA1, CA2, CA3, paraventricular nucleus of the thalamus (PVT), amygdala, anterior cingulate area, dorsal part (ACAd), and infralimbic area of prefrontal cortex (PFC), whereas dentate gyrus (DG) and prelimbic area (PL) of PFC were examined for BDNF levels. Our results demonstrate that levels of CREB and pCREB in male CA1, CA2 and CA3, PVT, amygdala, and ACAd were reduced by stress, whereas the same brain regions of female rats exhibited no change. BDNF levels were decreased by chronic stress in female PL but were increased by acute stress in female DG. BDNF levels in male DG and PL were found not to undergo change in response to stress. Abnormalities in morphology occurred after chronic stress in males but not in females. In all cases, the levels of CREB, pCREB, and BDNF in recovery animals were comparable to the levels of these proteins in control animals. These findings demonstrate a sexual dimorphism in the molecular response to stress and suggest that these differences may have important implications for potential therapeutic treatment of depression

Mice lacking interleukin-18 gene display behavioral changes in animal models of psychiatric disorders : Possible involvement of immunological mechanisms

Preclinical and clinical evidence suggests pro-inflammatory cytokines might play an important role in the neurobiology of schizophrenia and stress-related psychiatric disorders. Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and it is widely expressed in brain regions involved in emotional regulation. Since IL-18 involvement in the neurobiology of mental illnesses, including schizophrenia, remains unknown, this work aimed at investigating the behavior of IL-18 null mice (KO) in different preclinical models: 1. the prepulse inhibition test (PPI), which provides an operational measure of sensorimotor gating and schizophrenic-like phenotypes; 2. amphetamine-induced hyperlocomotion, a model predictive of antipsychotic activity; 3. resident intruder test, a model predictive of aggressive behavior. Furthermore, the animals were submitted to models used to assess depressive- and anxiety-like behavior. IL-18KO mice showed impaired baseline PPI response, which was attenuated by D-amphetamine at a dose that did not modify PPI response in wild-type (WT) mice, suggesting a hypodopaminergic prefrontal cortex function in those mice. D-Amphetamine, however, induced hyperlocomotion in IL-18KO mice compared to their WT counterparts, suggesting hyperdopaminergic activity in the midbrain. Moreover, IL-18KO mice presented increased basal levels of IL-1 beta levels in the hippocampus and TNF-alpha in the prefrontal cortex, suggesting an overcompensation of IL-18 absence by increased levels of other proinflammatory cytokines. Although no alteration was observed in the forced swimming or in the elevated plus maze tests in naive IL-18KO mice, these mice presented anxiogenic-like behavior after exposure to repeated forced swimming stress. In conclusion, deletion of the IL-18 gene resembled features similar to symptoms observed in schizophrenia (positive and cognitive symptoms, aggressive behavior), in addition to increased susceptibility to stress. The IL-18KO model, therefore, could provide new insights into how changes in brain immunological homeostasis induce behavioral changes related to psychiatric disorders, such as schizophrenia.Peer reviewe

Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory

Paraventricular thalamic nucleus: Subcortical connections and innervation by serotonin, orexin, and corticotropin-releasing hormone in macaque monkeys

The present study examines subcortical connections of paraventricular thalamic nucleus (Pa) following small anterograde and retrograde tracer injections in cynomolgus monkeys ( Macaca fascicularis ). An anterograde tracer injection into the dorsal midline thalamus revealed strong projections to the accumbens nucleus, basal amygdala, lateral septum, and hypothalamus. Retrograde tracer injections into these areas labeled neurons specifically in Pa. Following a retrograde tracer injection into Pa, labeled neurons were found in the hypothalamus, dorsal raphe, and periaqueductal gray. Pa contained a remarkably high density of axons and axonal varicosities immunoreactive for serotonin (5-HT) and orexin/hypocretin (ORX), as well as a moderate density of fibers immunoreactive for corticotropin-releasing hormone (CRH). A retrograde tracer injection into Pa combined with immunohistochemistry demonstrated that ORX and 5-HT axons originate from neurons in the hypothalamus and midbrain. Pa-projecting neurons were localized in the same nuclei of the hypothalamus, amygdala, and midbrain as CRH neurons, although no double labeling was found. The connections of Pa and its innervation by 5-HT, ORX, and CRH suggest that it may relay stress signals between the midbrain and hypothalamus with the accumbens nucleus, basal amygdala, and subgenual cortex as part of a circuit that manages stress and possibly stress-related psychopathologies. J. Comp. Neurol. 512:825–848, 2009. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61435/1/21934_ftp.pd

Complex movement disorders at disease onset in childhood narcolepsy with cataplexy

Narcolepsy with cataplexy is characterized by daytime sleepiness, cataplexy (sudden loss of bilateral muscle tone triggered by emotions), sleep paralysis, hypnagogic hallucinations and disturbed nocturnal sleep. Narcolepsy with cataplexy is most often associated with human leucocyte antigen-DQB1*0602 and is caused by the loss of hypocretin-producing neurons in the hypothalamus of likely autoimmune aetiology. Noting that children with narcolepsy often display complex abnormal motor behaviours close to disease onset that do not meet the classical definition of cataplexy, we systematically analysed motor features in 39 children with narcolepsy with cataplexy in comparison with 25 age- and sex-matched healthy controls. We found that patients with narcolepsy with cataplexy displayed a complex array of ‘negative’ (hypotonia) and ‘active’ (ranging from perioral movements to dyskinetic–dystonic movements or stereotypies) motor disturbances. ‘Active’ and ‘negative’ motor scores correlated positively with the presence of hypotonic features at neurological examination and negatively with disease duration, whereas ‘negative’ motor scores also correlated negatively with age at disease onset. These observations suggest that paediatric narcolepsy with cataplexy often co-occurs with a complex movement disorder at disease onset, a phenomenon that may vanish later in the course of the disease. Further studies are warranted to assess clinical course and whether the associated movement disorder is also caused by hypocretin deficiency or by additional neurochemical abnormalities