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There is increasing evidence that chronic inflammation is tightly linked to diseases associated with endothelial dysfunction, including the induction of aberrant angiogenesis. While leukocytes have been described as mediators of inflammation-associated angiogenesis, the effects of direct chronic endothelial activation have not been addressed in this context. Using an uncleavable mutant of the transmembrane form of tumor necrosis factor-α (TNF-α), we have established models of stable TNF-α expression in endothelial cells in vitro and in transgenic mice in vivo. In the in vitro model, continuous endothelial activation leads to increased leukocyte cellular adhesion molecule expression and intracellular reactive oxygen species, hallmarks of a proinflammatory and dysfunctional endothelium. In addition, stable expression of TNF-α in endothelial cells increased angiogenic sprout formation in the presence but also in the absence of angiogenic growth factors. The partial neutralization of this effect by TNF-α antibodies and the inability of conditioned media from stable TNF-α-expressing endothelial cells to induce angiogenic activities in control endothelial cells suggest that this effect does not require expression of additional autocrine factors, but is an autonomous effect of the transmembrane TNF on the endothelial cells. Furthermore, using the Matrigel plug assay in vivo, increased angiogenesis was observed in endothelial TNF-α-expressing transgenic versus control mice. In conclusion, chronic inflammatory changes mediated by TNF-α can induce angiogenesis in vitro and in vivo, suggesting endothelial cell activation as a direct link between inflammation and angiogenesis. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Objective: To study awareness of cognitive dysfunction in patients with very mild Alzheimer’s disease (AD) and subjects with mild cognitive impairment (MCI). Methods: A complaint interview covering 13 cognitive domains was administered to 82 AD and 79 MCI patients and their caregivers. The patient groups were comparable according to age and education, and Mini Mental State Examination (MMSE) scores were ≥24 in all cases. The discrepancy between the patients’ and caregivers’ estimations of impairments was taken as a measure of anosognosia. Results: Self-reports of cognitive difficulties were comparable for AD and MCI patients. However, while in comparison to caregivers MCI patients reported significantly more cognitive impairment (p < 0.05), AD patients complained significantly less cognitive dysfunctions (p < 0.001). Conclusions: While most MCI patients tend to overestimate cognitive deficits when compared to their caregiver’s assessment, AD patients in early stages of disease underestimate cognitive dysfunctions. Anosognosia can thus be regarded as a characteristic symptom at a stage of very mild AD (MMSE ≥24) but not MCI. Accordingly, medical history even in mildly affected patients should always include information from both patient and caregiver. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Bakgrund: När individer diagnostiseras med ADHD är det inte ovanligt att individen påbörjar en centralstimulerande läkemedelsbehandling. Men forskningen kring läkemedelsbehandlingens påverkan på sexualiteten är skral både nationellt och internationellt. Det finns ett behov av att få bättre förståelse de konsekvenser som centralstimulerande läkemedelsbehandling kan ha för individers sexuella hälsa och välbefinnande. Syfte: För att fördjupa kunskapen inom detta område syftade denna studie att undersöka hur vuxna personer med ADHD upplever att centralstimulerande läkemedelsbehandling påverkar deras sexuella hälsa och välbefinnande samt vilka upplevelser de har av hälso- och sjukvårdens bemötande i relation till frågor som rör sexualitet och ADHD-läkemedel.Metod: Studien utgår ifrån en kvalitativ forskningsdesign bestående av nio semistrukturerade intervjuer. Empirin har analyserats utifrån en reflexiv tematisk analys.Resultat: Resultatdelen bygger på tre huvudteman: Medicinska biverkningars påverkan på sexualitet, Intervjupersoners upplevelser av sitt medicinerande sexuella jag – individuellt och relationellt och Sexualitet i en vårdkontext. Dessa har analyserats med hjälp av begreppen compulsory sexuality och compulsory able-bodiedness för att förstå hur normer kring sexualitet och kroppslig funktion samverkar och påverkar individers upplevelse av sin sexualitet. Slutsats: Resultaten visar att centralstimulerande läkemedel påverkar sexualiteten både positivt och negativt i relation till kroppsliga, psykologiska och sociala faktorer. I studien uppkommer även behov och önskemål om att sexologiska frågeställningar och information om sexuella biverkningar lyfts i hälso- och sjukvården. Resultaten är av vikt för den kliniska sexologin för att ämnet ska synliggöras och uppmärksammas i praktiken för att möjliggöra sexuellt välbefinnande hos vuxna personer med ADHD. / Background: When individuals are diagnosed with ADHD it is not uncommon that they begin a treatment with stimulant medication. However, research about the impact of said treatment is sparse, both nationally as well as internationally. There lies a need to make better understanding of what consequences central stimulants can have for the individual's sexual health and well-being. Aim: To deepen the knowledge within this field, the study aims to examine how adults diagnosed with ADHD experience how being treated with central stimulants affects their sexual health and well-being, as well as what experiences these individuals have regarding how they are being approached by health care professionals with reference to questions about sexuality and medication for ADHD. Method: A qualitative research method has been used in this study, consisting of nine semi-structured interviews. The observations have been analyzed with a reflexive thematic analysis.Results: The results are divided into three major themes: The influence that medical side effects have on sexuality, How the interviewees view their medicating sexual self - individually and with others and Sexuality in a health care context. The themes have been analyzed together with the concepts of compulsory sexuality and compulsory able-bodiedness in order to understand how social norms regarding sexuality and bodily function intertwine with - and affect – individuals’ view on their own sexuality. Conclusion: The results show that central stimulants affect sexuality in both positive and negative ways regarding bodily, psychological and social factors. The study also shows that there is a need for questions of sexological matter to be brought up by health care professionals, as well as giving information about potential side effects that have an impact on sexual health. The results are important for the clinical sexology field and practition, in order to raise awareness for this subject and to enable sexual well-being for adults with ADHD.

The hypothalamus-pituitary-adrenal (HPA) axis is activated in response to inflammation leading to increased production of anti-inflammatory glucocorticoids by the adrenal cortex, thereby representing an endogenous feedback loop. However, severe inflammation reduces the responsiveness of the adrenal gland to adrenocorticotropic hormone (ACTH), although the underlying mechanisms are poorly understood. Here, we show by transcriptomic, proteomic, and metabolomic analyses that LPS-induced systemic inflammation triggers profound metabolic changes in steroidogenic adrenocortical cells, including downregulation of the TCA cycle and oxidative phosphorylation, in mice. Inflammation disrupts the TCA cycle at the level of succinate dehydrogenase (SDH), leading to succinate accumulation and disturbed steroidogenesis. Mechanistically, IL-1β reduces SDHB expression through upregulation of DNA methyltransferase 1 (DNMT1) and methylation of the SDHB promoter. Consequently, increased succinate levels impair oxidative phosphorylation and ATP synthesis and enhance ROS production, leading to reduced steroidogenesis. Together, we demonstrate that the IL-1β-DNMT1-SDHB-succinate axis disrupts steroidogenesis. Our findings not only provide a mechanistic explanation for adrenal dysfunction in severe inflammation, but also offer a potential target for therapeutic intervention.

<p>Hintergrund: Es gibt nur begrenzte Kenntnisse über Surrogat-Parameter für eine Verschlechterung der körperlichen Funktionsfähigkeit (SF-36) im Verlauf bei Patienten mit diastolischer Dysfunktion/Herzinsuffizienz bzw. mit Risikofaktoren hierfür. Diese Arbeit untersuchte die Assoziation neurohumoraler Aktivierung mit physischer Lebensqualität (SF-36) im Ein-Jahres-Verlauf.</p> <p> Methoden: In der bevölkerungsbasierten Diast-CHF-Studie wurden n=1937 Patienten mit Risikofaktoren für eine diastolische Herzinsuffizienz oder bereits diagnostizierter Herzinsuffizienz eingeschlossen. Für die Fragestellung wurden n=855 Patienten analysiert (Einschlusskriterien: LVEF≥50%, vorhandene Daten für LQ zu beiden Messzeitpunkten im Ein-Jahres-Verlauf (SF-36)). Alle Patienten wurden dichotomisiert in eine Gruppe mit unveränderter/verbesserter (PhF+) vs. verschlechterter körperlicher Funktionsfähigkeit (PhF-) nach einem Jahr (1-FU) im Vergleich zu den erhobenen Baseline-Werten. Verschlechterte körperliche Lebensqualität (PhF-) wurde definiert als eine Verschlechterung um mindestens eine halbe Standardabweichung gegenüber den Werten aus der Baseline. Bei allen Patienten wurden Blutentnahmen, detaillierte echokardiographische Untersuchungen sowie ein 6-Minuten-Gehtest (6-MWD) durchgeführt.</p><p> Ergebnisse: Die analysierte Population (n=855) setzte sich aus n=718 (84%) mit PhF+ sowie n=137 (16%) mit PhF- zusammen. PhF+/PhF-: Alter: 65,6±7,3/69,4±7,7 (p<0,001), BMI: 28,6±4,6/30,4±5,1 (p<0,001), LVEF: 61,6±6,2/61,9±5,8% (p=0,646), 6-MWD: 524,4±109,5/486,0±86,8 (p<0,001), NT-proBNP: 129,8/220,3 (p=0,030), MR-proADM: 0,58/0,69 (p=0,001), MR-proANP: 95,1/121,5 (p=0,009), CT-proET1: 54,6/62,4 (p=0.001). E/é: 9,8/10,9 (p=0,003), LAVI: 23,9/26,3 (p=0,007) und LVMI: 115,1/120,2 (p=0,045). Aus den Ergebnissen der linearen und logistischen Regression ging hervor, dass insbesondere das MR-proADM eine signifikante Assoziation zum Ein-Jahres-Verlauf körperlichen Funktionsfähigkeit (p<0,001) zeigte. Diese Assoziation war unabhängig von Parametern wie Alter, BMI und E/é.</p><p> Fazit: Neurohormone scheinen sich als Surrogat-Parameter für eine Verschlechterung der physischen Lebensqualität im Verlauf bei Patienten mit diastolischer Dysfunktion/Herzinsuffizienz oder kardiovaskulären Risikofaktoren hierfür zu eignen.

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No description available.

Restless legs syndrome (RLS) is a sensory-motor disorder characterized by abnormal circadian rhythm with an increase in the severity of sensory and motor symptoms at night. Even though many neurological diseases have shown a strong nexus between motor and cognitive symptoms, to date, cognitive functions especially cognitive control in RLS has been poorly understood. Given that cognitive control is a key to leading a self-serving and successful life, including many aspects of employment, social life, and attaining long-term goals, this thesis aimed to examine cognitive control and the underlying mechanisms in RLS. Thalamic gamma aminobutyric acid (GABA), which has been linked to RLS sensory-motor symptoms, also plays an important role in cognitive control. Therefore, the potential relationship between thalamic GABA level and cognitive control in RLS was examined (Study I). RLS patients displayed reduced working memory-based control performances as compared to healthy controls. Elevated thalamic GABA was found to attenuate the observed control deficits in RLS, even though changes in thalamic GABA levels might not be the ultimate causes of these deficits. According to the modulatory effect of thalamic GABA on thalamic activity and thalamo-cortical connectivity, relatively higher GABA levels may have helped RLS patients compensate for their pathological changes such as thalamic hyperactivity and hypoconnectivity, which may underpin the observed control deficits. The critical feature of RLS, abnormal circadian rhythm is thought to be related to nocturnal striatal dopamine deficiency. Concerning the dopaminergic modulation of cognitive control, the circadian variation of cognitive control processes has been investigated (Study II & III). RLS patients displayed reduced attentional control (Study II) and automatic response activation (Study III) at night, which resulted from decreased activation within the extra-striate visual cortex, the superior parietal cortex, and the premotor cortex. As there were no activity changes within the prefrontal cortex, it is likely that cortico-basal ganglia cognitive loops were less prone to RLS. Instead, striatal dopamine deficiency at night may have influenced the cortico-cortical functional connectivity and cortico-basal ganglia motor loops in RLS. These findings not only shed light on the underlying mechanisms of cognitive control, but also advance early clinical treatment possibilities for cognitive changes in RLS patients. Furthermore, recent insights into daytime-related cognition may help patients develop a suitable daytime schedule to minimize the detrimental effects induced by cognitive deficits.

Background Alterations of mental status are characteristic of psychiatric disorders but may also result from a multitude of organic causes. Generally, physical examination and blood analysis are a part of basic psychiatric differential diagnostics, whereas more sophisticated procedures (for example, brain imaging) are applied only in cases with pathologic diagnostic findings. Our report challenges this approach by describing a case of glioblastoma multiforme presenting as postpartum depression without abnormalities in basic differential diagnostics. Case presentation A 28-year-old white woman who had been in outpatient treatment for postpartum depression was taken to the psychiatric emergency room. The psychopathological assessment, however, showed mild disorientation and severe deficits of long-term memory. Moreover, she complained of stabbing, bilateral headaches, but results of her physical examination and blood analysis were unremarkable. Magnetic resonance imaging of the brain was performed, which showed a contrast-enhanced mass lesion in the left frontal lobe. The patient underwent urgent tumor resection, and histologic results revealed an IDH-mutant glioblastoma multiforme. The patient was discharged with a substantially improved psychopathology and without neurological deficits. Conclusions This report adds to the evidence that postpartum depression may have organic causes in some cases, a fact that needs to be considered in the clinical setting. Atypical neurocognitive findings in a psychiatric interview may alone justify brain imaging, despite normal physical examination and blood analysis results.