Patients with chronic pain exhibit individually unique cortical signatures of pain encoding

Chronic pain is characterised by an ongoing and fluctuating intensity over time. Here, we investigated how the trajectory of the patients'' endogenous pain is encoded in the brain. In repeated functional MRI (fMRI) sessions, 20 patients with chronic back pain and 20 patients with chronic migraine were asked to continuously rate the intensity of their endogenous pain. Linear mixed effects models were used to disentangle cortical processes related to pain intensity and to pain intensity changes. At group level, we found that the intensity of pain in patients with chronic back pain is encoded in the anterior insular cortex, the frontal operculum, and the pons; the change of pain in chronic back pain and chronic migraine patients is mainly encoded in the anterior insular cortex. At the individual level, we identified a more complex picture where each patient exhibited their own signature of endogenous pain encoding. The diversity of the individual cortical signatures of chronic pain encoding results bridge between clinical observations and neuroimaging; they add to the understanding of chronic pain as a complex and multifaceted disease.     

Belastungsabhängige Dysphonie, rezidivierende Pleuropneumonie und supraglottische Raumforderung

Urbach-Wiethe syndrome (hyalinosis cutis et mucosae) is an autosomal-recessive inherited disease. It often presents with typical symptoms such as skin lesions (especially in the face and neck area), dyspnea, and maldigestion. Hoarseness is a leading symptom in young children. These manifestations are caused by the assimilation of glycoproteins in mesenchymal tissue. Our case report shows that hoarseness does not necessarily appear only in children, but can also appear later. Furthermore, the assimilation of glycoproteins in the supraglottic area may also cause dysphonia. Due to the varied features of this disease, interdisciplinary check-ups are necessary at regular intervals.     

Sorting in early endosomes reveals connections to docking- and fusion-associated factors

The early endosomes constitute a major sorting platform in eukaryotic cells. They receive material through fusion with endocytotic vesicles or with trafficking vesicles from the Golgi complex and later sort it into budding vesicles. While endosomal fusion is well understood, sorting is less characterized; the 2 processes are generally thought to be effected by different, unrelated machineries. We developed here a cell-free assay for sorting/budding from early endosomes, by taking advantage of their ability to segregate different cargoes (such as transferrin, cholera toxin subunit B, and low-density lipoprotein, LDL) into different carrier vesicles. Cargo separation required both carrier vesicle formation and active maturation of the endosomes. Sorting and budding were insensitive to reagents perturbing clathrin coats, coatomer protein complex-I (COPI) coats, dynamin, and actin, but were inhibited by anti-retromer subunit antibodies. In addition, the process required Rab-GTPases, phosphatidylinositol-3-phosphate, and, surprisingly, the docking factor early endosomal autoantigen 1 (EEA1). Sorting also required the function of the N-ethylmaleimide-sensitive factor (NSF), a well-known fusion cofactor, while it did not depend on preceding fusion of endosomes. We conclude that fusion, docking, and sorting/budding are interconnected at the molecular level.     

DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets

Background  

The epigenetics of ovarian carcinogenesis remains poorly described. We have in the present study investigated the promoter methylation status of 13 genes in primary ovarian carcinomas (n = 52) and their in vitro models (n = 4; ES-2, OV-90, OVCAR-3, and SKOV-3) by methylation-specific polymerase chain reaction (MSP). Direct bisulphite sequencing analysis was used to confirm the methylation status of individual genes. The MSP results were compared with clinico- pathological features.     

Geschlecht und Gesundheit

Ohne Zusammenfassung     

Is withdrawal-induced anxiety in alcoholism based on β-endorphin deficiency?

RATIONALE: Associations between several psychopathological alterations and lowered beta-endorphin(beta E) plasma levels have already been stated in former studies. However, whereas single measures during static conditions generally failed in linking beta E levels with psychopathology, dynamic changes of beta E in particular have been shown to be associated with spells of anxiety and depression. During alcohol withdrawal, a decreased secretion of beta E with a delayed normalization has been reported, but up to now only few data became available regarding the interaction of plasma beta E and psychopathological parameters. OBJECTIVES: The aim of our study was to test the hypothesis whether beta E during acute alcohol withdrawal is associated with anxiety, depression, and craving. METHODS: We observed self-rated anxiety, depression, and craving during alcohol withdrawal and assessed beta E levels (RIA) in a consecutive sample of 60 alcoholics on day 1 and day 14 after onset of withdrawal, and in 30 healthy volunteers. To control for mutual interactions of beta E and the pituitary-adrenocortical hormone secretion, plasma corticotropin (ACTH) and cortisol were also determined. RESULTS: In accordance with prior studies, beta E was significantly lowered on day 1 and day 14 of alcohol withdrawal relative to controls. Plasma levels of ACTH correlated significantly with beta E in alcoholics at both time points and in controls, without differing significantly between the groups. Self-rated anxiety, depression, and alcohol craving decreased significantly between day 1 and day 14. Levels of beta E were inversely correlated with anxiety day 1 (r=-0.58) and day 14 (r=-0.71). Partial correlation coefficients controlling for ACTH plasma levels revealed that this correlation was largely independent from ACTH. In addition, a significant inverse relationship was found between beta E and craving on day 14 (r=-0.28). No association appeared between beta E and depression. CONCLUSIONS: Our results give first evidence that lowered beta E during alcohol withdrawal may contribute to anxiety as a common disturbance during this state.     

Modulation of sympathetic activity by corticotropin-releasing hormone and atrial natriuretic peptide

BACKGROUND: Heart rate variability represents a reliable marker to delineate the status of autonomic nervous system (ANS) function and alterations due to stress in vivo. Interestingly, up to now the effects of corticotropin-releasing hormone (CRH), a key regulator of the stress hormone system, upon heart rate variability are not sufficiently described. Hence, we attempted to investigate the ANS-effects of a CRH bolus and the modulatory influences of atrial natriuretic peptide (ANP), one of the most important functional antagonist of CRH actions.METHODS: 12 healthy male volunteers were administered 100 microg CRH as bolus injection at 15:00. Six randomly chosen subjects received 150 microg ANP dissolved in normal saline and six subjects a normal saline infusion from 14:45 to 15:15. From 13:00 to 17:00 an ECG was recorded and mean heart rate (HR), total power (TP), very low frequency (VLF), low frequency (LF), LF in normalized units (LF [nu]), high frequency (HF) domains and the LF/HF-ratio in the interval from 14:00 to 16:00 were determined.RESULTS: After administration of CRH a significant increase in HR and a fast reduction of TP were observed, which lasted about 1 h. Based upon spectral domain analyses the sympathetic activity after CRH administration as indicated by LF [nu] increased by 31% (mean location) during saline. Applying ANP this increase was reduced to 19% (mean location). The VLF component, which is considered to be based in part also on sympathetic influences, indicates comparable effect. During saline the VLF after CRH bolus remained largely unchanged, but was reduced to 66% by ANP. Though the vagal activity indicated by the HF component was reduced after CRH, no significant differences emerged between both treatments. The changes of the LF/HF-ratio were pronounced in both groups. During saline this ratio increased by about 111%, during ANP only by 43% (mean location).CONCLUSIONS: Based upon HRV analysis the CRH administration induced sympathotonic effects which were antagonized by ANP. The observed vagal changes were less pronounced and need further investigation. Further studies of autonomic effects by alterations of CRH secretion in depression and anxiety disorder are strongly warranted.     

Increased level of tonic sympathetic arousal in high-vs. low-alexithymic cervical dystonia patients

The purpose of this study was to assess whether alexithymia is a risk factor for autonomic dysregulation in cervical dystonia (spasmodic torticollis, ST). Alexithymia was assessed by an authorized German version of the TAS-20. In a first step, we recruited 10 ST-patients with high alexithymia scores (> 62; M = 69.2, SD = 3.0) and compared them with 10 ST-patients with low alexithymia scores (< 35; M = 28.7, SD = 4.3) on physiological and subjective responses to a cognitive and an emotional laboratory stressor. High-alexithymic ST-patients generally showed increased levels of autonomic arousal (higher SCL, more NS.SCF and lower T; 0.016 /= 57 vs. low 相似文献