Oestradiol‐Induced Synapse Formation in the Female Hippocampus: Roles of Oestrogen Receptor Subtypes

During the oestrus cycle, varying spine synapse density correlates positively with varying local synthesis of oestradiol in the hippocampus. In this context, the roles of the oestrogen receptor (ER) subtypes ERα and β are not fully understood. In the present study, we used neonatal hippocampal slice cultures from female rats because these cultures synthesise oestradiol and express both receptor subtypes, and inhibition of oestradiol synthesis in these cultures results in spine synapse loss. Using electron microscopy, we tested the effects on spine synapse density in response to agonists of both ERα and ERβ. Application of agonists to the cultures had no effect. After inhibition of oestradiol synthesis, however, agonists of ERα induced spine synapse formation, whereas ERβ agonists led to a reduction in spine synapse density in the CA1 region of these cultures. Consistently, up‐regulation of ERβ in the hippocampus of adult female aromatase‐deficient mice is paralleled by hippocampus‐specific spine synapse loss in this mutant. Finally, we found an increase in spine synapses in the adult female ERβ knockout mouse, but no effect in the adult female ERα knockout mouse. Our data suggest antagonistic roles of ERβ and ERα in spine synapse formation in the female hippocampus, which may contribute to oestrus cyclicity of spine synapse density in the hippocampus.     

Expertise modulates local regional homogeneity of spontaneous brain activity in the resting brain: An fMRI study using the model of skilled acupuncturists

Studies on training/expertise‐related effects on human brain in context of neuroplasticity have revealed that plastic changes modulate not only task activations but also patterns and strength of internetworks and intranetworks functional connectivity in the resting state. Much has known about plastic changes in resting state on global level; however, how training/expertise‐related effect affects patterns of local spontaneous activity in resting brain remains elusive. We investigated the homogeneity of local blood oxygen level‐dependent fluctuations in the resting state using a regional homogeneity (ReHo) analysis among 16 acupuncturists and 16 matched nonacupuncturists (NA). To prove acupuncturists' expertise, we used a series of psychophysical tests. Our results demonstrated that, acupuncturists significantly outperformed NA in tactile‐motor and emotional regulation domain and the acupuncturist group showed increased coherence in local BOLD signal fluctuations in the left primary motor cortex (MI), the left primary somatosensory cortex (SI) and the left ventral medial prefrontal cortex/orbitofrontal cortex (VMPFC/OFC). Regression analysis displayed that, in the acupuncturists group, ReHo of VMPFC/OFC could predict behavioral outcomes, evidenced by negative correlation between unpleasantness ratings and ReHo of VMPFC/OFC and ReHo of SI and MI positively correlated with the duration of acupuncture practice. We suggest that expertise could modulate patterns of local resting state activity by increasing regional clustering strength, which is likely to contribute to advanced local information processing efficiency. Our study completes the understanding of neuroplasticity changes by adding the evidence of local resting state activity alterations, which is helpful for elucidating in what manner training effect extends beyond resting state. Hum Brain Mapp 35:1074–1084, 2014. © 2013 Wiley Periodicals, Inc.     

Hypersensitivity and hyperalgesia in somatoform pain disorders

Objective

In psychiatry, pain disorders not explained by structural lesions have been classified for decades as somatoform pain disorders, the underlying concept being somatization. In a parallel move, somatic medicine has defined an expanding group of similar pain disorders, known as functional pain syndromes. Functional pain syndromes are characterized by enhanced pain sensitivity. The aim of our study was to investigate the proportion of patients with somatoform pain disorders who also meet the criteria of functional pain syndromes and the extent to which patients with somatoform pain disorders also show enhanced pain sensitivity.

Methods

Data on pain sensitivity in 120 hospitalized patients were obtained by means of two algometric methods. The group of patients with somatoform pain disorders was further divided into two subsets: patients with and those without a co-diagnosis of a functional pain syndrome. Patients with nociceptive pain served as control group.

Results

Of the 120 in-patients selected, 67 fulfilled the criteria of a somatoform pain disorder of which 41 (61%) also met the co-diagnosis of a functional pain syndrome. Patients with somatoform pain disorder differed from controls in that they showed enhanced pain sensitivity, irrespective of whether a functional pain syndrome was concomitantly present (P< .001).

Conclusions

Somatoform pain disorders show considerable overlap with functional pain syndromes, including enhanced pain sensitivity. This suggests the relevance of integrating somatosensory aspects of pain into a modified understanding of somatoform pain disorders.     

Translating in vitro prediction of cytotoxic T cell alloreactivity to hematopoietic stem cell transplantation outcome

IntroductionPreviously we developed a weighted amino acid (AA) mismatch score predictive for cytotoxic T cell (CTL) alloreactivity (in vitro CTLp assay) based on the structure of the HLA class I molecule. The aim of this study is to confirm the clinical relevance of the CTLp assay and to validate the AA mismatch score as an alternative and easy to use tool to predict permissible mismatches in hematopoietic stem cell transplantation (HSCT).MethodsWe selected patients transplanted with a 9/10 single HLA class I mismatched graft (n = 171) at three Dutch HSCT centers. A CTLp assay was performed in 73 donor–recipient pairs. As a control we selected 168 10/10 HLA matched pairs that were matched to the 9/10 single HLA class I mismatched pairs for HSCT year, donor type, patient age and diagnosis.ResultsWe observed that pairs with negative a CTLp assay had statistically significant decreased incidence of mortality after HSCT comparable to that of 10/10 HLA matched pairs. However, the weighted AA mismatch score did not significantly predict any HSCT end point of interest.ConclusionFurther investigation is needed to unravel the mechanisms involved in causing the beneficial effect of a negative CTLp assay, before other alternative tools to predict HSCT outcome may be developed.     

Effect of perioperative complications and functional outcomes on health-related quality of life after radical prostatectomy

Purpose

Radical prostatectomy is a commonly performed procedure with perioperative complication rates of 30 % using standardized reporting methodology. We aim to determine whether perioperative complications and functional outcomes impact quality of life 1 year after surgical treatment.

Patients and methods

Quality of life, functional and oncological outcomes were assessed in patients who underwent open retropubic radical prostatectomy at a single academic institution between 2003 and 2009, preoperatively and 1 year after surgery using the EORTC QLQ-C30, the IIEF-5 and an institutional questionnaire. Perioperative complications were recorded using the Clavien–Dindo classification. Patients without complications were compared to patients with any, low- or high-grade complications. The global health score domain of the EORTC QLQ-C30 is reported for various oncological and functional outcomes and contrasted to stratified categories of complications and functional outcomes.

Results

A full dataset was available for 29.5 % (n = 856) of all patients. The overall complication rate was 27.5 % (235/856). A total of 307 complications were recorded of whom 88.9 % (273/307) were low grade. In this study, population global health perception did not decline after surgery (70.5 ± 21.2 vs. 74.4 ± 19.7; p < 0.0001). Complications showed only statistical but no clinical meaningful influence on global health perception as well as on functional and symptom scales. Patients who met combined outcome criteria experienced the best postoperative global health score (86.0 ± 13.1 and 86.0 ± 14.2).

Conclusions

Perioperative complications and functional outcomes have a measurable impact on quality of life 1 year following surgery. While perioperative complications have a statistical effect, functional outcomes showed a clinically more profound effect on postoperative global health perception.     

Stress-related changes in financial risk taking: Considering joint effects of cortisol and affect

Many decisions under risk and uncertainty are made under physical or emotional stress. A recent meta-analysis suggested that stress reliably influences risk taking but did not find a relation between single measures of stress such as cortisol and risk taking. One reason for the conflicting findings could be that the influence of stress on risk taking depends not only on physiological but also on psychological stress responses, in particular affective valence. We tested this hypothesis in an exploratory empirical study: Seventy participants worked on a financial risk-taking task. In half of the participants acute stress was induced with a cold pressor task. For all participants we measured cortisol and α-amylase levels, blood pressure, subjective arousal, and affective valence before and after the task. The stress induction increased participants' levels of cortisol, subjective arousal, and systolic blood pressure but did not directly influence negative affect or risky decision making. Examining the interplay between physiological and psychological stress responses, a moderation analysis revealed an interaction between stress induction and affect valence: Negative affect predicted an increase in risk-seeking decision making in the stress condition, but not in the control group. A similar moderation was found with cortisol reactivity, that is, negative affect predicted an increase in risk-seeking decision making in participants with high cortisol reactivity but not in participants with low cortisol reactivity. These results suggest that the effect of stress on risky decision making depends on the interplay of affective valence and cortisol reactivity.