A pilot study on perceived stress and PTSD symptomatology in relation to four dimensions of older women's physical health

Objectives: The authors examined whether selected demographic and psychological factors would predict physical health dimensions in a sample of 53 cognitively high-functioning and ethnically diverse women (age 65–105 years).

Method: Predictors encompassed posttraumatic stress disorder (PTSD) symptomatology and perceived stress (of a nontraumatic nature and beyond health status) in relation to four dimensions of physical health. Age and income, well-known correlates of health in the target population, were included as potential predictors. The authors first tested the relationship between potential predictors and health dimensions via a canonical correlation analysis, and then employed full multiple regression analyses to simultaneously test the predictors in each health dimension model.

Results: Perceived stress was a significant predictor of lower levels of general health (GH), but not of physical role limitations or physical functioning (PF). Conversely, PTSD symptomatology predicted more limitations in role fulfillment (and, to a lesser extent, impairedPF), but not lower levels of GH. As expected, age and income were predictive of some physical health dimensions. The hypothesized predictors failed to account for a significant portion of variance in pain scores.

Conclusion: PTSD symptomatology and perceived stress might influence older women's physical health dimensions differentially; additional research on larger samples is needed to corroborate these findings.     

Altered bone matrix mineralization in a patient with Rett syndrome

Rett syndrome (RTT) is a common X-linked neurodevelopmental disorder caused by mutations in the coding region of methyl-CpG-binding 2 (MECP2) gene. Patients with RTT have a low bone mineral density and increased risk of fracture. However, very little is known if bone matrix mineralization is altered in RTT. A 17-year-old girl with a classical form of RTT with a heterozygous nonsense mutation in exon 3 in the MECP2-gene was treated in our hospital. Her femoral neck BMD is 43.3% below the 3rd percentile when compared to age and sex-matched controls. She underwent surgery for correction of her scoliosis, which provided a unique opportunity to obtain bone tissue to study bone matrix mineralization (Bone Mineralization Density Distribution—BMDD) using quantitative backscattered electron imaging (qBEI) and histomorphometry. BMDD outcomes were compared to recently published normative reference data for young individuals. qBEI analysis showed a significant shift to lower matrix mineralization despite histomorphometric indices indicate a low bone turnover. There was a reduction in CaMean (? 7.92%) and CaPeak (? 3.97%), which describe the degree of mineralization. Furthermore the fraction of low mineralized matrix (CaLow: + 261.84%) was dramatically increased, which was accompanied with an increase in the heterogeneity of mineralization (CaWidth: + 86.34%).Our findings show a significantly altered bone matrix mineralization of a typical patient with RTT. This may partly explain the low bone density seen in these patients. These results also warrant further studies on the molecular role of MECP2 in bone matrix mineralization.     

Adenosine A2A receptor gene: Evidence for association of risk variants with panic disorder and anxious personality

Adenosine A_2A receptors are suggested to play an important role in different brain circuits and pathways involved in anxiety reactions. A variant within the corresponding ADORA2A gene (rs5751876) increased the risk for panic disorder (PD), for elevated anxiety during challenge tests in healthy probands and for anxiety-related arousal in blood-injury phobia. These multiple effects may mirror a more general effect of the SNP on basic personality traits. In the present study we therefore aimed to replicate the original finding in a large PD sample and extend it by investigating an additional proband sample characterized for different anxiety-related personality scores. In addition, as rs5751876 is assumed not to be the disease variant itself but to be in linkage disequilibrium (LD) with the true functional polymorphism other SNPs of potentially functional relevance were identified by re-sequencing the whole gene including several newly identified regions of putative regulatory potential and analysed for their impact on PD and anxious personality. We were indeed able to replicate rs5751876 as risk factor for PD, particularly PD with agoraphobia. Rs5751876 and several other variants in high LD (rs5751862, rs2298383 and rs3761422) as well as the corresponding haplotypes were also associated with different anxiety-related personality scores (Bonferroni corrected P_all < 0.05). Of these variants, rs2298383 shows functional potential based on in silico analyses and might therefore represent the true underlying causal variant. Our data provide further support for an important role of ADORA2A variants in the pathogenesis of anxiety disorders and anxious personality reflecting their potential as basic susceptibility factors.     

Acceptance of female urologists among patients with suspected prostate disease

BackgroundsThe number of practicing female urologists is rising. The aim of this study is to evaluate the acceptance of female urologists by male patients and their partners.MethodsMen who underwent a prostate MRI or a prostate biopsy between January and December 2018 and their partners, were sent questionnaires prior to the examination. Two types of questionnaires were used. One questionnaire asked “I want to be seen by: (I) a male urologist or (II) a female urologist or (III) no preference” (Group_np), the other questionnaire only offered two possible answers: “I want to be seen by: (I) a male urologist or (II) a female urologist” (Group_m,f). All other questions were on prostate MRI and prostate biopsies.ResultsOverall, 377 questionnaires were sent to patients. One hundred and ninety-six questionnaires (52.0%) were returned. In Group_np, 34.7% wanted to be seen by a male urologist, 60.8% of patients chose “no preference”. The answers of the patients’ female partners in Group_np did not differ statistically significant (57.3% chose “no preference”, 0% chose a female urologist). In Group_m,f, 54.5% of patients preferred a male urologist, one patient wanted to be seen by a female urologist, 44.3% did not answer the question. In Group_m,f, there was no statistically significant difference in preference in regard to the doctor’s gender between the patients and their female partners (57% of partners wanted a male urologist, 0% wanted a female urologist).ConclusionsA large number of patients with prostate disease and their partners prefer male urologists rather than female urologists.     

Bone morphogenetic protein 4 is induced in hepatocellular carcinoma by hypoxia and promotes tumour progression

Striking similarities exist between molecular mechanisms driving embryonic liver development and progression of hepatocellular carcinoma (HCC). Bone morphogenetic proteins (BMPs), particularly BMP4, have been proposed to regulate embryonic hepatic development. BMP expression has been observed in neoplasia but the expression and biological role of BMP4 in human HCC are unknown. We found increased BMP4 mRNA and protein in HCC cell lines and tissue samples compared to primary human hepatocytes and corresponding non‐tumourous tissue. Hypoxia further induced BMP4 expression in HCC cells, which was abolished by transfection of a dominant negative form of HIF‐1alpha (dnHIF‐1alpha). However, gel shift assays revealed only minor binding activity in nuclear extracts from (hypoxic) HCC cells to a putative hypoxia‐response element in the BMP4 promoter. Sequence analysis of the BMP4 promoter revealed two Ets‐1 binding sites, and Ets‐1 activity was increased in HCC cells under hypoxic conditions. Transfection of dnHIF‐1alpha completely abrogated hypoxia‐induced Ets‐1 activity as well as BMP4 expression. Overexpression of Ets‐1 markedly enhanced BMP4 promoter activity, while antisense Ets‐1 almost completely abolished basal as well as hypoxia‐induced BMP4 expression. These data demonstrate that Ets‐1 activity contributes to baseline expression of the BMP4 gene and is the predominant mediator of the HIF‐dependent BMP4 induction under hypoxic conditions. To determine the functional relevance of BMP4 expression, HCC cell lines were treated with antisense BMP4 constructs or siRNA against BMP4. BMP4 suppression resulted in a strong reduction of the migratory and invasive potential and anchorage‐independent growth. Furthermore, tube formation assays indicated that BMP4 expressed by HCC cells promotes vasculogenesis. Our findings demonstrate that BMP4 is increased in HCC and promotes HCC progression. Therefore, BMP4 expression may have clinical relevance, and interfering with BMP4 signalling appears as an attractive therapeutic target for this highly aggressive tumour. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Divergent modulation of Chlamydia pneumoniae infection cycle in human monocytic and endothelial cells by iron,tryptophan availability and interferon gamma

Chlamydia pneumoniae is an obligatory intracellular bacterium causing chronic inflammatory diseases in humans. We studied the role of the nutritive factors, iron and tryptophan, towards the course of infection and immune response pathways in C. pneumoniae infected endothelial cells and monocytes.Human endothelial (EA.hy923) and monocytic cells (THP-1) were infected with C. pneumoniae, supplemented with iron or 1-methyltryptophan (1-MT), an inhibitor of the tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO), and subsequently stimulated with IFN-γ or left untreated. The number of infected cells, the morphology and quantity of C. pneumoniae inclusion bodies, IDO activity and innate immune effector pathways were analysed.While neither iron challenge, IDO inhibition or IFN-γ treatment had a significant effect on C. pneumoniae morphology or numbers within THP-1 monocytic cells, iron supplementation to EA.hy926 cells resulted in promotion of C. pneumoniae proliferation and differentiation while IFN-γ had an inhibitory effect. Furthermore, the number of infected endothelial cells was significantly decreased upon 1-MT treatment. C. pneumoniae infection induced a pro-inflammatory immune response as evidenced by increased IDO activity, neopterin formation or TNF-α production in THP-1 but not in endothelial cells. These pathways were superinduced upon IFN-γ treatment and partly modulated by iron supplementation.Our results demonstrate that the infectious cycle of C. pneumoniae behaves differently between monocytic and endothelial cells. While the intracellular pathogen remains in a persistent form within monocytes, it can differentiate and proliferate within endothelial cells indicating that endothelial cells are a preferred environment for Chlamydia. Nutritive factors such as iron have subtle effects on C. pneumoniae biology in endothelial, but not monocytic cells. Our results contribute to a better understanding of C. pneumoniae infection and its role in chronic inflammatory diseases such as atherosclerosis.     

Interoceptive sensitivity in anxiety and anxiety disorders: An overview and integration of neurobiological findings

Interoceptive sensitivity, particularly regarding heartbeat, has been suggested to play a pivotal role in the pathogenesis of anxiety and anxiety disorders. This review provides an overview of methods which are frequently used to assess heartbeat perception in clinical studies and summarizes presently available results referring to interoceptive sensitivity with respect to heartbeat in anxiety-related traits (anxiety sensitivity, state/trait anxiety), panic disorder and other anxiety disorders. In addition, recent neurobiological studies of neuronal activation correlates of heartbeat perception using positron emission tomography (PET), functional magnetic resonance imaging (fMRI) or electroencephalographic (EEG) techniques are presented. Finally, possible clinical and therapeutic implications (e.g., beta-blockers, biofeedback therapy, cognitive interventions and interoceptive exposure) of the effects of heartbeat perception on anxiety and the anxiety disorders and the potential use of interoceptive sensitivity as an intermediate phenotype of anxiety disorders in future neurobiological and genetic studies are discussed.