Dilution of candidates: the case of iron-related genes in restless legs syndrome

Restless legs syndrome (RLS) is a common multifactorial disease. Some genetic risk factors have been identified. RLS susceptibility also has been related to iron. We therefore asked whether known iron-related genes are candidates for association with RLS and, vice versa, whether known RLS-associated loci influence iron parameters in serum. RLS/control samples (n=954/1814 in the discovery step, 735/736 in replication 1, and 736/735 in replication 2) were tested for association with SNPs located within 4 Mb intervals surrounding each gene from a list of 111 iron-related genes using a discovery threshold of P=5 × 10⁻⁴. Two population cohorts (KORA F3 and F4 with together n=3447) were tested for association of six known RLS loci with iron, ferritin, transferrin, transferrin-saturation, and soluble transferrin receptor. Results were negative. None of the candidate SNPs at the iron-related gene loci was confirmed significantly. An intronic SNP, rs2576036, of KATNAL2 at 18q21.1 was significant in the first (P=0.00085) but not in the second replication step (joint nominal P-value=0.044). Especially, rs1800652 (C282Y) in the HFE gene did not associate with RLS. Moreover, SNPs at the known RLS loci did not significantly affect serum iron parameters in the KORA cohorts. In conclusion, the correlation between RLS and iron parameters in serum may be weaker than assumed. Moreover, in a general power analysis, we show that genetic effects are diluted if they are transmitted via an intermediate trait to an end-phenotype. Sample size formulas are provided for small effect sizes.     

Functional Characterization of Novel Mutations Affecting Survivin (BIRC5)‐Mediated Therapy Resistance in Head and Neck Cancer Patients

Survivin (BIRC5) is an acknowledged cancer therapy‐resistance factor and overexpressed in head and neck squamous cell carcinomas (HNSCC). Driven by its nuclear export signal (NES), Survivin shuttles between the nucleus and the cytoplasm, and is detectable in both cellular compartments in tumor biopsies. Although predominantly nuclear Survivin is considered a favorable prognostic disease marker for HNSCC patients, the underlying molecular mechanisms are not resolved. Hence, we performed immunohistochemical and mutational analyses using laser capture microdissection on HNSCC biopsies from patients displaying high levels of nuclear Survivin. We found somatic BIRC5 mutations, c.278T>C (p.Phe93Ser), c.292C>T (p.Leu98Phe), and c.288A>G (silent), in tumor cells, but not in corresponding normal tissues. Comprehensive functional characterization of the Survivin mutants by ectopic expression and microinjection experiments revealed that p.Phe93Ser, but not p.Leu98Phe inactivated Survivin's NES, resulted in a predominantly nuclear protein, and attenuated Survivin's dual cytoprotective activity against chemoradiation‐induced apoptosis. Notably, in xenotransplantation studies, HNSCC cells containing the p.Phe93Ser mutation responded significantly better to cisplatin‐based chemotherapy. Collectively, our results underline the disease relevance of Survivin's nucleocytoplasmic transport, and provide first evidence that genetic inactivation of Survivin's NES may account for predominantly nuclear Survivin and increased therapy response in cancer patients.     

Bipolar patients show mood‐congruent biases in sensitivity to facial expressions of emotion when exhibiting depressed symptoms,but not when exhibiting manic symptoms

Introduction?A number of studies have reported mood‐congruent biases in processing facial expressions of emotion in depression and mania. Most of them have failed to establish that mood reliably affects relevant more than irrelevant expressions, or that the effect is specifically mood‐related rather than due to resource or task difficulty artefacts. The aim was to examine, using appropriate statistical methods, whether depressed mood in bipolar patients decreases and manic mood increases sensitivity to facial expressions of happiness and vice versa for facial expressions of negative emotion.

Methods?Sensitivity to facial expression of six basic emotions in bipolar patients when depressed and when manic was compared to closely matched controls.

Results?Mood‐related biases in sensitivity to facial expressions of happiness and of negative affect in general operate in persons with bipolar disorder when depressed. There is little evidence of similar biases in persons with bipolar disorder when manic.

Conclusions?These data show a mood‐congruent bias in sensitivity to facial expressions in bipolar depressed patients.     

Reduced sensitivity in the recognition of anger and disgust in social anxiety disorder

Introduction. The aim of this study was to investigate the recognition of facial expressions in patients with a generalised social anxiety disorder. It is well documented that in different psychiatric disorders (e.g., depression, schizophrenia) patients may show an altered processing of emotions. However, in generalised social anxiety, emotion recognition has not been studied.

Methods. 24 Patients with generalised social anxiety disorder and 26 healthy controls, matched on age, education, and sex were included. The task entailed the emotional labelling of faces with different facial expressions (happiness, fear, disgust, sadness, surprise, anger) presented in different intensities. Subjects were asked to make a forced‐choice response.

Results. These revealed that patients with a generalised social anxiety disorder were less sensitive for the negative facial expressions of anger and disgust compared to the control group.

Conclusions. This deficit could play a role in the development and/or the maintaining of the social anxiety. Both explanations are discussed.     

Profiles of Irish survivors of institutional abuse with different adult attachment styles

Two hundred and forty seven survivors of institutional abuse in Ireland were classified with the Experiences in Close Relationships Inventory as having fearful (44%), preoccupied (13%), dismissive (27%), or secure (17%) adult attachment styles. The group with the secure adult attachment style had the most positive profile, while the most negative profile occurred for the fearful group in terms of DSM IV diagnoses and scores on the Trauma Symptom Inventory, the Global Assessment of Functioning Scale, the World Health Organization Quality of Life 100 scale, and the Kansas Marital Satisfaction Scale. The profile of the preoccupied group was more similar to that of the fearful group. The profile of the dismissive group was more similar to that of the secure group.     

Can attachment and peer relation constructs predict anxiety in ethnic minority youths? A longitudinal exploratory study

ABSTRACT

Anxiety is the most prevalent psychiatric disturbance in childhood effecting typically 15–20% of all youth. It has been associated with attachment insecurity and reduced competence in peer relations. Prior work has been limited by including mainly White samples, relying on questionnaires, and applying a cross-sectional design. The present study addressed these limitations by considering how at-risk non-White youth (n = 34) responded to the Friends and Family Interview (FFI) in middle childhood and how this linked up with anxiety symptoms and an anxiety diagnosis three years later in early adolescence. Five dimensions of secure attachment, namely, (i) to mother, (ii) to father, (iii) coherence, (iv) developmental understanding, and (v) social competence and quality of contact with best friend in middle childhood, were found to correlate significantly (and negatively) with self-reported anxiety symptoms. Linear regression results showed independent influences of female gender, and (low) quality of best friend contact as the most efficient model predicting anxiety symptoms. Logistic regression results suggested a model that included female gender, low social competence, and immature developmental understanding as efficient predictors of an anxiety diagnosis, evident in only 18% of the sample. These results point to the usefulness of after-school programs for at-risk minority youth in promoting peer competence, developmental awareness, and minimizing anxiety difficulties.     

Immune response to Helicobacter pylori infection and gastric cancer development

Gastric adenocarcinoma is a global health concern, and Helicobacter pylori (H. pylori) infection is the main risk factor for its occurrence. Of note, the immune response against the pathogen seems to be a determining factor for gastric oncogenesis, and increasing evidence have emphasized several host and bacterium factors that probably influence in this setting. The development of an inflammatory process against H. pylori involves a wide range of mechanisms such as the activation of pattern recognition receptors and intracellular pathways resulting in the production of proinflammatory cytokines by gastric epithelial cells. This process culminates in the establishment of distinct immune response profiles that result from the cytokine-induced differentiation of T naïve cells into specific T helper cells. Cytokines released from each type of T helper cell orchestrate the immune system and interfere in the development of gastric cancer in idiosyncratic ways. Moreover, variants in genes such as single nucleotide polymorphisms have been associated with variable predispositions for the occurrence of gastric malignancy because they influence both the intensity of gene expression and the affinity of the resultant molecule with its receptor. In addition, various repercussions related to some H. pylori virulence factors seem to substantially influence the host immune response against the infection, and many of them have been associated with gastric tumorigenesis.     

The Impact of Music on Patient Satisfaction,Anxiety, and Depression in Patients Undergoing Gynecologic Surgery

PurposeThe project piloted a perioperative music listening program to explore the feasibility and acceptability of the use of music in a perioperative setting for female surgical patients in an academic hospital in Singapore. The aim was also to examine the most commonly chosen music genres, timing, and length of time listening to music for perioperative patients to assess the impact of music on patients' satisfaction, anxiety, and depression.DesignThis was a quality improvement project.MethodsMusic playlists developed by a music therapist were installed on three iPod Touch^TM devices (Apple, Cupertino, CA). After obtaining consent, female patients undergoing elective gynecologic day surgery selected their preferred music from the playlists on the iPods to listen to during the preoperative and postoperative periods. Patients' anxiety and depression were measured using the Hospital Anxiety and Depression Scale and the three-level version of the EuroQol five-dimensional questionnaire. Patients' satisfaction with listening to music, duration, and chosen music genres were recorded.FindingsIn the project, 135 patients listened to music during the preoperative period, and 70 patients chose to listen to music in the postoperative period. Patients were satisfied with the music listening program in both the preoperative (95.5%) and the postoperative (91.5%) periods. In the preoperative period, the most popular music genres were Disney songs (17.7%), classical music (11.6%), and the Piano Guys (7.5%). In the postoperative period, the most favorable music genres were classical music (26.3%), Disney songs (7.9%), and the Beatles (7.9%). This project suggests that music listening may be associated with patients' decreased anxiety and depression as measured by the three-level version of the EuroQol five-dimensional questionnaire questionnaire (P = .008).ConclusionsImplementation of a music listening program in perioperative settings is feasible and accepted well by patients as evidenced by the high satisfaction scores. The project addressed patients' satisfaction, anxiety, and depression before and after elective surgery. The findings suggest that music listening is a safe, inexpensive, and effective intervention in perioperative settings.