Multigene interactions and the prediction of depression in the Wisconsin Longitudinal Study

Objectives: Single genetic loci offer little predictive power for the identification of depression. This study examined whether an analysis of gene-gene (G x G) interactions of 78 single nucleotide polymorphisms (SNPs) in genes associated with depression and agerelated diseases would identify significant interactions with increased predictive power for depression. Design: A retrospective cohort study. Setting: A survey of participants in the Wisconsin Longitudinal Study. Participants: A total of 4811 persons (2464 women and 2347 men) who provided saliva for genotyping; the group comes from a randomly selected sample of Wisconsin high school graduates from the class of 1957 as well as a randomly selected sibling, almost all of whom are non-Hispanic white. Primary outcome measure: Depression as determine by the Composite International Diagnostic Interview-Short-Form. Results: Using a classification tree approach (recursive partitioning (RP)), the authors identified a number of candidate G 3 G interactions associated with depression. The primary SNP splits revealed by RP (ANKK1 rs1800497 (also known as DRD2 Taq1A) in men and DRD2 rs224592 in women) were found to be significant as single factors by logistic regression (LR) after controlling for multiple testing (p=0.001 for both). Without considering interaction effects, only one of the five subsequent RP splits reached nominal significance in LR (FTO rs1421085 in women, p=0.008). However, after controlling for G x G interactions by running LR on RP-specific subsets, every split became significant and grew larger in magnitude (OR (before) → (after): men: GNRH1 novel SNP: (1.43 → 1.57); women: APOC3 rs2854116: (1.28 → 1.55), ACVR2B rs3749386: (1.11 → 2.17), FTO rs1421085: (1.32 → 1.65), IL6 rs1800795: (1.12 → 1.85)). Conclusions: The results suggest that examining G x G interactions improves the identification of genetic associations predictive of depression. 4 of the SNPs identified in these interactions were located in two pathways well known to impact depression: neurotransmitter (ANKK1 and DRD2) and neuroendocrine (GNRH1 and ACVR2B) signalling. This study demonstrates the utility of RP analysis as an efficient and powerful exploratory analysis technique for uncovering genetic and molecular pathway interactions associated with disease aetiology

Is total glossectomy for advanced carcinoma of the tongue justified?

Total glossectomy (with or without total laryngectomy) followed by postoperative radiotherapy remains the principal treatment method for advanced base of tongue carcinoma. The procedure remains controversial owing to poor cure rates and the inevitable functional deficits associated with it. However, even though total glossectomy is a major surgical procedure that impacts on speech, deglutition and quality of life, it may offer patients the best chance of cure in many centres, especially in the developing world. Methods: We did a retrospective chart review of all patients at Groote Schuur Hospital, Cape Town, who had undergone total glossectomy, with or without total laryngectomy, for stage IV squamous cell carcinoma (SCC) of the tongue between 1998 and 2004. Results: Eight patients had a total glossectomy performed during the study period. At 2, 3 and 5 years 63%, 38% and 25% of patients respectively were alive without disease. No patient required permanent nasogastric or gastrostomy feeding, and all returned to a full oral diet. Three of 5 patients who had laryngeal preservation and could be assessed for speech had intelligible speech. All but 1 patient (88%) reported pain relief following surgical excision. Perineural invasion was present in 75%, and 38% had positive resection margins. Five patients had recurrence, 2 cervical, 1 local, and 2 local and cervical. Conclusion: Advanced SCC of the tongue is a devastating disease causing severe pain and disorders of speech and swallowing. Total glossectomy (with or without total laryngectomy) and postoperative radiotherapy is a reasonable treatment option, particularly in the developing world setting. It has cure rates superior to primary radiotherapy, and provides motivated patients with excellent pain relief and a reasonable quality of life

Surveillance of Transmitted HIV-1 Drug Resistance in Gauteng and KwaZulu-Natal Provinces, South Africa, 2005-2009

Surveillance of human immunodeficiency virus type 1 transmitted drug resistance (TDR) was conducted among pregnant women in South Africa over a 5-year period after the initiation of a large national antiretroviral treatment program. Analysis of TDR data from 9 surveys conducted between 2005 and 2009 in 2 provinces of South Africa suggests that while TDR remains low (<5%) in Gauteng Province, it may be increasing in KwaZulu-Natal, with the most recent survey showing moderate (5%-15%) levels of resistance to the nonnucleoside reverse transcriptase inhibitor drug clas

AGN effect on cooling flow dynamics

We analyzed the feedback of AGN jets on cooling flow clusters using three-dimensional AMR hydrodynamic simulations. We studied the interaction of the jet with the intracluster medium and creation of low X-ray emission cavities (Bubbles) in cluster plasma. The distribution of energy input by the jet into the system was quantified in its different forms, i.e. internal, kinetic and potential. We find that the energy associated with the bubbles, (pV + gamma pV/(gamma-1)), accounts for less than 10 percent of the jet energy.Comment: "Accepted for publication in Astrophysics & Space Science

Effects of Low-Dose Gestational TCDD Exposure on Behavior and on Hippocampal Neuron Morphology and Gene Expression in Mice.

BACKGROUND: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a persistent and toxic environmental pollutant. Gestational exposure to TCDD has been linked to cognitive and motor deficits, and increased incidence of autism spectrum disorder (ASD) traits in children. Most animal studies of these neurodevelopmental effects involve acute TCDD exposure, which does not model typical exposure in humans. OBJECTIVES: The aim of the study was to establish a dietary low-dose gestational TCDD exposure protocol and performed an initial characterization of the effects on offspring behavior, neurodevelopmental phenotypes, and gene expression. METHODS: Throughout gestation, pregnant C57BL/6J mice were fed a diet containing a low dose of TCDD (9 ng TCDD/kg body weight per day) or a control diet. The offspring were tested in a battery of behavioral tests, and structural brain alterations were investigated by magnetic resonance imaging. The dendritic morphology of pyramidal neurons in the hippocampal Cornu Ammonis (CA)1 area was analyzed. RNA sequencing was performed on hippocampi of postnatal day 14 TCDD-exposed and control offspring. RESULTS: TCDD-exposed females displayed subtle deficits in motor coordination and reversal learning. Volumetric difference between diet groups were observed in regions of the hippocampal formation, mammillary bodies, and cerebellum, alongside higher dendritic arborization of pyramidal neurons in the hippocampal CA1 region of TCDD-exposed females. RNA-seq analysis identified 405 differentially expressed genes in the hippocampus, enriched for genes with functions in regulation of microtubules, axon guidance, extracellular matrix, and genes regulated by SMAD3. DISCUSSION: Exposure to 9 ng TCDD/kg body weight per day throughout gestation was sufficient to cause specific behavioral and structural brain phenotypes in offspring. Our data suggest that alterations in SMAD3-regulated microtubule polymerization in the developing postnatal hippocampus may lead to an abnormal morphology of neuronal dendrites that persists into adulthood. These findings show that environmental low-dose gestational exposure to TCDD can have significant, long-term impacts on brain development and function. https://doi.org/10.1289/EHP7352

Multidimensional sexual perfectionism and female sexual function: A longitudinal investigation

Research on multidimensional sexual perfectionism differentiates four forms of sexual perfectionism: self-oriented, partner-oriented, partner-prescribed, and socially prescribed. Self-oriented sexual perfectionism reflects perfectionistic standards people apply to themselves as sexual partners; partner-oriented sexual perfectionism reflects perfectionistic standards people apply to their sexual partner; partner-prescribed sexual perfectionism reflects people’s beliefs that their sexual partner imposes perfectionistic standards on them; and socially prescribed sexual perfectionism reflects people’s beliefs that society imposes such standards on them. Previous studies found partner-prescribed and socially prescribed sexual perfectionism to be maladaptive forms of sexual perfectionism associated with a negative sexual self-concept and problematic sexual behaviors, but only examined cross-sectional relationships. The present article presents the first longitudinal study examining whether multidimensional sexual perfectionism predicts changes in sexual self-concept and sexual function over time. A total of 366 women aged 17-69 years completed measures of multidimensional sexual perfectionism, sexual esteem, sexual anxiety, sexual problem self-blame, and female sexual function (cross-sectional data). Three to six months later, 164 of the women completed the same measures again (longitudinal data). Across analyses, partner-prescribed sexual perfectionism emerged as the most maladaptive form of sexual perfectionism. In the cross-sectional data, partner-prescribed sexual perfectionism showed positive relationships with sexual anxiety, sexual problem self-blame, and intercourse pain and negative relationships with sexual esteem, desire, arousal, lubrication, and orgasmic function. In the longitudinal data, partner-prescribed sexual perfectionism predicted increases in sexual anxiety and decreases in sexual esteem, arousal, and lubrication over time. The findings suggest that partner-prescribed sexual perfectionism contributes to women’s negative sexual self-concept and female sexual dysfunction

Oh Comrade, What Times those Were! History, Capital Punishment and the Urban Square.

From the perspective of traditional Western histories of the urban realm, public squares have been seen to represent a privileged site of urban containment expressive of a community's highest values of individual freedom, social inclusion and cultural refinement. But such views can be misleading. For what is omitted from the scope of these conventional historical visions and their ideal and conforming subjects of public spatial discourse, is an entire array of other and darker narratives that equally speak of personal choice, collective participation and cultural value. Capital punishment reflects such an example, a practice that once comprised an integral part of the political, social and cultural landscape of a Western city's squares and streets. Drawing from Michel Foucault's Discipline and Punish and its implications on how we might begin to re-read the history of the urban square, the following seeks to explore those practices and modes of rationality that underpinned the once public spectacle of executions and torture as a vital condition of urban life. In particular, this discussion will question the assumptions of an historical tradition that continues to reduce our understanding of the city and its open spaces of public appearance and action to an idealistic and illusory reality of the urban realm and its narrow framing of collective conduct, necessity and significance

An empirical investigation of dance addiction

Although recreational dancing is associated with increased physical and psychological well-being, little is known about the harmful effects of excessive dancing. The aim of the present study was to explore the psychopathological factors associated with dance addiction. The sample comprised 447 salsa and ballroom dancers (68% female, mean age: 32.8 years) who danced recreationally at least once a week. The Exercise Addiction Inventory (Terry, Szabo, & Griffiths, 2004) was adapted for dance (Dance Addiction Inventory, DAI). Motivation, general mental health (BSI-GSI, and Mental Health Continuum), borderline personality disorder, eating disorder symptoms, and dance motives were also assessed. Five latent classes were explored based on addiction symptoms with 11% of participants belonging to the most problematic class. DAI was positively associated with psychiatric distress, borderline personality and eating disorder symptoms. Hierarchical linear regression model indicated that Intensity (ß=0.22), borderline (ß=0.08), eating disorder (ß=0.11) symptoms, as well as Escapism (ß=0.47) and Mood Enhancement (ß=0.15) (as motivational factors) together explained 42% of DAI scores. Dance addiction as assessed with the Dance Addiction Inventory is associated with indicators of mild psychopathology and therefore warrants further research

Remnant radio-loud AGN in the Herschel-ATLAS field

Only a small fraction of observed active galactic nuclei (AGN) display large-scale radio emission associated with jets, yet these radio-loud AGN have become increasingly important in models of galaxy evolution. In determining the dynamics and energetics of the radio sources over cosmic time, a key question concerns what happens when their jets switch off. The resulting ‘remnant' radio-loud AGN have been surprisingly evasive in past radio surveys, and therefore statistical information on the population of radio-loud AGN in their dying phase is limited. In this paper, with the recent developments of Low-Frequency Array (LOFAR) and the Very Large Array, we are able to provide a systematically selected sample of remnant radio-loud AGN in the Herschel-ATLAS field. Using a simple core-detection method, we constrain the upper limit on the fraction of remnants in our radio-loud AGN sample to 9 per cent, implying that the extended lobe emission fades rapidly once the core/jets turn off. We also find that our remnant sample has a wide range of spectral indices (−1.5 ⩽ α1400150 ⩽ −0.5), confirming that the lobes of some remnants may possess flat spectra at low frequencies just as active sources do. We suggest that, even with the unprecedented sensitivity of LOFAR, our sample may still only contain the youngest of the remnant population