Some authors have argued that worry cues lateralization of frontal brain activity leftward, whereas other varieties of avoidance motivation cue lateralization of frontal brain activity rightward. By ...comparison, more right-than-left parietal activity correlates with anxious arousal. The purpose of the present report was to test two models of brain lateralization and anxiety: one model that proposed that worry correlates with more left-frontal activity and another model that proposed that avoidance motivation (including worry) correlates with more right-frontal activity. Undergraduate students were selected for worry, obsessive-compulsive symptoms, and trait anxiety using self-report questionnaires. A subset of participants also met DSM-IV criteria for Generalized Anxiety Disorder (GAD) or Obsessive-Compulsive Disorder (OCD). Alpha asymmetry and also a global-power-adjusted metric of alpha power were calculated from each participant's resting-state EEG. It was expected that participants with elevated worry and participants meeting criteria for GAD would show more left-than-right frontal activity. In contrast, participants with elevated trait anxiety, obsessive-compulsive symptoms, and those with an OCD diagnosis were expected to exhibit more right-than-left frontal activity. Participants with elevated worry, participants with a GAD diagnosis, and participants with elevated obsessive-compulsive symptoms, had more left frontal activity than low symptom individuals. Those with high scores on trait anxiety, but low worry, had greater right frontal and parietal activity compared to controls. The present results suggest that brain lateralization is not solely related to avoidance motivation, and suggest that facets of anxiety may cut across dimensions not well-represented by DSM-based categories.
•Results supported a neuropsychological verbal/visual model of alpha asymmetry.•Results were incompatible with a motivational model of alpha asymmetry.•Worry and GAD were related to more left-than-right frontal activity.•Worry may be a moderator of frontal alpha asymmetry.
This book is about the renaissance of cities in the twenty first century and their increasing role as centers of creative economic activity. It attempts to put some conceptual and descriptive order ...around issues of urbanization in the contemporary world, emphasizing the idea of the social economy of the metropolis, which is to say, a view of the urban organism as an intertwined system of social and economic life played out through the arena of urban space. The book opens with a review of some essentials of urban theory, the book aims to re-articulate the urban question in a way that is relevant to city life and politics in the present era. It then analyses the functional characteristics of the urban economy, with special reference to the rise of a group of core sectors such as media, fashion, music, etc., focused on cognitive and cultural forms of work. These sectors are growing with great rapidity in the world's largest cities at the present time, and they play a major role in the urban resurgence that has been occurring of late. The discussion then explores the spatial ramifications of this new economy in cities and the ways in which it appears to be ushering in major shifts in divisions of labor and urban social stratification, as marked by a growing divide between a stratum of elite workers on the one side and a low-wage proletariat on the other. Allen Scott is one of the world's foremost thinkers on the economies of modern cities, and in this book presents a concise introduction to his innovative and insightful perspective. Available in OSO: http://www.oxfordscholarship.com/oso/public/content/management/9780199549306/toc.html
Background: The Alcohol Use Disorders Identification Test (AUDIT) has been extensively researched to determine its capability to accurately and practically screen for alcohol problems.
Methods: ...During the 5 years since our previous review of the literature, a large number of additional studies have been published on the AUDIT, abbreviated versions of it, its psychometric properties, and the applicability of the AUDIT for a diverse array of populations. The current article summarizes new findings and integrates them with results of previous research. It also suggests some issues that we believe are particularly in need of further study.
Results: A growing body of research evidence supports the criterion validity of English version of the AUDIT as a screen for alcohol dependence as well as for less severe alcohol problems. Nevertheless, the cut‐points for effective detection of hazardous drinking as well as identification of alcohol dependence or harmful use in women need to be lowered from the originally recommended value of 8 points. The AUDIT‐C, the most popular short version of the AUDIT consisting solely of its 3 consumption items, is approximately equal in accuracy to the full AUDIT. Psychometric properties of the AUDIT, such as test–retest reliability and internal consistency, are quite favorable. Continued research is urged to establish the psychometric properties of non‐English versions of the AUDIT, use of the AUDIT with adolescents and with older adults, and selective inclusion of alcohol biomarkers with the AUDIT in some instances.
Conclusions: Research continues to support use of the AUDIT as a means of screening for the spectrum of alcohol use disorders in various settings and with diverse populations.
This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a ...core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette's syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader-Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.
Limitations of current antidepressants highlight the need to identify novel treatments for major depressive disorder. A prior open trial found that a single session of whole-body hyperthermia (WBH) ...reduced depressive symptoms; however, the lack of a placebo control raises the possibility that the observed antidepressant effects resulted not from hyperthermia per se, but from nonspecific aspects of the intervention.
To test whether WBH has specific antidepressant effects when compared with a sham condition and to evaluate the persistence of the antidepressant effects of a single treatment.
A 6-week, randomized, double-blind study conducted between February 2013 and May 2015 at a university-based medical center comparing WBH with a sham condition. All research staff conducting screening and outcome procedures were blinded to randomization status. Of 338 individuals screened, 34 were randomized, 30 received a study intervention, and 29 provided at least 1 postintervention assessment and were included in a modified intent-to-treat efficacy analysis. Participants were medically healthy, aged 18 to 65 years, met criteria for major depressive disorder, were free of psychotropic medication use, and had a baseline 17-item Hamilton Depression Rating Scale score of 16 or greater.
A single session of active WBH vs a sham condition matched for length of WBH that mimicked all aspects of WBH except intense heat.
Between-group differences in postintervention Hamilton Depression Rating Scale scores.
The mean (SD) age was 36.7 (15.2) years in the WBH group and 41.47 (12.54) years in the sham group. Immediately following the intervention, 10 participants (71.4%) randomized to sham treatment believed they had received WBH compared with 15 (93.8%) randomized to WBH. When compared with the sham group, the active WBH group showed significantly reduced Hamilton Depression Rating Scale scores across the 6-week postintervention study period (WBH vs sham; week 1: -6.53, 95% CI, -9.90 to -3.16, P < .001; week 2: -6.35, 95% CI, -9.95 to -2.74, P = .001; week 4: -4.50, 95% CI, -8.17 to -0.84, P = .02; and week 6: -4.27, 95% CI, -7.94 to -0.61, P = .02). These outcomes remained significant after evaluating potential moderating effects of between-group differences in baseline expectancy scores. Adverse events in both groups were generally mild.
Whole-body hyperthermia holds promise as a safe, rapid-acting, antidepressant modality with a prolonged therapeutic benefit.
clinicaltrials.gov Identifier: NCT01625546.
In oxygenic photosynthesis there are two ‘light states’ – adaptations of the photosynthetic apparatus to spectral composition that otherwise favours either photosystem I or photosystem II. In ...chloroplasts of green plants the transition to light state 2 depends on phosphorylation of apoproteins of a membrane‐intrinsic antenna, the chlorophyll‐a/b‐binding, light‐harvesting complex II (LHC II), and on the resulting redistribution of absorbed excitation energy from photosystem II to photosystem I. The transition to light state 1 reverses these events and requires a phospho‐LHC II phosphatase. Current structures of LHC II reveal little about possible steric effects of phosphorylation. The surface‐exposed N‐terminal domain of an LHC II polypeptide contains its phosphorylation site and is disordered in its unphosphorylated form. A molecular recognition hypothesis proposes that state transitions are a consequence of movement of LHC II between binding sites on photosystems I and II. In state 1, LHC II forms part of the antenna of photosystem II. In state 2, a unique but as yet unidentified 3‐D structure of phospho‐LHC II may attach it instead to photosystem I. One possibility is that the LHC II N‐terminus becomes ordered upon phosphorylation, adopting a local alpha‐helical secondary structure that initiates changes in LHC II tertiary and quaternary structure that sever contact with photosystem II while securing contact with photosystem I. In order to understand redistribution of absorbed excitation energy in photosynthesis we need to know the structure of LHC II in its phosphorylated form, and in its complex with photosystem I.
Progesterone is a critical hormone in early pregnancy. A low level of serum progesterone is associated with threatened miscarriage. We aim to establish the distribution of maternal serum progesterone ...in normal pregnancies compared to pregnancies complicated by threatened miscarriage from 5 to 13 weeks gestation.
This is a single centre, prospective cohort study of 929 patients. Women from the Normal Pregnancy NP cohort were recruited from antenatal clinics, and those in the Threatened Miscarriage TM cohort were recruited from emergency walk-in clinics. Women with multiple gestations, missed, incomplete or inevitable miscarriage were excluded from the study. Quantile regression was used to characterize serum progesterone levels in the NP and TM cohorts by estimating the 10th, 50th and 90th percentiles from 5 to 13 weeks gestation. Pregnancy outcome was determined at 16 weeks of gestation. Subgroup analysis within the TM group compared progesterone levels of women who subsequently miscarried with those who had ongoing pregnancies at 16 weeks of gestation.
Median serum progesterone concentration demonstrated a linearly increasing trend from 57.5 nmol/L to 80.8 nmol/L from 5 to 13 weeks gestation in the NP cohort. In the TM cohort, median serum progesterone concentration increased from 41.7 nmol/L to 78.1 nmol/L. However, median progesterone levels were uniformly lower in the TM cohort by approximately 10 nmol/L at every gestation week. In the subgroup analysis, median serum progesterone concentration in women with ongoing pregnancy at 16 weeks gestation demonstrated a linearly increasing trend from 5 to 13 weeks gestation. There was a marginal and non-significant increase in serum progesterone from 19.0 to 30.3 nmol/L from 5 to 13 weeks gestation in women who eventually had a spontaneous miscarriage.
Serum progesterone concentration increased linearly with gestational age from 5 to 13 weeks in women with normal pregnancies. Women with spontaneous miscarriage showed a marginal and non-significant increase in serum progesterone. This study highlights the pivotal role of progesterone in supporting an early pregnancy, with lower serum progesterone associated with threatened miscarriage and a subsequent complete miscarriage at 16 weeks gestation.
Photosynthetic electron transport is coupled to ATP synthesis. This process – photosynthetic phosphorylation – proceeds by several alternative electron-transport pathways in isolated chloroplasts. ...The question: ‘Which of these works in real life?’ has long occupied students of photosynthesis. Recent results from structural biology and genomics suggest that the answer is ‘All of them’. The interplay between the pathways might explain the flexibility of photosynthesis in meeting different metabolic demands for ATP.
G protein-coupled receptors (GPCRs) are an evolutionarily conserved family of signaling molecules comprising approximately 2% of the human genome; this receptor family remains a central focus in ...basic pharmacology studies and drug discovery efforts. Detailed studies of drug action at GPCRs over the past decade have revealed existing and novel ligands that exhibit polypharmacology-that is, drugs with activity at more than one receptor target for which they were designed. These "off-target" drug actions can be a liability that causes adverse side effects; however, in several cases, drugs with less selectivity demonstrate better clinical efficacy. Here we review physical screening and cheminformatic approaches that define drug activity at the GPCR receptorome. In many cases, such profiling has revealed unexpected targets that explain therapeutic actions as well as off-targets underlying drug side effects. Such drug-receptor profiling has also provided new insights into mechanisms of action of existing drugs and has suggested directions for future drug development.
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