The Thiamine diphosphate dependent Enzyme Engineering Database: A tool for the systematic analysis of sequence and structure relations

<p>Abstract</p> <p>Background</p> <p>Thiamine diphosphate (ThDP)-dependent enzymes form a vast and diverse class of proteins, catalyzing a wide variety of enzymatic reactions including the formation or cleavage of carbon-sulfur, carbon-oxygen, carbon-nitrogen, and especially carbon-carbon bonds. Although very diverse in sequence and domain organisation, they share two common protein domains, the pyrophosphate (PP) and the pyrimidine (PYR) domain. For the comprehensive and systematic comparison of protein sequences and structures the Thiamine diphosphate (ThDP)-dependent Enzyme Engineering Database (TEED) was established.</p> <p>Description</p> <p>The TEED <url>http://www.teed.uni-stuttgart.de</url> contains 12048 sequence entries which were assigned to 9443 different proteins and 379 structure entries. Proteins were assigned to 8 different superfamilies and 63 homologous protein families. For each family, the TEED offers multisequence alignments, phylogenetic trees, and family-specific HMM profiles. The conserved pyrophosphate (PP) and pyrimidine (PYR) domains have been annotated, which allows the analysis of sequence similarities for a broad variety of proteins. Human ThDP-dependent enzymes are known to be involved in many diseases. 20 different proteins and over 40 single nucleotide polymorphisms (SNPs) of human ThDP-dependent enzymes were identified in the TEED.</p> <p>Conclusions</p> <p>The online accessible version of the TEED has been designed to serve as a navigation and analysis tool for the large and diverse family of ThDP-dependent enzymes.</p

Gender differences in the genetic and environmental determinants of adolescent depression

Background: The well-documented gender differences in the risk for depression may be explained by genetic factors, by different responses to social context, or by a combination of both. We sought to assess whether there were gender differences in the longitudinal associations between serotonin transporter promoter ( 5-HTTLPR ) genotype and depressive symptoms in adolescents, and whether macrosocial context plays a role in explaining any observed differences. Methods: Using data from a nationally representative survey of adolescents, we applied multilevel mixed models to assess, separately for adolescent males and females (a) the relation between 5-HTTLPR genotype and depressive symptoms and (b) the interaction of county-level deprivation and 5- HTTLPR genotype in models predicting depressive symptoms. All models adjusted for age and other covariates. Results: Among females ( n =560), main effects models showed an association between the sl genotype and lowered risk of depressive symptoms ( b =−.18, P =.03). Among males ( n =524), interaction models showed an association between sl genotype and lowered risk of depressive symptoms in deprived counties only ( b =−.32, P =.04). Conclusions: In adolescent females, the 5-HTTLPR sl genotype confers protection against depressive symptoms independent of county-level social context, whereas in adolescent males, protection by the same genotype is conferred only within the context of county-level deprivation. Future work should aim to understand how genetic and macrosocial factors jointly shape risk for mental illness, and how these factors shape gender differences in mental illness. Depression and Anxiety, 2010.© 2010 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77512/1/20692_ftp.pd

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

An epidemiological approach to depression prevention in old age.

Objective: To identify target groups for prevention of chronic or recurrent depression in old age such that prevention is likely to become cost-effective. Methods: Data were used from a population-based cohort study (N = 2,200). Chronic or recurrent depression was defined when people presented with clinically high levels of depression at two time points separated by 3 years. Risk profiles of these conditions were identified using classification and regression trees analysis. The combinations of risk factors were then evaluated in multivariate models to ascertain their utility for preventing depression in high-risk groups. Results: People are placed at a high risk of depression when having symptoms of anxiety, functional impairments, two or more chronic illnesses, and either a low attained educational level or below average levels of mastery, while living without a partner. These risk profiles correspond with groups no larger than 8.3% of the older population. Containing the adverse effects of the risk factors would help to reduce the incidence of depression by possibly as much as 48.7%, indicating that large health gains can be generated, which can also be done efficiently with numbers-needed-to-betreated, perhaps as small as three. Conclusion: Targeting prevention on the selected high-risk groups is likely to become a cost-effective endeavor, because optimal health gains can be generated efficiently in groups small enough to be logistically manageable. The burden of illness associated with depression, particularly depression, in aging populations underscores the public health significance of such an approach

A cross-sectional exploratory analysis between pet ownership and sleep, exercise, health and neighborhood perceptions : The Whitehall II cohort study

A cross-sectional exploratory analysis between pet ownership and sleep, exercise, health and neighbourhood perceptions: The Whitehall II cohort study Gill Mein (corresponding author), Robert Grant. Faculty of Health, Social Care and Education. Kingston University and St George’s University of London Background: To explore associations between pets, and specifically dog ownership and sleep, health, exercise and neighbourhood. Methods: Cross sectional examination of 6575 participants of the Whitehall II study aged between 59-79 years. We used self-assessed measurement scales of the Short Form (SF36), General Health Questionnaire (GHQ), Control, Autonomy, Self-realisation and Pleasure (CASP), Centre for Epidemiologic Studies Depression Scale (CES-D), sleep, exercise, and perceptions of local neighbourhood. In addition the Mini Mental State Examination which is administered to test global cognitive status (MMSE) Results: We found 2/7 people owned a pet and of those 64% were “very” attached to their pet. Mild exercise in metabolic equivalents (MET-hours) was significantly higher in pet owners than non-owners (median 27.8 (IQR 18.1 to 41.8) vs 25.7 (IQR 16.8 to 38.7), p=0.0001), and in dog owners than other pets (median 32.3 (IQR 20.8 to 46.1) vs 25.6 (IQR 16.8 to 38.5), p<0.0001). Moderate exercise was also significantly higher in pet owners than non pet owners (median 11.8 (IQR 4.2 to 21.9) vs 9.8 (IQR 2.8 to 19.5), p<0.0001), and dog owners than owners of other pets (median 12.3 (IQR 4.2 to 22.2) vs 10.1 (3.1 to 20.0), p=0.0002) but there were no significant differences with vigorous exercise. We found that pet owners were significantly more positive about their neighbourhood than non-owners on 8/9 questions, while dog owners were (significantly) even more positive than owners of other pets on 8/9 questions. Associations with sleep were mixed, although dog owners had less trouble falling asleep than non-dog owners, with borderline statistical significance. Conclusion: Dog owners feel more positive about their neighbourhood, do more exercise, and fall asleep more easily than non-dog owners. These results suggest that dog owners could be more likely to exercise by walking their dogs and therefore may be more familiar and positive about the area in which they walk their dog

Dyspnea-related cues engage the prefrontal cortex - evidence from functional brain imaging in COPD

Dyspnea is the major source of disability in chronic obstructive pulmonary disease (COPD). In COPD, environmental cues (e.g. the prospect of having to climb stairs) become associated with dyspnea, and may trigger dyspnea even before physical activity commences. We hypothesised that brain activation relating to such cues would be different between COPD patients and healthy controls, reflecting greater engagement of emotional mechanisms in patients. Methods: Using FMRI, we investigated brain responses to dyspnea-related word cues in 41 COPD patients and 40 healthy age-matched controls. We combined these findings with scores of self-report questionnaires thus linking the FMRI task with clinically relevant measures. This approach was adapted from studies in pain that enables identification of brain networks responsible for pain processing despite absence of a physical challenge. Results: COPD patients demonstrate activation in the medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) which correlated with the visual analogue scale (VAS) response to word cues. This activity independently correlated with patient-reported questionnaires of depression, fatigue and dyspnea vigilance. Activation in the anterior insula, lateral prefrontal cortex (lPFC) and precuneus correlated with the VAS dyspnea scale but not the questionnaires. Conclusions: Our findings suggest that engagement of the brain's emotional circuitry is important for interpretation of dyspnea-related cues in COPD, and is influenced by depression, fatigue, and vigilance. A heightened response to salient cues is associated with increased symptom perception in chronic pain and asthma, and our findings suggest such mechanisms may be relevant in COPD

Chronic Maternal Depression Is Associated with Reduced Weight Gain in Latino Infants from Birth to 2 Years of Age

BACKGROUND: Latino children are at increased risk for mirconutrient deficiencies and problems of overweight and obesity. Exposures in pregnancy and early postpartum may impact future growth trajectories. OBJECTIVES: To evaluate the relationship between prenatal and postnatal maternal depressive symptoms experienced in pregnancy and infant growth from birth to 2 years of age in a cohort of Latino infants. METHODS: We recruited pregnant Latina mothers at two San Francisco hospitals and followed their healthy infants to 24 months of age. At 6, 12 and 24 months of age, infants were weighed and measured. Maternal depressive symptoms were assessed prenatally and at 4-6 weeks postpartum. Women who had high depressive symptoms at both time periods were defined as having chronic depression. Logistic mixed models were applied to compare growth curves and risk for overweight and underweight based on exposure to maternal depression. RESULTS: We followed 181 infants to 24 months. At 12 and 24 months, respectively, 27.4% and 40.5% were overweight, and 5.6% and 2.2% were underweight. Exposure to chronic maternal depression was associated with underweight (OR = 12.12, 95%CI 1.86-78.78) and with reduced weight gain in the first 2 years of life (Coef = -0.48, 95% CI -0.94-0.01) compared with unexposed infants or infants exposed to episodic depression (depression at one time point). Exposure to chronic depression was also associated with reduced risk for overweight in the first 2 years of life (OR 0.28, 95%CI 0.03-0.92). CONCLUSIONS: Exposure to chronic maternal depression in the pre- and postnatal period was associated with reduced weight gain in the first two years of life and greater risk for failure to thrive, in comparison with unexposed infants or those exposed episodically. The infants of mothers with chronic depression may need additional nutritional monitoring and intervention

Ethnicity, sleep, mood, and illumination in postmenopausal women

BACKGROUND: This study examined how ethnic differences in sleep and depression were related to environmental illumination and circadian rhythms. METHODS: In an ancillary study to the Women's Health Initiative, 459 postmenopausal women were recorded for one week in their homes, using wrist monitors. Sleep and illumination experience were estimated. Depression was self-rated with a brief adjective check list. Affective diagnoses were made using the SCID interview. Sleep disordered breathing was monitored with home pulse oximetry. RESULTS: Hispanic and African-American women slept less than European-American women, according to both objective recordings and their own sleep logs. Non-European-American women had more blood oxygen desaturations during sleep, which accounted for 26% of sleep duration variance associated with ethnicity. Hispanic women were much more depressed. Hispanic, African-American and Native-American women experienced less daily illumination. Less daily illumination experience was associated with poorer global functioning, longer but more disturbed sleep, and more depression. CONCLUSIONS: Curtailed sleep and poor mood were related to ethnicity. Sleep disordered breathing was a factor in the curtailed sleep of minority women. Less illumination was experienced by non-European-American women, but illumination accounted for little of the contrasts between ethnic groups in sleep and mood. Social factors may be involved

The prevalence of anxiety and depression in people with age-related macular degeneration: a systematic review of observational study data

Background Comorbid mental health problems have been shown to have an adverse effect on the quality of life of people with common eye disorders. This study aims to assess whether symptoms of anxiety and/or depression are more prevalent in people with age-related macular degeneration (AMD) than in people without this condition. Methods A systematic search of electronic databases (Medline, CINAHL, EMBASE, PsycINFO) from inception to February 2012 was conducted to identify studies of AMD populations which measured symptoms of anxiety and/or depression. Reference checking of relevant articles was also performed. Data on the study setting, prevalence and how anxiety and depression were measured were extracted from the papers. Critical appraisal was performed using the Critical Appraisal Skills Programme (CASP) tools. Results A total of 16 papers were included in the review, from an original search result of 597. The prevalence estimates, taken from nine cross-sectional and cohort studies, ranged from 15.7%-44% for depressive symptoms and 9.6%-30.1% for anxiety symptoms in people with AMD. The seven case–control studies found that people with AMD were more likely to experience symptoms of depression compared with those without AMD, but not more likely to experience symptoms of anxiety. Conclusions Overall, the evidence suggests that symptoms of depression are more prevalent amongst AMD populations than anxiety symptoms. The heterogeneity of the studies included in this review means that it is difficult to draw strong conclusions as to the true estimates of depression and anxiety symptoms in AMD populations and prevented formal meta-analysis. Further research which specifies clinical anxiety and gives clear definitions as to the type of AMD being investigated is required