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Nonviral siRNA Delivery for Gene Silencing in Neurodegenerative Diseases.

Methods Mol Biol. 2010; 623: 211-29
Prakash S, Malhotra M, Rengaswamy V

Linking genes with the underlying mechanisms of diseases is one of the biggest challenges of genomics-driven drug discovery research. Designing an inhibitor for any neurodegenerative disease that effectively halts the pathogenicity of the disease is yet to be achieved. The challenge lies in crossing the blood-brain barrier (BBB)/blood-cerebrospinal fluid barrier (BCSFB) to reach the catalytic pockets of the enzyme/protein involved in the molecular mechanism of the disease process. Designing siRNA with exquisite specificity may result in selective suppression of the disease-linked gene. Although siRNA is the most promising method, it loses its potency in downregulating the gene due to its inherent instability, off-target effects, and lack of on-target effective delivery systems. Viral as well as nonviral delivery methods have been effectively tested in vivo for silencing of molecular targets and have resulted in significant efficacy in animal models of Alzheimer's disease, amyotrophic lateral sclerosis (ALS), anxiety, depression, encephalitis, glioblastoma, Huntington's disease, neuropathic pain, and spinocerebellar ataxia. To realize the full therapeutic potential of siRNA for neurodegenerative diseases, we need to overcome many hurdles and challenges such as selecting suitable tissue-specific delivery vectors, minimizing the off-target effects, and achieving distribution in sufficient concentrations at the target tissue without any side effects. Cationic nanoparticle-mediated targeted siRNA delivery for therapeutic purposes has gained considerable clinical importance as a result of its promising efficacy.

Depression in husbands of breast cancer patients: relationships to coping and social support.

Support Care Cancer. 2010 Mar 10;
Bigatti SM, Wagner CD, Lydon-Lam JR, Steiner JL, Miller KD

PURPOSE: The purpose of the present study was to examine depression in husbands of women with breast cancer, as depression is typically as high in husbands as in patients, and impacts functioning in both. METHODS: We compared husbands of patients to husbands of women without chronic illness on depressive symptoms with the Center for Epidemiological Studies Depression Scale, social support with the Interpersonal Support Evaluation List, and coping with the Ways of Coping Questionnaire. Using the stress and coping model, we examined whether coping mediated social support and depression differently by group, as has been found in the literature. RESULTS: Husbands of patients reported higher scores on the measure of depression and lower use of problem-focused coping, while groups reported equivalent social support. Escape-avoidance coping emerged as a full mediator between social support and depression in husbands of patients, but only a partial mediator in comparison husbands. Accepting responsibility coping partially mediated social support and depression in both groups. Low social support appears particularly detrimental in husbands of patients as it is associated with ineffective coping and depression. CONCLUSIONS: Findings suggest that among husbands of patients, social support relates to depression only through its relationship with coping, indicating healthcare providers should direct attention and intervention to the coping strategies employed by husbands with low social support.

Differences in negative mood-induced smoking reinforcement due to distress tolerance, anxiety sensitivity, and depression history.

Psychopharmacology (Berl). 2010 Mar 10;
Perkins KA, Karelitz JL, Giedgowd GE, Conklin CA, Sayette MA

RATIONALE: Negative mood increases smoking reinforcement and may do so to a greater degree in smokers vulnerable to negative mood dysregulation. METHODS: Adult smokers (N = 71) without current depression were randomly assigned to one of two smoking conditions (nicotine or denic cigarettes, presented blind) maintained across all sessions. Subjects completed one neutral mood session and four negative mood induction sessions. Negative mood inductions included one each of the following: 1) overnight smoking abstinence, 2) challenging computer task, 3) public speech preparation, 4) watching negative mood slides. In each session, subjects took 4 puffs on their assigned cigarette, rated it for "liking" (reward), and then smoked those cigarettes ad libitum (reinforcement) during continued mood induction. Affect was assessed intermittently before and after smoking. Differences in responses were examined as functions of self-reported history of major depression and levels of distress tolerance and anxiety sensitivity. RESULTS: Smoking reinforcement, but not reward or negative affect relief, was greater in all sessions in those with a history of depression and greater after overnight abstinence in those with lower distress tolerance. Reward and affect relief, but not reinforcement, were greater during speech preparation among those high in anxiety sensitivity. CONCLUSIONS: Low distress tolerance may enhance acute smoking reinforcement due to abstinence, while depression history may broadly increase acute smoking reinforcement regardless of mood. Neither smoking reward nor affect help explain these individual differences in smoking reinforcement.

Enhancing Standard Cardiac Rehabilitation With Stress Management Training: BACKGROUND, METHODS, AND DESIGN FOR THE ENHANCED STUDY.

J Cardiopulm Rehabil Prev. 2010 March/April; 30(2): 77-84
Blumenthal JA, Wang JT, Babyak M, Watkins L, Kraus W, Miller P, Hinderliter A, Sherwood A

PURPOSE: Enhancing Standard Cardiac Rehabilitation with Stress Management Training in Patients with Heart Disease (ENHANCED) is a randomized clinical trial funded by the National Heart Lung and Blood Institute to evaluate the effects of stress management training (SMT) on changes in biomarkers of risk and quality of life for patients enrolled in traditional exercise-based cardiac rehabilitation (CR). METHODS: One hundred fifty cardiac patients recruited from Duke University and the University of North Carolina will be evaluated and randomized to CR enhanced by SMT (including sessions devoted to relaxation training, cognitive restructuring, communication skills, and problem solving) or to standard exercise-based CR. Before and after 12 weeks of treatment, patients will undergo a battery of psychometric questionnaires and evaluation of cardiovascular biomarkers, including measures of flow-mediated dilation, heart rate variability, baroreflex sensitivity, platelet function and inflammation, and ischemia during laboratory mental stress testing. The primary outcomes include a composite measure of stress (distress, depression, anxiety, and hostility and 24-hour urinary catecholamines and cortisol) and a composite measure of cardiac biomarkers of risk (vascular endothelial function, cardiac vagal control, inflammation, platelet function, and mental stress-induced myocardial ischemia). Secondary outcomes include measures of quality of life as well as clinical events, including death, hospitalizations, myocardial infarction, and revascularization procedures. RESULTS: This article reviews prior studies in the area and describes the design of the ENHANCED study. Several key methodological issues are discussed including the assessment of biomarkers of risk and barriers to the integration of SMT into traditional CR. CONCLUSIONS: The ENHANCED study will provide important information by determining to what extent SMT combined with exercise-based CR may improve prognosis and quality of life in vulnerable cardiac patients.

Development of the Italian Version of the Tampa Scale of Kinesiophobia (TSK-I): Cross-Cultural Adaptation, Factor Analysis, Reliability, and Validity.

Spine (Phila Pa 1976). 2010 Mar 5;
Monticone M, Giorgi I, Baiardi P, Barbieri M, Rocca B, Bonezzi C

STUDY DESIGN.: Evaluation of the psychometric properties of a translated and culturally adapted questionnaire. OBJECTIVE.: Translating, culturally adapting, and validating the Italian version of the Tampa Scale of Kinesiophobia (TSK-I) to allow its use for Italian-speaking patients with low back pain. SUMMARY OF BACKGROUND DATA.: Increasing attention is being given to standardized outcome measures as a means of improving interventions for low back pain. A translated form of the TSK in patients with low back pain has never been validated in the Italian population. METHODS.: The development of the TSK-I questionnaire involved its translation and back-translation, a final review by an expert committee, and testing of the prefinal version to establish its correspondence to the original English version. Psychometric testing included factor analysis, reliability by internal consistency (Cronbach's alpha) and test-retest repeatability (Intraclass Coefficient Correlation), discriminant validity (Pearson correlation) by comparing TSK-I to a visual analogue scale, the Roland Morris Disability Questionnaire, Beck's Depression Inventory and Anxiety Inventory. RESULTS.: It took the authors 5 months to achieve a shared version of the TSK-I, which proved to be satisfactorily acceptable when administered to 178 subjects. Factor analysis indicated a 2-factor 13-item solution (38% of explained variance). The questionnaire showed acceptable internal consistency (alpha = 0.772) and high test-retest reliability (ICC = 0.956). Discriminant validity showed moderate to low correlations with visual analogue scale (r = 0.345), the Roland Morris Disability (r = 0.337), and Beck's Depression Inventory and Anxiety Inventory (r = 0.258 and r = 283). The subscales were also psychometrically analyzed. CONCLUSION.: The TSK was successfully translated into Italian, showing a good factorial structure and psychometric properties, and replicating the results of existing English versions of the questionnaire. Its use is recommended for research purposes.

Serotonin transporter gene and inhibition of conflicting emotional information.

Neuroreport. 2010 Mar 5;
Koizumi A, Kitagawa N, Kitamura MS, Kondo HM, Sato T, Kashino M

Genetic variation of the serotonin-transporter-linked promoter region has been reported to be associated with susceptibility to mood disorders. However, little is known about the behavioral characteristics that mediate this genetic variation and susceptibility to depression. We examined whether the serotonin-transporter genotype modulates inhibition of facial expressions and emotional words in the emotional 'face-word' Stroop task. Although negative word distractors interfered with the valence identification of positive faces among carriers of two short alleles, positive word distractors interfered with that of negative faces among carriers of one or two long alleles. We discuss a possible role of the reduced inhibitory control over semantic negative information in carriers of two short alleles in the risk of developing depressive mental state.

An update on the blood vessel in migraine.

Curr Opin Neurol. 2010 Mar 4;
Brennan K, Charles A

PURPOSE OF REVIEW: The cranial blood vessel is considered an integral player in the pathophysiology of migraine, but its perceived role has been subject to much discussion and controversy over the years. We will discuss the evolution in our scientific understanding of cranial blood vessels (primarily arteries) in migraine. RECENT FINDINGS: Recent developments have clarified the role of cranial blood vessels in the trigemino-vascular system and in cortical spreading depression. An underlying theme is the intimate relation between vascular activity and neural function, and we will emphasize the various roles of the blood vessel that go beyond delivering blood. We conclude that migraine cannot be understood, either from a research or clinical point of view, without an understanding of the vascular derangements that accompany it. SUMMARY: Migraine is accompanied by significant derangements in vascular function that may represent important targets for investigation and treatment.

Cycling Progressive Resistance Training for People with Multiple Sclerosis: A Randomized Controlled Study.

Am J Phys Med Rehabil. 2010 Mar 3;
Cakt BD, Nacir B, Genç H, Saraçoğlu M, Karagöz A, Erdem HR, Ergün U

ABSTRACT: Cakit BD, Nacir B, Genç H, Saraçoğlu M, Karagöz A, Erdem HR, Ergün U: Cycling progressive resistance training for people with multiple sclerosis: A randomized controlled study. OBJECTIVE:: To evaluate the effects of cycling progressive resistance training combined with balance exercises on walking speed, balance, fatigue, fear of falling, depression, and quality of life in patients with multiple sclerosis. DESIGN:: In this prospective randomized controlled trial, 45 patients were randomized into two exercise training (n = 30) groups and one control (n = 15) group. The patients in training group 1 (n = 15) underwent progressive resistance training on a bicycle ergometer and balance exercise, whereas group 2 (n = 15) patients received a home-based lower-limb strengthening and balance exercise. Outcome measures, including the duration of exercise, tolerated maximum workload, timed up and go test, Dynamic Gait Index, functional reach, Falls Efficacy scale, 10-m walk test, Fatigue Severity Scale, Beck Depression Inventory, and Short Form 36 scores, were assessed initially and at 8 wks. RESULTS:: After dropouts, the whole study group consisted of 20 women and 13 men (mean age, 37.9 +/- 10.43 yrs). In training group 1, duration of exercise, tolerated maximum workload, timed up and go test, Dynamic Gait Index, functional reach, falls efficacy scale, 10-m walk test, Fatigue Severity scale, and Beck Depression Inventory scores, and in group 2, the mean duration of exercise, tolerated maximum workload, and Falls Efficacy scale scores were significantly improved after the training program (P < 0.05). There were no significant improvements in any of the outcome measurements in the control group (P > 0.05). In between-group comparisons, improvements in outcome measures of group 1 patients were significantly higher than those in other groups, except for 10-m walking test. Group 1 patients showed statistically significant improvement in physical functioning and role-physical functioning scales of the Short Form 36 (P < 0.01 and P < 0.05, respectively), and group 2 patients showed statistically significant improvement in only physical functioning scale of Short Form 36 (P < 0.05) after 8 wks. CONCLUSIONS:: Specific exercise programs, including cycling progressive resistance training, may improve balance, fatigue, and depression and reduce fear of falling in patients with multiple sclerosis without worsening multiple sclerosis signs and symptoms.

Impairment of mother-infant relationship: validation of the chinese version of postpartum bonding questionnaire.

J Nerv Ment Dis. 2010 Mar; 198(3): 174-9
Siu BW, Ip P, Chow HM, Kwok SS, Li OL, Koo ML, Cheung EF, Yeung TM, Hung SF

The implementation of the Comprehensive Child Development Service in Hong Kong brought about the need for the development of an instrument for assessing mother-infant relationship impairments in women with postnatal depression. The Postpartum Bonding Questionnaire by was first translated into Chinese, then back-translated into English. An expert panel was set up to evaluate the content validity and a focus group discussion was held to explore the face validity and acceptability of the questionnaire. The Chinese version of the Postpartum Bonding Questionnaire (C-PBQ) was administered to 62 women suffering from postnatal depression. Scale 1 of the C-PBQ had a sensitivity of 84% for detecting women with any forms of mother-infant relationship impairments and scale 2 had a sensitivity of 89% for detecting rejection of infant and a sensitivity of 77% for detecting pathological anger towards infant. The C-PBQ is a useful instrument for detecting mother-infant relationship impairments as perceived by women with postnatal depression.

Attachment-based family therapy for adolescents with suicidal ideation: a randomized controlled trial.

J Am Acad Child Adolesc Psychiatry. 2010 Feb; 49(2): 122-31
Diamond GS, Wintersteen MB, Brown GK, Diamond GM, Gallop R, Shelef K, Levy S

OBJECTIVE: To evaluate whether Attachment-Based Family Therapy (ABFT) is more effective than Enhanced Usual Care (EUC) for reducing suicidal ideation and depressive symptoms in adolescents. METHOD: This was a randomized controlled trial of suicidal adolescents between the ages of 12 and 17, identified in primary care and emergency departments. Of 341 adolescents screened, 66 (70% African American) entered the study for 3 months of treatment. Assessment occurred at baseline, 6 weeks, 12 weeks, and 24 weeks. ABFT consisted of individual and family meetings, and EUC consisted of a facilitated referral to other providers. All participants received weekly monitoring and access to a 24-hour crisis phone. Trajectory of change and clinical recovery were measured for suicidal ideation and depressive symptoms. RESULTS: Using intent to treat, patients in ABFT demonstrated significantly greater rates of change on self-reported suicidal ideation at post-treatment evaluation, and benefits were maintained at follow-up, with a strong overall effect size (ES = 0.97). Between-group differences were similar on clinician ratings. Significantly more patients in ABFT met criteria for clinical recovery on suicidal ideation post-treatment (87%; 95% confidence interval [CI] = 74.6-99.6) than patients in EUC (51.7%; 95% CI = 32.4-54.32). Benefits were maintained at follow-up (ABFT, 70%; 95% CI = 52.6-87.4; EUC 34.6%; 95% CI = 15.6-54.2; odds ratio = 4.41). Patterns of depressive symptoms over time were similar, as were results for a subsample of adolescents with diagnosed depression. Retention in ABFT was higher than in EUC (mean = 9.7 versus 2.9). CONCLUSIONS: ABFT is more efficacious than EUC in reducing suicidal ideation and depressive symptoms in adolescents. Additional research is warranted to confirm treatment efficacy and to test the proposed mechanism of change (the Family Safety Net Study).Clinical Trial Registry Information: Preventing Youth Suicide in Primary Care: A Family Model, URL: http://www.clinicaltrials.gov, unique identifier: NCT00604097.

A Hypericum Extract in the Treatment of Depressive Symptoms in Outpatients: An Open Study.

Forsch Komplementmed. 2010; 17(1): 7-14
Melzer J, Brignoli R, Keck ME, Saller R

Background: Extracts of Hypericum perforatum have demonstrated in randomized trials (RCTs) to be effective in mild to moderate depressive episodes. However, as their use in daily practice may differ from that in RCTs we have conducted a study to achieve a better estimate of the range and frequency of adverse drug reactions (ADR) and the efficacy. Patients and Methods: In an observational study in Germany, adult outpatients with depressive syndrome were treated with an extract of St. John's Wort. Study duration was 12 weeks, with control visits every 4 weeks. Besides anamnestic data, the variables assessed were: evolution of ICD-10 derived symptom score, Global Clinical Impression scale (GCI), and tolerability. Results: 1,778 patients from 304 centers participated in the study (mean duration of disorder 7.3 +/- 18.9 months), and 1,541 patients completed it. At the last control visit the ICD-10 sum score had dropped by 63.1% and the proportion of patients described as 'normal to mildly ill' (GCI-s) had increased from 21.6% at admission to 72.4%. Regarding the GCI-i, 77% of the patients had improved 'very much' or 'much' at the last visit. This was consistent with their self-assessment (76%). Lower age and shorter duration of the disorder were associated with significantly better outcomes. The incidence of ADRs was 3.54% and had been decreasing continuously from the first control visit onwards; serious ADRs did not occure. Conclusions: The herbal drug was well tolerated, and no new or serious ADR were identified. In view of the limitations inherent to the study design, it can be concluded that extracts of St. John's Wort are effective as an antidepressant in the management of depression in daily practice.

Determinants of Quality of Life in Nursing Home Residents with Dementia.

Dement Geriatr Cogn Disord. 2010 Mar 6; 29(3): 189-197
Wetzels RB, Zuidema SU, de Jonghe JF, Verhey FR, Koopmans RT

Aims: The goal of this study is to assess the relationship between quality of life (QoL), neuropsychiatric symptoms (NPS), psychotropic drug use (PDU) and patient characteristics in a large group of nursing home residents with dementia. Methods: This cross-sectional observational study included 288 individuals with dementia who reside in 14 special care units in 9 nursing homes. The following measures were used: the Qualidem scale to assess QoL, the Neuropsychiatric Inventory-Nursing Home version, the Global Deterioration Scale (GDS), the Severe Impairment Battery-short version, an Activities of Daily Living scale and PDU. Associations between QoL and NPS were examined using multivariate linear regression models with corrections for potential covariates. Results: The average age of the residents was 84 years (SD = +/-7). Agitation, depression, psychosis, psychomotor agitation and psychotropic drugs were independently associated with poor QoL. In patients with mild to moderately severe dementia (GDS 4-6), NPS, PDU and cognitive impairment explained almost half of the variance in QoL scores. Agitation and depression were particularly strong predictors of poor QoL. In patients with severe dementia (GDS 7), agitation, depression, psychosis and cognitive impairment were associated with poor QoL. Conclusions: NPS, cognition and PDU independently impair QoL for patients in both the moderate and advanced stages of dementia. These results challenge existing pharmacological intervention strategies and highlight the need for psychosocial interventions in the treatment of NPS.

Psychosocial Functioning Among HIV-Affected Youth and Their Caregivers in Haiti: Implications for Family-Focused Service Provision in High HIV Burden Settings.

AIDS Patient Care STDS. 2010 Mar; 24(3): 147-58
Smith Fawzi MC, Eustache E, Oswald C, Surkan P, Louis E, Scanlan F, Wong R, Li M, Mukherjee J

Abstract The study is an analysis of baseline data from a pilot psychosocial support intervention for HIV-affected youth and their caregivers in Haiti. Six sites in Haiti's Central Department affiliated with Partners In Health/Zanmi Lasante (PIH/ZL) and the Haitian Ministry of Health were included. Participants were recruited from a list of HIV-positive patients receiving care at PIH/ZL. The baseline questionnaire was administered from February 2006 to January 2007 with HIV-affected youth (n = 492), ages 10-17, and their caregivers (n = 330). According to findings at baseline, the youth reported high levels of anxiety, including constant fidgeting (86%), restlessness (83%), and worrying a lot (56%). Their parents/caregivers also reported a high level of depressive symptoms, such as low energy (73%), feeling everything is an effort (71%), and sadness (69%). Parents' depressive symptoms were positively associated with their children's psychological symptoms (odds ratio [OR] =1.6-2.4) and psychosocial functioning (OR =1.6 according to parental report). The significant levels of anxiety and depression observed among HIV-affected youth and their caregivers suggest that psychosocial interventions are needed among HIV-affected families in central Haiti and other high HIV burden areas. The results suggest that a family-focused approach to service provision may be beneficial, possibly improving quality of life, as well as psychosocial and physical health-related outcomes among HIV-affected youth and their caregivers, particularly HIV-positive parents.

Corrected QT dispersion improves diagnostic performance of exercise testing in diagnosing coronary artery disease.

East Mediterr Health J. 2010 Jan; 16(1): 75-81
Hasan-Alia H, Maghraby MH, Fouad AA, Abd-Elsayed A

To determine the best combination of parameters that would improve the diagnostic performance of exercise testing, coronary angiography plus exercise testing were done on 112 patients with angina pectoris and normal electrocardiogram. The univariate predictors of coronary artery disease included: age > or = 40 years, male sex, hypertension, smoking, development of exertional chest pain, decrease in systolic blood pressure (BP) > or = 10 mmHg or systolic BP 3 min post-exercise > 90% of peak, heart rate drop < 12 beats/min 1 min postexercise, exercise-induced ST-segment depression > or = 1 mm. Multivariate logistic regression analysis showed that using either ST depression > or = 1 mm or peak exercise QTDc > 70 ms significantly improved sensitivity and negative predictive value of the test without a significant decrease in specificity.

Pattern and possible contributing factors to dialysis-associated arrhythmia in young patients.

East Mediterr Health J. 2009 Sep-Oct; 15(5): 1313-22
Hasan-Ali H, Maghraby MH, Mosad E, Abd-Elsayed AA

We studied dialysis-associated arrhythmia in 48 uraemic patients < 35 years on chronic haemodialysis (HD) (> 3 months). Holter findings showed only minor arrhythmia; atrial in 42% of patients and ventricular in 38%. ST-segment depression > 1 mm was observed in 58% of patients; 80% had arrhythmia, and 36% experienced anginal pain. HD caused a significant increase in QTc, QTdc and Ca2+ level, while K+ level was significantly decreased. Patients who experienced arrhythmia during HD had higher left ventricular mass and left ventricular mass index, lower post-dialysis K+ level, higher QTc and QTdc both before and after HD. They were more frequently hypertensive. ST-segment depression was significantly related to ventricular arrhythmia.

Clinical and biochemical profile of alcohol users in Basra.

East Mediterr Health J. 2009 Sep-Oct; 15(5): 1226-34
Mossawe JF, Ali NA, Ahmed JH, Al-Naama LM

All psychiatric and general medical male patients referred to 2 hospitals in Basra, Iraq from September 2000 to April 2001 were screened using the Alcohol Use Disorder Identification Test. A total of 189 men were identified as having alcohol-related problems. The majority were aged 30-49 years, and two-thirds had drunk alcohol for over 10 years. About 53% of patients exceeded 1 bottle (750 mL) of spirits daily, and 14.8% reported morning drinking. Elevation of liver enzymes, hepatomegaly, jaundice and cirrhosis were identified in 46.0%. Liver cirrhosis was more common in patients drinking locally made arak. Many of the patients suffered psychiatric disorders, including anxiety disorders, depression and suicide attempts, and 80.9% took other psychoactive drugs.

[Diagnostic and therapeutic activity moderation. Quaternary and genetic prevention]

Gac Sanit. 2006 Mar; 20 Suppl 1: 127-34
Gérvas J

Medical activities have more positive than negative outcomes. Because this balance, medicine has a great social recognition. But with new technology and more aggressive diagnostic and therapeutic interventions, there is a decreasing gap in between benefits and harms. Risk increases because more interventions, and because placing patients in more technology environments. As a consecuence, patient safety decreases. Quantity becomes as important as quality, and the place of care is crucial for patient safety. Medical activities should be of <>, performed in the low level of care possible. Then, quaternary prevention (to avoid unnecessary use and risk of medical interventions) should be a continuous parallel clinical activity. I consider four examples of needed quaternary prevention, with Spanish data: 1) cardiovascular prevention (where there is an inverse use of resources, as patients who need more receive less); 2) use of new antidepressants (which has provoke an artificial epidemic of <

Feasibility and diagnostic validity of the m-3 checklist: a brief, self-rated screen for depressive, bipolar, anxiety, and post-traumatic stress disorders in primary care.

Ann Fam Med. 2010 Mar-Apr; 8(2): 160-9
Gaynes BN, Deveaugh-Geiss J, Weir S, Gu H, Macpherson C, Schulberg HC, Culpepper L, Rubinow DR

PURPOSE: Mood and anxiety disorders are the most common psychiatric conditions seen in primary care, yet they remain underdetected and undertreated. Screening tools can improve detection, but available instruments are limited by the number of disorders assessed. We wanted to assess the feasibility and diagnostic validity of the My Mood Monitor (M-3) checklist, a new, 1-page, patient-rated, 27-item tool developed to screen for multiple psychiatric disorders in primary care. METHODS: We enrolled a sample of 647 consecutive participants aged 18 years and older who were seeking primary care at an academic family medicine clinic between July 2007 and February 2008. We used a 2-step scoring procedure to make screening more efficient. The main outcomes measured were the sensitivity and specificity of the M-3 for major depression, bipolar disorder, any anxiety disorder, and post-traumatic stress disorder (PTSD), a specific type of anxiety disorder. Using a split sample technique, analysis proceeded from determination of optimal screening thresholds to assessment of the psychometric properties of the self-report instrument using the determined thresholds. We used the Mini International Neuropsychiatric Interview as the diagnostic standard. Feasibility was assessed with patient and physician exit questionnaires. RESULTS: The depression module had a sensitivity of 0.84 and a specificity of 0.80. The bipolar module had a sensitivity of 0.88, and a specificity of 0.70. The anxiety module had a sensitivity of 0.82 and a specificity of 0.78, and the PTSD module had a sensitivity of 0.88 and a specificity of 0.76. As a screen for any psychiatric disorder, sensitivity was 0.83 and specificity was 0.76. Patients took less than 5 minutes to complete the M-3 in the waiting room, and less than 1% reported not having time to complete it. Eighty-three percent of clinicians reviewed the checklist in 30 or fewer seconds, and 80% thought it was helpful in reviewing patients' emotional health. CONCLUSIONS: The M-3 demonstrates utility as a valid, efficient, and feasible tool for screening multiple common psychiatric illnesses, including bipolar disorder and PTSD, in primary care. Its diagnostic accuracy equals that of currently used single-disorder screens and has the additional benefit of being combined into a 1-page tool. The M-3 potentially can reduce missed psychiatric diagnoses and facilitate proper treatment of identified cases.

Comparison of intravaginal electrical stimulation and trospium hydrochloride in women with overactive bladder syndrome: a randomized controlled study.

Clin Rehabil. 2010 Mar 8;
Ozdedeli S, Karapolat H, Akkoc Y

Objective: To compare the effects of trospium hydrochloride and electrical stimulation on urodynamic parameters, bladder diary, quality of life and psychological symptoms in female patients with overactive bladder syndrome.Design: Prospective, randomized controlled trial.Setting: Department of Physical Medicine and Rehabilitation, University Hospital. Subjects: Thirty-five patients were divided into either trospium chloride (Group 1) or intravaginal electrical stimulation therapy (Group 2). MAIN OUTCOME MEASURES: All patients were assessed at the beginning of the treatment, at weeks 6 (end of treatment), 10 and 18 according to urodynamic parameters, voiding diary parameters, severity of urgency (visual analogue scale, VAS), the Incontinence Impact Questionnaire Short Form (IIQ-7), and the Beck Depression Inventory.Results: Statistically significant improvements were observed in both groups according to some urodynamic parameters, voiding diary parameters, VAS urgency severity, Incontinence Impact Questionnaire Short Form and Beck Depression Inventory scores at the end of the treatment (P < 0.05). During the 18-week follow-up period, deteriorations were observed in many parameters in both groups although improvements in the frequency of urgency, the frequency of incontinence episodes, VAS urgency severity, and Beck Depression Inventory score in Group 2 persisted (P < 0.05). Significant differences were not detected between groups at the end of the treatment or during the posttreatment follow-up controls (P > 0.05).Conclusion: No difference was detected between trospium hydrochloride and intravaginal electrical stimulation in the treatment of female overactive bladder syndrome. Discontinuation of both treatments caused deterioration in most of the objective and subjective symptoms of overactive bladder syndrome.

Regulation of serotonin receptor function in the nervous system by lipid rafts and adaptor proteins.

Exp Cell Res. 2010 Mar 5;
Björk K, Sjögren B, Svenningsson P

5-HT is a phylogenetically conserved monoaminergic neurotransmitter which is crucial for a number of physiological processes and is dysregulated in several disease states including depression, anxiety and schizophrenia. 5-HT neurons in the central nervous system are localized in the raphe nuclei and project to a wide range of target areas. 5-HT exerts its functions through 14 subtypes of 5-HT receptors. The tertiary structures of seven transmembrane 5-HT receptors contain several important features, including cholesterol consensus motifs, prominent intracellular loops and free C-termini. Alterations of cholesterol levels affect binding of ligands to 5-HT receptors and cholesterol-enriched microdomains in the cell membrane, termed lipid rafts, regulate 5-HT receptor internalization and signaling. The intracellular loops and the C-termini of 5-HT receptors provide binding sites for interacting adaptor proteins. Adaptor proteins affect internalization, desensitization as well as G-protein dependent and independent signaling via 5-HT receptors. We will here briefly review recent progress on the role of lipid rafts and adaptor proteins in the regulation of localization, trafficking, signaling and ligand bias of 5-HT receptors.


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