Rotenoids and Other Specialized Metabolites from the Roots of Mirabilis multiflora: Opioid and Cannabinoid Receptor Radioligand Binding Affinities.

Mirabilis multiflora is an acclaimed hallucinogen consumed traditionally by the Hopi Indians to induce diagnostic visions. Its root extract afforded a new (3) and four known (2, 5, 6, and 7) 12a-hydroxyrotenoids, a known rotenoid (4), and two known secondary metabolites (1 and 8). The structures of the compounds were elucidated based on spectroscopic and spectrometric data analysis. Electronic circular dichroism data were used to define the (6aS,12aR) absolute configuration of the 12a-hydroxyrotenoids. Compounds 2-7 were screened for their radioligand binding affinities toward the opioid (δ, κ, and µ) and cannabinoid (CB1 and CB2) receptor subtypes. The 6-methoxy-substituted rotenoids 3, 4, and 7 showed the highest receptor binding affinity with moderate selectivity toward the δ-opioid receptor subtype, with negligible binding affinities for CB1 and CB2. Their binding affinities toward the δ-opioid receptor were 64.5% (4), 58.7% (7), and 55.3% (3) at 10 µM, respectively.

Nanoscale roughness affects the activity of enzymes adsorbed on cluster-assembled titania films.

In this study, we investigated how the adsorption properties governed by the nanometer-scale surface morphology of cluster-assembled titanium oxide films influence the catalytic activity of immobilized serine-protease trypsin. We developed an activity assay for the parallel detection of physisorbed enzyme activity and mass density of the adsorbed proteins in microarray format. The method combines a microarray-based technique and advanced quantitative confocal microscopy approaches based on fluorescent labeling of enzymes and covalent labeling of active sites of surface-bound enzymes. The observed diminishing trypsin binding affinity with increasing roughness, as opposed to the steep rise in its saturation uptake, was interpreted as heterogeneous nucleation-driven adsorption of trypsin at the rough nanoporous titania surface. The increase in relative activity of adsorbed trypsin is proportional to the fractional saturation of titania surfaces, expressed as percentage of saturation uptake. In turn, the specific activity, that is, the ratio of active proteins to the absolute number of adsorbed proteins, drops with growing saturation uptake and surface roughness, witnessing a reduction in the accessibility of enzyme active sites. Both geometrical constraints of titania nanopores and the clusterwise adsorption of trypsin were identified as the key factors underpinning the steric hindrance of the immobilized enzyme. These findings are relevant for the optimization of rough nanoporous surfaces as carriers of immobilized enzymes. The proposed activity assay is particularly advantageous in the screening of candidate materials for enzyme immobilization.

The Global Mental Health Assessment Tool-validation in Hindi: A validity and feasibility study.

BACKGROUND: A computer-assisted interview, the Global Mental Health Assessment Tool-validation (GMHAT/PC) has been developed to assist general practitioners and other health professionals to make a quick, convenient, yet reasonably comprehensive standardized mental health assessment. GMHAT/PC has been translated into various languages including Hindi. This is the first study conducted in India, using the Hindi version GMHAT/PC of the series of studies assessing its validity in different cultures. AIM: The study aims to assess the feasibility of using a computer assisted diagnostic interview by health professionals and to examine the level of agreement between the Hindi version GMHAT/PC diagnosis and psychiatrists' ICD-10 based clinical diagnosis. DESIGN: Cross-sectional validation study. SETTING: Psychiatric clinic of a General Hospital and an out patient (Neurology) clinic in the Teaching General Hospital in Jaipur, India. MATERIALS AND METHODS: All consecutive patients attending the psychiatric out patient clinic were interviewed using GMHAT/PC and psychiatrists made a diagnosis applying ICD-10 criteria for a period of six weeks. A small sample of subjects was interviewed in a similar way in a Neurology clinic for four weeks. RESULTS: The mean duration of interview was under 17 minutes. Most patients were pleased that they were asked about every aspect of their mental health. The agreement between psychologists' GMHAT/PC interview diagnoses and psychiatrists' clinical diagnoses was excellent (Kappa 0.96, sensitivity 1.00, and specificity 0.94). CONCLUSION: GMHAT/PC Hindi version detected mental disorders accurately and it was feasible to use GMHAT/PC in Indian settings.

Epidemiological and clinical use of GMHAT-PC (Global Mental Health assessment tool - primary care) in cardiac patients.

BACKGROUND: A computer assisted interview, the GMHAT/PC has been developed to assist General Practitioners and other Health Professionals to make a quick, convenient and comprehensive standardised mental health assessment. It has proved to be a reliable and valid tool in our previous studies involving General Practitioners and Nurses. Little is known about its use in cardiac rehabilitation settings. AIM: The study aims to assess the feasibility of using a computer assisted diagnostic interview by nurses for patients attending Cardiac Rehabilitation Clinics and to examine the level of agreement between the GMHAT/PC diagnosis and a Psychiatrist clinical diagnosis. Prevalence of mental illness was also measured. DESIGN: Cross sectional validation and feasibility study. METHODS: Nurses using GMHAT/PC examined consecutive patients presenting to a cardiac rehabilitation centre. A total of 118 patients were assessed by nurses and consultant psychiatrist in cardiac rehabilitation centres. The kappa coefficient (kappa), sensitivity, and specificity of the GMHAT/PC diagnosis were analysed as measures of validity. The time taken for the interview as well as feedback from patients and interviewers were indicators of feasibility. Data on prevalence of mental disorders in an outpatient cardiac rehabilitation setting was collected. RESULTS: The mean duration of the interview was 14 minutes. Feedback from patients and interviewers indicated good practical feasibility. The agreement between GMHAT/PC interview-based diagnoses and consultant psychiatrists' ICD-10 criteria-based clinical diagnosis was good or excellent (kappa = 0.76, sensitivity = 0.73, specificity = 0.90). The prevalence of mental disorders in this group was 22%, predominantly depression. Very few cases were on treatment. CONCLUSION: GMHAT/PC can assist nurses in making accurate mental health assessments and diagnoses in a cardiac rehabilitation setting and is acceptable to cardiac patients. It can successfully be used to gather epidemiological data and help in managing mental health problems in this group of patients.

Mental health diagnosis by nurses using the Global Mental Health Assessment Tool: a validity and feasibility study.

BACKGROUND: The Global Mental Health Assessment Tool-Primary Care Version (GMHAT/PC) has been developed to assist health professionals to make a quick and comprehensive standardised mental health assessment. It has proved to be a reliable and valid tool in a previous study involving GPs. Its use by other health professionals may help in detecting and managing mental disorders in primary care and general health settings. AIM: To assess the feasibility of using a computer-assisted diagnostic interview by nurses and to examine the level of agreement between the GMHAT/PC diagnosis and psychiatrists' clinical diagnosis. DESIGN OF STUDY: Cross-sectional validation study. SETTING: Primary care, general healthcare (cardiac rehabilitation clinic), and community mental healthcare settings. METHOD: A total of 215 patients between the ages of 16 and 75 years were assessed by nurses and psychiatrists in various settings: primary care centre (n = 54), cardiac rehabilitation centre (n = 98), and community mental health clinic (n = 63). The time taken for the interview, and feedback from patients and interviewers were indicators of feasibility, and the kappa coefficient (kappa), sensitivity, and specificity of the GMHAT/PC diagnosis were measures of validity. RESULTS: Mean duration of interview was under 15 minutes. The agreement between nurses' GMHAT/PC interview-based diagnosis and psychiatrists' International Classification of Diseases (ICD)-10 criteria-based clinical diagnosis was 80% (kappa = 0.76, sensitivity = 0.84, specificity = 0.92). CONCLUSION: The GMHAT/PC can assist nurses to make accurate mental health assessment and diagnosis in various healthcare settings and it is acceptable to patients.

The Global Mental Health Assessment Tool--Primary Care Version (GMHAT/PC). Development, reliability and validity.

The Global Mental Health Assessment Tool--Primary Care Version (GMHAT/PC) is a computerised clinical assessment tool developed to assess and identify a wide range of mental health problems in primary care. It generates a computer diagnosis, a symptom rating, a self-harm risk assessment, and a referral letter. Patients from primary care and community psychiatric outpatient clinics and a small sample of inpatients were interviewed for a period of two months using the GMHAT/PC. A proportion of patients were simultaneously rated by a psychiatrist and a general practitioner for inter-rater reliability. All patients also completed the Hospital Anxiety and Depression Scale (HAD). To conduct the interview was easy in all settings and took 10-15 minutes for patients who had psychiatric symptoms. Inter-rater agreement on mental state symptom groups ranged from 0.49 to 1 (kappa). The computer diagnosis correlated highly with the clinical diagnosis and there was a good level of agreement between HAD ratings and GMHAT/PC ratings. These data suggest that the GMHAT/PC is an easy to administer computerised tool which can be used in primary care for the standardised assessment of mental health problems.