22 research outputs found

    Differential ligand binding affinities of human estrogen receptor-α isoforms

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    Rapid non-genomic effects of 17β-estradiol are elicited by the activation of different estrogen receptor-α isoforms. Presence of surface binding sites for estrogen have been identified in cells transfected with full-length estrogen receptor-α66 (ER66) and the truncated isoforms, estrogen receptor-α46 (ER46) and estrogen receptor-α36 (ER36). However, the binding affinities of the membrane estrogen receptors (mERs) remain unknown due to the difficulty of developing of stable mER-transfected cell lines with sufficient mER density, which has largely hampered biochemical binding studies. The present study utilized cell-free expression systems to determine the binding affinities of 17β-estradiol to mERs, and the relationship among palmitoylation, membrane insertion and binding affinities. Saturation binding assays of human mERs revealed that [3H]-17β-estradiol bound ER66 and ER46 with Kd values of 68.81 and 60.72 pM, respectively, whereas ER36 displayed no specific binding within the tested concentration range. Inhibition of palmitoylation or removal of the nanolipoprotein particles, used as membrane substitute, reduced the binding affinities of ER66 and ER46 to 17β-estradiol. Moreover, ER66 and ER46 bound differentially with some estrogen receptor agonists and antagonists, and phytoestrogens. In particular, the classical estrogen receptor antagonist, ICI 182,780, had a higher affinity for ER66 than ER46. In summary, the present study defines the binding affinities for human estrogen receptor-α isoforms, and demonstrates that ER66 and ER46 show characteristics of mERs. The present data also indicates that palmitoylation and membrane insertion of mERs are important for proper receptor conformation allowing 17β-estradiol binding. The differential binding of ER66 and ER46 with certain compounds substantiates the prospect of developing mER-selective drugs.published_or_final_versio

    Psychiatric symptoms mediate the effects of neurological soft signs on functional outcomes in patients with chronic schizophrenia: A longitudinal path-analytic study

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    Neurological soft signs (NSS) in motor coordination and sequencing occur in schizophrenia patients and are an intrinsic sign of the underlying neural dysfunctions. The present longitudinal study explored the relationships among NSS, psychiatric symptoms, and functional outcomes in 151 Chinese patients with chronic schizophrenia across a 6-month period. The participants completed neurological assessments at baseline (Time 1), psychiatric interviews at Time 1 and 3-month follow-up (Time 2), and self-report measures on daily functioning at 6-month follow-up (Time 3). Two possible (combined and cascading) path models were examined on predicting the functional outcomes. Direct and indirect effects of Time 1 NSS on Time 3 functional outcomes via Time 2 psychiatric symptoms were evaluated using path analysis under bootstrapping. Motor coordination and sequencing NSS did not have significant direct effects on functional outcomes. Motor coordination NSS exerted significant and negative indirect effects on functional outcomes via psychiatric symptoms. These results contribute to a better understanding of the determinants of functional outcomes by showing significant indirect pathways from motor coordination NSS to functional outcomes via psychiatric symptoms. That motor sequencing NSS did not affect functional outcomes either directly or indirectly may be explained by their trait marking features.postprin

    The psychophysiological effects of Tai-chi and exercise in residential Schizophrenic patients: a 3-arm randomized controlled trial

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    Background Patients with schizophrenia are characterized by high prevalence rates and chronicity that often leads to long-term institutionalization. Under the traditional medical model, treatment usually emphasizes the management of psychotic symptoms through medication, even though anti-psychotic drugs are associated with severe side effects, which can diminish patients’ physical and psychological well-being. Tai-chi, a mind-body exercise rooted in Eastern health philosophy, emphasizes the motor coordination and relaxation. With these potential benefits, a randomized controlled trial (RCT) is planned to investigate the effects of Tai-chi intervention on the cognitive and motor deficits characteristic of patients with schizophrenia. Methods/design A 3-arm RCT with waitlist control design will be used in this study. One hundred and fifty three participants will be randomized into (i) Tai-chi, (ii) exercise or (iii) waitlist control groups. Participants in both the Tai-chi and exercise groups will receive 12-weeks of specific intervention, in addition to the standard medication and care received by the waitlist control group. The exercise group will serve as a comparison, to delineate any unique benefits of Tai-chi that are independent of moderate aerobic exercise. All three groups will undergo three assessment phases: (i) at baseline, (ii) at 12 weeks (post-intervention), and (iii) at 24 weeks (maintenance). All participants will be assessed in terms of symptom management, motor coordination, memory, daily living function, and stress levels based on self-perceived responses and a physiological marker. Discussion Based on a promising pilot study conducted prior to this RCT, subjects in the Tai-chi intervention group are expected to be protected against deterioration of motor coordination and interpersonal functioning. They are also expected to have better symptoms management and lower stress level than the other treatment groups.published_or_final_versio

    Towards a holistic approach to spiritual healthcare for people with schizophrenia

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    Medical and behavioral treatments are the predominant types of rehabilitation services for people with schizophrenia. Spirituality in people with schizophrenia remains poorly conceptualized, thereby limiting knowledge advancement in the area of spiritual health care services. To provide a framework for better clinical and research practices, we advocate a holistic approach to investigating spirituality and its application in spiritual health care services of people with schizophrenia

    An examination of psychometric properties of the Chinese version of the Positive and Negative Syndrome Scale for schizophrenia

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    BACKGROUND: The Positive and Negative Syndrome Scale (PANSS) is commonly used for assessment of severity of schizophrenic symptoms. In view of the ambivalent results over the factor structure of the scale, the present study aimed to examine the psychometric properties of PANSS by examining the consensus five-factor model by Wallwork in Chinese schizophrenic patients. METHODS: Participants were 146 Chinese patients with schizophrenia (mean age = 54.0 years, SD = 8.5) who resided in a rehabilitation hostel. They completed the Chinese PANSS, which is a 20-item, 7-point scale of psychiatric symptoms with five proposed factors. The five-factor structure of the PANSS and its convergent validity was evaluated via exploratory structural equation modelling using weighted least square estimator in Mplus 7.2. RESULTS: The five-factor consensus model fitted the data significantly better than a four-factor model (Δχ2(16) = 64.4, p < .01). Overall, the five-factor model provided an excellent model fit (χ2(100) = 119.8, p = .09, CFI = .99, TLI = .99, RMSEA = .04, SRMR = .03). The five factors were weakly to moderately correlated (r = .20 - .57, p < .05) except for positive-negative (r = .04), negative-cognitive (r = .19), and depression-cognitive (r = .03). All of the five factors showed satisfactory reliability. DISCUSSIONS: These results supported the use of the five-factor consensus model derived by Wallwork for PANSS in the Chinese context. Future studies should apply the PANSS in the Chinese patients with schizophrenia for assessment of psychiatric symptoms
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