Disparate effects of lithium and a GSK-3 inhibitor on neuronal oscillatory activity in prefrontal cortex and hippocampus

© 2018 Nguyen, Fan, George and Perreault. Glycogen synthase kinase-3 (GSK-3) plays a critical role in cognitive dysfunction associated with Alzheimer's disease (AD), yet the mechanism by which GSK-3 alters cognitive processes in other disorders, such as schizophrenia, remains unknown. In the present study, we demonstrated a role for GSK-3 in the direct regulation of neuronal oscillations in hippocampus (HIP) and prelimbic cortex (PL). A comparison of the GSK-3 inhibitors SB 216763 and lithium demonstrated disparate effects of the drugs on spatial memory and neural oscillatory activity in HIP and PL. SB 216763 administration improved spatial memory whereas lithium treatment had no effect. Analysis of neuronal local field potentials in anesthetized animals revealed that whereas both repeated SB 216763 (2.5 mg/kg) and lithium (100 mg/kg) induced a theta frequency spike in HIP at approximately 10 Hz, only SB 216763 treatment induced an overall increase in theta power (4-12 Hz) compared to vehicle. Acute administration of either drug suppressed slow (32-59 Hz) and fast (61-100 Hz) gamma power. In PL, both drugs induced an increase in theta power. Repeated SB 216763 increased HIP-PL coherence across all frequencies except delta, whereas lithium selectively suppressed delta coherence. These findings demonstrate that GSK-3 plays a direct role in the regulation of theta oscillations in regions critically involved in cognition, and highlight a potential mechanism by which GSK-3 may contribute to cognitive decline in disorders of cognitive dysfunction

A way forward: Process mapping and the delivery of mental health services

YesIntroduction: This paper demonstrates the practical application of process mapping principles as a model for evaluating NHS improvement. The NHS improvement in question was the merger of three crisis resolution teams within an NHS trust in 2012. The aims were to improve overall operational efficiency and enhance multidisciplinary working to meet operational targets. This paper examined changes following the merger to capture the effects of service improvement and the reality of the patient journey. Methods: A pooled cross-sectional approach, using six years of aggregated hospital data, was taken. To achieve operational efficiency, a process map of referrals, readmissions, length of stay and waiting times for crisis resolution team assessments was examined. Prevalence of clinical referral rates and disease classification before and after the merger were compared. Conclusion: Between 1 April 2009 and 30 March 2015, length of stay and readmissions for patients to crisis resolution team rates reduced. Operational sustainability and capacity was enhanced through the redistribution of clinical human resources. Multidisciplinary skill mix (e.g. through improved team composition) also improved

Indonesia Role on Formulating Association of Southeast Asian Nations Treaty Regarding on Health Protection Toward Global Pandemic

The application of public international law is important to response the global pandemic caused by the spread of Covid-19. Therefore, one of the strategies that the Association of Southeast Asian Nations shall apply to continue ASEAN responses on Covid-19 is by formulating an international treaty regarding on health protection toward global pandemic. This strategy or mechanism shall integrate ASEAN Member States legal system diversities to collectively responses the Covid-19 Pandemic or any other epidemic or pandemic. As one of ASEAN Member State, Indonesia needs to initiate the formulation of this treaty to achieve Indonesia Purpose written in Indonesia Constitution. By knowing that Indonesia regulations regarding Covid-19 is overlapping and the number of Covid-19 Mortality Rate is increasing, Indonesia have a strong reason to initiate a summit with other ASEAN Member State. Besides having an initiative, Indonesia shall also conduct this summit by determining the mechanism to formulate this treaty. That mechanism consists of virtual diplomacy according to ASEAN Charter. Besides that, this treaty shall adopt the World Health Organization Protocol and shall also consist of legal norms base on ASEAN Member States consensus, ASEAN Human Rights Body and ASEAN Health Expertise. This summit shall be conducted online or by a virtual diplomacy in order to effectively and efficiently formulate this treaty. Keywords: ASEAN Treaty, Covid-1

Evaluation of demand in a rural English hospital emergency department

The purpose of this article is to analyse the patient demand placed on a rural district general hospital (DGH) emergency department within the context of the Purpose, Process, People (PPP) framework used in the private sector. This analysis was undertaken to inform wider evaluation of the implementation of the enterprise culture—the NHS policy to adopt private sector best practice to produce resource use, quality and efficiency improvements. The article concludes with a view that the PPP framework provides methods of calculating the level of discharge necessary to meet the four-hour wait target. Data describing the characteristics and patterns of attending patients can be used to develop an emergency department’s processes and people to achieve its time-based target

Geometric invariant theory of syzygies, with applications to moduli spaces

We define syzygy points of projective schemes, and introduce a program of studying their GIT stability. Then we describe two cases where we have managed to make some progress in this program, that of polarized K3 surfaces of odd genus, and of genus six canonical curves. Applications of our results include effectivity statements for divisor classes on the moduli space of odd genus K3 surfaces, and a new construction in the Hassett-Keel program for the moduli space of genus six curves.Comment: v1: 23 pages, submitted to the Proceedings of the Abel Symposium 2017, v2: final version, corrects a sign error and resulting divisor class calculations on the moduli space of K3 surfaces in Section 5, other minor changes, In: Christophersen J., Ranestad K. (eds) Geometry of Moduli. Abelsymposium 2017. Abel Symposia, vol 14. Springer, Cha

Social representations of HIV/AIDS in five Central European and Eastern European countries: A multidimensional analysis

Cognitive processing models of risky sexual behaviour have proliferated in the two decades since the first reporting of HIV/AIDS, but far less attention has been paid to individual and group representations of the epidemic and the relationship between these representations and reported sexual behaviours. In this study, 494 business people and medics from Estonia, Georgia, Hungary, Poland and Russia sorted free associations around HIV/AIDS in a matrix completion task. Exploratory factor and multidimensional scaling analyses revealed two main dimensions (labelled ‘Sex’ and ‘Deadly disease’), with significant cultural and gender variations along both dimension scores. Possible explanations for these results are discussed in the light of growing concerns over the spread of the epidemic in this region

Chlorpromazine for schizophrenia: a Cochrane systematic review of 50 years of randomised controlled trials

BACKGROUND: Chlorpromazine (CPZ) remains one of the most common drugs used for people with schizophrenia worldwide, and a benchmark against which other treatments can be evaluated. Quantitative reviews are rare; this one evaluates the effects of chlorpromazine in the treatment of schizophrenia in comparison with placebo. METHODS: We sought all relevant randomised controlled trials (RCT) comparing chlorpromazine to placebo by electronic and reference searching, and by contacting trial authors and the pharmaceutical industry. Data were extracted from selected trials and, where possible, synthesised and random effects relative risk (RR), the number needed to treat (NNT) and their 95% confidence intervals (CI) calculated. RESULTS: Fifty RCTs from 1955–2000 were included with 5276 people randomised to CPZ or placebo. They constitute 2008 person-years spent in trials. Meta-analysis of these trials showed that chlorpromazine promotes a global improvement (n = 1121, 13 RCTs, RR 0.76 CI 0.7 to 0.9, NNT 7 CI 5 to 10), although a considerable placebo response is also seen. People allocated to chlorpromazine tended not to leave trials early in both the short (n = 945, 16 RCTs, RR 0.74 CI 0.5 to 1.1) and medium term (n = 1861, 25 RCTs, RR 0.79 CI 0.6 to 1.1). There were, however, many adverse effects. Chlorpromazine is sedating (n = 1242, 18 RCTs, RR 2.3 CI 1.7 to 3.1, NNH 6 CI 5 to 8), increases a person's chances of experiencing acute movement disorders, Parkinsonism and causes low blood pressure with dizziness and dry mouth. CONCLUSION: It is understandable why the World Health Organization (WHO) have endorsed and included chlorpromazine in their list of essential drugs for use in schizophrenia. Low- and middle-income countries may have more complete evidence upon which to base their practice compared with richer nations using recent innovations

The Prevalence of Latent Mycobacterium Tuberculosis Infection Based on an Interferon-γ Release Assay: A Cross-Sectional Survey Among Urban Adults in Mwanza, Tanzania.

One third of the world's population is estimated to be latently infected with Mycobacterium tuberculosis (LTBI). Surveys of LTBI are rarely performed in resource poor TB high endemic countries like Tanzania although low-income countries harbor the largest burden of the worlds LTBI. The primary objective was to estimate the prevalence of LTBI in household contacts of pulmonary TB cases and a group of apparently healthy neighborhood controls in an urban setting of such a country. Secondly we assessed potential impact of LTBI on inflammation by quantitating circulating levels of an acute phase reactant: alpha-1-acid glycoprotein (AGP) in neighborhood controls. The study was nested within the framework of two nutrition studies among TB patients in Mwanza, Tanzania. Household contacts- and neighborhood controls were invited to participate. The study involved a questionnaire, BMI determination and blood samples to measure AGP, HIV testing and a Quantiferon Gold In tube (QFN-IT) test to detect signs of LTBI. 245 household contacts and 192 neighborhood controls had available QFN-IT data. Among household contacts, the proportion of QFT-IT positive was 59% compared to 41% in the neighborhood controls (p = 0.001). In a linear regression model adjusted for sex, age, CD4 and HIV, a QFT-IT positive test was associated with a 10% higher level of alpha-1-acid glycoprotein(AGP) (10(B) 1.10, 95% CI 1.01; 1.20, p = 0.03), compared to individuals with a QFT-IT negative test. LTBI is highly prevalent among apparently healthy urban Tanzanians even without known exposure to TB in the household. LTBI was found to be associated with elevated levels of AGP. The implications of this observation merit further studies