Neural Dynamics in Parkinsonian Brain:The Boundary Between Synchronized and Nonsynchronized Dynamics

Synchronous oscillatory dynamics is frequently observed in the human brain. We analyze the fine temporal structure of phase-locking in a realistic network model and match it with the experimental data from parkinsonian patients. We show that the experimentally observed intermittent synchrony can be generated just by moderately increased coupling strength in the basal ganglia circuits due to the lack of dopamine. Comparison of the experimental and modeling data suggest that brain activity in Parkinson's disease resides in the large boundary region between synchronized and nonsynchronized dynamics. Being on the edge of synchrony may allow for easy formation of transient neuronal assemblies

Rapid turnover of T cells in acute infectious mononucleosis.

During acute infectious mononucleosis (AIM), large clones of Epstein-Barr virus-specific T lymphocytes are produced. To investigate the dynamics of clonal expansion, we measured cell proliferation during AIM using deuterated glucose to label DNA of dividing cells in vivo, analyzing cells according to CD4, CD8 and CD45 phenotype. The proportion of labeled CD8(+)CD45R0(+) T lymphocytes was dramatically increased in AIM subjects compared to controls (mean 17.5 versus 2.8%/day; p<0.005), indicating very rapid proliferation. Labeling was also increased in CD4(+)CD45R0(+) cells (7.1 versus 2.1%/day; p<0.01), but less so in CD45RA(+) cells. Mathematical modeling, accounting for death of labeled cells and changing pool sizes, gave estimated proliferation rates in CD8(+)CD45R0(+) cells of 11-130% of cells proliferating per day (mean 47%/day), equivalent to a doubling time of 1.5 days and an appearance rate in blood of about 5 x 10(9) cells/day (versus 7 x 10(7) cells/day in controls). Very rapid death rates were also observed amongst labeled cells (range 28-124, mean 57%/day),indicating very short survival times in the circulation. Thus, we have shown direct evidence for massive proliferation of CD8(+)CD45R0(+) T lymphocytes in AIM and demonstrated that rapid cell division continues concurrently with greatly accelerated rates of cell disappearance

Cortex – basal ganglia synchronization in Parkinson’s disease

poster abstractIncreased synchrony in the beta band in cortico-basal ganglia circuits is well described in patients with PD. Less is known, however, about how these abnormal firing patterns are correlated across these brain regions. In this study we investigated how this intra-operative data recorded from STN correlates with scalp recorded EEG. Intraoperative single unit recordings and LFPs were obtained from STN and scalp EEG recordings were collected from four electrodes positioned over prefrontal and motor areas. We computed the STN spike-LFP (Local Filed Potential) phase synchrony over short temporal windows as it fluctuates in time. We also computed the EEG phase synchrony index time series for all 6 pairs of EEG electrodes. Next we explored cross-correlation between the two synchrony level time-series of the spike-LFP vs. EEG pairs. EEG synchrony was found to be correlated with spike-LFP synchrony. Correlation between surface EEG and STN was strongest for ipsilateral EEG and STN recordings. Spike-LFP synchronization is believed to characterize the input-output characteristics of STN dynamics and to be strongly relevant to the expression of motor symptoms. Our results indicate that non-invasive and relatively simple EEG recordings retain some information about synchronous dynamics in the subcortical regions, which can be access only in an invasive manner during functional neurosurgical procedures

Guidelines (1988) for training in clinical laboratory management

Trainees in laboratory medicine must develop skills in laboratory management. Guidelines are detailed for laboratory staff in training, directors responsible for staff development and professional bodies wishing to generate material appropriate to their needs. The syllabus delineates the knowledge base required and includes laboratory planning and organization, control of operations, methodology and instrumentation, data management and statistics, financial management, clinical use of tests, communication, personnel management and training and research and development. Methods for achievement of the skills required are suggested. A bibliography of IFCC publications and other material is provided to assist in training in laboratory management

FragmentStore—a comprehensive database of fragments linking metabolites, toxic molecules and drugs

Consideration of biomolecules in terms of their molecular building blocks provides valuable new information regarding their synthesis, degradation and similarity. Here, we present the FragmentStore, a resource for the comparison of fragments found in metabolites, drugs or toxic compounds. Starting from 13 000 metabolites, 16 000 drugs and 2200 toxic compounds we generated 35 000 different building blocks (fragments), which are not only relevant to their biosynthesis and degradation but also provide important information regarding side-effects and toxicity. The FragmentStore provides a variety of search options such as 2D structure, molecular weight, rotatable bonds, etc. Various analysis tools have been implemented including the calculation of amino acid preferences of fragments’ binding sites, classification of fragments based on the enzyme classification class of the enzyme(s) they bind to and small molecule library generation via a fragment-assembler tool. Using the FragmentStore, it is now possible to identify the common fragments of different classes of molecules and generate hypotheses about the effects of such intersections. For instance, the co-occurrence of fragments in different drugs may indicate similar targets and possible off-target interactions whereas the co-occurrence of fragments in a drug and a toxic compound/metabolite could be indicative of side-effects. The database is publicly available at: http://bioinformatics.charite.de/fragment_store

Predicting toxicity through computers: a changing world

The computational approaches used to predict toxicity are evolving rapidly, a process hastened on by the emergence of new ways of describing chemical information. Although this trend offers many opportunities, new regulations, such as the European Community's 'Registration, Evaluation, Authorisation and Restriction of Chemicals' (REACH), demand that models be ever more robust

Interpolated wave functions for nonadiabatic simulations with the fixed-node quantum Monte Carlo method

Simulating nonadiabatic effects with many-body wave function approaches is an open field with many challenges. Recent interest has been driven by new algorithmic developments and improved theoretical understanding of properties unique to electron-ion wave functions. Fixed-node diffusion Monte Caro is one technique that has shown promising results for simulating electron-ion systems. In particular, we focus on the CH molecule for which previous results suggested a relatively significant contribution to the energy from nonadiabatic effects. We propose a new wave function ansatz for diatomic systems which involves interpolating the determinant coefficients calculated from configuration interaction methods. We find this to be an improvement beyond previous wave function forms that have been considered. The calculated nonadiabatic contribution to the energy in the CH molecule is reduced compared to our previous results, but still remains the largest among the molecules under consideration.Comment: 7 pages, 3 figure

BMQ

BMQ: Boston Medical Quarterly was published from 1950-1966 by the Boston University School of Medicine and the Massachusetts Memorial Hospitals

Experiences in managing problematic crystal methamphetamine use and associated depression in gay men and HIV positive men: in-depth interviews with general practitioners in Sydney, Australia

© 2008 Saltman et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background This paper describes the experiences of Australian general practitioners (GPs) in managing problematic crystal methamphetamine (crystal meth) use among two groups of male patients: gay men and HIV positive men. Methods Semi-structured qualitative interviews with GPs with HIV medication prescribing rights were conducted in Sydney, Adelaide and a rural-coastal town in New South Wales between August and October 2006. Participants were recruited from practices with high caseloads of gay and HIV positive men. Results Sixteen GPs were recruited from seven practices to take part in interviews. Participants included 14 male GPs and two female GPs, and the number of years each had been working in HIV medicine ranged from two to 24. Eleven of the GPs who were based in Sydney raised the issue of problematic crystal meth use in these two patient populations. Five key themes were identified: an increasing problem; associations with depression; treatment challenges; health services and health care; workforce issues. Conclusion Despite study limitations, key implications can be identified. Health practitioners may benefit from broadening their understandings of how to anticipate and respond to problematic levels of crystal meth use in their patients. Early intervention can mitigate the impact of crystal meth use on co-morbid mental illness and other health issues. Management of the complex relationships between drug use, depression, sexuality and HIV can be addressed following a 'stepped care' approach. General practice guidelines for the management of crystal meth use problems should address specific issues associated with gay men and HIV positive men. GPs and other health practitioners must appreciate drug use as a social practice in order to build trust with gay men to encourage full disclosure of drug use. Education programs should train health practitioners in these issues, and increased resourcing provided to support the often difficult task of caring for people who use crystal meth. Greater resourcing of acute care and referral services can shift the burden away from primary care and community services. Further investigation should consider whether these findings are reproducible in other general practice settings, the relationship between depression, drug use and HIV medication, and challenges facing the HIV general practice workforce in Australia