Frequency-dependent response of neurons to oscillating electric fields

Neuronal interactions with electric fields depend on the biophysical properties of the neuronal membrane as well as the geometry of the cell relative to the field vector. Biophysically detailed modeling of these spatial effects is central to understanding neuron-to-neuron electrical (ephaptic) interactions as well as how externally applied electrical fields, such as radio-frequency radiation from wireless devices or therapeutic Deep Brain Stimulation (DBS), interact with neurons. Here we examine in detail the shape-dependent response properties of cells in oscillating electrical fields by solving Maxwell's equations for geometrically extended neurons. Early modeling for compact (spherical) cells in alternating fields predicts a smaller effective membrane time constant for the field-cell system compared to direct current injection via whole-cell patch clamp. This result, predicting that cells should respond strongly to field oscillations in the kHz range, was verified later in vitro for murine myeloma cells. However, recent experiments on CA3 pyramidal cells (highly elongated neurons) in the hippocampus do not exhibit this high frequency response. In this thesis we examine the implications of modeling full two-way coupling between three-dimensional cylindrical neurons and the extracellular field utilizing three different methodologies, namely: cable equation, finite-difference and finite-element. Our modeling demonstrates that the electrotonic length and orientation of the cell to the field are key determinants of the neuronal response to oscillating fields. This explains the experimentally observed absence of the high frequency response for pyramidal neurons when the applied field direction is oriented along their dendritic axis. Additionally, we developed biophysically detailed models of neuronal membranes with quasi-active electrical properties stemming from voltage-gated currents. These are known to lead to resonances at characteristic frequencies in the case of current injection via whole-cell patch clamp. Interestingly, in the field-cell system, the resonance was masked in compact, spherical neurons but recovered in elongated neurons. Utilizing our cable and finite-element models, we investigate the effect of point-source stimulation on cylindrical neurons and find a novel type of "passive resonance" not reported before in the literature. We further extend our modeling by incorporating Hodgkin Huxley channels in to the membrane and construct a fully active, spiking model of a neuron, fully coupled to the applied electric fields. We then go on to embed the neuron in to an array of cells to validate our results at the tissue-level. These findings delineate the relationship between neuron shape, orientation and susceptibility to high frequency electric fields, with implications for DBS efficacy, ephaptic coupling in networks and the filtering properties of cortical tissue

Investigation of the cardiac depressant effect of Caralluma tuberculate N.E.Br on isolated rabbit heart

Purpose: To investigate the histopathological and cardiac depressant effect of the aqueous methanol extract of Caralluma tuberculata N.E. Br (AMECT) (family: Asclepiadaceae)’ and to determine if there is a scientific basis for its cardiovascular diseases-related folkloric use. Methods: The effect of AMECT in different concentrations ranging from 0.00001 to 1.0 mg/mL were evaluated in isolated perfused rabbit heart to assess their effect on the force of contraction and heart rate using Langendorff’s apparatus. Atropine and adrenaline were used to identify the underlying mechanism of response produced by AMECT. The extract was studied for its possible mechanism in the absence and presence of atropine and adrenaline. In addition, sub-chronic toxicity and histopathological study of heart tissues in rats were assessed by administering 500 mg/kg of extract. Results: At all concentrations, AMECT produced significant (p < 0.001) negative ionotropic and negative chronotropic effects. The most significant effect was observed at 0.001 mg/mL and higher concentrations hence 0.001 mg/mL was selected for further studies. Pre-incubation with atropine did not significantly inhibit the effects of AMECT. However, AMECT significantly (p < 0.01) blocked the cardiac stimulant effect of adrenaline. In the histopathological studies, AMECT did not produce any significant cellular changes or signs of toxicity in the sub-chronic toxicity study. Conclusion: The cardiac-depressant responses of AMECT may involve the β-adrenergic receptors in the myocardium of isolated rabbit heart thus confirming the rationale for its use in ethnomedicine for cardiac diseases

Hepatoprotective effect of Cichorium Intybus linn (Kasni) Extracts against Carbon Tetrachloride induced Liver Damage

Abstract Background: To assess the effect of aqueous an

Genetic susceptibility loci for cardiovascular disease and their impact on atherosclerotic plaques

Background: Atherosclerosis is a chronic inflammatory disease in part caused by lipid uptake in the vascular wall, but the exact underlying mechanisms leading to acute myocardial infarction and stroke remain poorly understood. Large consortia identified genetic susceptibility loci that associate with large artery ischemic stroke and coronary artery disease. However, deciphering their underlying mechanisms are challenging. Histological studies identified destabilizing characteristics in human atherosclerotic plaques that associate with clinical outcome. To what extent established susceptibility loci for large artery ischemic stroke and coronary artery disease relate to plaque characteristics is thus far unknown but may point to novel mechanisms. Methods: We studied the associations of 61 established cardiovascular risk loci with 7 histological plaque characteristics assessed in 1443 carotid plaque specimens from the Athero-Express Biobank Study. We also assessed if the genotyped cardiovascular risk loci impact the tissue-specific gene expression in 2 independent biobanks, Biobank of Karolinska Endarterectomy and Stockholm Atherosclerosis Gene Expression. Results: A total of 21 established risk variants (out of 61) nominally associated to a plaque characteristic. One variant (rs12539895, risk allele A) at 7q22 associated to a reduction of intraplaque fat, P=5.09×10−6 after correction for multiple testing. We further characterized this 7q22 Locus and show tissue-specific effects of rs12539895 on HBP1 expression in plaques and COG5 expression in whole blood and provide data from public resources showing an association with decreased LDL (low-density lipoprotein) and increase HDL (high-density lipoprotein) in the blood. Conclusions: Our study supports the view that cardiovascular susceptibility loci may exert their effect by influencing the atherosclerotic plaque characteristics

Privacy-aware relationship semantics–based XACML access control model for electronic health records in hybrid cloud

State-of-the-art progress in cloud computing encouraged the healthcare organizations to outsource the management of electronic health records to cloud service providers using hybrid cloud. A hybrid cloud is an infrastructure consisting of a private cloud (managed by the organization) and a public cloud (managed by the cloud service provider). The use of hybrid cloud enables electronic health records to be exchanged between medical institutions and supports multipurpose usage of electronic health records. Along with the benefits, cloud-based electronic health records also raise the problems of security and privacy specifically in terms of electronic health records access. A comprehensive and exploratory analysis of privacy-preserving solutions revealed that most current systems do not support fine-grained access control or consider additional factors such as privacy preservation and relationship semantics. In this article, we investigated the need of a privacy-aware fine-grained access control model for the hybrid cloud. We propose a privacy-aware relationship semantics–based XACML access control model that performs hybrid relationship and attribute-based access control using extensible access control markup language. The proposed approach supports fine-grained relation-based access control with state-of-the-art privacy mechanism named Anatomy for enhanced multipurpose electronic health records usage. The proposed (privacy-aware relationship semantics–based XACML access control model) model provides and maintains an efficient privacy versus utility trade-off. We formally verify the proposed model (privacy-aware relationship semantics–based XACML access control model) and implemented to check its effectiveness in terms of privacy-aware electronic health records access and multipurpose utilization. Experimental results show that in the proposed (privacy-aware relationship semantics–based XACML access control model) model, access policies based on relationships and electronic health records anonymization can perform well in terms of access policy response time and space storage

Digital Signal Processing

Contains an introduction and reports on seventeen research projects.U.S. Navy - Office of Naval Research (Contract N00014-77-C-0266)Amoco Foundation FellowshipU.S. Navy - Office of Naval Research (Contract N00014-81-K-0742)National Science Foundation (Grant ECS80-07102)U.S. Army Research Office (Contract DAAG29-81-K-0073)Hughes Aircraft Company FellowshipAmerican Edwards Labs. GrantWhitaker Health Sciences FundPfeiffer Foundation GrantSchlumberger-Doll Research Center FellowshipGovernment of Pakistan ScholarshipU.S. Navy - Office of Naval Research (Contract N00014-77-C-0196)National Science Foundation (Grant ECS79-15226)Hertz Foundation Fellowshi

Digital Signal Processing

Contains research objectives and reports on sixteen research projects.U.S. Navy - Office of Naval Research (Contract N00014-75-C-0852)National Science Foundation FellowshipNational Science Foundation (Grant ENG76-24117)U.S. Navy - Office of Naval Research (Contract N00014-77-C-0257)U.S. Air Force (Contract F19628-80-C-0002)U.S. Navy - Office of Naval Research (Contract N00014-75-C-0951)Schlumberger-Doll Research Center FellowshipHertz Foundation FellowshipGovernment of Pakistan ScholarshipU.S. Navy - Office of Naval Research (Contract N00014-77-C-0196

Digital Signal Processing

Contains summary of research and reports on sixteen research projects.U.S. Navy - Office of Naval Research (Contract N00014-75-C-0852)National Science Foundation FellowshipNATO FellowshipU.S. Navy - Office of Naval Research (Contract N00014-75-C-0951)National Science Foundation (Grant ECS79-15226)U.S. Navy - Office of Naval Research (Contract N00014-77-C-0257)Bell LaboratoriesNational Science Foundation (Grant ECS80-07102)Schlumberger-Doll Research Center FellowshipHertz Foundation FellowshipGovernment of Pakistan ScholarshipU.S. Navy - Office of Naval Research (Contract N00014-77-C-0196)U.S. Air Force (Contract F19628-81-C-0002)Hughes Aircraft Company Fellowshi

Association of various reproductive rights, domestic violence and marital rape with depression among Pakistani women

<p>Abstract</p> <p>Background</p> <p>Depression among women is common in developing countries. Gender inequality can contribute to women's risk for depression. Lack of reproductive and sexual rights is an important marker of gender inequality and women do not have the freedom to express their reproductive and sexual needs in many parts of the world. Therefore we designed this study to determine the association of depression with lack of various reproductive rights and domestic violence among married women in Karachi, Pakistan.</p> <p>Methods</p> <p>A case-control study with 152 cases and 152 controls, which included women 15-48 years, recruited from two teaching hospitals from 1^stJune 2007 through 31^stAugust 2007. The SRQ was administered to all subjects. A cut off score of 8 was used to confirm cases of depression diagnosed by physicians, and to exclude cases of depression from the controls. Self-administered questionnaire was used to assess the risk factors.</p> <p>Results</p> <p>61% of the cases and 43% of the controls were ever abused by spouse and the frequency of marital rape was 33% in cases and 13% in controls. After adjusting for the effects of other variables in the model, less than 18 years of age at marriage (OR 2.00; 95% CI = 1.07, 3.7), decision for marriage by parents (OR 3.51; 95% CI = 1.67, 7.37), abuse by in laws (OR 4.91; 95% CI = 2.66, 9.06), ≤ 3 hours per day spent with husband (OR 2.33; 95% CI = 1.34, 4.08), frequency of intercourse ≤ 2 times per week (OR 1.85; 95% CI = 1.06, 3.22) and marital rape (OR 3.03; 95% CI = 1.50, 6.11) were associated with depression among women.</p> <p>Conclusion</p> <p>In our study depression in married women was associated with younger age at marriage, lack of autonomy in marriage decisions, marital rape and domestic abuse by in-laws. Efforts should be directed towards creating awareness about the reproductive and sexual rights of women in Pakistan. Physicians should be trained to screen and identify women who may be at risk for psychological distress as a result of denial of reproductive rights so that they can support positive mental health outcomes through individual, family or marital counseling.</p

Use of multidimensional item response theory methods for dementia prevalence prediction: an example using the Health and Retirement Survey and the Aging, Demographics, and Memory Study.

BACKGROUND: Data sparsity is a major limitation to estimating national and global dementia burden. Surveys with full diagnostic evaluations of dementia prevalence are prohibitively resource-intensive in many settings. However, validation samples from nationally representative surveys allow for the development of algorithms for the prediction of dementia prevalence nationally. METHODS: Using cognitive testing data and data on functional limitations from Wave A (2001-2003) of the ADAMS study (n = 744) and the 2000 wave of the HRS study (n = 6358) we estimated a two-dimensional item response theory model to calculate cognition and function scores for all individuals over 70. Based on diagnostic information from the formal clinical adjudication in ADAMS, we fit a logistic regression model for the classification of dementia status using cognition and function scores and applied this algorithm to the full HRS sample to calculate dementia prevalence by age and sex. RESULTS: Our algorithm had a cross-validated predictive accuracy of 88% (86-90), and an area under the curve of 0.97 (0.97-0.98) in ADAMS. Prevalence was higher in females than males and increased over age, with a prevalence of 4% (3-4) in individuals 70-79, 11% (9-12) in individuals 80-89 years old, and 28% (22-35) in those 90 and older. CONCLUSIONS: Our model had similar or better accuracy as compared to previously reviewed algorithms for the prediction of dementia prevalence in HRS, while utilizing more flexible methods. These methods could be more easily generalized and utilized to estimate dementia prevalence in other national surveys