Seizure detection and epileptogenic zone localisation on heavily skewed MEG data using RUSBoost machine learning technique.

Background: Epilepsy is a neurological disorder which is characterised by recurrent and involuntary seizures. Magnetoencephalography (MEG) is clinically used as a presurgical tool in locating the epileptogenic zone by localising either interictal epileptic discharges (IEDs) or ictal activities. The localisation of ictal onset provides reliable and more accurate seizure onset zones rather than localising the IEDs. Ictals or seizures are presently detected during MEG analysis by manually inspecting the recorded data. This is laborious when the duration of recordings is longer. Methods: We propose a novel method which uses statistical features such as short-time permutation entropy (STPE), gradient of STPE (GSTPE), short-time energy (STE) and short-time mean (STM) extracted from the ictal and interictal MEG data of drug resistant epilepsy patients group. Since the data is heavily skewed, the RUSBoost algorithm with k-fold cross-validation is used to classify the data into ictal and interictal by using the four feature vectors. This method is further used for localising the epileptogenic region using region-specific classifications by means of the RUSBoost algorithm. Results: The accuracy obtained for seizure detection is 93.4%. The specificity and sensitivity for the same are 93%. The localisation accuracies for each lobe are in the range of 88.1-99.1%. Discussion: Through this ictus detection method, the current scenario of laborious inspection of the ictal MEG can be reduced. The proposed system, thus, can be implemented in real-time as a better and more efficient method for seizure detection and further it can prove to be highly beneficial for patients and health-care professionals during real-time MEG recording. Furthermore, the identification of the epileptogenic lobe can provide clinicians with useful insights, and a pre-cursor for source localisation.

EEG-based P300 in mesial temporal lobe epilepsy and its correlation with cognitive functions: A case-control study.

OBJECTIVE: P300 is an event-related potential, being explored as an objective tool to assess cognition. This study aimed to investigate the characteristics of auditory and visual P300 in patients with TLE having unilateral HS using electroencephalography (EEG) and to study its correlation with cognition. METHODS: This is a cross-sectional case-control study, where P300 characteristics in thirty patients with unilateral hippocampal sclerosis with refractory epilepsy were compared with fifteen age-, gender-, and years of education-matched healthy controls (M: F-10:5, mean age-28 ±â€¯4.76 years). Among patients, 15 belonged to the right HS group (M: F-9:6, age at onset-12.92 ±â€¯10.22 years, duration of epilepsy-16.67 ±â€¯9.38 years) and 15 to the left HS group (M: F-8:7, age at onset-10.62 ±â€¯7.18 years, duration of epilepsy-15.53 ±â€¯10.14 years). All subjects underwent EEG-based auditory and visual oddball tasks and cognitive assessment. The P300 latencies (in milliseconds) as well as amplitudes (in microvolts) were predicted in EEG and were correlated with cognitive scores. Source localization of P300 was performed with the CLARA algorithm. RESULTS: The auditory P300 latencies in controls, right HS, and left HS were 323.93 ±â€¯40.28, 351.06 ±â€¯47.23, and 328.80 ±â€¯36.03, respectively (p = 0.18) and its amplitudes were 2.3040 ±â€¯1.46, 2.77 ±â€¯1.19, and 2.68 ±â€¯1.78, respectively (p = 0.48). Visual P300 latencies in controls, right HS, and left HS were 365.87 ±â€¯47.37, 359.67 ±â€¯64.45, and 376.00 ±â€¯60.06, respectively (p = 0.51) and its amplitudes were 3.93 ±â€¯2.28, 2.09 ±â€¯1.45, and 3.56 ±â€¯1.74, respectively (p = 0.014). Further, when compared to the control group the cognitive scores were lower in the patient group (p < 0.05). SIGNIFICANCE: In comparison to the controls, patients with right HS recorded lesser amplitude on visual P300 and lower scores on cognitive tests. P300 and cognitive parameters exhibited varied relationship. P300 could be a complementary objective tool to assess cognition in patients with TLE.

P300 in mesial temporal lobe epilepsy and its correlation with cognition - A MEG based prospective case-control study.

PURPOSE: To assess the role of P300 in patients with temporal lobe epilepsy (TLE) with unilateral hippocampal sclerosis (HS) using magnetoencephalography (MEG) based auditory and visual oddball tasks, and to assess its correlation with neuropsychological tests. METHODS: Thirty-patients (M:F-17:13, onset-11.77 ±â€¯8.75 years, duration-16.10 ±â€¯9.61 years) with TLE-HS (Left:15, Right:15) and fifteen-healthy age, gender and years of education matched controls (M:F-10:5, age-28.13 ±â€¯4.76 years) underwent auditory and visual oddball tasks in MEG and cognition assessment using Indian Council of Medical Research (ICMR)-cognitive test battery. Independent component analysis (ICA) was applied to the magnetic evoked field responses for the detection of the P300 component. Source localization of P300 was performed with Classical LORETA Analysis Recursively Applied (CLARA). The latency and amplitude of P300 were estimated and subsequently correlated with cognitive scores. RESULTS: The visual P300 amplitude in the TLE group was lower when compared to the control group. In subgroup comparison (controls vs. right HS vs. left HS), visual P300 amplitudes were lower in the right HS group compared to both left HS and control groups (p-value = 0.014). On the other hand, no significant difference for auditory P300 latency or amplitude was noted between patients and controls as well as between subgroups. A negative correlation found between the MEG visual P300 amplitude and Indian Trial Making Test (TMT)-B duration in the patient group. CONCLUSION: Patients with TLE-HS have decreased visual-P300 amplitude. A significant correlation found between visual P300 amplitude and cognitive tests of visuospatial attention and working memory. Overall, MEG based visual P300 amplitude can be further explored with large sample size studies to establish as a complementary objective test for cognitive assessment in TLE.

Content-Based Estimation of Brain MRI Tilt in Three Orthogonal Directions.

In a general scenario, the brain images acquired from magnetic resonance imaging (MRI) may experience tilt, distorting brain MR images. The tilt experienced by the brain MR images may result in misalignment during image registration for medical applications. Manually correcting (or estimating) the tilt on a large scale is time-consuming, expensive, and needs brain anatomy expertise. Thus, there is a need for an automatic way of performing tilt correction in three orthogonal directions (X, Y, Z). The proposed work aims to correct the tilt automatically by measuring the pitch angle, yaw angle, and roll angle in X-axis, Z-axis, and Y-axis, respectively. For correction of the tilt around the Z-axis (pointing to the superior direction), image processing techniques, principal component analysis, and similarity measures are used. Also, for correction of the tilt around the X-axis (pointing to the right direction), morphological operations, and tilt correction around the Y-axis (pointing to the anterior direction), orthogonal regression is used. The proposed approach was applied to adjust the tilt observed in the T1- and T2-weighted MR images. The simulation study with the proposed algorithm yielded an error of 0.40 ± 0.09°, and it outperformed the other existing studies. The tilt angle (in degrees) obtained is ranged from 6.2 ± 3.94, 2.35 ± 2.61, and 5 ± 4.36 in X-, Z-, and Y-directions, respectively, by using the proposed algorithm. The proposed work corrects the tilt more accurately and robustly when compared with existing studies.

Spontaneous caloric restriction associated with increased leptin levels in obesity-resistant αMUPA mice.

BACKGROUND: αMUPA mice carry as a transgene the cDNA encoding urokinase-type plasminogen activator, a member of the plasminogen/plasmin system that functions in fibrinolysis and extracellular proteolysis. These mice spontaneously consume less food when fed ad libitum and live longer compared with wild-type (WT) control mice. αMUPA mice are obesity resistant and they share many similarities with calorically restricted animals. However, extensive metabolic characterization of this unique transgenic model has never been performed. METHOD: Metabolism of αMUPA mice was analyzed by measuring hormone, lipid and glucose levels in the serum, as well as gene and protein expression levels in the liver, hypothalamus and brainstem. RESULTS: αMUPA mice were found to be leaner than WT mice mainly because of reduced fat depots. Serum analyses showed that αMUPA mice have high levels of the anorexigenic hormones insulin and leptin, and low levels of the orexigenic hormone ghrelin. Analyses of brain neuropeptides showed that the transcript of the anorexigenic neuropeptide Pomc is highly expressed in the brainstem, whereas the expression of the orexigenic neuropeptides Npy, Orexin and Mch is blunted in the hypothalamus of αMUPA mice. In addition, adenosine monophosphate (AMP)-activated protein kinase (AMPK) levels were higher in the liver and lower in the hypothalamus, thus promoting simultaneously central reduction in appetite and peripheral loss of fat. The levels of SIRT1 were low in the liver, but high in the hypothalamus, a feature that αMUPA mice share with calorically restricted animals. CONCLUSION: Taken together, αMUPA mice exhibit a unique metabolic phenotype of low-calorie intake and high leptin levels, and could serve as a model for both spontaneous calorie restriction and resistance to obesity.

Imidazole-fe interaction in an aqueous chloride medium: effect of cathodic reduction of the native oxide.

The effect of the reduction of the native surface oxide of Fe on the binding of imidazole (as a corrosion inhibitor) with Fe in an aqueous brine solution has been addressed here. The surface interactions and corrosion inhibition efficiency were studied using X-ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS). It was shown that imidazole dissolved in brine bonds with the unreduced iron oxide surface via pyrrole-type nitrogen. However, surface interactions with Fe occur via both pyridine-type and pyrrole-type nitrogen atoms when imidazole is added to brine containing a cathodically reduced iron surface. The packing density of imidazole is found to be higher in the latter case with a corresponding increase in the corrosion inhibition efficiency.

Improvement in Obsessive-Compulsive Disorder Following Right Anterior Temporal Lobectomy and Amygdalohippocampectomy in a Patient with Refractory Temporal Lobe Epilepsy with Right Mesial Temporal Sclerosis.

There are reports of co-occurrence of obsessive-compulsive disorder (OCD) in patients with temporal lobe epilepsy (TLE). We present a report of a patient with refractory TLE due to hippocampal sclerosis with concomitant OCD on pharmacotherapy for both. She underwent surgery for standard anterior temporal lobectomy with amygdalohippocampectomy and reported improvement in obsessive-compulsive symptoms subsequently. We seek to further evidence of interaction between the two conditions and argue to undertake future research exploration on the same.

Crystal structure of human mitochondrial NAD(P)+-dependent malic enzyme: a new class of oxidative decarboxylases.

BACKGROUND: Malic enzymes catalyze the oxidative decarboxylation of malate to pyruvate and CO2 with the concomitant reduction of NAD(P)+ to NAD(P)H. They are widely distributed in nature and have important biological functions. Human mitochondrial NAD(P)+-dependent malic enzyme (mNAD-ME) may have a crucial role in the metabolism of glutamine for energy production in rapidly dividing cells and tumors. Moreover, this isoform is unique among malic enzymes in that it is a cooperative enzyme, and its activity is controlled allosterically. RESULTS: The crystal structure of human mNAD-ME has been determined at 2.5 A resolution by the selenomethionyl multiwavelength anomalous diffraction method and refined to 2.1 A resolution. The structure of the monomer can be divided into four domains; the active site of the enzyme is located in a deep cleft at the interface between three of the domains. Three acidic residues (Glu255, Asp256 and Asp279) were identified as ligands for the divalent cation that is required for catalysis by malic enzymes. CONCLUSIONS: The structure reveals that malic enzymes belong to a new class of oxidative decarboxylases. The tetramer of the enzyme appears to be a dimer of dimers. The active site of each monomer is located far from the tetramer interface. The structure also shows the binding of a second NAD+ molecule in a pocket 35 A away from the active site. The natural ligand for this second binding site may be ATP, an allosteric inhibitor of the enzyme.

Characterization of a mammary carcinoma elaborated factor stimulating gamma-glutamyltranspeptidase expression in bone marrow cells.

The elevation of bone marrow gamma-glutamyltranspeptidase (GGT) and alkaline phosphatase (AP) content in rats carrying mammary carcinoma 5A (MC), reproduced in a short-term (48-h) liquid culture of normal bone marrow cells, was found to be attributable to a blood-borne protein factor with an apparent molecular weight of 60,000. Partial purification, based on the extent of stimulation of GGT expression in this culture, increased the specific activity of the host serum from 1.5 to 40 units and that of MC extracts from 6 to 560 units. Production of the factor by MC in vitro, however, resulted in specific activities of 3000 units in the conditioned medium, and a further 60-fold purification was achieved by DEAE-cellulose, Sephadex G-100, and hydroxylapatite chromatography. The chemical characteristics of the MC-elaborated protein indicate nonidentity to previously isolated colony formation stimulating factors which also induced GGT (and AP) expression by rat bone marrow cells. Most of the AP inducing ability of the MC-serum and MC-conditioned medium copurified with and was still present in preparations with the highest specific activity vis à vis GGT. In mouse (instead of rat) bone marrow cells, however, no AP response accompanied the stimulation of GGT expression by MC (or colony formation stimulating factor) preparations.

Effect of tunicamycin on the turnover of epidermal growth factor receptors in cultured calf aorta smooth muscle cells. Comparison with IMR-90 human lung fibroblasts.

Treatment of cultured calf aorta smooth muscle cells with tunicamycin, a potent inhibitor of dolichol-mediated glycosylation, resulted in progressive loss of receptors for epidermal growth factor with 50% of receptors lost after 6 h. Receptor half-life was also 6 h with cycloheximide treatment but was 12 h with either actinomycin D or camptothesin treatment. The epidermal growth factor-induced processing (internalization and/or degradation) of residual receptors remaining after tunicamycin treatment appeared to be unaltered. 50% decrease in 125I-labeled epidermal growth factor binding was observed also with IMR-90 fibroblasts upon 6 h treatment with tunicamycin, although these cells were less sensitive to inhibition by tunicamycin of glycosylation and protein synthesis.

Regulation of insulin receptors in the human ovary: in vitro studies.

The association between insulin resistance and ovarian hyperstimulation has led to a hypothesis that insulin stimulates ovarian steroidogenesis. This possible effect of insulin on the ovary could be mediated by either the insulin receptor or the type I insulin-like growth factor (IGF) receptor, both of which have been described in the human ovary. We examined the in vitro regulation of insulin receptors by LH, FSH, multiplication-stimulating activity (MSA), and insulin in ovarian stromal fragments from 24 women. [125I]Insulin binding was measured in the presence and absence of increasing concentrations of insulin, IGF-I, LH, and FSH. Neither LH nor FSH competed with [125I]insulin for binding sites, but preincubation with LH or FSH reduced [125I]insulin binding by 19-38%. Preincubation with MSA reduced [125I]insulin binding by 34-48%. The affinity of the insulin receptors, determined by Scatchard analysis, did not change (Ka = 3.3 X 10(8) mol-1). A concentration of 10 ng/mL insulin in the preincubation medium reduced [125I]insulin binding by 40%, whereas an insulin concentration of 50 or 500 ng/mL completely obliterated specific [125I]insulin binding. [125I]Insulin binding fully recovered, however, 4 h after termination of tissue exposure to insulin. The specificity of [125I] insulin binding was confirmed by studies with IGF-I. We conclude that of the hormones examined, insulin is the most potent regulator of human ovarian insulin receptors in vitro. Down-regulation of insulin receptors by insulin was reversed within 4 h after withdrawal of insulin. MSA, FSH, and LH also down-regulated the number of human ovarian insulin receptors in vitro, but were less potent. These phenomena, if also present in vivo, could be important factors in the regulation of ovarian function by insulin in normal and pathological states.

Regulation of human ovarian insulin receptors in vivo.

Insulin participates in regulating ovarian function in normal and in pathological states. This effect of insulin may be mediated by ovarian insulin receptors. We have previously characterized human ovarian insulin receptors and began to examine their regulation in vitro. The present study examines regulation of human ovarian insulin receptors in vivo. Stromal ovarian tissue was obtained from 21 women during an indicated surgical procedure. Ten women were premenopausal and 11 were postmenopausal. Specific 125I-insulin binding to stromal ovarian fragments ranged from 2.5% to 7.3%/mg protein. 125I-insulin binding to stromal fragments correlated positively with 125I-insulin binding to circulating leucocytes (r = .57; P less than .01). When postmenopausal and premenopausal women were analyzed separately, this relationship persisted in postmenopausal women (r = .70; P less than .05), but not premenopausal women. 125I-insulin binding to stromal ovarian fragments correlated negatively with age (r = -.63; P = .005). 125I-insulin binding to stromal ovarian fragments tended to correlate negatively with plasma insulin levels in postmenopausal women (r = -.67; P = .06), but not in premenopausal women. Plasma insulin levels correlated negatively with serum SHBG (r = -.62; P = .003). The percent free testosterone levels correlated positively with plasma insulin levels in premenopausal women (r = .95; P = .0001), but not in postmenopausal women.(ABSTRACT TRUNCATED AT 250 WORDS)

Hormonally active long-term culture of human ovarian cells: initial characterization.

At present, to our knowledge, there are no long-term hormonally active cultures of normal human stromal ovarian cells. This report describes a method of developing such a system. Normal human stromal ovarian cells from three patients were cultured in McCoy's 5A tissue culture medium at 37 degrees C, 5% CO2, 95% humidity. The cells rapidly acquired fibroblastic appearance and grew in monolayers. The cells were trypsinized and passaged weekly. Tissue culture medium was collected and assayed for progesterone. The cells were initially producing 33.2 +/- 2.64 ng/mg protein of progesterone. By the eighth to twelfth passage, however, progesterone was no longer detectable in the medium. When the cells of the 12th passage were incubated with cholesterol, progesterone production resumed (8.9 +/- 0.09 ng/mg protein). When pregnenolone was used as a substrate, progesterone production was also present (8.06 +/- 0.24 ng/mg protein). Moreover, in the cells incubated with pregnenolone, progesterone production could be stimulated by adding 50 ng/mL FSH, or 50 ng/mL insulin to the incubation medium. Progesterone content of the medium increased to 11.3 +/- 0.29 ng/mg protein and 10.97 +/- 0.54 ng/mg protein respectively (P less than .05). The cells were also able to convert androstenedione to estrone. When the cells were incubated with 3 mumol/L androstenedione, estrone content of the medium ranged from 318 +/- 13 to 382 +/- 14 pg/mg protein. This finding suggests that aromatase is present in cultured human ovarian cells. These cells have now been maintained for 12 passages. A hormonally active long-term culture of normal human ovarian cells could be a useful tool in studies of ovarian physiology.

Mitogenic and chemotactic responses of human periodontal ligament cells to the different isoforms of platelet-derived growth factor.

A major focus of studies that center on regeneration of the periodontium is to determine the efficacy of the use of polypeptide growth factors. Platelet-derived growth factor has been reported to be a possible agent for clinical use. PDGF has various isoforms. Therefore, we decided to study the mitogenic and chemotactic responses of human periodontal ligament (PDL) cells to recombinant human PDGF-AB, AA, and BB. Addition of each isoform of PDGF to in vitro mitogenesis assays induced PDL cell proliferation in a dose-dependent manner. The maximum mitogenic effect was evident at the concentration of 100 ng/mL. In these assays, PDGF-BB was found to be the most potent mitogen. PDGF-AB elicited an intermediate response, and PDGF-AA was the least effective. The results of chemotaxis assays closely parallel those of the mitogenesis assays. PDGF-BB exhibited the most potent chemotactic effect. The maximal effect was observed at 10 ng/mL. The findings of these experiments indicate that PDGF-BB is more effective than the other isoforms in promoting mitogenesis and chemotaxis of PDL cells in vitro, and may therefore be a suitable ethical pharmaceutical for use in periodontal regeneration procedures.

Professional identification: a study of female students at a medical college in India.

This paper explores female medical students' identification with their profession at a medical college in India by comparing it with that of male students. The professional identification is conceptualized as having three elements: career commitment, career-satisfaction and professional self-image, each elicited by a single question. Compared to males, females were found to perceive medicine as more satisfying, and yet they were less sure than males of pursuing a medical career throughout their lives. The female students' commitment to their career was basically conditional, whereas for the males, it was primarily categorical. Additionally, females expressed less professional ambition than males and preferred different specialties. The main thrust of this paper is that the professional identification of both males and females is qualitatively different. The reasons for these differences are sought in sex-role socialization, cultural norms and informal social pressures at home and at the college.

Sex-stereotyping and sex-congruency: components in the sex role definition of medical specialties in India.

This paper draws a distinction between sex-stereotyping and sex-congruency by analyzing medical students' specialty preferences and choices and faculty views on the sex-suitability of various specialties at a medical college in India. Sex-stereotyping is seen as being rooted in and stemming from the nature of a society, particularly its normative structure. Thus the female stereotyping of obstetrics and gynecology in India is rooted in the widely accepted norm of sex segregation. Sex-congruency refers to the perceived compatibility between sex role expectations and the demands of a specialty. In addition, there was a growing realization among S.M.S. female medical students and among most of the faculty at the college that specialties such as ophthalmology, pathology and anesthesiology involving delicate surgery, less competition, infrequent emergencies and regular hours are better suited for females than are the more demanding specialties. The rationalization of sex-congruency seems to be much more logically consistent than stereotyping. Yet it is the latter that constitutes the most widely shared, and highly consensual rationalization within a given cultural context. These two forms of rationalization may overlap, but they basically differ from each other in many ways: stereotyping has a much longer past, is passed on from generation to generation, is culturally specific, highly crystallized, rigid, and resistant to change. Congruency, by contrast, is based on cross-culturally accepted standards, yet is less structured, more flexible and subject to local variations and finally to individual interpretation.

Intra-professional marriage: mate choices of medical students in India.

The desire to marry a doctor varied between male and female students at a medical school in India. The females' inclination was significantly stronger than that of males. Also, females were more likely than males to perceive their parents desire to arrange such a marriage for them. The correlation between students' desire to find a marriage match and the students' perception of such a desire in their parents, was higher for females than for males. A follow-up of the selected women students showed that a majority of those who expressed a desire to marry a doctor were in fact so married. Three explanations are advanced for this marriage pattern: (a) Status-congruency, which assumes that the higher status conferred on females by a medical education can best be maintained by marrying within the profession. (b) The second refers to the perceived complementarity between intra-professional marriage and the enactment of professional role (c) The third refers to the socialization of women medical students to prefer this marriage pattern.

Persistent insulin resistance after normalization of androgen levels in a woman with congenital adrenal hyperplasia. A case report.

Treatment of a woman who had 21-hydroxylase deficiency and insulin resistance resulted in normalization of her high androgen levels. The insulin resistance persisted, indicating that the hyperandrogenism was not contributing to it.

Scleral rigidity in glaucoma, before and during topical antiglaucoma drug therapy.

A study of 30 subjects (10 normal and 20 having glaucoma) was done to find out the scleral rigidity in glaucoma cases as compared to normal. The effect of miotics, timolol (0.25%) and pilocarpine (2%) eye drops on the scleral rigidity in cases of glaucoma was observed.