The biological activity of serum bacterial lipopolysaccharides associates with disease activity and likelihood of achieving remission in patients with rheumatoid arthritis.

BACKGROUND: Dysbiotic intestinal and oral microbiota have been implicated in the pathogenesis of rheumatoid arthritis (RA), but the mechanisms how microbiota could impact disease activity have remained elusive. The aim of this study was to assess the association of the biological activity of serum lipopolysaccharides (LPS) with disease activity and likelihood of achieving remission in RA patients. METHODS: We measured Toll-like receptor (TLR) 4-stimulating activity of sera of 58 RA patients with a reporter cell line engineered to produce secreted alkaline phosphatase in response to TLR4 stimulation. Levels of LPS-binding protein, CD14, and CD163 were determined by ELISA assays. RESULTS: The patient serum-induced TLR4 activation (biological activity of LPS) was significantly associated with inflammatory parameters and body mass index at baseline and at 12 months and with disease activity (DAS28-CRP, p<0.001) at 12 months. Importantly, baseline LPS bioactivity correlated with disease activity (p=0.031) and, in 28 early RA patients, the likelihood of achieving remission at 12 months (p=0.009). The level of LPS bioactivity was similar at baseline and 12-month visits, suggesting that LPS bioactivity is an independent patient-related factor. Neutralization of LPS in serum by polymyxin B abrogated the TLR4 signaling, suggesting that LPS was the major contributor to TLR4 activation. CONCLUSION: We describe a novel approach to study the biological activity of serum LPS and their impact in diseases. The results suggest that LPS contribute to the inflammatory burden and disease activity on patients with RA and that serum-induced TLR4 activation assays can serve as an independent prognostic factor. A graphical summary of the conclusions of the study.

Induction of remission in female rheumatoid arthritis patients is associated with stabilization of myocardial abnormalities: a prospective cardiac magnetic resonance follow-up study.

Objectives: To study whether female patients with active rheumatoid arthritis (RA) have myocardial abnormalities and whether progression of myocardial involvement can be attenuated by disease-modifying anti-rheumatic drugs (DMARDs).Method: Cardiac magnetic resonance (cMR; 1.5 or 3.0 T), including late gadolinium enhancement (LGE), T1 relaxation time, and ventricular functions, was performed in 30 patients with untreated active early RA starting first DMARDs, and 28 patients with chronic RA with inadequate response to conventional synthetic DMARDs starting biological DMARDs. cMR was repeated in RA patients 1 year later. cMR was conducted once in 22 fibromyalgia (FM) subjects and in 35 healthy volunteers serving as controls. All subjects were non-smoking females without coronary heart disease, heart failure, or diabetes.Results: Compared with controls, 58 RA patients had slightly lower ventricular function, although in the normal range, and longer T1 time at baseline. None of the FM subjects had LGE, but it was frequent in RA (67%). During the 1 year DMARD treatment, Disease Activity Score based on 28-joint count-C-reactive protein declined, ventricular functions tended to improve, but the number of patients with LGE remained unchanged. However, the number of LGE-positive heart segments either decreased or stayed the same in 91% of RA patients. In early RA patients, achieving tight remission was associated with LGE stabilization, after adjustment for age, metabolic syndrome, baseline inflammatory activity, and leisure-time physical activity.Conclusion: Treatment targeted to tight remission in early stages of RA seems to be important to prevent not only joint damage but also myocardial abnormalities.

Neural activity underlying the detection of an object movement by an observer during forward self-motion: Dynamic decoding and temporal evolution of directional cortical connectivity.

Relatively little is known about how the human brain identifies movement of objects while the observer is also moving in the environment. This is, ecologically, one of the most fundamental motion processing problems, critical for survival. To study this problem, we used a task which involved nine textured spheres moving in depth, eight simulating the observer's forward motion while the ninth, the target, moved independently with a different speed towards or away from the observer. Capitalizing on the high temporal resolution of magnetoencephalography (MEG) we trained a Support Vector Classifier (SVC) using the sensor-level data to identify correct and incorrect responses. Using the same MEG data, we addressed the dynamics of cortical processes involved in the detection of the independently moving object and investigated whether we could obtain confirmatory evidence for the brain activity patterns used by the classifier. Our findings indicate that response correctness could be reliably predicted by the SVC, with the highest accuracy during the blank period after motion and preceding the response. The spatial distribution of the areas critical for the correct prediction was similar but not exclusive to areas underlying the evoked activity. Importantly, SVC identified frontal areas otherwise not detected with evoked activity that seem to be important for the successful performance in the task. Dynamic connectivity further supported the involvement of frontal and occipital-temporal areas during the task periods. This is the first study to dynamically map cortical areas using a fully data-driven approach in order to investigate the neural mechanisms involved in the detection of moving objects during observer's self-motion.

Combined aerobic and resistance training decreases inflammation markers in healthy men.

Our primary aim was to study the effects of 24 weeks of combined aerobic and resistance training performed on the same day or on different days on inflammation markers. Physically active, healthy young men were randomly divided into three groups that performed: aerobic and resistance training consecutively in the same training session (SS) 2-3 days wk-1 or on alternating days (AD) 4-6 days wk-1 as well as control (C). The total training volume was matched in the training groups. The control group was asked to maintain their habitual physical activity and exercise level. Maximal leg press strength (1RM) and peak oxygen uptake (VO2peak ) were measured. Abdominal fat mass was estimated with dual-energy absorptiometry (DXA). High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α), and adipocytokines resistin, adiponectin, and leptin were analyzed from plasma samples. Training significantly reduced circulating hs-CRP, leptin, and resistin in both training groups (P<.05), whereas MCP-1 and TNF-α decreased only in AD (P<.05). Significant correlations were observed between changes in abdominal fat mass and corresponding changes in MCP-1, leptin, adiponectin, and resistin. Long-term combined aerobic and resistance training reduced markers of subclinical inflammation in healthy young men. The results indicate that a higher frequency of individual exercise sessions might be more beneficial with respect to the anti-inflammatory effects of physical activity. The decreases in inflammation markers seem to be related to decreases in abdominal fat mass.

Signalling Profiles of Blood Leucocytes in Sepsis and in Acute Pancreatitis in Relation to Disease Severity.

Intracellular signalling in blood leucocytes shows multiple aberrations in acute pancreatitis (AP) complicated by organ dysfunction (OD). We studied whether the aberrations associate with severity of AP and occur in sepsis complicated by OD. The study comprises 14 sepsis patients (11 with shock), 18 AP patients (nine mild; six moderately severe; three severe) and 28 healthy volunteers. Within 48 h after admission to hospital, phosphorylation of nuclear factor-ĸB (NF-ĸB), signal transducers and activators of transcription (STATs) 1,3, and extracellular signal-regulated kinases 1/2 were measured from stimulated or non-stimulated leucocytes using phosphospecific whole blood flow cytometry. In sepsis, as compared with healthy subjects, phosphorylated NF-ĸB levels of monocytes promoted by bacterial lipopolysaccharides, tumour necrosis factor or Escherichia coli cells were lower (P < 0.001 for all), pSTAT1 levels of monocytes promoted by IL-6 were lower (P < 0.05 for all), and STAT3 was constitutively phosphorylated in monocytes, neutrophils and lymphocytes (P < 0.001 for all). In AP, severity was associated with proportions of pSTAT1-positive monocytes and lymphocytes promoted by IL-6 (P < 0.01 for both), constitutive STAT3 phosphorylation in neutrophils (P < 0.05), but not with any of the pNF-ĸB levels. Monocyte pSTAT3 fluorescence intensity, promoted by IL-6, was lower in sepsis and AP patients with OD than in AP patients without OD (P < 0.001). Collectively, signalling aberrations in sepsis with OD mimic those described previously in AP with OD. Possibility that aberrations in STAT1 and STAT3 pathways provide novel markers predicting evolution of OD warrants studies including patients presenting without OD but developing it during follow-up.

Toward noninvasive monitoring of ongoing electrical activity of human uterus and fetal heart and brain.

OBJECTIVE: To evaluate whether a full-coverage fetal-maternal scanner can noninvasively monitor ongoing electrophysiological activity of maternal and fetal organs. METHODS: A simulation study was carried out for a scanner with an array of magnetic field sensors placed all around the torso from the chest to the hip within a horizontal magnetic shielding enclosure. The magnetic fields from internal organs and an external noise source were computed for a pregnant woman with a 35-week old fetus. Signal processing methods were used to reject the external and internal interferences, to visualize uterine activity, and to detect activity of fetal heart and brain. RESULTS: External interference was reduced by a factor of 1000, sufficient for detecting signals from internal organs when combined with passive and active shielding. The scanner rejects internal interferences better than partial-coverage arrays. It can be used to estimate currents around the uterus. It clearly detects spontaneous activity from the fetal heart and brain without averaging and weaker evoked brain activity at all fetal head positions after averaging. CONCLUSION: The simulated device will be able to monitor the ongoing activity of the fetal and maternal organs. SIGNIFICANCE: This type of scanner may become a novel tool in fetal medicine.

Adipokines played a limited role in predicting temporary growth differences between very low birthweight infants with and without bronchopulmonary dysplasia.

AIMS: This study explored whether growth was poorer among very low birthweight (VLBW) infants with bronchopulmonary dysplasia (BPD) and assessed adipokine levels as predictors of early growth. METHODS: We studied 53 VLBW infants born in Tampere University Hospital up to 12 months of corrected age (CA). The median gestational age of the 21 infants with BPD and 32 infants without BPD was 29 weeks, and the median birthweights were 930 (635-1470) and 1185 (650-1470) grams. Growth parameters, macronutrients intake and plasma levels of adipokines were measured. RESULTS: Bronchopulmonary dysplasia infants were lighter than controls until 36 weeks of CA, with catch-up growth achieved by three months of CA. Adipsin levels were lower in BPD infants at 28 days of postnatal age. High leptin levels seemed protective for low weight for height at nine months of CA. The duration of ventilator therapy predicted low weight for height, length for age and body mass index and BPD predicted low length for age at 12 months of CA. CONCLUSIONS: Catch-up growth in VLBW infants with BPD was achieved by three months of CA, but adipokines played a limited role in predicting growth. Shortening ventilator therapy could help growth in VLBW infants.

Impaired Akt Phosphorylation in Monocytes of Patients with Rheumatoid Arthritis.

It has been proposed that the Akt kinase pathway provides a regulatory mechanism to limit the inflammatory response. We examined the activation of Akt upon lipopolysaccharide (LPS) challenge in monocytes of patients with rheumatoid arthritis (RA) and correlated it with disease activity. Twelve subjects with recent-onset, DMARD-naïve RA, thirteen patients with chronic, DMARD therapy-non-responding RA and 27 healthy volunteers provided whole blood samples for phosphospecific flow cytometric measurement of unstimulated and LPS-stimulated Akt phosphorylation at serine 473 in monocytes, determined in relative fluorescence units (RFU). Activation capability, that is responsiveness of monocytes, was determined as the difference between stimulated and unstimulated samples and compared between groups using Mann-Whitney test. CRP and ESR, swollen and tender joint counts, patients' global assessment of disease activity, DAS28 score and plasma IL-6 determined by ELISA were correlated with Akt activation using Spearman method. Median (interquartile range) Akt activation capability was significantly lower in DMARD-naïve (379 RFU [285, 432], P = 0.016) and even lower in DMARD-non-responding RA (258 RFU [213, 338], P < 0.001), compared to healthy controls (505 RFU[408, 639]) and showed a negative correlation with swollen joint count (r = -0.48, CI -0.78 to -0.05, P = 0.014), CRP (r = -0.42, CI -0.80 to -0.02, P = 0.039) and plasma IL-6 levels (r = -0.44, CI -0.65 to -0.17, P = 0.001). In conclusion, Akt activation capability of monocytes is low in early untreated RA and even lower in chronic, DMARD-non-responding RA, suggesting a role for Akt pathway in the pathogenesis of RA.

Association study of arcuate nucleus neuropeptide Y neuron receptor gene variation and serum NPY levels in clozapine treated patients with schizophrenia.

BACKGROUND: Antipsychotic-induced weight gain (AIWG) leads to metabolic consequences and comorbidity, social stigmatization and nonadherence in patients with schizophrenia. Neuropeptide Y (NPY) has an important role in appetite and body weight regulation. Associations between AIWG and serum NPY levels, and genetic polymorphisms (SNPs) associated with its serum levels have been little studied in these patients. SUBJECTS AND METHODS: Associations between serum NPY concentration and other metabolic and inflammatory markers, and 215 SNPs in 21 genes (NPY gene, NPY receptor genes and genes encoding arcuate nucleus NPY neuron receptors) were studied in 180 patients with schizophrenia on clozapine treatment. RESULTS: The serum levels of NPY correlated with levels of resistin (r=0.31, P<0.001) and age (r=0.22, P=0.003). In the general linear univariate model the best-fitting model with explanatory factors age, serum resistin level, serum insulin level, BMI and gender explained 18.0% (P<0.001) of the variance of serum NPY. Genetic risk score (GRSNPY) analysis found twelve significant (P<0.05) serum NPY concentration related SNPs among α7 nicotinic acetylcholine receptor gene CHRNA7, insulin receptor gene INSR, leptin receptor gene LEPR, glucocorticoid receptor (GR) gene NR3C1, and NPY gene. However, after permutation test of gene score the predictive value of GRSNPY remained non-significant (P=0.078). CONCLUSIONS: Serum NPY level does not seem to be a feasible biomarker of AIWG. Serum NPY level alterations are not significantly associated with the candidate gene polymorphisms studied.

Changes in interleukin-6 levels during electroconvulsive therapy may reflect the therapeutic response in major depression.

OBJECTIVE: Interleukin-6 (IL-6) has been reported to be elevated in major depressive disorder (MDD) but decreased by antidepressive medication. IL-6 levels are markedly elevated both after epileptic seizures and single electroconvulsive therapy (ECT) session, but long-term changes in IL-6 levels after ECT have not been studied. The correlation between immediate and long-term changes in proinflammatory cytokines and outcome after ECT was investigated. METHOD: Thirty patients suffering from MDD participated in the study. IL-6, interleukin-1ß (IL-1ß) and interleukin-1 receptor antagonist (IL-1RA) levels were examined at baseline and at 2 and 4 h after the first, fifth and the last ECT sessions. The response to ECT was measured with Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: ECT repeatedly caused an increase in IL-6 levels at the 4-h time point. However, the baseline IL-6 levels decreased among remitters, but not among non-remitters, towards the end of ECT. IL-1ß levels were mostly below detectable level, and IL-1Ra levels did not change during and after ECT. CONCLUSION: ECT has distinct acute and long-term effects on IL-6 levels. Interestingly, the long-term effect of ECT on IL-6 seems to correlate with outcome, providing further evidence of the mechanism of action of ECT and supporting the inflammation theory in MDD.

Monosodium iodoacetate-induced inflammation and joint pain are reduced in TRPA1 deficient mice--potential role of TRPA1 in osteoarthritis.

OBJECTIVES: Intra-articularly injected monosodium iodoacetate (MIA) induces joint pathology mimicking osteoarthritis (OA) and it is a widely used experimental model of OA. MIA induces acute inflammation, cartilage degradation and joint pain. Transient Receptor Potential Ankyrin 1 (TRPA1) is an ion channel known to mediate nociception and neurogenic inflammation. Here, we tested the hypothesis that TRPA1 would be involved in the development of MIA-induced acute inflammation, cartilage changes and joint pain. METHODS: The effects of pharmacological blockade (by TCS 5861528) and genetic depletion of TRPA1 were studied in MIA-induced acute paw inflammation. Cartilage changes (histological scoring) and joint pain (weight-bearing test) in MIA-induced experimental OA were compared between wild type and TRPA1 deficient mice. The effects of MIA were also studied in primary human OA chondrocytes and in mouse cartilage. RESULTS: MIA evoked acute inflammation, degenerative cartilage changes and joint pain in wild type mice. Interestingly, these responses were attenuated in TRPA1 deficient animals. MIA-induced paw inflammation was associated with increased tissue levels of substance P; and the inflammatory edema was reduced by pretreatment with catalase, with the TRPA1 antagonist TCS 5861528 and with the neurokinin 1 receptor antagonist L703,606. In chondrocytes, MIA enhanced interleukin-1 induced cyclooxygenase-2 (COX-2) expression, an effect that was blunted by pharmacological inhibition and genetic depletion of TRPA1. CONCLUSIONS: TRPA1 was found to mediate acute inflammation and the development of degenerative cartilage changes and joint pain in MIA-induced experimental OA in the mouse. The results reveal TRPA1 as a potential mediator and drug target in OA.

Effects of FGF-2 and FGF receptor antagonists on MMP enzymes, aggrecan, and type II collagen in primary human OA chondrocytes.

OBJECTIVES: Fibroblast growth factor (FGF)-2 is a member of the FGF family and is found in the synovial fluid of patients with osteoarthritis (OA). The aim of this study was to investigate the effects of FGF-2 on human OA cartilage/chondrocytes by examining the association between FGF-2 and the cartilage degrading enzymes matrix metalloproteinase (MMP)-1 and MMP-13 and the major cartilage matrix components aggrecan and collagen II. METHOD: Cartilage samples were obtained from 97 OA patients undergoing total knee replacement surgery. Cartilage tissue cultures were conducted and levels of FGF-2, MMP-1, and MMP-13 released into the culture medium were measured by immunoassay. The effects of FGF-2 on the expression of MMP-1, MMP-13, aggrecan, and collagen II were further investigated in cultures of primary human OA chondrocytes. RESULTS: FGF-2, MMP-1, and MMP-13 were released into the culture medium from cartilage samples obtained from patients with OA. FGF-2 concentrations correlated positively with the concentrations of MMP-1 (r = 0.414, p < 0.001) and MMP-13 (r = 0.362, p < 0.001). FGF-2 also up-regulated the production of MMP-1 and MMP-13, and down-regulated the expression of aggrecan and collagen II, in human OA chondrocyte cultures. Furthermore, FGF receptor antagonists AZD4547 and NVP-BGJ398 down-regulated the expression of MMP-1 and MMP-13 and up-regulated aggrecan and collagen II both in the absence and in the presence of exogenous FGF-2. CONCLUSIONS: Our results suggest that, in contrast to its growth factor-like effects in some other tissues, FGF-2 induces catabolic effects in human OA cartilage. Moreover, FGF receptor antagonists showed promising beneficial effects on the balance of catabolic and anabolic factors within OA cartilage.

Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia.

Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment.

Aurothiomalate inhibits the expression of mPGES-1 in primary human chondrocytes.

OBJECTIVES: Microsomal prostaglandin E synthase-1 (mPGES-1) is a terminal enzyme in the production of prostaglandin E2 (PGE2) and its expression is upregulated during inflammation. mPGES-1 is considered as a potential drug target for the treatment of arthritis to reduce adverse effects related to the current non-steroidal anti-inflammatory drugs (NSAIDs). Our aim was to study the expression of mPGES-1 in primary human chondrocytes and whether the expression is affected by clinically used antirheumatic drugs. METHOD: Primary human chondrocytes were isolated from cartilage samples obtained from patients undergoing total knee replacement surgery. Expression of mPGES-1 was studied by quantitative real-time polymerase chain reaction (PCR) and Western blot analysis. PGE2 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: mPGES-1 expression in primary human chondrocytes was enhanced when the cells were exposed to interleukin-1ß (IL-1ß) and mPGES-1 protein levels continued to increase up to the 96-h follow-up. Aurothiomalate inhibited mPGES-1 expression and PGE2 production in a dose-dependent manner, as did the anti-inflammatory steroid dexamethasone. Other disease-modifying antirheumatic drugs (DMARDs) studied (sulfasalazine, methotrexate, and hydroxychloroquine) did not alter mPGES-1 expression. CONCLUSIONS: The results introduce aurothiomalate as the first, and so far the only, DMARD found to be able to inhibit mPGES-1 expression. The effect is likely involved in the mechanisms of action of this gold-containing DMARD in rheumatic diseases. The results are implicated in the regulatory mechanisms of mPGES-1 expression, which are under intensive research.

EEG functional connectivity is partially predicted by underlying white matter connectivity.

Over the past decade, networks have become a leading model to illustrate both the anatomical relationships (structural networks) and the coupling of dynamic physiology (functional networks) linking separate brain regions. The relationship between these two levels of description remains incompletely understood and an area of intense research interest. In particular, it is unclear how cortical currents relate to underlying brain structural architecture. In addition, although theory suggests that brain communication is highly frequency dependent, how structural connections influence overlying functional connectivity in different frequency bands has not been previously explored. Here we relate functional networks inferred from statistical associations between source imaging of EEG activity and underlying cortico-cortical structural brain connectivity determined by probabilistic white matter tractography. We evaluate spontaneous fluctuating cortical brain activity over a long time scale (minutes) and relate inferred functional networks to underlying structural connectivity for broadband signals, as well as in seven distinct frequency bands. We find that cortical networks derived from source EEG estimates partially reflect both direct and indirect underlying white matter connectivity in all frequency bands evaluated. In addition, we find that when structural support is absent, functional connectivity is significantly reduced for high frequency bands compared to low frequency bands. The association between cortical currents and underlying white matter connectivity highlights the obligatory interdependence of functional and structural networks in the human brain. The increased dependence on structural support for the coupling of higher frequency brain rhythms provides new evidence for how underlying anatomy directly shapes emergent brain dynamics at fast time scales.

Effect of the antenna-body distance on the on-ext and on-on channel link path gain in UWB WBAN applications.

This paper investigates the effect of the operation distance (i.e., practical use) between an antenna and a human body on wireless body area network (WBAN) channel path gain. Different use cases in WBAN on-external (ext) and on-on links with different antenna-body distances for ultra wideband (UWB) technology are considered. These studies are carried out with two types of planar UWB antennas in the vicinity of a real human body. Corresponding scenarios are repeated by computer simulations, and differences between these environs (i.e., challenges in the modelling of the measurement situation) are analysed and discussed.

Time-frequency mixed-norm estimates: sparse M/EEG imaging with non-stationary source activations.

Magnetoencephalography (MEG) and electroencephalography (EEG) allow functional brain imaging with high temporal resolution. While solving the inverse problem independently at every time point can give an image of the active brain at every millisecond, such a procedure does not capitalize on the temporal dynamics of the signal. Linear inverse methods (minimum-norm, dSPM, sLORETA, beamformers) typically assume that the signal is stationary: regularization parameter and data covariance are independent of time and the time varying signal-to-noise ratio (SNR). Other recently proposed non-linear inverse solvers promoting focal activations estimate the sources in both space and time while also assuming stationary sources during a time interval. However such a hypothesis holds only for short time intervals. To overcome this limitation, we propose time-frequency mixed-norm estimates (TF-MxNE), which use time-frequency analysis to regularize the ill-posed inverse problem. This method makes use of structured sparse priors defined in the time-frequency domain, offering more accurate estimates by capturing the non-stationary and transient nature of brain signals. State-of-the-art convex optimization procedures based on proximal operators are employed, allowing the derivation of a fast estimation algorithm. The accuracy of the TF-MxNE is compared with recently proposed inverse solvers with help of simulations and by analyzing publicly available MEG datasets.

Language lateralization represented by spatiotemporal mapping of magnetoencephalography.

BACKGROUND AND PURPOSE: Determination of hemispheric language dominance is critical for planning epilepsy surgery. We assess the usefulness of spatiotemporal source analysis of magnetoencephalography for determining language laterality. MATERIALS AND METHODS: Thirty-five patients with epilepsy were studied. The patients performed a semantic word-processing task during MEG recording. Epochs containing language-related neuromagnetic activity were averaged after preprocessing. The averaged data between 250 and 550 ms after stimulus were analyzed by using dynamic statistical parametric mapping. ROIs were obtained in the opercular and triangular parts of the inferior frontal gyrus, superior temporal gyrus, and supramarginal gyrus in both hemispheres. We calculated laterality indices according to 1) dSPM-amplitude method, based on the amplitude of activation in the ROIs, and 2) dSPM-counting method, based on the number of unit dipoles with activation over a threshold in the ROIs. The threshold was determined as half of the maximum value in all ROIs for each patient. A LI ≥0.10 or ≤-0.10 was considered left- or right-hemisphere dominance, respectively; a LI between -0.10 and 0.10 was considered bilateral. All patients underwent an intracarotid amobarbital procedure as part of presurgical evaluation. RESULTS: The dSPM-counting method demonstrated laterality consistent with the IAP in 32 of 35 patients (91.4%), the remaining 3 (8.6%) demonstrated bilateral language representation, whereas the dSPM-amplitude method showed 18 (51.4%) concordant and 17 (48.6%) bilateral. No laterality opposite to the IAP was found. CONCLUSIONS: Spatiotemporal mapping of language lateralization with the dSPM-counting method may reduce the necessity for an IAP in as many as 90% of patients.

Multimodal imaging of spike propagation: a technical case report.

We report an 11-year-old boy with intractable epilepsy, who had cortical dysplasia in the right superior frontal gyrus. Spatiotemporal source analysis of MEG and EEG spikes demonstrated a similar time course of spike propagation from the superior to inferior frontal gyri, as observed on intracranial EEG. The tractography reconstructed from DTI showed a fiber connection between these areas. Our multimodal approach demonstrates spike propagation and a white matter tract guiding the propagation.

Adoption of single incision laparoscopic cholecystectomy in small-volume hospitals: initial experiences of 51 consecutive procedures.

BACKGROUND AND AIMS: Laparoscopic cholecystectomy (LC) via three or four ports has been the standard operation for gallstone disease. Recently, the development of multichannel port devices has allowed LCs to be performed through a single fascial incision in the umbilicus. Here, we report our experiences of the adoption of the single incision laparoscopic cholecystectomy (SILC) in two small-volume community hospitals. MATERIAL AND METHODS: From January until July 2010, 51 consecutive patients (41 females and 10 males, the mean age 44 (21-75) years, BMI 26 (18-35)) underwent elective SILC for symptomatic gallstone disease in Salo (n = 29) and Loimaa (n = 22) hospitals. RESULTS: Of the 51 operations, 42 (82%) were accomplished without additional troacars. Seven (14%) procedures were converted to multiple-port technique and two (4%) to open cholecystectomy. In 25 (49%) operations, transabdominal retraction sutures through the gallbladder were used to maintain a good view of the triangle of Calot. The mean operative time was 74 (31-155) min. No major intraoperative complications occurred. The mean hospital stay was 0.6 (0-3) days. During a mean follow up of 4 (1-7) months, five (10%) patients had wound infection, and one (2%) had hematoma and prolonged pain in the insertion site of the retraction suture. One (2%) patient was reoperated for continuous pain in umbilical wound without findings at operation but with good results. One (2%) patient had subphrenic abscess seven months postoperatively. CONCLUSIONS: Our initial experiences indicate that SILC can be adopted without major complications in small-volume hospitals but the rate of wound infections seems to increase with the introduction of SIL.