Subspace partitioning in the human prefrontal cortex resolves cognitive interference.

The human prefrontal cortex (PFC) constitutes the structural basis underlying flexible cognitive control, where mixed-selective neural populations encode multiple task features to guide subsequent behavior. The mechanisms by which the brain simultaneously encodes multiple task-relevant variables while minimizing interference from task-irrelevant features remain unknown. Leveraging intracranial recordings from the human PFC, we first demonstrate that competition between coexisting representations of past and present task variables incurs a behavioral switch cost. Our results reveal that this interference between past and present states in the PFC is resolved through coding partitioning into distinct low-dimensional neural states; thereby strongly attenuating behavioral switch costs. In sum, these findings uncover a fundamental coding mechanism that constitutes a central building block of flexible cognitive control.

Multiple intrinsic timescales govern distinct brain states in human sleep.

Human sleep exhibits multiple, recurrent temporal regularities, ranging from circadian rhythms to sleep stage cycles and neuronal oscillations during non-rapid eye movement (non-REM) sleep. Moreover, recent evidence revealed a functional role of aperiodic activity, which reliably discriminates different sleep stages. Aperiodic activity is commonly defined as the spectral slope χ of the 1/frequency (1/fχ) decay function of the electrophysiological power spectrum. However, several lines of inquiry now indicate that the aperiodic component of the power spectrum might be better characterized by a superposition of several decay processes with associated timescales. Here, we determined multiple timescales, which jointly shape aperiodic activity using human intracranial encephalography (iEEG). Across three independent studies (47 participants, 23 female), our results reveal that aperiodic activity reliably dissociated sleep stage-dependent dynamics in a regionally-specific manner. A principled approach to parametrize aperiodic activity delineated several, spatially- and state-specific timescales. Lastly, we employed pharmacological modulation by means of propofol anesthesia to disentangle state-invariant timescales that may reflect physical properties of the underlying neural population from state-specific timescales that likely constitute functional interactions. Collectively, these results establish the presence of multiple intrinsic timescales that define the electrophysiological power spectrum during distinct brain states.Significance Statement Sleep is characterized by prominent temporal regularities. In this study, we unveil a previously unrecognized principle that governs neural activity during human sleep. Our results shed light on the existence of a set of intrinsic timescales that fundamentally define the current state of the sleeping brain. These timescales serve as indicators of both physiological and functional interactions within the underlying neural population. Through pharmacological modulation, we differentiated state-specific functional interactions from state-invariant timescales, suggesting that the latter may reflect the inherent physical properties of the neural population at play.

Symptom Change during Waitlist for Medicated and Nonmedicated Patients with Chronic Depression.

INTRODUCTION: Patients seeking psychotherapy often spend time on waitlist (WL), the effect of which is largely unknown. WL patients may forego alternative non-psychotherapeutic assistance and thus do more poorly than had they not been placed on a WL. The course of symptoms might also be influenced by use of antidepressant medication (ADM), an issue that remains unexplored in the literature. OBJECTIVE: In a naturalistic setting, WL symptom change before inpatient psychotherapy (mean weeks of waiting = 22.6) was assessed in a sample (N = 313) of chronically depressed patients. METHODS: Using the Beck Depression Inventory-II, patients' symptoms were tracked at assessment, when admitted to treatment (i.e., after WL), at posttreatment and 1-year follow-up. Multilevel growth curve analysis was used to examine waitlist change for the whole sample as well as for ADM users and nonmedicated patients. RESULTS: Symptoms were reduced significantly from assessment to admittance (Cohen's d = 0.47). Symptoms reduced less for ADM users (d = 0.39) than for nonmedicated patients (d = 0.65). CONCLUSION: The findings indicate that chronically depressed patients experience a decrease in symptoms during WL, quite likely due to treatment expectations. We discuss whether less symptom improvement for ADM users could be attributed to iatrogenic comorbidity and a higher degree of demoralization in this group.

Early spectral EEG in preterm infants correlates with neurocognitive outcomes in late childhood.

BACKGROUND: Evidence regarding the predictive value of early amplitude-integrated electroencephalography (aEEG)/EEG on neurodevelopmental outcomes at school age and beyond is lacking. We  aimed to investigate whether there is an association between early postnatal EEG and neurocognitive outcomes in late childhood. METHODS: This study is an observational prospective cohort study of premature infants with a gestational age <28 weeks. The total absolute band powers (tABP) of the delta, theta, alpha, and beta bands were analyzed from EEG recordings during the first three days of life. At 10-12 years of age, neurocognitive outcomes were assessed using the Wechsler Intelligence Scale for Children 4th edition (WISC-IV), Vineland adaptive behavior scales 2nd edition, and Behavior Rating Inventory of Executive Function (BRIEF). The mean differences in tABP were assessed for individuals with normal versus unfavorable neurocognitive scores. RESULTS: Twenty-two infants were included. tABP values in all four frequency bands were significantly lower in infants with unfavorable results in the main composite scores (full intelligence quotient, adaptive behavior composite score, and global executive composite score) on all three tests (p < 0.05). CONCLUSIONS: Early postnatal EEG has the potential to assist in predicting cognitive outcomes at 10-12 years of age in extremely premature infants <28 weeks' gestation. IMPACT: Evidence regarding the value of early postnatal EEG in long-term prognostication in preterm infants is limited. Our study suggests that early EEG spectral analysis correlates with neurocognitive outcomes in late childhood in extremely preterm infants. Early identification of infants at-risk of later impairment is important to initiate early and targeted follow-up and intervention.

Hypertension attenuates the link of osteoprotegerin to reduced baroreflex sensitivity in type 2 diabetes mellitus patients on oral antidiabetic and antihypertensive therapy - a cross sectional study.

PURPOSE: Decreased baroreflex sensitivity (BRS) has been shown to be a marker of cardiovascular (CV) risk. In the present study, the difference in CV risk biomarkers in type 2 diabetes (T2D) patients receiving oral antidiabetic drugs (OAD) with and without hypertension has been assessed. MATERIALS AND METHODS: Ninety-two T2D patients on OAD without hypertension (control group) and eighty-eight diabetic patients with hypertension on OAD and antihypertensive drugs (test group) matched for age, gender, body mass index, serum glucose, glycated haemoglobin, and duration of the disease were recruited for the study. Their blood pressure (BP) variability including BRS, heart rate variability (HRV), insulin, lipid profile, osteoprotegerin (OPG), and tumor necrosis factor-α (TNF-α) were estimated. The association of various factors with BRS was assessed by Spearman correlation and multiple regression analysis. RESULTS: BRS was decreased (13.90 ± 5.27 vs 6.76 ± 4.58), HRV sympathetic indices [LFnu, LF-HF ratio (1.30 ± 0.49 vs 1.93 ± 0.62)], HOMA-IR, atherogenic index of plasma (AIP), OPG (223.08 ± 103.86 vs 287.60 ± 121.36) and TNF-α were increased, and parasympathetic indices [TP (1012.90 ± 316.18 vs 625.88 ± 229.84), RMSSD, SDNN, NN50, pNN50] were decreased in the test group compared to control group. In control group, parasympathetic indices, AIP, OPG, and TNF-α had a significant correlation and OPG had an independent association (ß - 0.344; p 0.004) with BRS. In test group, BP, LF-HF ratio, parasympathetic indices, AIP, OPG, and TNF-α had significant correlation, and TNF-α alone (ß - 0.297; p 0.022) had an independent contribution to decreased BRS. CONCLUSION: Despite antidiabetic and antihypertensive treatments, T2D patients with hypertension had more cardiometabolic risks in comparison to normotensive T2D patients. Inflammation could be the inciting factor for rise in BP and decrease in BRS (CV risk) in hypertensive T2D patients. Hypertension in diabetes could attenuate the link of OPG to the reduction in BRS. Reduction in BRS could be a physiological marker of CV risk in T2D patients treated with OAD.

Top-Down Attentional Modulation in Human Frontal Cortex: Differential Engagement during External and Internal Attention.

Decades of electrophysiological research on top-down control converge on the role of the lateral frontal cortex in facilitating attention to behaviorally relevant external inputs. However, the involvement of frontal cortex in the top-down control of attention directed to the external versus internal environment remains poorly understood. To address this, we recorded intracranial electrocorticography while subjects directed their attention externally to tones and responded to infrequent target tones, or internally to their own thoughts while ignoring the tones. Our analyses focused on frontal and temporal cortices. We first computed the target effect, as indexed by the difference in high frequency activity (70-150 Hz) between target and standard tones. Importantly, we then compared the target effect between external and internal attention, reflecting a top-down attentional effect elicited by task demands, in each region of interest. Both frontal and temporal cortices showed target effects during external and internal attention, suggesting this effect is present irrespective of attention states. However, only the frontal cortex showed an enhanced target effect during external relative to internal attention. These findings provide electrophysiological evidence for top-down attentional modulation in the lateral frontal cortex, revealing preferential engagement with external attention.

It's the therapist and the treatment: The structure of common therapeutic relationship factors.

Objective: Prior research has established that common therapeutic relationship factors are potent predictors of change in psychotherapy, but such factors are typically studied one at a time and their underlying structure when studied simultaneously is not clear. We assembled empirically validated relationship factors (e.g., therapist empathy; patient expectations; agreement about goals) into a single instrument and subjected it to factor analysis. Method: The instrument was applied to patients (N = 332) undergoing intensive psychotherapy of different types for depressive disorders, anxiety disorders, eating disorders, and childhood trauma in an inpatient specialized mental health setting. In order to examine the psychometric properties of the scale, we used half the sample (N=164) to conduct exploratory factor analysis (EFA) and parallel analysis before we tested the solution using exploratory structural equation modeling (ESEM) on the second half of the sample (N=168). Measurement invariance analysis was conducted to examine the stability of the factor structure. Results: The analysis yielded two factors, which were termed 1. "Confidence in the therapist" and 2. "Confidence in the treatment." Discussion: When assessed simultaneously, patients differentiate between their evaluation of the therapist and of the treatment. The results indicate that there is substantial overlap among previously established relationship factors.Trial registration: ClinicalTrials.gov identifier: NCT03503981.

Intracranial Recordings Demonstrate Both Cortical and Medial Temporal Lobe Engagement in Visual Search in Humans.

Visual search is a fundamental human behavior, providing a gateway to understanding other sensory domains as well as the role of search in higher-order cognition. Search has been proposed to include two component processes: inefficient search (Search) and efficient search (Pop-out). According to extant research, these two processes map onto two separable neural systems located in the frontal and parietal association cortices. In this study, we use intracranial recordings from 23 participants to delineate the neural correlates of Search and Pop-out with an unprecedented combination of spatiotemporal resolution and coverage across cortical and subcortical structures. First, we demonstrate a role for the medial temporal lobe in visual search, on par with engagement in frontal and parietal association cortex. Second, we show a gradient of increasing engagement over anatomical space from dorsal to ventral lateral frontal cortex. Third, we confirm previous intracranial work demonstrating nearly complete overlap in neural engagement across cortical regions in Search and Pop-out. We further demonstrate Pop-out selectivity, manifesting as activity increase in Pop-out as compared to Search, in a distributed set of sites including frontal cortex. This result is at odds with the view that Pop-out is implemented in low-level visual cortex or parietal cortex alone. Finally, we affirm a central role for the right lateral frontal cortex in Search.

Dynamic frontotemporal systems process space and time in working memory.

How do we rapidly process incoming streams of information in working memory, a cognitive mechanism central to human behavior? Dominant views of working memory focus on the prefrontal cortex (PFC), but human hippocampal recordings provide a neurophysiological signature distinct from the PFC. Are these regions independent, or do they interact in the service of working memory? We addressed this core issue in behavior by recording directly from frontotemporal sites in humans performing a visuospatial working memory task that operationalizes the types of identity and spatiotemporal information we encounter every day. Theta band oscillations drove bidirectional interactions between the PFC and medial temporal lobe (MTL; including the hippocampus). MTL theta oscillations directed the PFC preferentially during the processing of spatiotemporal information, while PFC theta oscillations directed the MTL for all types of information being processed in working memory. These findings reveal an MTL theta mechanism for processing space and time and a domain-general PFC theta mechanism, providing evidence that rapid, dynamic MTL-PFC interactions underlie working memory for everyday experiences.

Endophyte roles in nutrient acquisition, root system architecture development and oxidative stress tolerance.

Plants associate with communities of microbes (bacteria and fungi) that play critical roles in plant development, nutrient acquisition and oxidative stress tolerance. The major share of plant microbiota is endophytes which inhabit plant tissues and help them in various capacities. In this article, we have reviewed what is presently known with regard to how endophytic microbes interact with plants to modulate root development, branching, root hair formation and their implications in overall plant development. Endophytic microbes link the interactions of plants, rhizospheric microbes and soil to promote nutrient solubilization and further vectoring these nutrients to the plant roots making the soil-plant-microbe continuum. Further, plant roots internalize microbes and oxidatively extract nutrients from microbes in the rhizophagy cycle. The oxidative interactions between endophytes and plants result in the acquisition of nutrients by plants and are also instrumental in oxidative stress tolerance of plants. It is evident that plants actively cultivate microbes internally, on surfaces and in soils to acquire nutrients, modulate development and improve health. Understanding this continuum could be of greater significance in connecting endophytes with the hidden half of the plant that can also be harnessed in applied terms to enhance nutrient acquisition through the development of favourable root system architecture for sustainable production under stress conditions.

Validation of a new approach for distinguishing anesthetized from awake state in patients using directed transfer function applied to raw EEG.

We test whether a measure based on the directed transfer function (DTF) calculated from short segments of electroencephalography (EEG) time-series can be used to monitor the state of the patients also during sevoflurane anesthesia as it can for patients undergoing propofol anesthesia. We collected and analyzed 25-channel EEG from 7 patients (3 females, ages 41-56 years) undergoing surgical anesthesia with sevoflurane, and quantified the sensor space directed connectivity for every 1-s epoch using DTF. The resulting connectivity parameters were compared to corresponding parameters from our previous study (n = 8, patients anesthetized with propofol and remifentanil, but otherwise using a similar protocol). Statistical comparisons between and within studies were done using permutation statistics, a data driven algorithm based on the DTF-parameters was employed to classify the epochs as coming from awake or anesthetized state. According to results of the permutation tests, DTF-parameter topographies were significantly different between the awake and anesthesia state at the group level. However, the topographies were not significantly different when comparing results computed from sevoflurane and propofol data, neither in the awake nor in anesthetized state. Optimizing the algorithm for simultaneously having high sensitivity and specificity in classification yielded an accuracy of 95.1% (SE = 0.96%), with sensitivity of 98.4% (SE = 0.80%) and specificity of 94.8% (SE = 0.10%). These findings indicate that the DTF changes in a similar manner when humans undergo general anesthesia caused by two distinct anesthetic agents with different molecular mechanisms of action.

Increased osteoprotegerin level is associated with impaired cardiovagal modulation in type-2 diabetic patients treated with oral antidiabetic drugs.

BACKGROUND: An increased osteoprotegerin (OPG) level has been reported in both type-2 diabetes mellitus (T2DM) and cardiovascular diease (CVD) that are linked to sympathovagal imbalance (SVI). We explored the link of osteoprotegerin with cardiovagal modulation in T2DM. METHODS: We assessed fasting serum OPG, high-sensitive C-reactive protein (hsCRP), glucose, insulin and lipid profile in patients having T2DM receiving oral antidiabetic drugs (OAD) (n = 42) compared with age, gender and body composition-matched healthy participants without diabetes (n = 42). Rate pressure product (RPP), spectral indices of heart rate variability (HRV) and body composition were recorded in both the groups. Association of HOMA-IR and OPG with various parameters were assessed. RESULTS: Osteoprotegerin, HOMA-IR, hsCRP, coronary lipid risk factor were significantly increased, markers of cardiovagal modulation (TP, SDNN, RMSSD) were considerably decreased, ratio of low-frequency to high-frequency (LH-HF ratio), the indicator of SVI, and RPP, the marker of myocardial work stress were significantly higher in patients with diabetes, suggesting an overall elevated CVD risks in them. HOMA-IR was correlated with RMSSD, lipid risk factors and OPG. Rise in OPG was correlated with decreased cardiovagal modulation in patients with diabetes. There was significant contribution of OPG in decreasing TP, suggesting impaired cardiovagal modulation. CONCLUSION: T2DM patients receiving OAD had higher cardiometabolic risks compared to age, gender and body composition-matched healthy individuals. Increased level of OPG is linked to decreased cardiovagal modulation in T2DM patients.

Safety aspects of antiepileptic drugs-a population-based study of adverse effects relative to changes in utilisation.

PURPOSE: Antiepileptic drugs (AEDs) are increasingly used, and knowledge about adverse effects is scarce based on clinical studies. The purpose of the present study was to characterise adverse effects reports of AEDs in Norway relative to changes in utilisation in various indications from population-based data to elucidate important safety aspects of use of AEDs. METHODS: Aggregated data of adverse effects reported for AEDs in Norway from the EudraVigilance-database (2004-2013) in addition to indication-specific use of AEDs during 2004-2015 from the Norwegian Prescription Database were used. RESULTS: The use of AEDs increased twofold the last decade due to use in psychiatry and neuropathic pain: lamotrigine, pregabalin, gabapentin, valproate, and carbamazepine. There were 1593 adverse effects reported (403 Individual Case Safety Reports, 2/3 women), 0-95 years (mean 46). Most adverse effects were reported for pregabalin (593), carbamazepine (265), lamotrigine (206), gabapentin (144), and valproate (119), where pregabalin had by far the highest reports in relation to the number of users. The most frequently reported adverse drug effects included rash, dizziness, cross-sensitivity reactions, and pyrexia. Overall, nervous system disorders constitute the largest organ class with the majority of the reports. Reporting of fatal outcomes is mandatory, and sudden unexplained death in epilepsy (SUDEP) was reported in 34 occasions. CONCLUSIONS: This study demonstrates that most adverse effects reported concerned AEDs increasingly used in non-epilepsy indications: neuropathic pain (pregabalin, gabapentin, carbamazepine) and psychiatry (lamotrigine, valproate, carbamazepine). Pregabalin had the highest prevalence of adverse effects reported in relation to number of users. This elucidates an important part of pharmacovigilance for improved safety and considerations in clinical practice.

Metacognition and cognition in inpatient MCT and CBT for comorbid anxiety disorders: A study of within-person effects.

Psychotherapists have long questioned what mediating processes are linked to outcome of psychotherapy. Few studies examining this question have assessed within-person changes in the process outcome relationship over time. The present study examined changes in cognition and metacognition over the course of therapy using a dataset from a randomized controlled trial comparing Metacognitive therapy (MCT) and Cognitive-behavioral therapy (CBT). The sample included 74 patients measured on process and symptom instruments weekly throughout therapy. Multilevel longitudinal models (sessions nested within patients) were used to examine the relationship between metacognition, cognition, and anxiety. Main effects of metacognition and cognition on anxiety and the interaction with treatment, as well as the reciprocal relationships, were investigated. The results indicate a main effect of both cognitions and metacognitions on predicting anxiety. However, there was no interaction with treatment condition. The reciprocal relationship of anxiety on metacognitions was larger in MCT compared with CBT. This is the first study documenting within-person effects of both cognitions and metacognitions on anxiety over the course of therapy. Implications for therapy are discussed. (PsycINFO Database Record

Seizure outcomes of temporal lobe epilepsy surgery in patients with normal MRI and without specific histopathology.

BACKGROUND: Seizure outcome following surgery in pharmacoresistant temporal lobe epilepsy patients with normal magnetic resonance imaging and normal or non-specific histopathology is not sufficiently presented in the literature. METHODS: In a retrospective design, we reviewed data of 263 patients who had undergone temporal lobe epilepsy surgery and identified 26 (9.9%) who met the inclusion criteria. Seizure outcomes were determined at 2-year follow-up. Potential predictors of Engel class I (satisfactory outcome) were identified by logistic regression analyses. RESULTS: Engel class I outcome was achieved in 61.5% of patients, 50% being completely seizure free (Engel class IA outcome). The strongest predictors of satisfactory outcome were typical ictal seizure semiology (p = 0.048) and localised ictal discharges on scalp EEG (p = 0.036). CONCLUSION: Surgery might be an effective treatment choice for the majority of these patients, although outcomes are less favourable than in patients with magnetic resonance imaging-defined lesional temporal lobe epilepsy. Typical ictal seizure semiology and localised ictal discharges on scalp EEG were predictors of Engel class I outcome.

Current use of imaging and electromagnetic source localization procedures in epilepsy surgery centers across Europe.

OBJECTIVE: In 2014 the European Union-funded E-PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers. METHODS: A survey on the clinical use of imaging, electromagnetic source localization, and postprocessing methods in epilepsy surgery candidates was distributed among the 25 centers of the consortium. A descriptive analysis was performed, and results were compared to existing guidelines and recommendations. RESULTS: Response rate was 96%. Standard epilepsy magnetic resonance imaging (MRI) protocols are acquired at 3 Tesla by 15 centers and at 1.5 Tesla by 9 centers. Three centers perform 3T MRI only if indicated. Twenty-six different MRI sequences were reported. Six centers follow all guideline-recommended MRI sequences with the proposed slice orientation and slice thickness or voxel size. Additional sequences are used by 22 centers. MRI postprocessing methods are used in 16 centers. Interictal positron emission tomography (PET) is available in 22 centers; all using 18F-fluorodeoxyglucose (FDG). Seventeen centers perform PET postprocessing. Single-photon emission computed tomography (SPECT) is used by 19 centers, of which 15 perform postprocessing. Four centers perform neither PET nor SPECT in children. Seven centers apply magnetoencephalography (MEG) source localization, and nine apply electroencephalography (EEG) source localization. Fourteen combinations of inverse methods and volume conduction models are used. SIGNIFICANCE: We report a large variation in the presurgical diagnostic workup among epilepsy surgery centers across Europe. This diversity underscores the need for high-quality systematic reviews, evidence-based recommendations, and harmonization of available diagnostic presurgical methods.

Changes in utilisation of antiepileptic drugs in epilepsy and non-epilepsy disorders-a pharmacoepidemiological study and clinical implications.

PURPOSE: The purpose of this study was to investigate changes in utilisation of antiepileptic drugs (AEDs) in epilepsy and non-epilepsy disorders in Norway and furthermore to study the retention rates of the most commonly used AEDs in these indications in long-term use. METHODS: The data consisted of all prescriptions of AEDs from Norwegian pharmacies in the Norwegian Prescription Database (NorPD) (2004-2012). Variables included anonymous data regarding age, gender, diagnosis specific reimbursement codes and utilisation of AEDs. RESULTS: In recent years (2008-2012), the utilisation of AEDs in non-epilepsy disorders accounted for 45-53 % of the total use. In epilepsy, the most commonly used AED was lamotrigine, followed by levetiracetam, carbamazepine and valproate. Lamotrigine was also the predominant AED used in psychiatry, while pregabalin and gabapentin were mostly used in neuropathic pain. In migraine, topiramate predominated but accounted for <1 % of the total utilisation of AEDs. The majority of prescriptions were by general practitioners and only 20 % by specialists. Regardless of indication, newer AEDs had higher retention rates (34-48 %) and were used for a longer period before discontinuation. CONCLUSIONS: The use of AEDs in non-epilepsy disorders is increasing and accounted for 53 % in 2012. Newer AEDs were predominantly used and demonstrated higher retention rates than older AEDs in all indications. This nationwide study demonstrates an increased exposure to AEDs in new patient groups, and details in prescription patterns and clinical and safety considerations should be closely monitored. This contributes to long-term post-marketing data of AED and accordingly improved pharmacovigilance.

Decreased baroreflex sensitivity is linked to sympathovagal imbalance, low-grade inflammation, and oxidative stress in pregnancy-induced hypertension.

Pregnancy-induced hypertension (PIH) has been reported as a cardiovascular (CV) risk. We assessed the sympathovagal imbalance (SVI) and the association of inflammation and oxidative stress (OS) with CV risks in PIH. A total of 125 pregnant women having a risk factor for PIH were followed till term and the incidence of PIH was observed. Retrospectively, they were divided into two groups: Group I (those who did not develop PIH, n = 82) and Group II (those who developed PIH, n = 43). Blood pressure variability (BPV) parameters including baroreflex sensitivity (BRS), spectral heart rate variability (HRV), autonomic function tests (AFTs), inflammatory markers (interleukin-6, TNF-α, interferon-γ), and OS markers were measured in both the groups. Alterations in parasympathetic and sympathetic components of AFTs were analyzed. Link of various parameters to BRS was assessed by correlation and multiple regression analysis. Parasympathetic components of AFTs were decreased from the early part of pregnancy and sympathetic components were increased toward the later part of pregnancy. Decreased BRS, the marker of CV risk, was more prominent in Group II subjects. Independent contribution of interleukin-6 (ß = 0.276, P = 0.020), TNF-α (ß = 0.408, P = 0.002), interferon-γ (ß = 0.355, P = 0.008), and thiobarbituric-acid reactive substance (ß = 0.287, P = 0.015) to BRS was found to be significant. It was concluded that sympathetic overactivity that develops more in the later part (third trimester) of pregnancy contributes to SVI and genesis of PIH. In PIH women, CV risks are present from the beginning of pregnancy that intensifies in the later part of pregnancy. Retrograde inflammation and oxidative stress contribute to the decreased BRS in PIH.

Photochemical internalization of bleomycin and temozolomide--in vitro studies on the glioma cell line F98.

Here we evaluate the photosensitizer meso-tetraphenyl chlorin disulphonate (TPCS2a) in survival studies of rat glioma cancer cells in combination with the novel photochemical internalization (PCI) technique. The tested anticancer drugs were bleomycin (BLM) and temozolomide (TMZ). Glioma cells were incubated with TPCS2a (0.2 µg ml(-1), 18 h, 37 °C) before BLM or TMZ stimulation (4 h) prior to red light illumination (652 nm, 50 mW cm(-2)). The cell survival after BLM (0.5 µm)-PCI (40 s light) quantified using the MTT assay was reduced to about 25% after 24 h relative to controls, and to 31% after TMZ-PCI. The supplementing quantification by clonogenic assays, using BLM (0.1 µm), indicated a long-term cytotoxic effect: the surviving fraction of clonogenic cells was reduced to 5% after light exposure (80 s) with PCI, compared to 70% in the case of PDT. In parallel, structural and morphological changes within the cells upon light treatment were examined using fluorescence microscopy techniques. The present study demonstrates that PCI of BLM is an effective method for killing F98 glioma cells, but smaller effects were observed using TMZ following the "light after" strategy. The results are the basis for further in vivo studies on our rat glioma cancer model using PDT and PCI.

Alliance and symptom improvement in inpatient treatment for eating disorder patients: A study of within-patient processes.

OBJECTIVE: This study examined the reciprocal relationship between alliance and symptoms during treatment for patients with eating disorders (ED). METHODS: Ninety one patients with EDs received inpatient cognitive-behavioral therapy treatment over 14 weeks. The study used repeated measurements during treatment and collected alliance and symptom measures. The analysis separated the effects of alliance and symptoms into between- and within-patient effects in a multilevel analysis. RESULTS: The results show a reciprocal relationship with between-patient alliance predicting ED symptoms and between-patient ED symptoms predicting alliance the subsequent weeks. However, for within-patient effects only alliance predicted ED symptoms the subsequent week. DISCUSSION: The results nuance the effect of the alliance in this patient group, and paint a complex picture of alliance in the psychotherapy process.