Search

Aim: Thiocolchicoside (THC) is a drug under the category of BCS III. Due to its high molecular weight, it has poor oral bioavailability and low skin permeability. This study aims to find an alternative delivery method for THC that enhances its bioavailability through nasal application approach. In situ gels containing plain or liposomal THC with different combinations of Pluronic® F127 and PEG 400 were prepared., Method: Liposome formulations were prepared using the thin film hydration method and tested for their characterization such as for drug content, particle size, and zeta potential. In vivo pharmacokinetic parameters of formulations such as C max , T max , and AUC were tested on the rabbit model. The formulations were also scrutinized for their cell viability properties., Result: Formulation composition with 2% soybean phosphatidylcholine and 10 mg THC exhibited ∼94% entrapment efficiency, minimum particle size 101.32 nm, low polydispersity index 0.225 and +0.355 zeta potential. In situ liposomal dispersion containing 15% Pluronic® F127 turned into gel at nasal temperature. Cell lines were unharmed for 48 h. İn situ liposomal gels showed 1.5x higher blood concentration than the control formula., Conclusion: In situ gels of liposomal THC formulations offer advantages over traditional nasal solutions, demonstrating comparable bioavailability to parenteral medication while also preserving the health of nasal mucosa cells.

The focus of the research was to overcome the limitations of metoclopramide (MTC) when administered intranasally. The aim was to improve its bioavailability, increase patient compliance, and prolong its residence time in the nasal cavity. MTC-loaded liposomes were prepared by applying the film hydration method. A study was conducted to determine how formulation variables affected encapsulation efficiency (EE %), mean particle size (MPS), and zeta potential (ZP). The MTC-liposomes were further loaded into the in situ gel (gellan gum) for longer residence times following intranasal administration. pH, gelling time, and in vitro release tests were conducted on the formulations produced. In vivo performance of the MTC-loaded in situ gels was appraised based on disparate parameters such as plasma peak concentration, plasma peak time, and elimination coefficient compared to intravenous administration. When the optimal liposome formulation contained 1.98% of SPC, 0.081% of cholesterol, 97.84% of chloroform, and 0.1% of MTC, the EE of MTC was 83.21%, PS was 107.3 nm. After 5 h, more than 80% of the drug was released from MTC-loaded liposome incorporated into gellan gum in situ gel formulation (Lip-GG), which exhibited improved absorption and higher bioavailability compared to MTC loaded into gellan gum in situ gel (MTC-GG). Acceptable cell viability was also achieved. It was found out that MTC-loaded liposomal in situ gel formulations administered through the nasal route could be a better choice than other options due to its ease of administration, accurate dosing, and higher bioavailability in comparison with MTC-GG., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Ocular drug delivery methods are highly favored for boosting bioavailability, patient compliance, and lower adverse effects and dose frequency. In addition to preventing adverse effects from the active ingredient, the parts of drug delivery systems must be nontoxic and nonallergic as well. Mitochondrial toxicity test (MTT) and Hen's egg chorioallantois membrane (HET-CAM) assay are the most often utilized tests based on this dilemma. The toxicity of loteprednol etabonate loaded solid lipid nanoparticles, lipid nanostructured carriers, and nanoemulsion were compared. Oleic acid, Precirol ® ATO5, and Pluronic ® F68 were used in the preparation. Their toxicities were evaluated by using two different toxicity tests (MTT and HET-CAM). The results suggest that there are no significant differences between the HET-CAM and MTT assays. It is noteworthy that the HET-CAM assay offers a more cost-effective and environmentally friendly alternative to the MTT assay, as it does not require cell culture and generates less toxic waste. This information may be useful to consider when selecting between the two assays .

Context: Eplerenone is a member of antihypertensives used individually or in combination with other medicines. Eplerenone exhibits poor solubility and is considered a class II drug., Objective: Increasing the solubility of eplerenone by using both liquid and solid self-emulsifying drug delivery systems as an alternative to its marketed tablet product., Methods: Solubility studies of eplerenone were done with different oils, surfactants, and co-surfactants to determine which one has the highest solubility for eplerenone and determine the preference in the formulations of liquid self-emulsifying drug delivery system. The solidification process was carried out with the adsorption to solid carrier method. Optimal ratios of components were specified with the pseudo-ternary phase diagram technique. Self-emulsifying drug delivery system formulations were characterized in terms of chemical interaction, droplet size/distribution, crystallization behaviors, and rheological evaluation. In vitro drug release studies were conducted and compared to pure drugs and marketed products., Results: The solubility screening results showed high solubility of EPL in triacetin (11.99 mg/mL) as oil, Kolliphor®EL (≈ 2.65 mg/mL), and Tween80 (≈ 1.91 mg/mL) as surfactant and polyethylene glycol 200 (PEG200) (≈ 8.50 mg/mL), dimethyl sulfoxide (≈ 7.57 mg/mL), TranscutolP (≈ 6.03 mg/mL) as co-surfactant, respectively. Rheology studies revealed that liquid self-emulsifying drug delivery formulations exhibited non-Newtonian pseudoplastic flow., Conclusion: Solid self-emulsifying drug delivery systems prepared with Aerosil and Neusilin have shown tremendous improvement in terms of eplerenone dissolution by releasing the entire dose with boosted effect within 5 and 30 min respectively compared to the marketed product and pure eplerenone ( p  < 0.05).

Loteprednol etabonate (LE) is a topical corticosteroid that uses inflammatory conditions of the eye. It has a low ocular bioavailability and side effects such as corneal disorder, eye discharge, and ocular discomfort. Therefore, it was decided to select the delivery systems, which are solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE). Design of experiments (DoE) of SLN, NLC, and NE formulations were formulated by using the quality by design (QbD) approach. Precirol® ATO 5 and oleic acid were used as solid and liquid lipids, respectively, in SLN, NLC, and NE formulations. Physiochemical characterization was performed on the formulations. The optimized formulations' inflammatory effects have been appraised on human corneal epithelial cells employing the ELISA test. Physicochemical characterization studies and inflammatory effects were appraised. The sizes of optimized formulations of SLN, NLC, and NE were 86.19 nm, 82.38 nm, and 126.35 nm, respectively, with minimum polydispersity. The release behavior of the formulations is composed of both diffusion and erosion. ELISA test results proved that the formulations significantly reduced IL-1 and IL-6 levels (p < 0.05). D-optimal mixture experimental design allowed us to develop the most precise formulations of SLN, NLC, and NE. Furthermore, the optimized formulations could be promising candidates for treating an inflammation-based corneal disease of the eye., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Essential oils have a high volatility that leads to evaporation and loss of their pharmacological effect when exposed to the environment. The objectives of the present work were to prepare microcapsules with oregano essential oil by extrusion using sodium alginate as a shell material and non-ionic surfactant polysorbate 80 as an emulsifier to stabilize the emulsion. The present study was aimed to evaluate the physical parameters of microcapsules and to compare the influence of the amount of emulsifier and the essential oil-to-emulsifier ratio on the capsules' physical parameters and encapsulation efficiency; to our knowledge, the existing research had not yet revealed whether unstable emulsion affects the encapsulation efficiency of oregano essential oil. This study showed that increasing the emulsifier amount in the formulation significantly influenced encapsulation efficiency and particle size. Moreover, increasing the emulsion stability positively influenced the encapsulation efficiency. The emulsion creaming index depended on the emulsifier amount in the formulation: the highest creaming index (%) was obtained with the highest amount of polysorbate 80. However, the essential oil-to-polysorbate 80 ratio and essential oil amount did not affect the hardness of the microcapsules ( p > 0.05). In conclusion, the obtained results could be promising information for production of microcapsules. Despite the fact that microencapsulation of essential oils is a promising and extremely attractive application area for the pharmaceutical industry, further basic research needs to be carried out.

The purpose of this study was to investigate the effect of formulation variables on properties related to critical functionality for their use in indomethacin buccal tablets. Chitosan (CH), carbopol (PAA), and hydroxypropyl methyl cellulose (HPMC) concentration and filler type were evaluated as parameters for describing tablet hardness, swelling index, indomethacin release, and mucoadhesion in controlled release buccal tablets. Moreover, a 3 2 full factorial design was employed to study the effect of each polymer ratio in CH and PAA combination, which significantly influenced characteristics. A slower indomethacin release and a considerably larger degree of swelling were found for different concentrations of PAA or CH ( p  < 0.05). The buccal tablets formed a continuous gel layer while in contact with the aqueous medium undergoing a combination of swelling and erosion. In vitro drug release in simulated saliva (pH 6.75) appears to occur both by diffusion and a swelling-controlled mechanism, exhibiting anomalous, Case II type transport or Super Case II type transport. The diluent present in all study samples, mannitol (MAN), spray-dried lactose (SDL), and microcrystalline cellulose (MC) were believed to contribute minimally to hydrogel formation and drug release regulation. The dissolution values for the three co-excipients were decreasing order mannitol, spray-dried lactose, and microcrystalline cellulose. In conclusion, the type and concentration of all polymers seem to change the functionality of buccal tablets and it seems important to understand and characterize these excipients to fully predict the drug release, mucoadhesion, and swelling of buccal tablets.

Various studies have suggested that auditory deviance detection is organized in a hierarchical manner with ascending levels of complexity. Event-related potentials (ERP) are considered to reflect different cortical processing stages. In the current electroencephalographic study, we employed an auditory sequence oddball paradigm to investigate different levels of cortical auditory processing and the contribution of neuronal habituation and prediction error mechanism to N1 and Mismatch Negativity (MMN). Our findings suggest that N1 reflects a lower cortical process primarily involved in the encoding of simple physical features and is thus mainly modulated by neuronal attenuation and not complex top-down mechanisms. By analyzing within-sequence signal differences, we divided the MMN into distinct subcomponents reflecting different hierachical levels of auditory processing. We determined a "first-order" MMN that reflects the processing of simple deviant features (such as frequency) and "higher-order" MMNs that occur at regularity violation of complex patterns or unexpected inputs that do not allow further predictions. In our source localization analysis, both the primary auditory cortex and left IFG were primarily involved in the detection of simple, physically deviant features, while the right IFG was associated with the processing of novel, unexpected auditory inputs and the ACC with regularity violation of known patterns. Summarizing, our results might contribute to a better understanding of the different complexities of neuronal habituation and prediction error mechanisms at different levels of cortical auditory processing., Competing Interests: Declaration of competing interest There is no conflict of interest, financial or otherwise, related to this work for any of the authors., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Logistic regression (LR) and artificial neural networks (ANNs) are widely referred approaches in medical data classification studies. LR, a statistical fitting model, is suggested in medical problems because of its well-established methodology and coefficients contributing to the evaluation of clinical interpretations. ANNs are graphical models structured with node networks interconnected with arcs each of which is expressed in terms of weights discovered throughout the modeling process. Since ANNs have a complex structure with its layers and nodes in the layers, which provides ANNs the ability to model any data with complex relationships. Among the various models having origins in statistics and computer science, LR and ANNs have prevailed in the area of mass medical data classification. In this study, we introduce the 2 aforementioned approaches in order to generate a model dichotomizing 75 opioid-dependent patients and 59 control subjects from each other. Quantitative electroencephalography (QEEG) absolute power value of each electrode were calculated for 4 consecutive frequency bands namely delta, theta, alpha, and beta with the frequencies, 0.5 to 4, 4 to 8, 8 to 12, and 12 to 20 Hz, respectively. Significant independent variables contributing to the classification were underlined in LR while a feature selection (FS) method, genetic algorithm, is being applied to the ANN model to reveal more informative features. The performances of the classifiers were finally compared considering overall classification accuracies, area under receiver operating characteristic curve scores, and Gini coefficient. Although ANN-based classifier outperformed compared with LR, both models performed satisfactorily for absolute power measure in beta frequency band. Our results underline the potential benefit of the introduced methodology is promising and is to be treated as a clinical interface in dichotomizing substance use disorders subjects and for other medical data analysis studies.

Dihydroergotamine mesylate (DHE), ergotamine derivative, has been offered for clinical use to stop or treat symptoms of an emerging migraine as injection for more than a half century. It is shown that bioavailability of DHE greatly changes between the subjects and up to 99% of the orally absorbed dose may be cleared by first pass metabolism. The aim of this study was to design and optimize DHE fast-dissolving sublingual films for migraine treatment. For this purpose pullulan and maltodextrin was chosen as film-forming polymers and propylene glycol as plasticizer. For optimization process Box Behnken design was used. The formed films were free from air bubbles, cuttings, or cracks. Disintegration, mechanical strength and dissolution of films were compared. It is found that pullulan and maltodextrin formed films with the most desired properties at the concentration of 1.5% and 2%. The application of optimum formulation to rabbits showed that bioavailability of formulation is about 23.35% with a t max 20 min. Due to this fast onset of action and higher bioavailability than oral administration, it is suggested that the polymer combinations of pullulan and maltodextrin formed successful films and were considered as an alternative dosage form for DHE in migraine therapy.

Previous studies reported attenuated cortisol reactivity as one explanation for poor social functioning in schizophrenia. Recent research has demonstrated that both glucocorticoid and oxytocin systems are central to stress regulation. Here, we studied the associations between basal oxytocin, stress-induced cortisol levels, and social functioning and social support in schizophrenia. A mock job interview was used as an ecologically-valid social stressor in 32 schizophrenia patients. Blood samples were taken before and after stress induction to assess basal oxytocin and cortisol levels. In addition social functioning and social support scales were collected. Patients were divided into cortisol responders and non-responders according to percentage change following stress induction. Our findings revealed a possible subgroup of patients who did not exhibit attenuated cortisol responses. Importantly, cortisol responders had generally better social functioning, but perceived social support was not different between groups. There was also no evidence of a relationship between cortisol and oxytocin. This study highlights the heterogeneity of cortisol responses to stress in a schizophrenia population, and the importance of the relationship between social functioning and cortisol reactivity. These findings could be relevant when considering therapeutic interventions that manipulate endocrinology in order to improve real-world functioning., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Alterations in reward processing are frequently reported in attention deficit hyperactivity disorder (ADHD). One important factor affecting reward processing is the quality of reward as social and monetary rewards are processed by different neural networks. However, the effect of reward type on reward processing in ADHD has not been extensively studied. Hence, in the current study, an exploratory research was conducted to investigate the effect of reward type (i.e., social or monetary) on different phases of reward processing. We recorded event-related potentials (ERPs) during a spatial attention paradigm in which cues heralded availability and type of the upcoming reward and feedbacks informed about the reward earned. Thirty-nine (19 males) healthy individuals (age range: 19-27 years) participated in the study. ADHD symptoms were assessed by using ADHD self-report scale (ASRS). Our results revealed a consistent negative correlation between the hyperactivity subscale of ASRS and almost all social-feedback related ERPs (P2, P3, and FRN). ERP amplitudes after social feedbacks were less positive for P2 and P3 and more negative for FRN for individuals with greater hyperactivity levels. Our findings suggest that hyporesponsiveness to social feedbacks may be associated with hyperactivity. However, the results have to be confirmed with clinical populations.

Superficial fungal infections caused by Candida species are common skin diseases. Therefore, this study aimed to develop a new formulation containing oxiconazole nitrate, which is an azole group derivative for antifungal treatment, as a thermosensitive gel since there has been no literature study until now. MIC value of the novel thermosensitive formulation against three Candida species was calculated and time-dependent antifungal activity analysis was performed. Viscosity, transition temperature T sol-gel (°C) and gelation time of the thermosensitive gel formulation were also determined in the viscometer. The measurements performed on the tensilometer device were analyzed for adhesion hardness and elongation percentages of the formulation. In the FT-IR spectrometer, the spectrum of solution and gel state was compared between 650 and 4000 cm -1 and it was found that there is no difference between them. It was found that the temperature is reversible on the formulation and did not cause any disruption of its components. Characterization parameters of the thermosensitive gel formulation containing oxiconazole nitrate and time-dependent activity against Candida species was observed to be the same as those of the solution containing only oxiconazole nitrate. MIC, MFC and time-dependent antifungal analysis did not show any particular difference between formulation and oxiconazole nitrate itself. Thermosensitive gel formulation containing oxiconazole nitrate was found to be effective on superficial fungal infections. We believe it is also appropriate for in vivo usage, but it is necessary to perform animal and human research. It is also needed to evaluate the formulation against other etiologic agents of superficial fungal infections.

Migraine is a widespread neurological disease with negative effects on quality of life and productivity. Moderate to severe acute migraine attacks can be treated with dihydroergotamine mesylate (DHE), an ergot derivative that is especially effective in non-responders to triptan derivatives. To overcome limitations of current DHE formulations in subcutaneous injection and nasal spray such as pain, adverse side effects and poor bioavailability, a new approach is needed for DHE delivery enabling painless self-administration, quick onset of action, and high bioavailability. In this study, we developed a dissolving microneedle patch (MNP) made of polyvinylpyrrolidone, due to its high aqueous solubility and solubility enhancement properties, using a MNP design previously shown to be painless and simple to administer. DHE-loaded MNPs were shown to have a content uniformity of 108±9% with sufficient mechanical strength for insertion to pig skin ex vivo and dissolution within 2min. In vivo pharmacokinetic studies were carried out on hairless rats, and DHE plasma levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The area under curve (AUC) value after DHE delivery by MNP (1259±917ng/mL min) was not significantly different (p>0.05) as compared to subcutaneous injection, with a relative bioavailability of 97%. Also, appreciable plasma levels of DHE were seen within 5min for both delivery methods and t max value of MNPs (38±23min) showed no significant difference (p>0.05) compared to subcutaneous injection (24±13min). These results suggest that DHE-loaded MNPs have promise as an alternative DHE delivery method that can be painlessly self-administered with rapid onset and high bioavailability., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The deficits in metacognition have been observed in schizophrenia but developmental roots of impaired metacognition are not well understood. Accordingly, this study compared metacognitive abilities of patients with schizophrenia and healthy group and examined the relationship between childhood trauma, attachment style and caregiver attitudes with metacognitive capacity which might contribute to metacognitive deficits in patient group. 35 patients with schizophrenia and 35 healthy people were included in the study. Metacognitive capacity was measured using the Metacognition Assessment Scale Abbreviated (MAS-A). This scale comprises four domains: self-reflectivity, understanding other's mind, decentration and mastery. Group comparisons revealed that schizophrenia patients had greater deficits in metacognitive ability. We found that the report of childhood emotional abuse, a pattern of anxious attachment and over protection by caregivers were uniquely related to metacognitive capacity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Lack of empathy is a critical factor impacting on social functioning and quality of life in schizophrenia. There is, however, a paucity of research into the underlying neurophysiological correlates of empathy deficits in this disorder. Accordingly, we sought: (1) to identify whether dysfunctional empathic abilities in schizophrenia are related to alterations in early or late brain processes, and (2) to explore the potential relationship between brain activity and mood, self-reported empathy and symptom severity. Eighteen patients with schizophrenia and 21 healthy matched controls performed an empathy-for-pain paradigm where photographs of hands in neutral or painful situations were shown while we recorded their electroencephalography (EEG), and we examined mood, empathic concern for others and symptom severity. Significant group differences between patients and controls emerged in early (50-150ms after stimulus onset) and late (after 300ms) timeframes. Moreover, brain activity was related with unpleasantness ratings in all participants, with self-reported empathic concern only in controls and with negative mood and personal distress only in patients. Differences in social behavior in schizophrenia may be explained by early as well as late differences, affecting mostly the early frontocentral ERPs, i.e. those suggested to correspond to the emotional sharing component of empathy., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Impairments in the mirror neuron system (MNS) have been implicated as a possible underlying neurological basis for deficits in higher-level social cognition in schizophrenia. Previous work testing this hypothesis has used the electroencephalographic mu rhythm as an index of MNS activity, with studies showing mixed results. Here we investigated the role that reward plays in modulating the mu rhythm, and its association with empathy and emotional mental state reasoning. A group of schizophrenia patients and a healthy control group completed an action observation paradigm in which they watched actions that were financially rewarding, punishing, or neutral. Patients showed intact reward-related modulation of the mu rhythm, and greater mu suppression was associated with greater negative symptoms. There was also a trend for reduced mu suppression in patients. Furthermore, both empathy and emotional mental state reasoning were associated with the degree of mu suppression, but only in healthy controls. These findings confirm the association between the mu suppression and high-level social cognition. It is possible that schizophrenia patients utilize different cognitive routes to infer mental states. The demonstration that reward influences the degree of mu suppression in schizophrenia patients may help to account for previous conflicting findings in the literature.

Objective: To evaluate the changes in psychological distress level and quality of life (QoL) scores of keratoconus (KC) patients 1 year after corneal collagen cross-linking (CXL)., Methods: Observational cross-sectional study. Thirty-three, consecutive progressive KC patients who received CXL treatment were enrolled in the study. All patients were evaluated before and 1 year after CXL ophthalmologically and psychologically. Main outcome measures were the visual, refractive, and topographic changes and the Beck Depression Inventory, State-Trait Anxiety Inventory (STAI), Short Form-36 (SF-36), and The National Eye Institute Visual Function Questionnaire (NEI-VFQ-25)., Results: There were significant improvements in the keratometric readings at flat axis, steep axis, the mean keratometric reading, the corneal astigmatism (Kast), and the maximum keratometric reading. State-Trait Anxiety Inventory-II scores, QoL dimensions, such as physical role difficulty, general health, mental health, ocular pain, near activities, distance activities, peripheral vision, and mental health scores, and the composite score of NEI-VFQ-25, were higher after surgery. There was a positive correlation between the changes observed in Kast and mental health; a negative correlation between the changes in Kast and STAI-II, and a negative correlation between the changes in mental health and STAI-II. Change in STAI-II has significantly predicted the improvement observed in general health., Conclusions: Our results suggested lower trait anxiety and better vision-related and health-related QoL in KC patients 1 year after successful CXL treatment. Better QoL in these patients seems to be related not only with the visual and refractive results but also improvement observed in trait anxiety.

Feature selection (FS) and classification are consecutive artificial intelligence (AI) methods used in data analysis, pattern classification, data mining and medical informatics. Beside promising studies in the application of AI methods to health informatics, working with more informative features is crucial in order to contribute to early diagnosis. Being one of the prevalent psychiatric disorders, depressive episodes of bipolar disorder (BD) is often misdiagnosed as major depressive disorder (MDD), leading to suboptimal therapy and poor outcomes. Therefore discriminating MDD and BD at earlier stages of illness could help to facilitate efficient and specific treatment. In this study, a nature inspired and novel FS algorithm based on standard Ant Colony Optimization (ACO), called improved ACO (IACO), was used to reduce the number of features by removing irrelevant and redundant data. The selected features were then fed into support vector machine (SVM), a powerful mathematical tool for data classification, regression, function estimation and modeling processes, in order to classify MDD and BD subjects. Proposed method used coherence, a promising quantitative electroencephalography (EEG) biomarker, values calculated from alpha, theta and delta frequency bands. The noteworthy performance of novel IACO-SVM approach stated that it is possible to discriminate 46 BD and 55 MDD subjects using 22 of 48 features with 80.19% overall classification accuracy. The performance of IACO algorithm was also compared to the performance of standard ACO, genetic algorithm (GA) and particle swarm optimization (PSO) algorithms in terms of their classification accuracy and number of selected features. In order to provide an almost unbiased estimate of classification error, the validation process was performed using nested cross-validation (CV) procedure., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Understanding the biological underpinnings of unipolar (UD) and bipolar depression (BD) is vital for avoiding inappropriate treatment through the misdiagnosis of bipolar patients in their first depressive episode. One plausible way to distinguish between UD and BD is to compare EEG brain dynamics to identify potential neurophysiological biomarkers. Here we aimed to test group differences in EEG power, cordance and coherence values between UD and BD., Methods: Twenty-five bipolar and 56 unipolar depression patients were recruited. Sociodemographic and clinical variables were collected in addition to resting state EEG. Data was analyzed with multivariate and repeated analyses of variance where parametric assumptions were met., Results: Accordingly, we did not find any differences in the EEG absolute power and frontal asymmetry indexes between UD and BD. Regarding cordance, significant group differences were observed in the right theta cordance values (p=0.031). Regarding coherence, BD patients (as compared to UD) exhibited greater central-temporal theta (p=0.003), and parietal-temporal alpha (p=0.007) and theta (p=0.001) coherence. Lastly, less alpha coherence in BD was present at right frontal-central (p=0.007) and central inter-hemispheric (p=0.019) regions., Conclusions: Our results demonstrate that EEG cordance and coherence values have potential to discriminate between UD and BD. The loss of temporal synchronization in the frontal interhemispheric and right sided frontolimbic neuronal networks may be a unique feature that distinguishes between BD and UD., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Patients with schizophrenia suffer from dysfunctional social behaviour. Social approach and avoidance (AA) has been associated with motor responses, as the affective valence and gaze direction of facial stimuli can bias push and pull motor tendencies. The aim of this study was to investigate the role of endogenous oxytocin in social AA behaviour in schizophrenia. Basal plasma oxytocin levels were collected from 28 patients who were then given a joystick-based Approach-Avoidance Task (AAT). Reaction times were recorded and AAT effect scores calculated for responses to happy and angry faces, which either had direct or averted gaze. Individual differences in basal oxytocin had a significant relationship with AAT responses, and patients with higher levels of oxytocin tended to avoid angry faces more. Furthermore, greater avoidance of angry faces was correlated with more severe psychotic (positive and general) symptoms and greater paranoia. This suggests that the endogenous effects of oxytocin may be specific to the interpretation of negative threatening emotions in schizophrenia patients, and also provides evidence that psychotic symptoms and paranoia can impact on social AA behaviour by heightening threat avoidance., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

While deficits in metacognition have been observed in schizophrenia (SZ), it is less clear whether these are specific to the disorder. Accordingly, this study compared metacognitive abilities of patients with schizophrenia and bipolar disorder (BD) and examined the degree to which neurocognition contributed to metacognitive deficits in both groups. Participants were 30 patients with SZ and 30 with BD. Metacognitive capacity was measured using the Metacognition Assessment Scale Abbreviated (MAS-A). This scale comprises four domains: self-reflectivity, understanding others' minds, decentration and mastery. Verbal memory, executive functioning and symptoms were concurrently assessed. Group comparisons revealed that SZ patients had greater deficits in metacognitive self-reflectivity, which correctly classified 85.2% of patients with SZ in a logistic regression. Self-reflectivity and understanding others'minds were related to verbal memory and executive functioning in the SZ group, but not in the BD group. Furthermore, greater positive and general psychotic symptoms were associated with poorer metacognition in SZ. Results suggest SZ involves unique deficits in the ability to self-reflect and that these deficits may be uniquely linked with neurocognition., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Schizophrenia is a debilitating mental disorder that presents impairments in neurocognition and social cognition. Several studies have suggested that the etiology of schizophrenia can be partly explained by oxidative stress. However, our knowledge about the implications of oxidative stress on illness-related cognitive deficits is still far from being clear. The aim of this work was to study the role of oxidative stress molecules on social cognition and neurocognition in patients with schizophrenia., Methods: We assessed the peripheral levels of several molecules associated with oxidative stress, namely nitric oxide (NO), malondialdehyde (MDA), glutathione (GSH), homocysteine, superoxide dismutase (SOD) and neurotrophin 4/5 (NT4/5), in forty-one patients with schizophrenia and forty-three healthy participants. A battery of tests to measure neurocognition and social cognition was also administered to the schizophrenia group., Results: We found that the schizophrenia group presented substantially higher levels of oxidative stress than the control group, as revealed by elevated quantities of the pro-oxidants NO and MDA, and decreased levels of the antioxidants GSH, SOD and NT4/5. Interestingly, the levels of NT4/5, which have been shown to have antioxidant effects, correlated with executive functioning, as measured by two distinct tests (WCST and TMT). However, social cognition and symptom severity were not found to be associated with oxidative stress., Conclusions: We propose a protective role of NT4/5 against oxidative stress, which appears to have a potentially beneficial impact on neurocognition in schizophrenia.

Empathy is a complex emotional process that involves sharing an emotional state with another organism. The extent to which nonhuman animals are capable of empathizing with others is still far from clear, partly due to a lack of empirical work in this domain, but also due to definitional confusion of empathy with emotional contagion and other related terms. In this study, an observer mouse witnessed a familiar cagemate or an unfamiliar non-cagemate receiving electric foot shocks in an experiment that consisted of three periods: baseline (no shocks), test (shocks) and recovery (no shocks). Freezing behavior in the observer was significantly increased in the cagemate, as opposed to the non-cagemate condition during the test period, but not during baseline or recovery, emphasizing the role of familiarity in empathy-like processes. In agreement with this, we also found a correlation that approached significance between the total number of fecal droppings of the observers, as an indication of distress, and those of the demonstrator in the cagemate, but not in the non-cagemate, condition. While the freezing behavior of the demonstrators increased with time, reaching a maximum at the recovery period, the observers froze the most during the test period while the demonstrators were receiving the electric foot shocks. The observation that the freezing response of the observers ceased when the shocks in the adjacent compartment stopped could be due to a decrease in saliency of the demonstrators' behavioral response. Finally, the presence of a cagemate, as compared to a stranger, possibly reduced the demonstrator's pain-induced behavior, suggesting an ameliorating effect of familiarity on stress responses., (Copyright © 2014 Elsevier B.V. All rights reserved.)