Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis.

Background: Earlier contributions have documented significant changes in sensory, attention-related endogenous event-related potential (ERP) components and θ band oscillatory responses during working memory activation in patients with schizophrenia. In patients with first-episode psychosis, such studies are still scarce and mostly focused on auditory sensory processing. The present study aimed to explore whether subtle deficits of cortical activation are present in these patients before the decline of working memory performance. Methods: We assessed exogenous and endogenous ERPs and frontal θ event-related synchronization (ERS) in patients with first-episode psychosis and healthy controls who successfully performed an adapted 2-back working memory task, including 2 visual n-backworking memory tasks as well as oddball detection and passive fixation tasks. Results: We included 15 patients with first-episode psychosis and 18 controls in this study. Compared with controls, patients with first-episode psychosis displayed increased latencies of early visual ERPs and phasic θ ERS culmination peak in all conditions. However, they also showed a rapid recruitment of working memory-related neural generators, even in pure attention tasks, as indicated by the decreased N200 latency and increased amplitude of sustained θ ERS in detection compared with controls. Limitations: Owing to the limited sample size, no distinction was made between patients with first-episode psychosis with positive and negative symptoms. Although we controlled for the global load of neuroleptics, medication effect cannot be totally ruled out. Conclusion: The present findings support the concept of a blunted electroencephalographic response in patients with first-episode psychosis who recruit the maximum neural generators in simple attention conditions without being able to modulate their brain activation with increased complexity of working memory tasks.

Cognitive errors assessed by observer ratings in bipolar affective disorder: relationship with symptoms and therapeutic alliance

The construct of cognitive errors is clinically relevant for cognitive therapy of mood disorders. Beck's universality hypothesis postulates the relevance of negative cognitions in all subtypes of mood disorders, as well as positive cognitions for manic states. This hypothesis has rarely been empirically addressed for patients presenting bipolar affective disorder (BD). In-patients (n = 30) presenting with BD were interviewed, as were 30 participants of a matched control group. Valid and reliable observer-rater methodology for cognitive errors was applied to the session transcripts. Overall, patients make more cognitive errors than controls. When manic and depressive patients were compared, parts of the universality hypothesis were confirmed. Manic symptoms are related to positive and negative cognitive errors. These results are discussed with regard to the main assumptions of the cognitive model for depression; thus adding an argument for extending it to the BD diagnostic group, taking into consideration specificities in terms of cognitive errors. Clinical implications for cognitive therapy of BD are suggested.

Diagnostic performance of Fluorine-18-Fluorodeoxyglucose positron emission tomography in the assessment of pleural abnormalities in cancer patients: A systematic review and a meta-analysis.

OBJECTIVE: To systematically review and meta-analyze published data about the diagnostic performance of Fluorine-18-Fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and PET/computed tomography (PET/CT) in the assessment of pleural abnormalities in cancer patients. METHODS: A comprehensive literature search of studies published through June 2013 regarding the role of (18)F-FDG-PET and PET/CT in evaluating pleural abnormalities in cancer patients was performed. All retrieved studies were reviewed and qualitatively analyzed. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR+ and LR-) and diagnostic odd ratio (DOR) of (18)F-FDG-PET or PET/CT on a per patient-based analysis were calculated. The area under the summary ROC curve (AUC) was calculated to measure the accuracy of these methods in the assessment of pleural abnormalities. Sub-analyses considering (18)F-FDG-PET/CT and patients with lung cancer only were carried out. RESULTS: Eight studies comprising 360 cancer patients (323 with lung cancer) were included. The meta-analysis of these selected studies provided the following results: sensitivity 86% [95% confidence interval (95%CI): 80-91%], specificity 80% [95%CI: 73-85%], LR+ 3.7 [95%CI: 2.8-4.9], LR- 0.18 [95%CI: 0.09-0.34], DOR 27 [95%CI: 13-56]. The AUC was 0.907. No significant improvement considering PET/CT studies only and patients with lung cancer was found. CONCLUSIONS: (18)F-FDG-PET and PET/CT demonstrated to be useful diagnostic imaging methods in the assessment of pleural abnormalities in cancer patients, nevertheless possible sources of false-negative and false-positive results should be kept in mind. The literature focusing on the use of (18)F-FDG-PET and PET/CT in this setting remains still limited and prospective studies are needed.

Visceral leishmaniasis and hemophagocytic syndrome

A 11 months old female infant from Portugal, free of family history, consults for apathy, weight loss, tachycardia, tachypnea, petechiae, pallor without icterus and hepatoslenomegaly. Seven months earlier, while being in Portugal, she presented a persistent bluish pimple on her buttock. Laboratory results showed anemia (35 g/l), leucopenia (3.3 G/l), thrombocytopenia (13 G/l), impaired coagulation (INR 1.4, PTT 41 sec.), hyponatremia (124 mmol/l), elevated CRP (139 mg/l), high ferritin (34.775 μg/l) and high triglycerides (5.22 mmol/l). After correction of vital parameters, a bone marrow aspiration and biopsy (BMB) revealed both the etiological diagnosis, namely a visceral leishmaniasis (VL) as well as one of its potential complications, the hemophagocytic syndrome (HS). Transfusions of whole blood, platelets and fresh frozen plasma were immediately started. Dexamethasone (10 mg/m2) and amphotericin B (3 mg/kg/day) have also been administrated. Visceral leishmaniasis is caused by a protozoan (Leishmania donovani) transmitted by the female sandfly. It is endemic in the Mediterranean basin (including France, Italy, Spain and Portugal), South America, sub-Saharan Africa as well as in India and Bangladesh. The parasite infects macrophages and, after several weeks of incubation, the disease occurs by affection of bloodlines (anemia, leucopenia, thrombocytopenia), hepatosplenomegaly, cachexia, gastrointestinal damage. The complications of the disease may lead to death. Liposomal amphotericin B is the currently recommended treatment. HS is caused by the proliferation and activation of macrophages in the marrow in response to a cytokine storm. It may be of primary cause. When it is secondary, it may be related to infections such as leishmaniasis. Patients present with fever and laboratory diagnostic criteria include cytopenia, hypertriglyceridemia, high ferritin and hemophagocytosis in the BMB. The treatment consists among other in the administration of high doses corticosteroids and, in secondary cases, in the treatment of the underlying cause. In conclusion, the clinical and biological features of VL may mimic haematological disorders as leukemia, but an enlargement of the liver and especially of the spleen should remind in this parasitic infection and its potential fatal complication, the HS.

SET translocation is associated with increase in caspase cleaved amyloid precursor protein in CA1 of Alzheimer and Down syndrome patients.

Caspase cleaved amyloid precursor protein (APPcc) and SET are increased and mislocalized in the neuronal cytoplasm in Alzheimer Disease (AD) brains. Translocated SET to the cytoplasm can induce tau hyperphosphorylation. To elucidate the putative relationships between mislocalized APPcc and SET, we studied their level and distribution in the hippocampus of 5 controls, 3 Down syndrome and 10 Alzheimer patients. In Down syndrome and Alzheimer patients, APPcc and SET levels were increased in CA1 and the frequency of both localizations in the neuronal cytoplasm was high in CA1, and low in CA4. As the increase of APPcc is already present at early stages of AD, we overexpressed APPcc in CA1 and the dentate gyrus neurons of adult mice with a lentiviral construct. APPcc overexpression in CA1 and not in the dentate gyrus induced endogenous SET translocation and tau hyperphosphorylation. These data suggest that increase in APPcc in CA1 neurons could be an early event leading to the translocation of SET and the progression of AD through tau hyperphosphorylation.

Daytime sleepiness with and without cataplexy in Chinese-Taiwanese patients.

BACKGROUND AND PURPOSE: Investigation of Chinese-Taiwanese patients with excessive sleepiness, but no association with other sleep disorders, and with the presence or absence of cataplexy. PATIENTS AND METHODS: Thirty-five patients, successively referred between 2002 and 2004, underwent polysomnography (PSG), repeat multiple sleep latency test (MSLT), and human leukocyte antigen (HLA) typing. Three patients without cataplexy also had cerebrospinal fluid (CSF) hypocretin measurements. RESULTS: DQB1*0602 was associated with cataplexy in over 90% of Chinese-Taiwanese cases. Absence of cataplexy and <2 sleep-onset REM periods (SOREMPs) was seen in only two subjects, but presence of two SOREMPs did not dissociate DQB1*0602 positive and negative or cataplexy positive and negative subjects. As a group, narcoleptics with cataplexy had a higher number of SOREMPs, and the mean sleep latency was much shorter in narcoleptics with cataplexy than in the non-cataplectic patients, independent of the number of SOREMPs. CONCLUSIONS: Chinese-Taiwanese patients with cataplexy present with similar HLA findings as Black and Caucasian patients, but the presence of two or more SOREMPs in Chinese-Taiwanese patients is not a sufficient diagnostic tool to identify narcolepsy. When cataplexy is not present, description of PSG nd HLA findings may be a better approach than using a label with little scientific significance, allowing for better collection of patients' phenotype.

Fourth cranial nerve palsy and brown syndrome: two interrelated congenital cranial dysinnervation disorders?

Based on neuroimaging data showing absence of the trochlear nerve, congenital superior oblique palsy is now classified as a congenital cranial dysinnervation disorder. A similar absence of the abducens nerve is accompanied by misinnervation to the lateral rectus muscle from a branch of oculomotor nerve in the Duane retraction syndrome. This similarity raises the question of whether some cases of Brown syndrome could arise from a similar synkinesis between the inferior and superior oblique muscles in the setting of congenital superior oblique palsy. This hypothesis has gained support from the confluence of evidence from a number of independent studies. Using Duane syndrome as a model, we critically review the accumulating evidence that some cases of Brown syndrome are ultimately attributable to dysgenesis of the trochlear nerve.

Expanding scroll rings and negative tension turbulence in a model of excitable media

Scroll waves in excitable media, described by the Barkley model, are studied. In the parameter region of weak excitability, negative tension of wave filaments is found. It leads to expansion of scroll rings and instability of wave filaments. A circular filament tends to stretch, bend, loop, and produce an expanding tangle that fills up the volume. The filament does not undergo fragmentation before it touches the boundaries. Statistical properties of such Winfree turbulence of scroll waves are numerically investigated.

Schizotypy as an organizing framework for social and affective sciences

Schizotypy, defined in terms of commonly occurring personality traits related to the schizophrenia spectrum, has been an important construct for understanding the neurodevelopment and stress-diathesis of schizophrenia. However, as schizotypy nears its sixth decade of application, it is important to acknowledge its impressively rich literature accumulating outside of schizophrenia research. In this article, we make the case that schizotypy has considerable potential as a conceptual framework for understanding individual differences in affective and social functions beyond those directly involved in schizophrenia spectrum pathology. This case is predicated on (a) a burgeoning literature noting anomalies in a wide range of social functioning, affiliative, positive and negative emotional, expressive, and social cognitive systems, (b) practical and methodological features associated with schizotypy research that help facilitate empirical investigation, and (c) close ties to theoretical constructs of central importance to affective and social science (eg, stress diathesis, neural compensation). We highlight recent schizotypy research, ie providing insight into the nature of affective and social systems more generally. This includes current efforts to clarify the neurodevelopmental, neurobiological, and psychological underpinnings of affiliative drives, hedonic capacity, social cognition, and stress responsivity systems. Additionally, we discuss neural compensatory and resilience factors that may mitigate the expression of stress-diathesis and functional outcome, and highlight schizotypy's potential role for understanding cultural determinants of social and affective functions.

Morbidity and outcome after sentinel lymph node dissection in patients with early-stage malignant cutaneous melanoma.

OBJECTIVE: Prospective analysis of the morbidity and outcome of the sentinel lymph node (SLN) technique in a consecutive series of patients with early-stage melanoma. METHODS: Between 1997 and 1998, 60 patients with stage IB-II malignant melanoma underwent SLN dissection. Preoperative dynamic lymphoscintigraphy with mapping of the lymph vessels and lymph nodes and location of the sentinel node was performed the day before SLN dissection. SLN was identified by use of the blue dye technique. SLN was assessed for histopathological and immunohistochemical examination. Postoperative morbidity and mortality were recorded. Follow-up consisted of repetitive clinical examination with lymph nodes status, laboratory and radiologic findings. RESULTS: Tumor-positive SLN was observed in 18% of the patients and stage II disease was found in 91% of the patients with positive SLN. Breslow thickness was the only significant factor predicting involvement of a SLN (p = 0.02). In 36% of the positive SLN, metastases could be assessed only by immunohistochemical examination. Postoperative complications after SLN dissection were observed in 5% in comparison with 36% after elective lymph node dissection. After a mean follow-up of 32 months, recurrence was observed in 3% with a mean disease-free survival of 8 months. Overall survival was 82% and 90% in patients with positive and negative SLN, respectively. Overall mortality was 15%, due to distant metastases in 78% of the cases. CONCLUSIONS: Staging of early-stage melanoma with the SLN dissection by use of the blue dye technique combined to lymphoscintigraphy and immunohistochemistry is reliable and safe, with less morbidity than elective lymphadenectomy. Long-term follow-up is mandatory to establish the exact reliability of SLN dissection.

Factor structure of early smoking experiences and associations with smoking behavior: valence or sensitivity model?

The Early Smoking Experience (ESE) questionnaire is the most widely used questionnaire to assess initial subjective experiences of cigarette smoking. However, its factor structure is not clearly defined and can be perceived from two main standpoints: valence, or positive and negative experiences, and sensitivity to nicotine. This article explores the ESE's factor structure and determines which standpoint was more relevant. It compares two groups of young Swiss men (German- and French-speaking). We examined baseline data on 3,368 tobacco users from a representative sample in the ongoing Cohort Study on Substance Use Risk Factors (C-SURF). ESE, continued tobacco use, weekly smoking and nicotine dependence were assessed. Exploratory structural equation modeling (ESEM) and structural equation modeling (SEM) were performed. ESEM clearly distinguished positive experiences from negative experiences, but negative experiences were divided in experiences related to dizziness and experiences related to irritations. SEM underlined the reinforcing effects of positive experiences, but also of experiences related to dizziness on nicotine dependence and weekly smoking. The best ESE structure for predictive accuracy of experiences on smoking behavior was a compromise between the valence and sensitivity standpoints, which showed clinical relevance.

The habenula encodes negative motivational value associated with primary punishment in humans.

Learning what to approach, and what to avoid, involves assigning value to environmental cues that predict positive and negative events. Studies in animals indicate that the lateral habenula encodes the previously learned negative motivational value of stimuli. However, involvement of the habenula in dynamic trial-by-trial aversive learning has not been assessed, and the functional role of this structure in humans remains poorly characterized, in part, due to its small size. Using high-resolution functional neuroimaging and computational modeling of reinforcement learning, we demonstrate positive habenula responses to the dynamically changing values of cues signaling painful electric shocks, which predict behavioral suppression of responses to those cues across individuals. By contrast, negative habenula responses to monetary reward cue values predict behavioral invigoration. Our findings show that the habenula plays a key role in an online aversive learning system and in generating associated motivated behavior in humans.

T and B lymphocytes exert distinct effects on the homeostasis of NK cells.

There is growing evidence that lymphocytes impact the development and/or function of other lymphocyte populations. Based on such observations we have tested whether the NK cell compartment was phenotypically and functionally altered in the absence of B and/or T cells. Here we show that T cell deficiency significantly accelerates BM NK cell production and the subsequent seeding of splenic and liver NK cell compartments. In contrast, B cell deficiency reduces splenic NK cell survival. In the absence of T and B cells, the size of the NK cell compartments is determined by the combination of these positive and negative effects. Even though NK cell homeostasis is significantly altered, NK cells from T and/or B cell-deficient mice show a normal capacity to kill a susceptible target cell line and to produce IFN. Nevertheless, we noted that the usage of MHC class I-specific Ly49 family receptors was significantly altered in the absence of T and/or B cells. In general, B cell deficiency expanded Ly49 receptor usage, while T cell deficiency exerted both positive and negative effects. These findings show that B and T cells significantly and differentially influence the homeostasis and the phenotype of NK cells.

Influence of micronutrients on dry matter yield and interaction with other nutrients in annual crops

The objective of this work was to determine the influence of Zn, Mn and Cu on shoot dry matter yield and uptake of macro and micronutrients in upland rice, common bean and corn. Six greenhouse experiments were conducted using a Dark Red Latosol (Typic Haplusthox). Treatments consisted of application of Zn at 0, 5, 10, 20, 40, 80 and 120 mg kg-1, of Mn at 0, 10, 20, 40, 80, 160, 320 and 640 mg kg-1 and of Cu application at 0, 2, 4, 8, 32, 64 and 96 mg kg-1. Zinc increased yield of rice, Mn increased yields of corn and bean and Cu improved yields of rice and bean. Uptake of N, Ca, and Cu in rice was decreased by zinc treatment. In common bean, uptake of N, Mg, and Cu was increased by zinc application, whereas, uptake of P was decreased. Manganese increased uptake of Mg, Zn and Fe and decreased uptake of Ca, in corn. Uptake of K, Zn and Mn was increased and uptake of P and Cu was decreased by Mn application, in bean. Copper had positive and negative interactions in the uptake of macro and micronutrients, depending on crop species and nutrients involved.

Neuroendocrine deregulation of food intake, adipose tissue and the gastrointestinal system in obesity and metabolic syndrome.

Obesity is an excess of fat mass. Fat mass is an energy depot but also an endocrine organ. A deregulation of the sympathetic nervous system (SNS) might produce obesity. Stress exaggerates diet-induced obesity. After stress, SNS fibers release neuropeptide Y (NPY) which directly increases visceral fat mass producing a metabolic syndrome (MbS)-like phenotype. Adrenergic receptors are the main regulators of lipolysis. In severe obesity, we demonstrated that the adrenergic receptor subtypes are differentially expressed in different fat depots. Liver and visceral fat share a common sympathetic pathway, which might explain the low-grade inflammation which simultaneously occurs in liver and fat of the obese with MbS. The neuroendocrine melanocortinergic system and gastric ghrelin are also greatly deregulated in obesity. A specific mutation in the type 4 melanocortin receptor induces early obesity onset, hyperphagia and insulin-resistance. Nonetheless, it was recently discovered that a mutation in the prohormone convertase 1/3 simultaneously produces severe gastrointestinal dysfunctions and obesity.