Miracle-dz/UniFAR-FTUs huggingface dataset:
Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder.

BACKGROUND As patients with mood disorders manifest heterogeneity in phenomenology, pathophysiology, etiology, and treatment response, a biological classification of mental disease is urgently needed to advance research. Patient and methodological variability complicates the comparison of neuroimaging study results and limits heuristic model development and a biologically-based diagnostic schema. OBJECTIVE We have critically reviewed and compared the magnetic resonance neuroimaging literature to determine the degree and directionality of volumetric changes in brain regions putatively implicated in the pathophysiology of major depressive disorder (MDD) versus bipolar disorder (BD). METHODS A total of 140 published magnetic resonance imaging investigations evaluating subjects with BD or MDD were selected to provide a summary and interpretation of volumetric neuroimaging results in MDD and BD. Further commentary on the pathophysiological implications, and putative cellular and pharmacological mechanisms, is also provided. RESULTS While whole brain volumes of patients with mood disorders do not differ from those of healthy controls, regional deficits in the frontal lobe, particularly in the anterior cingulate and the orbitofrontal cortex, appear to consistently differentiate subjects with mood disorders from the general population. Preliminary findings also suggest that subcortical structures, particularly the striatum, amygdala, and hippocampus, may be differentially affected in MDD and BD. CONCLUSIONS Structural neuroimaging studies have consistently identified regional abnormalities in subjects with mood disorders. Future studies should strive to definitively establish the influence of age and medication.
Iterative learning control for a class of nonlinear discrete-time systems with multiple input delays

This article, addresses the robust iterative learning control (ILC) problem for nonlinear discrete time-delay systems. The derivation of convergence and robustness for the proposed ILC rule is based on two-dimensional (2D) linear inequalities. For a class of nonlinear discrete-time systems with multiple input delays, it is shown that the ILC tracking errors are bounded in the presence of state, output disturbances and initial state uncertainty. As these disturbances and uncertainty satisfy required conditions, the ILC tracking errors even can be driven to zero. Two numerical examples are used to validate the proposed ILC method.
Verapamil augmentation of lithium treatment improves outcome in mania unresponsive to lithium alone: preliminary findings and a discussion of therapeutic mechanisms.

OBJECTIVES Attenuation of protein kinase C (PKC) is a mechanism common to both established (lithium, valproate) and some novel (tamoxifen) antimanic agents. Verapamil, although primarily known as a calcium channel blocker, also has PKC inhibitory activity. Verapamil has shown antimanic activity in some but not all studies. Therefore, we investigated verapamil, used alone or as an adjunctive treatment, in manic patients who did not respond to an initial adequate trial of lithium. METHODS Each study phase lasted three weeks. Subjects were treated openly with lithium in Phase 1 (n = 45). Those who failed to respond were randomly assigned to double-blind treatment in Phase 2 with either verapamil (n = 10) or continued-lithium (n = 8). Phase 2 nonresponders (n = 10) were assigned to combined verapamil/lithium in Phase 3. RESULTS Response in Phase 2 did not differ significantly between verapamil and continued-lithium. During Phase 3, response to combined treatment was significantly better than overall response to monotherapy in Phase 2 (Fisher's Exact test, p = 0.043). Mania ratings improved during combined treatment in Phase 3 by 88.2% (linear mixed model analysis, F = 4.34, p = 0.013), compared with 10.5% improvement during Phase 2. CONCLUSIONS In this preliminary investigation, verapamil monotherapy did not demonstrate antimanic efficacy. By contrast, the combination of verapamil plus lithium was highly efficacious. Our findings thus suggest that verapamil may have potential utility as an adjunct to lithium. This effect may be mediated by additive actions on PKC inhibition, which may be an important mechanism for antimanic agents in general.
Polymorphism of the Glucocorticoid Receptor Gene associates with mania and hypomania in Bipolar Disorder

Objectives In affective disorders, dysregulation of the hypothalamus-pituitary-adrenal (HPA)-axis is a frequently observed phenomenon. Subtle changes in Glucocorticoid Receptor (GR) functioning caused by polymorphisms of the GR gene ( NR3C1 ) may be at the base of the altered reaction of the HPA-axis to stress and subsequently related to the development and course of affective disorders. The aim of our study is to evaluate associations between GR gene polymorphisms and bipolar disorder (BD). the influence of stress vulnerability as revealed by GR and MR gene polymorphisms on the prognosis of BD. This might offer avenues for the development of new therapeutic interventions targeting the stress system.
Brief report: airways abnormalities and rheumatoid arthritis-related autoantibodies in subjects without arthritis: early injury or initiating site of autoimmunity?

OBJECTIVE To evaluate the presence of pulmonary abnormalities in rheumatoid arthritis (RA)-related autoantibody-positive subjects without inflammatory arthritis. METHODS Forty-two subjects who did not have inflammatory arthritis but were positive for anti-cyclic citrullinated peptide antibodies and/or ≥2 rheumatoid factor isotypes (a profile that is 96% specific for RA), 15 autoantibody-negative controls, and 12 patients with established seropositive early RA (<1-year duration) underwent spirometry and high-resolution computed tomography (HRCT) lung imaging. RESULTS The median age of autoantibody-positive subjects was 54 years, 52% were female, and 38% were ever-smokers; these characteristics were not significantly different from those of autoantibody-negative control subjects. No autoantibody-positive subject had inflammatory arthritis based on joint examination. HRCT revealed that 76% of autoantibody-positive subjects had airways abnormalities including bronchial wall thickening, bronchiectasis, centrilobular opacities, and air trapping, compared with 33% of autoantibody-negative controls (P = 0.005). The prevalence and type of lung abnormalities among autoantibody-positive subjects were similar to those among patients with early RA. In 2 autoantibody-positive subjects with airways disease, inflammatory arthritis classifiable as articular RA developed ∼13 months after the lung evaluation. CONCLUSION Airways abnormalities that are consistent with inflammation are common in autoantibody-positive subjects without inflammatory arthritis and are similar to airways abnormalities seen in patients with early RA. These findings suggest that the lung may be an early site of autoimmune-related injury and potentially a site of generation of RA-related autoimmunity. Further studies are needed to define the mechanistic role of lung inflammation in the development of RA.
A flexible visual inspection system based on neural networks

In this work, we propose a neural networks-based machine vision system, which is intended to act as a reconfigurable inspection tool, for use in manufacturing environments. The processing engine of the system is a second-order neural network, which extracts geometric features invariant to translation and rotation. A major issue with the use of higher-order neural networks is the combinatorial explosion of the higher-order terms, which is addressed here with the use of the alternative image representation strategy of coarse coding. We developed a genetic algorithms tool, which allows the automated determination of the optimal number of hidden units in the neural networks architecture. The inspection system is tested in two application areas, namely inspection of axisymmetric components and classification of rivets. Numerous tests are carried out to evaluate the robustness of the proposed system to complex noise sources.
Gray matter, white matter, brain, and intracranial volumes in first-episode bipolar disorder: a meta-analysis of magnetic resonance imaging studies.

OBJECTIVES To perform a comprehensive quantitative analysis of the existing magnetic resonance imaging (MRI) studies of the brain conducted on patients with first-episode bipolar disorder (BD). METHODS A systematic search was performed of MRI studies that reported quantitative measurements of brain volumes of first-episode bipolar patients and healthy controls. Four meta-analyses were performed for four cerebral regions. RESULTS Significant overall effect sizes were demonstrated, with a reduction detected in patients with BD for total intracranial and white matter volumes, but not for gray matter and whole brain volumes. CONCLUSIONS The available MRI literature indicates that specific structural brain abnormalities are already present in first-episode bipolar patients. These do not overlap with those emerging from previous meta-analyses performed in patients with chronic BD. These findings support the hypothesis of different patterns of changes in brain morphology over the time course of bipolar disorder.
A Wnt/β-catenin negative feedback loop inhibits interleukin-1-induced matrix metalloproteinase expression in human articular chondrocytes.

OBJECTIVE The results of recent animal studies suggest that activation of Wnt/β-catenin signaling in articular chondrocytes might be a driving factor in the pathogenesis of osteoarthritis (OA) by stimulating, for instance, the expression of matrix metalloproteinases (MMPs). The aim of this study was to investigate the role of Wnt/β-catenin signaling in interleukin-1β (IL-1β)-induced MMP expression in human chondrocytes. METHODS Primary cultures of human, murine, and bovine articular chondrocytes as well as human mesenchymal stem cells and mouse embryonic fibroblasts were used in the experiments. Multiple strategies for the activation and inhibition of signaling pathways were utilized. Reporter assays and coimmunoprecipitation were performed to study the interaction between β-catenin and NF-κB. RESULTS In contrast to the role of Wnt/β-catenin in animal chondrocytes, in human chondrocytes it was a potent inhibitor of MMP-1, MMP-3, and MMP-13 expression and generic MMP activity both in basal conditions and after IL-1β stimulation. This effect was independent of the T cell factor/lymphoid enhancer factor family of transcription factors but rather was attributable to an inhibitory protein-protein interaction between β-catenin and NF-κB. IL-1β indirectly activated β-catenin signaling by inducing canonical Wnt-7B expression and by inhibiting the expression of canonical Wnt antagonists. CONCLUSION Wnt/β-catenin signaling in human chondrocytes had an unexpected anticatabolic role by counteracting NF-κB-mediated MMP expression induced by IL-1β in a negative feedback loop.
Antithetical asymmetry in schizophrenia and bipolar affective disorder: a line bisection study.

OBJECTIVE Evolutionary theories link the pathogenesis of psychosis with anomalous brain asymmetry. Research shows that aberrant lateralization is linked to schizophrenia with elevated rates of left-handedness and reversal of normal cerebral asymmetries. However, lateralization is underexamined in bipolar affective disorder (BPAD) and the available literature suggests the possibility of greater lateralization, which is diametrically opposite to what is observed in schizophrenia. For the first time, we report concurrent analyses of asymmetry in BPAD and schizophrenia using a line bisection task. METHODS We examined 164 subjects (31 patients with BPAD in remission, 30 patients with schizophrenia, and 103 healthy controls) using a two-hand line bisection task with established methodology. Raters with good inter-rater reliability (intraclass correlation coefficient > 0.8) measured deviation from the center. Task performance was compared using analysis of covariance with age, sex, and education as covariates. RESULTS Study groups did not differ significantly on age, sex, and handedness (p > 0.06). Patients (both schizophrenia and BPAD) had significantly more errors in identifying the center than controls (p < 0.001). Patients with schizophrenia bisected fewer lines at center than controls and BPAD subjects (p < 0.001). Using their right hand, schizophrenia patients had significant rightward deviation and BPAD patients had leftward deviation (p = 0.001). A significant interaction between diagnosis and direction of deviation (p = 0.01) was noted, with significant rightward deviation in schizophrenia and a trend toward leftward deviation in BPAD. CONCLUSIONS Study findings suggest attenuation of normal pseudoneglect in schizophrenia and accentuation of normal pseudoneglect in BPAD, indicating lesser lateralization in schizophrenia and possibly greater lateralization in BPAD. From an evolutionary perspective, schizophrenia and BPAD might have antithetical origins.
Preclinical and clinical evaluation of carbohydrate immunopharmaceuticals in the prevention of sepsis and septic sequelae

Sepsis and sepsis syndrome are significant causes of morbidity and mortality in critically ill patients. Despite technological and therapeutic advances in critical care, sepsis continues to be a pivotal factor in 20-50 % of deaths in surgical intensive care units. It is clear that alternative approaches to the prevention and/or treatment of sepsis must be found. Preclinical data indicate that macrophage activation with (1→3)-β-D-glucans will ameliorate sequelae associated with Gram-negative septicemia. Recent clinical data indicate that macrophage activation with (1→3)-β-D-glucans will significantly reduce septic morbidity and mortality in trauma and/or high-risk surgical patients. This work reviews the preclinical and clinical evaluation of (1→3)-β-D-glucans in the prevention of sepsis and septic sequelae.
Occupational health problems of municipal solid waste management workers in India

Aims: The present study aimed to assess the occupational health problems of municipal solid waste management workers. Material and Methods: Cross-sectional descriptive study was conducted among solid waste management workers of Kerala, India. All workers (408) were included the study of which 313 (77%) participated. Data were collected by direct interview and clinical examination using a structured questionnaire. The observed morbidity like respiratory diseases, eye diseases, dermatological problems and nail infections were elicited by clinical examination. The point prevalence of other occupational related health events present either during the study time or during 1 month recall period and that occurred ever after entry in present occupation was collected by self-reported complaints and doctors diagnoses. Results: The mean age was 42.5 ± 7.2 years. The observed morbidity like respiratory diseases, eye diseases, dermatological problems, nail infections were high ranged from 21% to 47%. The reported prevalence of occupation related morbidities like falls (63.6%), accidents (22%), injuries (73.2%), and water-vector borne disease (7.1%) were high. The current prevalence of musculoskeletal morbidities showing that all major joints are involved (17-39%). Conclusions: The work related health-problems were reported to be high. The prevalence of Respiratory, dermatological, eye problems and injury, musculoskeletal problems were reported to be high among municipal solid work handlers. Measures are needed to improve the work environment of waste handlers by ensuring availability protective gears based on ergonomic principles, clean drinking water and washing and sanitation facilities during working hours.
Electrocardiography 100 Years Ago

IN 1987, we will celebrate the 100th anniversary of electrocardiography.1 It may be appropriate now to review the principal contributors to the early development of the field and the critical role of one piece of equipment, the string galvanometer. The recording from the body surface of electrical potentials generated by the heart was first described in 1887,1 but early electrocardiographic instruments, which were called "electrometers," were not practical. They were delicate and inconvenient, and they had inherent distortion.2 It was only after the introduction of the sensitive and more convenient string galvanometer that clinical electrocardiography was launched. The string galvanometer .
The common adolescent bipolar phenotype shows positive biases in emotional processing.

OBJECTIVES Bipolar disorder is associated with abnormalities in emotional processing that persist into periods of remission. However, studies of euthymic bipolar disorder patients may be confounded by the experience of mood episodes and medication. We therefore assessed an adolescent group for vulnerability markers associated with the bipolar phenotype. METHODS The Mood Disorder Questionnaire (MDQ) is a screening tool for bipolar disorder that targets mood-elevation symptoms. We selected 32 high-scoring students (≥ 7 symptoms) with the adolescent bipolar phenotype and 30 low-scoring controls (≤ 3 symptoms) and screened them with the Mini International Neuropsychiatric Interview-Plus for bipolar disorder and other psychiatric disorders. We investigated emotional processing by assessing facial expression recognition, emotional memory, emotion-potentiated startle, and a dot-probe task. RESULTS Of the high-MDQ participants, 12 were in remission from bipolar disorder defined by DSM-IV-TR and interview (bipolar II disorder/bipolar disorder not otherwise specified) and 3 from major depressive disorder. High-MDQ participants had higher levels of neuroticism, low mood, and lifetime anxiety comorbidity and alcohol dependence compared with low-MDQ participants. The high-MDQ group showed facilitated recognition of surprised and neutral facial expressions and enhanced processing of positive versus negative information in emotional recognition memory and emotion-potentiated startle. There were no effects on emotional categorisation/recall memory or attentional bias in the dot-probe task. CONCLUSIONS These results suggest that students with the common adolescent bipolar phenotype show positive emotional processing biases despite increased levels of neuroticism, low mood, and anxiety. Such effects may represent a psychological vulnerability marker associated with the bipolar phenotype.
Ethmoidal Encephalocele Associated With Cerebrospinal Fluid Fistula: Indications and Results of Mini-Invasive Transnasal Approach

AbstractAnterior skull base defects with encephalocele in adults are quite rare and can be a cause of spontaneous rhinoliquorrhea; however, cerebrospinal fluid (CSF) fistula can be not rarely misdiagnosed for several months or years. Five adult patients affected by ethmoidal encephalocele with CSF fistula were treated in our institute from 2006 through to 2011. Onset of clinical history was represented by rhinoliquorrhea, which was precociously recognized in only 1 patient; in the other 4, it was misdiagnosed for a period ranging from 11 months to 5 years. After clinical diagnosis of CSF fistula and after brain magnetic resonance imaging, ethmoidal encephalocele was evident in all patients; preoperative study was completed by spiral computed tomography scan, to clearly identify the skull base bone defect. All patients were operated on by transsphenoidal endonasal endoscope-assisted microsurgical approach through 1 nostril. The herniated brain was coagulated and removed, and reconstruction of cranial base was performed. Postoperative rhinoliquorrhea or other complications did not occur in any patient at short and late follow-up. All patients were discharged after a few days. Endonasal endoscope-assisted microsurgical approach was effective in exposing and repairing the ethmoidal bone defect; tridimensional vision and wide lateral and superior exposition of the operative field were possible in each patient, thanks to the use of microscope and angulated endoscope.
Evidence for the involvement of the glucocorticoid receptor gene in bipolar disorder in an isolated northern Swedish population

Ceulemans S, De Zutter S, Heyrman L, Norrback K‐F, Nordin A, Nilsson L‐G, Adolfsson R, Del‐Favero J, Claes S. Evidence for the involvement of the glucocorticoid receptor gene in bipolar disorder in an isolated northern Swedish population. Bipolar Disord 2011: 13: 614–623. © 2011 The Authors. Journal compilation © 2011 John Wiley & Sons A/S.
Generalised gramian framework for model/controller order reduction of switched systems

In this article, a general method for model/controller order reduction of switched linear dynamical systems is presented. The proposed technique is based on the generalised gramian framework for model reduction. It is shown that different classical reduction methods can be developed into a generalised gramian framework. Balanced reduction within a specified frequency bound is developed within this framework. In order to avoid numerical instability and also to increase the numerical efficiency, generalised gramian‐based Petrov–Galerkin projection is constructed instead of the similarity transform approach for reduction. The framework is developed for switched controller reduction. To the best of our knowledge, there is no other reported result on switched controller reduction in the literature. The method preserves the stability under an arbitrary switching signal for both model and controller reduction. Furthermore, it is applicable to both continuous and discrete time systems for different classical gramian‐based reduction methods. The performance of the proposed method is illustrated by numerical examples.
Therapeutic efficacy of Tyro3, Axl, and Mer tyrosine kinase agonists in collagen-induced arthritis.

OBJECTIVE Hyperactivation of innate immunity by Toll-like receptors (TLRs) can contribute to the development of autoinflammatory or autoimmune diseases. This study evaluated the activation of Tyro3, Axl, Mer (TAM) receptors, physiologic negative regulators of TLRs, by their agonists, growth arrest-specific protein 6 (GAS-6) and protein S, in the prevention of collagen-induced arthritis (CIA). METHODS Adenoviruses overexpressing GAS-6 and protein S were injected intravenously or intraarticularly into mice during CIA. Splenic T helper cell subsets from intravenously injected mice were studied by flow cytometry, and the knee joints of mice injected intravenously and intraarticularly were assessed histologically. Synovium from mice injected intraarticularly was evaluated for cytokine and suppressor of cytokine signaling (SOCS) expression. RESULTS Protein S significantly reduced ankle joint swelling when overexpressed systemically. Further analysis of knee joints revealed a moderate reduction in pathologic changes in the joint and a significant reduction in the number of splenic Th1 cells when protein S was overexpressed systemically. Local overexpression of GAS-6 decreased joint inflammation and joint pathology. Protein S treatment showed a similar trend of protection. Consistently, GAS-6 and protein S reduced cytokine production in the synovium. Moreover, levels of messenger RNA for interleukin-12 (IL-12) and IL-23 were reduced by GAS-6 and protein S treatment, with a corresponding decrease in the production of interferon-γ and IL-17. TAM ligand overexpression was associated with an increase in SOCS-3 levels, which likely contributed to the amelioration of arthritis. CONCLUSION This study provides the first evidence that TAM receptor stimulation by GAS-6 and protein S can be used to ameliorate arthritis when applied systemically or locally. TAM receptor stimulation limits proinflammatory signaling and adaptive immunity. This pathway provides a novel strategy by which to combat rheumatoid arthritis.