Microglia: an interface between the loss of neuroplasticity and depression

Depression has been widely accepted as a major psychiatric disease affecting nearly 350 million people worldwide. Research focus is now shifting from studying the extrinsic and social factors of depression to the underlying molecular causes. Microglial activity is shown to be associated with pathological conditions, such as psychological stress, pathological aging, and chronic infections. These are primary immune effector cells in the CNS and regulate the extensive dialogue between the nervous and the immune systems in response to different immunological, physiological, and psychological stressors. Studies have suggested that during stress and pathologies, microglia play a significant role in the disruption of neuroplasticity and have detrimental effects on neuroprotection causing neuroinflammation and exacerbation of depression. After a systematic search of literature databases, relevant articles on the microglial regulation of bidirectional neuroimmune pathways affecting neuroplasticity and leading to depression were reviewed. Although, several hypotheses have been proposed for the microglial role in the onset of depression, it is clear that all molecular pathways to depression are linked through microglia-associated neuroinflammation and hippocampal degeneration. Molecular factors such as an excess of glucocorticoids and changes in gene expression of neurotrophic factors, as well as neuro active substances secreted by gut microbiota have also been shown to affect microglial morphology and phenotype resulting in depression. This review aims to critically analyze the various molecular pathways associated with the microglial role in depression.Gaurav Singhal and Bernhard T. Baun

Non-Compositional Term Dependence for Information Retrieval

Modelling term dependence in IR aims to identify co-occurring terms that are too heavily dependent on each other to be treated as a bag of words, and to adapt the indexing and ranking accordingly. Dependent terms are predominantly identified using lexical frequency statistics, assuming that (a) if terms co-occur often enough in some corpus, they are semantically dependent; (b) the more often they co-occur, the more semantically dependent they are. This assumption is not always correct: the frequency of co-occurring terms can be separate from the strength of their semantic dependence. E.g. "red tape" might be overall less frequent than "tape measure" in some corpus, but this does not mean that "red"+"tape" are less dependent than "tape"+"measure". This is especially the case for non-compositional phrases, i.e. phrases whose meaning cannot be composed from the individual meanings of their terms (such as the phrase "red tape" meaning bureaucracy). Motivated by this lack of distinction between the frequency and strength of term dependence in IR, we present a principled approach for handling term dependence in queries, using both lexical frequency and semantic evidence. We focus on non-compositional phrases, extending a recent unsupervised model for their detection [21] to IR. Our approach, integrated into ranking using Markov Random Fields [31], yields effectiveness gains over competitive TREC baselines, showing that there is still room for improvement in the very well-studied area of term dependence in IR

Early childhood obesity: a survey of knowledge and practices of physicians from the Middle East and North Africa

BACKGROUND: Childhood obesity is one of the most serious public health issues of the twenty-first century affecting even low- and middle-income countries. Overweight and obese children are more likely to stay obese into adulthood. Due to the paucity of data on local practices, our study aimed to assess the knowledge and practices of physicians from the Middle East and North Africa region with respect to early-onset obesity. METHODS: A specific questionnaire investigating the perception and knowledge on early-onset obesity was circulated to healthcare providers (general physicians, pediatricians, pediatric gastroenterologist, neonatologists) practicing in 17 Middle East and North African countries. RESULTS: A total of 999/1051 completed forms (95% response) were evaluated. Of all respondents, 28.9% did not consistently use growth charts to monitor growth during every visit and only 25.2% and 46.6% of respondents were aware of the correct cut-off criterion for overweight and obesity, respectively. Of those surveyed, 22.3, 14.0, 36.1, 48.2, and 49.1% of respondents did not consider hypertension, type 2 diabetes, coronary heart disease, fatty liver disease, and decreased life span, respectively, to be a long-term complication of early childhood obesity. Furthermore, only 0.7% of respondents correctly answered all survey questions pertaining to knowledge of early childhood overweight and obesity. CONCLUSION: The survey highlights the low use of growth charts in the evaluation of early childhood growth in Middle East and North Africa region, and demonstrated poor knowledge of healthcare providers on the short- and long-term complications of early-onset obesity. This suggests a need for both continued professional education and development, and implementation of guidelines for the prevention and management of early childhood overweight and obesity

Functional MRI of Rehabilitation in Chronic Stroke Patients Using Novel MR-Compatible Hand Robots

We monitored brain activation after chronic stroke by combining functional magnetic resonance imaging (fMRI) with a novel MR-compatible, hand-induced, robotic device (MR_CHIROD). We evaluated 60 fMRI datasets on a 3 T MR system from five right-handed patients with left-sided stroke ≥6 months prior and mild to moderate hemiparesis. Patients trained the paretic right hand at approximately 75% of maximum strength with an exercise ball for 1 hour/day, 3 days/week for 4 weeks. Multi-level fMRI data were acquired before, during training, upon completion of training, and after a non-training period using parallel imaging employing GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) while the participant used the MR_CHIROD. Training increased the number of activated sensorimotor cortical voxels, indicating functional cortical plasticity in chronic stroke patients. The effect persisted four weeks after training completion, indicating the potential of rehabilitation in inducing cortical plasticity in chronic stroke patients

Metabolomic Evidence for a Field Effect in Histologically Normal and Metaplastic Tissues in Patients with Esophageal Adenocarcinoma

Patients with Barrett's esophagus (BO) are at increased risk of developing esophageal adenocarcinoma (EAC). Most Barrett's patients, however, do not develop EAC, and there is a need for markers that can identify those most at risk. This study aimed to see if a metabolic signature associated with the development of EAC existed. For this, tissue extracts from patients with EAC, BO, and normal esophagus were analyzed using 1H nuclear magnetic resonance. Where possible, adjacent histologically normal tissues were sampled in those with EAC and BO. The study included 46 patients with EAC, 7 patients with BO, and 68 controls who underwent endoscopy for dyspeptic symptoms with normal appearances. Within the cancer cohort, 9 patients had nonneoplastic Barrett's adjacent to the cancer suitable for biopsy. It was possible to distinguish between histologically normal, BO, and EAC tissue in EAC patients [area under the receiver operator curve (AUROC) 1.00, 0.86, and 0.91] and between histologically benign BO in the presence and absence of EAC (AUROC 0.79). In both these cases, sample numbers limited the power of the models. Comparison of histologically normal tissue proximal to EAC versus that from controls (AUROC 1.00) suggests a strong field effect which may develop prior to overt EAC and hence be useful for identifying patients at high risk of developing EAC. Excellent sensitivity and specificity were found for this model to distinguish histologically normal squamous esophageal mucosa in EAC patients and healthy controls, with 8 metabolites being very significantly altered. This may have potential diagnostic value if a molecular signature can detect tissue from which neoplasms subsequently arise

IQGAP1 regulates actin cytoskeleton organization in podocytes through interaction with nephrin

Increasing data has shown that the cytoskeletal reorganization of podocytes is involved in the onset of proteinuria and the progression of glomerular disease. Nephrin behaves as a signal sensor of the slit diaphragm to transmit cytoskeletal signals to maintain the unique structure of podocytes. However, the nephrin signaling cascade deserves further study. IQGAP1 is a scaffolding protein with the ability to regulate cytoskeletal organization. It is hypothesized that IQGAP1 contributes to actin reorganization in podocytes through interaction with nephrin. IQGAP1 expression and IQGAP1-nephrin colocalization in glomeruli were progressively decreased and then gradually recovered in line with the development of foot process fusion and proteinuria in puromycin aminonucleoside-injected rats. In cultured human podocytes, puromycin aminonudeoside-induced disruption of F-actin and disorders of migration and spreading were aggravated by IQGAP1 siRNA, and these effects were partially restored by a wild-type IQGAP1 plasmid. Furthermore, the cytoskeletal disorganization stimulated by cytochalasin D in COS7 cells was recovered by cotransfection with wild-type IQGAP1 and nephrin plasmids but was not recovered either by single transfection of the wild-type IQGAP1 plasmid or by cotransfection of mutant IQGAP1 [Delta 1443(S -\u3e A)] and wild-type nephrin plasmids. Co-immunoprecipitation analysis using lysates of COS7 cells overexpressing nephrin and each derivative-domain molecule of IQGAP1 demonstrated that the poly-proline binding domain and RasGAP domain in the carboxyl terminus of IQGAP1 are the target modules that interact with nephrin. Collectively, these findings showed that activated IQGAP1, as an intracellular partner of nephrin, is involved in actin cytoskeleton organization and functional regulation of podocytes. (c) 2015 Elsevier Inc. All rights reserved

The SOS Pilot Study: a RCT of routine oxygen supplementation early after acute stroke—effect on recovery of neurological function at one week

Mild hypoxia is common after stroke and associated with poor long-term outcome. Oxygen supplementation could prevent hypoxia and improve recovery. A previous study of routine oxygen supplementation showed no significant benefit at 7 and 12 months. This pilot study reports the effects of routine oxygen supplementation for 72 hours on oxygen saturation and neurological outcomes at 1 week after a stroke

Functional MRI of Rehabilitation in Chronic Stroke Patients Using Novel MR-Compatible Hand Robots

We monitored brain activation after chronic stroke by combining functional magnetic resonance imaging (fMRI) with a novel MR-compatible, hand-induced, robotic device (MR_CHIROD). We evaluated 60 fMRI datasets on a 3 T MR system from five right-handed patients with left-sided stroke ≥6 months prior and mild to moderate hemiparesis. Patients trained the paretic right hand at approximately 75% of maximum strength with an exercise ball for 1 hour/day, 3 days/week for 4 weeks. Multi-level fMRI data were acquired before, during training, upon completion of training, and after a non-training period using parallel imaging employing GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) while the participant used the MR_CHIROD. Training increased the number of activated sensorimotor cortical voxels, indicating functional cortical plasticity in chronic stroke patients. The effect persisted four weeks after training completion, indicating the potential of rehabilitation in inducing cortical plasticity in chronic stroke patients