Showing papers by "Ashutosh Kumar published in 2017"

Regulatory role of NGFs in neurocognitive functions

Abstract: Nerve growth factors (NGFs), especially the prototype NGF and brain-derived neurotrophic factor (BDNF), have a diverse array of functions in the central nervous system through their peculiar set of receptors and intricate signaling. They are implicated not only in the development of the nervous system but also in regulation of neurocognitive functions like learning, memory, synaptic transmission, and plasticity. Evidence even suggests their role in continued neurogenesis and experience-dependent neural network remodeling in adult brain. They have also been associated extensively with brain disorders characterized by neurocognitive dysfunction. In the present article, we aimed to make an exhaustive review of literature to get a comprehensive view on the role of NGFs in neurocognitive functions in health and disease. Starting with historical perspective, distribution in adult brain, implied molecular mechanisms, and developmental basis, this article further provides a detailed account of NGFs' role in specified neurocognitive functions. Furthermore, it discusses plausible NGF-based homeostatic and adaptation mechanisms operating in the pathogenesis of neurocognitive disorders and has presents a survey of such disorders. Finally, it elaborates on current evidence and future possibilities in therapeutic applications of NGFs with an emphasis on recent research updates in drug delivery mechanisms. Conclusive remarks of the article make a strong case for plausible role of NGFs in comprehensive regulation of the neurocognitive functions and pathogenesis of related disorders and advocate that future research should be directed to explore use of NGF-based mechanisms in the prevention of implicated diseases as well as to target these molecules pharmacologically.

Evidence of continuity of mesentery from duodenum to rectum from human cadaveric dissection - a video vignette.

Abstract: Standard dissection techniques have not resolved uncertainties about the continuity of the peritoneal fold, also termed the mesentery, which attachesthe intra-abdominal gut tube to the posterior abdominal wall. [1, 2]. This is readily observed in jejunum, ileum, and the transverse and sigmoid colon. In contrast, the fold is less obvious in duodenum, ascending and descending colon. This article is protected by copyright. All rights reserved.

Altered Expression Of A Unique Set Of Genes Reveals Complex Etiology Of Schizophrenia

Abstract: Purpose: The etiology of schizophrenia is extensively debated, and multiple factors have been contended to be involved. A panoramic view of the contributing factors in a genome-wide study can be an effective strategy to provide a comprehensive understanding of its causality. Materials and Methods: GSE53987 dataset downloaded from GEO-database, which comprised mRNA expression data of post-mortem brain tissue across three regions from control and age-matched subjects of schizophrenia (N= Hippocampus (HIP): C-15, T-18, Prefrontal cortex (PFC): C-15, T-19, Associative striatum (STR): C-18, T-18). Bio-conductor ‘affy’ package used to compute mRNA expression, and further t-test applied to investigate differential gene expression. The functional and disease association analyses of the derived genes performed using PANTHER Classification System, GeneCards and NCBI database. Results: A set of 40 genes showed significantly altered (p<0.01) expression across all three brain regions (38 protein coding, 2 noncoding). The functional analysis revealed, genes involved in maintaining basic housekeeping functions as catalysis (44.7%), binding (34.2%), and nucleic acid binding transcription factor activity (13.2%), transporter activity (10.50%), enzyme regulation (7.90%), and structural molecule activity (5.3%), and implicated in biological processes and events, and molecular pathways relating basic neuronal functions. The gene set found associated with neoplasm, inflammatory/immune cell, and immunodeficiency/virus-mediated, neurodegenerative and neurological, metabolic, and congenital diseases respectively. Conclusions: The functional analysis of the gene set unravels gross components of the multi-factorial etiology of schizophrenia. The deviant expression of genes maintaining basic cell machinery explains compromised neuronal processing, and associated pathology may involve intricate mechanisms shared with various other diseases.

Induction – reversal modeling of psychiatric disorders by functional manipulation of habenular pathways in zebrafish

Abstract: The etiomechanism of psychiatric disorders is still poorly understood. Optogenetically induced changes in neural networks and consequent change of behavior in transgenic animals has provided a novel opportunity to develop animal models of various psychiatric disorders. We hereby propose zebrafish as a model organism based on the premise of its comprehensive similitude with the mammalian brain. The habenula is an evolutionarily conserved bilateral structure located at the interface of diencephalon, basal nuclei and brainstem working as a gateway between cortical-subcortical and brainstem structures. Many studies have suggested master role of habenula in control of adaptive behavior through regulation of brainstem aminergic nuclei. It is thought to function as a switchboard for regulating emotional behavior in conditions facing survival challenges. The dysregulation of the emotional behavior has been at the base of psychiatric disorders and a functional manipulation of specific habenular nuclei using optogenetics combined with incremental levels of stress challenge may prove to be a basic model for the genesis of psychiatric disorders. Conversely, reversing the manipulation, scaling down stress levels, and providing enriched environment may ease psychiatric symptoms. The present article has proposed a hypothesis on the development of a basic zebrafish model for the psychiatric disorders based on this concept. Such a model may be of great help in understanding the common mechanism involved in genesis and progression of various psychiatric disorders. The article has also elaborated on the operational mechanisms and validity of the methodology and has suggested an experimental design for the proposed study model.

Nerve Growth Factor(s) Mediated Hypothalamic Pituitary Axis Activation Model in Stress Induced Genesis of Psychiatric Disorders

Abstract: Apart from their established role in embryonic development Nerve Growth Factors (NGFs) have diverse functions in the nervous system. Their role in integration of physiological functioning of the nervous system is now attracting attention. In the present analysis, we propose a new paradigm about a novel role of NGFs. We hypothesize that NGFs play imperative role in maintaining psychological integrity of an individual as a biological system. This function may be mediated through HPA-axisoperated homeostatic mechanisms; stress induced disruption of which may lead to psychiatric disorders. Current literature suggests existence of constitutive homeostatic regulatory mechanisms for NGFs disruption which may lead to important behavioural effects. NGFs have been shown to play crucial parts in endocrine regulation. This is especially true with the prototype ‘NGF’ and Brain Derived Neurotrophic Factor (BDNF). These moieties have been observed to play important role in maintaining neuro-endocrine homeostasis thereby having a profound impact on the psychological health of an individual. Role of NGFs and HPA-axis activation (in separate studies) in developing psychiatric disorders especially those born of stress have been established. Literature suggests their unique interplay for producing a common effect which might be implicated in stress induced genesis of psychiatric disorders. This aspect, therefore, needs to be elucidated further as a disease etiogenesis model. This model may yield important insights into the evolution of psychiatric disorders and may open ways for new therapeutic approaches.

Results of pronator quadratus pedicle bone graft as primary procedure for treatment of scaphoid nonunion

Abstract: Pedicle bone graft as primary procedure for treatment of scaphoid nonunion. Pedicle bone graft use in delayed and nonunion of fractures and avascular necrosis scaphoid fracture. The most common indications for Pedicle bone graft have been for scaphoid nonunion, lunatomalacia (Kienbock's disease), and osteonecrosis of the scaphoid (Preiser's disease). Advantages over non vascularized bone graft have been established. Pedicle bone graft provide improved blood flow, osteocyte preservation, and accelerated healing rates. Local pedicle VBGs are the most commonly used methods. They are technically less demanding than are free VBGs and are associated with less morbidity. In managing osteonecrosis, most surgeons would agree that VBG should be reserved for scaphoid nonunion with an intact cartilaginous shell and no collapse. In treating scaphoid pathology, indications for pedicle bone graft include fractures/nonunions with proximal pole avascular necrosis and/or small proximal pole fragments.

Nerve Growth Factor(s) Mediated Hypothalamic Pituitary Adrenal Axis Dysregulation Model in Stress Induced Genesis of Psychiatric Disorders

Abstract: Nerve Growth Factor(s) Mediated Hypothalamic Pituitary Adrenal Axis Dysregulation Model in Stress Induced Genesis of Psychiatric Disorders Ashutosh Kumar*1,6, Pavan Kumar*1,6, Muneeb A. Faiq3,6, Vikas Pareek2,6, Khursheed Raza1,6, Sankat Mochan1,6 , Pranav Prasoon4,6, Vivek Sharma5,6 1. Department of Anatomy, All India Institute of Medical Sciences (AIIMS). New Delhi, India 2. Computational Neuroscience and Neuroimaging Division, National Brain Research Centre (NBRC), Manesar, Haryana, India 3. Department of Ophthalmology, All India Institute of Medical Sciences (AIIMS). New Delhi, India. 4. Spinal Cord and Brain Injury Research center, Department of Physiology, University of Kentucky, Lexington, KY, USA 5. Department of Physiology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India 6. Etiologically Elusive Disorders Research Network (EEDRN)

Management of pathological femoral fracture secondary to Ewing sarcoma in pregnancy: A case report

Abstract: Ewing's sarcoma is an ultra-orphan disease (2/1,000,000/year) which requires a multimodal therapy approach in high-volume centers. Treatment consists of pre-operative therapy followed by surgery and post-operative combination of chemo-radiotherapy. Experience with diagnosis and therapy of Ewing's sarcoma in pregnancy is very limited. We herein report the case of an atypical Ewing's sarcoma detected in the second trimester of gestation. The present study reports a case of a 24-week primigravida presenting with presented with chief complains of sudden onset of pain in left proximal thigh and inability to stand from bed on 28 feb.2017 in early mornig. Consult local doctor where x ray advice & some analgesic given. X-ray done at periphery which shows pathological subtrochantric fracture. From there she refer to higher centre for further management. An internal fixator was placed in the left femur for definitive treatment of the fracture. Normal delivery was performed at 32 gestational weeks. Following delivery, staging of cancer was conducted. Subsequently, adjuvant treatment started. The rare nature of this condition underlines once more the need for a multidisciplinary team to improve the quality of care for this highly special patient collective.