The effect of MC3/4 receptor agonist and antagonist injections into the ventral tegmental area on motivated food behavior

Obesity has become a serious problem in the US. According to the Centers for Disease Control and Prevention, currently ~70% of the US population can be considered overweight or obese. In order to tackle the issue of obesity, it is very important to identify the neural mechanisms that regulate feeding. This will aid us to combat the bigger issue of obesity. The Arcuate nucleus contains two sets of neurons that play an important role in the control of feeding, while the mesolimbic dopamine system plays a major role in most reward based behavior including the reward-related responses to drugs and food. There have been increasing evidence of the melanocortin system interacting with the mesolimbic dopamine system in mediating hedonic feeding. In these studies we tested whether injecting the melanocortin receptor antagonist and agonist, SHU 9119 and MTII, in the ventral tegmental area (VTA) has an effect on reward-based food intake. MTII decreased reward based food intake while SHU9119 affected motivated food intake behavior at a high concentration. Overall, these studies increase our understanding the role of αMSH in the VTA on motivated food reward behavior

Basics of Facial Transplantation: Surgical Principles and Management of Risks

Facial transplantation offers an alternative approach towards restoring gross facial disfigurement. Since its advent in 2005, the surgical principles have become continually refined depending on the nature of the injury and anatomical requirements posed by the recipients. Owing to the complex nature of the procedure, it bears a number of different risks. These have included graft rejection from alloimmune responses, complications from the effects of immunosuppression and risk of mortality; in addition, there is an inherent predisposition for the development of psychological complications. This chapter outlines the stepwise process of conducting a facial transplantation with emphasis on key surgical principles. It also provides details with case examples of how to minimize complications associated with the procedure

Carcinoma of the uncinate process of the pancreas presenting with deep vein thrombosis: a case report

The uncinate process is a hook-like projection of the inferior aspect of the head of the pancreas. Carcinoma of the uncinate process of the pancreas is considered to be rare, difficult to diagnose and particularly devastating. The current method of detection is computed tomography. We report a case of carcinoma of the uncinate process of the pancreas in a patient who initially presented with deep vein thrombosis. The diagnosis of carcinoma of the uncinate process of the pancreas should be considered in patients who present with primary thromboembolic disease and other nonspecific signs

Cerebellar degeneration in epilepsy: a systematic review

Introduction: Cerebellar degeneration has been associated in patients with epilepsy, though the exact pathogenic mechanisms are not understood. The aim of this systematic review was to identify the prevalence of cerebellar degeneration in patients with epilepsy and identify any pathogenic mechanisms. Methodology: A systematic computer-based literature search was conducted using the PubMed database. Data extracted included prevalence, clinical, neuroradiological, and neuropathological characteristics of patients with epilepsy and cerebellar degeneration. Results: We identified three consistent predictors of cerebellar degeneration in the context of epilepsy in our review: temporal lobe epilepsy, poor seizure control, and phenytoin as the treatment modality. Whole brain and hippocampal atrophy were also identified in patients with epilepsy. Conclusions: Cerebellar degeneration is prevalent in patients with epilepsy. Further prospective studies are required to confirm if the predictors identified in this review are indeed linked to cerebellar degeneration and to establish the pathogenic mechanisms that result in cerebellar insult

Automatic Glaucoma Detection by Using Funduscopic Images

This paper describes an automatic system to identify glaucoma disease from funduscopic images by using digital image processing. Glaucoma caused by increase of pressure in eye and damages in optic nerve. Glaucoma tends to be grown and may not show until final stage. Through this system, doctors can easily identify patient’s condition quickly and do treatment. Rural people also will get advantage through this system. Glaucoma is identified through cup to disc ratio (CDR) calculation and orientation of the blood vessels in this system. For that Optical disk’s inner circle (cup) and outer circle (disc) is extracted. From that radius is calculated. The outer and inner circles are extracted by using average and maximum grey level pixels respectively with the use of histogram. Then find contours and draw circle which is best fitting the contours. The radius of cup and disc are found. After calculating CDR, the abnormal image can be found if CDR exceeds a particular threshold value. Otherwise it is normal image. The system extracts the blood vessels and through the orientation of the blood vessel glaucoma is identified

Can CANVAS due to RFC1 biallelic expansions present with pure ataxia?

BACKGROUND: Biallelic expansion of AAGGG in the replication factor complex subunit 1 (RFC1) was identified as a major cause of cerebellar ataxia, neuropathy (sensory ganglionopathy, or SG) and vestibular areflexia syndrome (CANVAS). We wanted to clarify if RFC1 expansions can present with pure ataxia and if such expansions could be responsible for some cases where an alternative diagnosis had been made. METHODS: We identified patients with a combination of ataxia and SG and no other cause found, patients where an alternative diagnosis had been made, and patients with pure ataxia. Testing for RFC1 expansions was done using established methodology. RESULTS: Among 54 patients with otherwise idiopathic sporadic ataxia without SG, none was found to have RFC1 expansions. Among 38 patients with cerebellar ataxia and SG in which all other causes were excluded, 71% had RFC1 expansions. Among 27 patients with cerebellar ataxia and SG diagnosed with coeliac disease or gluten sensitivity, 15% had RFC1 expansions. CONCLUSIONS: Isolated cerebellar ataxia without SG makes the diagnosis of CANVAS due to RFC1 expansions highly improbable, but CANVAS is frequently the cause of the combination of idiopathic cerebellar ataxia with SG. It is important to screen patients diagnosed with other causes of acquired ataxia and SG as a small percentage were found to have RFC1 expansions

Indirect immunofluorescent assay as an aid in the diagnosis of suspected immune mediated ataxias

Background and purpose Immune mediated cerebellar ataxias account for a substantial proportion of all progressive ataxias. A diagnostic serological test is not always available. This is particularly problematic in Primary Autoimmune Cerebellar Ataxia, hence the necessity for diagnostic criteria recently devised and published by an International Task Force. We present our experience in the use of a commercially available indirect immunofluorescence assay, intended to be used for the detection of antibodies associated with paraneoplastic neurological syndromes. Methods Retrospective review of patients with ataxia who underwent serological testing using this assay as part of their diagnostic evaluation. We were interested in 3 groups: suspected immune mediated ataxias, genetically confirmed ataxias and patients with cerebellar variant of multi-system atrophy (MSA-C). The indirect immunofluorescence assay was performed using commercially available monkey cerebellum slides and anti-human IgG FITC conjugated antiserum. Results A total of 300 patients that had this test and fitted into one of these 3 groups (immune ataxias 190, genetic ataxias 60, MSA-C 50) were identified. The prevalence of positive immunofluorescence but negative immunoblot was 172/190 (91%) in the suspected immune ataxia group, 3/60 (5%) in the genetic group and 2/50 (4%) in the MSA-C group. The difference between the first and the other groups was significant χ2 (1, N = 291) = 64.2, p < 00001. Conclusions This report demonstrates that a commercially available immunofluorescence assay can be used to provide additional diagnostic aid for suspected immune mediated ataxias and in particular Primary Autoimmune Cerebellar Ataxia where no diagnostic marker exists

Mitochondrial pathology in progressive cerebellar ataxia.

BACKGROUND: Mitochondrial disease can manifest as multi-organ disorder, often with neurological dysfunction. Cerebellar ataxia in isolation or in combination with other features can result from mitochondrial disease yet genetic testing using blood DNA is not sufficient to exclude this as a cause of ataxia. Muscle biopsy is a useful diagnostic tool for patients with ataxia suspected of mitochondrial disease. Our aim was to determine specific patient selection criteria for muscle biopsy to see how frequent mitochondrial mutations are responsible for progressive ataxia. We performed a two centre retrospective review of patients with unexplained progressive ataxia who underwent muscle biopsy for suspected mitochondrial disease between 2004 and 2014 (Sheffield and Newcastle Ataxia Centres). RESULTS: A total of 126 patients were identified; 26 assessed in Newcastle and 100 in Sheffield. Twenty-four patients had pure ataxia and 102 had ataxia with additional features. The total number of patients with histologically suspected and/or genetically confirmed mitochondrial disease was 29/126 (23 %). CONCLUSIONS: A large proportion of patients (23 %) with progressive ataxia who underwent muscle biopsy were found to have features of mitochondrial dysfunction, with molecular confirmation in some. Muscle biopsy is a helpful diagnostic tool for mitochondrial disease in patients with progressive ataxia

Lipotoxicity and immunometabolism in ischemic acute kidney injury: current perspectives and future directions

Dysregulated lipid metabolism is implicated in the pathophysiology of a range of kidney diseases. The specific mechanisms through which lipotoxicity contributes to acute kidney injury (AKI) remain poorly understood. Herein we review the cardinal features of lipotoxic injury in ischemic kidney injury; lipid accumulation and mitochondrial lipotoxicity. We then explore a new mechanism of lipotoxicity, what we define as “immunometabolic” lipotoxicity, and discuss the potential therapeutic implications of targeting this lipotoxicity using lipid lowering medications

Upper extremity transplantation in non-human primates: an orthotopic model for translational research

Vascularized composite allotransplantation (VCA) offers unparalleled restoration of function and form following devastating musculoskeletal and soft tissue injury. However, the potential adverse effects of life-long immunosuppression remain a significant cause for concern. Therefore, while the surgical techniques necessary for VCA have developed rapidly, the immunological aspects of these procedures and the potential functional significance of immunological processes on vascularized composite allografts remain areas in which further research is required. The functional complexity of these procedures, combined with the preclinical nature of many of the research questions, necessitates the use of large animal models to most effectively address some of the outstanding hypotheses. Cynomolgus macaques are among the premier large animal models for immunological research. This manuscript describes development of an orthotopic model of upper extremity transplantation in cynomolgus macaques. Following study of the anatomy to determine feasibility, in vivo proof of concept was achieved by autologous amputation and replantation in two animals, following which a preliminary series of four allotransplants was performed. The anatomy encountered and techniques required for successful transplantation are closely comparable to those in clinical upper extremity transplantation. This is a technically challenging model, but offers a rigorous pre-clinical platform for translational research in transplant immunology, and is suitable for detailed study of the impact of immunologic processes on functional outcomes following VCA