Evaluation and Management of Seizures and Status Epilepticus.

Seizures are frequently triggered by an inciting event and result from uninhibited excitation and/or decreased inhibition of a pool of neurons. If physiologic seizure abortive mechanisms fail, the ensuing unrestrained synchronization of neurons-status epilepticus-can be life-threatening and is associated with the potential for marked morbidity in survivors and high medical care costs. Prognosis is intimately related to etiology and its response to therapeutic measures.

Lazy Glass Microsurgical Trainer: A Frugal Solution for Microsurgical Training.

Background: The art of surgery is becoming increasingly complex and dependent on scopes, screens, and technology, inviting a complex learning curve and development of hand-eye coordination and dexterity among other skills. We introduce an affordable, do-it-yourself microsurgical simulator that can be set up using a smartphone and a pair of reflective prism glasses. The glasses employ periscopic prisms on either side that reflect light perpendicularly.

Endogenous amdoparvovirus-related elements reveal insights into the biology and evolution of vertebrate parvoviruses.

Amdoparvoviruses (family genus ) infect carnivores, and are a major cause of morbidity and mortality in farmed animals. In this study, we systematically screened animal genomes to identify endogenous parvoviral elements (EPVs) disclosing a high degree of similarity to amdoparvoviruses, and investigated their genomic, phylogenetic and protein structural features. We report the first examples of full-length, amdoparvovirus-derived EPVs in the genome of the Transcaucasian mole vole ().

"Dopamine homeostasis" requires balanced polypharmacy: Issue with destructive, powerful dopamine agents to combat America's drug epidemic.

The well-researched pro-dopamine regulator KB220 and variants result in increased functional connectivity in both animal and human brains, and prolonged neuroplasticity (brain cell repair) having been observed in rodents. Moreover, in addition to increased functional connectivity, recent studies show that KB220Z increases overall brain connectivity volume, enhances neuronal dopamine firing, and eliminates lucid dreams in humans over a prolonged period. An unprecedented number of clinical studies validating this patented nutrigenomic technology in re-balancing brain chemistry and optimizing dopamine sensitivity and function have been published.

GLOBAL OPIOID EPIDEMIC: DOOMED TO FAIL WITHOUT GENETICALLY BASED PRECISION ADDICTION MEDICINE (PAM): LESSONS LEARNED FROM AMERICA.

It is a reality that globally opioid deaths have soared for men and women of all social, economic status and age from heroin and fentanyl overdoses. Specifically, in the United States, deaths from narcotic overdoses have reached alarming metrics since 2010. In fact, the Fentanyl rise is driven by drug dealers who sell it as heroin or who use it to lace cocaine or to make illegal counterfeit prescription opioids.

Practice guideline summary: Reducing brain injury following cardiopulmonary resuscitation: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

Objective: To assess the evidence and make evidence-based recommendations for acute interventions to reduce brain injury in adult patients who are comatose after successful cardiopulmonary resuscitation.

Methods: Published literature from 1966 to August 29, 2016, was reviewed with evidence-based classification of relevant articles.

Results And Recommendations: For patients who are comatose in whom the initial cardiac rhythm is either pulseless ventricular tachycardia (VT) or ventricular fibrillation (VF) after out-of-hospital cardiac arrest (OHCA), therapeutic hypothermia (TH; 32-34°C for 24 hours) is highly likely to be effective in improving functional neurologic outcome and survival compared with non-TH and should be offered (Level A).

Hypothesizing Las Vegas and Sutherland Springs Mass Shooters Suffer from Reward Deficiency Syndrome: "Born Bad".

The slaughters in Las Vegas and Sutherland Springs demand explanation, in the face of the ineffable. An understanding of the shooters' motives could restore our trust in our mutually cooperative existence. In this short communication we provide post-hoc rationale of both Stephen Paddock (Las Vegas mass shooting) and Devin Kelley (Southerland Springs mass shooting) and hypothesize that these shooters had genetically induced "Reward Deficiency Syndrome" (RDS) and a hypodopaminergia trait/state.

Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats.

Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings.

Cocaine-associated odor cue re-exposure increases blood oxygenation level dependent signal in memory and reward regions of the maternal rat brain.

Background: Cue triggered relapse during the postpartum period can negatively impact maternal care. Given the high reward value of pups in maternal rats, we designed an fMRI experiment to test whether offspring presence reduces the neural response to a cocaine associated olfactory cue.

Methods: Cocaine conditioned place preference was carried out before pregnancy in the presence of two distinct odors that were paired with cocaine or saline (+Cue and -Cue).

In vivo functional brain mapping in a conditional mouse model of human tauopathy (tauP301L) reveals reduced neural activity in memory formation structures.

Background: Tauopathies are characterized by intracellular deposition of the microtubule-associated protein tau as filamentous aggregates. The rTg4510 mouse conditionally expresses mutant human tau protein in various forebrain areas under the Tet-off expression system. Mice develop neurofibrillary tangles, with significant neuronal loss and cognitive deficits by 6 months of age.

Spinal respiratory motoneurons and interneurons.

Maintenance of life among higher vertebrates depends on permanent, rhythmic and coordinated activity of respiratory muscles. Fundamental to our understanding of breathing is an appreciation for the neural components involved in the generation, maintenance and modulation of respiratory rhythm. Multidisciplinary studies have revealed important perspectives about the spinal and supraspinal components contributing to breathing, but a complete understanding of respiratory pathways and their interconnectivity remains unknown.

Bicistronic lentiviruses containing a viral 2A cleavage sequence reliably co-express two proteins and restore vision to an animal model of LCA1.

The disease processes underlying inherited retinal disease are complex and are not completely understood. Many of the corrective gene therapies designed to treat diseases linked to mutations in genes specifically expressed in photoreceptor cells restore function to these cells but fail to stop progression of the disease. There is growing consensus that effective treatments for these diseases will require delivery of multiple therapeutic proteins that will be selected to treat specific aspects of the disease process.

Expression characteristics of dual-promoter lentiviral vectors targeting retinal photoreceptors and Müller cells.

Purpose: Growing evidence suggests that successful treatment of many inherited photoreceptor diseases will require multi-protein therapies that not only correct the genetic defects linked to these diseases but also slow or halt the related degenerative phenotypes. To be effective, it is likely that therapeutic protein expression will need to be targeted to specific cell types. The purpose of this study was to develop dual-promoter lentiviral vectors that target expression of two proteins to retinal cones and rods, rods only, or Müller cells.

Identical neural risk factors predict cognitive deficit in dyslexia and schizophrenia.

In previous work, the authors found that an anatomical risk index created from the combination of 7 neuroanatomical measures predicted reading and oral language skills in individuals with learning disabilities. Individuals with small auditory brain structures and reduced asymmetry had more deficits than those with large structures and exaggerated asymmetry. In the present study, the same anatomical index predicted reading and other cognitive abilities in 45 individuals with chronic schizophrenia.

Central leptin insufficiency syndrome: an interactive etiology for obesity, metabolic and neural diseases and for designing new therapeutic interventions.

This review critically reappraises recent scientific evidence concerning central leptin insufficiency versus leptin resistance formulations to explain metabolic and neural disorders resulting from subnormal or defective leptin signaling in various sites in the brain. Research at various fronts to unravel the complexities of the neurobiology of leptin is surveyed to provide a comprehensive account of the neural and metabolic effects of environmentally imposed fluctuations in leptin availability at brain sites and the outcome of newer technology to restore leptin signaling in a site-specific manner. The cumulative new knowledge favors a unified central leptin insufficiency syndrome over the, in vogue, central resistance hypothesis to explain the global adverse impact of deficient leptin signaling in the brain.

Targeted expression of two proteins in neural retina using self-inactivating, insulated lentiviral vectors carrying two internal independent promoters.

Purpose: There is increasing interest in developing viral vectors capable of reliably delivering multiple therapeutic genes to targeted cell populations. Currently, bicistronic vectors carrying two transgenes linked by an internal ribosomal entry site (IRES) are the most commonly employed vectors to accomplish this goal. We and others have found that the protein encoded downstream of the IRES in these vectors is not reliably expressed.

Global life-long health benefits of repression of hypothalamic NPY system by central leptin gene therapy.

A minute-to-minute crosstalk between the hypothalamic neuropeptide Y (NPY) network and the hormone leptin is essential for energy homeostasis. Leptin insufficiency i.e.

Leptin gene transfer in the hypothalamus enhances longevity in adult monogenic mutant mice in the absence of circulating leptin.

Leptin, a product of the ob gene, is a pleiotropic signal implicated in regulation of multiple physiological functions in the periphery and centrally, including hypothalamic integration of energy homeostasis. Recessive mutations of ob gene result in early onset of hyperphagia, morbid obesity, metabolic disorders, early mortality and shortened life-span. Intracerebroventricular injection of recombinant adeno-associated virus vector (rAAV) encoding the leptin gene in adult obese ob/ob mice enhanced leptin transgene expression only in the hypothalamus, normalized food intake, body weight and more than doubled the life-span as compared to control cohorts and extended it to near that of normal wild type mice.

Central leptin gene therapy blocks ovariectomy-induced adiposity.

Objective: In this study, we tested the hypothesis that insufficiency of leptin restraint in the hypothalamus is responsible for promoting weight gain and adiposity after ovariectomy (ovx). Whether increasing leptin transgene expression can overcome the diminution in leptin restraint was evaluated in ovx rats.

Research Methods And Procedures: Enhanced leptin or green fluorescent protein (GFP; control) transgene expression was induced by a single intracerebroventricular injection of recombinant adeno-associated viral vector encoding either leptin gene (rAAV-lep) or GFP gene (rAAV-GFP; control) in acutely and chronically ovx rats.

Increased leptin expression in the dorsal vagal complex suppresses adiposity without affecting energy intake and metabolic hormones.

Objective: Increased leptin transgene expression locally in hypothalamic sites suppresses weight and energy intake, enhances thermogenic energy expenditure, and differentially modulates metabolic hormones for an extended period. We evaluated whether a similar localized expression of leptin transgene in the dorsal vagal complex (DVC) in the caudal brain stem that also displays the biologically relevant leptin receptor would reproduce these varied responses and thus demonstrate functional connectivity between the hypothalamus and DVC.

Research Methods And Procedures: Adult female rats were microinjected with a recombinant adeno-associated virus encoding either rat leptin or green fluorescent protein gene (control) in the DVC.

Lentiviral expression of retinal guanylate cyclase-1 (RetGC1) restores vision in an avian model of childhood blindness.

Background: Leber congenital amaurosis (LCA) is a genetically heterogeneous group of retinal diseases that cause congenital blindness in infants and children. Mutations in the GUCY2D gene that encodes retinal guanylate cyclase-1 (retGC1) were the first to be linked to this disease group (LCA type 1 [LCA1]) and account for 10%-20% of LCA cases. These mutations disrupt synthesis of cGMP in photoreceptor cells, a key second messenger required for function of these cells.