Author Interviews, Lancet, Neurology, Surgical Research / 05.07.2019

MedicalResearch.com Interview with: [caption id="attachment_50105" align="alignleft" width="158"]Natasha van Zyl, MBChB (Cape Town), FRACS FRACS Plastic and Reconstructive Surgeon Melbourne, Australia  Dr Natasha van Zy[/caption] Dr. Natasha van Zyl, MBChB (Cape Town), FRACS FRACS Plastic and Reconstructive Surgeon Melbourne, Australia  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The estimated global incidence of spinal cord injury (SCI) from all causes is 40 to 80 new cases per million population per year which means that every year between 250 000 to 500 000 people worldwide suffer SCI (1)(chap 2 p 17). In Australia the age standardised, annual incident rate of persisting traumatic SCI for Australian residents aged 15 years and above is 11.8 cases per million.(2) Just over 50% of all spinal cord injuries  in Australia occur at the cervical level resulting in tetraplegia. (2) Cervical spinal cord injury is a devastating, life-changing injury impacting almost every aspect of a person’s work, family and social life. Although compared to many other health conditions it has a relatively low incidence, it is certainly a high cost health condition, with the lifetime cost per tetraplegia incident case estimated to be AU$9.5 million.(3) For those living with tetraplegia improvement in hand function is their highest ranked goal.(4) As such, reconstruction of upper extremity function in cervical spinal cord injury is a crucial component of the surgical rehabilitation of people with mid/low cervical spinal cord injury as it has the capacity to restore critical functions such as elbow extension, wrist extension, grasp, key pinch and release. Traditionally these functions have been reconstructed using tendon transfers, which move a functioning muscle to a new insertion site to recreate the function of a paralysed muscle.(5)
Author Interviews, Brain Injury, Columbia, Critical Care - Intensive Care - ICUs, NEJM, Neurology / 27.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49981" align="alignleft" width="134"]Jan Claassen, MD, PhD, FNCS Associate Professor of Neurology Division of Division of Critical Care and Hospitalist Neurology Columbia University Medical Center Dr. Claassen[/caption] Jan Claassen, MD, PhD, FNCS Associate Professor of Neurology Division of Division of Critical Care and Hospitalist Neurology Columbia University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: Unconsciousness is common and predicting recovery is challenging – often inaccurate. Many patients do not show movements on commands and typically this is interpreted as unconsciousness. Some of these patients may be able to have brain response to these commands raising the possibility of some preservation of consciousness. This has previously been shown months or years after the injury mostly using MRI. We were able to detect this activation at the bedside in the ICU shortly after brain injury. For this we applied machine learning to the EEG to distinguish the brain’s responses to commands. Patients that showed this activation were more likely to follow commands prior to discharge and had better outcomes one year later. 
Author Interviews, Hospital Readmissions, JAMA, Neurology, Outcomes & Safety, University of Pennsylvania / 20.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49220" align="alignleft" width="180"]Sameed Khatana, MDFellow, Cardiovascular Medicine, Perleman School of MedicineAssociate Fellow, Leonard Davis Institute of Health EconomicsUniversity of Pennsylvania Dr. Khatana[/caption] Sameed Khatana, MD Fellow, Cardiovascular Medicine, Perleman School of Medicine Associate Fellow, Leonard Davis Institute of Health Economics University of Pennsylvania MedicalResearch.com: What is the background for this study? Response: There has been a growing use of quality metrics and indices in the US healthcare system. Much attention has been paid to quality measurement programs used by public payors, however, the use of such programs by commercial payors is much less studied. "Centers of excellence" are one type of quality designation program that is growing in use by commercial payors where certain hospitals are determined to be "high quality" for a certain disease state or procedure based on meeting certain criteria. For some people, this is even impacting the choice of providers and hospitals they can use by payors. We evaluated centers of excellence programs from three large commercial payors, Aetna, Cigna and Blue Cross Blue Shield, targeted at cardiovascular diseases and interventions and examined publicly reported outcomes for all hospitals performing percutaneous coronary interventions (cardiac stenting) in New York State. 
Accidents & Violence, Author Interviews, Diabetes, Neurology / 17.05.2019

MedicalResearch.com Interview with: foot-neuropathyMonica Perazzolo Research Centre for Musculoskeletal Science and Sports Medicine School of Healthcare Science, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK Department of Biomedical and Neuromotor Sciences University of Bologna, Bologna, Italy  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our research on motor control in diabetes focussed on the effect of diabetic peripheral neuropathy on driving. Drivers with diabetic peripheral neuropathy showed a less well controlled use of the accelerator pedal and sometimes larger, faster steering corrections needed to stay in lane when driving a simulator compared to healthy drivers and people with diabetes but no neuropathy. Despite these negative findings, an important result is that drivers with diabetic peripheral neuropathy demonstrated an improvement in their driving with practice. 
Author Interviews, Education, Neurology, NYU / 17.05.2019

MedicalResearch.com Interview with: Dr. Rebecca Stainman Dr. Arielle Kurzweil MD Adult Neurology Program Director New York University School of Medicine NYU Langone Health MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Physician burnout is prevalent. Neurologists have among the highest burnout rates, ranked third among specialties in a 2011 study, and over half of US Neurologists report at least 1 symptom of burnout in a 2016 survey.  Efforts to address burnout in training programs have mostly been aimed at implementing wellness curricula and offering mental health resources. Training neurology residents to effectively identify, address, and help impaired colleagues is equally crucial in these efforts, yet there is a paucity of literature on this topic. We used simulation as a means of addressing this topic, via identifying and addressing an impaired colleague through an objective structured clinical examination (OSCE). 
Author Interviews, Brain Injury, Neurological Disorders, Neurology, Stroke / 12.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49129" align="alignleft" width="128"]Thomas M Van Vleet PhDPosit Science  Dr. Van Vleet[/caption] Thomas M Van Vleet PhD Posit Science  Dr. Tom Van Vleet,  presented results on a common symptom of stroke and acquired brain injury (hemi-spatial neglect) at the American Academy of Neurology May 2019 MedicalResearch.com: What makes this study newsworthy? Response For the first time ever a highly-scalable intervention — computerized brain training (BrainHQ made by Posit Science) —was found to improve symptoms of hemi-spatial neglect, which is a common and often intractable and debilitating problem after stroke or other acquired brain injury. MedicalResearch.com: What can you tell us about the medical condition (hemi-spatial neglect) investigated in this study? Response About a third of patients with a brain injury exhibit a complex and debilitating array of neurological deficits known as the “neglect syndrome” (sometimes called, “hemi-spatial neglect” or “neglect”). The most apparent symptom of neglect is the inability of patients to efficiently process information on the side of space opposite the injury; often completely missing relevant events without awareness. As a result, patients often fail to adopt compensatory strategies or respond to other conventional rehabilitation protocols. The cost is significant, as patients with neglect experience longer hospital stays and have higher requirements for assistance, including greater skilled nursing home placements relative to patients with similar extent of brain injury without neglect. To date, there’s been no broadly-applicable and highly-scalable intervention for addressing neglect. An alarming reality given the increasing cost of stroke, which is currently estimated to exceed $34 billion per annum
Author Interviews, Clots - Coagulation, NEJM, Neurology / 09.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49060" align="alignleft" width="165"]Geoffrey A Donnan AOMBBS, MD, FRCP, FRACP, FAAHMSProfessor of NeurologyUniversity of Melbourne, Melbourne Brain Centre,Royal Melbourne and Austin Hospitals Prof. Donnan[/caption] Geoffrey A Donnan AO MBBS, MD, FRCP, FRACP, FAAHMS Professor of Neurology University of Melbourne, Melbourne Brain Centre Royal Melbourne and Austin Hospital MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Currently the thrombolysis time window for acute ischemic stroke is restricted to less than 4.5 hours from stroke onset and patients with wake-up stroke are not eligible. EXTEND is a multi-centre randomised placebo-controlled trial involving patient with acute ischemic stroke who presented between 4.5 to 9 hours of stroke onset or with wake-up-stroke and had penumbral tissue demonstrated on automated perfusion imaging. Patients were randomised to receive either alteplase or placebo. In total there were 225 patients recruited and the patients who received alteplase had higher rate of excellent functional outcome at 3 months (35.4% vs 29.5% adjusted odd ration 1.44 with 95% confidence interval 1.01 – 2.06 p=0.04). Patients who received alteplase achieved higher rate of early neurological improvement at day 3, reperfusion and recanalization at 24 hours. There was numerically more haemorrhage in the alteplase group but this not negate the functional benefit and there was no difference in the rate of mortality between the two groups. 
Author Interviews, McGill, Multiple Sclerosis, Neurology / 09.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49095" align="alignleft" width="146"]Douglas Arnold, MDThe Montreal Neurological Institute & HospitalMcGill University Montreal, QC, Canada Dr. Arnold[/caption] Douglas Arnold, MD The Montreal Neurological Institute & Hospital McGill University Montreal, QC, Canada MedicalResearch.com: What is the background for this study? Response: Diroximel fumarate (DRF) is a novel oral fumarate, with a distinct chemical structure that is being developed for relapsing forms of multiple sclerosis (MS). It is hypothesized that the distinct chemical structure of DRF may elicit less localized irritation in the gastrointestinal (GI) tract, potentially leading to improved GI tolerability. Diroximel fumarate is expected to have similar efficacy as dimethyl fumarate (marketed as TECFIDERA®), as both are converted to equivalent levels of monomethyl fumarate in the body. The EVOLVE-MS-1 study is primarily evaluating the safety of DRF and also exploring efficacy endpoints.  
Alzheimer's - Dementia, Author Interviews, Biomarkers, Neurological Disorders, Neurology, University of Pennsylvania / 08.05.2019

MedicalResearch.com Interview with: Lauren McCollum, MDCognitive and Behavioral Neurology FellowPenn Memory Center / Cognitive Neurology DivisionLauren McCollum, MD Cognitive and Behavioral Neurology Fellow Penn Memory Center / Cognitive Neurology Division MedicalResearch.com: What is the background for this study?   Response: Alzheimer’s Disease (AD) is a heterogenous condition, with considerable variability in cognitive symptoms and progression rates. One major reason for this heterogeneity is “mixed pathology,” – i.e., both AD- and non-AD pathology. Examples of non-AD pathology include cerebrovascular disease (CVD), Lewy Bodies, and TDP-43. Pathologically, Alzheimer’s Disease is defined by characteristic amyloid plaques and neurofibrillary tangles, which can be assessed for in living patients with CSF- or PET-based biomarkers for amyloid and tau, respectively. Classically, amyloid deposition begins years or even decades before pathologic tau accumulation, which is in turn associated with brain atrophy and cognitive decline. The recently developed NIA-AA “ATN” research framework allows for the classification of individuals with regard to 3 binary biomarkers: Amyloid (A), Tau (T), and Neurodegeneration (N). An individual’s ATN biomarker status indicates where along the “Alzheimer’s Disease continuum” they lie. Additionally, some ATN statuses are on the “typical AD” continuum, while others are not. Research has shown that 15-30% of cognitively normal older adults have elevated amyloid. It stands to reason that some portion of cognitively impaired individuals with elevated amyloid and neurodegeneration have something other than AD driving their neuronal injury. Within the context of the ATN research framework, this subset of people is the A+T-N+ group (i.e., people who have elevated amyloid and neurodegeneration, but are tau-negative), as amyloid alone (that is, amyloid without tau) is not thought to cause significant cognitive impairment or brain atrophy. Our hypothesis was that, compared to A+T+N+ (a set of typical-AD biomarkers), A+T-N+ have cognitive and neuroimaging profiles that deviate from a typical Alzheimer’s Disease pattern – i.e., with less memory loss and less atrophy in AD-signature regions – and may have biomarkers suggestive of alternate non-AD pathologies [e.g., white matter hyperintensities (WMHs), a marker of CVD].
Author Interviews, JAMA, Neurology, Stroke / 27.11.2018

MedicalResearch.com Interview with: [caption id="attachment_46196" align="alignleft" width="150"]Giacomo Koch, MD, PhD Laboratorio di Neurologia Clinica e Comportamentale Fondazione S. Lucia I.R.C.C.S. taly Dr. Koch[/caption] Giacomo Koch, MD, PhD Laboratorio di Neurologia Clinica e Comportamentale Fondazione S. Lucia I.R.C.C.S. Italy MedicalResearch.com: What is the background for this study? What are the main findings?  Response: We show in this paper that non invasive stimulation of the cerebellum in patients with stroke is able to improve motor functions. In particular we found that after three weeks of repetitive TMS of the intact cerebellum patients with hemiparesis due to stroke in the cerebral hemisphere remarkably improved their ability to walk and keep their balance, thus highly reducing the risk of fall. 
Addiction, Author Interviews, Neurology / 02.11.2018

MedicalResearch.com Interview with: "Be careful what you wish for #drugs #heroin #addiction #camp #church" by Matthew Kang is licensed under CC BY-ND 2.0Michaël Loureiro, PhD Research Assistant - Group Lüscher Dpt. of Fundamental Neuroscience University of Geneva - Faculty of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Addiction refers to the repeated and irrepressible urge to consume a drug even in the light of negative consequences. All addictive drugs are initially rewarding and have powerful reinforcing properties, which drive users to use the drug again and again. Within the scientific community, it has been repeatedly argued that for opioids, this initial reinforcing effect does not involve dopamine, and no consensus was emerging. In our study we used some of the most advanced genetic tools to observe that in less than a minute heroin strongly increased the activity of neurons in the midbrain causing a release of dopamine in the striatum, a brain region essential for reward seeking. We further used neuroanatomical tracing methods and found that dopamine neurons activated by heroin were projecting to the very medial region of the ventral striatum. Finally, when we silenced dopamine neurons, heroin lost its reinforcing power, confirming the validity of the dopamine activation hypothesis for opioids.
Author Interviews, Brain Injury, Heart Disease, JAMA, Neurology / 31.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45585" align="alignleft" width="133"]Dr-Marion Moseby-Knappe Dr. Moseby-Knappe[/caption] Marion Moseby-Knappe, MD Neurologist and Researcher Center for Cardiac Arrest at Lund University and Skane University Hospital Lund, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: Our research focuses on improving methods for examining unconscious patients treated on intensive care units after cardiac arrest. If a patient does not wake up within the first days after cardiac arrest, physicians need to evaluate how likely it is that the patient will awaken at all and to which extent there is brain injury. According to European and American guidelines, decisions on further medical treatment of cardiac arrest patients should always be based on a combination of examinations and not only one single method. Various methods are combined when assessing the patient such as examining different neurologic reflexes, head scans (computed tomography or magnetic resonance imaging), other specialist examinations (electroencephalogram or somatosensory evoked potentials) or blood markers. Our research focuses on patients included in the largest cardiac arrest trial to date, the Targeted Temperature Management after Out-of-Hospital Cardiac Arrest (TTM) Trial.
Author Interviews, JAMA, Neurology, Outcomes & Safety, Parkinson's, Pharmacology, University of Pennsylvania / 04.10.2018

MedicalResearch.com Interview with: [caption id="attachment_45003" align="alignleft" width="148"]Allison W. Willis, MD, MS Assistant Professor of Neurology Assistant Professor of Biostatistics and Epidemiology Senior Fellow, Leonard Davis Institute Senior Scholar, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania School of Medicine Dr. Willis[/caption] Allison W. Willis, MD, MS Assistant Professor of Neurology Assistant Professor of Biostatistics and Epidemiology Senior Fellow, Leonard Davis Institute Senior Scholar, Center for Clinical Epidemiology and Biostatistics University of Pennsylvania School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study was motivated by my own experiences as a neurologist-neuroscientist. I care for Parkinson disease patients, and over the year, have had numerous instances in which a person was taking a medication that could interact with their Parkinson disease medications, or could worsen their PD symptoms.
Author Interviews, Neurology, Pain Research / 25.09.2018

MedicalResearch.com Interview with: [caption id="attachment_44791" align="alignleft" width="172"]John Douglas Markman, M.D. Director, Translational Pain Research Program Department of Neurosurgery Associate Professor University of Rochester School of Medicine and Dentistry Dr. Markman[/caption] John Douglas Markman, M.D. Director, Translational Pain Research Program Department of Neurosurgery Professor University of Rochester School of Medicine and Dentistry  MedicalResearch.com: What is the background for this study? Response: Peripheral nerve injury after trauma and surgery is a leading cause of chronic pain and disability. These pain syndromes are often considered to have an underlying neuropathic mechanism because there is altered sensory processing (e.g., numbness, allodynia) at the site of trauma or surgical incision that localizes to the anatomic distribution of a peripheral nerve. A previous eight-week randomized clinical trial demonstrated efficacy for pregabalin in patients with chronic post-traumatic or -surgical pain.(10) The longer duration of treatment of this study was designed to meet the regulatory standard for a chronic pain indication in the US, 12 weeks of treatment at maintenance or fixed dosing.
Author Interviews, Exercise - Fitness, JAMA, Neurology, Parkinson's / 23.09.2018

MedicalResearch.com Interview with: Fudi Wang, M.D., Ph.D. Qiushi Chair Professor Nutrition Discovery Innovation Center School of Public Health/School of Medicine Zhejiang University Hangzhou 310058, ChinaFudi Wang, M.D., Ph.D. Qiushi Chair Professor Nutrition Discovery Innovation Center School of Public Health/School of Medicine Zhejiang University Hangzhou  China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Parkinson disease (PD) is the second most common neurodegenerative disease affecting approximately 10 million people around the world. To date, the cause of PD remains poorly understood. It is reported that 90% PD cases have no identifiable genetic cause. What’s worse, few therapeutic advances for the treatment of PD have been made in the past decades. Nevertheless, growing prospective longitudinal studies shed lights on the potential beneficial effect of lifestyle factors on reducing the risk of developing Parkinson disease. In this study, we performed a a dose-response meta-analysis of more than half a million participants. We found that physical activity, particularly moderate to vigorous physical activity, could significantly reduce PD risk.
Author Interviews, Cannabis, Neurology, University Texas / 17.09.2018

MedicalResearch.com Interview with: [caption id="attachment_44588" align="alignleft" width="149"]Dr. Francesca M. Filbey PhD Professor Program Head, Cognition and Neuroscience PhD Bert Moore Chair in BrainHealth UT Dallas Dr. Filbey[/caption] Dr. Francesca M. Filbey PhD Professor Program Head, Cognition and Neuroscience PhD Bert Moore Chair in BrainHealth UT Dallas MedicalResearch.com: What is the background for this study? What are the main findings? Response: The cannabis literature has generally focused on changes in brain function when engaged in a task. We were interested in examining whether these differences are present when not engaged in a task (i.e., during resting state) to understand baseline functional organization of the brain. Changes to baseline functional organization may reflect changes in brain networks underlying cognition. We also wanted to investigate whether specific brain waves, as measured by electroencephalography (EEG), are associated with measures of cannabis use, such as craving.
Author Interviews, Kidney Disease, Neurology, Sleep Disorders / 01.09.2018

MedicalResearch.com Interview with: [caption id="attachment_44254" align="alignleft" width="80"]Rachel Marie E. Salas, MD, MEHP, FAAN Associate Professor, Neurology and Nursing at Johns Hopkins Medicine Director, Interprofessional Education and Interprofessional Collaborative Practice Director, Neurology Clerkship Director, PreDoc Program Meyer/Neuro Sleep Baltimore, MD Dr Salas[/caption] Rachel Marie E. Salas, MD, MEHP, FAAN Associate Professor, Neurology and Nursing at Johns Hopkins Medicine Director, Interprofessional Education and Interprofessional Collaborative Practice Director, Neurology Clerkship Director, PreDoc Program Meyer/Neuro Sleep Baltimore, MD MedicalResearch.com: What is the background for this study? Can you briefly describe what is meant by RLS  and who suffers from it? Response: Restless Legs Syndrome (RLS) is a common neurological disorder characterized by an irritating, overwhelming urge to move (akathisia) the legs while at rest or sleep (conditions of diminished arousal), which almost immediately abates with mental or physical activity (conditions of maintained arousal). One of the most clinically-profound and scientifically relevant consequences of this disease process is an increased arousal state producing significant wake during sleep times and a relative sustainable degree of daytime alertness despite the degree of diseased-imposed sleep loss. The focus of most previous RLS research has been on the (limb) akathisia with associated periodic movements and reduction of these with dopaminergic treatment. Little research has been done to understand the broader biological dimensions​ of RLS. Patients with RLS have altered sleep-wake homeostasis with increased arousal and wakefulness (hyperarousal) not only driving the signature clinical symptoms (“the urge to move” and sleep loss) but also supporting arousal over sleep drive at night and in the day. We hypothesize that there is a basic glutamate-hyperarousal process producing both disrupted sleep (increased wake time) and cortical excitability (as demonstrated by transcranial magnetic stimulation (TMS)).​ 
Author Interviews, Neurology / 24.08.2018

MedicalResearch.com Interview with: MedicalResearch.comCaroline Schlüter, M.Sc. Psychologie Fakultät für Psychologie AE Biopsychologie Ruhr-Universität Bochum MedicalResearch.com: What is the background for this study? What are the main findings? Response: Individuals differ in their ability to initiate intended actions. While some people tend to put tasks off, others easily manage to tackle them directly. Although interindividual differences in what we call ‘action control’ make a major contribution to our everyday life by affecting our physical and mental health as well as our academic and occupational performance, their neural foundation was mostly unknown. Our study is the first to use both structural and functional neuroimaging methods to investigate the neural correlates of action control. We were able to show that poorer action control is significantly related to greater amygdala volume. The amygdala is considered to be a neuroanatomical hub for fear-motivated behavior. It processes sensory information in order to evaluate a given situation, behaviour or outcome. Hence, it is conceivable that individuals with a larger amygdala tend to evaluate future actions and their possible consequences more extensively. This, in turn, might lead to greater concern and hesitation, as observed in individuals with poorer action control. Further, we were able to show that weaker functional resting-state connectivity between the amygdala and the dorsal anterior cingulate cortex (dACC) is significantly associated with lower action control scores, which are typical for procrastinators. Previous studies indicate that the dACC has reciprocal connections with the amygdala, playing a significant role in purposive behaviour and self-control mechanisms. Thus, a weaker functional connection between both brain areas might hinder successful action control, as interfering negative emotions and 
Author Interviews, Neurology, Social Issues / 22.08.2018

MedicalResearch.com Interview with: [caption id="attachment_43852" align="alignleft" width="124"]Prof. Carmen Sandi Director, Brain Mind Institute Laboratory of Behavioral Genetics Brain Mind Institute Ecole Polytechnique Federale de Lausanne Lausanne, Switzerland  Prof. Sandi[/caption] Prof. Carmen Sandi Director, Brain Mind Institute Laboratory of Behavioral Genetics Brain Mind Institute Ecole Polytechnique Federale de Lausanne Switzerland  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Social hierarchies are pervasive and social status has deep consequences for health, wellbeing and societal organizations. Socially dominant individuals have priority access to resources and are more likely to become leaders. Although there are drastic differences in the predisposition of individuals to attain or strive for dominance, very little is known regarding the factors that predispose individuals to attain dominance. Does dominance become visible only in social context? Here, we performed five behavioral experiments and consistently found that individuals high in dominance are faster than less dominant ones to respond in choice situations, though not less accurate, which suggests that promptness to respond may predispose individuals to become dominant. Strikingly, using high-density EEG, we find that promptness to respond in dominant individuals is reflected in a strongly amplified brain signal at approximately 240 ms post-stimulus presentation. At this latency, participants’ reaction times were negatively correlated with activity in the cingulate cortex. Our results may open a new research approach using EEG signatures as a measure for dominance, independent of social context.
Alcohol, Author Interviews, Neurology / 22.08.2018

MedicalResearch.com Interview with: [caption id="attachment_44053" align="alignleft" width="133"]Erica Grodin, Ph.D. Postdoctoral Fellow Dept. of Psychology and Psychiatry  University of California Dr. Grodin[/caption] Erica Grodin, Ph.D. Postdoctoral Fellow Dept. of Psychology and Psychiatry University of California  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The hallmark of addictive disorders, including alcohol use disorder, is drug use that continues despite negative consequences. This pattern of use is referred to as “compulsive” and is one of the major barriers to treating addiction. We don’t yet fully understand what brain regions are responsible for compulsive alcohol use. Our study used a neuroimaging method called functional magnetic resonance imaging which allows us to see which areas of the brain are more active when an individual is performing a task. To investigate what brain regions are involved in compulsive alcohol seeking, we designed a task during which study participants could try to earn alcohol and food points at the risk of receiving a negative consequence, an electric shock. Study participants were light drinkers (men who drank <15 drinks/week and women who drank <10 drinks/week) and heavy drinkers (men who drank ≥20 drinks/week and women who drank ≥15 drinks/week). We found that heavy drinking individuals were more likely to try to earn alcohol points that were paired with a potential negative consequence than light drinkers were. This behavior of compulsive alcohol seeking was associated with increased brain activation in the medial prefrontal cortex, anterior insula, and ventral and dorsal striatum. 
ALS, Author Interviews, Neurology / 21.08.2018

MedicalResearch.com Interview with: [caption id="attachment_44022" align="alignleft" width="200"]Pier Lorenzo Puri, M.D PhD Professor in the Development, Aging and Regeneration Program Sanford Burnham Prebys Medical Discovery Institute  Dr. Puri[/caption] Pier Lorenzo Puri, M.D PhD Professor in the Development, Aging and Regeneration Program Sanford Burnham Prebys Medical Discovery Institute  MedicalResearch.com: What is the background for this study? What are the main findings? Response: My lab has been studying special repair cells called fibro-adipogenic progenitors (FAPs) and how these cells change in models of motor neuron diseases. These cells usually repair muscles after acute injury. But we are finding the FAPs change dramatically in disease settings. In this study we looked at these cells in models of spinal cord injury, ALS and spinal muscular atrophy, including muscle tissue from ALS patients. We found that FAPs change radically in several ways. Most importantly, the cells used a different signaling pathway, IL-6-STAT3, and when we blocked this signaling muscle atrophy and fibrosis halted. While further studies in humans are needed, this is a promising finding as FDA-approved medicines that block IL-6 and STAT3 are available. 
Annals Internal Medicine, Author Interviews, Neurology, Opiods / 21.08.2018

MedicalResearch.com Interview with: [caption id="attachment_29503" align="alignleft" width="200"]Tara Gomes, MHSc Li Ka Shing Knowledge Institute, St Michael’s Hospital, The Institute for Clinical Evaluative Sciences Leslie Dan Faculty of Pharmacy Department of Health Policy, Management, and Evaluation University of Toronto, Toronto, Ontario, Canada Tara Gomes[/caption] Tara Gomes, MHSc Li Ka Shing Knowledge Institute, St Michael’s Hospital, The Institute for Clinical Evaluative Sciences Leslie Dan Faculty of Pharmacy Department of Health Policy, Management, and Evaluation University of Toronto, Toronto, Ontario, Canada  MedicalResearch.com: What is the background for this study? Response: Pregabalin is a medication increasingly being prescribed to manage pain, however there is emerging evidence that this drug may increase one's risk of opioid overdose when prescribed with opioids.
Author Interviews, Neurology / 15.08.2018

MedicalResearch.com Interview with: [caption id="attachment_43897" align="alignleft" width="200"]People demonstrate biased belief updating: They tend to regard good news indicating that personal risks are lower than expected, and to disregard bad news indicating that personal risks are higher than expected. Kuzmanovic and colleagues show that this optimism bias depends on the update valuation by the ventromedial prefrontal cortex (vmPFC) and its influence on the dorsomedial prefrontal cortex (dmPFC) associated with self-referential reasoning. Credit: Bojana Kuzmanovic People demonstrate biased belief updating: They tend to regard good news indicating that personal risks are lower than expected, and to disregard bad news indicating that personal risks are higher than expected. Kuzmanovic and colleagues show that this optimism bias depends on the update valuation by the ventromedial prefrontal cortex (vmPFC) and its influence on the dorsomedial prefrontal cortex (dmPFC) associated with self-referential reasoning.
Credit: Bojana Kuzmanovic[/caption] Dr. Bojana Kuzmanovic PhD Max Planck Institute for Metabolism Research Translational Neurocircuitry Group Cologne, Germany MedicalResearch.com: What is the background for this study? What are the main findings? Response: Do our beliefs depend on what we want to believe? Until now, researchers failed to show how interactions between brain regions mediate the influence of motivation to adopt desirable notions on ongoing reasoning. Our study used optimized design and analyses to rule out alternative explanations and to identify underlying neurocircuitry mechanisms. MedicalResearch.com: What are the main findings? Response: First, we demonstrated that people’s belief formation behavior depends on their preferences. When people were asked to reconsider their beliefs about their future outcomes, they tended to rely more strongly on good news and to disregard bad news. Second, we showed that favorable belief updating activated the brain valuation system known to be responsive to rewards such as food or money (ventromedial prefrontal cortex, vmPFC). That is, the valuation system was activated when participants incorporated good news to improve their risk estimates, and when they disregarded bad news to avoid a worsening of their risk estimates. And third, the valuation system influenced other brain regions that are involved in deriving conclusions about oneself (dorsomedial prefrontal cortex, dmPFC). Importantly, the more participants were biased in their belief formation behavior, the stronger was the engagement and the influence of the valuation system. The influence of the valuation system on the reasoning system helps to understand how motivation can affect reasoning. It supports the idea that memories and knowledge we recall to form our beliefs are selected in such a way as to yield the desired conclusions. For example, when we wish to convince ourselves that our risk of having a heart attack is low although federal statistics indicate a higher risk, we might recall our healthy life style but not our family history of heart-related diseases, or neglect the fact that the federal population may have a comparable life style.
Author Interviews, Duke, Genetic Research, Neurology, Pediatrics / 30.07.2018

MedicalResearch.com Interview with:  [caption id="attachment_43604" align="alignleft" width="128"]Paul C Marcogliese, Ph.D. Postdoctoral Associate, Laboratory of Dr. Hugo Bellen Department of Molecular and Human Genetics Baylor College of Medicine Houston, Texas 77030 Dr. Marcogliese[/caption] Paul C Marcogliese, Ph.D. Postdoctoral Associate, Laboratory of Dr. Hugo Bellen Department of Molecular and Human Genetics Baylor College of Medicine Houston, Texas 77030 [caption id="attachment_43603" align="alignleft" width="99"]Loren D. Pena, MD PhD Pediatric Medical Genetics Specialist Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine, Durham, NC Dr. Peña[/caption] Loren D. Pena, MD PhD Division of Human Genetics Cincinnati Children's Hospital Medical Center Department of Pediatrics University of Cincinnati Cincinnati, OH 45229 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Undiagnosed Diseases Network (UDN) is a multi-site collaboration across the US that seeks to help diagnose patients with rare disorders that are ill-defined. Dr. Loren D.M. Pena and Dr. Vandana Shashi at the Duke-Columbia clinical site of the UDN had seen a patient with a severe neurological disorder. While the patient had no symptoms at birth, the patient began falling at about 3 years of age, eventually losing motor coordination and developing seizures. In the interim, the regression has progressed to a severely debilitating state. Re-analysis of the participant’s exome data by our site bioinformatician at Columbia (Nicholas Stong) in Dr. David Goldstein’s laboratory revealed a truncating variant in the single exon gene IRF2BPL that could be the candidate disease-causing gene. The UDN clinicians at Duke then contacted the UDN Model Organism Screening Center (MOSC) led by Dr. Hugo Bellen at Baylor College of Medicine and the Howard Hughes Medical Institute for functional analysis. In parallel, four more patients were found with truncating mutations causing a similar disorder though the UDN and GeneMatcher.org. Additionally, two patients with missense variants in IRF2BPL were identified that displayed seizures and some developmental delay or autism spectrum disorder but no motor regression. Work in MOSC by Dr. Paul Marcogliese using fruit flies revealed that the IRF2BPL truncating variants are severe loss of function mutations and one of the missense variants was a partial loss of function. Additionally, it was found that the fruit fly IRF2BPL gene, called pits, is expressed in the neurons of the adult fly brain. Lowering the levels of pits by about 50% in fly neurons leads to progressive behavioural abnormalities and neurodegeneration. By combining the human genetics, bioinformatics and model organism data, IRF2BPL was found to be a novel disease-causing gene in humans.
Author Interviews, JAMA, Neurology, Surgical Research / 30.07.2018

MedicalResearch.com Interview with: Jianning Zhang MD, Ph.D Chairman, II, VII Chinese Medical Association of Neurosurgery President, Tianjin Medical University General Hospital, China  Jianning Zhang MD, Ph.D Chairman, II, VII Chinese Medical Association of Neurosurgery President, Tianjin Medical University General Hospital, China   MedicalResearch.com: What is the background for this study? Response: The elderly population is growing dramatically world widely, especially in China. The incidence of chronic subdural hematoma has been rising over the past years. Although the surgery is not a difficult process, the risk of death and recurrence persist, and the affliction and economic expenditure of the patients are relatively higher in the elderly. For these reasons, it is urgent to develop novel pharmacological therapies with sufficient safety and efficacy.  It has been known that the high expression of VEGF and inflammatory factors in chronic subdural hematoma can lead to abundant angiogenesis of immature vessels on the wall of hematoma. In our previous study, patients with chronic subdural hematoma have impaired ability to promote vascular maturation. For example, the number of endothelial progenitor cells in circulating blood is about 67% of the healthy individuals with similar age.  Atorvastatin can mobilize endothelial progenitor cells to reduce inflammation. It increases the number of circulating endothelial cells that are inversely correlated with the volume of hematoma. We have demonstrated that atorvastatin can promote endothelial cell formation and reduce the leakage of endothelial cell barrier in vitro. Results from in vivo experiments in animal models of subdural hematoma suggest that atorvastatin can promote the maturation of blood vessels and reduce inflammation on the margin of hematoma, and thus improve the neurological outcome.
Author Interviews, Emergency Care, Neurology, Stroke / 13.07.2018

MedicalResearch.com Interview with: [caption id="attachment_43169" align="alignleft" width="125"]Perttu J. Lindsberg, MD, PhD Professor of Neurology Clinical Neurosciences and Molecular Neurology Research Programs Unit, Biomedicum Helsinki University of Helsinki Helsinki, Finland Dr. Lindsberg[/caption] Perttu JLindsberg, MD, PhD Professor of Neurology Clinical Neurosciences and Molecular Neurology Research Programs Unit, Biomedicum Helsinki University of Helsinki Helsinki, Finland MedicalResearch.com: What is the background for this study? Response: The past 20 years in shaping the Helsinki model in stroke thrombolysis have proven that we can be very fast in examining the patient, completing the imaging and starting thrombolytic therapy. This is a university hospital center that receives roughly three stroke suspects per day for evaluation of recanalization therapies. Already seven years ago we were able to push the median ’door-to-needle’ time permanently below 20 minutes. What we had not been monitoring was how well we had kept up the accuracy of our emergengy department (ED) diagnostic process. Prehospital emergency medical services (EMS) have been trained to focus on suspecting thrombolysis-eligible stroke and we usually get also pre-notifications of arriving stroke code patients during transportation, but the diagnosis on admission is an independent clinical judgment as the CT findings are largely nondiagnostic for acute changes. The admission evaluation of suspected acute stroke is therefore a decisive neurologic checkpoint, building the success of acute treatments such as recanalization therapy, but is complicated by differential diagnosis between true manifestations of stroke and numerous mimicking conditions. Although we have invested a lot on training and standardized ED procedures, time pressure and therapy-geared expectations may blur the diagnostic process. With this background, we embarked on an in-depth-analysis of the admission and final diagnoses of stroke code patients, as well as misdiagnoses, immediate treatment decisions and their consequences.
Author Interviews, Neurological Disorders, Neurology, Personalized Medicine, Radiology, Surgical Research / 13.07.2018

MedicalResearch.com Interview with: [caption id="attachment_43125" align="alignleft" width="139"]Yasser Iturria-Medina, PhD Primary Investigator, Ludmer Centre for Neuroinformatics & Mental Health Assistant Professor, Department of Neurology and Neurosurgery Faculty of Medicine McGill University Dr. turria-Medina[/caption] Yasser Iturria-Medina, PhD Primary Investigator, Ludmer Centre for Neuroinformatics & Mental Health Assistant Professor, Department of Neurology and Neurosurgery Faculty of Medicine McGill University MedicalResearch.com: What is the background for this study? What are the main findings? Response: There are millions of patients following therapeutic interventions that will not benefit them. In this study, we aimed to illustrate that it is possible to identify the most beneficial intervention for each patient, in correspondence with the principles of the personalized medicine (PM). Our results show that using multimodal imaging and computational models it is possible to predict individualized therapeutic needs. The predictions are in correspondence with the individual molecular properties, which validate our findings and the used computational techniques. The results highly also the imprecision of the traditional clinical evaluations and categories for understanding the individual therapeutic needs, evidencing the positive impact that would have to use multimodal data and data-driven techniques in the clinic, in addition to the medical doctor's criterion/evaluations.  
Author Interviews, Columbia, Neurology / 09.07.2018

MedicalResearch.com Interview with: Andrew Goldman PhD Laboratory for Intelligent Imaging and Neural Computing Department of Biomedical Engineering, Columbia University Presidential Scholar in Society and Neuroscience, Columbia University Andrew Goldman PhD Laboratory for Intelligent Imaging and Neural Computing Department of Biomedical Engineering, Columbia University Presidential Scholar in Society and Neuroscience, Columbia University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Many Western musicians have difficulty improvising, despite having extensive training and experience. These musicians learn about and use similar musical structures in their playing (like chords, scales, rhythmic patterns, etc.) as experienced improvisers, but they may know about them in different ways. In other words, different musicians have different ways of knowing and learning about similar musical structures. To understand which ways of knowing facilitate the ability to improvise contributes to an understanding of how people are able to use knowledge creatively. Western music provides an important opportunity to compare these different ways of knowing because in other improvisatory domains of behavior (like speaking), it is difficult to find people who know how to do it but cannot improvise with it (e.g., if you know a language, you can very likely improvise with that language). In order to advance our understanding of these improvisatory ways of knowing, we compared musicians with varying degrees of improvisation experience in a task that tested how they categorized musical chords. In Western music, different chords are theorized to have similar “functions.” For example, on a guitar, there are different ways to play a C chord, and you could often substitute one for the other. You might even play another chord in place of the C chord and have it sound similar, or lead to a similar subsequent harmony. Improvisers often use notation that specifies classes of chords rather than specific realizations (versions) of a chord whereas those who do not typically improvise use notation that specifies the full realization of the chord. By analogy, one chef might use a recipe that calls for “citrus” (in music, a class of musical chord) while another chef’s recipe might specifically call for “lemon” (in music, a specific realization of a functional class of chords). We tested whether improvisers categorize similar-functioning harmonies as more similar to each other than different-functioning harmonies, and compared how less experienced improvisers categorize the same harmonies. Our task required the musicians to listen to a series of repeating harmonies (the “standard” stimuli) and pick out occasional chords that were different in any way (the “deviant” stimuli). Some deviant stimuli were different versions of the standard chord (like limes in place of lemons) and some deviant stimuli were chords with different musical functions (like bananas instead of lemons). The more experienced improvisers were better at detecting the function deviants than the exemplar deviants whereas the less experienced improvisers showed little difference in their ability to detect the two types of deviants. In other words, because improvisers categorize the different versions of the same chord as similar, they have a relatively harder time picking out the similarly functioning harmonies. This was measured using behavioral data, and electroencephalography (EEG), which can be used to provide a neural measure of how different stimuli are perceived to be from each other.
Author Interviews, Neurology / 05.07.2018

MedicalResearch.com Interview with: Prof. David Adams Head of the French National Reference Centre for Familial Amyloidotic Polyneuropathy (NNERF)/APHP/INSERM Paris FranceProf. David Adams Head of the French National Reference Centre for Familial Amyloidotic Polyneuropathy (NNERF)/APHP/INSERM Paris France MedicalResearch.com:  What is the background for this study? Response: Hereditary transthyretin amyloidosis is an autosomal dominant, multisystemic, progressive, life-threatening disease caused by mutations in the gene encoding transthyretin (TTR ). The liver is the primary source of circulating tetrameric TTR protein. In hereditary transthyretin amyloidosis, both mutant and wild-type transthyretin deposit as amyloid in peripheral nerves and the heart, kidney, resulting in polyneuropathy and cardiomyopathy. Neuropathic changes result in profound sensorimotor disturbances, with deterioration in activities of daily living and ambulation, hypotension, diarrhea, impotence, and bladder disturbances. Until now,  only few patients have access to anti-amyloid therapy : Liver Transplantation or TTR stabilizers which are able only to slow progression of the disease at very early stage of the disease. Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin and is specifically addressed to the liver by lipid nanoparticle (LNP) formulation. This study carried out a multicenter, international, randomized, double-blind, placebo-controlled, phase 3 trial of patisiran in patients with hereditary transthyretin amyloidosis with polyneuropathy.