Publications by authors named "Bindu Menon"

70 Publications

Impact of Nutritional Epigenetics in Essential Hypertension: Targeting microRNAs in the Gut-Liver Axis.

Curr Hypertens Rep 2021 05 7;23(5):28. Epub 2021 May 7.

Microbiome Consortium, Center for Hypertension and Precision Medicine, Department of Physiology and Pharmacology, The University of Toledo College of Medicine and Life Sciences, Block Health Science Bldg, 3000 Arlington Ave, Toledo, OH, 43614, USA.

Purpose Of Review: To review the current knowledge on interactions between dietary factors and microRNAs (miRNAs) in essential hypertension (EH) pathogenesis.

Recent Findings: There exists an integration of maintenance signals generated by genetic, epigenetic, immune, and environmental (e.g., dietary) factors that work to sustain balance in the gut-liver axis. It is well established that an imbalance in this complex, intertwined system substantially increases the risk for EH. As such, pertinent research has been taken to decipher how each signal operates in isolation and together in EH progression. Recent literature indicates that both macro- and micronutrients interrupt regulatory miRNA expressions and thus, alter multiple cellular processes that contribute to EH and its comorbidities. We highlight how carbohydrates, lipids, proteins, salt, and potassium modify miRNA signatures during EH. The disruption in miRNA expression can negatively impact communication systems such as over activating the renin-angiotensin-aldosterone system, modulating the vascular smooth muscle cell phenotype, and promoting angiogenesis to favor EH. We also delineate the prognostic value of miRNAs in EH and discuss the pros and cons of surgical vs dietary prophylactic approaches in EH prevention. We propose that dietary-dependent perturbation of the miRNA profile is one mechanism within the gut-liver axis that dictates EH development.
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http://dx.doi.org/10.1007/s11906-021-01142-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105193PMC
May 2021

Global Impact of COVID-19 on Stroke Care and IV Thrombolysis.

Neurology 2021 06 25;96(23):e2824-e2838. Epub 2021 Mar 25.

Department of Neurology (R.G.N., M.H.M., M.Frankel, D.C.H.), Marcus Stroke and Neuroscience Center, Grady Memorial Hospital, Emory University School of Medicine, Atlanta; Department of Radiology (M.M.Q., M.A., T.N.N., A.K.) and Radiation Oncology (M.M.Q.), Boston Medical Center, Boston University School of Medicine, Massachusetts; Department of Neurology (S.O.M.), Federal University of Rio Grande do Sul, Porto Alegre; Hospital de Clínicas de Porto Alegre (S.O.M.), Brazil; Department of Stroke Neurology (H. Yamagami), National Hospital Organization, Osaka National Hospital, Japan; Department of Neurology (Z.Q.), Xinqiao Hospital of the Army Medical University, Chongqing, China; Department of Neurology (O.Y.M.), Stroke and Neurointervention Division, Alexandria University Hospital, Alexandria University, Egypt; Boston University School of Medicine (A.S.), Massachusetts; 2nd Department of Neurology (A.C.), Institute of Psychiatry and Neurology, Warsaw, Poland; Department of Neurology (G.T., L.P.), National & Kapodistrian University of Athens, School of Medicine, Attikon University Hospital, Athens, Greece; Faculdade de Medicina (D.A.d.S.), Universidade de Lisboa, Lisbon, Portugal; Department of Neurology (J.D., R.L.), Leuven University Hospital, Belgium; International Clinical Research Center and Department of Neurology (R.M.), St. Anne´s University Hospital in Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Neurology (P.V.), Groeninge Hospital, Kortrijk; Department of Neurology (P.V.), University Hospitals Antwerp; Department of Translational Neuroscience (P.V.), University of Antwerp, Belgium; Department of Neurology (J.E.S., T.G.J.), Cooper Neurological Institute, Cooper University Hospital, Camden, New Jersey; Department of Neurology and Neurosurgery (J. Kõrv), University of Tartu, Estonia; Department of Neurology (J.B., R.V.,S.R.), Loyola University Chicago Stritch School of Medicine, Illinois; Department of Neurosurgery (C.W.L.), Kaiser Permanente Fontana Medical Center; Department of Neurology (N.S.S.), Kaiser Permanente Los Angeles Medical Center; Department of Neurology (A.M.Z., S.A.S.), UT Health McGovern Medical School, Houston, Texas; Department of Neurology (A.L.Z.), Medical University of South Carolina, Charleston; Department of Internal Medicine (G.N.), School of Health Sciences, University of Thessaly, Larissa, Greece; Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, Pennsylvania; Department of Neurology (A.L.), Ohio Health Riverside Methodist Hospital Columbus; Department of Medicine and Neurology (A.R.), University of Otago and Wellington Hospital, New Zealand; Department of Neurology (E.A.M.), Vanderbilt University Medical Center, Nashville, Tennessee; Department of Neurology (A.W.A., D. Alsbrook), University of Tennessee Health Center, Memphis; Department of Neurology (D.Y.H.), University of North Carolina at Chapel Hill; Departments of Neurology (S.Y.) and Radiology (E.R.), New York University Grossman School of Medicine; Douala Gynaeco-Obstetric and Pediatric Hospital (E.G.B.L.), University of Douala, Faculty of Medicine and Pharmaceutical Science, Cameroon; Ain Shams University Specialized Hospital (H.M.A., H.M.S., A.E., T.R.); Cairo University Affiliated MOH Network (F.H.); Department of Neurology (TM.), Nasser Institute for Research and Treatment, Cairo; Mansoura University Affiliated Private Hospitals Network (W.M.), Egypt; Kwame Nkrumah University of Science and Technology (F.S.S.), Kumasi, Ghana; Stroke Unit (T.O.A., K.W.), University of Ilorin Teaching Hospital; Neurology Unit (B.A.), Department of Medicine, Lagos State University Teaching Hospital; Department of Medicine (E.O.N.), Federal Medical Centre Owerri, Imo State, Nigeria; Neurology Unit (T.A.S.), Department of Medicine, Federal Medical Centre, Owo, Ondo State, Nigeria; University College Hospital (J.Y.), Ibadan, Nigeria; The National Ribat University Affiliated Hospitals (H.H.M.), Khartoum, Sudan; Neurology Section (P.B.A.), Department of Internal Medicine, Aga-Khan University, Medical College East Africa, Dar es Salaam, Tanzania; Tunis El Manar University (A.D.R.), Military Hospital of Tunis; Department of Neurology (S.B.S.), Mongi Ben Hmida National Institute of Neurology, Faculty of Medicine of Tunis, University Tunis El Manar, Tunisia; Department of Physiology (L.G.), Parirenyatwa Hospital, and Departments of Physiology and Medicine (G.W.N.), University of Zimbabwe, Harare; Department of Cerebrovascular/Endovascular Neurosurgery Division (D.S.), Erebouni Medical Center, Yerevan, Armenia; Department of Neurology (A.R.), Sir Salimulah College, Dhaka, Bangladesh; Department of Neurology (Z.A.), Taihe Hospital of Shiyan City, Hubei; Department of Neurology (F.B.), Nanyang Central Hospital, Henan; Department of Neurology (Z.D.), Wuhan No. 1 Hospital, Hubei, China; Department of Neurology (Y. Hao.), Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Department of Neurology (W.H.), Traditional Chinese Medicine Hospital of Maoming, Guangdong; Department of Neurology (G.Li.), Affiliated Hospital of Qingdao University, Shandong; Department of Neurology (W.L), The First Affiliated Hospital of Hainan Medical College; Department of Neurology (G.Liu.), Wuhan Central Hospital, Hubei; Department of Neurology (J.L.), Mianyang 404th Hospital, Sichuan; Department of Neurology (X.S.), Yijishan Hospital of Wannan Medical College, Anhui; Department of Neurology and Neuroscience (Y.S.), Shenyang Brain Institute, Shenyang First People's Hospital, Shenyang Medical College Affiliated Brain Hospital; Department of Neurology (L.T.), Affiliated Yantai Yuhuangding Hospital of Qingdao University, Shandong; Department of Neurology (H.W.), Xiangyang Central Hospital, Hubei; Department of Neurology (B.W., Y.Yan), West China Hospital, Sichuan University, Chengdu; Department of Neurology (Z.Y.), Affiliated Hospital of Southwest Medical University, Sichuan; Department of Neurology (H.Z.), Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine; Department of Neurology (J.Z.), The First Affiliated Hospital of Shandong First Medical University; Department of Neurology (W.Z.), First Affiliated Hospital of Fujian Medical University, China; Acute Stroke Unit (T.W.L.), The Prince of Wales Hospital, Kwok Tak Seng Centre for Stroke Research and Intervention, The Chinese University of Hong Kong; Interventional Neurology (C.C.), MAX Superspecialty Hospital, Saket, New Delhi; NH Institute of Neurosciences (V.H.), NH Mazumdar Shaw Medical Center, Bangalore; Department of Neurology (B.M.), Apollo Speciality Hospitals Nellore; Department of Neurology (J.D.P.), Christian Medical College, Ludhiana, Punjab; Sree Chitra Tirunal Institute for Medical Sciences and Technology (P.N.S.), Kerala, India; Stroke Unit (F.S.U.), Pelni Hospital, Jakarta, Indonesia; Neurosciences Research Center (M. Farhoudi, E.S.H.), Tabriz University of Medical Sciences, Tabriz, Iran; Beer Sheva Hospital (A.H.); Department of Interventional Neuroradiology, Rambam Healthcare Campus, Haifa, Israel (A.R., R.S.H.); Departments of Neurology (N.O.) and Neurosurgery (N.S.), Kobe City Medical Center General Hospital, Kobe; Department of Stroke and Neurovascular Surgery (D.W.), IMS Tokyo-Katsushika General Hospital; Yokohama Brain and Spine Center (R.Y.); Iwate Prefectural Central (R.D.); Department of Neurology and Stroke Treatment (N.T.), Japanese Red Cross Kyoto Daiichi Hospital; Department of Neurology (T.Y.), Kyoto Second Red Cross Hospital; Department of Neurology (T.T.), Japanese Red Cross Kumamoto Hospital; Department of Stroke Neurology (Y. Yazawa), Kohnan Hospital, Sendai; Department of Cerebrovascular Medicine (T.U.), Saga-Ken Medical Centre; Department of Neurology (T.D.), Saitama Medical Center, Kawagoe; Department of Neurology (H.S.), Nara City Hospital; Department of Neurology (Y.S.), Toyonaka Municipal Hospital, Osaka; Department of Neurology (F. Miyashita), Kagoshima City Hospital; Department of Neurology (H.F.), Japanese Red Cross Matsue Hospital, Shimane; Department of Neurology (K.M.), Shiroyama Hospital, Osaka; Department of Cerebrovascular Medicine (J.E.S.), Niigata City General Hospital; Department of Neurology (Y.S.), Sugimura Hospital, Kumamoto; Stroke Medicine (Y. Yagita), Kawasaki Medical School, Okayama; Department of Neurology (Y.T.), Osaka Red Cross Hospital; Department of Stroke Prevention and Treatment (Y.M.), Department of Neurosurgery, University of Tsukuba, Ibaraki; Department of Neurology (S.Y.), Stroke Center and Neuroendovascular Therapy, Saiseikai Central Hospital, Tokyo; Department of Neurology (R.K.), Kin-ikyo Chuo Hospital, Hokkaido; Department of Cerebrovascular Medicine (T.K.), NTT Medical Center Tokyo; Department of Neurology and Neuroendovascular Treatment (H. Yamazaki), Yokohama Shintoshi Neurosurgical Hospital; Department of Neurology (M.S.), Osaka General Medical Center; Department of Neurology (K.T.), Osaka University Hospital; Department of Advanced Brain Research (N.Y.), Tokushima University Hospital Tokushima; Department of Neurology (K.S.), Saiseikai Fukuoka General Hospital, Fukuoka; Department of Neurology (T.Y.), Tane General Hospital, Osaka; Division of Stroke (H.H.), Department of Internal Medicine, Osaka Rosai Hospital; Department of Comprehensive Stroke (I.N.), Fujita Health University School of Medicine, Toyoake, Japan; Department of Neurology (A.K.), Asfendiyarov Kazakh National Medical University; Republican Center for eHealth (K.F.), Ministry of Health of the Republic of Kazakhstan; Department of Medicine (S.K.), Al-Farabi Kazakh National University; Kazakh-Russian Medical University (M.Z.), Kazakhstan; Department of Neurology (J.-H.B.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul; Department of Neurology (Y. Hwang), Kyungpook National University Hospital, School of Medicine, Kyungpook National University; Ajou University Hospital (J.S.L.); Department of Neurology (S.B.L.), Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea; Department of Neurology (J.M.), National Medical Center, Seoul; Department of Neurology (H.P., S.I.S.), Keimyung University School of Medicine, Dongsan Medical Center, Daegu; Department of Neurology (J.H.S.), Busan Paik Hospital, School of Medicine, Inje University, Busan; Department of Neurology (K.-D.S.), National Health Insurance Service Ilsan Hospital, Goyang; Asan Medical Center (C.J.Y.), Seoul, South Korea; Department of Neurology (R.A.), LAU Medical Center-Rizk Hospital, Beirut, Lebanon; Department of Medicine (W.A.W.Z., N.W.Y.), Pusat Perubatan Universiti Kebangsaan Malaysia, Kuala Lumpur; Sultanah Nur Zahirah (Z.A.A., K.A.I.), Kuala Terengganu; University Putra Malaysia (H.b.B.); Sarawak General Hospital, Kuching (L.W.C.); Hospital Sultan Abdul Halim (A.B.I.), Sungai Petani Kedah; Hospital Seberang Jaya (I.L.), Pulau Pinang; Thomson Hospital Kota Damansara (W.Y.T.), Malaysia; "Nicolae Testemitanu" State University of Medicine and Pharmacy (S.G., P.L.), and Department of Neurology, Emergency Medicine Institute, Chisinau, Republic of Moldova; Department of Stroke Unit (A.M.A.H.), Royal Hospital Muscat, Oman; Neuroscience Institute (Y.Z.I., N.A.), Hamad Medical Corporation, Doha, Qatar; St. Luke's Medical Center-Institute of Neurosciences (M.C.P.-F., C.O.C.), Quezon City, Philippines; Endovascular Neurosurgery (D.K.), Saint-Petersburg Dzhanelidze Research Institute of Emergency Medicine, St. Petersburg, Russia; Department of Neurology (A.A.), Stroke Unit, King Saud University, College of Medicine, Riyadh; Department of Neurosurgery (H.A.-J.), Interventional Radiology, and Critical Care Medicine, King Fahad Hospital of the University, Imam Abdulrahman bin Faisal University, Saudi Arabia; Singapore National Neuroscience Institute (C.H.T.); Changi General Hospital (M.J.M.), Singapore; Neuroscience Center, Raffles Hospital (N.V.), Singapore; Department of Neurology (C.-H.C., S.-C.T.), National Taiwan University Hospital; Department of Radiology (A.C.), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Dicle University Medical School and Hospital (E.A.), Diyarbakir; Stroke and Neurointervention Unit (O.A., A.O.O.), Eskisehir Osmangazi University; Gaziantep University Faculty of Medicine (S.G.), Turkey; Department of Neurology (S.I.H., S.J.), Neurological Institute at Cleveland Clinic Abu Dhabi, United Arab Emirates; Stroke Center (H.L.V., A.D.C.), Hue Central Hospital, Hue, Vietnam; Stroke Department (H.H.N., T.N.P.), Da Nang Hospital, Da Nang City; 115 People's Hospital (T.H.N., T.Q.N.), Ho Chi Minh City, Vietnam; Department of Neurology (T.G., C.E.), Medical University of Graz; Department of Neurology (M. K.-O.), Research Institute of Neurointervention, University Hospital Salzburg/Paracelsus Medical University, Austria; Department of Neurology (F.B., A.D.), Centre Hospitalier Universitaire de Charleroi, Belgium; Department of Neurology (S.D.B., G.V.), Sint Jan Hospital, Bruges; Department of Neurology (S.D.R.), Brussels University Hospital (UZ Brussel); Department of Neurology (N.L.), ULB Erasme Hospitals Brussels; Department of Neurology (M.P.R.), Europe Hospitals Brussels; Department of Neurology (L.Y.), Antwerp University Hospital, Belgium; Neurology Clinic (F.A., T.S.), St. Anna University Hospital, Sofia, Bulgaria; Department of Neurology (M.R.B.), Sestre Milosrdnice University Hospital, Zagreb; Department of Neurology (H.B.), Sveti Duh University Hospital, Zagreb; Department of Neurology (I.C.), General Hospital Virovitica; Department of Neurology (Z.H.), General Hospital Zabok; Department of Radiology (F. Pfeifer), University Hospital Centre Zagreb, Croatia; Regional Hospital Karlovy Vary (I.K.); Masaryk Hospital Usti nad Labem (D.C.); Military University Hospital Praha (M. Sramek); Oblastní Nemocnice Náchod (M. Skoda); Regional Hospital Pribram (H.H.); Municipal Hospital Ostrava (L.K.); Hospital Mlada Boleslav (M. Koutny); Hospital Vitkovice (D.V.); Hospital Jihlava (O.S.); General University Hospital Praha (J.F.); Hospital Litomysl (K.H.); Hospital České Budejovice (M.N.); Hospital Pisek (R.R.); Hospital Uherske Hradiste (P.P.); Hospital Prostejov (G.K.); Regional Hospital Chomutov (J.N.); Hospital Teplice (M.V.); Mining Hospital Karvina (H.B.); Thomayer Hospital Praha (D.H.); Hospital Blansko (D.T.); University Hospital Brno (R.J.); Regional Hospital Liberec (L.J.); Hospital Ceska Lipa (J.N.); Hospital Sokolov (A.N.); Regional Hospital Kolin (Z.T.); Hospital Trutnov (P. Fibrich); Hospital Trinec (H.S.); Department of Neurology (O.V.), University Hospital Ostrava, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Bispebjerg Hospital (H.K.C.), University of Copenhagen; Stroke Center (H.K.I., T.C.T.), Rigshospitalet, University of Copenhagen; Aarhus University Hospital (C.Z.S.), Aarhus; Neurovascular Center, Zealand University Hospital, University of Copenhagen (T.W.), Roskilde, Denmark; Department of Neurology and Neurosurgery (R.V.), University of Tartu, Estonia; Neurology Clinic (K.G.-P.), West Tallinn Central Hospital; Center of Neurology (T.T.), East Tallinn Central Hospital, School of Natural Sciences and Health, Tallinn University; Internal Medicine Clinic (K.A.), Pärnu Hospital, Estonia; Université Lille, Inserm, CHU Lille, Lille Neuroscience & Cognition (C.C., F.C.); Centre Hospitalier d'Arcachon (M.D.), Gujan-Mestras; Centre Hospitalier d'Agen (J.-M.F.); Neurologie Vasculaire (L.M.) and Neuroradiologie (O.E.), Hospices Civils de Lyon, Hôpital Pierre Wertheimer, Bron; Centre Hospitalier et Universitaire de Bordeaux (E.L., F.R.); Centre Hospitalier de Mont de Marsan (B.O.); Neurologie (R.P.), Fondation Ophtalmologique Adolphe de Rothschild; Versailles Saint-Quentin-en-Yvelines University (F. Pico); Neuroradiologie Interventionelle (M.P.), Fondation Ophtalmologique Adolphe de Rothschild; Neuroradiologie Interventionelle (R.P.), Hôpitaux Universitaires de Strasbourg, France; K. Eristavi National Center of Experimental and Clinical Surgery (T.G.), Tbilisi; Department of Neurosurgery (M. Khinikadze), New Vision University Hospital, Tbilisi; Vivamedi Medical Center (M. Khinikadze), Tbilisi; Pineo Medical Ecosystem (N.L.), Tbilisi; Ivane Javakhishvili Tbilisi State University (A.T.), Tbilisi, Georgia; Department of Neurology (S.N., P.A.R.), University Hospital Heidelberg; Department of Neurology (M. Rosenkranz), Albertinen Krankenhaus, Hamburg; Department of Neurology (H.S.), Elbe Klinken Stade, University Medical Center Göttingen; Department of Neurology (T.S.), University Hospital Carl Gustav Carus, Dresden; Kristina Szabo (K.S.), Department of Neurology, Medical Faculty Mannheim, University Heidelberg, Mannheim; Klinik und Poliklinik für Neurologie (G.T.), Kopf- und Neurozentrum, Universitätsklinikum Hamburg-Eppendorf, Germany; Department of Internal Medicine (D.S.), School of Health Sciences, University of Thessaly, Larissa; Second Department of Neurology (O.K.), Stroke Unit, Metropolitan Hospital, Piraeus, Greece; University of Szeged (P.K.), Szeged; University of Pecs (L.S., G.T.), Hungary; Stroke Center (A.A.), IRCCS Istituto di Ricovero e Cura a Carattere Scientifico, Negrar, Verona; Department of Neurology (F.B.), Ospedale San Paolo, Savona,; Institute of Neurology (P.C., G.F.), Fondazione Policlinico Universitario Agostino Gemelli, Rome; Interventional Neurovascular Unit (L.R.), Careggi University Hospital, Florence; Stroke Unit (D.S.), Azienda Socio Sanitaria Territoriale (ASST) di Lecco, Italy; Maastricht University Medical Center; Department of Neurology (M.U.), Radiology, University Medical Center Groningen; Department of Neurology (I.v.d.W.), Haaglanden Medical Center, the Hague, the Netherlands; Department of Neurology (E.S.K.), Akershus University Hospital, Lørenskog, General Practice, HELSAM, University of Oslo, Norway; Neurological Ward with Stroke Unit (W.B.), Specialist Hospital in Konskie, Gimnazjalna, Poland and Collegium Medicum, Jan Kochanowski University, Kielce, Poland; Neurological Ward with Stroke Unit (M.F.), District Hospital in Skarzysko-Kamienna; Department of Neurology (E.H.L.), Szpitala im T. Marciniaka in Wroclaw; 2nd Department of Neurology (M. Karlinski), Institute of Psychiatry and Neurology, Warsaw; Department of Neurology and Cerebrovascular Disorders (R.K., P.K.), Poznan University of Medical Sciences; 107th Military Hospital with Polyclinic (M.R.), Walcz; Department of Neurology (R.K.), St. Queen Jadwiga, Clinical Regional Hospital No. 2, Rzeszow; Department of Neurology (P.L.), Medical University of Lublin; 1st Department of Neurology (H.S.-J.), Institute of Psychiatry and Neurology, Warsaw; Department of Neurology and Stroke Unit (P.S.), Holy Spirit Specialist Hospital in Sandomierz, Collegium Medicum Jan Kochanowski University in Kielce; Copernicus PL (W.F.), Neurology and Stroke Department, Hospital M. Kopernik, Gdansk; Stroke Unit (M.W.), Neurological Department, Stanislaw Staszic University of Applied Sciences, Pila, Poland; Hospital São José (Patricia Ferreira), Centro Hospitalar Universitário de Lisboa Central, Lisbon; Stroke Unit (Paulo Ferreira, V.T.C.), Hospital Pedro Hispano, Matosinhos; Stroke Unit, Internal Medicine Department (L.F.), Neuroradiology Department, Centro Hospitalar Universitário de São João, Porto; Department of Neurology (J.P.M.), Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal; Department of Neurosciences (T.P.e.M.), Hospital de Santa Maria-CHLN, North Lisbon University Hospital; Hospital São José (A.P.N.), Centro Hospitalar Universitário de Lisboa Central, Lisbon; Department of Neurology (M. Rodrigues), Hospital Garcia de Orta, Portugal; Department of Neurology (C.F.-P.), Transilvania University, Brasov, Romania; Department of Neurology (G.K., M. Mako), Faculty Hospital Trnava, Slovakia; Department of Neurology and Stroke Center (M.A.d.L., E.D.T.), Hospital Universitario La Paz, Madrid; Department of Neurology (J.F.A.), Hospital Clínico Universitario, Universidad de Valladolid; Department of Neurology (O.A.-M.), Complejo Hospitalario Universitario de Albacete; Department of Neurology (A.C.C.), Unidad de Ictus, Hospital Universitario Ramon y Cajal, Madrid; Department of Neurology (S.P.-S), Hospital Universitario Virgen Macarena & Neurovascular Research Laboratory (J.M.), Instituto de Biomedicina de Sevilla-IbiS; Rio Hortega University Hospital (M.A.T.A.), University of Valladolid; Cerebrovascular Diseases (A.R.V.), Hospital Clinic of Barcelona, Spain; Department of Neurology (M. Mazya), Karolinska University Hospital and Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Department of Interventional Neuroradiology (G.B.), University Hospitals of Geneva; Department of Interventional and Diagnostic Neuroradiology (A.B., M.-N.P.), Radiology and Nuclear Medicine, University Hospital Basel; Department of Neurology (U.F.), University of Bern; Department of Neuroradiology (J.G.), University of Bern; Department of Neuroscience (P.L.M., D.S.), Lausanne University Hospital, Switzerland; Department of Stroke Medicine (S.B., J. Kwan), Imperial College Healthcare NHS Trust, Charing Cross Hospital, London; Department of Neurology (K.K.), Queen's Medical Centre, Nottingham University Hospitals NHS Trust, United Kingdom; Department of Neurology (A.B., A. Shuaib), University of Alberta, Edmonton; Department of Neurology (L.C., A. Shoamanesh), McMaster University, Hamilton; Department of Clinical Neurosciences and Hotchkiss Brain Institute (A.M.D., M.D.H.), University of Calgary; Department of Neurology (T.F., S.Y.), University of British Columbia, Vancouver; Mackenzie Health (J.H., C.A.S.) Richmond Hill, Ontario; Department of Neurology (H.K.), Sunnybrook Health Sciences Centre, University of Toronto; Department of Neurology (A. Mackey), Hopital Enfant Jesus, Centre Hospitalier de l'Universite Laval, Quebec City; Department of Neurology (A.P.), University of Toronto; Medicine (G.S.), St. Michael's Hospital, University of Toronto, Canada; Department of Neurosciences (M.A.B.), Hospital Dr. Rafael A. Calderon Guardia, CCSS. San Jose, Costa Rica; Neurovascular Service (J.D.B.), Hospital General San Juan de Dios, Guatemala City; Department of Neurología (L.I.P.R.), Hospital General de Enfermedades, Instituto Guatemalteco de Seguridad Social, Guatemala City, Guatemala; Department of Neurology (F.G.-R.), University Hospital Jose Eleuterio Gonzalez, Universidad Autonoma de Nuevo Leon, Mexico; Pacífica Salud-Hospital Punta Pacífica (N.N.-E., A.B., R.K.), Panama; Department of Neurology, Radiology (M.A.), University of Kansas Medical Center; Department of Neurointerventional Neurosurgery (D. Altschul), The Valley Baptist Hospital, Ridgewood, New Jersey; Palmetto General Hospital (A.J.A.-O.), Tenet, Florida; Neurology (I.B., P.K.), University Hospital Newark, New Jersey Medical School, Rutgers, Newark, New Jersey; Community Healthcare System (A.B.), Munster, Indiana; Department of Neurology (N.B., C.B.N.), California Pacific Medical Center, San Francisco; Department of Neurology (C.B.), Mount Sinai South Nassau, New York; University of Toledo (A.C.), Ohio; Department of Neurology (S.C.), University of Maryland School of Medicine, Baltimore, Maryland; Neuroscience (S.A.C.), Inova Fairfax Hospital, Virginia; Department of Neurology (H.C.), Abington Jefferson Hospital, Pennsylvania; Department of Neurology (J.H.C.), Mount Sinai South Nassau, New York; Baptist Health Medical Center (S.D.), Little Rock, Arkansas; Department of Neurology (K.D.), HCA Houston Healthcare Clearlake, Texas; Department of Neurology (T.G.D., R.S.), Erlanger, Tennessee; Wilmington North Carolina (V.T.D.); Department of Vascular and Neurointerventional Services (R.E.), St. Louis University, Missouri; Department of Neurology (M.E.), Massachusetts General Hospital, Boston; Department of Neurology, Neurosurgery, and Radiology (M.F., S.O.-G., N.R.), University of Iowa Hospitals and Clinics, Iowa City; Department of Radiology (D.F.), Swedish Medical Center, Englewood, Colorado; Department of Radiology (D.G.), Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland; Adventist Health Glendale Comprehensive Stroke Center (M.G.), Los Angeles, California; Wellstar Neuroscience Institute (R.G.), Marietta, Georgia; Department of Neurology (A.E.H.), University of Texas Rio Grande Valley-Valley Baptist Medical Center, Texas; Department of Neurology (J.H., B.V.), Lahey Hospital & Medical Center, Beth Israel Lahey Health, Burlington, Massachusetts; Department of Neurology (A.M.K.), Wayne State, Detroit, Michigan; HSHS St. John's Hospital (N.N.K.), Southern Illinois University School of Medicine, Springfield; Virginia Hospital Center (B.S.K.), Arlington; Department of Neurology, University of Michigan, Ann Arbor; Weill-Cornell Medical College (D.O.K.), New York-Presbyterian Queens; Department of Neurology (V.H.L.), Ohio State University, Columbus; Department of Neurology (L.Y.L.), Tufts Medical Center, Boston, Massachusetts; Vascular and Neurointerventional Services (G.L.), St. Louis University, Missouri; Miami Cardiac & Vascular Institute (I.L., A.K.S.), Florida; Department of Neurology (H.L.L.), Oregon Health & Science University, Portland; Department of Emergency Medicine (L.M., M.S.), Steward Holy Family Hospital, Methuen, MA; Vidant Medical Center (S.M.), Greenville, North Carolina; Department of Neurology (A.M.M., D.R.Y.) and Neurosurgery (D.R.Y.), University of Miami Miller School of Medicine, Florida; Department of Neurology (H.M.), SUNY Upstate New York, Syracuse; Memorial Neuroscience Institute (B.P.M.), Pembroke Pines, Florida; Neurosciences (J.M., J.P.T.), Spectrum Health, Michigan State University College of Medicine, Grand Rapids, Michigan; Sutter Health (M.M.), Sacramento, California; Department of Neurology (J.G.M.), Maine Medical Center, Portland; Department of Neurology (S.S.M.), Bayhealth, Dover, Delaware; Department of Neurology and Pediatrics (F.N.), Emory University, Atlanta, Georgia; Department of Neurology (K.N.), University of Arkansas for Medical Sciences, Little Rock; Department of Radiology and Neurology (R.N.-W.), UT Southwestern Medical Center, Dallas, Texas; Ascension St. John Medical Center (R.H.R.), Tulsa, Oklahoma; Riverside Regional Medical Center (P.R.), Newport, Virginia; Department of Neurology (J.R.R., T.N.N.), Boston University School of Medicine, MA; Department of Neurology (A.R.), Hospital of the University of Pennsylvania, Philadelphia; Department of Neurology (M.S.), University of Washington School Medicine, Seattle; Department of Neurology (B.S.), University of Massachusetts Medical Center, Worcester; Department of Neurology (A.S.), CHI-Immanuel Neurological Institute, Creighton University, Omaha, Nebraska; Holy Cross Hospital (S.L.S.), Fort Lauderdale, Florida; Department of Neurology (V.S.), Interventional Neuroradiology, University of California in Los Angeles; Banner Desert Medical Center (M.T.), Mesa, Arizona; Hospital de Agudos Dr. Ignacio Privano (O.B., A.L.), Argentina; Institute for Neurological Research, FLENI (V.A.P.L.), Buenos Aires, Argentina; Hospital das Clinicas/São Paulo University (M.S.A., A.C.); Sumare State Hospital (F.B.C., L.V.), São Paulo; Hospital Vera Cruz (L.D.D.S.), Deus Campinas; Irmanandade Santa Casa de Porto Alegre (L.V.G.); Stroke Unit (F.O.L., F. Mont'alverne), Hospital Geral de Fortaleza; Stroke Unit (A.L.L., P.S.C.M.), Hospital Sao Jose, Joinville, Santa Catarina; Stroke Unit (R.T.M.), Neurology, Nossa Senhora da Conceição Hospital, Porto Alegre; Department of Neurology (D.L.M.C.), Hospital Moinhos de Vento, Porto Alegre; Department of Neurology (L.C.R.), Hospital de Base do Distrito Federal; Hospital Ana (V.F.C.), Hospital Juliane, Federal University of Parana, Curitiba, Brazil; Vascular Neurology Unit (P.M.L., V.V.O.), Neurology Service, Department of Neurology and Psychiatry, Clínica Alemana, Universidad del Desarrollo, Santiago; Hospital Padre Hurtado (V.N., J.M.A.T.) Santiago, Chile; Fundación Valle del Lili (P.F.R.A.), Cali; Stroke Center (H.B.), Fundación Santa Fe de Bogotá; Department of Neurology (A.B.C.-Q.), Hospital Departamental Universitario del Quindio San Juan de Dios, Armenia; Clinica Universitaria Colombia (C.E.R.O.), Bogotá; University Hospital of San Vicente Foundation (D.K.M.B.), Medellin; Barranquilla, Colombia (O.L.); Hospital Infantil Universitario de San Jose (M.R.P.), Bogota; Stroke Unit (L.F.D.-E.), Hospital de Clínicas, Facultad de Ciencias Médicas, Universidad Nacional de Asunción; Neurology Service (D.E.D.M.F., A.C.V.), Hospital Central del Instituto de Prevision Social, Paraguay; Internal Medicine Service (A.J.Z.Z.), Hospital Central de Policia "Rigoberto Caballero", Paraguay; National Institute of Neurological Sciences of Lima Peru (D.M.B.I.); Hospital Edgardo Rebagliati Martins Lima-Peru (L.R.K.); Department of Neurology (B.C.), Royal Melbourne Hospital; Department of Neurology (G.J.H.), Sir Charles Gairdner Hospital and Medical School, Faculty of Health and Medical Sciences, The University of Western Australia, Perth; University of Melbourne (C.H., R.S.), Ballarat Health Service, Australia University of Melbourne; Department of Neurology (T.K.), Royal Adelaide Hospital; Department of Neurosurgery (A. Ma), Royal North Shore Hospital, Sydney; Department of Neurology (R.T.M.), Mater Hospital, Brisbane; Department of Neurology (R.S.), Austin Health, Victoria; Florey Institute of Neuroscience and Mental Health (R.S.), Parkville, Melbourne, Australia; Greymouth Base Hospital (D.S.), New Zealand; Department of Neurology (T.Y.-H.W.), Christchurch Hospital, New Zealand; Department of Neurology (D.L.), University of California in Los Angeles; and Department of Neurology (O.O.Z.), Mercy Health Neurosciences, Toledo, Ohio.

Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
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http://dx.doi.org/10.1212/WNL.0000000000011885DOI Listing
June 2021

COVID-19, Moral Injury and the Bhagvad Gita.

J Relig Health 2021 Apr 26;60(2):654-662. Epub 2021 Feb 26.

Midam Charitable Trust, Pondicherry, India.

During life challenging times like the present COVID-19 pandemic, the health care worker (HCW) is faced with a number of questions of an existential nature. There is a sense of guilt, anguish, helplessness, uncertainty and powerlessness when one is fighting something on such a powerful scale with limited resources and no definite end in sight. There are circumstances when these feelings can overwhelm a person leading to demoralization and potentially a moral injury. Spiritual practices and advice may help to deal with moral paradoxes and ethical dilemmas when other secular supports are undermined or inaccessible. The Holy Indian Epic, the Bhagvad Gita has described the moral distress of the warrior Arjuna, during the battle of Kurukshetra and the advice given to him by the Lord Krishna the gist of which can be encapsulated in the form of the four Ds- Detachment, Duty, Doer-ship and Dhyana or meditation. In this article, the authors explore how these concepts may be useful aids to the HCW faced with moral and psychological distress.
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http://dx.doi.org/10.1007/s10943-021-01210-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908940PMC
April 2021

Migraine in Nursing Students-A Study from a Tertiary Care Center in South India.

J Neurosci Rural Pract 2021 Jan 29;12(1):129-132. Epub 2021 Jan 29.

Department of Nursing, Apollo Speciality Hospitals, Nellore, Andhra Pradesh, India.

 Nursing profession is subject to occupational stress, which can be a trigger for headaches. Our study aimed to study the prevalence of migraine, its characteristics, triggers, and relieving factors among nursing students in a tertiary care center. This study was performed in a super-specialty hospital in South India. A structured questionnaire captured data on the occurrence of headache, demographics, aura, triggering factors, relieving factors, and lifestyle habits. Results are presented in numbers and percentage.  A total of 20% of nursing students in the study had headache of which 85% had migraine. Weekly and daily attacks were reported in 12 and 4% students, respectively. Twenty-two percent had headache severity of more than 5 visual analogue scale. Most common accompanying symptoms were photophobia (80%), phonophobia (70%), nausea (75%), vomiting (71%), neck pain (25%), and vertigo (20%). Thirty-nine percent had auras. Ninety-five percent reported triggers with 70% students having more than one trigger. Sleep was the relieving factor in 69%, head massage in 50%, and relaxing from work in 48%.  The most common type of primary headache in nurses in our study was migraine. More than three-fourths nurses reported triggers and relieving factors. Addressing these factors could help in managing migraines and help in improving the quality of life and increased work productivity of nurses.
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http://dx.doi.org/10.1055/s-0040-1721556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846327PMC
January 2021

Roflumilast: A potential drug for the treatment of cognitive impairment?

Neurosci Lett 2020 09 28;736:135281. Epub 2020 Jul 28.

Department of Neurology, Jawaharlal Institute of Postgraduate Medical Education and Research, Dhanvantri Nagar, Gorimedu, Puducherry, India. Electronic address:

Phosphodiesterase-4 regulates the intracellular level of cAMP. Roflumilast, a selective PDE-4 inhibitor was the first agent in this class to have reached the market for patients with chronic obstructive pulmonary disease worldwide. Numerous preclinical evidences indicate the role of PDE-4 inhibitors in reversal of ageing-related alterations induced in animal models by various pharmacological agents, overexpression of mutant forms of human amyloid precursor proteins and in aging, as well. Roflumilast was capable of decreasing PDE-4B and 4D subtypes with an increase in the expression of pCREB and BDNF in hippocampus of rats. The beneficial effects of roflumilast on cognition are believed to be mediated through the above-mentioned cellular effects. Recently, Jabaris et al had shown that roflumilast has improved the short and long-term memory in rodents. Several lines of evidence indicate that targeting PDE-4 inhibition might offer novel approaches in the treatment of age-associated memory impairment and in Alzheimer's disease. Likewise, in a recent report, roflumilast improved the memory functions in humans after administration of 100 μg of the drug, without the typical side effects of PDE-4 inhibitors, which might offer a novel therapeutic option for the treatment of cognitive impairment and Alzheimer disease. In the current article, the author reviews the most recent evidences demonstrating the beneficial effects of roflumilast on learning and memory in animal models and humans.
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http://dx.doi.org/10.1016/j.neulet.2020.135281DOI Listing
September 2020

Chronic Neurology in COVID-19 Era: Clinical Considerations and Recommendations From the REPROGRAM Consortium.

Front Neurol 2020 24;11:664. Epub 2020 Jun 24.

Pandemic Health System REsilience PROGRAM (REPROGRAM) Consortium, Chronic Neurology REPROGRAM Sub-committee†.

With the rapid pace and scale of the emerging coronavirus 2019 (COVID-19) pandemic, a growing body of evidence has shown a strong association of COVID-19 with pre- and post- neurological complications. This has necessitated the need to incorporate targeted neurological care for this subgroup of patients which warrants further reorganization of services, healthcare workforce, and ongoing management of chronic neurological cases. The social distancing and the shutdown imposed by several nations in the midst of COVID-19 have severely impacted the ongoing care, access and support of patients with chronic neurological conditions such as Multiple Sclerosis, Epilepsy, Neuromuscular Disorders, Migraine, Dementia, and Parkinson disease. There is a pressing need for governing bodies including national and international professional associations, health ministries and health institutions to harmonize policies, guidelines, and recommendations relating to the management of chronic neurological conditions. These harmonized guidelines should ensure patient continuity across the spectrum of hospital and community care including the well-being, safety, and mental health of the patients, their care partners and the health professionals involved. This article provides an in-depth analysis of the impact of COVID-19 on chronic neurological conditions and specific recommendations to minimize the potential harm to those at high risk.
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http://dx.doi.org/10.3389/fneur.2020.00664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339863PMC
June 2020

Association between LH receptor regulation and ovarian hyperstimulation syndrome in a rodent model.

Reproduction 2020 08;160(2):239-245

Departments of Obstetrics/Gynecology and Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, USA.

Ovarian hyperstimulation syndrome (OHSS) is a common complication of ovarian stimulation associated with the administration of human chorionic gonadotropin (hCG) during assisted reproduction. We have determined the expression of luteinizing hormone receptor (Lhcgr) mRNA, vascular endothelial growth factor (VEGF), and its transcription factor, HIF1α, during the periovulatory period in a rodent model of OHSS and compared these results with normal ovulatory periods. These results showed that the downregulation of Lhcgr mRNA in response to conditions that mimic preovulatory LH surge was significantly impaired in the OHSS group compared to the complete downregulation seen in the control group. Most importantly, the downregulation of luteinizing hormone receptor mRNA expression following hCG administration was sustained in the control group up to 48 h, whereas it remained at significantly higher levels in the OHSS group. This impairment of hCG-induced Lhcgr downregulation in the OHSS group was accompanied by significantly elevated levels of VEGF and its transcription factor, HIF1α. Furthermore, the downregulation of Lhcgr that occurs in response to a preovulatory LH surge in normal cycles was accompanied by low levels of VEGF. This study shows that, while downregulation of Lhcgr as well as low VEGF levels are seen in response to a preovulatory LH surge in normal ovarian cycle, impaired Lhcgr downregulation and elevated VEGF levels were found in the OHSS group.
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http://dx.doi.org/10.1530/REP-20-0058DOI Listing
August 2020

Evaluating the Role of Oxidative Stress in Acute Ischemic Stroke.

J Neurosci Rural Pract 2020 Jan 3;11(1):156-159. Epub 2020 Mar 3.

Unit of Psychiatry and Addiction Medicine, Australian National University Medical School, Canberra, Australia.

The role of oxidative stress in neuronal injury due to ischemic stroke has been an interesting topic in stroke research. Malondialdehyde (MDA) has emerged as a sensitive oxidative stress biomarker owing to its ability to react with the lipid membranes. Total antioxidant power (TAP) is another biomarker to estimate the total oxidative stress in stroke patients. We aimed to determine the oxidative stress in acute stroke patients by measuring MDA and TAP. MDA and TAP were determined in 100 patients with ischemic stroke and compared with that in 100 age- and sex-matched healthy adults. Demographic data, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), and disability measured by the Barthel index (BI) were recorded. The association of MDA and TAP with other variables was analyzed by paired -test. Of the whole sample, 74% represented males. The mean NIHSS score was 13.11 and BI was 38.87. MDA was significantly higher in stroke patients (7.11 ± 1.67) than in controls (1.64 ± 0.82; = 0.00). TAP was significantly lower in stroke patients (5.72 ± 1.41) than in controls (8.53 ± 2.4; = 0.00). The lipid profile and blood sugar levels were also significantly higher in stroke patients. There was no association of MDA and TAP with other variables. We found that oxidative stress was associated with acute ischemic stroke. However, we could not establish an association between oxidative stress and the severity of acute stroke.
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http://dx.doi.org/10.1055/s-0039-3402675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055613PMC
January 2020

Poor Awareness of Role of Helmet in Preventing the Head Injury.

Indian J Community Med 2019 Jul-Sep;44(3):291-292

Department of Neurology, Apollo Speciality Hospitals, Nellore, Andhra Pradesh, India.

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http://dx.doi.org/10.4103/ijcm.IJCM_205_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776931PMC
October 2019

Towards a new model of understanding - The triple network, psychopathology and the structure of the mind.

Authors:
Bindu Menon

Med Hypotheses 2019 Dec 29;133:109385. Epub 2019 Aug 29.

Department of Psychiatry, Srivenkatesheswaraa Medical College, Pondicherry, India. Electronic address:

With progress in neurosciences, neuroimaging and brain stimulation techniques, mental illnesses are now being seen as development anomalies at the molecular-structural level of synapses, resulting in abnormal cross wiring in areas responsible for complex cognitive and emotional processing. These include the multimodal association cortices situated in the prefrontal lobes, the insula in the temporal lobes, midline cortical structures, and their connections to the thalamus, amygdala and the basal ganglia. Three key networks have been identified which are considered the brain hubs for complex perceptual, emotional and behavior processing as well as introspection, theory of mind and self-awareness; namely the salience network (SN), the central executive network (CEN) and the default mode network (DMN). They function in an interconnected manner and involve in higher information processing of the entire internal and external milieu of the organism to determine the behavior strategies to be adopted. A triple network model of aberrant saliency mapping and cognitive dysfunction in psychopathology has been put forward recently and an attempt is being made to understand core cognitive networks and their dysfunction across multiple disorders including schizophrenia, depression, anxiety, autism and dementia. Against this background, the author would like to take the triple network dysfunction model a step further to hypothesize the following. 1. All or some of the three core networks (CEN, SN & DMN) are affected variably in psychiatric disorders, the severity and the nature of the clinical symptoms depending upon the degree of damage and the number of networks that are dysfunctional and whether that dysfunction is reversible or permanent. For example, in a condition like schizophrenia, all three networks would more or less be affected giving rise to plethora of symptoms like executive deficits, negative symptoms, abnormal salience and mood states. In milder conditions like anxiety and depressive disorders, on the other hand, the dysfunction is of a lesser degree and reversible. 2. These networks are the final common pathway through which a variety of internal or environment insults to the brains may act, the degree of damage and reversibility being determined by the critical period of brain development in which these occur. 3. The harmonious functioning of these core networks is what gives rise to the complex phenomenon of the mind in the brain.
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http://dx.doi.org/10.1016/j.mehy.2019.109385DOI Listing
December 2019

Asian Study of Cerebral Venous Thrombosis.

J Stroke Cerebrovasc Dis 2019 Oct 24;28(10):104247. Epub 2019 Jul 24.

Department of Medicine, Aga Khan University, Karachi, Pakistan.

Background/objective: Most of the studies and registries related to cerebral venous thrombosis (CVT) are reported from European countries and the United States. The objective of the present study is to identify risk factors, presentation, and outcome of CVT in Asian patients.

Methods: Asian CVT registry is a prospective multinational observational study that included patients (aged > 16 years) with symptomatic CVT.

Results: Eight hundred and twelve patients (59% women) from 20 centers in 9 Asian countries were included. Mean age of the patients was 31 years. Motor weakness in limbs was present in 325 (40%) patients. One hundred and eighty (22.1%) patients had a normal Glasgow coma scale (GCS) at presentation, and another 529 patients (65%) had GCS between 11 and 14. The rest (103; 13%) had a GCS of less than 10 at presentation. Permanent risk factors were present in 264 (33%) patients, transient in 342 (42%) patients, both in 43 (5%) patients and no risk factors were found in 163 (20%) patients. Anemia was present in 51%, use of oral contraceptive pills (OCP) was present in 12% women and a hypercoaguable state was present in more than 40% of those tested. One hundred and forty-three cases (18%) were in women who were either pregnant (18; 2%) or in the puerperium (up to 6 weeks postpartum; N = 125; 15%). A total of 86 (10.5%) patients were diagnosed with infection in any part of the body. The most common MRI finding was local brain edema or ischemia (53.3%) followed by hemorrhage (26.7%). Twenty-seven patients (3.3%) died during hospital stay. The mRS score at discharge was available for 661 (81%) patients. Of these, 577 (87.3%) had good functional outcome at discharge. Motor weakness at presentation, GCS of 9 or less and mental status disorder were the strongest independent predictors of mortality at last follow-up among patients with CVT.

Conclusions: Important differences were identified as compared to western data including younger age, high frequency of anemia, low use of OCP, and high frequency of hypercoaguable states. Functional outcome at discharge was good.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2019.06.005DOI Listing
October 2019

SREBP Plays a Regulatory Role in LH/hCG Receptor mRNA Expression in Human Granulosa-Lutein Cells.

J Clin Endocrinol Metab 2019 10;104(10):4783-4792

Departments of Obstetrics and Gynecology and Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan.

Context: LH receptor (LHR) expression has been shown to be regulated posttranscriptionally by LHR mRNA binding protein (LRBP) in rodent and human ovaries. LRBP was characterized as mevalonate kinase. The gene that encodes mevalonate kinase is a member of a family of genes that encode enzymes involved in lipid synthesis and are regulated by the transcription factor sterol regulatory element binding proteins (SREBPs).

Objective: The current study examined the regulation of LHR mRNA expression in human granulosa-lutein cells in response to alterations in cholesterol metabolism.

Design: Using atorvastatin, an inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase to inhibit cholesterol biosynthesis, we examined its effect on LHR mRNA expression. The effect of atorvastatin on SREBP and mRNA expression as well as LHR mRNA binding protein expression was examined. Finally, the effect of atorvastatin on human chorionic gonadotropin (hCG)-stimulated progesterone production and the expression of key steroidogenic enzymes was also examined.

Results: Statin treatment reduced LHR mRNA expression by increasing the levels of SREBP1a and SREBP2, leading to an increase in LRBP. RNA gel shift assay showed that increased binding of LHR mRNA to LRBP occurred in response to atorvastatin, leading to LHR mRNA degradation. The granulosa-lutein cells pretreated with atorvastatin also showed decreased responsiveness to hCG by decreasing the mRNA and protein expression of steroidogenic enzymes. Atorvastatin also attenuated LH/hCG-induced progesterone production.

Conclusion: These results imply that LHR mRNA expression by the human granulosa-lutein cells is regulated by cholesterol, through a mechanism involving SREBP and SREBP cleavage activating protein serving as the cholesterol sensor.
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http://dx.doi.org/10.1210/jc.2019-00913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736214PMC
October 2019

Study of Ischemia Modified Albumin as a Biomarker in Acute Ischaemic Stroke.

Ann Neurosci 2018 Dec 28;25(4):187-190. Epub 2018 Jun 28.

Narayana Medical College and Hospitals, Nellore, India.

Background And Purpose: Stroke is one of the leading causes of mortality and long-term disability. Prompt diagnosis and treatment of stroke are crucial for a better outcome. A blood test, which serves as a biomarker in rural areas will help in immediately transferring patients to a hospital for thrombolytic therapy. The aim of the present study was to examine the role of ischemia modified albumin (IMA) as a screening biomarker in acute ischaemic stroke.

Materials And Methods: Serum samples were collected from 50 patients with acute ischaemic stroke within one, 24, 48, 72 and 144 h of time of admission for IMA. We compared patients' 1st-hour value with age- and sex-matched controls by independent sample test. value < 0.05 was considered significant.

Results: The serum IMA levels of patients 1st hour (108 ± 8.9) were significantly higher than those of the controls (79 ± 6.3) < 0.05. The IMA levels showed a steady decline at 1 h (108 ± 8.9), 24 h (94 ± 4.2), 48 h (82 ± 6.1), 72 h (77 ± 5.6) and 144 h (76 ± 3.8) of admission in patients.

Conclusion: We observed that serum IMA was significantly higher in stroke patients as compared to controls. IMA was elevated in the acute phase of stroke and had a gradual graded decline over 1 week. We concluded that IMA may be a sensitive and rapid biomarker for screening of early ischaemic stroke in rural settings.
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http://dx.doi.org/10.1159/000488188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6470340PMC
December 2018

Role of Leptin in Acute Ischemic Stroke.

J Neurosci Rural Pract 2018 Jul-Sep;9(3):376-380

Department of Biochemistry, Narayana Medical College, Nellore, Andhra Pradesh, India.

Purpose: Leptin has been implicated as a pathogenetic contributor to atherosclerosis. We aimed to investigate the association of leptin level with ischemic stroke.

Materials And Methods: We prospectively enrolled 52 patients with acute ischemic stroke and measured leptin levels and compared with age- and sex-matched healthy controls. Risk factors, body mass index (BMI), biochemical parameters, intima-media thickness (IMT) on carotid vertebral Doppler and neuroimaging was done. Data were entered into MS-Excel and appropriate statistical analysis was done using SPSS software version 21.0. = 0.05 was considered statistically significant.

Results: Serum leptin was significantly elevated in stroke patients (6598.1 ± 1035.1) compared to controls (3090.7 ± 698.86) ( < 0.01). Patients had higher BMI (26.9 ± 1.7) than controls (26.9 ± 1.7) ( < 0.00). BMI, total cholesterol, low-density lipoprotein (LDL) cholesterol, white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C reactive protein (CRP) were significantly elevated in stroke patients than controls. Correlation analysis among patient group showed that serum leptin positively correlated with CRP ( - 0.41, - <0.05), WBCs ( - 0.28, - <0.05), ESR ( - 0.429, - <0.01) total cholesterol ( - 0.31, - <0.05), LDL-cholesterol ( - 0.19, - <0.05), and IMT ( - 0.714, - <0.001).

Conclusion: Our study showed high leptin levels in patients with stroke. Stroke patients with high leptin had higher BMI and inflammatory markers. The results of our study indicate that leptin may have a role in atherosclerosis mediated through inflammation. Future research should be directed toward understanding the role of leptin in the pathogenesis of cerebrovascular diseases and its potential role in preventive treatment of ischemic stroke.
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http://dx.doi.org/10.4103/jnrp.jnrp_5_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050775PMC
August 2018

miR-122 Regulates LHR Expression in Rat Granulosa Cells by Targeting Insig1 mRNA.

Endocrinology 2018 05;159(5):2075-2082

Department of Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor, Michigan.

Luteinizing hormone/chorionic gonadotropin receptor (LHR) expression in the ovary is regulated by a messenger RNA (mRNA) binding protein, which specifically binds to the coding region of LHR mRNA. We have shown that miR-122, a short noncoding RNA, mediates LHR mRNA levels by modulating the expression of LHR mRNA-binding protein (LRBP) through the regulation of sterol regulatory element binding protein (SREBP) activation. The present results show that miR-122 regulates LRBP levels by increasing the processing of SREBP through the degradation of Insig1, the anchoring protein of SREBP. We present evidence showing that mRNA and protein levels of Insig1 undergo a time-dependent increase following the treatment of rat granulosa cells with follicle-stimulating hormone (FSH), which leads to a decrease in LRBP levels. Furthermore, overexpression of miR-122 using an adenoviral vector (AdmiR-122) abolished FSH-induced increases in Insig1 mRNA and protein. We further confirmed the role of Insig1 by showing that inhibition of Insig1 using a specific small interfering RNA prior to FSH treatment resulted in the abrogation of LHR upregulation. Silencing of Insig1 also reversed FSH-mediated decreases in SREBP and LRBP activation. These results show that decreased levels of miR-122 increase Insig1 and suppress SREBP processing in response to FSH stimulation of rat granulosa cells.
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http://dx.doi.org/10.1210/en.2017-03270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5905391PMC
May 2018

Regulation of Luteinizing Hormone Receptor mRNA Expression in the Ovary: The Role of miR-122.

Vitam Horm 2018 19;107:67-87. Epub 2018 Feb 19.

The University of Michigan Medical School, Ann Arbor, MI, United States.

The expression of luteinizing hormone receptor (LHR) in the mammalian ovary is regulated in response to changes in the secretion of follicle-stimulating hormone and luteinizing hormone by the anterior pituitary, at least in part, through posttranscriptional mechanisms. The steady-state levels of LHR mRNA are maintained by controlling its rate of degradation by an RNA-binding protein designated as LHR mRNA-binding protein (LRBP). LRBP forms a complex with LHR mRNA and targets it for degradation in the p bodies. miR-122, an 18 nucleotide noncoding RNA, regulates the expression of LRBP. Thus, the levels of miR-122 determine the cellular levels of LHR mRNA expression. This phenomenon has been examined during the induction of LHR mRNA expression that occurs during follicle maturation in response to rising levels of FSH. In this situation, miR-122 and LRBP levels decrease as LHR mRNA expression undergoes downregulation in response to preovulatory LH surge. miR-122 expression as well as LRBP levels show robust increases. The mechanism of induction of LRBP by miR-122 has also been discussed.
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http://dx.doi.org/10.1016/bs.vh.2018.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140328PMC
November 2018

Female Caregivers and Stroke Severity Determines Caregiver Stress in Stroke Patients.

Ann Indian Acad Neurol 2017 Oct-Dec;20(4):418-424

Department of Community Medicine, Narayana Medical College, Nellore, Andhra Pradesh, India.

Background: Stroke is among the major causes of short- and long-term disability. This study aimed to understand the caregivers (CGs) stress in stroke survivors.

Materials And Methods: A 22-item questionnaire was administered to 201 CGs of stroke survivors. The variables tested were physical and mental health, social support, financial, and personal problems. CGs were divided into Group A (Barthel index [BI] <75) and B (BI >75) according to patient's BI, according to gender (male and female CG) and relation; spouses (wife, husband), daughters, sons, daughter-in-law, grandchildren, and rest (father, mother, brother, sister, and in-laws). Data were analyzed using SPSS software version-21. Data were analyzed to determine which variables of the patient effects the CG stress.

Results: Majority of the CGs (74.62%) were females. 65% of CGs graded their burden as moderate to severe. 81% of CGs had left their work for caregiving. More than half of the CGs felt sleep disturbance and physical strain. Psychological instability and financial burdens were reported in 3/4 of CGs. Group A CGs faced more sleep, financial, health, and social life disturbance. Patient's bladder and bowel problems, shoulder pain, patients noncooperative attitude for medication administration, and physiotherapy were more upsetting for Group A CGs. Female CGs were subjected to more sleep disturbance, physical and psychological stress, faced more difficulty regarding the patient's bladder, bowel, personal hygiene needs, and physiotherapy. Female CGs felt less motivated in caregiving than male CGs. Wives and daughters-in-law experienced more burden. Time spent and burden perceived was more by female CGs (χ = 15.199, = 0.002) than males (χ = 11.931, = 0.018); wives and daughters than other relations (χ = 32.184, = 0.000), (χ = 35.162, = 0.019).

Conclusion: Our study showed that caregiving burden was predominantly shouldered by females CGs. CGs faced physical, psychological, and socioeconomic burden. The burden was more evident in female CGs and in patients with severe stroke.
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http://dx.doi.org/10.4103/aian.AIAN_203_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5682751PMC
November 2017

LHCGR Expression During Follicle Stimulating Hormone-Induced Follicle Growth Is Negatively Regulated by Eukaryotic Initiation Factor 5A.

Endocrinology 2017 08;158(8):2672-2679

Department of Obstetrics/Gynecology, University of Michigan Medical School, Ann Arbor, Michigan 48109.

We have shown that the transient changes in the expression of luteinizing hormone/choriogonadotropin receptor (LHCGR) messenger RNA (mRNA) during the ovarian cycle occurs, at least in part, through a posttranscriptional mechanism involving an LHCGR mRNA-binding protein (LRBP). Eukaryotic initiation factor 5A (eIF5A), an LRBP-interacting protein, participates in this process. eIF5A undergoes hypusination, a unique posttranslational modification that is necessary for its functions. This study examined the role of eIF5A in follicle-stimulating hormone (FSH)-induced LHCGR expression during follicular growth. Treatment of primary cultures of rat granulosa cells with FSH and 17β-estradiol (E2) showed a time-dependent increase in LHCGR mRNA expression. Conversely, inhibition of endogenous hypusination of eIF5A using N1-guanyl-1,7-diaminoheptane (GC7), a hypusination inhibitor, showed a greater increase in LHCGR mRNA expression over that produced by FSH and E2 alone. Further studies were carried out to determine the mechanism by which inhibition of hypusination of eIF5A causes an increase in LHCGR mRNA expression. Because LHCGR expression is negatively regulated by LRBP, the effect of inhibiting hypusination of eIF5A on LRBP expression was examined. The results showed a decrease in the expression of LRBP mRNA and protein when hypusination of eIF5A was inhibited by GC7. Because LRBP promotes LHCGR mRNA degradation, the results of this study support the notion that by inhibiting eIF5A hypusination, FSH reduces the expression of LRBP. This increases LHCGR mRNA expression by abrogating the inhibitory action of LRBP.
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http://dx.doi.org/10.1210/en.2017-00113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5551546PMC
August 2017

Role of brain natriuretic peptide as a novel prognostic biomarker in acute ischemic stroke.

Ann Indian Acad Neurol 2016 Oct-Dec;19(4):462-466

Department of Community Medicine, Narayana Medical College and Hospital, Nellore, Andhra Pradesh, India.

Aim: We investigated to study the prognostic importance of brain natriuretic peptide (BNP) in ischemic stroke.

Materials And Methods: We prospectively enrolled 100 patients with acute ischemic stroke and measured plasma BNP levels and compared with age- and sex-matched healthy controls. Risk factors, biochemical parameters, lipid profile, carotid and vertebral Doppler, imaging, and cardiac evaluation were done. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS) score on admission and functional disability by Barthel Index (BI) at 3 months. Ischemic stroke subtype was classified according to the Oxfordshire Community Stroke Project (OCSP). Data were entered in MS Excel, and appropriate statistical analysis was done using the SPSS software version 21.0. A = 0.05 was considered as significant.

Results: Mean age of patients was 55.17 ± 11.37 years with a male:female ratio 3:1. OCSP showed total anterior circulation infarct (TACI) 35, partial anterior circulation infarct 9, lacunar infarct 12, and posterior circulation infarct 44. NIHSS on admission was average 10 ± 7 and BI was 57 ± 30. BNP in patients (435 ng/ml) was very high as compared to controls (<60 ng/ml) ( < 0.001). There was a positive correlation between age and BNP ( = 0.34; < 0.00); NIHSS and BNP ( = 0.255; < 0.01), negative correlation between BI and BNP ( = -0.064; < 0.01). Mean BNP levels across the OCSP showed higher values in TACI ( = 4.609 = 0.005). Regression analysis showed that BNP can predict BI which was statistically significant.

Conclusion: Plasma BNP levels was significantly elevated in patients with ischemic stroke. Our study concludes that high BNP levels are seen in large anterior circulation stroke and is a predictor for the poor functional outcome at 3 months. Determination of BNP levels as a biomarker could be helpful in predicting the outcome in stroke patients.
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http://dx.doi.org/10.4103/0972-2327.194422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5144466PMC
December 2016

A novel method for immobilization of proteins via entrapment of magnetic nanoparticles through epoxy cross-linking.

Anal Biochem 2017 Feb 11;519:42-50. Epub 2016 Dec 11.

MagGenome Technologies Pvt. Ltd., CSEZ, Kakkanad, PIN-682037, Kochi, Kerala, India.

A method for immobilization of functional proteins by chemical cross-linking of the protein of interest and uncoated iron oxide nanoparticles in the presence of Epichlorohydrin is described. As a result of the cross-linking, the proteins form a matrix in which the particles get entrapped. The optimum concentration of Epichlorohydrin that facilitates immobilization of protein without affecting the functional properties of the protein was determined. This method was used to immobilize several functional proteins and the development and functional activity of Protein A-magnetic nanoparticles (MNPs) is described here in detail. The Protein A-MNPs possess high binding capacity due to the increased surface area of uncoated nanoparticles and robust magnetic separation due to the absence of polymeric coating materials. Protein A-MNPs were successfully used for purification of antibodies and also for immunoprecipitation. We also immobilized enzymes such as horse radish peroxidase and esterase and found that by providing the optimum incubation time, temperature and protein to nanoparticle ratio, we can retain the activity and improve the stability of the enzyme. This study is the first demonstration that Epichlorohydrin can be used to entrap nanoparticles in a cross-linked matrix of protein without impairing the activity of immobilized protein.
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http://dx.doi.org/10.1016/j.ab.2016.12.007DOI Listing
February 2017

Molecular regulation of LHCGR expression by miR-122 during follicle growth in the rat ovary.

Mol Cell Endocrinol 2017 02 8;442:81-89. Epub 2016 Dec 8.

Departments of Obstetrics/Gynecology and Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, 48109-0617, USA. Electronic address:

We have previously reported that LHCGR expression in the ovary is regulated through a post-transcriptional mechanism involving an mRNA binding protein designated as LRBP, which is regulated, at least in part, by a non-coding RNA, miR-122. Our present study examined the regulatory role of miR-122 in FSH-induced LHCGR expression during follicle development. Treatment of rat granulosa cells concurrently with FSH and 17β estradiol showed, as expected, a time-dependent increase in LHCGR mRNA levels as well as hCG-induced progesterone production. However, miR-122 expression was decreased during the early time periods, which preceded the increased expression of LHCGR mRNA. The role of miR-122 in FSH-induced LHCGR mRNA expression was then examined by overexpressing miR-122 prior to FSH stimulation by infecting granulosa cells with an adenoviral vector containing a miR-122 insert (AdmiR-122). Pretreatment with AdmiR-122 resulted in complete abrogation of FSH- mediated upregulation of LHCGR. AdmiR-122 also blocked FSH-induced decrease in LRBP expression and increased the binding of LHCGR mRNA to LRBP. Based on these results, we conclude that miR-122 plays a regulatory role in LHCGR expression by modulating LRBP levels during FSH-induced follicle growth.
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http://dx.doi.org/10.1016/j.mce.2016.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5371357PMC
February 2017

HCG-mediated activation of mTORC1 signaling plays a crucial role in steroidogenesis in human granulosa lutein cells.

Endocrine 2016 Oct 8;54(1):217-224. Epub 2016 Aug 8.

Department of Obstetrics and Gynecology, University of Michigan Hospitals and Health System, Ann Arbor, MI.

Luteinizing hormone/human chorionic gonadotropin stimulates progesterone biosynthesis in the corpus luteum by activating cyclic adenosine monophosphate/protein kinase A cascade. Recent studies have shown that cyclic adenosine monophosphate-mediated activation of protein kinase A interacts with the mammalian target of rapamycin signaling pathways. Furthermore, the use of mammalian target of rapamycin inhibitors for immunosuppression in transplant patients has shown adverse effects in reproductive functions. This study examined whether the mammalian target of rapamycin pathway plays any role in luteinizing hormone-mediated regulation of progesterone production. Human granulosa lutein cells were isolated from follicular aspirates of women undergoing in vitro fertilization. Cells were cultured for 72 h and treated with human chorionic gonadotropin (50 ng/ml) for different time periods with or without pretreatment with mammalian target of rapamycin complex 1 inhibitor, rapamycin, (20 nM) for 1 h. Expression of steroidogenic enzymes, including steroidogenic acute regulatory protein, cholesterol side chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase type 1 messenger RNA, were examined by real-time polymerase chain reaction after 6 h of human chorionic gonadotropin treatment. Expressions of phospho-ribosomal protein S6 kinase and cholesterol side chain cleavage enzyme were analyzed after 15 min and 24 h of human chorionic gonadotropin treatment, respectively. Progesterone production was analyzed by an enzyme immunoassay kit after human chorionic gonadotropin (50 ng/ml) or forskolin (10 μM) treatment for 24 h. Treatment with human chorionic gonadotropin increased the expression of downstream targets of mammalian target of rapamycin complex 1, as well as cholesterol side chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase type 1 and steroidogenic acute regulatory protein messenger RNAs. These increases were inhibited by rapamycin pretreatment. Increased progesterone production in response to treatment with human chorionic gonadotropin or forskolin was also blocked by rapamycin pretreatment. Our findings support a role for mammalian target of rapamycin complex 1 in regulating steroidogenesis in human granulosa lutein cells.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5071160PMC
http://dx.doi.org/10.1007/s12020-016-1065-8DOI Listing
October 2016

The dilemma of arranged marriages in people with epilepsy. An expert group appraisal.

Epilepsy Behav 2016 08 8;61:242-247. Epub 2016 Jul 8.

Samvedana Epilepsy Group, Pune, India.

Introduction: Matrimony remains a challenging psychosocial problem confronting people with epilepsy (PWE). People with epilepsy are less likely to marry; however, their marital prospects are most seriously compromised in arranged marriages.

Aims: The aim of this study was to document marital prospects and outcomes in PWE going through arranged marriage and to propose optimal practices for counseling PWE contemplating arranged marriage.

Methods: A MEDLINE search and literature review were conducted, followed by a cross-disciplinary meeting of experts to generate consensus.

Results: People with epilepsy experience high levels of felt and enacted stigma in arranged marriages, but the repercussions are heavily biased against women. Hiding epilepsy is common during marital negotiations but may be associated with poor medication adherence, reduced physician visits, and poor marital outcome. Although divorce rates are generally insubstantial in PWE, divorce rates appear to be higher in PWE undergoing arranged marriages. In these marriages, hiding epilepsy during marital negotiations is a risk factor for divorce.

Conclusions: In communities in which arranged marriages are common, physicians caring for PWE are best-equipped to counsel them about their marital prospects. Marital plans and aspirations should be discussed with the family of the person with epilepsy in a timely and proactive manner. The benefits of disclosing epilepsy during marital negotiations should be underscored.
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http://dx.doi.org/10.1016/j.yebeh.2016.05.034DOI Listing
August 2016

Sleep quality and health complaints among nursing students.

Ann Indian Acad Neurol 2015 Jul-Sep;18(3):363-4

College of Nursing Narayana Medical College and Hospital, Nellore, Andhra Pradesh, India.

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http://dx.doi.org/10.4103/0972-2327.157252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564485PMC
October 2015

miR-122 Regulates LH Receptor Expression by Activating Sterol Response Element Binding Protein in Rat Ovaries.

Endocrinology 2015 Sep 30;156(9):3370-80. Epub 2015 Jun 30.

Departments of Obstetrics/Gynecology and Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109-0617.

LH/human chorionic gonadotropin receptor (LHR) undergoes down-regulation during preovulatory LH surge or in response to exposure to a supraphysiological concentration of its ligands through a posttranscriptional mechanism involving an RNA binding protein designated as LHR mRNA binding protein (LRBP). miR-122, a short noncoding RNA, has been shown to mediate the up-regulation of LRBP. In the present study, we show that inhibition of miR-122 using a locked nucleic acid (LNA)-conjugated antagomir suppressed human chorionic gonadotropin (hCG)-induced up-regulation of LRBP as well as its association with LHR mRNA, as analyzed by RNA EMSA. Most importantly, inhibition of miR-122 resulted in the abolishment of hCG-mediated LHR mRNA down-regulation. We also show that the transcription factor, sterol regulatory element binding protein (SREBP) (SREBP-1a and SREBP-2 isoforms), is an intermediate in miR-122-mediated LHR mRNA regulation. HCG-stimulated increase in the activation of both SREBP-1a and SREBP-2 was inhibited by pretreatment with the miR-122 antagomir. The inhibition of cAMP/protein kinase A (PKA) and ERK pathways, upstream activators of miR-122, abolished SREBP activation after hCG treatment. SREBP-mediated regulation of LRBP expression is mediated by recruitment of LRBP promoter element to SREBP-1a, because chromatin immunoprecipitation assay revealed that association of LRBP promoter to SREBP was increased by hCG treatment. Pretreatment with miR-122 antagomir suppressed this response. Inhibition of SREBP activation by pretreating the rats with a chemical compound, fatostatin abrogated hCG-induced up-regulation of LRBP mRNA and protein. Fatostatin also inhibited LHR-LRBP mRNA-protein complex formation and LHR down-regulation. These results conclusively show that miR-122 plays a regulatory role in LH/hCG-induced LHR mRNA down-regulation by increasing LRBP expression through the activation of SREBP pathway.
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http://dx.doi.org/10.1210/en.2015-1121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541618PMC
September 2015

Hypusination of eukaryotic initiation factor 5A via cAMP-PKA-ERK1/2 pathway is required for ligand-induced downregulation of LH receptor mRNA expression in the ovary.

Mol Cell Endocrinol 2015 Sep 23;413:90-5. Epub 2015 Jun 23.

Departments of Obstetrics/Gynecology and Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI 48109-0617, USA. Electronic address:

Luteinizing hormone receptor (LHR) mRNA expression in the ovary is regulated post-transcriptionally by an LH receptor mRNA binding protein (LRBP). Eukaryotic initiation factor 5A (EIF5A), identified as an LRBP-interacting protein plays a crucial role in LHR mRNA expression. In this study, we have demonstrated that during hCG-induced LHR downregulation, a significant upregulation of eIF5A mRNA expression and hypusination of eIF5A protein occurs in a time dependent manner. Pretreatment with H89, a specific inhibitor of PKA, and U0126, a specific inhibitor of ERK1/2 significantly inhibited both hCG-induced eIF5A mRNA expression and hypusination of eIF5A protein. Pretreatment with GC7, a specific inhibitor of eIF5A hypusination significantly abolished hCG-induced LRBP mRNA and protein expression. Furthermore, GC7 pretreatment significantly inhibited hCG-induced interaction of LRBP with LHR mRNA as assessed by RNA electrophoretic mobility gel shift assay (REMSA). GC7 treatment also reversed LHR mRNA downregulation. Taken together, these results suggest that hCG-induced LHR mRNA downregulation is mediated by cAMP-PKA-ERK1/2 signaling leading to activation of eIF5A hypusination.
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http://dx.doi.org/10.1016/j.mce.2015.06.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4523407PMC
September 2015

Parkinson's Disease, Depression, and Quality-of-Life.

Indian J Psychol Med 2015 Apr-Jun;37(2):144-8

Department of Biostatistics, Amrita Institute of Medical Sciences, Cochin, Kerala, India.

Background: Depression is the most common psychiatric disorder associated with Parkinson's disease (PD) but is often under diagnosed and under treated leading to worsening of symptoms and deterioration of the quality-of-life of the people suffering from this disease.

Aims: The current study aims to determine the correlation between depression and health-related quality-of-life (HRQOL) domains in patients with PD.

Materials And Methods: A sample of 65 consecutive patients attending the specialty Parkinson's clinic was assessed by a psychiatrist as part of the treatment protocol. Diagnosis of depression was done using the International Classification of Diseases-10 by a psychiatrist and depression was scored using the Geriatric Depression Scale (GDS). QOL-BREF Malayalam version was used to assess quality-of-life in the patients.

Statistical Analysis: One-way ANOVA was used to find the difference in the quality-of-life experienced by different age categories, duration of the disease, psychiatric co-morbidity. Independent sample t-test was used to find the difference in the quality-of-life experienced by genders, co morbid conditions and to find the difference in the scores on GDS and domains of WHO QOL BREF. Association of H and Y staging and duration of Parkinsonism with GDS Scores were computed using Pearson's Chi-square test.

Results And Conclusions: There was a significant association of female gender and depression with the physical and psychological domains of QOL while the duration and staging of PD did not have any association with QOL Domains. Depression thus emerges as one of the main predictors of poor quality-of-life in PD.
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http://dx.doi.org/10.4103/0253-7176.155611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418244PMC
May 2015

Regulation of luteinizing hormone receptor expression by an RNA binding protein: role of ERK signaling.

Indian J Med Res 2014 Nov;140 Suppl:S112-9

Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI, USA.

A specific luteinizing hormone receptor (LHR) mRNA binding protein (LRBP) has been identified and purified. This LH receptor mRNA binding protein selectively binds to the polypyrimidine rich bipartite sequence in the coding region of the LHR mRNA and accelerates its degradation. In response to preovulatory LH surge, the LH receptor expression in the ovary undergoes downregulation by accelerated degradation of LH receptor mRNA through the involvement of this RNA binding protein. Here we describe the intracellular mechanism triggered by LH/hCG (human chorionic gonadotropin) that leads to the regulated degradation of LH receptor mRNA. Downregulation of LH receptor mRNA was induced by treatment of cultured human granulosa cells with 10 IU of hCG. Activation of downstream target, extracellular signal-regulated protein kinase 1 and 2 (ERK 1/2) showed an increase within five min and sustained up to 1 h. Confocal analysis showed that ERK1/2 translocates to the nucleus after 15 min of hCG treatment. This leads to an increase in LRBP expression which then causes downregulation of LH receptor mRNA by accelerating its degradation. Treatment with UO126 or transfection with ERK specific siRNA (small interfering RNA) resulted in the abolishment of ERK activation as well as LHR mRNA downregulation. RNA electrophoretic mobility gel shift assay of the cytosolic fractions showed that hCG-induced increase in the LH receptor mRNA binding activity was also abrogated by these treatments. These results show that LH/hCG-induced LH receptor mRNA downregulation is initiated by the activation of ERK1/2 pathway by regulating the expression and activity of LH receptor mRNA binding activity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4345741PMC
November 2014

Low plasma antioxidant status in patients with epilepsy and the role of antiepileptic drugs on oxidative stress.

Ann Indian Acad Neurol 2014 Oct;17(4):398-404

Department of Biochemistry, Narayana Medical College and Superspeciality Hospital, Chintareddypalem, Nellore, Andhra Pradesh, India.

Background: Oxidative stress has been implicated in various disorders including epilepsy. We studied the antioxidant status in patients with epilepsy and aimed at determining whether there was any difference in the antioxidant levels between patients and controls, patients who are not on antiepileptic drugs (AEDs), and on treatment, between individual AEDs and patients on monotherapy and polytherapy.

Materials And Methods: Antioxidant levels like catalase, glutathione peroxidase (GPx), vitamin E, glutathione (GSH), thiol group (SH), uric acid, and total antioxidant capacity (TAC) were compared between 100 patients with epilepsy and equal number of controls. Twenty-five patients who were not on AEDs were compared with patients on AEDs and the control group. Patients were divided into monotherapy and polytherapy group and antioxidant status was compared between the two groups and between individual drugs.

Results: Catalase, SH, vitamin E, and TAC were significantly low in patients with epilepsy than those in the control group (P < 0.001). GSH and uric acid did not show any difference; GPx in patients was significantly higher than those in the control group There were no differences in the antioxidant levels between the treated and the untreated groups; however, it was lower in untreated patients than controls (P < 0.001), suggesting that AEDs do not modify the oxidative stress. Patients on Valproate (VPA) showed higher catalase and GPx levels. Catalase was higher in the monotherapy than polytherapy group (P < 0.04).

Conclusion: Our study found significantly low levels of antioxidant in patients as compared to controls. AED did not influence the antioxidant status suggesting that seizures induce oxidative stress.
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http://dx.doi.org/10.4103/0972-2327.144008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4251012PMC
October 2014

Eukaryotic initiation factor 5A plays an essential role in luteinizing hormone receptor regulation.

Mol Endocrinol 2014 Nov 12;28(11):1796-806. Epub 2014 Sep 12.

Departments of Obstetrics/Gynecology and Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109-0617.

Down-regulation of LH receptor (LHR) in the ovary by its ligand is mediated by a specific RNA-binding protein, designated LH receptor mRNA-binding protein (LRBP), through translational suppression and mRNA degradation. Using yeast 2-hybrid screens, we previously identified eukaryotic initiation factor 5A (eIF5A) as one of the proteins that interacts with LRBP during LHR mRNA down-regulation. The present study examined the role of eIF5A and its hypusination in the context of LHR mRNA down-regulation. The association of eIF5A with LRBP or LHR mRNA was determined using immunoprecipitation and RNA immunoprecipitation assays. The results showed that the association of eIF5A with the LHR mRNA-LRBP complex increased significantly during down-regulation. Furthermore, gel fractionation and the hypusination activity assay both showed increased hypusination of eIF5A during LHR mRNA down-regulation. Abolishment of hypusination by pretreatment with the chemical inhibitor GC7 prevented the association of eIF5A with LHR mRNA and LRBP. Inhibition of hypusination also reduced the extent of ligand-induced down-regulation of LHR mRNA as well as the expression of functional LHRs assessed by real-time PCR and (125)I-human chorionic gonadotropin (hCG) binding assays, respectively. The loss of human chorionic gonadotropin-mediated downstream signaling during LHR down-regulation was also restored by inhibition of hypusination of eIF5A. Thus, the present study, for the first time, reveals the crucial role of eIF5A and its hypusination in the regulation of LHR expression in the ovary.
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http://dx.doi.org/10.1210/me.2014-1132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4213366PMC
November 2014