Publications by authors named "Patrick Manning"

59 Publications

Age- and sex-specific visceral fat reference cutoffs and their association with cardio-metabolic risk.

Int J Obes (Lond) 2021 Jan 20. Epub 2021 Jan 20.

The Centre for Biostatistics, University of Otago, Dunedin, New Zealand.

Background: Although excess visceral fat (VAT) is associated with numerous cardio-metabolic risk factors, measurement of this fat depot has historically been difficult. Recent dual X-ray absorptiometry approaches have provided an accessible estimate of VAT that has shown acceptable validity against gold standard methods. The aims of this study were to (i) evaluate DXA measured VAT as a predictor of elevated blood lipids and blood pressure and (ii) calculate thresholds associated with these cardio-metabolic risk factors.

Subjects/methods: The sample comprised 1482 adults (56.4% women) aged 18-66 years. Total body scans were performed using a GE Lunar Prodigy, and VAT analyses were enabled through Corescan software (v 16.0). Blood pressure and blood lipids were measured by standard procedures. Regression models assessed how VAT mass was associated with each cardio-metabolic risk factor compared to other body composition measures. Measures of sensitivity and specificity were used to determine age- and sex-specific cut points for VAT mass associated with high cardio-metabolic risk.

Results: Similar to waist circumference, VAT mass was a strong predictor of cardio-metabolic risk especially in men over age 40. Four cut-offs for VAT mass were proposed, above which the cardio-metabolic risk increased: 700 g in women <40 yrs; 800 g in women 40+ yrs; 1000g in men <40 yrs; and 1200 g in men 40+ yrs. In general, these cut-offs discriminated well between those with high and low cardio-metabolic risk.

Conclusions: In both sexes, DXA measured VAT was associated with traditional cardio-metabolic risk factors, particularly high blood pressure in those 40+ yrs and low HDL < 40 yrs. These reference values provide a simple, accessible method to assess cardio-metabolic risk in adults.
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http://dx.doi.org/10.1038/s41366-021-00743-3DOI Listing
January 2021

The role of rivaroxaban for patients with atherosclerotic vascular disease in the modern era.

Catheter Cardiovasc Interv 2020 Jul 8. Epub 2020 Jul 8.

Division of Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA.

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http://dx.doi.org/10.1002/ccd.29089DOI Listing
July 2020

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice.

Authors:
Jean Bousquet Josep M Anto Claus Bachert Tari Haahtela Torsten Zuberbier Wienczyslawa Czarlewski Anna Bedbrook Sinthia Bosnic-Anticevich G Walter Canonica Victoria Cardona Elisio Costa Alvaro A Cruz Marina Erhola Wytske J Fokkens Joao A Fonseca Maddalena Illario Juan-Carlos Ivancevich Marek Jutel Ludger Klimek Piotr Kuna Violeta Kvedariene Ltt Le Désirée E Larenas-Linnemann Daniel Laune Olga M Lourenço Erik Melén Joaquim Mullol Marek Niedoszytko Mikaëla Odemyr Yoshitaka Okamoto Nikos G Papadopoulos Vincenzo Patella Oliver Pfaar Nhân Pham-Thi Christine Rolland Boleslaw Samolinski Aziz Sheikh Mikhail Sofiev Charlotte Suppli Ulrik Ana Todo-Bom Peter-Valentin Tomazic Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Maria-Teresa Ventura Samantha Walker Sian Williams Arzu Yorgancioglu Ioana Agache Cezmi A Akdis Rute Almeida Ignacio J Ansotegui Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagaña Eric D Bateman Annabelle Bédard Martin Bedolla-Barajas Sven Becker Kazi S Bennoor Samuel Benveniste Karl C Bergmann Michael Bewick Slawomir Bialek Nils E Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Matteo Bonini Philippe Bonniaud Isabelle Bosse Jacques Bouchard Louis-Philippe Boulet Rodolphe Bourret Koen Boussery Fluvio Braido Vitalis Briedis Andrew Briggs Christopher E Brightling Jan Brozek Guy Brusselle Luisa Brussino Roland Buhl Roland Buonaiuto Moises A Calderon Paulo Camargos Thierry Camuzat Luis Caraballo Ana-Maria Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Niels H Chavannes Ekaterine Chkhartishvili Derek K Chu Cemal Cingi Jaime Correia de Sousa David J Costa Anne-Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejan Dokic Yves Dauvilliers Giulia De Feo Govert De Vries Philippe Devillier Stefania Di Capua Gerard Dray Ruta Dubakiene Stephen R Durham Mark Dykewicz Motohiro Ebisawa Mina Gaga Yehia El-Gamal Enrico Heffler Regina Emuzyte John Farrell Jean-Luc Fauquert Alessandro Fiocchi Antje Fink-Wagner Jean-François Fontaine José M Fuentes Perez Bilun Gemicioğlu Amiran Gamkrelidze Judith Garcia-Aymerich Philippe Gevaert René Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam Yunuen R Huerta Villalobos Marc Humbert Guido Iaccarino Despo Ierodiakonou Tomohisa Iinuma Ewa Jassem Guy Joos Ki-Suck Jung Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Musa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Rostislav Kouznetsov Marek L Kowalski Vicky Kritikos Inger Kull Stefania La Grutta Lisa Leonardini Henrik Ljungberg Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Catarina Lopes-Pereira Claudia C Loureiro Renaud Louis Alpana Mair Bassam Mahboub Michaël Makris Joao Malva Patrick Manning Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Pedro Carreiro-Martins Mika Makela Eve Mathieu-Dupas Marcus Maurer Esteban De Manuel Keenoy Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Yann Micheli Neven Miculinic Florin Mihaltan Branislava Milenkovic Dimitirios I Mitsias Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralph Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leyla Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Björn Nordlund Ettore Novellino Dieudonné Nyembue Robyn O'Hehir Ken Ohta Kimi Okubo Gabrielle L Onorato Valentina Orlando Solange Ouedraogo Julia Palamarchuk Isabella Pali-Schöll Peter Panzner Hae-Sim Park Gianni Passalacqua Jean-Louis Pépin Ema Paulino Ruby Pawankar Jim Phillips Robert Picard Hilary Pinnock Davor Plavec Todor A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Fotis Psarros Benoit Pugin Francesca Puggioni Pablo Quinones-Delgado Filip Raciborski Rojin Rajabian-Söderlund Frederico S Regateiro Sietze Reitsma Daniela Rivero-Yeverino Graham Roberts Nicolas Roche Erendira Rodriguez-Zagal Christine Rolland Regina E Roller-Wirnsberger Nelson Rosario Antonino Romano Menachem Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Joaquin Sastre Glenis K Scadding Sophie Scheire Peter Schmid-Grendelmeier Holger J Schünemann Faradiba Sarquis Serpa Mohamed Shamji Juan-Carlos Sisul Mikhail Sofiev Dirceu Solé David Somekh Talant Sooronbaev Milan Sova François Spertini Otto Spranger Cristiana Stellato Rafael Stelmach Michel Thibaudon Teresa To Mondher Toumi Omar Usmani Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Marilyn Urrutia Pereira Rianne van der Kleij Michiel Van Eerd Olivier Vandenplas Tuula Vasankari Antonio Vaz Carneiro Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Yun Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Osman M Yusuf Heather J Zar Stéphane Zeng Mario E Zernotti Luo Zhang Nan Shan Zhong Mihaela Zidarn

Allergy 2021 01 23;76(1):168-190. Epub 2020 Oct 23.

University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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http://dx.doi.org/10.1111/all.14422DOI Listing
January 2021

Upregulation of microRNA-532 enhances cardiomyocyte apoptosis in the diabetic heart.

Apoptosis 2020 06;25(5-6):388-399

Department of Physiology-HeartOtago, School of Biomedical Sciences, University of Otago, 270, Great King Street, Dunedin, 9016, New Zealand.

Type 2 diabetes has a strong association with the development of cardiovascular disease, which is grouped as diabetic heart disease (DHD). DHD is associated with the progressive loss of cardiovascular cells through the alteration of molecular signalling pathways associated with cell death. In this study, we sought to determine whether diabetes induces dysregulation of miR-532 and if this is associated with accentuated apoptosis. RT-PCR analysis showed a significant increase in miR-532 expression in the right atrial appendage tissue of type 2 diabetic patients undergoing coronary artery bypass graft surgery. This was associated with marked downregulation of its anti-apoptotic target protein apoptosis repressor with caspase recruitment domain (ARC) and increased TUNEL positive cardiomyocytes. Further analysis showed a positive correlation between apoptosis and miR-532 levels. Time-course experiments in a mouse model of type 2 diabetes showed that diabetes-induced activation of miR-532 occurs in the later stage of the disease. Importantly, the upregulation of miR-532 preceded the activation of pro-apoptotic caspase-3/7 activity. Finally, inhibition of miR-532 activity in high glucose cultured human cardiomyocytes prevented the downregulation of ARC and attenuated apoptotic cell death. Diabetes induced activation of miR-532 plays a critical role in accelerating cardiomyocytes apoptosis. Therefore, miR-532 may serve as a promising therapeutic agent to overcome the diabetes-induced loss of cardiomyocytes.
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http://dx.doi.org/10.1007/s10495-020-01609-1DOI Listing
June 2020

Anterior Cingulate Cortex Implants for Alcohol Addiction: A Feasibility Study.

Neurotherapeutics 2020 07;17(3):1287-1299

Department of Surgical Sciences, University of Otago, Dunedin, New Zealand.

Abnormal neural activity, particularly in the rostrodorsal anterior cingulate cortex (rdACC), appears to be responsible for intense alcohol craving. Neuromodulation of the rdACC using cortical implants may be an option for individuals with treatment-resistant alcohol dependence. This study assessed the effectiveness and feasibility of suppressing alcohol craving using cortical implants of the rdACC using a controlled one-group pre- and post-test study design. Eight intractable alcohol-dependent participants (four males and four females) were implanted with two Lamitrode 44 electrodes over the rdACC bilaterally connected to an internal pulse generator (IPG). The primary endpoint, self-reported alcohol craving reduced by 60.7% (p = 0.004) post- compared to pre-stimulation. Adverse events occurred in four out of the eight participants. Electrophysiology findings showed that among responders, there was a post-stimulation decrease (p = 0.026) in current density at the rdACC for beta 1 band (13-18 Hz). Results suggest that rdACC stimulation using implanted electrodes may potentially be a feasible method for supressing alcohol craving in individuals with severe alcohol use disorder. However, to further establish safety and efficacy, larger controlled clinical trials are needed.
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http://dx.doi.org/10.1007/s13311-020-00851-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641294PMC
July 2020

Radial access: So much progress but a way to go.

Catheter Cardiovasc Interv 2020 03;95(4):684-685

Division of Cardiology, Rhode Island Hospital, Brown Medical School, Providence, Rhode Island.

Transradial access is the key bleeding avoidance strategy in percutaneous coronary intervention. This study showed a marked adoption of transradial access over a 10-year period, however, women had a significantly lower rate compared to men and overall bleeding events did not decrease over time. Strategies to overcome barriers to radial access in women and to maintaining competency in femoral access in all patients are needed.
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http://dx.doi.org/10.1002/ccd.28794DOI Listing
March 2020

Next-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases.

Authors:
J Jean Bousquet Holger J Schünemann Alkis Togias Marina Erhola Peter W Hellings Torsten Zuberbier Ioana Agache Ignacio J Ansotegui Josep M Anto Claus Bachert Sven Becker Martin Bedolla-Barajas Michael Bewick Sinthia Bosnic-Anticevich Isabelle Bosse Louis P Boulet Jean Marc Bourrez Guy Brusselle Niels Chavannes Elisio Costa Alvaro A Cruz Wienczyslawa Czarlewski Wytske J Fokkens Joao A Fonseca Mina Gaga Tari Haahtela Maddalena Illario Ludger Klimek Piotr Kuna Violeta Kvedariene L T T Le Desiree Larenas-Linnemann Daniel Laune Olga M Lourenço Enrica Menditto Joaquin Mullol Yashitaka Okamoto Nikos Papadopoulos Nhân Pham-Thi Robert Picard Hilary Pinnock Nicolas Roche Regina E Roller-Wirnsberger Christine Rolland Boleslaw Samolinski Aziz Sheikh Sanna Toppila-Salmi Ioanna Tsiligianni Arunas Valiulis Erkka Valovirta Tuula Vasankari Maria-Teresa Ventura Samantha Walker Sian Williams Cezmi A Akdis Isabella Annesi-Maesano Sylvie Arnavielhe Xavier Basagana Eric Bateman Anna Bedbrook K S Bennoor Samuel Benveniste Karl C Bergmann Slawomir Bialek Nils Billo Carsten Bindslev-Jensen Leif Bjermer Hubert Blain Mateo Bonini Philippe Bonniaud Jacques Bouchard Vitalis Briedis Christofer E Brightling Jan Brozek Roland Buhl Roland Buonaiuto Giorgo W Canonica Victoria Cardona Ana M Carriazo Warner Carr Christine Cartier Thomas Casale Lorenzo Cecchi Alfonso M Cepeda Sarabia Eka Chkhartishvili Derek K Chu Cemal Cingi Elaine Colgan Jaime Correia de Sousa Anne Lise Courbis Adnan Custovic Biljana Cvetkosvki Gennaro D'Amato Jane da Silva Carina Dantas Dejand Dokic Yves Dauvilliers Antoni Dedeu Giulia De Feo Philippe Devillier Stefania Di Capua Marc Dykewickz Ruta Dubakiene Motohiro Ebisawa Yaya El-Gamal Esben Eller Regina Emuzyte John Farrell Antjie Fink-Wagner Alessandro Fiocchi Jean F Fontaine Bilun Gemicioğlu Peter Schmid-Grendelmeir Amiran Gamkrelidze Judith Garcia-Aymerich Maximiliano Gomez Sandra González Diaz Maia Gotua Nick A Guldemond Maria-Antonieta Guzmán Jawad Hajjam John O'B Hourihane Marc Humbert Guido Iaccarino Despo Ierodiakonou Maddalena Illario Juan C Ivancevich Guy Joos Ki-Suck Jung Marek Jutel Igor Kaidashev Omer Kalayci Przemyslaw Kardas Thomas Keil Mussa Khaitov Nikolai Khaltaev Jorg Kleine-Tebbe Marek L Kowalski Vicky Kritikos Inger Kull Lisa Leonardini Philip Lieberman Brian Lipworth Karin C Lodrup Carlsen Claudia C Loureiro Renaud Louis Alpana Mair Gert Marien Bassam Mahboub Joao Malva Patrick Manning Esteban De Manuel Keenoy Gailen D Marshall Mohamed R Masjedi Jorge F Maspero Eve Mathieu-Dupas Poalo M Matricardi Eric Melén Elisabete Melo-Gomes Eli O Meltzer Enrica Menditto Jacques Mercier Neven Miculinic Florin Mihaltan Branislava Milenkovic Giuliana Moda Maria-Dolores Mogica-Martinez Yousser Mohammad Steve Montefort Ricardo Monti Mario Morais-Almeida Ralf Mösges Lars Münter Antonella Muraro Ruth Murray Robert Naclerio Luigi Napoli Leila Namazova-Baranova Hugo Neffen Kristoff Nekam Angelo Neou Enrico Novellino Dieudonné Nyembue Robin O'Hehir Ken Ohta Kimi Okubo Gabrielle Onorato Solange Ouedraogo Isabella Pali-Schöll Susanna Palkonen Peter Panzner Hae-Sim Park Jean-Louis Pépin Ana-Maria Pereira Oliver Pfaar Ema Paulino Jim Phillips Robert Picard Davor Plavec Ted A Popov Fabienne Portejoie David Price Emmanuel P Prokopakis Benoit Pugin Filip Raciborski Rojin Rajabian-Söderlund Sietze Reitsma Xavier Rodo Antonino Romano Nelson Rosario Menahenm Rottem Dermot Ryan Johanna Salimäki Mario M Sanchez-Borges Juan-Carlos Sisul Dirceu Solé David Somekh Talant Sooronbaev Milan Sova Otto Spranger Cristina Stellato Rafael Stelmach Charlotte Suppli Ulrik Michel Thibaudon Teresa To Ana Todo-Bom Peter V Tomazic Antonio A Valero Rudolph Valenta Marylin Valentin-Rostan Rianne van der Kleij Olivier Vandenplas Giorgio Vezzani Frédéric Viart Giovanni Viegi Dana Wallace Martin Wagenmann De Y Wang Susan Waserman Magnus Wickman Dennis M Williams Gary Wong Piotr Wroczynski Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heahter J Zar Stéphane Zeng Mario Zernotti Luo Zhang Nan S Zhong Mihaela Zidarn

Clin Transl Allergy 2019 9;9:44. Epub 2019 Sep 9.

260University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.

Background: In all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.

Main Body: As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care.

Conclusion: In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.
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http://dx.doi.org/10.1186/s13601-019-0279-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734297PMC
September 2019

ARIA pharmacy 2018 "Allergic rhinitis care pathways for community pharmacy": AIRWAYS ICPs initiative (European Innovation Partnership on Active and Healthy Ageing, DG CONNECT and DG Santé) POLLAR (Impact of Air POLLution on Asthma and Rhinitis) GARD Demonstration project.

Authors:
Sinthia Bosnic-Anticevich Elisio Costa Enrica Menditto Olga Lourenço Ettore Novellino Slawomir Bialek Vitalis Briedis Roland Buonaiuto Henry Chrystyn Biljana Cvetkovski Stefania Di Capua Vicky Kritikos Alpana Mair Valentina Orlando Ema Paulino Johanna Salimäki Rojin Söderlund Rachel Tan Dennis M Williams Piotr Wroczynski Ioana Agache Ignacio J Ansotegui Josep M Anto Anna Bedbrook Claus Bachert Mike Bewick Carsten Bindslev-Jensen Jan L Brozek Giorgio Walter Canonica Victoria Cardona Warner Carr Thomas B Casale Niels H Chavannes Jaime Correia de Sousa Alvaro A Cruz Wienczyslawa Czarlewski Giuseppe De Carlo Pascal Demoly Philippe Devillier Mark S Dykewicz Mina Gaga Yehia El-Gamal João Fonseca Wytske J Fokkens Maria Antonieta Guzmán Tari Haahtela Peter W Hellings Maddalena Illario Juan Carlos Ivancevich Jocelyne Just Igor Kaidashev Musa Khaitov Nikolai Khaltaev Thomas Keil Ludger Klimek Marek L Kowalski Piotr Kuna Violeta Kvedariene Désirée E Larenas-Linnemann Daniel Laune Lan T T Le Karin C Lodrup Carlsen Bassam Mahboub Dieter Maier Joao Malva Patrick J Manning Mário Morais-Almeida Ralph Mösges Joaquim Mullol Lars Münter Ruth Murray Robert Naclerio Leyla Namazova-Baranova Kristof Nekam Tshipukane Dieudonné Nyembue Kimi Okubo Robyn E O'Hehir Ken Ohta Yoshitaka Okamoto Gabrielle L Onorato Susanna Palkonen Petr Panzner Nikolaos G Papadopoulos Hae-Sim Park Ruby Pawankar Oliver Pfaar Jim Phillips Davor Plavec Todor A Popov Paul C Potter Emmanuel P Prokopakis Regina E Roller-Wirnsberger Menachem Rottem Dermot Ryan Bolesław Samolinski Mario Sanchez-Borges Holger J Schunemann Aziz Sheikh Juan Carlos Sisul David Somekh Cristiana Stellato Teresa To Ana Maria Todo-Bom Peter Valentin Tomazic Sanna Toppila-Salmi Antonio Valero Arunas Valiulis Errka Valovirta Maria Teresa Ventura Martin Wagenmann Dana Wallace Susan Waserman Magnus Wickman Panayiotis K Yiallouros Arzu Yorgancioglu Osman M Yusuf Heather J Zar Mario E Zernotti Luo Zhang Mihaela Zidarn Torsten Zuberbier Jean Bousquet

Allergy 2019 07 30;74(7):1219-1236. Epub 2019 Apr 30.

MACVIA-France, Fondation Partenariale FMC VIA-LR, Montpellier, France.

Pharmacists are trusted health care professionals. Many patients use over-the-counter (OTC) medications and are seen by pharmacists who are the initial point of contact for allergic rhinitis management in most countries. The role of pharmacists in integrated care pathways (ICPs) for allergic diseases is important. This paper builds on existing studies and provides tools intended to help pharmacists provide optimal advice/interventions/strategies to patients with rhinitis. The Allergic Rhinitis and its Impact on Asthma (ARIA)-pharmacy ICP includes a diagnostic questionnaire specifically focusing attention on key symptoms and markers of the disease, a systematic Diagnosis Guide (including differential diagnoses), and a simple flowchart with proposed treatment for rhinitis and asthma multimorbidity. Key prompts for referral within the ICP are included. The use of technology is critical to enhance the management of allergic rhinitis. However, the ARIA-pharmacy ICP should be adapted to local healthcare environments/situations as regional (national) differences exist in pharmacy care.
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http://dx.doi.org/10.1111/all.13701DOI Listing
July 2019

Guidelines for Gender Affirming Healthcare for Gender Diverse and Transgender Children, Young People and Adults in Aotearoa, New Zealand.

N Z Med J 2018 12 14;131(1487):86-96. Epub 2018 Dec 14.

Endocrinologist, Endocrinology Department, Dunedin Hospital, Dunedin.

Internationally and within Aotearoa, New Zealand, there has been a substantial increase in the demand for gender affirming healthcare over the past decade. It is likely that this level of referrals to health services will continue in the foreseeable future. The Guidelines for Gender Affirming Healthcare for Gender Diverse and Transgender Children, Young People and Adults in Aotearoa, New Zealand were developed following the recognition that the previous good practice guide required updating to be in step with current practice and international standards. This article presents a summary of the guideline focusing on puberty blockers, hormonal therapies, access to surgery and other gender affirming healthcare. We hope these guidelines will support the development and provision of services providing gender affirming healthcare around the country and provide helpful guidance to all health professionals involved in the care of trans people.
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December 2018

Acute Weight Loss Restores Dysregulated Circulating MicroRNAs in Individuals Who Are Obese.

J Clin Endocrinol Metab 2019 04;104(4):1239-1248

Department of Physiology, HeartOtago, School of Biomedical Science, University of Otago, Dunedin, New Zealand.

Context: Obesity is a global epidemic and an independent risk factor for several diseases. miRNAs are gaining interest as early molecular regulators of various pathological processes.

Objective: To examine the miRNA signatures in women who are obese and determine the response of miRNAs to acute weight loss.

Methods: Plasma samples were collected from women who are obese (n = 80) before and after acute weight loss (mean, 7.2%). Plasma samples from age-matched lean volunteers (n = 80) were used as controls. Total RNA was extracted from the plasma samples and subjected to NanoString analysis of 822 miRNAs. The expression level of candidate miRNAs was validated in all participants using quantitative real-time PCR analysis.

Results: NanoString analysis identified substantial dysregulation of 21 miRNAs in women who are obese that were associated with impaired glucose tolerance, senescence, cardiac hypertrophy, angiogenesis, inflammation, and cell death. Acute weight loss reversed the expression pattern of 18 of these miRNAs toward those seen in the lean control group. Furthermore, real-time PCR validation of all the samples for 13 miRNAs with at least twofold upregulation or downregulation confirmed substantial dysregulation of all the chosen miRNAs in women who are obese at baseline. After acute weight loss, the levels of seven miRNAs in women who are obese and who are lean were comparable, with no statistically significant evidence for differences between the two groups.

Conclusions: Our study has provided evidence that the circulating miRNAs associated with various disorders are dysregulated in women who are obese. We also found that seven of these miRNAs showed levels comparable to those in lean controls after acute weight loss in women who are obese.
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http://dx.doi.org/10.1210/jc.2018-00684DOI Listing
April 2019

Pharmaceutical interventions for weight-loss maintenance: no effect from cabergoline.

Int J Obes (Lond) 2018 11 6;42(11):1871-1879. Epub 2018 Aug 6.

Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.

Background: Weight regain is a major limitation to successful weight maintenance following weight loss. Observational studies suggest that stimulation of dopamine receptors in the central nervous system is associated with weight loss and inhibition of weight gain. Our objective was to test the hypothesis that dopamine agonist treatment would prevent weight regain following acute weight loss in individuals with obesity.

Methods: We conducted a 2-year double blind randomised controlled trial comparing the effect of a dopamine agonist, cabergoline, with placebo on weight regain in obese individuals who had lost at least 5% of their body weight using an 800 kcal/day commercial meal replacement programme. The primary outcome measure was the difference in mean weight between the treatment and control groups over the 2-year period following randomisation.

Results: At 24 months, there was no difference in body weight between cabergoline and placebo treatment after adjustment for age, gender and baseline values (0.6 kg (95% CI: -1.5, 2.6), p = 0.58). The mean (±SD) baseline body weight of the randomised participants was 101.8 kg, the mean (±SD) weight loss with the 800 kcal/day diet was 7.1 ± 1.8 kg and the mean (±SD) weight regain at 24 months was 5.1 ± 7.5 kg. There were no significant differences in BMI, percent weight loss, waist circumference, resting energy expenditure, blood pressure or metabolic parameters at 24 months between the two groups.

Conclusions: Treatment with the dopamine agonist cabergoline does not prevent weight regain in obese individuals following weight loss.
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http://dx.doi.org/10.1038/s41366-018-0165-3DOI Listing
November 2018

A randomised, double-blind, placebo-controlled parallel trial of closed-loop infraslow brain training in food addiction.

Sci Rep 2018 08 3;8(1):11659. Epub 2018 Aug 3.

Section of Neurosurgery, Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.

The posterior cingulate cortex (PCC) is involved in food craving in obese food addicted individuals. This randomised, double-blind, placebo-controlled parallel study explored the potential therapeutic effects of infraslow neurofeedback (ISF-NF) on food craving targeting the PCC in obese women with symptoms of food addiction. Participants received six sessions of either ISF-NF (n = 11) or placebo (n = 10) over a three-week period. There were no reported adverse effects. Electrophysiologically, there were significant increases in infraslow activity (p = 0.0002) and infraslow/beta nesting (p < 0.001) in the PCC in the ISF-NF group (mean r = 0.004 ± 0.002) compared to placebo (mean r = 0.02 ± 0.002) two days after the last intervention. Also, there was a significant decrease in different dimensions of state food craving compared to baseline and to placebo. Findings suggest that source localized IFS-NF results in electrophysiological changes and may be associated with reduced food craving. This trial is registered at www.anzctr.org.au , identifier, ACTRN12617000601336. This study was funded by the Otago Medical Research Grant: CT375.
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http://dx.doi.org/10.1038/s41598-018-30181-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6076277PMC
August 2018

High definition transcranial pink noise stimulation of anterior cingulate cortex on food craving: An explorative study.

Appetite 2018 Jan 24;120:673-678. Epub 2017 Oct 24.

Department of Medicine, Dunedin School of Medicine, University of Otago, New Zealand. Electronic address:

Dysfunctional neural activity in the cortical reward system network has been implicated in food addiction. This is the first study exploring the potential therapeutic effects of high definition transcranial pink noise stimulation (HD-tPNS) targeted at the anterior cingulate cortex (ACC) on craving and brain activity in women with obesity who showed features of food addiction (Yale Food Addiction Scale score of ≥3). Sixteen eligible females participated in a randomized, double-blind, parallel group study. Participants received six 20-minute sessions of either 1 mA (n = 8) or sham (n = 8) stimulation with HD-tPNS over two weeks. Anode was placed above the ACC (Fz) with 4 cathodes (F7, T3, F8, and T4). Food craving was assessed using the Food Cravings Questionnaire State (FCQ-S) and brain activity was measured using electroencephalogram (EEG). Assessments were at baseline, and two days, four weeks, and six weeks after stimulation. A 22% decrease (mean decrease of -1.11, 95% CI -2.09, -0.14) was observed on the 5-point 'intense desire to eat' subscale two days after stimulation in the HD-tPNS group compared to sham. Furthermore, whole brain analysis showed a significant decrease in beta 1 activity in the ACC in the stimulation group compared to sham (threshold 0.38, p = 0.04). These preliminary findings suggest HD-tPNS of the ACC transiently inhibits the desire to eat and, thus, warrants further examination as a potential tool in combating food craving.
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http://dx.doi.org/10.1016/j.appet.2017.10.034DOI Listing
January 2018

Resting heart rate variability and exercise capacity in Type 1 diabetes.

Physiol Rep 2017 Apr;5(8)

Department of Medicine, University of Otago, Dunedin, New Zealand.

People with type 1 diabetes (T1D) have lower exercise capacity (O) than their age-matched nondiabetic counterparts (CON), which might be related to cardiac autonomic dysfunction. We examined whether Heart Rate Variability (HRV; indicator of cardiac autonomic modulation) was associated with exercise capacity in those with and without T1D. Twenty-three participants with uncomplicated T1D and 17 matched CON were recruited. Heart rate (HR; ECG), blood pressure (BP; finger photo-plethysmography), and respiratory rate (respiratory belt) were measured during baseline, paced-breathing and clinical autonomic reflex tests (CARTs); deep breathing, lying-to-stand, and Valsalva maneuver. Baseline and paced-breathing ECG were analyzed for HRV (frequency-domain). Exercise capacity was determined during an incremental cycle ergometer test while O, 12-lead ECG, and BP were measured. In uncomplicated T1D, resting HR was elevated and resting HRV metrics were reduced, indicative of altered cardiac parasympathetic modulation; this was generally undetected by the CARTs. However, BP and plasma catecholamines were not different between groups. In T1D, O tended to be lower ( = 0.07) and HR reserve was lower ( < 0.01). Resting Total Power (TP) had stronger positive associations with O ( ≥ 0.3) than all other traditional indicators such as age, resting HR, and self-reported exercise (= 0.042-0.3) in both T1D and CON Alterations in cardiac autonomic modulation are an early manifestation of uncomplicated T1D. Total Power was associated with reduced exercise capacity regardless of group, and these associations were generally stronger than traditional indicators.
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http://dx.doi.org/10.14814/phy2.13248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5408283PMC
April 2017

Down-regulation of miR-15a/b accelerates fibrotic remodelling in the Type 2 diabetic human and mouse heart.

Clin Sci (Lond) 2017 May 13;131(9):847-863. Epub 2017 Mar 13.

Department of Physiology, HeartOtago, University of Otago, Dunedin, New Zealand

Myocardial fibrosis is a well-established cause of increased myocardial stiffness and subsequent diastolic dysfunction in the diabetic heart. The molecular regulators that drive the process of fibrotic events in the diabetic heart are still unknown. We determined the role of the microRNA (miR)-15 family in fibrotic remodelling of the diabetic heart. Right atrial appendage (RAA) and left ventricular (LV) biopsy tissues collected from diabetic and non-diabetic (ND) patients undergoing coronary artery bypass graft surgery showed significant down-regulation of miR-15a and -15b. This was associated with marked up-regulation of pro-fibrotic transforming growth factor-β receptor-1 (TGFβR1) and connective tissue growth factor (CTGF), direct targets for miR-15a/b and pro-senescence p53 protein. Interestingly, down-regulation of miR-15a/b preceded the development of diastolic dysfunction and fibrosis in Type 2 diabetic mouse heart. Therapeutic restoration of miR-15a and -15b in HL-1 cardiomyocytes reduced the activation of pro-fibrotic TGFβR1 and CTGF, and the pro-senescence p53 protein expression, confirming a causal regulation of these fibrotic and senescence mediators by miR-15a/b. Moreover, conditioned medium (CM) collected from cardiomyocytes treated with miR-15a/b markedly diminished the differentiation of diabetic human cardiac fibroblasts. Our results provide first evidence that early down-regulation of miR-15a/b activates fibrotic signalling in diabetic heart, and hence could be a potential target for the treatment/prevention of diabetes-induced fibrotic remodelling of the heart.
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http://dx.doi.org/10.1042/CS20160916DOI Listing
May 2017

The sensitivity and specificity of thyroglobulin concentration using repeated measures of urinary iodine excretion.

Eur J Nutr 2018 Jun 11;57(4):1313-1320. Epub 2017 Mar 11.

Department of Human Nutrition, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.

Purpose: Iodine deficiency affects 30% of populations worldwide. The amount of thyroglobulin (Tg) in blood increases in iodine deficiency and also in iodine excess. Tg is considered as a sensitive index of iodine status in groups of children and adults, but its usefulness for individuals is unknown. The aim of this study was to determine the diagnostic performance of Tg as an index of iodine status in individual adults.

Methods: Adults aged 18-40 years (n = 151) provided five spot urine samples for the measurement of urinary iodine concentration expressed as μg/L (UIC), μg/g of creatinine (I:Cre), and μg/day (estimated UIE); the mean of the five samples was used as the reference standard. Participants also provided a blood sample for the determination of Tg, thyroid-stimulating hormone (TSH), and free thyroxine (FT4).

Results: The median of UIC, I:Cre, estimated UIE, and Tg was 72 (range 16-350) μg/L, 90 (range 33-371) μg/g, 129 (range 41-646) μg/day, and 16.4 (range 0.8-178.9) μg/L, respectively. Using Tg cut-offs of >10, >11, >13, and >15 μg/L, the sensitivity and specificity for UIC, I:Cre, and estimated UIE ranged from 52 to 79% and 20-48%, respectively, below the acceptable value of ≥80%. Furthermore, receiver-operating characteristic (ROC) curves for Tg using the three measurements of urinary iodine were situated close to the chance line and the area under the curve ranged from 0.49 to 0.52.

Conclusions: The results from this cross-sectional study indicate that Tg has low sensitivity and specificity to repeated measures of urinary iodine excretion. Further studies are still needed to investigate the usefulness of Tg as a biomarker of individual iodine status.
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http://dx.doi.org/10.1007/s00394-017-1410-6DOI Listing
June 2018

Down-regulation of proangiogenic microRNA-126 and microRNA-132 are early modulators of diabetic cardiac microangiopathy.

Cardiovasc Res 2017 01 8;113(1):90-101. Epub 2017 Jan 8.

Department of Physiology-HeartOtago, Otago School of Medical Sciences;

Aim: Microangiopathy due to endothelial dysfunction is a major contributing factor to the development of diabetes-induced cardiovascular disease (CVD). Dysregulation of endothelial-specific microRNAs (miRs) is correlated with impaired angiogenesis and cell survival. We investigated the profile of two angiomiRs, miR-126, and miR-132, in the plasma of type 2 diabetic individuals without any known history of CVD as well as in the cardiac tissues collected from diabetics undergoing cardiac surgery.

Methods And Results: The presence of diabetes alone significantly decreased both angiomiRs in the plasma and the myocardium. The down-regulation of angiomiRs was also associated with reduced capillaries and arterioles and increased endothelial cell apoptosis, the hallmark of microangiopathy. Importantly, a time course study in a type 2 diabetic mouse model confirmed that the down-regulation of angiomiRs preceded endothelial apoptosis as well as alterations in the density of the microvasculature. Finally, therapeutic overexpression of both angiomiRs in diabetic aortic rings and human umbilical vein endothelial cells exposed to high glucose (HG) abrogated the deleterious effects of diabetes and HG on cell survival and proliferation and restored their angiogenic potential.

Conclusions: These novel findings demonstrate that the down-regulation of angiomiRs is a major underlying mechanism for the development of microangiopathy in diabetic hearts. Therefore, therapeutic restoration of angiomiRs could become a potential approach to combat the cardiovascular complications of diabetes.
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http://dx.doi.org/10.1093/cvr/cvw235DOI Listing
January 2017

Allostasis in health and food addiction.

Sci Rep 2016 11 23;6:37126. Epub 2016 Nov 23.

School of Behavioral and Brain Sciences, University of Texas at Dallas, USA.

Homeostasis is the basis of modern medicine and allostasis, a further elaboration of homeostasis, has been defined as stability through change, which was later modified to predictive reference resetting. It has been suggested that pleasure is related to salience (behavioral relevance), and withdrawal has been linked to allostasis in addictive types. The question arises how the clinical and neural signatures of pleasure, salience, allostasis and withdrawal relate, both in a non-addicted and addicted state. Resting state EEGs were performed in 66 people, involving a food-addicted obese group, a non-food addicted obese group and a lean control group. Correlation analyses were performed on behavioral data, and correlation, comparative and conjunction analyses were performed to extract electrophysiological relationships between pleasure, salience, allostasis and withdrawal. Pleasure/liking seems to be the phenomenological expression that enough salient stimuli are obtained, and withdrawal can be seen as a motivational incentive because due to allostatic reference resetting, more stimuli are required. In addition, in contrast to non-addiction, a pathological, non-adaptive salience attached to food results in withdrawal mediated through persistent allostatic reference resetting.
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http://dx.doi.org/10.1038/srep37126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5120365PMC
November 2016

Anterior Cingulate Implant for Obsessive-Compulsive Disorder.

World Neurosurg 2017 Jan 15;97:754.e7-754.e16. Epub 2016 Oct 15.

Department of Psychological Medicine, Dunedin School of Medicine, University of Otago, New Zealand.

Background: Obsessive-compulsive disorder (OCD) is a brain disorder with a lifetime prevalence of 2.3%, causing severe functional impairment as a result of anxiety and distress, persistent and repetitive, unwanted, intrusive thoughts (obsessions), and repetitive ritualized behavior (compulsions). Approximately 40%-60% of patients with OCD fail to satisfactorily respond to standard treatments. Intractable OCD has been treated by anterior capsulotomy and cingulotomy, but more recently, neurostimulation approaches have become more popular because of their reversibility.

Objective: Implants for OCD are commonly being used, targeting the anterior limb of the internal capsula or the nucleus accumbens, but an implant on the anterior cingulate cortex has never been reported.

Methods: We describe a patient who was primarily treated for alcohol addiction, first with transcranial magnetic stimulation, then by implantation of 2 electrodes overlying the rostrodorsal part of the anterior cingulate cortex bilaterally.

Results: Her alcohol addiction developed as she was relief drinking to self-treat her OCD, anxiety, and depression. After the surgical implant, she underwent placebo stimulation followed by real stimulation of the dorsal anterior cingulate cortex, which dramatically improved her OCD symptoms (decrease of 65.5% on the Yale-Brown Obsessive Compulsive Drinking Scale) as well as her alcohol craving (decrease of 87.5%) after 36 weeks of treatment. Although there were improvements in all the scores, there was only a modest reduction in the patient's weekly alcohol consumption (from 50 units to 32 units).

Conclusions: Based on these preliminary positive results we propose to further study the possible beneficial effect of anterior cingulate cortex stimulation for intractable OCD.
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http://dx.doi.org/10.1016/j.wneu.2016.10.046DOI Listing
January 2017

The brain, obesity and addiction: an EEG neuroimaging study.

Sci Rep 2016 Sep 23;6:34122. Epub 2016 Sep 23.

School of Behavioral and Brain Sciences, University of Texas at Dallas, USA.

Obesity is among the greatest challenges facing healthcare systems with 20% of the world's population afflicted. Great controversy exists whether obesity can be regarded as an addictive disorder or not. Recently the Yale Food Addiction Scale questionnaire has been developed as a tool to identify individuals with traits of addiction towards food. Using clinical and source localized EEG data we dichotomize obesity. Brain activity in food-addicted and non-food-addicted obese people is compared to alcohol-addicted and non-addicted lean controls. We show that food addiction shares common neural brain activity with alcohol addiction. This 'addiction neural brain activity' consists of the dorsal and pregenual anterior cingulate cortex, parahippocampal area and precuneus. Furthermore, common neural obesity neural brain activity exists as well. The 'obesity neural brain activity' consists of dorsal and pregenual anterior cingulate cortex, posterior cingulate extending into the precuneus/cuneus as well as the parahippocampal and inferior parietal area. However food-addicted differ from non-food-addicted obese people by opposite activity in the anterior cingulate gyrus. This food addiction and non-food-addiction obesity dichotomy demonstrates there is at least 2 different kinds of obesity with overlapping network activity, but different in anterior cingulate cortex activity.
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http://dx.doi.org/10.1038/srep34122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034231PMC
September 2016

Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study.

Metabolism 2016 May 21;65(5):783-793. Epub 2015 Dec 21.

Royal Prince Alfred Hospital, Sydney NSW, Australia; National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney NSW, Australia. Electronic address:

Aims: Reported associations between liver enzymes and mortality may not hold true in type 2 diabetes, owing to a high prevalence of non-alcoholic fatty liver disease, which has been linked to cardiovascular disease and mortality in its own right. Our study aimed to determine whether alanine aminotransferase (ALT) or γ-glutamyl transferase (GGT) levels predict mortality in type 2 diabetes, and to examine possible mechanisms.

Methods: Data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study were analyzed to examine the relationship between liver enzymes and all-cause and cause-specific mortality over 5years.

Results: Over 5years, 679 (6.9%) individuals died. After adjustment, for every standard deviation increase in ALT (13.2U/L), the HR for death on study was 0.85 (95% CI 0.78-0.93), p<0.001. Conversely, GGT >70U/L, compared with GGT ≤70U/L, had HR 1.82 (1.48-2.24), p<0.001. For cause-specific mortality, lower ALT was associated with a higher risk of cardiovascular death only, whereas GGT >70U/L was associated with higher risks of death due to cardiovascular disease, cancer and non-cancer/non-cardiovascular causes. The relationship for ALT persisted after adjustment for indirect measures of frailty but was attenuated by elevated hsCRP.

Conclusions: As in the general population, ALT has a negative, and GGT a positive, correlation with mortality in type 2 diabetes when ALT is less than two times the upper limit of normal. The relationship for ALT appears specific for death due to cardiovascular disease. Links of low ALT with frailty, as a potential mechanism for relationships seen, were neither supported nor conclusively refuted by our analysis and other factors are also likely to be important in those with type 2 diabetes.
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http://dx.doi.org/10.1016/j.metabol.2015.12.008DOI Listing
May 2016

Anterior Cingulate Implant for Alcohol Dependence: Case Report.

Neurosurgery 2016 Jun;78(6):E883-93

*Section of Neurosurgery, Department of Surgical Sciences, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; ‡Section of Endocrinology, Department of Internal Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; §Department of Psychological Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand; ¶Department of Psychiatry and Psychotherapy, University Regensburg, Regensburg, Germany; ‖School of Behavioral and Brain Sciences, The University of Texas, Dallas, Texas.

Background And Importance: Alcohol dependence is related to dysfunctional brain processes, in which a genetic background and environmental factors shape brain mechanisms involved with alcohol consumption. Craving, a major component determining relapses in alcohol abuse, has been linked to abnormal brain activity.

Clinical Presentation: We report the results of a treatment-intractable, alcohol-addicted patient with associated agoraphobia and anxiety. Functional imaging studies consisting of functional magnetic resonance imaging and resting-state electroencephalogram were performed as a means to localize craving-related brain activation and for identification of a target for repetitive transcranial magnetic stimulation and implant insertion. Repetitive transcranial magnetic stimulation of the dorsal anterior cingulate cortex with a double-cone coil transiently suppressed his very severe alcohol craving for up to 6 weeks. For ongoing stimulation, 2 "back-to-back" paddle electrodes were implanted with functional magnetic resonance imaging neuronavigation guidance for bilateral dorsal anterior cingulate cortex stimulation. Using a recently developed novel stimulation design, burst stimulation, a quick improvement was obtained on craving, agoraphobia, and associated anxiety without the expected withdrawal symptoms. The patient has remained free of alcohol intake and relieved of agoraphobia and anxiety for over 18 months, associated with normalization of his alpha and beta activity on electroencephalogram in the stimulated area. He perceives a mental freedom by not being constantly focused on alcohol.

Conclusion: This case report proposes a new pathophysiology-based target for the surgical treatment of alcohol dependence and suggests that larger studies are warranted to explore this potentially promising avenue for the treatment of intractable alcohol dependence with or without anxiety and agoraphobia.

Abbreviations: ACC, anterior cingulate cortexBOLD, blood oxygen level dependentdACC, dorsal anterior cingulate cortexDBS, deep brain stimulationEEG, electroencephalogramfMRI, functional magnetic resonance imagingrTMS, repetitive transcranial magnetic stimulationSMA, supplementary motor areaTMS, transcranial magnetic stimulation.
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http://dx.doi.org/10.1227/NEU.0000000000001248DOI Listing
June 2016

Psychosurgery Reduces Uncertainty and Increases Free Will? A Review.

Neuromodulation 2016 Apr 21;19(3):239-48. Epub 2016 Feb 21.

Department of Psychiatry and Psychotherapy, Interdisciplinary Tinnitus Clinic, University of Regensburg, Regensburg, Germany.

Objective: A definition of free will is the ability to select for or against a course of action to fulfill a desire, without extrinsic or intrinsic constraints that compel the choice. Free will has been linked to the evolutionary development of flexible decision making. In order to develop flexibility in thoughts and behavioral responses, learning mechanisms have evolved as a modification of reflexive behavioral strategies. The ultimate goal of the brain is to reduce uncertainty inherently present in a changing environment. A way to reduce the uncertainty, which is encoded by the rostral anterior cingulate, is to make multiple predictions about the environment which are updated in parallel by sensory inputs. The prediction/behavioral strategy that fits the sensory input best is then selected, becomes the next percept/behavioral strategy, and is stored as a basis for future predictions. Acceptance of predictions (positive feedback) is mediated via the accumbens, and switching to other predictions by the dorsal anterior cingulate cortex (ACC) (negative feedback). Maintenance of a prediction is encoded by the pregenual ACC. Different cingulate territories are involved in rejection, acceptance and maintenance of predictions. Free will is known to be decreased in multiple psychopathologies, including obsessive compulsive disorder and addictions.

Methodology: In modern psychosurgery three target structures exist for obsessive compulsive disorder and addiction: the dorsal ACC, the nucleus accumbens, and/or the anterior limb of the internal capsula. Research in all three areas reports favorable results with acceptable side effects. Psychosurgical interventions seem to exert their effect by a common final common pathway mediated via the pregenual ACC.

Conclusion: Successful neuromodulation increases the capacity to choose from different options for the affected individual, as well as inhibiting unwanted options, therefore increasing free will and free won't.
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http://dx.doi.org/10.1111/ner.12405DOI Listing
April 2016

Iodine Supplementation of Mildly Iodine-Deficient Adults Lowers Thyroglobulin: A Randomized Controlled Trial.

J Clin Endocrinol Metab 2016 04 18;101(4):1737-44. Epub 2016 Feb 18.

Departments of Human Nutrition (Z.F.M., B.J.V., S.A.S.), Medicine (P.J.M.), and Social and Preventive Medicine (C.M.C.), University of Otago, Dunedin 9054, New Zealand.

Context: An inverse relationship between thyroglobulin (Tg) and urinary iodine concentration (UIC) has been found in children, potentially making Tg a viable blood marker of iodine status. The application of Tg in adults is unknown.

Objective: The objective of the study was to determine the efficacy of Tg to assess iodine status in adults.

Design: This was a randomized, double-blind, placebo-controlled, clinical trial.

Setting: The study was conducted in Dunedin, New Zealand.

Participants: Mildly iodine deficient adults (n = 112) aged 18–40 years participated in the study.

Intervention: Participants were supplemented with 150 μg of iodine as potassium iodate or placebo daily for 24 weeks. At baseline and 24 weeks, participants provided five casual urine samples for UIC determination; serum TSH and free T4 (FT4) was also measured. Tg was determined at baseline and 8, 16, and 24 weeks.

Main Outcome Measures: A change in Tg concentration between the iodine-supplemented and placebo groups at 24 weeks.

Results: At baseline, the overall median UIC was 65 μg/L, confirming that participants were mildly iodine deficient (ie, median UIC between 50 and 99 μg/L). The overall median Tg was 16.6 μg/L; TSH and FT4 were within normal reference ranges. At 24 weeks, the median UIC of the placebo and supplemented groups was significantly different, 79 and 168 μg/L, respectively (P < .001). Tg in the iodine-supplemented group decreased by 12%, 20%, and 27% compared with the placebo group at 8 (P = .045), 16 (P < .001), and 24 weeks (P < .001); there were no significant changes in TSH and FT4.

Conclusion: Improved iodine status as assessed by UIC was associated with a concomitant decrease in Tg concentration, demonstrating that Tg is a useful biomarker of iodine status in a group of adults.
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http://dx.doi.org/10.1210/jc.2015-3591DOI Listing
April 2016

Adults With Left-Sided Pressure Loading Lesions.

Curr Treat Options Cardiovasc Med 2015 Dec;17(12):55

Division of Cardiology, CardioVascular Center, Tufts Medical Center, 800 Washington Street, Box 315, Boston, MA, 02111, USA.

Opinion Statement: Adults with congenital heart disease represent a growing population. Now, more adults are living with congenital heart disease than children. Thus, adult cardiologists are likely to care for patients with either new diagnoses of congenital heart defects or complications of previously diagnosed defects or their interventions. In the present article, we review congenital conditions that lead to left-sided pressure overload states, specifically, subaortic stenosis, aortic stenosis, and coarctation of the aorta. We discuss the anatomy, epidemiology, and diagnosis of these specific lesions and review the current literature for management considerations.
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http://dx.doi.org/10.1007/s11936-015-0416-8DOI Listing
December 2015

Optimizing Deep Brain Stimulation of the Nucleus Accumbens in a Reward Preference Rat Model.

Neuromodulation 2015 Oct 13;18(7):531-40; discussion 540-1. Epub 2015 Aug 13.

Department of Anatomy, Brain Health Research Centre, School of Medical Sciences, University of Otago, Dunedin, New Zealand.

Objective/hypothesis: Deep brain stimulation (DBS) has become the preferred therapy for a growing number of treatment-resistant neuropsychiatric conditions, offering the benefit of being amenable to fine-tuning to enhance its efficacy. However, while some DBS parameters are routinely adjusted, the stimulation is almost always delivered in a continuous "tonic" pattern, which may be suboptimal at times. Our overall aim is to investigate the application of differing levels of rewarding DBS to the reconditioning of behavioral "trigger" and "non-trigger" stimuli in impulse-control disorders (including addiction). As a first step, we used a rat model of nucleus accumbens (NAc) DBS to rigorously compare the relative reward values of different stimulation paradigms. We hypothesized that delivering pulses in a more physiological pattern would prove more rewarding than delivering tonic stimulation.

Materials And Methods: We implanted microelectrodes in the left NAc shell and trained rats to initiate and terminate DBS to demonstrate their "preference" between different brain stimulation reward (BSR) paradigms. We tested a range of BSR paradigms, including tonic, intermittent tonic, and burst paradigms. Two paradigms were compared at a time, and paired t-tests were used to determine whether the rats significantly "preferred" one paradigm over another.

Results: The rats significantly preferred intermittent tonic BSR paradigms to continuous and burst paradigms, and generally preferred paradigms that delivered more pulses over the stimulation period.

Conclusions: These findings highlight that the standard approach of delivering tonic DBS is not optimal under all circumstances. Further research should investigate which DBS paradigms are best for different brain disorders.
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http://dx.doi.org/10.1111/ner.12339DOI Listing
October 2015

Systemic capillary leak syndrome: a case-report.

N Z Med J 2015 May 29;128(1415):51-3. Epub 2015 May 29.

Department of Medicine, Dunedin, New Zealand.

We report a case of a patient presenting with episodic hypotension, tachycardia and oedema, with an elevated serum IgG kappa paraprotein level. She was diagnosed as having systemic capillary leak syndrome and upon commencing oral theophylline has had no further presentations. The patient has since progressed to multiple myeloma.
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May 2015

OSA and pulmonary hypertension: time for a new look.

Chest 2015 Mar;147(3):847-861

Tufts Medical Center, Boston, MA.

OSA is a common yet underdiagnosed disorder encountered in everyday practice. The disease is a unique physiologic stressor that contributes to the development or progression of many other disorders, particularly cardiovascular conditions. The pulmonary circulation is specifically affected by the intermittent hypoxic apneas associated with OSA. The general consensus has been that OSA is associated with pulmonary hypertension (PH), but only in a minority of OSA patients and generally of a mild degree. Consequently, there has been no sense of urgency to screen for either condition when evaluating the other. In this review, we explore available evidence describing the interaction between OSA and PH and seek to better understand underlying pathophysiology. We describe certain groups of patients who have a particular preponderance of OSA and PH. Failure to recognize the mutual additive effects of these disorders can lead to suboptimal patient outcomes. Among patients with PH and OSA, CPAP, the mainstay treatment for OSA, may ameliorate pulmonary pressure elevations, but has not been studied adequately. Conversely, among patients with OSA, PH significantly limits functional capacity and potentially shortens survival; yet, there is no routine screening for PH in patients with OSA. We think it is time to study the interaction between OSA and PH more carefully to identify high-risk subgroups. These would be screened for the presence of combined disorders, facilitating earlier institution of therapy and improving outcomes.
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http://dx.doi.org/10.1378/chest.14-0614DOI Listing
March 2015

'Exercise snacks' before meals: a novel strategy to improve glycaemic control in individuals with insulin resistance.

Diabetologia 2014 Jul 10;57(7):1437-45. Epub 2014 May 10.

School of Physical Education, Sport and Exercise Sciences, University of Otago, 46 Union St West, PO Box 56, Dunedin, 9076, New Zealand.

Aims/hypothesis: The aim of this study was to investigate whether small doses of intense exercise before each main meal ('exercise snacks') would result in better blood glucose control than a single bout of prolonged, continuous, moderate-intensity exercise in individuals with insulin resistance.

Methods: Nine individuals completed three exercise interventions in randomised order. Measures were recorded across 3 days with exercise performed on the middle day, as either: (1) traditional continuous exercise (CONT), comprising 30 min moderate-intensity (60% of maximal heart rate [HRmax]) incline walking before dinner; (2) exercise snacking (ES), consisting of 6 × 1 min intense (90% HRmax) incline walking intervals 30 min before each meal; or (3) composite exercise snacking (CES), encompassing 6 × 1 min intervals alternating between walking and resistance-based exercise, 30 min before meals. Meal timing and composition were controlled within participants for exercise interventions.

Results: ES attenuated mean 3 h postprandial glucose concentration following breakfast (by 1.4 ± 1.5 mmol/l, p = 0.02) but not lunch (0.4 ± 1.0 mmol/l, p = 0.22), and was more effective than CONT following dinner (0.7 ± 1.5 mmol/l below CONT; p = 0.04). ES also reduced 24 h mean glucose concentration by 0.7 ± 0.6 mmol/l (p = 0.01) and this reduction persisted for the subsequent 24 h (lower by 0.6 ± 0.4 mmol/l vs CONT, relative to their baselines; p = 0.01). CES was just as effective as ES (p > 0.05 for all glycaemic variables) at improving glycaemic control.

Conclusions/interpretation: Dosing exercise as brief, intense 'exercise snacks' before main meals is a time-efficient and effective approach to improve glycaemic control in individuals with insulin resistance.
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http://dx.doi.org/10.1007/s00125-014-3244-6DOI Listing
July 2014