bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute mitogen‐activated protein kinase 1/2 inhibition improves functional recovery and vascular changes after ischaemic stroke in rat‐monitored by 9.4 T magnetic resonance imaging
Authors: Mostajeran M. , Wetterling F. , W. Blixt F. , Edvinsson L. , Ansar S.
Published: October 2017

Aim

The aim was to evaluate the beneficial effect of early mitogen‐activated protein kinase (MEK)1/2 inhibition administered at a clinical relevant time‐point using the transient middle cerebral artery occlusion model and a dedicated rodent magnetic resonance imaging system (9.4T) to monitor cerebrovascular changes non‐invasively for 2 weeks.

Method

Transient middle cerebral artery occlusion was induced in male rats for two hours followed by reperfusion. The specific MEK1/2 inhibitor U0126 was administered ip at 6 and 24 hours post‐reperfusion. Neurological functions were evaluated by 6‐ and 28‐point tests. 9.4 T magnetic resonance imaging was used to monitor morphological infarct changes at day 2, 8 and 14 after stroke and to evaluate cerebral perfusion at day 14. Immunohistochemistry evaluation of Ki67 was performed 14 days post‐stroke.

Results

U0126 improved long‐term behavioural outcome and significantly reduced infarct size. In addition, cerebral perfusion in U0126‐treated animals was improved compared to the vehicle group. Immunohistochemistry showed a significant increase in Ki67+ cells in U0126‐treated animals compared to the vehicle group.

Conclusion

Early MEK1/2 inhibition improves long‐term functional outcome, promotes recovery processes after stroke and most importantly provides a realistic time window for therapy.
Functional interaction of Junctophilin 2 with small‐ conductance Ca2+‐activated potassium channel subtype 2(SK2) in mouse cardiac myocytes
Authors: Fan H. K. , Luo T. X. , Zhao W. D. , Mu Y. H. , Yang Y. , Guo W. J. , Tu H. Y. , Zhang Q.
Published: October 2017

Aim

Junctophilins (JPs), a protein family of the junctional membrane complex, maintain the close conjunction between cell surface and intracellular membranes in striate muscle cells mediating the crosstalk between extracellular Ca2+ entry and intracellular Ca2+ release. The small‐conductance Ca2+‐activated K+ channels are activated by the intracellular calcium and play an essential role in the cardiac action potential profile. Molecular mechanisms of regulation of the SK channels are still uncertain. Here, we sought to determine whether there is a functional interaction of junctophilin type 2 (JP2) with the SK channels and whether JP2 gene silencing might modulate the function of SK channels in cardiac myocytes.

Methods

Association of JP2 with SK2 channel in mouse heart tissue as well as HEK293 cells was studied using in vivo and in vitro approaches. siRNA knockdown of JP2 gene was assessed by real‐time PCR. The expression of proteins was analysed by Western blotting. Ca2+‐activated K+ current (IK,Ca) in infected adult mouse cardiac myocytes was recorded using whole‐cell voltage‐clamp technique. The intracellular Ca2+ transient was measured using an IonOptix photometry system.

Results

We showed for the first time that JP2 associates with the SK2 channel in native cardiac tissue. JP2, via the membrane occupation and recognition nexus (MORN motifs) in its N‐terminus, directly interacted with SK2 channels. A colocalization of the SK2 channel with its interaction protein of JP2 was found in the cardiac myocytes. Moreover, we demonstrated that JP2 is necessary for the proper cell surface expression of the SK2 channel in HEK293. Functional experiments indicated that knockdown of JP2 caused a significant decrease in the density of IK,Ca and reduced the amplitude of the Ca2+ transient in infected cardiomyocytes.

Conclusion

The present data provide evidence that the functional interaction between JP2 and SK2 channels is present in the native mouse heart tissue. Junctophilin 2, as junctional membrane complex (JMC) protein, is an important regulator of the cardiac SK channels.
Domestic Factors and Strategic Partnership: Redefining Philippines‐Japan Relations in the 21st Century
Authors: Trinidad Dennis D.
Published: October 2017

The Joint Statements and declarations on the establishment, promotion, and strengthening of strategic partnership by the leaders of Japan and the Philippines since 2011 indicate an ardent desire toward making security and defense cooperation a salient feature of their 21st century bilateral relationship. Scholars would point to the “China factor” as a convenient reason to explain the strategic trajectory of this evolving relationship. While this study does not discount the “China factor” as a motivating force behind this change, it asserts that both nations were able to extend their partnership into the security realm because of some enabling domestic factors. Nonetheless, a Duterte Presidency may seriously derail this effort.
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Catalytic receptors
Authors: Alexander Stephen PH , Fabbro Doriano , Kelly Eamonn , Marrion Neil V , Peters John A , Faccenda Elena , Harding Simon D , Pawson Adam J , Sharman Joanna L , Southan Christopher , Davies Jamie A ,   CGTP Collaborators
Published: October 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13876/full. Catalytic receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ligand‐gated ion channels, voltage‐gated ion channels, other ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Enzymes
Authors: Alexander Stephen PH , Fabbro Doriano , Kelly Eamonn , Marrion Neil V , Peters John A , Faccenda Elena , Harding Simon D , Pawson Adam J , Sharman Joanna L , Southan Christopher , Davies Jamie A ,   CGTP Collaborators
Published: October 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13877/full. Enzymes are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ligand‐gated ion channels, voltage‐gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: G protein‐coupled receptors
Authors: Alexander Stephen PH , Christopoulos Arthur , Davenport Anthony P , Kelly Eamonn , Marrion Neil V , Peters John A , Faccenda Elena , Harding Simon D , Pawson Adam J , Sharman Joanna L , Southan Christopher , Davies Jamie A ,   CGTP Collaborators
Published: October 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13878/full. G protein‐coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand‐gated ion channels, voltage‐gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Ligand‐gated ion channels
Authors: Alexander Stephen PH , Peters John A , Kelly Eamonn , Marrion Neil V , Faccenda Elena , Harding Simon D , Pawson Adam J , Sharman Joanna L , Southan Christopher , Davies Jamie A ,   CGTP Collaborators
Published: October 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13879/full. Ligand‐gated ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, voltage‐gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Nuclear hormone receptors
Authors: Alexander Stephen PH , Cidlowski John A , Kelly Eamonn , Marrion Neil V , Peters John A , Faccenda Elena , Harding Simon D , Pawson Adam J , Sharman Joanna L , Southan Christopher , Davies Jamie A ,   CGTP Collaborators
Published: October 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13880/full. Nuclear hormone receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ligand‐gated ion channels, voltage‐gated ion channels, other ion channels, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate. © 2015 The British Pharmacological Society
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Other ion channels
Authors: Alexander Stephen PH , Kelly Eamonn , Marrion Neil V , Peters John A , Faccenda Elena , Harding Simon D , Pawson Adam J , Sharman Joanna L , Southan Christopher , Davies Jamie A ,   CGTP Collaborators
Published: October 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13881/full. Other ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ligand‐gated ion channels, voltage‐gated ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Overview
Authors: Alexander Stephen PH , Kelly Eamonn , Marrion Neil V , Peters John A , Faccenda Elena , Harding Simon D , Pawson Adam J , Sharman Joanna L , Southan Christopher , Buneman O Peter , Cidlowski John A , Christopoulos Arthur , Davenport Anthony P , Fabbro Doriano , Spedding Michael , Striessnig Jörg , Davies Jamie A ,   CGTP Collaborators
Published: October 2017

The Concise Guide to PHARMACOLOGY 2017/18 is the third in this series of biennial publications. This version provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13882/full. In addition to this overview, in which are identified ‘Other protein targets’ which fall outside of the subsequent categorisation, there are eight areas of focus: G protein‐coupled receptors, ligand‐gated ion channels, voltage‐gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Transporters
Authors: Alexander Stephen PH , Kelly Eamonn , Marrion Neil V , Peters John A , Faccenda Elena , Harding Simon D , Pawson Adam J , Sharman Joanna L , Southan Christopher , Davies Jamie A ,   CGTP Collaborators
Published: October 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13883/full. Transporters are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ligand‐gated ion channels, voltage‐gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Voltage‐gated ion channels
Authors: Alexander Stephen PH , Striessnig Jörg , Kelly Eamonn , Marrion Neil V , Peters John A , Faccenda Elena , Harding Simon D , Pawson Adam J , Sharman Joanna L , Southan Christopher , Davies Jamie A ,   CGTP Collaborators
Published: October 2017

The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13884/full. Voltage‐gated ion channels are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ligand‐gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
Editorial: Global child mental health – emerging challenges and opportunities
Authors: Vostanis Panos
Published: October 2017

Children in low‐ and middle‐income countries (LMIC), particularly those living in disadvantaged and conflict‐ridden communities, are faced with extensive unmet health and social care needs (UNICEF, ). A substantial body of research has also provided evidence specifically relating to children's mental health, thereby increasing our understanding regarding the impact of cumulative and interlinked risk factors such as war, conflict and displacement, natural disasters, poverty, child labour and other forms of exploitation. Attempts to improve children's mental health in LMICs is, however, constrained by a range of factors including stigma relating to mental illness, limited policy input as reflected by the low level of specialist resources, lack of contextualised evidence regarding culturally appropriate psychosocial interventions (Patel & Rahman, ), and underrepresentation of LMICs in the research literature (Helal, Ahmed, & Vostanis, ).
The intersection of adolescent depression and peer violence: baseline results from a randomized controlled trial of 1752 youth in Pakistan
Authors: Asad Nargis , Karmaliani Rozina , McFarlane Judith , Bhamani Shireen Shehzad , Somani Yasmeen , Chirwa Esnat , Jewkes Rachel
Published: October 2017

Background

Depression and peer violence are global issues impacting youth. We are presenting baseline data as part of a cluster randomized control trial underway, on adolescent depression, and associated factors among boys and girls in schools.

Method

Cluster randomized control trial is underway for measuring the effectiveness of school‐based play intervention program of the NGO Right to Play, in a sample of 1752 grade 6 youth in 40 public schools of Hyderabad, Pakistan. Students responded to Child Depression Inventory (CDI‐2), the Peer Victimization Scale (PVS), the Peer Perpetration Scale (PPS), and investigator‐driven seven‐item School Performance Scale.

Results

We report baseline assessments to examine the prevalence of depressive symptoms, and associated occurrence of peer perpetration and victimization. Boys report significantly more depressive symptoms as well as perpetration and victimization compared to girls (p ≤ .0001). Our analysis indicates that among boys, depression was found associated with greater age, food insecurity, poorer school performance and working for money, as well as being beaten at home and witnessing beating of their mother by their father or other relatives. Among girls, depression was associated with a younger age, greater food insecurity and poorer school performance. Depression was also associated with a great likelihood of engagement in peer violence, experience of punishment at home, and witnessing their father fighting with other men or beating their mother.

Conclusions

Engagement in violent behaviors, exposure to violent acts and poverty surfaces as detrimental to mental health in youth age groups, suggesting strong measures to address youth violence, and poverty reduction for positive mental health outcomes in school age children.
Everolimus in advanced, progressive, well‐differentiated, non‐functional neuroendocrine tumors: RADIANT‐4 lung subgroup analysis
Authors: Fazio Nicola , Buzzoni Roberto , Delle Fave Gianfranco , Tesselaar Margot E. , Wolin Edward , Van Cutsem Eric , Tomassetti Paola , Strosberg Jonathan , Voi Maurizio , Bubuteishvili‐Pacaud Lida , Ridolfi Antonia , Herbst Fabian , Tomasek Jiri , Singh Simron , Pavel Marianne , Kulke Matthew H. , Valle Juan W. , Yao James C.
Published: October 2017

In the phase III RADIANT‐4 study, everolimus improved median progression‐free survival (PFS) by 7.1 months in patients with advanced, progressive, well‐differentiated (grade 1 or grade 2), non‐functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35‐0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT‐4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8‐10.9) months in the everolimus arm vs 3.6 (1.9‐5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28‐0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3‐4 drug‐related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well‐differentiated, non‐functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT‐4 cohort. These results support the use of everolimus in patients with advanced, non‐functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783).
Long‐term safety of growth hormone—A combined registry analysis
Authors: Stochholm Kirstine , Kiess Wieland
Published: October 2017

Objectives

Preliminary data from the French cohort of the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) study raised concerns regarding the safety of recombinant human GH, suggesting that GH may increase mortality and incidence of stroke in patients treated during childhood for GH deficiency or short stature. We evaluated published safety data, focusing on mortality, neoplasms, cerebrovascular events and diabetes across a number of large‐scale pharmaceutical company GH registries.

Design

A literature review was conducted using PubMed, EMBASE and Google Scholar to identify all relevant safety data from manufacturers' GH registries published between 1988 and April 2016. Results were hand‐sorted to exclude nonrelevant publications; bibliographic references from retrieved articles were evaluated for any additional references.

Results

The published data do not support an increased risk of mortality in children or adults treated with GH. There was no evidence of an increased risk of stroke, new malignancy, leukaemia, nonleukaemic extracranial tumours or recurrence of intracranial malignancy in patients without risk factors. The risk of a second neoplasm is increased, particularly if patients have received radiation therapy for a central nervous system tumour. There may be an increased risk of type 2 diabetes in GH‐treated patients, but this appears to be confined to those with pre‐existing risk factors.

Conclusions

Patients with risk factors for malignancy or type 2 diabetes should be treated with caution and monitored during follow‐up, but current published data provide reassurance on the long‐term safety profile of GH in patients receiving GH treatment.
Current use of baseline medical treatment in chronic rhinosinusitis: Data from the National Chronic Rhinosinusitis Epidemiology Study (CRES)
Authors: Philpott C. , Erskine S. , Smith R. , Hopkins C. , Kara N. , Farboud A. , Salam M. , Robertson A. , Almeyda R. , Kumar B.N. , Anari S. , Ray J. , Cathcart R. , Carrie S. , Ahmed S. , Khalil H. , Clark A. , Thomas M. ,   the CRES group
Published: October 2017

Objectives

According to clinical and comissioning guidelines for chronic rhinosinusitis (CRS), patients being referred to secondary care should have failed primary medical treatment with nasal douching (ND) and intranasal corticosteroids (INCS). The study objectives were to identify the rate of specific medical therapy in CRS patients and establish any differences in medication use, for both CRS and associated medical conditions, between CRS phenotypes.

Design and setting

Case–control study in a secondary care setting.

Methods

Participant‐reported study‐specific questionnaire capturing free text data on current medication use at the time of study entry. Qualitative interviews with 21 participants also explored their experience of CRS and its management.

Particpants

Patients both without (CRSsNPs) and with polyps (CRSwNPs).

Main outcome measures

Reported use of CRS‐related and non‐related medications.

Results

Within a total of 1243 CRS participants, current INCS usage was low (18% in CRSwNPs, 12% in CRSsNPs); ND was being performed by only 1% of all participants. Bronchodilators and inhaled corticosteroids use was significantly higher in CRSwNPs participants (P < .0001). Antidepressant use was significantly higher in CRSsNPs (14% vs 7%, P < .0002). There were no significant regional variations in rates of INCS use, nor any significant influence of social deprivation.

Conclusions

The current use of baseline medical therapy in CRS appears to be very low, representing a combination of poor patient compliance, possible ineffectiveness of treatment and a lack of familiarity with current guidelines amongst general practitioners and some ENT specialists. Work is needed to disseminate guidelines to all practitioners involved and reduce unnecessary burden on existing healthcare resources for this common condition by ensuring timely referral and definitive management.
Cognitive function among long‐term survivors of heart transplantation
Authors: Bürker Britta S. , Gude Einar , Gullestad Lars , Grov Ingelin , Relbo Authen Anne , Andreassen Arne K. , Havik Odd E. , Dew Mary Amanda , Fiane Arnt E. , Haraldsen Ira R. , Malt Ulrik F. , Andersson Stein
Published: October 2017

Background

Cognitive impairment is documented early after heart transplantation (HTx), but we lack data on cognitive function beyond the fourth year post‐transplant. Against the background of good long‐term survival, this knowledge is necessary to improve clinical care throughout the entire post‐transplant period.

Methods

We assessed cognitive function with a neuropsychological test battery in a sample of HTx recipients ≥16 years post‐transplant. To improve clinical utility, we also applied adapted consensus criteria for Mild Cognitive Impairment (MCI). Furthermore, we explored sociodemographic and clinical characteristics possibly related to cognitive function.

Results

Thirty‐seven subjects were included 20.3 (±3.8) years after HTx. Mean age was 57.5 (±14.2) years, and 18.9% were women. Up to 38.9% exhibited impaired test performance (ie, performance at least 1.5 standard deviations below the normative mean) on several individual cognitive measures, especially on measures of processing speed, executive functions, memory, and language functions. One subject was diagnosed with dementia, and 30.1% qualified for MCI. Those with MCI had lower hemoglobin than those without.

Conclusions

A substantial proportion of long‐term survivors of HTx might be cognitively impaired. The level of impairment appears comparable to what is defined as MCI in the literature. Modifiable factors related to cognitive impairment might exist.
Prevention and management of spouting bleeding during endoscopic submucosal dissection for large subpedunculated‐type colonic tumor
Authors: Tamaru Yuzuru , Oka Shiro , Tanaka Shinji
Published: October 2017

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Multicenter prospective evaluation study of endoscopic ultrasound‐guided hepaticogastrostomy combined with antegrade stenting (with video)
Authors: Ogura Takeshi , Kitano Masayuki , Takenaka Mamoru , Okuda Atsushi , Minaga Kosuke , Yamao Kentaro , Yamashita Yukitaka , Hatamaru Keiichi , Noguchi Chishio , Gotoh Yasuhiko , Kuroda Taira , Yokota Tomoyuki , Nishikiori Hidefumi , Sagami Ryota , Higuchi Kazuhide , Chiba Yasutaka
Published: October 2017

Background and Aim

Endoscopic ultrasonography‐guided hepaticogastrostomy (EUS‐HGS) is often indicated for advanced stage patients. Therefore it is important to prevent adverse events associated with EUS‐HGS procedures and obtain long stent patency. EUS‐guided antegrade stenting (AS) has been developed as an advanced technique. Thus, to prevent adverse events and achieve long stent patency, EUS‐AS combined with EUS‐HGS (EUS‐HGAS) has been reported. The aim of the present study was to evaluate the technical feasibility and efficacy of EUS‐HGAS in a multicenter, prospective study.

Methods

This prospective study was carried out at each hospital of the Therapeutic Endoscopic Ultrasound Group. Primary endpoint of this multicenter prospective study was stent patency of EUS‐HGAS.

Results

A total of 49 patients were enrolled. Technical success rate of EUS‐HGS was 95.9% (47/49). EUS‐AS failed in five patients because the guidewire could not be advanced into the intestine across the bile duct obstruction site. Therefore, EUS‐HGAS was successfully carried out in 40 patients (technical success rate: 85.7%). Median overall survival was 114 days. Median stent patency including stent dysfunction and patient death was 114 days. In contrast, mean stent patency was 320 days. Adverse events were seen in 10.2% (5/49) of cases. Hyperamylasemia was seen in four patients, and bleeding was seen in one patient.

Conclusions

The present study is the first to evaluate EUS‐HGAS. EUS‐HGAS has clinical benefit for obtaining long stent patency and avoiding adverse events, although the possibility of acute pancreatitis as a result of obstruction of the orifice of the pancreatic duct must be considered.
Advanced diagnostic endoscopy in the lower gastrointestinal tract: A review of JGES core sessions
Authors: Oka Shiro , Tanaka Shinji , Sano Yasushi , Saitoh Yusuke , Shimoda Ryo , Tajiri Hisao
Published: October 2017

At each of the 89th to the 92nd congresses of the Japan Gastroenterological Endoscopy Society, a series of featured discussion sessions concerning advanced diagnostic endoscopy in the lower gastrointestinal tract were presented. In total, 45 lectures were presented in this subject area. It was shown that, in recent years, several convenient and less invasive colonoscopic modalities have been developed. This review article summarizes these core sessions and the efficacy of the techniques discussed.
Transcranial direct current stimulation for rehabilitating the brain
Authors: Dan Bernard
Published: October 2017

Video Podcast: https://www.youtube.com/watch?v=0TpwwvuSXGY&feature=youtu.be
Focal cortical malformations in children with early infantile epilepsy and PCDH19 mutations: case report
Authors: Kurian Mary , Korff Christian M , Ranza Emmanuelle , Bernasconi Andrea , Lübbig Anja , Nangia Srishti , Ramelli Gian Paolo , Wohlrab Gabriele , Nordli Douglas R , Bast Thomas
Published: October 2017

In this case report we assess the occurrence of cortical malformations in children with early infantile epilepsy associated with variants of the gene protocadherin 19 (PCDH19). We describe the clinical course, and electrographic, imaging, genetic, and neuropathological features in a cohort of female children with pharmacoresistant epilepsy. All five children (mean age 10y) had an early onset of epilepsy during infancy and a predominance of fever sensitive seizures occurring in clusters. Cognitive impairment was noted in four out of five patients. Radiological evidence of cortical malformations was present in all cases and, in two patients, validated by histology. Sanger sequencing and Multiplex Ligation‐dependent Probe Amplification analysis of PCDH19 revealed pathogenic variants in four patients. In one patient, array comparative genomic hybridization showed a microdeletion encompassing PCDH19. We propose molecular testing and analysis of PCDH19 in patients with pharmacoresistant epilepsy, with onset in early infancy, seizures in clusters, and fever sensitivity. Structural lesions are to be searched in patients with PCDH19 pathogenic variants. Further, PCDH19 analysis should be considered in epilepsy surgery evaluation even in the presence of cerebral structural lesions.

What this paper adds

Focal cortical malformations and monogenic epilepsy syndromes may coexist.

Structural lesions are to be searched for in patients with protocadherin 19 (PCDH19) pathogenic variants with refractory focal seizures.
Type 2 diabetes remission 2 years post Roux‐en‐Y gastric bypass and sleeve gastrectomy: the role of the weight loss and comparison of DiaRem and DiaBetter scores
Authors: Pucci A. , Tymoszuk U. , Cheung W. H. , Makaronidis J. M. , Scholes S. , Tharakan G. , Elkalaawy M. , Guimaraes M. , Nora M. , Hashemi M. , Jenkinson A. , Adamo M. , Monteiro M. P. , Finer N. , Batterham R. L.
Published: October 2017

Aims

The comparative efficacy of Roux‐en‐Y gastric bypass (RYGB) and sleeve gastrectomy on Type 2 diabetes remission and the role of weight loss are unclear. The DiaRem diabetes remission prediction score uses HbA1c, age and diabetes medications but not diabetes duration. The aim of this study was to compare the DiaRem with the DiaBetter score that includes diabetes duration, upon combined (complete plus partial) 2‐year post‐surgery diabetes remission in people following RYGB and sleeve gastrectomy, and to investigate the relationship between weight loss and diabetes remission.

Methods

A retrospective single‐centre cohort study of obese people with diabetes who underwent RYGB (107) or sleeve gastrectomy (103) and a validation cohort study (173) were undertaken. Diabetes remission, % weight loss, DiaRem, DiaBetter scores and areas under receiving operator characteristic (ROC) curves were calculated. The relationship between % weight loss and diabetes remission was investigated using logistic regression.

Results

The proportion of people achieving diabetes remission was highest for those with the lowest DiaBetter and DiaRem scores. Areas under the ROC curves were comparable [DiaBetter: 0.867 (95%CI: 0.817–0.916); DiaRem: 0.865 (95%CI: 0.814–0.915), P=0.856]. Two‐year % weight loss was higher post RYGB [26.6 (95%CI: 24.8–28.4)] vs post‐sleeve gastrectomy [20.6 (95%CI: 18.3–22.8), P<0.001]. RYGB had 151% higher odds of diabetes remission [OR 2.51 (95%CI: 1.12–5.60), P=0.025]. This association became non‐significant when adjusted for % weight loss.

Conclusion

DiaBetter and DiaRem scores predict diabetes remission following both procedures. Two‐year % weight loss plays a key role in determining diabetes remission.
How house price appreciation affects homeowners' labour force participation
Authors: Zhao Jianmei , Liu Lin , Liu Ruihan
Published: October 2017

This paper investigates the effects of house price appreciation on homeowners' labour force participation (LFP). Although economic theories predict that housing capital gains will reduce labour supply, empirical evidence from urban China revealed that house price appreciation significantly boosts homeowners' LFP. Heterogeneous analyses indicate that LFP behaviour is more likely to be affected by house price appreciation for female and younger homeowners. Furthermore, homeowners living in provinces with greater house price appreciation tend to be more active in job participation than those living in provinces with lower price appreciation.
The neural oscillations of speech processing and language comprehension: state of the art and emerging mechanisms
Authors: Meyer Lars
Published: October 2017

Neural oscillations subserve a broad range of functions in speech processing and language comprehension. On the one hand, speech contains—somewhat—repetitive trains of air pressure bursts that occur at three dominant amplitude modulation frequencies, physically marking the linguistically meaningful progressions of phonemes, syllables and intonational phrase boundaries. To these acoustic events, neural oscillations of isomorphous operating frequencies are thought to synchronise, presumably resulting in an implicit temporal alignment of periods of neural excitability to linguistically meaningful spectral information on the three low‐level linguistic description levels. On the other hand, speech is a carrier signal that codes for high‐level linguistic meaning, such as syntactic structure and semantic information—which cannot be read from stimulus acoustics, but must be acquired during language acquisition and decoded for language comprehension. Neural oscillations subserve the processing of both syntactic structure and semantic information. Here, I synthesise a mapping from each linguistic processing domain to a unique set of subserving oscillatory mechanisms—the mapping is plausible given the role ascribed to different oscillatory mechanisms in different subfunctions of cortical information processing and faithful to the underlying electrophysiology. In sum, the present article provides an accessible and extensive review of the functional mechanisms that neural oscillations subserve in speech processing and language comprehension.
Deep brain stimulation of the nucleus basalis of Meynert attenuates early EEG components associated with defective sensory gating in patients with Alzheimer disease – a two‐case study
Authors: Dürschmid Stefan , Reichert Christoph , Kuhn Jens , Freund Hans‐Joachim , Hinrichs Hermann , Heinze Hans‐Jochen
Published: October 2017

Alzheimer′s disease (AD) is associated with deterioration of memory and cognitive function and a degeneration of neurons of the nucleus basalis of Meynert (NBM). The NBM is the major input source of acetylcholine (ACh) to the cortex. The decreasing cholinergic innervation of the cortex due to degeneration of the NBM might be the cause of loss of memory function. NBM‐Deep brain stimulation (NBM‐DBS) is considered to serve as a potential therapeutic option for patients with AD by supporting residual cholinergic transmission to stabilize oscillatory activity in memory‐relevant circuits. However, whether DBS could improve sensory memory functions in patients with AD is not clear. Here, in a passive auditory oddball paradigm, patients with AD (N = 2) listened to repetitive background tones (standard tones) randomly interrupted by frequency deviants in two blocks with NBM‐DBS OFF and then NBM‐DBS ON, while age‐matched healthy controls (N = 6) repeated the experiment twice. The mismatch negativity in NBM‐DBS OFF significantly differed from controls in both blocks, but not under NBM‐DBS, which was likely due to a pronounced P50 increase overlapping with the N1 in NBM‐DBS OFF. This early complex of EEG components recovered under stimulation to a normal level as defined by responses in controls. In this temporal interval, we found in patients with NBM‐DBS ON (but not with NBM‐DBS OFF) and in controls a strong repetition suppression effect to standard tones – with more attenuated responses to frequently repeated standard tones. This highlights the role of NBM‐DBS for sensory gating of familiar auditory information into sensory memory.
Substance P and dopamine interact to modulate the distribution of delta‐opioid receptors on cholinergic interneurons in the striatum
Authors: Heath Emily , Chieng Billy , Christie Macdonald J. , Balleine Bernard W.
Published: October 2017

It has been recently demonstrated that predictive learning induces a persistent accumulation of delta‐opioid receptors (DOPrs) at the somatic membrane of cholinergic interneurons (CINs) in the nucleus accumbens shell (Nac‐S). This accumulation is required for predictive learning to influence subsequent choice between goal‐directed actions. The current experiments investigated the local neurochemical events responsible for this translocation. We found that (1) local administration of substance P into multiple striatal sub‐territories induced DOPr translocation and (2) that this effect was mediated by the NK1 receptor, likely through its expression on CINs. Interestingly, whereas intrastriatal infusion of the D1 agonist chloro‐APB reduced the DOPr translocation on CINs and infusion of the D2 agonist quinpirole had no effect, co‐administration of both agonists again generated DOPr translocation, suggesting the effect of the D1 agonist alone was due to receptor internalisation. In support of this, local administration of cocaine was found to increase DOPr translocation as was chloro‐APB when co‐administered with the DOPr antagonist naltrindole. These studies provide the first evidence of delta‐opioid receptor translocation in striatal cholinergic interneurons outside of the accumbens shell and suggest that, despite differences in local striatal neurochemical microenvironments, a similar molecular mechanism – involving an interaction between dopamine and SP signalling via NK1R – regulates DOPr translocation in multiple striatal regions. To our knowledge, this represents a novel mechanism by which DOPr distribution is regulated that may be particularly relevant to learning‐induced DOPr trafficking.