bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kv4.2 channel activity controls intrinsic firing dynamics of arcuate kisspeptin neurons
Authors: Mendonça Philipe R. F. , Kyle Victoria , Yeo Shel‐Hwa , Colledge William H. , Robinson Hugh P. C. 
Published: December 2017

Key points
Neurons in the hypothalamus of the brain which secrete the peptide kisspeptin are important regulators of reproduction, and normal reproductive development.
Electrical activity, in the form of action potentials, or spikes, leads to secretion of peptides and neurotransmitters, influencing the activity of downstream neurons; in kisspeptin neurons, this activity is highly irregular, but the mechanism of this is not known.
In this study, we show that irregularity depends on the presence of a particular type of potassium ion channel in the membrane, which opens transiently in response to electrical excitation.
The results contribute to understanding how kisspeptin neurons generate and time their membrane potential spikes, and how reliable this process is.
Improved understanding of the activity of kisspeptin neurons, and how it shapes their secretion of peptides, is expected to lead to better treatment for reproductive dysfunction and disorders of reproductive development.
AbstractKisspeptin neurons in the hypothalamus are critically involved in reproductive function, via their effect on GnRH neuron activity and consequent gonadotropin release. Kisspeptin neurons show an intrinsic irregularity of firing, but the mechanism of this remains unclear. To address this, we carried out targeted whole‐cell patch‐clamp recordings of kisspeptin neurons in the arcuate nucleus (Kiss1Arc), in brain slices isolated from adult male Kiss‐Cre:tdTomato mice. Cells fired irregularly in response to constant current stimuli, with a wide range of spike time variability, and prominent subthreshold voltage fluctuations. In voltage clamp, both a persistent sodium (NaP) current and a fast transient (A‐type) potassium current were apparent, activating at potentials just below the threshold for spiking. These currents have also previously been described in irregular‐spiking cortical interneurons, in which the A‐type current, mediated by Kv4 channels, interacts with NaP current to generate complex dynamics of the membrane potential, and irregular firing. In Kiss1Arc neurons, A‐type current was blocked by phrixotoxin, a specific blocker of Kv4.2/4.3 channels, and consistent expression of Kv4.2 transcripts was detected by single‐cell RT‐PCR. In addition, firing irregularity was correlated to the density of A‐type current in the membrane. Using conductance injection, we demonstrated that adding Kv4‐like potassium conductance (gKv4) to a cell produces a striking increase in firing irregularity, and excitability is reduced, while subtracting gKv4 has the opposite effects. Thus, we propose that Kv4 interacting dynamically with NaP is a key determinant of the irregular firing behaviour of Kiss1Arc neurons, shaping their physiological function in gonadotropin release.
Modeling the Flow of Non-Newtonian Fluids Through Sharp
Orifices
Authors: Rituraj  , Vacca Andrea 
Published: December 2017

Abstract
This paper proposes a novel orifice flow model for non-Newtonian fluids. The orifice model is developed for sharp orifices with small apertures (orifice to pipe diameter ratio: 0.04 ≤ β ≤ 0.16) for which predictive models are not present in the literature. The orifice flow experiment is conducted with three different orifices and three different fluids. From the experimental data, a correlation is developed that relates Euler number to Reynolds number and orifice diameter ratio. It also accounts for elastic effects of the fluid on orifice flow by including Weissenberg number in the model. The developed model predicts the experimental data within reasonable accuracy.
Choroidal neovascular membrane in paediatric patients: clinical characteristics and outcomes
Authors: Padhi Tapas Ranjan , Anderson Bradley J , Abbey Ashkan M , Yonekawa Yoshihiro , Stem Maxwell , Alam Danish , Modi Rohit Ramesh , Savla Laxmi Prabhavathi , Trese Michael T , Capone Antonio , Drenser Kimberly A , Besirli Cagri G 
Published: December 2017

PurposeTo analyse the clinical characteristics and treatment outcomes of choroidal neovascular membranes (CNVM) in paediatric subjects at three paediatric retina referral centres.MethodsMedical charts of patients aged 18 years or less with a diagnosis of CNVM were retrospectively reviewed. The demographic profile, laterality, presenting complaint, corrected vision, underlying pathology, fundus, fundus fluorescein angiogram and optical coherence tomogram (OCT) were analysed. CNVM type, frequency, treatment indications, recurrences and final visual acuity were noted.ResultsThere were a total of 35 subjects (43 eyes) with a mean age of 11.2 years. The CNVMs were mostly type 2 (90.0%), classic (90.9%), subfoveal (59.09%) and active (84.1%). Best vitelliform macular dystrophy was found to be the most common association (32.5%). Intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent was the initial therapy of choice in all. Eyes with CNVMs responsive to anti-VEGF alone required a mean of 2.11 injections. Patients with recurrent disease (21.21%) had an average of 1.14 episodes per eye. While 50% of recurrent CNVMs stabilised with repeat anti-VEGF treatment, the remaining patients required photodynamic therapy, laser or surgery.ConclusionPaediatric CNVMs in this series differed from those in the adult population with regard to aetiology, OCT and angiographic characteristics, treatment response and rate of recurrence.
Successfully implementing and embedding guidelines to improve the nutrition and growth of preterm infants in neonatal intensive care: a prospective interventional study
Authors: Johnson Mark J , Leaf Alison A , Pearson Freya , Clark Howard W , Dimitrov Borislav D , Pope Catherine , May Carl R 
Published: December 2017

ObjectivesWe aimed to improve the nutritional care of preterm infants by developing a complex (multifaceted) intervention intended to translate current evidence into practice. We used the sociological framework of Normalization Process Theory (NPT), to guide implementation in order to embed the new practices into routine care.DesignA prospective interventional study with a before and after methodology.ParticipantsInfants <30 weeks gestation or <1500 g at birth.SettingTertiary neonatal intensive care unit.InterventionsThe intervention was introduced in phases: phase A (control period, January–August 2011); phase B (partial implementation; improved parenteral and enteral nutrition solutions, nutrition team, education, August–December 2011); phase C (full implementation; guidelines, screening tool, ‘nurse champions’, January–December 2012); phase D (postimplementation; January–June 2013). Bimonthly audits and staff NPT questionnaires were used to measure guideline compliance and ‘normalisation’, respectively. NPT Scores were used to guide implementation in real time. Data on nutrient intakes and growth were collected continuously.ResultsThere were 52, 36, 75 and 35 infants in phases A, B, C and D, respectively. Mean guideline compliance exceeded 75% throughout the intervention period, peaking at 85%. Guideline compliance and NPT scores both increased over time, (r=0.92 and 0.15, p<0.03 for both), with a significant linear association between the two (r=0.21, p<0.01). There were significant improvements in daily protein intake and weight gain between birth and discharge in phases B and Ccompared with phase A (p<0.01 for all), which were sustained into phase D.ConclusionsNPT and audit results suggest that the intervention was rapidly incorporated into practice, with high guideline compliance and accompanying improvements in protein intake and weight gain. NPT appears to offer an effective way of implementing new practices such that they lead to sustained changes in care. Complex interventions based on current evidence can improve both practice and clinical outcomes.
‘At-risk’ individuals’ responses to direct to consumer advertising of prescription drugs: a nationally representative cross-sectional study
Authors: Khalil Zadeh Neda , Robertson Kirsten , Green James A 
Published: December 2017

ObjectivesThe factors determining individuals’ self-reported behavioural responses to direct to consumer advertising of prescription drugs were explored with an emphasis on ‘at-risk’ individuals’ responses.DesignNationally representative cross-sectional survey.SettingCommunity living adults in New Zealand.Participants2057 adults (51% women).Primary outcome measuresSelf-reported behavioural responses to drug advertising (asking a physician for a prescription, asking a physician for more information about an illness, searching the internet for more information regarding an illness and asking a pharmacist for more information about a drug).MethodsMultivariate logistic regressions determined whether participants’ self-reported behavioural responses to drug advertising were predicted by attitudes towards advertising and drug advertising, judgements about safety and effectiveness of advertised drugs, self-reported health status, materialism, online search behaviour as well as demographic variables.ResultsIdentifying as Indian and to a less extent Chinese, Māori and ‘other’ ethnicities were the strongest predictors of one or more self-reported responses (ORs 1.76–5.00, Ps<0.05). Poorer self-reported health status (ORs 0.90–0.94, all Ps<0.05), favourable attitude towards drug advertising (ORs 1.34–1.61, all Ps<0.001) and searching for medical information online (ORs 1.32–2.35, all Ps<0.01) predicted all self-reported behavioural outcomes. Older age (ORs 1.01–1.02, Ps<0.01), less education (OR 0.89, P<0.01), lower income (ORs 0.89–0.91, Ps<0.05) and higher materialism (ORs 1.02–1.03, Ps<0.01) also predicted one or more self-reported responses.ConclusionsTaken together, the findings suggest individuals, especially those who are ‘at-risk’ (ie, with poorer self-reported health status, older, less educated, lower income and ethnic minorities), may be more vulnerable to drug advertising and may make uninformed decisions accordingly. The outcomes raise significant concerns relating to the ethicality of drug advertising and suggest a need for stricter guidelines to ensure that drug advertisements provided by pharmaceutical companies are ethical.
Atrial fibrillation in patients with severe mental disorders and the risk of stroke, fatal thromboembolic events and bleeding: a nationwide cohort study
Authors: Søgaard Mette , Skjøth Flemming , Kjældgaard Jette Nordstrøm , Larsen Torben Bjerregaard , Hjortshøj Søren Pihlkjær , Riahi Sam 
Published: December 2017

ObjectivesOutcomes of atrial fibrillation (AF) in patients with severe mental disorders are largely unknown. We compared rates of stroke, fatal thromboembolic events and bleeding in patients with AF with and without mental disorders.DesignNationwide registry-based cohort study.SettingDenmark (population 5.6 million), 2000–2015.ParticipantsPatients with AF with schizophrenia (n=534), severe depression (n=400) or bipolar disease (n=569) matched 1:5 on age, sex and calendar time to patients with AF without mental disorders.ExposureInpatient or hospital-based outpatient diagnosis of schizophrenia, severe depression or bipolar disease.Primary and secondary outcome measuresHRs for stroke, fatal thromboembolic events and major bleeding comparing patients with and without mental disorders estimated by Cox regression with sequential adjustment for risk factors for stroke and bleeding, comorbidity and initiation of oral anticoagulant therapy (OAT).ResultsCompared with matched comparisons, crude 5-year HRs of ischaemic stroke were 1.37 (95% CI 0.88 to 2.14) for schizophrenia, 1.36 (95% CI 0.89 to 2.08) for depression and 1.04 (95% CI 0.69 to 1.56) for bipolar disease. After adjusting for risk factors, comorbidity and OAT, these HRs declined towards the null. Crude HRs of fatal thromboembolic events were 3.16 (95% CI 1.78 to 5.61) for schizophrenia, 1.31 (95% CI 0.67 to 2.56) for depression and 1.53 (95% CI 0.93 to 2.53) for bipolar disease. Rates of major bleeding were increased in patients with schizophrenia (crude HR 1.37, 95% CI 0.99 to 1.90) and severe depression (HR 1.25, 95% CI 0.87 to 1.78) but not bipolar disease (HR 0.82, 95% CI 0.58 to 1.15).ConclusionPatients with AF with schizophrenia or severe depression experienced increased rates of stroke and major bleeding compared with matched comparisons. This increase was largely explained by differences in the prevalence of risk factors for stroke and bleeding, comorbidity and initiation of OAT during follow-up. Patients with AF with schizophrenia further experienced higher mortality following thromboembolic events than matched comparisons without mental disorders.
The association between the use of biomedical services and the holistic use of traditional East Asian medicine: a national survey of outpatients in South Korea
Authors: Shim Jae-Mahn , Lee Yun-Suk 
Published: December 2017

ObjectivesThe holistic use of a system of complementary and alternative medicine (CAM) is potentially linked to its treatment outcomes. This paper examines how the use of biomedicine is associated with the holistic use of CAM, focusing on traditional East Asian medicine (EM) that is uniquely integrated in the medical system in South Korea.Design/SettingsA representative national sample of EM outpatients in South Korea.Participants3861 survey respondents.MethodsBy using the 2011 Korean National Survey of EM patients, ordered logistic regression models specify the relationship between EM outpatients’ use of biomedicine and their holistic use of EM modalities.ResultsAmong EM outpatients who used at least one EM modality in the past 3 months, people who used two (33.3%) or three (29.4%) modalities together are the two highest proportions, followed by users of four (18.1%), five (7.2%), six (2.1%) and seven (0.6%) modalities. The odds for EM users to use EM holistically are 17% greater among EM users who used biomedicine as well, compared with EM users who did not use biomedicine.ConclusionsThe healthcare community should recognise that CAM use likely becomes holistic as people use biomedicine concomitantly, when the practice rights over a CAM system are comprehensively and exclusively entitled to a group of CAM professionals who are independent from practitioners of biomedicine.
Advancing the science of health research capacity strengthening in low-income and middle-income countries: a scoping review of the published literature, 2000–2016
Authors: Dean Laura , Gregorius Stefanie , Bates Imelda , Pulford Justin 
Published: December 2017

ObjectivesSubstantial development assistance and research funding are invested in health research capacity strengthening (HRCS) interventions in low-income and middle-income countries, yet the effectiveness, impact and value for money of these investments are not well understood. A major constraint to evidence-informed HRCS intervention has been the disparate nature of the research effort to date. This review aims to map and critically analyse the existing HRCS effort to better understand the level, type, cohesion and conceptual sophistication of the current evidence base. The overall goal of this article is to advance the development of a unified, implementation-focused HRCS science.MethodsWe used a scoping review methodology to identify peer-reviewed HRCS literature within the following databases: PubMed, Global Health and Scopus. HRCS publications available in English between the period 2000 and 2016 were included. 1195 articles were retrieved of which 172 met the final inclusion criteria. A priori thematic analysis of all included articles was completed. Content analysis of identified HRCS definitions was conducted.ResultsThe number of HRCS publications increased exponentially between 2000 and 2016. Most publications during this period were perspective, opinion or commentary pieces; however, original research publications were the primary publication type since 2013. Twenty-five different definitions of research capacity strengthening were identified, of which three aligned with current HRCS guidelines.ConclusionsThe review findings indicate that an HRCS research field with a focus on implementation science is emerging, although the conceptual and empirical bases are not yet sufficiently advanced to effectively inform HRCS programme planning. Consolidating an HRCS implementation science therefore presents as a viable option that may accelerate the development of a useful evidence base to inform HRCS programme planning. Identifying an agreed operational definition of HRCS, standardising HRCS-related terminology, developing a needs-based HRCS-specific research agenda and synthesising currently available evidence may be useful first steps.
Hepatitis delta virus persists during liver regeneration and is amplified through cell division both in vitro and in vivo
Authors: Giersch Katja , Bhadra Oliver D , Volz Tassilo , Allweiss Lena , Riecken Kristoffer , Fehse Boris , Lohse Ansgar W , Petersen Joerg , Sureau Camille , Urban Stephan , Dandri Maura , Lütgehetmann Marc 
Published: December 2017

ObjectiveHepatitis delta virus (HDV) was shown to persist for weeks in the absence of HBV and for months after liver transplantation, demonstrating the ability of HDV to persevere in quiescent hepatocytes. The aim of the study was to evaluate the impact of cell proliferation on HDV persistence in vitro and in vivo.DesignGenetically labelled human sodium taurocholate cotransporting polypeptide (hNTCP)-transduced human hepatoma(HepG2) cells were infected with HBV/HDV and passaged every 7 days for 100 days in the presence of the entry inhibitor Myrcludex-B. In vivo, cell proliferation was triggered by transplanting primary human hepatocytes (PHHs) isolated from HBV/HDV-infected humanised mice into naïve recipients. Virological parameters were measured by quantitative real time polymerase chain reaction (qRT-PCR). Hepatitis delta antigen (HDAg), hepatitis B core antigen (HBcAg) and cell proliferation were determined by immunofluorescence.ResultsDespite 15 in vitro cell passages and block of viral spreading by Myrcludex-B, clonal cell expansion permitted amplification of HDV infection. In vivo, expansion of PHHs isolated from HBV/HDV-infected humanised mice was confirmed 3 days, 2, 4 and 8 weeks after transplantation. While HBV markers rapidly dropped in proliferating PHHs, HDAg-positive hepatocytes were observed among dividing cells at all time points. Notably, HDAg-positive cells appeared in clusters, indicating that HDV was transmitted to daughter cells during liver regeneration even in the absence of de novo infection.ConclusionThis study demonstrates that HDV persists during liver regeneration by transmitting HDV RNA to dividing cells even in the absence of HBV coinfection. The strong persistence capacities of HDV may also explain why HDV clearance is difficult to achieve in HBV/HDV chronically infected patients.
Knowledge sharing about deep-sea ecosystems to inform conservation and research decisions
Authors: Januchowski-Hartley Stephanie R. , Selkoe Kimberly A. , Gallo Natalya D. , Bird Christopher E. , Hogan J. Derek 
Published: December 2017

The Marianas Trench Marine National Monument (MNM) currently extends policy-based protection to deep-sea ecosystems contained within it, but managers require better understanding of the current knowledge and knowledge gaps about these ecosystems to guide decision-making. To address this need, we present a case study of the Marianas Trench MNM using in-depth interviews to determine scientists’ (1) current understanding of anthropogenic drivers of change and system vulnerability in deep-sea ecosystems; and (2) perceptions of the least understood deep-sea ecosystems and processes in the Marianas Trench MNM, and which of these, if any, should be research priorities to fill knowledge gaps about these systems and the impacts from anthropogenic drivers of change. Interview respondents shared similar views on the current knowledge of deep-sea ecosystems and potential anthropogenic drivers of change in the Marianas Trench MNM. Respondents also identified trench and deep pelagic (bathyal, abyssal, and hadal zones) ecosystems as the least understood, and highlighted climate change, litter and waste, mining and fishing, and interactions between these drivers of change as critical knowledge gaps. To fill key knowledge gaps and inform conservation decision-making, respondents identified the need for monitoring networks and time-series data. Our approach demonstrates how in-depth interviews can be used to elicit knowledge to inform decision-making in data-limited situations.
Climatological trends and anticipated karst spring quantity and quality: case study of the Slovene Istria
Authors: Ravbar Nataša , Kovačič Gregor , Petrič Metka , Kogovšek Janja , Brun Clarissa , Koželj Alenka 
Published: December 2017

Abstract

The behaviour of aquifers with karst porosity is dependent on hydrological conditions. This is due to the peculiar characteristics of the groundwater flow and dynamics of hydrological processes in karst. As a result, karst aquifers are especially vulnerable to the effects of environmental change. We assessed the long-term climatological and hydrological trends and the short-term effects of increasingly frequent extreme hydrological events (droughts) for the Mediterranean karst spring Rižana in SW Slovenia. The findings predict higher mean annual air temperatures of 0.34°C decade
−1
, lower annual precipitation of
c.
60 mm decade
−1
and higher annual actual evapotranspiration (especially during spring and summer) of 32–49 mm decade
−1
. As a consequence, we can expect a decrease in the mean annual discharge of the spring of
c.
480 l s
−1
decade
−1
with prolonged dry summer periods. Detailed monitoring of the physical, chemical and microbiological parameters showed that the flood pulses caused by precipitation events after a long dry period cause a significant deterioration in water quality. In such situations, contaminants stored in the unsaturated zone are flushed out and counts of coliform bacteria can reach >1400 cfu (100 ml)
−1
, with total Al and Fe concentrations up to 206 and 474 μg l
−1
, respectively. These results suggest that there should be urgent adherence to water quality standards to protect karst water sources in view of the anticipated climatological stresses. Management strategies should promote monitoring and the rational use of karst water supplies.
A construção socioeconômica da cannabis no Marrocos: o kif como produto tradicional, produto manufaturado e produto de contrabando
Authors: Afsahi Kenza 
Published: December 2017

Designado kif no Marrocos, a cannabis passou por importantes transformações que impactaram o seu valor social e econômico neste país. O presente artigo analisa essas mudanças no que se refere à evolução das normas, modos de uso e técnicas, e no que diz respeito às mudanças dos atores que produzem e comercializam a cannabis, em um primeiro momento num contexto tradicional, e em um segundo momento em dois mercados no período dos protetorados francês e espanhol (1912-1956): o mercado de monopólio e o mercado de contrabando.