bluuebunny/crossref_metadata_2025 huggingface dataset:
Type and density of independent takeaway outlets: a geographical mapping study in a low socioeconomic ward, Manchester
Authors: Blow Jennifer , Gregg Rebecca , Davies Ian G , Patel Sumaiya
Published: July 2019

Objectives

The socioeconomic disparity in childhood and early adult obesity prevalence has been well characterised. Takeaway outlets may cluster in lower socioeconomic areas and their proximity to schools is of concern. This study aimed to map takeaway food outlets, characterise takeaway types and their proximity to educational institutions within a low socioeconomic ward in Manchester.

Design

The Rusholme ward and a 2 km Euclidean buffer were included as the study area. Local authority Environmental Health data were used to map the takeaway outlets, using QGIS V.2.18.0 (OPENGIS.ch LLC, Einsiedeln, Switzerland). The types of takeaway outlets and major roads were included. Number of outlets within a 400 m Euclidean walking buffer of educational institutions were mapped.

Setting

Rusholme, Manchester, UK.

Results

Within the study area, 202 takeaway food outlets were identified and mapped as cluster points. Of these, 62.3% are located on major (A and B) roads, while the remaining outlets were located on minor roads. The majority (57.4%) of takeaway outlets sold similar items (fried chicken, burgers, pizzas, kebabs), with the remainder offering more diverse menus. Of the 53 schools, colleges and universities within the study area, 28 (52.8%) had 1–5 takeaway food outlets within 400 m, 9 (17.0%) had 6–10 outlets; 4 (7.5%) more than 11 outlets with 12 (22.6%) having zero outlets within 400 m.

Conclusion

Within this low socioeconomic area, there was a high concentration of takeaway food outlets, predominantly along major roads and in easy walking distance of educational establishments with the majority offering similar foods. In addition, a high proportion of these outlets were in easy walking distance of educational establishments. Public health policy needs to consider the implications of current takeaway food outlets and not just the proliferation of these outlets with current planning laws.
Glycaemic, blood pressure and low-density lipoprotein-cholesterol control among patients with diabetes mellitus in a specialised clinic in Botswana: a cross-sectional study
Authors: Mwita Julius Chacha , Francis Joel M , Omech Bernard , Botsile Elizabeth , Oyewo Aderonke , Mokgwathi Matshidiso , Molefe-Baikai Onkabetse Julia , Godman Brian , Tshikuka Jose-Gaby
Published: July 2019

Objective

Control of glycaemic, hypertension and low-density lipoprotein-cholesterol (LDL-C) among patients with type 2 diabetes mellitus (T2DM) is vital for the prevention of cardiovascular diseases. The current study was an audit of glycaemic, hypertension and LDL-C control among ambulant patients with T2DM in Botswana. Also, the study aimed at assessing factors associated with attaining optimal glycaemic, hypertension and LDL-C therapeutic goals.

Design

A cross-sectional study.

Setting

A specialised public diabetes clinic in Gaborone, Botswana.

Participants

Patients with T2DM who had attended the clinic for ≥3 months between August 2017 and February 2018.

Primary outcome measure

The proportion of patients with optimal glycaemic (HbA1c<7%), hypertension (blood pressure <140/90 mm Hg) and LDL-C (<1.8 mmol/L) control.

Results

The proportions of patients meeting optimal targets were 32.3% for glycaemic, 54.2% for hypertension and 20.4% for LDL-C. Age≥ 50 years was positively associated with optimal glycaemic control (adjusted OR [AOR] 5.79; 95% CI 1.08 to 31.14). On the other hand, an increase in diabetes duration was inversely associated with optimal glycemic control (AOR 0.91; 95% CI 0.85 to 0.98). Being on an ACE inhibitor was inversely associated with optimal hypertension control (AOR 0.35; 95% CI 0.14 to 0.85). Being female was inversely associated with optimal LDL-C control (AOR 0.24; 95% CI (0.09 - 0.59).

Conclusion

Patients with T2DM in Gaborone, Botswana, presented with suboptimal control of recommended glycaemic, hypertension and LDL-C targets. These findings call for urgent individual and health systems interventions to address key determinants of the recommended therapeutic targets among patients with diabetes in this setting.
Systematic review protocol for facilitators and barriers to integrating health services for traumatic brain injury and mental health or addictions
Authors: Chan Vincy , Toccalino Danielle , Colantonio Angela
Published: July 2019

Introduction

In the most populous province of Canada, one in five adults and one in six students report a lifetime history of traumatic brain injury (TBI). These individuals were also more likely to report elevated psychological distress and use illicit substances compared with those without TBI. The need for integrated health services has been recognised globally, yet efforts to develop more comprehensive and effective care for TBI and mental health and/or addictions (MHA) continue to be challenged by the siloing of the two systems. This protocol is for a systematic review that describes the current types of integrated care for TBI and MHA and identifies the barriers and facilitators to integrating healthcare for these populations.

Methods and analysis

This review will systematically search MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Sociological Abstracts, and Dissertations & Theses Global. References of eligible articles will also be searched for additional relevant studies. The search strategy will include the use of text words and subject headings relevant to the concepts ‘TBI,’ ‘substance abuse, gambling, or mental health,’ ‘integrated healthcare,’ ‘barriers and facilitators,’ and ‘healthcare access.’ Two reviewers will independently screen all articles based on predetermined inclusion and exclusion criteria and perform quality assessment on eligible studies. A narrative synthesis will be conducted using the data abstracted by the two reviewers.

Ethics and dissemination

Findings from the systematic review will be published in peer-reviewed journals, presented at scientific meetings, and summarised for key stakeholders in the field of TBI and/or MHA. This protocol will form a systematic review that holds the potential to impact policy and planning in the development of integrated person-centred care for TBI and MHA and addresses a recognised gap in TBI care.

Trial registration number

CRD42018108343
Fostering the physician–scientist workforce: a prospective cohort study to investigate the effect of undergraduate medical students’ motivation for research on actual research involvement
Authors: Ommering Belinda WC , van Blankenstein Floris M , Wijnen-Meijer Marjo , van Diepen Merel , Dekker Friedo W
Published: July 2019

Objectives

The medical field is facing a physician–scientist shortage. Medical schools could contribute to developing physician–scientists by stimulating student involvement in research. Studies have examined motivation for research as a key parameter of success. However, previous studies did not investigate if students act on their self-reported motivation. The aim of this study is to examine if motivation for research of medical students is related to actual research involvement. Furthermore, this study distinguishes intrinsic (IM) and extrinsic motivation (EM) for research and aims to investigate if a type of motivation matters in the relation between research motivation and involvement.

Design and setting

Prospective cohort study in which students were surveyed at the start of medical school and reported IM and EM for research, self-efficacy, perceptions of research and curiosity on a 7-point Likert scale. One year later, students involved in research were identified. Logistic regression was used to examine influences of IM and EM on research involvement.

Participants

All undergraduate medical students starting at one medical school in the Netherlands in 2016. In total, 315 out of 316 students participated (99.7%), of whom 55 became involved in research (17.5%).

Main outcome measure

Research involvement, which was operationalised as the enrolment of students in the research-based honours programme or the involvement of students in voluntary research activities outside of the regular curriculum.

Results

Students with higher levels of IM were more often involved in research (OR 3.4; 95% CI 2.08 to 5.61), also after adjusting for gender, age, extracurricular high school activities, self-efficacy, perceptions and curiosity (OR 2.5; 95% CI 1.35 to 4.78). Higher levels of EM increased the odds of research involvement (OR 1.4; 95% CI 0.96 to 2.11). However, the effect of EM disappeared after adjusting for the above-mentioned factors (OR 1.05; 95% CI 0.67 to 1.63). Furthermore, the effect of IM remained after adjusting for EM, whereas the effect of EM disappeared after adjusting for IM.

Conclusions

Our findings suggest that the type of motivation matters and IM influences research involvement. Therefore, IM could be targeted to stimulate research involvement and could be seen as the first step towards success in fostering the physician–scientist workforce.
Psychometric properties of the Depression Stigma Scale (DSS) in Chinese cancer patients: a cross-sectional study
Authors: Zhu Lei , Yao Juntao , Wu Liyang , Wang Jun , Qiu Mengting , Zhang Chunyu , Zhang Hongmei , Xie Juan , Liu Ailan , Ranchor Adelita , Schroevers Maya
Published: July 2019

Objectives

The Depression Stigma Scale (DSS) is commonly used to assess depression stigma in the general population and in people with depression. The DSS includes two 9-item subscales assumed to measure personal depression stigma (ie, personal perceptions of depression) and perceived depression stigma (ie, perceptions of how others perceive depression). The aim of the present study was to examine its psychometric properties in terms of validity and reliability in Chinese cancer patients.

Design

A cross-sectional study design.

Participants and settings

This study focused on 301 Chinese cancer patients recruited from two hospitals in Xi’an, China.

Methods

Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess the factor structure. Internal consistency was assessed using Cronbach’s alpha. To examine concurrent validity, symptoms of depression were used as the criterion.

Results

For each subscale of the DSS (ie, personal and perceived depression stigma), the EFA and CFA confirmed a two-factor structure: weak-not-sick (ie, perceiving that depression is not a real illness, but rather a sign of weakness) and discrimination (ie, perceiving that depressed people are discriminated against). The Cronbach’s alphas were adequate, ranging from 0.70 to 0.80. Symptoms of depression were positively but weakly correlated to personal and perceived depression stigma.

Conclusions

The DSS appeared to show satisfactory psychometric properties in our sample of cancer patients. Both personal depression stigma and perceived depression stigma subscales consisted of two underlying aspects.
Oral antidiabetic medication adherence and glycaemic control among patients with type 2 diabetes mellitus: a cross-sectional retrospective study in a tertiary hospital in Saudi Arabia
Authors: Balkhi Bander , Alwhaibi Monira , Alqahtani Nasser , Alhawassi Tariq , Alshammari Thamir M , Mahmoud Mansour , Almetwazi Mansour , Ata Sondus , Kamal Khalid M
Published: July 2019

Objectives

The purpose of this study is to measure the adherence rates of oral antidiabetic drugs (OADs) in patients with type 2 diabetes mellitus (T2DM) and assess the relationship of glycaemic control and adherence to OADs after controlling for other associated factors.

Design

Cross-sectional retrospective study.

Setting

Large tertiary hospital in the central region of Saudi Arabia.

Participants

5457patients aged 18 years and older diagnosed with T2DM during the period from 1 January 2016 to 31 December 2016.

Primary and secondary outcome measures

The modified medication possession ratio (mMPR) was calculated as a proxy measure for adherence of OADs. The factors associated with OADs non-adherence and medication oversupply were assessed using multinomial logistic regression models. The secondary outcomes were to measure the association between OADs adherence and glycaemic control.

Results

Majority of patients with T2DM were females (n=3400, 62.3%). The average glycated haemoglobin was 8.2±1.67. Among the study population, 48.6% had good adherence (mMPR >0.8) and 8.6% had a medication oversupply (mMPR >1.2). Good adherence was highest among those using repaglinide (71.0%) followed by pioglitazone (65.0%) and sitagliptin (59.0%). In the multivariate analysis, women with T2DM were more likely to have poor adherence (adjusted OR (AOR)=0.76, 95% CI=0.67, 0.86) compared with men. Also, medication oversupply was more likely among patients with hyperpolypharmacy (AOR=1.88, 95% CI=1.36, 2.63), comorbid osteoarthritis (AOR=1.72, 95% CI=1.20, 02.45) and non-Saudi patients (AOR=1.53, 95% CI=1.16, 2.01). However, no association was found between glycaemic control and adherence to OADs.

Conclusion

The study findings support the growing concern of non-adherence to OADs among patients with T2DM in Saudi Arabia. Decision makers have to invest in behavioural interventions that will boost medication adherence rates. This is particularly important in patients with polypharmacy and high burden of comorbid conditions.
Emergence of digital biomarkers to predict and modify treatment efficacy: machine learning study
Authors: Guthrie Nicole L , Carpenter Jason , Edwards Katherine L , Appelbaum Kevin J , Dey Sourav , Eisenberg David M , Katz David L , Berman Mark A
Published: July 2019

Objectives

Development of digital biomarkers to predict treatment response to a digital behavioural intervention.

Design

Machine learning using random forest classifiers on data generated through the use of a digital therapeutic which delivers behavioural therapy to treat cardiometabolic disease. Data from 13 explanatory variables (biometric and engagement in nature) generated in the first 28 days of a 12-week intervention were used to train models. Two levels of response to treatment were predicted: (1) systolic change ≥10 mm Hg (SC model), and (2) shift down to a blood pressure category of elevated or better (ER model). Models were validated using leave-one-out cross validation and evaluated using area under the curve receiver operating characteristics (AUROC) and specificity- sensitivity. Ability to predict treatment response with a subset of nine variables, including app use and baseline blood pressure, was also tested (models SC-APP and ER-APP).

Setting

Data generated through ad libitum use of a digital therapeutic in the USA.

Participants

Deidentified data from 135 adults with a starting blood pressure ≥130/80, who tracked blood pressure for at least 7 weeks using the digital therapeutic.

Results

The SC model had an AUROC of 0.82 and a sensitivity of 58% at a specificity of 90%. The ER model had an AUROC of 0.69 and a sensitivity of 32% at a specificity at 91%. Dropping explanatory variables related to blood pressure resulted in an AUROC of 0.72 with a sensitivity of 42% at a specificity of 90% for the SC-APP model and an AUROC of 0.53 for the ER-APP model.

Conclusions

Machine learning was used to transform data from a digital therapeutic into digital biomarkers that predicted treatment response in individual participants. Digital biomarkers have potential to improve treatment outcomes in a digital behavioural intervention.
Regulation of mitochondrial quality following repeated bouts of hindlimb unloading
Authors: Rosa-Caldwell Megan E. , Brown Jacob L. , Perry Richard A. , Shimkus Kevin L. , Shirazi-Fard Yasaman , Brown Lemuel A. , Hogan Harry A. , Fluckey James D. , Washington Tyrone A. , Wiggs Michael P. , Greene Nicholas P.
Published: July 2019

Muscle disuse impairs muscle quality and is associated with increased mortality. Little is known regarding additive effects of multiple bouts of disuse, which is a common occurrence in patients experiencing multiple surgeries. Mitochondrial quality is vital to muscle health and quality; however, to date mitochondrial quality control has not been investigated following multiple bouts of disuse. Therefore, the purpose of this study was to investigate mitochondrial quality controllers during multiple bouts of disuse by hindlimb unloading. Male rats (n ∼ 8/group) were assigned to the following groups: hindlimb unloading for 28 days, hindlimb unloading with 56 days of reloading, 2 bouts of hindlimb unloading separated by a recovery phase of 56 days of reloading, 2 bouts of hindlimb unloading and recovery after each disuse, or control animals with no unloading. At designated time points, tissues were collected for messenger RNA and protein analysis of mitochondrial quality. Measures of mitochondrial biogenesis, such as proliferator-activated receptor gamma coactivator 1 alpha, decreased 30%–40% with unloading with no differences noted between unloading conditions. Measures of mitochondrial translation were 40%–50% lower in unloading conditions, with no differences noted between bouts of unloading. Measures of mitophagy were 40%–50% lower with reloading, with no differences noted between reloading conditions. In conclusion, disuse causes alterations in measures of mitochondrial quality; however, multiple bouts of disuse does not appear to have additive effects.

Novelty Disuse atrophy causes multiple alterations to mitochondrial quality control. With sufficient recovery most detriments to mitochondrial quality control are fixed. In general, multiple bouts of disuse do not produce additive effects.
Decohering power of thermal fluctuating electromagnetic field with a boundary
Authors: Huang Zhiming , Zhang Wei , Zheng Shenggen , Wang Tianqing , Bian Yungang , Zhao Lianghui
Published: July 2019

In this paper, we analyze the decohering power behaviors for an atom immersed in a thermal bath of fluctuating electromagnetic field in the presence of a perfectly reflecting plane boundary. Firstly, we analytically solve the master equation that governs the system evolution. Then, we discuss the behaviors of decohering power for an atom affected by thermal fluctuating electromagnetic field. It is found that the behaviors of decohering power are dependent on the field temperature, atomic position and polarization. Decohering power fluctuates to relatively stable values with the increasing atom’s distance from the boundary, which suggests a possible way of detecting the vacuum fluctuating and boundary effect. Additional conditions on the electromagnetic field give one more freedom to manipulate the variations of decohering power. Decohering power variations can efficiently reflect the behaviors of quantum coherence affected by electromagnetic vacuum fluctuation, and it is shown that quantum coherence can be effectively enhanced with the presence of a reflecting boundary.
NNLO classical solution for Lipatov’s effective action for reggeized gluons
Authors: Bondarenko S. , Pozdnyakov S.
Published: July 2019

We consider the formalism of small-[Formula: see text] effective action for reggeized gluons[Formula: see text] and, following the approach developed in Refs. 11–17, calculate the classical gluon field to NNLO precision with fermion loops included. It is demonstrated that for each perturbative order, the self-consistency of the equations of motion is equivalent to the transversality conditions applied to the solution of the equations, these conditions allow to construct the general recursive scheme for the solution’s calculation. The one fermion loop contribution to the classical solutions and application of the obtained results are also discussed.
Temperature-driven dynamics of quantum liquids: Logarithmic nonlinearity, phase structure and rising force
Authors: Zloshchastiev Konstantin G.
Published: July 2019

We study a large class of strongly interacting condensate-like materials, which can be characterized by a normalizable complex-valued function. A quantum wave equation with logarithmic nonlinearity is known to describe such systems, at least in a leading-order approximation, wherein the nonlinear coupling is related to temperature. This equation can be mapped onto the flow equations of an inviscid barotropic fluid with intrinsic surface tension and capillarity; the fluid is shown to have a nontrivial phase structure controlled by its temperature. It is demonstrated that in the case of a varying nonlinear coupling an additional force occurs, which is parallel to a gradient of the coupling. The model predicts that the temperature difference creates a direction in space in which quantum liquids can flow, even against the force of gravity. We also present arguments explaining why superfluids, be it superfluid components of liquified cold gases or Cooper pairs inside superconductors, can affect closely positioned acceleration-measuring devices.
The ground state energy of the polaron: An asymmetrical semi-exponential polar slab
Authors: Wang Xiu-Qing
Published: July 2019

In this work, the influence of the temperature (T) and RbCl asymmetrical semi-exponential confinement potential on intermediate coupling polaron in a polar slab was studied by applying the Lee-Low-Pines (LLP) unitary transformation and linear combination operation methods, based on the quantum statistical theory. We have derived the ground state energy (E0) and the mean phonon number (N). According to the obtained results, E0 increases with increasing T and parameter [Formula: see text], whereas it is a decaying function with raising parameter U0.
One-Step Synthesis of Rod-Shaped NiFe-MOF as a Highly Efficient Oxygen Evolution Catalyst
Authors: Zhang Dandan , Huang Renxing , Xie Huaming , Liu Xingyong , Lei Ying , Pan Ming
Published: July 2019

Development of low-cost, highly active catalyst for efficient oxygen evolution reaction based on earth-abundant metals is still a great challenge. Here, we report that a rod-like bimetallic NiFe metal-organic framework (NiFe-MOF) can directly act as a highly efficient oxygen evolution reaction (OER) catalyst synthesized by a convenient-to-operate hydrothermal method. The rod-like NiFe-MOF can derive 10[Formula: see text]mA[Formula: see text]cm[Formula: see text] with a low overpotential of only 26[Formula: see text]mV, and its Tafel slope is 40.82[Formula: see text]mV[Formula: see text]dec[Formula: see text], which is superior to that of monometallic Ni-MOF or Fe-MOF, and even can be comparable to that of RuO2. To identify the origin of enhancing OER activity, we resorted to X-ray diffraction, scanning electron microscope, transmission electron microscope, high resolution transmission electron microscopy image and nitrogen adsorption–desorption techniques and various electrochemical techniques to probe it gingerly. The results indicate that its high electrochemically active area and the synergistic effect of bimetallic node could be responsible for the surprisingly high catalytic performance of the NiFe-MOF. These results suggest that this kind of bimetallic MOF (NiFe-MOF) could be a promising electrocatalyst for oxygen evolution reaction.
VOLATILITY SPILLOVER EFFECT OF FEDERAL RESERVE’S BALANCE SHEET ON THE FINANCIAL AND GOODS MARKETS OF INDO-PAK REGION
Authors: SYED QASIM RAZA , MALIK WASEEM SHAHID , CHANG BISHARAT HUSSAIN
Published: July 2019

This paper examines the volatility spillover effect of the balance sheet of Federal Reserve (Fed) on the financial and goods markets of Pakistan, India and Bangladesh (collectively known as the Indo-Pak region). Diagonal BEKK-GARCH methodology is used to capture the volatility spillover effects on Indo-Pak economies. This study took data from the year 2004 to year 2019 on a monthly basis. The findings of the paper describe that there are volatility spillovers from Fed’s balance sheet to the financial markets of Pakistan, India and Bangladesh economies. On the other hand, there is also evidence of volatility spillovers from the balance sheet of Fed to the goods markets of these economies.
An Integrative Framework for Understanding the Mechanisms and Multigenerational Consequences of Transgenerational Plasticity
Authors: Bell Alison M. , Hellmann Jennifer K.
Published: July 2019

Transgenerational plasticity (TGP) occurs when the environment experienced by a parent influences the development of their offspring. In this article, we develop a framework for understanding the mechanisms and multigenerational consequences of TGP. First, we conceptualize the mechanisms of TGP in the context of communication between parents (senders) and offspring (receivers) by dissecting the steps between an environmental cue received by a parent and its resulting effects on the phenotype of one or more future generations. Breaking down the problem in this way highlights the diversity of mechanisms likely to be involved in the process. Second, we review the literature on multigenerational effects and find that the documented patterns across generations are diverse. We categorize different multigenerational patterns and explore the proximate and ultimate mechanisms that can generate them. Throughout, we highlight opportunities for future work in this dynamic and integrative area of study.
More Than the Sum of Its Parts: Microbiome Biodiversity as a Driver of Plant Growth and Soil Health
Authors: Saleem Muhammad , Hu Jie , Jousset Alexandre
Published: July 2019

Microorganisms drive several processes needed for robust plant growth and health. Harnessing microbial functions is thus key to productive and sustainable food production. Molecular methods have led to a greater understanding of the soil microbiome composition. However, translating species or gene composition into microbiome functionality remains a challenge. Community ecology concepts such as the biodiversity–ecosystem functioning framework may help predict the assembly and function of plant-associated soil microbiomes. Higher diversity can increase the number and resilience of plant-beneficial functions that can be coexpressed and unlock the expression of plant-beneficial traits that are hard to obtain from any species in isolation. We combine well-established community ecology concepts with molecular microbiology into a workable framework that may enable us to predict and enhance soil microbiome functionality to promote robust plant growth in a global change context.
Law and Refugee Crises
Authors: Pasquetti Silvia , Casati Noemi , Sanyal Romola
Published: July 2019

Refugees have an increasing global significance, as their numbers continue to grow and the nature of displacement continues to evolve. Different international, state, and local laws and policies play a part in refugee crises. On the one hand, then, it is important to theorize the role of the law in shaping different formations of displacement; on the other, it is also crucial to address how the people involved in these crises (government officials, street-level bureaucrats, forced migrants, and receiving populations) engage with the law. We highlight and develop three areas of sociolegal inquiry that can push forward the study of the law and politics of refuge: ( a) the uneven geography shaping the global humanitarian machine; ( b) the local contexts within which such a machine operates, interacting with different actors’ conceptualizations of justice; and ( c) the distinct dilemmas that the urban environment poses to both refugees and humanitarians. Advancing these areas of sociolegal inquiry requires enriching established theoretical sources in refugee studies with both neglected ones, such as postcolonial theory and Pierre Bourdieu's sociology of forced displacement, and newer ones, such as Didier Fassin's anthropology of morality and pragmatic sociology of ordinary judgments of fairness.
Law, Morality, and Health Care Professionals: A Multilevel Framework
Authors: Chiarello Elizabeth
Published: July 2019

Socio-legal scholars have long been interested in the relationship between law and morality. This article uses a multilevel approach to understanding this relationship by focusing on health care professionals, key actors in an institution that covers broad swaths of social life and that serves as a key site of moral meaning making and practice. I demonstrate how morality and law interface differently at three levels: through daily social interaction, during which providers assess patients’ deservingness while patients attempt to present themselves as morally worthy; through organizational structures and processes that establish legalistic rules and bring diverse workers into shared space; and through field-level legal and moral infrastructures that shape frontline decision making and that change due to social movement mobilization. The article concludes by describing the benefits of a multilevel approach to examining the interplay between law, morality, and health care work and suggesting strategies for theoretically investigating these relationships more completely.
Pharmacology of Small- and Intermediate-Conductance Calcium-Activated Potassium Channels
Authors: Brown Brandon M. , Shim Heesung , Christophersen Palle , Wulff Heike
Published: July 2019

The three small-conductance calcium-activated potassium (KCa2) channels and the related intermediate-conductance KCa3.1 channel are voltage-independent K+ channels that mediate calcium-induced membrane hyperpolarization. When intracellular calcium increases in the channel vicinity, it calcifies the flexible N lobe of the channel-bound calmodulin, which then swings over to the S4-S5 linker and opens the channel. KCa2 and KCa3.1 channels are highly druggable and offer multiple binding sites for venom peptides and small-molecule blockers as well as for positive- and negative-gating modulators. In this review, we briefly summarize the physiological role of KCa channels and then discuss the pharmacophores and the mechanism of action of the most commonly used peptidic and small-molecule KCa2 and KCa3.1 modulators. Finally, we describe the progress that has been made in advancing KCa3.1 blockers and KCa2.2 negative- and positive-gating modulators toward the clinic for neurological and cardiovascular diseases and discuss the remaining challenges.
Knockout of TRPA1 exacerbates angiotensin II-induced kidney injury
Authors: Ma Shuangtao , Zhang Yan , He Kecheng , Wang Peijian , Wang Donna H.
Published: July 2019

Macrophage-mediated inflammation plays a critical role in hypertensive kidney disease. Here, we investigated the role of transient receptor potential ankyrin 1 (TRPA1), a sensor of inflammation, in angiotensin II (ANG II)-induced renal injury. Subcutaneous infusion of ANG II (600 ng·min−1·kg−1) for 28 days was used to induce hypertension and renal injury in mice. The results showed that ANG II-induced hypertensive mice have decreased renal Trpa1 expression ( P < 0.01), whereas ANG II receptor type 1a-deficient hypotensive mice have increased renal Trpa1 expression ( P < 0.05) compared with their normotensive counterparts. ANG II induced similar elevations of systolic blood pressure in Trpa1−/− and wild-type (WT) mice but led to higher levels of blood urea nitrogen ( P < 0.05), serum creatinine ( P < 0.05), and renal fibrosis ( P < 0.01) in Trpa1−/− mice than WT mice. Similarly, ANG II increased both CD68+/inducible nitric oxide synthase+ M1 and CD68+/arginase 1+ M2 macrophages in the kidneys of both Trpa1−/− and WT mice (all P < 0.01), with higher extents in Trpa1−/− mice (both P < 0.01). Compared with WT mice, Trpa1−/− mice had significantly increased expression levels of inflammatory cytokines and their receptors in the kidney. Cultured murine macrophages were stimulated with phorbol 12-myristate 13-acetate, which downregulated gene expression of TRPA1 ( P < 0.01). A TRPA1 agonist, cinnamaldehyde, significantly inhibited phorbol 12-myristate 13-acetate-stimulated expression of IL-1β and chemokine (C-C motif) ligand 2 in macrophages, which were attenuated by pretreatment with a TRPA1 antagonist, HC030031 . Furthermore, activation of TRPA1 with cinnamaldehyde induced apoptosis of macrophages. These findings suggest that TRPA1 may play a protective role in ANG II-induced renal injury, likely through inhibiting macrophage-mediated inflammation.
Human Th17 cells produce a soluble mediator that increases podocyte motility via signaling pathways that mimic PAR-1 activation
Authors: May Carl J. , Welsh Gavin I. , Chesor Musleeha , Lait Phillipa J. , Schewitz-Bowers Lauren P. , Lee Richard W. J. , Saleem Moin A.
Published: July 2019

The specific pathogenesis of idiopathic nephrotic syndrome (NS) is poorly understood, and the role of immune mediators remains contentious. However, there is good evidence for the role of a circulating factor, and we recently postulated circulating proteases as candidate factors. Immunosuppressive therapy with glucocorticoids (GCs) and T cell inhibitors are widely used in the clinical treatment of NS. Given that T helper (CD4+) cells expressing IL-17A (so-called Th17 cells) have recently been reported to be resistant to GC treatment, and GC resistance remains a major challenge in the management of NS, we hypothesized that Th17 cells produce a circulating factor that is capable of signaling to the podocyte and inducing deleterious phenotypic changes. To test this, we generated human Th17 cells from healthy volunteers and added the supernatants from these T cell cultures to conditionally immortalized human podocytes in vitro. This demonstrated that podocytes treated with Th17 cell culture supernatant, as well as with patient disease plasma, showed significant stimulation of JNK and p38 MAPK pathways and an increase in motility, which was blocked using a JNK inhibitor. We have previously shown that nephrotic plasma elicits a podocyte response via protease-activated receptor-1 (PAR-1). Stimulation of PAR-1 in podocytes elicited the same signaling response as Th17 cell culture supernatant treatment. Equally, protease inhibitors with Th17 cell culture treatment blocked the signaling response. This was not replicated by the reagents added to Th17 cell cultures or by IL-17A. Hence, we conclude that an undefined soluble mediator produced by Th17 cells mimics the deleterious effect of PAR-1 activation in vitro. Given the association between pathogenic subsets of Th17 cells and GC resistance, these observations have potential therapeutic relevance for patients with NS.
Evidence for a dynorphin-mediated inner ear immune/inflammatory response and glutamate-induced neural excitotoxicity: an updated analysis
Authors: Sahley Tony L. , Anderson David J. , Hammonds Michael D. , Chandu Karthik , Musiek Frank E.
Published: July 2019

Acoustic overstimulation (AOS) is defined as the stressful overexposure to high-intensity sounds. AOS is a precipitating factor that leads to a glutamate (GLU)-induced Type I auditory neural excitotoxicity and an activation of an immune/inflammatory/oxidative stress response within the inner ear, often resulting in cochlear hearing loss. The dendrites of the Type I auditory neural neurons that innervate the inner hair cells (IHCs), and respond to the IHC release of the excitatory neurotransmitter GLU, are themselves directly innervated by the dynorphin (DYN)-bearing axon terminals of the descending brain stem lateral olivocochlear (LOC) system. DYNs are known to increase GLU availability, potentiate GLU excitotoxicity, and induce superoxide production. DYNs also increase the production of proinflammatory cytokines by modulating immune/inflammatory signal transduction pathways. Evidence is provided supporting the possibility that the GLU-mediated Type I auditory neural dendritic swelling, inflammation, excitotoxicity, and cochlear hearing loss that follow AOS may be part of a brain stem-activated, DYN-mediated cascade of inflammatory events subsequent to a LOC release of DYNs into the cochlea. In support of a DYN-mediated cascade of events are established investigations linking DYNs to the immune/inflammatory/excitotoxic response in other neural systems.
Case Studies in Neuroscience: Instability of the visual near triad in traumatic brain injury—evidence for a putative convergence integrator
Authors: Rucker Janet C. , Buettner-Ennever Jean A. , Straumann Dominik , Cohen Bernard
Published: July 2019

Deficits of convergence and accommodation are common following traumatic brain injury, including mild traumatic brain injury, although the mechanism and localization of these deficits have been unclear and supranuclear control of the near-vision response has been incompletely understood. We describe a patient who developed profound instability of the near-vision response with inability to maintain convergence and accommodation following mild traumatic brain injury, who was identified to have a structural lesion on brain MRI in the pulvinar of the caudal thalamus, the pretectum, and the rostral superior colliculus. We discuss the potential relationship between posttraumatic clinical near-vision response deficits and the MRI lesion in this patient. We further propose that the MRI lesion location, specifically the rostral superior colliculus, participates in neural integration for convergence holding, given its proven anatomic connections with the central mesencephalic reticular formation and C-group medial rectus motoneurons in the oculomotor nucleus, which project to extraocular muscle nontwitch fibers specialized for fatigue-resistant, slow, tonic activity such as vergence holding.

NEW & NOTEWORTHY Supranuclear control of the near-vision response has been incompletely understood to date. We propose, based on clinical and anatomic evidence, functional pathways for vergence that participate in the generation of the near triad, “slow vergence,” and vergence holding.
Fault “Corrosion” by Fluid Injection: A Potential Cause of the November 2017 MW 5.5 Korean Earthquake
Authors: Westaway Rob , Burnside Neil M.
Published: July 2019

The November 2017 MW 5.5 Pohang earthquake is one of the largest and most damaging seismic events to have occurred in the Korean peninsula over the last century. Its close proximity to an Enhanced Geothermal System (EGS) site, where hydraulic injection into granite had taken place over the previous two years, has raised the possibility that it was anthropogenic; if so, it was by far the largest earthquake caused by any EGS project worldwide. However, a potential argument that this earthquake was independent of anthropogenic activity considers the delay of two or three months before its occurrence, following the most recent injection into each of the wells. A better understanding of the physical and chemical processes that occur following fluid injection into granite is thus warranted. We show that hydrochemical changes occurring while surface water, injected into granite, reequilibrates chemically with its subsurface environment, can account for time delays for earthquake occurrence of such duration, provided the seismogenic fault was already critically stressed, or very close to the condition for slip. This candidate causal mechanism counters the potential argument that the time delay militates against an anthropogenic cause of the Pohang earthquake and can account for its relatively large magnitude as a consequence of a relatively small-volume injection. The resulting analysis places bounds on combinations of physical and chemical properties of rocks, injected volume, and potential postinjection time delays for significant anthropogenic seismicity during future EGS projects in granite.
The Negative Impact of Vehicular Intelligence on Energy Consumption
Authors: Liu Zongwei , Tan Hong , Kuang Xu , Hao Han , Zhao Fuquan
Published: July 2019

The development of intelligent vehicle will provide the Chinese automotive industry with a strategic opportunity for transformation and upgrading. Vehicular intelligence provides new solutions for energy conservation and emissions mitigation. However, the process of vehicular intelligence is progressive. The saving of energy consumption depends on the high smart car market penetration rate. But one thing that can be confirmed is that intelligent vehicles are equipped with advanced sensors, controllers, and actuators, in combination with connecting communication technologies compared with conventional vehicles, for which the energy consumption of the vehicle will definitely increase. In this study, vehicle fuel consumption cost at different levels of intelligence is calculated, considering the energy consumption of hardware used for automation and connecting functions, the energy consumption cost generated by the quality of the hardware, and the wind resistance. The results reveal that the energy consumption per 100 kilometers of an intelligent vehicle ranges from 0.78L to 1.86L, more than traditional vehicle. The energy consumption cost of automation functions is much higher than that of the connecting functions. Computing platform performance, connection strength, and radar performance are the three main factors that affect energy consumption cost. Based on the analysis, the high energy consumption cost of vehicular intelligence has a profound impact on choosing power platform.
Quality Traits of Fillet of Gilthead Sea Bream (Sparus aurataL.) of Two Market Sizes Reared according to an “Antibiotic-Free” Approach
Authors: Roncarati A. , Meligrana M. C. T. , Laus F. , Spaterna A.
Published: July 2019

Rearing of “antibiotic-free” fish is becoming one of the most important goals to be achieved in the near future. Strategies are going to be adopted to increase nonspecific immune system and biosecurity in fish farming. To show the quality traits of gilthead sea breams reared under a prescription of “antibiotic-free” (ABF), two different market sizes (R: about 350 g andM: about 490 g) were analysed at the end of the farming cycle performed in a floating cage plant in the Adriatic sea, in the Gulf of Valona (Albania). Proximate composition and fatty acid profile were determined in April and June 2018. The omega-3 content demonstrated that the ABF samples collected according to the fish size and the harvest month can be defined as “rich in omega-3,” in compliance with the Annex to the Regulation (EC) n. 1924/2006, with a trend to increase in relation to fish growth.
Postpartum Circulating Cell-Free Insulin DNA Levels Are Higher in Women with Previous Gestational Diabetes Mellitus Who Develop Type 2 Diabetes in Later Life
Authors: Lappas Martha , Georgiou Harry M. , Willcox Jane C. , Permezel Michael , Shub Alexis , Maynard Cody-Lee , Joglekar Mugdha V. , Hardikar Anandwardhan A.
Published: July 2019

Background. Women with previous gestational diabetes mellitus (GDM) have evidence of postpartum β-cell dysfunction, which increases their risk of developing type 2 diabetes (T2DM) later in life. Elevated levels of circulating cell-free preproinsulin (INS) DNA correlate with dying β-cells in both mice and humans. The aim of this study was to determine if cell-free circulating INS DNA levels are higher in women with previous GDM who develop T2DM. Methods. We used droplet digital (dd) PCR to measure the levels of cell-free circulating methylated and unmethylated INS DNA in plasma from 97 women with normal glucose tolerance (NGT), 12 weeks following an index GDM pregnancy. Women were assessed for up to 10 years for the development of T2DM. Results. In the follow-up period, 22% of women developed T2DM. Compared with NGT women, total cell-free INS DNA levels were significantly higher in women who developed T2DM (P=0.02). There was no difference in cell-free circulating unmethylated and methylated INS DNA levels between NGT women and women who developed T2DM (P=0.09 and P=0.07, respectively). Conclusions. In women with a previous index GDM pregnancy, postpartum levels of cell-free circulating INS DNA are significantly higher in those women who later developed T2DM.
Antidepressant and Antiaging Effects of Açaí (Euterpe oleracea Mart.) in Mice
Authors: Souza-Monteiro José Rogério , Arrifano Gabriela P. F. , Queiroz Ana Isabelle D. G. , Mello Bruna S. F. , Custódio Charllyany S. , Macêdo Danielle S. , Hamoy Moisés , Paraense Ricardo S. O. , Bittencourt Leonardo O. , Lima Rafael R. , Burbano Rommel R. , Rogez Hervé , Maia Cristiane F. , Macchi Barbarella M. , do Nascimento José Luiz M. , Crespo-López Maria Elena
Published: July 2019

Depression is a mental disorder that affects 300 million people of all ages worldwide, but fewer than half of those with the condition receive adequate treatment. In addition, the high pharmacological refractoriness (affecting 30%-50% of patients) and toxicity of some classical antidepressants support the pursuit of new therapies. People with this condition show depressed mood, loss of pleasure, high levels of oxidative stress, and accelerated biological aging (decreased telomere length and expression of the telomerase reverse transcriptase (TERT), the enzyme responsible for telomere maintenance). Because of the close relationship between depression and oxidative stress, nutraceuticals with antioxidant properties are excellent candidates for therapy. This study represents the first investigation of the possible antidepressant and antiaging effects of commercial samples of clarified açaí (Euterpe oleracea) juice (EO). This fruit is rich in antioxidants and widely consumed. In this study, mice were treated with saline or EO (10 μL/g, oral) for 4 days and then with saline or lipopolysaccharide (0.5 mg/kg, i.p.) to induce depressive-like behavior. Only four doses of EO were enough to abolish the despair-like and anhedonia behaviors and alterations observed in electromyographic measurements. The antidepression effect of EO was similar to that of imipramine and associated with antioxidant and antiaging effects (preventing lipid peroxidation and increasing TERT mRNA expression, respectively) in three major brain regions involved in depression (hippocampus, striatum, and prefrontal cortex). Additionally, EO significantly protected hippocampal cells, preventing neuronal loss associated with the depressive-like state and nitrite level increases (an indirect marker of nitric oxide production). Moreover, EO alone significantly increased TERT mRNA expression, revealing for the first time a potent antiaging action in the brain that suggests neuroprotection against long-term age-related consequences.
A Case of Psychosis and Renal Failure Associated with Excessive Energy Drink Consumption
Authors: Kelsey D. , Berry A. J. , Swain R. A. , Lorenz S.
Published: July 2019

Energy drinks are nonalcoholic beverages that are widely consumed in the general population, and worldwide usage is increasing. The main stimulant component of energy drinks is typically caffeine. Few case reports exist that link energy drink consumption to psychosis, and similarly few reports exist that associate energy drink consumption with acute renal failure. We present a patient who simultaneously developed psychosis and acute renal failure associated with excessive energy drink consumption. The patient required haemodialysis, and his psychosis resolved on cessation of energy drinks and a brief course of antipsychotic medication. We perform a review of similar cases where excessive caffeinated energy drink consumption has been linked to psychosis or acute renal failure. To our knowledge, this is the first case report describing both renal failure and psychosis occurring simultaneously in a patient. Recognising the spectrum of disorders associated with excessive energy drink consumption is vital for both physicians and psychiatrists, as this has important implications for both prognosis and treatment.