bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol Use and Cognitive Functioning Among Middle‐Aged and Older Adults in China: Findings of the China Health and Retirement Longitudinal Study Baseline Survey
Authors: Ge Song , Wei Zhe , Liu Tingting , Wang Jinjiao , Li Hongjin , Feng Juan , Li Changwei
Published: August 2018

Background

Alcohol use and its associated problems are on the rise in China. In this study, we examined the associations between alcohol use and cognitive functioning in a representative sample of adults aged 45 years and older in China.

Methods

Baseline data for 16,328 participants of the China Health and Retirement Longitudinal Study were analyzed. Alcohol use was measured by drinking status (never, former, moderate, and at‐risk drinkers), number of standard drinks per week, and years of drinking. Cognitive functioning was assessed for visuospatial ability, episodic memory, orientation/attention, and overall cognitive functioning. Multivariate linear and logistic regressions were used to examine the independent association between alcohol use and cognitive functioning controlling for age, gender, education, domestic partner status, and depressive symptoms.

Results

The study participants were, on average, 66 years old (median 59, range 45 to 102). The prevalence of ever drinking during lifetime and current at‐risk drinking (>14 drinks per week) in this population was 34.6 and 6.7%, respectively. Drinking was more common among men with 48.8% being ever drinkers and 14.4% current at‐risk drinkers, respectively. At‐risk drinkers, compared to people who never drank alcohol, had worse episodic memory (β = −0.11, p = 0.048). Moreover, number of standard drinks per week was associated with worse episodic memory (β = −0.001, p = 0.02). None of the other measures of alcohol use was associated with the overall or domain‐specific cognitive functioning.

Conclusions

At‐risk drinking status was associated with worse episodic memory. Clinicians should incorporate alcohol use assessment into routine care for middle‐aged and older adults in China and provide them with resources and strategies to effectively manage their alcohol use. This may help preserve episodic memory in this population.
Reversing Epigenetic Alterations Caused by Alcohol: A Promising Therapeutic Direction for Alcoholic Liver Disease
Authors: Lin Xiu‐Xian , Lian Guang‐Hui , Peng Shi‐Fang , Zhao Qing , Xu Ying , Ou‐Yang Dong‐Sheng , Zhang Wei , Chen Yao
Published: August 2018

Alcoholic liver disease (ALD), a liver function disorder caused by excessive alcohol intake, is a serious threat to global public health and social development. Toxic metabolites and reactive oxygen species produced during the metabolism of alcohol can alter the epigenetic state including DNA methylation, histone modifications, and expression of microRNAs. Epigenetic alterations can conversely involve various signaling pathways, which could contribute to the initiation and progression of ALD. To elucidate the relationship between epigenetic alterations and alcohol damage not only reinforces our understanding on pathogenesis of ALD, but also provides novel targets for clinical diagnosis, treatment, and drug research of ALD. In this review, we have summarized the research progress of epigenetic alterations and related mechanisms caused by alcohol in the pathogenesis of ALD. Considering the invertibility of epigenetic alterations, treatment of ALD through epigenetic modification with common less harmful compounds is also related.
Psychosocial factors and addiction in chronic orofacial neuropathic pain
Authors: Braunsteiner Natasha E. , Vickers E. Russell , Toole Bradley M. , Braunsteiner Jacob
Published: August 2018

Neuropathic trigeminal pain is a difficult condition to diagnose as the pain is an invisible non‐odontogenic phenomenon but typically presents as high intensity pain in the teeth and surrounding tissue. Persistent pain leads to psychological and behavioural issues. Medical conditions that consequently manifest include the co‐morbid psychological states of depression, anxiety and stress that can lead to suicide. Addiction plays a maladaptive role utilised by patients to escape their pain. Improved pain outcomes are achieved when instituting comprehensive psychological assessment and treatments with established medical and dental chronic pain protocols.
Systemic considerations for orofacial neuropathy
Authors: Tiwari Lalima , Alsarraf Abdulhameed , Yeoh Sue‐Ching , Balasubramaniam Ramesh
Published: August 2018

Patients with orofacial neuropathic pain typically present with symptoms first hand to their general dental practitioner. It is important dental practitioners recognise the clinical presentations of these conditions for prompt diagnosis and appropriate management. This review will focus on the systemic causes of orofacial neuropathy. Infectious and autoimmune diseases with orofacial neuropathic manifestations such as post‐herpetic neuralgia, paroxysmal neuralgias, painful trigeminal sensory neuropathies, peripheral neuritis and oral dysaesthesia will be discussed. Specifically, the prevalence, pathophysiology, clinical presentations and management of these conditions will be reviewed.
Tumour necrosis factor receptor‐1 is dispensable for the migration of marginal metallophilic macrophages into the B‐cell zone of the mouse spleen
Authors: Milićević Đorđe N. , Despotović Sanja Z. , Westermann Jürgen , Milićević Novica M.
Published: August 2018

The spleen is the only blood filter in the organism which removes foreign antigens and effete cells from circulation. The significant role in capturing, transporting and presentation of antigens to immune cells is executed by a special subset of splenic macrophages called marginal metallophilic macrophages. Upon stimulation with lipopolysaccharide, these cells promptly migrate from their preferential location at the inner aspect of the splenic marginal sinus into the B‐cell lymphoid follicles. This migration is executed via CXC chemokine ligand 13 in a lymphotoxin‐dependent fashion. However, the role of tumour necrosis factor‐α/tumour necrosis factor receptor‐1 signalling axis has not been studied, despite its critical role in the formation of B‐cell lymphoid follicles, follicular dendritic cell networks and germinal centres. Here, we show that signalling via tumour necrosis factor receptor‐1 is not required for the migration of marginal metallophilic macrophages into the B‐cell zone and that the presence of organized B‐cell lymphoid follicles is not a prerequisite for their dislocation.
Generalised additive mixed models analysis via gammSlice
Authors: Pham Tung H. , Wand Matt P.
Published: August 2018

We demonstrate the use of ourRpackage,gammSlice, for Bayesian fitting and inference in generalised additive mixed model analysis. This class of models includes generalised linear mixed models and generalised additive models as special cases. Accurate Bayesian inference is achievable via sufficiently large Markov chain Monte Carlo (MCMC) samples. Slice sampling is a key component of the MCMC scheme. Comparisons with existing generalised additive mixed model software shows thatgammSliceoffers improved inferential accuracy, albeit at the cost of longer computational time.
Proposed biosimilar pegfilgrastim shows similarity in pharmacokinetics and pharmacodynamics to reference pegfilgrastim in healthy subjects
Authors: Nakov Roumen , Gattu Sreekanth , Wang Jessie , Velinova Maria , Schaffar Gregor , Skerjanec Andrej
Published: August 2018

Aims

This study aimed to demonstrate that the pharmacokinetic (PK) and pharmacodynamic (PD) profile of Sandoz proposed biosimilar pegfilgrastim (LA‐EP2006) matches reference pegfilgrastim (Neulasta®) in healthy subjects. Safety and immunogenicity were also assessed.

Methods

The phase I, randomized, double‐blind, two‐period crossover study consisted of two treatment periods separated by an 8‐week washout period. Healthy subjects aged 18–45 were randomized to either proposed biosimilar/reference pegfilgrastim or reference pegfilgrastim/proposed biosimilar. Proposed biosimilar and reference pegfilgrastim were administered on Day 1 of each treatment period (single 6 mg subcutaneous injection). Blood samples for PK/PD analysis were taken predose and ≤336 h postdose. PK/PD similarity was claimed if 90% (PK) and 95% (PD) confidence intervals (CI) for geometric mean ratios of the area under the serum concentration–time curve (AUC) from time of dosing and extrapolated to infinity (AUC0–inf), or to the last measurable concentration (AUC0–last), maximum observed serum concentration (Cmax), absolute neutrophil count (ANC) area under the effect curve from the time of dosing to the last measurable concentration (AUEC0–last) and ANC maximum effect attributable to the therapy under investigation (Emax) were completely contained within the predefined margin (0.8 to 1.25).

Results

Overall, 169 subjects completed the study. PK/PD similarity was demonstrated; 90% CIs of geometric mean ratio of proposed biosimilar/reference for PK: AUC0–inf (1.0559–1.2244), AUC0–last (1.0607–1.2328), Cmax (1.0312–1.1909) and 95% CIs for PD (ANC): AUEC0–last (0.9948–1.0366), Emax (0.9737–1.0169) were completely contained within predefined margin of 0.8 to 1.25. Both biologics had similar safety profiles, were well tolerated and had low incidence of anti‐drug antibodies. No neutralizing or clinically relevant antibodies were detected.

Conclusions

PK/PD similarity of Sandoz proposed biosimilar pegfilgrastim and reference pegfilgrastim was confirmed. No clinically meaningful differences in safety, tolerability and immunogenicity were observed in healthy subjects.
Should human germ line editing be allowed? Some suggestions on the basis of the existing regulatory framework
Authors: de Miguel Beriain Iñigo
Published: August 2018

The application of genetic editing techniques for the prevention or cure of disease is a highly promising tool for the future of humanity. However, its implementation contains a number of ethical and legal challenges that should not be underestimated. On this basis, some sectors have already asked for a veto on any intervention that modifies the human germ line, while supporting somatic line editing. In this paper, I will support that this suggestion makes no sense at all, because the somatic/germ line disjunctive has no moral relevance and, therefore, it should not play any role in legal terms. I will provide a number of reasons to hold this assumption, such as the non‐sacred nature of the germ line, the difference between germ line and human genome modification, or the moral importance of the presence of a will to create modified descendants. While doing so, I will provide some examples of the different approaches to germ line editing adopted by different regulations so as to demonstrate that, contrary to what is sometimes stated, a general ban on this practice is not the rule, but the exception. Additionally, I will show how alternative options which currently exist, such as a selective ban based on criteria different to the germ line/somatic line distinction, match better with the need to conciliate research needs and legitimate ethical concerns. Finally, I will introduce some further suggestions to this same purpose.
Bayesian Additive Adaptive Basis Tensor Product Models for Modeling High Dimensional Surfaces: An Application to High-Throughput Toxicity Testing
Authors: Wheeler Matthew W.
Published: August 2018

Many modern datasets are sampled with error from complex high-dimensional surfaces. Methods such as tensor product splines or Gaussian processes are effective and well suited for characterizing a surface in two or three dimensions, but they may suffer from difficulties when representing higher dimensional surfaces. Motivated by high throughput toxicity testing where observed dose-response curves are cross sections of a surface defined by a chemical's structural properties, a model is developed to characterize this surface to predict untested chemicals’ dose-responses. This manuscript proposes a novel approach that models the multidimensional surface as a sum of learned basis functions formed as the tensor product of lower dimensional functions, which are themselves representable by a basis expansion learned from the data. The model is described and a Gibbs sampling algorithm is proposed. The approach is investigated in a simulation study and through data taken from the US EPA's ToxCast high throughput toxicity testing platform.
Flexible Parametric Approach to Classical Measurement Error Variance Estimation Without Auxiliary Data
Authors: Bertrand Aurélie , Van Keilegom Ingrid , Legrand Catherine
Published: August 2018

Measurement error in the continuous covariates of a model generally yields bias in the estimators. It is a frequent problem in practice, and many correction procedures have been developed for different classes of models. However, in most cases, some information about the measurement error distribution is required. When neither validation nor auxiliary data (e.g., replicated measurements) are available, this specification turns out to be tricky. In this article, we develop a flexible likelihood-based procedure to estimate the variance of classical additive error of Gaussian distribution, without additional information, when the covariate has compact support. The performance of this estimator is investigated both in an asymptotic way and through finite sample simulations. The usefulness of the obtained estimator when using the simulation extrapolation (SIMEX) algorithm, a widely used correction method, is then analyzed in the Cox proportional hazards model through other simulations. Finally, the whole procedure is illustrated on real data.
The effects of m‐learning on motivation, achievement and well‐being: A Self‐Determination Theory approach
Authors: Jeno Lucas M. , Adachi Paul J. C. , Grytnes John‐Arvid , Vandvik Vigdis , Deci Edward L.
Published: August 2018

From the lens of Self‐Determination Theory, this study investigated the effects of a mobile application tool for identifying species on biology students’ achievement and well‐being. It was hypothesized that the mobile application, compared to a textbook, would enhance feelings of competence and autonomy and, in turn, intrinsic motivation, positive affect and achievement, because the mobile application’s built‐in functions provide students with choice and volition, informational feedback, and optimal challenges. Fifty‐eight second‐year students were randomly assigned to use either the mobile application or a textbook for a learning task. Well‐being was assessed before and after the learning task, and intrinsic motivation, perceived competence, perceived autonomy and achievement were assessed after the task. Results indicated that the mobile application, relative to the textbook, produced higher levels of students’ perceived competence, perceived autonomy and intrinsic motivation. Further, the mobile application had indirect effects on positive affect through autonomy, competence and intrinsic motivation, and on achievement through competence.
Social support as a comfort or an encouragement: A systematic review on the contrasting effects of social support on cardiovascular reactivity
Authors: Teoh Ai Ni , Hilmert Clayton
Published: August 2018

Purpose

The stress‐buffering hypothesis (Cohen & McKay, 1984, Handbook of psychology and health IV: Social psychological aspects of health (pp. 253–256). Hillsdale, NJ: Lawrence Erlbaum) suggests that one way social support enhances health is by attenuating cardiovascular reactivity (CVR) to stress. Research that has tested this hypothesis has reported inconsistent findings. In this review, we systematically reviewed those findings and proposed a dual‐effect model of social support and CVR as a potential explanation for the inconsistency in the literature. Specifically, we proposed that when participants are more engaged during a stressor, social support acts primarily as social comfort, attenuating CVR; and when participants are not engaged, social support acts primarily as social encouragement, elevating CVR.

Methods

We reviewed 22 previous studies that (1) empirically manipulated social support in a stressful situation, (2) measured CVR, and (3) tested a moderator of social support effects on CVR.

Results

Although a majority of studies reported a CVR‐mitigating effect of social support resulting in an overall significant combined p‐value, we found that there were different effects of social support on CVR when we considered high‐ and low‐engagement contexts. That is, compared to control conditions, social support lowered CVR in more engaging situations but had no significant effect on CVR in less engaging situations.

Conclusion

Our results suggest that a dual‐effect model of social support effects on CVR may better capture the nature of social support, CVR, and health associations than the buffering hypothesis and emphasize a need to better understand the health implications of physiological reactivity in various contexts.

Statement of contribution

What is already known on this subject?

According to the stress‐buffering hypothesis (Cohen & McKay, ), one pathway social support benefits health is through mitigating the physiological arousal caused by stress. However, previous studies that examined the effects of social support on blood pressure and heart rate changes were not consistently supporting the hypothesis. Some studies reported that social support causes elevations in cardiovascular reactivity (CVR) to stress (Anthony & O'Brien, ; Hilmert, Christenfeld, & Kulik, ; Hilmert, Kulik, & Christenfeld, ) and others showed no effect of social support on CVR (Christian & Stoney, ; Craig & Deichert, ; Gallo, Smith, & Kircher, ).

What does this study add?

When participants were in more engaging conditions, social support decreased CVR relative to no support.

When participants were in less engaging conditions, social support did not have a significant effect on CVR.

Provide an alternative way to explain the ways social support affects cardiac health.
Improving anticancer activity towards colon cancer cells with a new p53‐activating agent
Authors: Raimundo Liliana , Espadinha Margarida , Soares Joana , Loureiro Joana B , Alves Marco G , Santos Maria M M , Saraiva Lucília
Published: August 2018

Background and Purpose

Impairment of the tumour suppressor p53 pathway is a major event in human cancers, making p53 activation one of the most attractive therapeutic strategies to halt cancer. Here, we have identified a new selective p53 activator and investigated its potential as an anticancer agent.

Experimental Approach

Anti‐proliferative activity of the (R)‐tryptophanol‐derived bicyclic lactam SYNAP was evaluated in a range of human cancer cells with different p53 status. The anticancer activity and mechanism of action of SYNAP was studied in two‐ and three‐dimensional models of human colon adenocarcinoma HCT116 cells with wild‐type p53 and corresponding p53‐null isogenic derivative cells, alone and in combination with known chemotherapeutic agents.

Key Results

SYNAP showed anti‐proliferative effect in human cancer cells dependent on p53 status. In HCT116 cells, SYNAP caused p53‐dependent growth inhibition, associated with cell cycle arrest and apoptosis, anti‐migratory activity and regulation of the expression of p53 transcriptional targets. Data also indicated that SYNAP targeted p53, inhibiting its interaction with its endogenous inhibitors, murine double minute (MDM)2 and MDMX. Moreover, SYNAP sensitized colon cancer cells to the cytotoxic effect of known chemotherapeutic agents. SYNAP did not induce acquired or cross‐resistance and re‐sensitized doxorubicin‐resistant colon cancer cells to chemotherapy. Additionally, SYNAP was non‐genotoxic and had low cytotoxicity against normal cells.

Conclusion and Implications

SYNAP revealed encouraging anticancer activity, either alone or in combination with known chemotherapeutic agents, in colon cancer cells. Apart from its promising application in cancer therapy, SYNAP may provide a starting point for improved p53 activators.
Reducing the harmful effect of work overload on creative behaviour: Buffering roles of energy‐enhancing resources
Authors: De Clercq Dirk , Belausteguigoitia Imanol
Published: August 2018

This study investigates how employees' perceptions of work overload might reduce their creative behaviours and how this negative relationship might be buffered by employees' access to three energy‐enhancing resources: their passion for work, their ability to share emotions with colleagues, and their affective commitment to the organization. Data from a manufacturing organization reveal that work overload reduces creative behaviour, but the effect is weaker with higher levels of passion for work, emotion sharing, and organizational commitment. The buffering effects of emotion sharing and organizational commitment are particularly strong when they combine with high levels of passion for work. These findings indicate how organizations marked by adverse work conditions, due to excessive workloads, can mitigate the likelihood that employees avoid creative behaviours.
Design, synthesis, and antiviral evaluation of novel hydrazone‐substituted thiophene[3,2‐d]pyrimidine derivatives as potent human immunodeficiency virus‐1 inhibitors
Authors: Wang Zhao , Kang Dongwei , Chen Meng , Wu Gaochan , Feng Da , Zhao Tong , Zhou Zhongxia , Huo Zhipeng , Jing Lanlan , Zuo Xiaofang , Daelemans Dirk , De Clercq Erik , Pannecouque Christophe , Zhan Peng , Liu Xinyong
Published: August 2018

In the previous studies of our laboratory, the thiophene[3,2‐d]pyrimidine was identified as a promising scaffold for seeking highly potent HIV‐1 non‐nucleoside reverse transcriptase inhibitors (NNRTIs). In this study, we designed, synthesized, and biologically evaluated a series of thiophene[3,2‐d]pyrimidine derivatives with changed linker between the thiophenepyrimidine core and the right wing. Some of the synthesized compounds exhibited excellent HIV‐1 inhibitory potency with low (double‐digit) nanomolar 50% effective concentration (EC50) values. Among them, compound 13a exhibited the most potent anti‐HIV‐1 activity (EC50 = 21.2 nM), which was 10‐fold greater than that of NVP (EC50 = 281 nM). Moreover, 13a showed much lower cytotoxicity (CC50 = 183 μM) and higher selection index (SI = 8,632) than NVP, ETV, and AZT. Besides, some physicochemical properties and water solubility were calculated or measured. The preliminary structure–activity relationships and molecular simulation studies of these compounds were also discussed comprehensively to provide valuable direction for further design and optimization.
Different effects of various anti‐angiogenic treatments in an experimental mouse model of retinopathy of prematurity
Authors: Heiduschka Peter , Plagemann Tanja , Li Lu , Alex Anne F , Eter Nicole
Published: August 2018

Background

Anti‐vascular endothelial growth factor (VEGF) drugs are an option for the treatment of retinopathy of prematurity (ROP). Blocking of other angiogenic factors is also of interest. We therefore investigated in which effects would result blocking of placental growth factor (PlGF).

Methods

C57BL/6 mice were exposed to 75% oxygen from P7 to P12. Intravitreal injections were performed at P12. Mice of control groups remained untouched after oxygen treatment, or phosphate buffered saline or neutral IgG molecules were injected. In the treatment groups, antibodies against VEGF or PlGF, a mixture of anti‐VEGF and anti‐PlGF, aflibercept or sunitinib were injected. On P17, electroretinographic (ERG) measurements were performed. Avascular zones and neovascularization were evaluated in retinal flat‐mounts. Results are expressed as percent of total retinal area (median with median absolute deviation, MAD).

Results

Eyes of control groups showed similar neovascularization (1.4–3.3%, MAD 0.4–0.9%). Neovascularization was significantly less (0.5–0.7%, MAD 0.1–0.3%) in all treatment groups. Avascular zones in the retinas of control groups showed similar values (18.3–25.7%, MAD 4.8–8.8%). Avascular zones were significantly reduced down to 3.6 ± 1.3% after anti‐VEGF injection, but they were not reduced significantly in the other treatment groups (13.3–22%, MAD 3.6–6.1%).

ERG measurements did not reveal significant differences between the controls and the treatment groups.

Conclusions

Blocking of PlGF or injection of sunitinib results in a similar inhibition of neovascularization as by anti‐VEGF treatment in the mouse model of ROP. However, physiological angiogenesis that occurs after anti‐VEGF treatment is blocked by anti‐PlGF or sunitinib treatment, indicating that pathological neovascularization may follow different pathways than physiological angiogenesis.
Cytokines and antibody responses during Trypanosoma congolense infections in two inbred mouse strains that differ in resistance
Authors: UZONNA J.E. , KAUSHIK R.S. , GORDON J.R. , TABEL H.
Published: August 2018

We studied IL‐4, IL‐10 and IFN‐γ secretion by splenocytes and the plasma levels of different isotypes of antibodies against various antigens of Trypanosoma congolense in highly susceptible BALB/c and relatively resistant C57BL/6 mice during the early course of infection with T. congolense. The patterns of appearance of cytokine spot‐forming cells in the spleens were essentially similar in the two mouse strains although higher numbers were detected in the spleens of BALB/c than C57BL/6 mice on some days post‐infection. However, the amount of IL‐4, IL‐10 and IFN‐γ secreted into the culture fluids was dramatically different. From day 4 forward, splenocytes from BALB/c mice secreted very high levels of these cytokines. In contrast, splenocytes from infected C57BL/6 mice did not secrete detectable levels of IL‐4 throughout the period tested. The secretion of IL‐10 and IFN‐γ by C57BL/6 splenocytes only became appreciable on day 6 and was down‐regulated by day 8, when the first wave of parasitaemia was being controlled. At days 6–8, splenocytes from infected C57BL/6 mice secreted two‐fold higher amounts of IL‐12 p40 than those from BALB/c mice. Infected BALB/c mice mounted an earlier IgM antibody response to variant surface glycoprotein (VSG), formalin‐fixed T. congolense and whole T. congolense lysates than did infected C57BL/6 mice. However, they failed to make any detectable IgG3 and IgG2a antibody responses to these antigens whereas infected C57BL/6 mice made strong IgG3 and IgG2a responses. We speculate that enhanced resistance against T. congolense infections in mice may be mediated by IL‐12 dependent synthesis of IgG2 antibodies to VSG and possibly also common trypanosomal antigens.
Positionspapier: Telemedizin in der Berufsdermatologie – Aktueller Stand und Perspektiven
Authors: Elsner Peter , Bauer Andrea , Diepgen Thomas Ludwig , Drexler Hans , Fartasch Manigé , John Swen Malte , Schliemann Sibylle , Wehrmann Wolfgang , Tittelbach Jörg
Published: August 2018

Die Teledermatologie ist die Verwendung von Telekommunikationstechnologien zum Austausch medizinischer Informationen für Diagnostik, Konsultation, Therapie und Lehre in der Dermatologie. Während ihr Einsatz bei einem breiten Spektrum dermatologischer Diagnosen evaluiert wurde, liegen nur wenige Studien zu Validität, diagnostischer Präzision, Machbarkeit und Kosteneffektivität in der Berufsdermatologie vor; diese zeigen aber ein erhebliches Potenzial sowohl für Diagnostik, Prävention, Therapiebegleitung und Nachsorge von Berufskrankheiten der Haut. Ein dermatologisches asynchrones (Store and Forward; SAF) oder synchrones Telekonsil könnte Arbeitsmediziner und Betriebsärzte bei der gesetzlichen arbeitsmedizinischen Vorsorge in hautbelastenden Berufen, aber auch beim Hautkrebsscreening von Outdoorworkern unterstützen und so zu rascherer Prävention oder gezielter Berufskrankheitenmeldung beitragen. Mittels moderner von Technologien der künstlichen Intelligenz unterstützter mobiler Smartphone‐Apps kann auch das Selbstmonitoring von Beschäftigten in Risikoberufen verbessert werden.
Declining Food Security in a Philippine Oil Palm Frontier: The Changing Role of Cooperatives
Authors: Montefrio Marvin Joseph F. , Dressler Wolfram H.
Published: August 2018

The long‐held redistributive function of agricultural cooperatives — one of moral economy and poverty alleviation — has changed dramatically as they emerge as core brokers for agro‐industrial development in the so‐called ‘green economy’. This article examines the changing role of cooperatives involved in brokering oil palm production and its impact upon the food security and livelihoods of smallholders who labour in plantation regimes situated in historically uneven agrarian political economies. Findings show how, increasingly, cooperatives reinforce uneven agrarian social relations of production and exchange in which indigenous smallholders experience loss of land, poor wage labour conditions tinged with insecurity and prejudice, and mounting debt in an expanding oil palm complex. The article suggests that these changes in agrarian social relations negatively influence indigenous farmers’ food security pathways, with their access to and use of appropriate foods diminishing. It asserts that understanding the impacts of cooperatives on food security pathways requires a relational and situated analysis of livelihood change and agrarian relations in extractive frontiers.
From disaster to devastation: drought as war in northern Uganda
Authors: Branch Adam
Published: August 2018

This paper proposes a shift from the concept of disaster to one of devastation when dealing with the destructive consequences of climate change. It argues that today, a discourse of climate‐change disaster has become dominant, in which present disasters are seen as harbingers of a future of widespread climate disaster, products of a global nature in upheaval. The paper contends that one needs to go beyond the series of dichotomies that the climate‐change disaster discourse relies upon: future/past, global/local, natural/social. To frame climate disaster as a product of global climate change, and conflict the product of those climate disasters, is to occlude the forms of environmental violence and experience of climate change among disaster‐affected communities. Through an exploration of the drought in Uganda, the paper asserts that disaster should be understood as embedded within ongoing, longstanding, multiscalar processes of devastation produced by histories of human engagement with the environment, including that of war.
The aquarium in the right heart
Authors: Lun Chung‐Tat , Shum Hoi‐Ping
Published: August 2018

We presented a case with massive hepatic portovenous gas (HPVG) and gastric emphysema, probably due to increased intraluminal pressure in the stomach after bagging and noninvasive ventilation. There are multiple microbubbles in the inferior vena cava, right atrium and right ventricle. There has been only one case report ever published showing the similar features of the “aquarium sign” in the right heart in a patient with intussusception. We believe our case is a good illustration of this extremely rare entity in echocardiography.
Echocardiographic diagnosis of atrial flutter in a neonate
Authors: Low Samantha , Kiper Carmen , Armstrong Aimee , Cua Clifford L.
Published: August 2018

A pregnant female presented at 37 weeks of gestation in labor. The fetus was noted to be tachycardic on fetal monitor. Postnatally, the male neonate was still noted to be tachycardic with heart rates in the low 200 bpm range. EKG was consistent with tachycardia, but rhythm diagnosis was not definitively made. Echocardiogram with M‐mode analysis clearly demonstrated 2:1 atrial to ventricular contraction pattern consistent with atrial flutter. The neonate was subsequently transferred to a tertiary pediatric hospital where the diagnosis of atrial flutter was confirmed.
Ultrasound imaging artifacts: How to recognize them and how to avoid them
Authors: Quien Mary M. , Saric Muhamed
Published: August 2018

Echocardiography has become a critical tool in clinical cardiology in evaluating cardiac physiology and diagnosing cardiac disease states. However, imaging artifacts are commonly encountered and often lead to misdiagnoses of life‐threatening diseases, such as aortic dissection and ventricular thrombus. It is, thus, critical for clinicians to understand these artifacts to avoid these misdiagnoses and protect patients from undue intervention. Artifacts can be broken down into two categories: those from violation of ultrasound system assumptions and those from interference by external equipment and devices. This review article discusses the most commonly encountered artifacts by category, explains their physical mechanisms, elaborates on their most common presentations, and instructs clinicians on how to avoid their misinterpretation.
Loans of the revolution: how Mexico borrowed as the state collapsed in 1912–13
Authors: Weller Leonardo
Published: August 2018

This article assesses why the French and US banks Paribas and Speyers underwrote a series of loans to revolutionary Mexico in 1912 and 1913, when the state was in the process of collapsing. This is a case of a war debt that failed to prevent the borrowing government from suspending payments and subsequently falling. Based on unpublished primary documents, the article shows that the 1913 loan involved a conflict of interest. The credit delayed a default and sustained the price of Mexican securities while Paribas, its main underwriter, was liquidating its Mexican portfolio. Evidence also suggests the existence of asymmetry of information. Paribas accessed pessimistic but accurate first‐hand information on Mexico, while the public read over‐optimistic press reports. Paribas forced the government to sell the bonds on the primary market at a price that was low, controlling for publicly available data. It subsequently sold the bonds at a margin on the secondary market. An additional reason for the lending is the Nacional railway, a state‐owned company that used a share of the funds to pay its debt. More exposed to Mexico than Paribas, the small and internationalized Speyers held the bad bonds it had underwritten.
The development of an entrepreneurial mindset in primary education
Authors: Zupan Blaž , Cankar Franc , Setnikar Cankar Stanka
Published: August 2018

This article provides insights into the design thinking method, a teaching strategy for developing creativity, innovative thinking, and an entrepreneurial mindset in young people as a universally applicable skill. It presents results from a study of 146 seventh‐ and eighth‐grade students, aged 12–14 and 20 teachers across 10 Slovene schools. Teachers used the design thinking method to facilitate hands‐on student projects and evaluated their effectiveness in cultivating an entrepreneurial mindset. The two teachers per class submitted a combined final report of their experience and observations. In addition, a study facilitator visited each school several times to discuss the project with the teachers, observe the class, and take notes. Thirteen factors that contributed to students’ entrepreneurial mindset were identified and organized into three clusters: project factors, the learning environment in which it was carried out, and the learning and teaching factors.
Evidence of equine influenza A (H3N8) activity in horses from Eastern and Central Saudi Arabia: 2013–2015
Authors: Hemida M. G. , Perera R. A. P. M. , Chu D. K. W. , Alnaeem A. A. , Peiris M.
Published: August 2018

Background

Equine influenza virus (EIV) is one of the main causes of viral respiratory affections in horses. Little is known about the prevalence of EIV in Saudi Arabia especially the H3N8 serotype.

Objectives

To assess prevalence of equine influenza in horse populations in Eastern and Central Saudi Arabia.

Study design

Cross‐sectional study.

Methods

We collected 145 sera, 323 nasal and 323 rectal swabs from horses from six major cities in Eastern and Central regions. None of the horses were vaccinated against EIV. Sera were tested in ELISA assays for influenza A type‐specific antibodies and by haemagglutination inhibition (HI) tests using equine H3N8. The swabs were tested by RT‐qPCR assay targeting a conserved region of the influenza A matrix gene that detects influenza A viruses of all subtypes.

Results

None of the swabs had detectable influenza A virus RNA. Of the 145 serasamples tested by ELISA, 81 (55.9%) were positive and 98 (67.6%) of 145 sera tested by HI tests were positive for equine H3.

Main limitations

Our failure to detect and sequence any EIV prevents identification of the lineage of virus that circulates in the Kingdom of Saudi Arabia.

Conclusions

These results confirm that EIV H3N8 is circulating in Saudi Arabia and should be considered as a possible cause when investigating horses with respiratory disease in Saudi Arabia.
Pharmacokinetics of intravenous flumetasone and effects on plasma hydrocortisone concentrations and inflammatory mediators in the horse
Authors: Knych H. K. , Arthur R. M. , McKemie D. S. , Baden R. , Oldberg N. , Kass P. H.
Published: August 2018

Background

Flumetasone is a potent corticosteroid reportedly used in horses to decrease inflammation associated with strenuous exercise. There are currently no reports describing the use of this drug in horses.

Objectives

To describe the pharmacokinetics and effects on cortisol and eicosanoid concentrations, following administration of flumetasone to exercised horses.

Study design

Parallel design.

Methods

Twelve exercised horses received a single i.v. administration of 5 mg of flumetasone. Blood and urine samples were collected before and for 72 h post‐drug administration for determination of flumetasone and cortisol concentrations. Whole blood samples were collected at various time and challenged with lipopolysaccharide, calcium ionophore or methanol to induce ex vivo synthesis of eicosanoids. Concentrations of flumetasone, cortisol and eicosanoids were measured using LC‐MS/MS and pharmacokinetic/pharmacodynamic analysis performed.

Results

Flumetasone was detected for 23.5 ± 1.73 h in blood. The volume of distribution at steady state, systemic clearance and elimination half‐life was 5.90 ± 0.200 L/kg, 30.7 ± 0.166 mL/min/kg and 4.84 ± 0.83 h respectively. Cortisol concentrations were still suppressed at last time point collected (72 h). For cortisol, Kin, Kout and the t1/2out were 30.3 ± 1.56 ng/mL × h, 0.331 ± 0.02 1/h and 2.1 h respectively. Stimulation with lipopolysaccharide resulted in a decrease in TXB2, PGF2, LTB4, 15‐HETE and 5‐HETE for up to 72 h and PGE2 for 24 h post‐flumetasone administration. Stimulation of whole blood with calcium ionophore resulted in a decrease in LTB4 for up to 6 h and 15‐HETE at 8 h.

Main limitations

Lack of sample collection for determination of biomarker concentrations beyond 72 h and the use of a single sample for determination of baseline cortisol concentrations.

Conclusions

Flumetasone is rapidly cleared from blood following administration to horses. It is a potent anti‐inflammatory with prolonged effects on production of cortisol and other inflammatory mediators.
The ribosome biogenesis protein Esf1 is essential for pharyngeal cartilage formation in zebrafish
Authors: Chen Jian‐Yang , Tan Xungang , Wang Zheng‐Hua , Liu Yun‐Zhang , Zhou Jian‐Feng , Rong Xiao‐Zhi , Lu Ling , Li Yun
Published: August 2018

Craniofacial malformations are common congenital birth defects and usually caused by abnormal development of the cranial neural crest cells. Some nucleolar ribosome biogenesis factors are implicated in neural crest disorders also known as neurocristopathies. However, the underlying mechanisms linking ribosome biogenesis and neural crest cell (NCC) development remain to be elucidated. Here we report a novel zebrafish model with a CRISPR/Cas9‐generated esf1 mutation, which exhibits severe NCC‐derived pharyngeal cartilage loss and defects in the eyes, brain, and heart. The expression of several typical NCC markers, including sox10, dlx2a, nrp2b, crestin, vgll2a, and sox9a, was reduced in the head of the esf1 mutants, which indicates that esf1 plays a role in the development of zebrafish NCCs. We demonstrate that, similar to the yeast, loss of esf1 in zebrafish leads to defects in 18S rRNA biogenesis and ribosome biogenesis. We also show strong upregulation of p53 signaling as well as apoptosis, and poor proliferation in mutants. Inactivation of p53 rescues the early tissue defects and pharyngeal cartilage loss observed in esf1 mutants, indicating that increased cell death and pharyngeal cartilage defects observed in esf1 mutants are mediated via upregulated p53 signaling pathways. Based on transplantation analysis, we found esf1 functions in NCC in a cell autonomous fashion. Together, our results suggest that esf1 is required for NCC development and pharyngeal cartilage formation. These studies provide a potential model for investigating the relationship between ribosome biogenesis defects and craniofacial neurocristopathies.
Amino acid sequence conservation of the algesic fragment of myelin basic protein is required for its interaction with CDK5 and function in pain
Authors: Chernov Andrei V. , Remacle Albert G. , Hullugundi Swathi K. , Cieplak Piotr , Angert Mila , Dolkas Jennifer , Shubayev Veronica I. , Strongin Alex Y.
Published: August 2018

Neurotrauma frequently results in neuropathic pain. Our earlier studies revealed that peripheral neurotrauma‐induced fragmentation of the myelin basic protein (MBP), a major component of the myelin sheath formed by Schwann cells, initiates a pain response from light touch stimuli (mechanical allodynia) in rodents. Here, we identified the cyclin‐dependent kinase 5 (CDK5), as an intracellular interactor of MBP in Schwann cells. The algesic peptide fragment of MBP directly associated with CDK5. When complexed with its p25 coactivator, CDK5 phosphorylated the conserved MBP sequence. The expressed MBP fragment colocalized with CDK5 in Schwann cell protrusions. Roscovitine, an ATP‐competitive CDK5 inhibitor, disrupted localization of the expressed MBP peptide. Mutations in the evolutionary conserved MBP algesic sequence resulted in the interference with intracellular trafficking of the MBP fragment and kinase activity of CDK5 and diminished pain‐like behavior in rodents. Our findings show that MBP fragment amino acid sequence conservation determines its interactions, trafficking, and pronociceptive activity. Because CDK5 activity controls both neurogenesis and nociception, the algesic MBP fragment may be involved in the regulation of the CDK5 functionality in pain signaling and postinjury neurogenesis in vertebrates.

Database

The novel RNA‐seq datasets were deposited in the GEO database under the accession number GSE107020.
Oral health and cancer screening in long‐term care nursing facilities: Motivation and opportunity as intervention targets
Authors: Maramaldi Peter , Cadet Tamara , Burke Shanna L. , LeCloux Mary , White Erina , Kalenderian Elsbeth , Kinnunen Taru
Published: August 2018

Objective

The objective of this study is to propose empirically and conceptually supported interventions that might increase the capability and opportunity to provide of oral hygiene care and oral cancer screening in long‐term nursing care facilities.

Background

Improving the oral health in the older adult population is a priority of the Healthy People 2020 initiative. Poor oral health disproportionably affects older populations, which indicates lower participation in regular oral health care (OHC) that includes screening and early detection of oral cancer.

Material and methods

A rigorous recruitment protocol yielded a purposive sample of nursing home Administrators and Directors of Nursing who participated in nine discrete focus groups (n = 34) in several regions of Massachusetts. Interview data were integrated with a conceptual framework of the Health Belief Model and the “capability,” “opportunity,” “motivation” and “behavior” of the COM‐B system to identify potential interventions to increase oral health and oral cancer screening. We used NVivo to identify conceptual themes related to potential intervention targets.

Results

Participants identified several impediments to oral hygiene and cancer screening in the context of the conceptual model. High barriers, low opportunities and low motivation were themes identified as potential targets for intervention.

Conclusions

Our findings suggest that the intervention likely to increase OHC and consequently oral cancer screening include: training certified nurses’ aides using dental students and volunteers; educating family members about OHC and oral cancer screening, and increasing oral cancer awareness.
Accuracy of calprotectin using the Quantum Blue Reader for the diagnosis of spontaneous bacterial peritonitis in liver cirrhosis
Authors: Weil Delphine , Heurgue‐Berlot Alexandra , Monnet Elisabeth , Chassagne Sophie , Cervoni Jean‐Paul , Feron Thomas , Grandvallet Céline , Muel Emilie , Bronowicki Jean‐Pierre , Thiefin Gérard , Di Martino Vincent , Bardonnet Karine , Thévenot Thierry
Published: August 2018

Aim

We aimed to evaluate the accuracy of the dosage of calprotectin in ascitic fluid (AF) using the Quantum Blue assay, for the prompt diagnosis of spontaneous bacterial peritonitis (SBP).

Methods

We prospectively collected 236 AF samples from 119 cirrhotic patients hospitalized in two French centers between May 2016 and May 2017. Bloody and chylous/cloudy AF, and secondary peritonitis were excluded. SBP was diagnosed if neutrophils in AF were >250/mm3 using standard cytology. The Quantum Blue Reader selectively measured the calprotectin antigen (MRP8/14) in 12 min within the measurable range from 0.18 to 1.80 μg/mL; values outside this range were registered as 0.17 and 1.81 μg/mL.

Results

A total of 36 AF were considered as SBP (15.2%). SBP had higher median levels of calprotectin than non‐SBP (1.81 vs. 0.25 μg/mL, P < 0.001). Calprotectin levels were positively correlated with neutrophils in AF (r = 0.57, P < 0.001) and C‐reactive protein (r = 0.43, P < 0.001), but not with the Child–Pugh and Model for End‐Stage Liver Disease scores. The optimal threshold of calprotectin to diagnose SBP was set at 1.51 μg/mL (80th percentile of calprotectin), yielding sensitivity, specificity, and positive and negative predictive values of 86.1%, 92.0%, 65.9%, and 97.3%, respectively. Only one asymptomatic patient with SBP had a low calprotectin level, but a high serum C‐reactive protein level that strongly suggested an ongoing infection. We also showed that intraclass correlation coefficients for inter‐ and intra‐observer agreement were excellent, with 0.95 and 0.89, respectively.

Conclusions

The dosage of calprotectin in AF using the Quantum Blue assay is a rapid and reliable method of ruling out SBP in hospitalized cirrhotic patients.