bluuebunny/crossref_metadata_2025_split huggingface dataset:
Penicillinase-resistant antibiotics induce non-immune-mediated cholestasis through HSP27 activation associated with PKC/P38 and PI3K/AKT signaling pathways
Authors: Burban Audrey , Sharanek Ahmad , Hüe Romain , Gay Marion , Routier Sylvain , Guillouzo André , Guguen-Guillouzo Christiane 
Published: May 2017

AbstractThe penicillinase-resistant antibiotics (PRAs), especially the highly prescribed flucloxacillin, caused frequent liver injury via mechanisms that remain largely non-elucidated. We first showed that flucloxacillin, independently of cytotoxicity, could exhibit cholestatic effects in human hepatocytes in the absence of an immune reaction, that were typified by dilatation of bile canaliculi associated with impairment of the Rho-kinase signaling pathway and reduced bile acid efflux. Then, we analyzed the sequential molecular events involved in flucloxacillin-induced cholestasis. A crucial role of HSP27 by inhibiting Rho-kinase activity was demonstrated using siRNA and the specific inhibitor KRIBB3. HSP27 activation was dependent on the PKC/P38 pathway, and led downstream to activation of the PI3K/AKT pathway. Other PRAs induced similar cholestatic effects while non PRAs were ineffective. Our results demonstrate that PRAs can induce cholestatic features in human hepatocytes through HSP27 activation associated with PKC/P38 and PI3K/AKT signaling pathways and consequently support the conclusion that in clinic they can cause a non-immune-mediated cholestasis that is not restricted to patients possessing certain genetic determinants.
Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation
Authors: Rodriguez Myosotys , Lapierre Jessica , Ojha Chet Raj , Kaushik Ajeet , Batrakova Elena , Kashanchi Fatah , Dever Seth M. , Nair Madhavan , El-Hage Nazira 
Published: May 2017

AbstractWe previously reported that activation of the host autophagic protein, Beclin1, by HIV-1 infection represents an essential mechanism in controlling HIV replication and viral-induced inflammatory responses in microglial cells. Existing antiretroviral therapeutic approaches have been limited in their ability to cross the blood-brain barrier effectively and recognize and selectively eliminate persistent HIV-infected brain reservoirs. In the present study and for the first time, the bio-distribution and efficacy of noninvasive intranasal delivery of small interfering RNA (siRNA) against the Beclin1 gene using the cationic linear polyethylenimines (PEI) as a gene carrier was investigated in adult mouse brain. Fluorescein isothiocyanate (FITC)-labeled control siRNA delivered intranasally was found in the cytoplasm of neurons and glial cells of the prefrontal cortex at 4 and 24 hours post-delivery, with no major adverse immune reaction encountered. Intranasal delivery of the siRNA targeting Beclin1 significantly depleted the target protein expression levels in brain tissues with no evidence of toxicity. Binding of siRNA to PEI-polymer was characterized and confirmed by Raman spectroscopy. These results indicate that the intranasal drug delivery allows for the direct delivery of the PEI-siRNA nano-complex to the central nervous system, which could potentially offer an efficient means of gene silencing-mediated therapy in the HIV-infected brain.
Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction – implications as a preeclampsia treatment
Authors: Hannan Natalie J. , Brownfoot Fiona C. , Cannon Ping , Deo Minh , Beard Sally , Nguyen Tuong V. , Palmer Kirsten R. , Tong Stephen , Kaitu’u-Lino Tu’uhevaha J. 
Published: May 2017

AbstractPreeclampsia is a disease of pregnancy associated with placental oxidative stress, inflammation and elevated release of anti-angiogenic factors sFlt-1 and soluble endoglin. These placental factors cause generalized maternal endothelial dysfunction. There are no treatments to halt disease progression; delivery is the only cure. Resveratrol modulates pathways involved in inflammation and oxidative stress and may offer a potential therapeutic for preeclampsia. Resveratrol reduced sFlt-1, sFlt-1 e15a and soluble endoglin secretion from primary trophoblasts and HUVECs and reduced mRNA expression of pro-inflammatory molecules NFκB, IL-6 and IL-1β in trophoblasts. IL-6, IL-1β and TNFα secretion were also significantly reduced. In HUVECs, resveratrol significantly increased mRNA of anti-oxidant enzymes HO-1, NQO1, GCLC and TXN but did not significantly alter HO-1 protein expression, whilst reducing HO-1 protein in trophoblast. Endothelial dysfunction was induced in HUVECs using TNFα, increasing expression of cell adhesion molecule VCAM1 and adhesion of peripheral blood mononuclear cells, both of which were increased further by resveratrol. In contrast, resveratrol significantly reduced TNFα-induced Endothelin-1 (a vasoconstrictor) and significantly increased the phosphorylation of endothelial nitric oxide synthase (eNOS). In summary, resveratrol decreases secretion of anti-angiogenic factors however its effects on the endothelium are mixed. Overall, it may have potential as a treatment for preeclampsia.
Airway Microbial Diversity is Inversely Associated with Mite-Sensitized Rhinitis and Asthma in Early Childhood
Authors: Chiu Chih-Yung , Chan Yi-Ling , Tsai Yu-Shuen , Chen Ssu-An , Wang Chia-Jung , Chen Kuan-Fu , Chung I.-Fang 
Published: May 2017

AbstractMicrobiota plays an important role in regulating immune responses associated with atopic diseases. We sought to evaluate relationships among airway microbiota, serum IgE levels, allergic sensitization and their relevance to rhinitis and asthma. Microbial characterization was performed using Illumina-based 16S rRNA gene sequencing of 87 throat swabs collected from children with asthma (n = 32) and rhinitis (n = 23), and from healthy controls (n = 32). Data analysis was performed using QIIME (Quantitative Insights Into Microbial Ecology) v1.8. Significantly higher abundance of Proteobacteria was found in children with rhinitis than in the healthy controls (20.1% vs. 16.1%, P = 0.009). Bacterial species richness (Chao1 index) and diversity (Shannon index) were significantly reduced in children with mite sensitization but not in those with food or IgE sensitization. Compared with healthy children without mite sensitization, the mite-sensitized children with rhinitis and asthma showed significantly lower Chao1 and Shannon indices. Moraxella and Leptotrichia species were significantly found in the interaction of mite sensitization with rhinitis and asthma respectively. Airway microbial diversity appears to be inversely associated with sensitization to house dust mites. A modulation between airway dysbiosis and responses to allergens may potentially cause susceptibility to rhinitis and asthma in early childhood.
Novel RRM2B Mutation and Severe Mitochondrial DNA Depletion: Report of 2 Cases and Review of the Literature
Authors: Scheuerman Oded , Straussberg Rachel , Kropach Nesia , Shkalim-Zemer Vered , Orenstein Naama 
Published: May 2017

Purpose To describe the clinical presentation and implications of mitochondrial DNA depletion disorder of two siblings with early fatal encephalomyopathy and a novel mutation in the RRM2B gene. The relevant literature is reviewed.
Methods We describe two brothers aged 2.5 months and 1 month, respectively, who were hospitalized in a tertiary pediatric medical center for evaluation of focal seizures, hypotonia, poor feeding, failure to thrive, lactic acidosis, and developmental delay. The older brother also had seizures, and the younger had severe bilateral neurosensory deafness.
Results Genetic sequencing of the RRM2B gene revealed the same novel mutation in both the siblings. Both children died due to respiratory failure at ages 3 and 2.5 months, respectively.
Conclusion The combination of neonatal hypotonia, developmental delay, and lactic acidosis should raise a clinician's suspicion of a mitochondrial depletion disorder and prompt further genetic studies.
Fascia Lata Free Flap Anastomosed to the Superior Trochlear System for Reconstruction of the Anterior Skull Base
Authors: Reyes Camilo , Fritz Michael , Groves Michael , Bentley Heather , Solares C. 
Published: May 2017

Objectives This study aims to introduce a novel technique for the reconstruction of the anterior skull base using a free vascularized anterolateral thigh fascia lata free flap (FLFF) anastomosed to the superior trochlear artery (STA).
Methods The diameter of the STA was measured in 38 (76 sides) computed tomography angiographies (CTAs). Independently, six cadaver heads were used to measure the diameter of the supratrochlear system, and the model was applied to one of them.
Results In women, the average diameter of the STA was 2.5 and 2.8 mm2 for the right and left sides, respectively; for men, it was 3.0 and 3.2 mm2, respectively. In cadavers, the average diameter of both STA was 2.5 mm2. There was no statistical difference when comparing the right and left STA diameters between the CTA from women and men (p < 0.208 and < 0.492, respectively). An FLFF advanced through the nose was anastomosed to the STA to reconstruct the anterior skull base.
Conclusion The STA is a constant vessel with a 2.5 to 3.0 mm2 diameter in men and women that can be used as a recipient free flap vessel. The FLFF can cover the entire skull base. This is a novel method to reconstruct the anterior skull base when local flaps are not available.
Terson Syndrome: Assessment of 53 Patients with Subarachnoid Hemorrhage by a Ruptured Aneurysm
Authors: Santos Roney Mendonça , Fagundes Walter 
Published: May 2017

Objective Terson syndrome (TS), also known as vitreous hemorrhage, is reported in patients with subarachnoid hemorrhage caused by a ruptured aneurysm. This study aims to evaluate the presence of ocular hemorrhage in such patients, trying to identify those who could benefit from the specific treatment for visual deficit recovery.
Methods Prospective study of 53 patients with spontaneous subarachnoid hemorrhage (SSAH) due to ruptured aneurysm. The patients were evaluated for vitreous hemorrhage through indirect fundoscopy with 6 to 12 months of follow-up.
Results The ages of the patients ranged from 17 to 79 years-old (mean age, 45.9 ± 11.7); 39 patients were female (73%) and 14 were male (27%). Six patients (11%) presented TS, and 83.3% had a transient loss of consciousness during ictus.
Conclusions An ophthalmologic evaluation must be routinely performed in subarachnoid hemorrhage patients, especially in those with worse neurological grade. Moreover, prognosis was bad in TS patients.
Abducens Nerve Palsy as Initial Manifestation of Chronic Subdural Hematoma: Case Report
Authors: Magalhães Marcelo José Silva , Oliva Henrique Nunes Pereira , Pereira Getúlio Paixão , Ramos Lucas Gabriel Quadros , Azevedo Henrique Caires Souza 
Published: May 2017

AbstractChronic subdural hematoma (CSDH) is a form of progressive intracranial hemorrhage, typically associated with cases of trauma. The manifestation of this comorbidity with abducens palsy is a rare finding. The present work aims to describe the case of an adult patient with abducens nerve palsy as a manifestation of CSDH. Chronic subdural hematoma is most commonly found in elderly patients, with systemic hypertension as a manifestation. The relation with the sixth cranial nerve is unusual and draws attention to the case reported. In addition, the prognosis is positive, since trepanation and drainage surgery was performed, as it is recommended in the literature.
Agreement and Reliability of Fasted and Oral Glucose Tolerance Test-Derived Indices of Insulin Sensitivity and Beta Cell Function in Boys
Authors: Cockcroft Emma , Williams Craig , Jackman Sarah , Armstrong Neil , Barker Alan 
Published: May 2017

AbstractAssessment of plasma insulin and glucose outcomes is important in paediatric studies aimed at reducing future risk of type 2 diabetes and cardiovascular disease. The aims of this study are to determine the between-method agreement and the day-to-day reliability of fasting and oral glucose tolerance test (OGTT)-derived estimates of insulin sensitivity and β-cell function in healthy boys. Fasting and OGTT assesments of insulin resistance and β-cell function were performed on 28 boys (12.3±2.9 years). Measurements were repeated after 1 week (fasting, n=28) and 1 day (OGTT, n=8). Agreement between estimates of insulin resistance and β-cell function was examined using Pearson’s correlation coefficient. Reliability was assessed using change in the mean, Pearson’s correlation coefficient, and typical error expressed as a coefficient of variation (CV). The Matsuda index was positively related with QUICKI (r=0.88, P<0.001) and negatively related to HOMA-IR (r=−0.76, P<0.001). The Cederholm index was not significantly related with fasting estimates of insulin resistance (all r<0.40, P>0.05). For reliability, QUICKI had the lowest CV% for the fasting (4.7%) and the Cederholm index for the OGTT (6.4%) estimates. The largest CV% was observed in fasting insulin (30.8%) and insulinogenic index 30’ (62.5%). This study highlights differences in between-method agreement and day-to-day reliability for estimates of insulin resistance in youth. The low CV supports the use of the FGIR (fasting) and Cederholm (OGTT) indices in this population.
The difference that ‘capitalism’ makes: on the merits and limits of critical political economy in African Studies
Authors: Ouma Stefan 
Published: May 2017

SUMMARY
The goal of this Briefing is to weigh in carefully on the respective merits and limits of critical political economy perspectives in African Studies (and beyond) and to make a case for ontological and theoretical modesty. Rather than taking African capitalist societies for granted, we should unpick how particular social entities are being made.
Swinging support? Economic cycles and changes in the public attitudes towards welfare recipients in Finland 1995–2010
Authors: Kuivalainen Susan , Erola Jani 
Published: May 2017

ABSTRACT
This article analyses the variation in public attitudes towards welfare recipients according to economic cycles. This question is of great importance at the time of recent fiscal crisis across Europe. Previous research has indicated that economic recession leads to declining welfare state support, although some findings show stronger support during times of increased financial strain. Finland provides ample opportunity to investigate the effects of situational factors, as it experienced two severe economic downturns during the period of examination. Unlike many previous studies, we also considered whether the association between economic cycles and attitudes was dependent on socioeconomic status. Analyses reveal that high unemployment and economic downturns diminish public support for welfare provisioning. Furthermore, the results show that both individual and spousal unemployment, as well as social class position, are associated with people's attitudes towards welfare recipients. These associations remain when the national unemployment rate and GDP growth rate are taken into account. Overall, the working class has stricter opinions of welfare recipients during economic downturns, whereas the opposite is true for the service classes and the self-employed. Moreover, men have stricter attitudes towards welfare recipients during economic recessions.
Protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice
Authors: Etani Reo , Kataoka Takahiro , Kanzaki Norie , Sakoda Akihiro , Tanaka Hiroshi , Ishimori Yuu , Mitsunobu Fumihiro , Taguchi Takehito , Yamaoka Kiyonori 
Published: May 2017

ABSTRACT
Radon therapy using radon (222Rn) gas is classified into two types of treatment: inhalation of radon gas and drinking water containing radon. Although short- or long-term intake of spa water is effective in increasing gastric mucosal blood flow, and spa water therapy is useful for treating chronic gastritis and gastric ulcer, the underlying mechanisms for and precise effects of radon protection against mucosal injury are unclear. In the present study, we examined the protective effects of hot spring water drinking and radon inhalation on ethanol-induced gastric mucosal injury in mice. Mice inhaled radon at a concentration of 2000 Bq/m3 for 24 h or were provided with hot spring water for 2 weeks. The activity density of 222Rn ranged from 663 Bq/l (start point of supplying) to 100 Bq/l (end point of supplying). Mice were then orally administered ethanol at three concentrations. The ulcer index (UI), an indicator of mucosal injury, increased in response to the administration of ethanol; however, treatment with either radon inhalation or hot spring water inhibited the elevation in the UI due to ethanol. Although no significant differences in antioxidative enzymes were observed between the radon-treated groups and the non-treated control groups, lipid peroxide levels were significantly lower in the stomachs of mice pre-treated with radon or hot spring water. These results suggest that hot spring water drinking and radon inhalation inhibit ethanol-induced gastric mucosal injury.
Why mindfulness at work matters – the ‘reboot’ for emotional intelligence development
Authors: Chapman-Clarke Margaret 
Published: May 2017

Purpose
The paper aims to inspire practitioners to look critically at how and in what ways mindfulness can enhance emotional intelligence interventions. The paper also aims to provide practical and evidence-based guidance on what and how to design, implement and evaluate mindfulness-based emotional intelligence (EI) programs.

Design/methodology/approach
This paper adopts a critical, practitioner-perspective on mindfulness as it transitions into the workplace. The author draws on her own work in the field of EI practice and research and the experiences of peers who have implemented mindfulness-based interventions to offer insights on how to navigate the “mindfulness phenomenon” to enhance EI interventions.

Findings
A series of practical steps on how to implement organizational mindfulness-based interventions (O-MBIs), distilled from case studies, entitled “top ten tips from the field”.

Research limitations/implications
The author argues that whilst organizational scholars debate as to whether mindfulness is a topic worthy of interest, practitioners are already engaged and generating practitioner-led research.

Practical implications
Mindfulness is rapidly capturing development and learning practitioner attention, yet there is little empirical work that is initiated by practitioners and shared with practitioners. This paper goes some way to helping peers navigate what has been described as the “mindfulness phenomenon”.

Social implications
Many commentators have noted that we operate in a volatile, uncertain, complex and ambiguous (VUCA) world. We are trapped in a “prison of busyness”, and the author argues that the popularity of mindfulness, not only in the workplace but more broadly in society, is indicative of the need to equip people to cope and a desire to create more compassionate and mindful organizations.

Originality/value
The paper summarizes themes captured in what has been described as a seminal book in the practitioner literature on mindfulness in the workplace. It is designed to provoke readers into looking critically at their existing EI programs and examine how and in what ways, a holistic, embodied practice (mindfulness) can hone the skills of attention, focus and presence. With the intention of facilitating kinder and more compassionate individuals and organizations, potentially leading to more mindful and ethical societies.
Dams on a Myanmar–Thai transboundary river
Authors: Chan Steve Kwok-Leung 
Published: May 2017

Purpose
This paper aims to study dams on transboundary rivers. In this study, the case of the Nu–Salween–Thanlwin River is reviewed. This study is an attempt toward developing a conceptual model to explain the unequal hydropower exchange of hydropower dams on transboundary rivers.

Design/methodology/approach
This paper reviews big dam project plans on the Salween–Thanlwin River near the Myanmar–Thailand border from the perspective of critical hydropolitics. The evidence is drawn from an extensive review of academic literature, reports, newspapers and websites on this topic. Cascao and Zeitoun’s (2010) four pillars of power, namely, geographical, material, bargaining and ideational power, are reviewed in the case of the Salween–Thanlwin River and its riparian states.

Findings
On the basis of a realist discourse, power relationships between dams and their socio-environmental effects are discussed from the perspective of critical hydropolitics. Multiple levels of power asymmetry regarding geographical, material, bargaining and ideational power are observed. The powerful states are high electricity consumers and importers. They invest in hydroelectric dams of adjacent developing states and buy back most of the electricity generated to fuel their industrialization and urbanization. Weak states generally do not have high bargaining power. They depend on the investment of high material power states for domestic and economic development and gain from the export of electricity. However, the externalities of hydropower dams are transferred to these weak states. This contributes to an unequal hydropower exchange model.

Practical implications
The model provides an analytical framework for hydropower dam projects through which comprehensive and multidimensional views are extracted. Academia, policymakers, private developers, international development agencies and nongovernment organizations will have a better understanding of hydropower dam projects and the interactions among riparian states.

Originality/value
This conceptual model stems from Cascao and Zeitoun’s (2010) four pillars of power – geographical, material, bargaining and ideational power. The author limits the framework to hydroelectric dams in transboundary rivers. The powerful states are high electricity consumers and importers that dominate the dam development projects and exchange process.
Modeling disruption in a fresh produce supply chain
Authors: MacKenzie Cameron A. , Apte Aruna 
Published: May 2017

PurposeThe purpose of this paper is to quantify elements that make fresh produce supply chains (FPSCs) vulnerable to disruptions and to quantify the benefits of different disruption-management strategies.Design/methodology/approachThis paper develops a mathematical model of a disruption in a FPSC and analyzes the relationships among variables.FindingsThe model determines the optimal safety stock as a function of the perishability of the produce, the length of time it takes to find the contamination, the level of demand during the disruption, and the amount of produce that can be rerouted. Applying the model to the 2006E. colispinach contamination reveals that the drop in customer demand for fresh spinach plays the largest role in Dole losing sales.Research limitations/implicationsThe model includes several parameters that may be difficult to estimate. Future models can incorporate uncertainty that is inherent in supply chain disruptions.Practical implicationsThe model in this paper can help a supply chain (SC) manager explore the trade-offs of different disruption-management strategies. For example, a SC manager can determine the value of holding additional safety stock vs trying to improve traceability in the SC.Originality/valueThis paper quantifies and models insights delivered in the qualitative analyses of FPSC disruptions. The theoretical contributions include an analysis of the interaction among safety stock, levels of demand, communication, and traceability parameters in order to help SC managers evaluate different strategies to mitigate the effects of contaminated produce.