bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Reported Versus Observed Measures: Validation of Child Caregiver Food Hygiene Practices in Rural Malawi
Authors: Chidziwisano Kondwani , Tilley Elizabeth , Morse Tracy
Published: June 2020

Few studies have attempted to measure the differences between self-reported and observed food hygiene practices in a household setting. We conducted a study to measure the level of agreement between self-reported and observed food hygiene practices among child caregivers with children under the age of five years in rural Malawi. Fifty-eight child caregivers from an intervention and 29 from a control group were recruited into the study. At the end of a nine-month food hygiene intervention, household observations were conducted followed by self-reported surveys. Overall, practices were found to be more frequently reported than observed in both groups. However, the difference between self-reports and observed practices was minimal in the intervention compared to the control group. The odds ratio results confirm that more desirable practices were observed in the intervention group compared to the control group. Despite the effects of reactivity during observations, the study results imply that the intervention group did not just improve their knowledge, but also translated the messaging into better practice. Researchers and implementing agencies in water, sanitation and hygiene and food hygiene sector should ensure that interventions are context-appropriate, and that effective methods of observation are used to confirm any reported effects of an intervention.
Advanced Clinical Practitioners in Primary Care in the UK: A Qualitative Study of Workforce Transformation
Authors: Evans Catrin , Pearce Ruth , Greaves Sarah , Blake Holly
Published: June 2020

Escalating costs and changing population demographics are putting pressure on primary care systems to meet ever more complex healthcare needs. Non-medical ‘advanced clinical practitioner’ (ACP) roles are increasingly being introduced to support service transformation. This paper reports the findings of a qualitative evaluation of nursing ACP roles across General Practices in one region of the UK. Data collection involved telephone interviews with 26 participants from 3 different stakeholder groups based in 9 practice sites: ACPs (n = 9), general practitioners (n = 8) and practice managers (n = 9). The data was analysed thematically. The study found a high degree of acceptance of the ACP role and affirmation of the important contribution of ACPs to patient care. However, significant variations in ACP education, skills and experience led to a bespoke approach to their deployment, impeding system-wide innovation and creating challenges for recruitment and ongoing professional development. In addition, a context of high workforce pressures and high service demand were causing stress and there was a need for greater mentorship and workplace support. System wide changes to ACP education and support are required to enable ACPs to realise their full potential in primary care in the UK.
Educational Inequalities in Self-Rated Health in Europe and South Korea
Authors: Kim Minhye , Khang Young-Ho , Kang Hee-Yeon , Lim Hwa-Kyung
Published: June 2020

While numerous comparative works on the magnitude of health inequalities in Europe have been conducted, there is a paucity of research that encompasses non-European nations such as Asian countries. This study was conducted to compare Europe and Korea in terms of educational health inequalities, with poor self-rated health (SRH) as the outcome variable. The European Union Statistics on Income and Living Conditions and the Korea National Health and Nutrition Examination Survey in 2017 were used (31 countries). Adult men and women aged 20+ years were included (207,245 men and 238,007 women). The age-standardized, sex-specific prevalence of poor SRH by educational level was computed. The slope index of inequality (SII) and relative index of inequality (RII) were calculated. The prevalence of poor SRH was higher in Korea than in other countries for both low/middle- and highly educated individuals. Among highly educated Koreans, the proportion of less healthy women was higher than that of less healthy men. Korea’s SII was the highest for men (15.7%) and the ninth-highest for women (10.4%). In contrast, Korea’s RII was the third-lowest for men (3.27), and the lowest among women (1.98). This high-SII–low-RII mix seems to have been generated by the high level of baseline poor SRH.
Behavior Change Following Pain Neuroscience Education in Middle Schools: A Public Health Trial
Authors: Louw Adriaan , Landrus Regina , Podolak Jessie , Benz Patricia , DeLorenzo Jen , Davis Christine , Rogers Alison , Cooper Kathy , Louw Colleen , Zimney Kory , Puentedura Emilio J. , Landers Merrill R.
Published: June 2020

Chronic pain and the opioid epidemic need early, upstream interventions to aim at meaningful downstream behavioral changes. A recent pain neuroscience education (PNE) program was developed and tested for middle-school students to increase pain knowledge and promote healthier beliefs regarding pain. In this study, 668 seventh-grade middle-school students either received a PNE lecture (n = 220); usual curriculum school pain education (UC) (n = 198) or PNE followed by two booster (PNEBoost) sessions (n = 250). Prior to, immediately after and at six-month follow-up, pain knowledge and fear of physical activity was measured. Six months after the initial intervention school, physical education, recess and sports attendance/participation as well as healthcare choices for pain (doctor visits, rehabilitation visits and pain medication use) were measured. Students receiving PNEBoost used 30.6% less pain medication in the last 6 months compared to UC (p = 0.024). PNEBoost was superior to PNE for rehabilitation visits in students experiencing pain (p = 0.01) and UC for attending school in students who have experienced pain > 3 months (p = 0.004). In conclusion, PNEBoost yielded more positive behavioral results in middle school children at six-month follow-up than PNE and UC, including significant reduction in pain medication use.
A Process Evaluation Protocol for Examining the Impact of Instructions for Correct Use of Child Car Seats Designed through a Consumer-Driven Process and Evaluated in a Field-Based Randomised Controlled Trial
Authors: Brown Julie , Elkington Jane , Hunter Kate , Charlton Judith L. , Bilston Lynne E. , Hayen Andrew , Keay Lisa
Published: June 2020

The incorrect use of child car seats is common, with significant negative effects on crash protection for child passengers. There is currently little evidence for effective, practical countermeasures for incorrect use. The provision of clear and comprehensible materials on correct use supplied with restraints at the point of sale could be highly cost-effective and achieve similar benefits to restraint-fitting services or hands-on training; however, routinely supplied instructions in their current form are frequently difficult to understand. We are conducting a randomised controlled trial of the consumer-driven redesign of instructional materials, consisting of an instruction sheet, swing tags and online training videos. This paper presents the protocol that will be used in an innovate process evaluation that will use the primary outcome of overall serious misuse assessed at six months, together with a survey and semi-structured interviews to determine fidelity, dose and outcomes for all intervention participants. The study will assess intervention delivery and external factors that may impact the effectiveness of the intervention, including experience, health literacy, confidence and attitudes. When it has been conducted, this process evaluation will provide enhanced understanding of the mechanisms through which the intervention works or not, aspects of the implementation process key to success of the intervention and insight into how external factors influence the success of the intervention.
Attributable Risk to Assess the Health Impact of Air Pollution: Advances, Controversies, State of the Art and Future Needs
Authors: Faustini Annunziata , Davoli Marina
Published: June 2020

Despite the increased attention given to the health impact assessment of air pollution and to the strategies to control it in both scientific literature and concrete interventions, the results of the implementations, especially those involving traffic, have not always been satisfactory and there is still disagreement about the most appropriate interventions and the methods to assess their effectiveness. This state-of-the-art article reviews the recent interpretation of the concepts that concern the impact assessment, and compares old and new measurements of attributable risk and attributable fraction. It also summarizes the ongoing discussion about the designs and methods for assessing the air pollution impact with particular attention to improvements due to spatio-temporal analysis and other new approaches, such as studying short term effects in cohorts, and the still discussed methods of predicting the values of attributable risk (AR). Finally, the study presents the more recent analytic perspectives and the methods for directly assessing the effects of not yet implemented interventions on air quality and health, in accordance with the suggestion in the strategic plan 2020−2025 from the Health Effect Institute.
Effects of Surfactants on the Degradation of Diclofenac by Manganese Oxide
Authors: Kuan Wen-Hui , Liu Yu-Jung , Hu Ching-Yao
Published: June 2020

Amine-containing pharmaceuticals are the most often detected pharmaceuticals in wastewater and ambient aquatic environments. They can usually be degraded by manganese oxide (MnO2), which is a common natural oxidant in soils. Surfactants often coexist with pharmaceuticals in wastewater. Some amine-containing pharmaceuticals, such as diclofenac (DIC), are acidic and are thus ionic compounds in neutral conditions. These compounds, therefore, have similar properties to surfactants. Surfactants, thus, may influence the adsorption and degradation processes of DIC by MnO2. The effect of the type of surfactant on the degradation of DIC by MnO2 was investigated in this study with the addition of two common biodegradable surfactants (cetyltrimethyl-ammonium bromide (CTAB) and sodium dodecylsulfate (SDS)). The results indicated that the cationic surfactant (CTAB) significantly increased the degradation rate in neutral and alkaline conditions. On the other hand, the anionic surfactant (SDS) slightly increased the DIC removal rate in an acidic condition but significantly decreased the removal in neutral and alkaline conditions. Coexisting cationic surfactants not only influenced the kinetics but also altered the transformation mechanism of DIC by MnO2. Decarboxylation is the main transformation mechanism of DIC in the presence of CTAB, while both decarboxylation and hydroxylation are the main transformation mechanisms in the absence of CTAB.
Health and Healthcare Utilization among Asylum-Seekers from Berlin’s LGBTIQ Shelter: Preliminary Results of a Survey
Authors: Gottlieb Nora , Püschmann Conny , Stenzinger Fabian , Koelber Julia , Rasch Laurette , Koppelow Martha , Al Munjid Razan
Published: June 2020

Background: LGBTIQ asylum-seekers face multiple health risks. Yet, little is known about their healthcare needs. In 2016, Berlin opened the only major shelter for LGBTIQ asylum-seekers in Germany. This preliminary study describes health and healthcare utilization by asylum-seekers living in Berlin’s LGBTIQ shelter. To identify particular healthcare needs, we compared our results to asylum-seekers from other shelters. Methods: We surveyed residents of the LGBTIQ shelter and 21 randomly selected shelters in Berlin, using a validated questionnaire in nine languages (n = 309 respondents, including 32 respondents from the LGBTIQ shelter). Bivariate tests and generalized linear mixed models were applied to examine differences in health and healthcare utilization between the two groups. Results: Residents of the LGBTIQ shelter show high rates of chronic and mental illness. They use ambulatory and mental health services more frequently than asylum-seekers from other shelters, including a significantly higher chance of obtaining psychotherapy/psychiatric care in case of need. Emergency room utilization is also higher in the LGBTIQ group. Conclusions: Asylum-seekers from the LGBTIQ shelter face high chronic and mental health burdens. Tailored services in the LGBTIQ shelter help obtain adequate healthcare; they should be scaled up to maximize their potential. Yet, unmet needs remain and warrant further research.
Empowering Health Workers to Protect their Own Health: A Study of Enabling Factors and Barriers to Implementing HealthWISE in Mozambique, South Africa, and Zimbabwe
Authors: Wilcox Elizabeth S. , Chimedza Ida Tsitsi , Mabhele Simphiwe , Romao Paulo , Spiegel Jerry M. , Zungu Muzimkhulu , Yassi Annalee
Published: June 2020

Ways to address the increasing global health workforce shortage include improving the occupational health and safety of health workers, particularly those in high-risk, low-resource settings. The World Health Organization and International Labour Organization designed HealthWISE, a quality improvement tool to help health workers identify workplace hazards to find and apply low-cost solutions. However, its implementation had never been systematically evaluated. We, therefore, studied the implementation of HealthWISE in seven hospitals in three countries: Mozambique, South Africa, and Zimbabwe. Through a multiple-case study and thematic analysis of data collected primarily from focus group discussions and questionnaires, we examined the enabling factors and barriers to the implementation of HealthWISE by applying the integrated Promoting Action on Research Implementation in Health Services (i-PARiHS) framework. Enabling factors included the willingness of workers to engage in the implementation, diverse teams that championed the process, and supportive senior leadership. Barriers included lack of clarity about how to use HealthWISE, insufficient funds, stretched human resources, older buildings, and lack of incident reporting infrastructure. Overall, successful implementation of HealthWISE required dedicated local team members who helped facilitate the process by adapting HealthWISE to the workers’ occupational health and safety (OHS) knowledge and skill levels and the cultures and needs of their hospitals, cutting across all constructs of the i-PARiHS framework.
Percutaneous Ablation-Induced Immunomodulation in Hepatocellular Carcinoma
Authors: Dumolard Lucile , Ghelfi Julien , Roth Gael , Decaens Thomas , Macek Jilkova Zuzana
Published: June 2020

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related deaths worldwide and its incidence is rising. Percutaneous locoregional therapies, such as radiofrequency ablation and microwave ablation, are widely used as curative treatment options for patients with small HCC, but their effectiveness remains restricted because of the associated high rate of recurrence, occurring in about 70% of patients at five years. These thermal ablation techniques have the particularity to induce immunomodulation by destroying tumours, although this is not sufficient to raise an effective antitumour immune response. Ablative therapies combined with immunotherapies could act synergistically to enhance antitumour immunity. This review aims to understand the different immune changes triggered by radiofrequency ablation and microwave ablation as well as the interest in using immunotherapies in combination with thermal ablation techniques as a tool for complementary immunomodulation.
Characterization and Evaluation of Ternary Complexes of Ascorbic Acid with γ-Cyclodextrin and Poly(vinyl Alcohol)
Authors: Saokham Phennapha , Burapapadh Kanokporn , Praphanwittaya Pitsiree , Loftsson Thorsteinn
Published: June 2020

Ascorbic acid (AA) is a general antioxidant used in aqueous pharmaceutical formulations. However, in aqueous solutions, AA is unstable and easily oxidized when exposed to air, light and/or heat. Cyclodextrins are well known for their ability to form inclusion complexes with various compounds to improve their solubility and stability. Previous studies demonstrate that cyclodextrins preserve the antioxidant capacity of AA but data for γ-cyclodextrin (γCD) have not been reported. Poly(vinyl alcohol) (PVA) is a hydrophilic polymer widely used as a drug matrix in various pharmaceutical fields, but its application for drug stabilization is limited. This study aimed to investigate the protective ability of γCD on AA through the formation of ternary complexes with PVA. Binary (i.e., AA/γCD, AA/PVA and γCD/PVA) and ternary (i.e., AA/γCD/PVA) complexes were first confirmed. It was reported that those complexes were formed through interactions between the heterocyclic ring of AA, hydroxyl group of PVA and hydrophobic cavity of γCD. The hydrodynamic diameter of complexes was then studied. It was found that the diameter of γCD/PVA complexes increased with respect to the concentration of γCD. Higher γCD concentrations also resulted in increasing hydrodynamic diameters of the ternary complex. The presence of AA in ternary complexes interfered with the aggregation tendency of γCD/PVA binary complexes. Furthermore, the antioxidant capacity of AA in binary and ternary complexes was investigated. It was found that the presence of γCD preserved the antioxidant activity of AA, whereas PVA showed a contrasting effect. The influence of γCD and PVA concentration on antioxidant capacity was then studied through central composite design (CCD). Even though the concentration of γCD significantly affected the inhibition efficiency of the ternary complex, the insignificant influence of PVA could not be ignored. A promising protective ternary complex should consist of an optimized concentration of PVA and a high concentration of γCD.
Transport of Extracellular Vesicles across the Blood-Brain Barrier: Brain Pharmacokinetics and Effects of Inflammation
Authors: Banks William A. , Sharma Priyanka , Bullock Kristin M. , Hansen Kim M. , Ludwig Nils , Whiteside Theresa L.
Published: June 2020

Extracellular vesicles can cross the blood–brain barrier (BBB), but little is known about passage. Here, we used multiple-time regression analysis to examine the ability of 10 exosome populations derived from mouse, human, cancerous, and non-cancerous cell lines to cross the BBB. All crossed the BBB, but rates varied over 10-fold. Lipopolysaccharide (LPS), an activator of the innate immune system, enhanced uptake independently of BBB disruption for six exosomes and decreased uptake for one. Wheatgerm agglutinin (WGA) modulated transport of five exosome populations, suggesting passage by adsorptive transcytosis. Mannose 6-phosphate inhibited uptake of J774A.1, demonstrating that its BBB transporter is the mannose 6-phosphate receptor. Uptake rates, patterns, and effects of LPS or WGA were not predicted by exosome source (mouse vs. human) or cancer status of the cell lines. The cell surface proteins CD46, AVβ6, AVβ3, and ICAM-1 were variably expressed but not predictive of transport rate nor responses to LPS or WGA. A brain-to-blood efflux mechanism variably affected CNS retention and explains how CNS-derived exosomes enter blood. In summary, all exosomes tested here readily crossed the BBB, but at varying rates and by a variety of vesicular-mediated mechanisms involving specific transporters, adsorptive transcytosis, and a brain-to-blood efflux system.
Liposome Consolidated with Cyclodextrin Provides Prolonged Drug Retention Resulting in Increased Drug Bioavailability in Brain
Authors: Lin En-Yi , Chen Yu-Shuan , Li Yuan-Sheng , Chen Syuan-Rong , Lee Chia-Hung , Huang Mao-Hsuan , Chuang Hong-Meng , Harn Horng-Jyh , Yang Hsueh-Hui , Lin Shinn-Zong , Tai Dar-Fu , Chiou Tzyy-Wen
Published: June 2020

Although butylidenephthalide (BP) is an efficient anticancer drug, its poor bioavailability renders it ineffective for treating drug-resistant brain tumors. However, this problem is overcome through the use of noninvasive delivery systems, including intranasal administration. Herein, the bioavailability, drug stability, and encapsulation efficiency (EE, up to 95%) of BP were improved by using cyclodextrin-encapsulated BP in liposomal formulations (CDD1). The physical properties and EE of the CDD1 system were investigated via dynamic light scattering, transmission electron microscopy, UV–Vis spectroscopy, and nuclear magnetic resonance spectroscopy. The cytotoxicity was examined via MTT assay, and the cellular uptake was observed using fluorescence microscopy. The CDD1 system persisted for over 8 h in tumor cells, which was a considerable improvement in the retention of the BP-containing cyclodextrin or the BP-containing liposomes, thereby indicating a higher BP content in CDD1. Nanoscale CDD1 formulations were administered intranasally to nude mice that had been intracranially implanted with temozolomide-resistant glioblastoma multiforme cells, resulting in increased median survival time. Liquid chromatography–mass spectrometry revealed that drug biodistribution via intranasal delivery increased the accumulation of BP 10-fold compared to oral delivery methods. Therefore, BP/cyclodextrin/liposomal formulations have potential clinical applications for treating drug-resistant brain tumors.
Analysis of Spatial Distribution and Prognostic Value of Different Pan Cytokeratin Immunostaining Intensities in Breast Tumor Tissue Sections
Authors: Vranes Velicko , Vujasinović Tijana , Rajković Nemanja , Kanjer Ksenija , Milošević Nebojša T. , Radulovic Marko
Published: June 2020

Cancer risk prognosis could improve patient survival through early personalized treatment decisions. This is the first systematic analysis of the spatial and prognostic distribution of different pan cytokeratin immunostaining intensities in breast tumors. The prognostic model included 102 breast carcinoma patients, with distant metastasis occurrence as the endpoint. We segmented the full intensity range (0–255) of pan cytokeratin digitized immunostaining into seven discrete narrow grey level ranges: 0–130, 130–160, 160–180, 180–200, 200–220, 220–240, and 240–255. These images were subsequently examined by 33 major (GLCM), fractal and first-order statistics computational analysis features. Interestingly, while moderate intensities were strongly associated with metastasis outcome, high intensities of pan cytokeratin immunostaining provided no prognostic value even after an exhaustive computational analysis. The intense pan cytokeratin immunostaining was also relatively rare, suggesting the low differentiation state of epithelial cells. The observed variability in immunostaining intensities highlighted the intratumoral heterogeneity of the malignant cells and its association with a poor disease outcome. The prognostic importance of the moderate intensity range established by complex computational morphology analyses was supported by simple measurements of its immunostaining area which was associated with favorable disease outcome. This study reveals intratumoral heterogeneity of the pan cytokeratin immunostaining together with the prognostic evaluation and spatial distribution of its discrete intensities.
Functional Heterogeneity of Protein Kinase A Activation in Multipotent Stromal Cells
Authors: Tyurin-Kuzmin Pyotr A. , Karagyaur Maxim N. , Kulebyakin Konstantin Yu. , Dyikanov Daniyar T. , Chechekhin Vadim I. , Ivanova Anastasiya M. , Skryabina Mariya N. , Arbatskiy Mikhail S. , Sysoeva Veronika Yu. , Kalinina Natalia I. , Tkachuk Vsevolod A.
Published: June 2020

Multipotent stromal cells (MSC) demonstrate remarkable functional heterogeneity; however, its molecular mechanisms remain largely obscure. In this study, we explored MSC response to hormones, which activate Gs-protein / cyclic AMP (cAMP) / protein kinase A (PKA) dependent signaling, at the single cell level using genetically encoded biosensor PKA-Spark. For the first time, we demonstrated that about half of cultured MSCs are not able to activate the cAMP/PKA pathway, possibly due to the limited availability of adenylyl cyclases. Using this approach, we showed that MSC subpopulations responding to various hormones largely overlapped, and the share of responding cells did not exceed 40%. Using clonal analysis, we showed that signaling heterogeneity of MSC could be formed de novo within 2 weeks.
Fyn Tyrosine Kinase as Harmonizing Factor in Neuronal Functions and Dysfunctions
Authors: Matrone Carmela , Petrillo Federica , Nasso Rosarita , Ferretti Gabriella
Published: June 2020

Fyn is a non-receptor or cytoplasmatic tyrosine kinase (TK) belonging to the Src family kinases (SFKs) involved in multiple transduction pathways in the central nervous system (CNS) including synaptic transmission, myelination, axon guidance, and oligodendrocyte formation. Almost one hundred years after the original description of Fyn, this protein continues to attract extreme interest because of its multiplicity of actions in the molecular signaling pathways underlying neurodevelopmental as well as neuropathologic events. This review highlights and summarizes the most relevant recent findings pertinent to the role that Fyn exerts in the brain, emphasizing aspects related to neurodevelopment and synaptic plasticity. Fyn is a common factor in healthy and diseased brains that targets different proteins and shapes different transduction signals according to the neurological conditions. We will primarily focus on Fyn-mediated signaling pathways involved in neuronal differentiation and plasticity that have been subjected to considerable attention lately, opening the fascinating scenario to target Fyn TK for the development of potential therapeutic interventions for the treatment of CNS injuries and certain neurodegenerative disorders like Alzheimer’s disease.
The Strategic Alliance between Clinical and Molecular Science in the War against SARS-CoV-2, with the Rapid-Diagnostics Test as an Indispensable Weapon for Front Line Doctors
Authors: Gaddi Antonio Vittorino , Capello Fabio , Aluigi Leonardo , Antignani Pier Luigi , Callegaro Annapaola , Casu Gavino , Cipolla Enrico , Cipolla Maurizio , Cosco Lucio , Culzoni Federico , Dentali Francesco , Elexpuru-Zabaleta Maria , Forbes-Hernandez Tamara Y. , Fragiacomo Claudia , Giampieri Francesca , Gnasso Agostino , Mancini Raffaele , Modena Maria Grazia , Nichelatti Michele , Paradiso Angelo Virgilio , Ortasi Pasquale , Savo Maria Teresa , Tangianu Flavio , Tempesta Sergio , Voci Tommaso Diego , Battino Maurizio
Published: June 2020

Our work concerns the actual problem of spread of SARS- CoV-2 outbreak which requires fast and correct as possible answer. In current scenario, the need of rapid answer put away the imperative of proper methodology. We focus on the serogical immunoassay for diagnosis of Covid-19 as an important weapon not only for diagnostic purpose, but also for epidemiologic one. The right equilibrium between high speed, low cost and accuracy is obtained with easy-to-use decentralized point-of-care test as the colloidal gold-based immunochromatographic strip assay which detects IgM and IgG antibodies directed against SARS-CoV-2. As our aim is to evaluate the efficacy of Covid-19 rapid tests and of serological assays in real-life settings, we designed a research protocol aimed to establish how to use correctly these diagnostics, taking into account the different possible clinical and epidemiological scenarios.
Interleukin-4 Improves Metabolic Abnormalities in Leptin-Deficient and High-Fat Diet Mice
Authors: Lin Shih-Yi , Yang Ching-Ping , Wang Ya-Yu , Hsiao Chiao-Wan , Chen Wen-Ying , Liao Su-Lan , Lo Yu-Li , Chang Yih-Hsin , Hong Chen-Jee , Chen Chun-Jung
Published: June 2020

Obesity is a metabolic disorder that results from complex interactions between genetic predisposition and dietary factors. Interleukin-4 (IL-4), besides its role in immunity, has metabolic effects on insulin efficacy. We studied the effects of IL-4 on metabolic abnormalities in a mice model of obesity involving leptin deficiency and leptin resistance. Leptin-deficient 145E and leptin-resistant high-fat diet (HFD) mice showed lower levels of circulating IL-4. 145E and HFD mice showed a number of abnormalities: Obesity, hyperglycemia, hyperinsulinemia, insulin resistance, dyslipidemia, liver injury, and adiposity with concurrent inflammation, decreases in Akt, signal transducer and activator of transcription 3 (STAT3), and STAT6 phosphorylation in the hypothalamus, liver, and epididymal fat. Independent of leptin-deficient obesity and dietary obesity, a course of 8-week IL-4 supplementation improved obesity and impairment in Akt, STAT3, and STAT6 signaling. Amelioration of cytokine expression, despite variable extents, was closely linked with the actions of IL-4. Additionally, the browning of white adipocytes by IL-4 was found in epididymal white adipose tissues and 3T3-L1 preadipocytes. Chronic exercise, weight management, and probiotics are recommended to overweight patients and IL-4 signaling is associated with clinical improvement. Thus, IL-4 could be a metabolic regulator and antiobesity candidate for the treatment of obesity and its complications.
A Peptidic Thymidylate-Synthase Inhibitor Loaded on Pegylated Liposomes Enhances the Antitumour Effect of Chemotherapy Drugs in Human Ovarian Cancer Cells
Authors: Marverti Gaetano , Gozzi Gaia , Maretti Eleonora , Lauriola Angela , Severi Leda , Sacchetti Francesca , Losi Lorena , Pacifico Salvatore , Ferrari Stefania , Ponterini Glauco , Leo Eliana , Costi Maria Paola , D’Arca Domenico
Published: June 2020

There is currently no effective long-term treatment for ovarian cancer (OC) resistant to poly-chemotherapy regimens based on platinum drugs. Preclinical and clinical studies have demonstrated a strong association between development of Pt-drug resistance and increased thymidylate synthase (hTS) expression, and the consequent cross-resistance to the hTS inhibitors 5-fluorouracil (5-FU) and raltitrexed (RTX). In the present work, we propose a new tool to combat drug resistance. We propose to treat OC cell lines, both Pt-sensitive and -resistant, with dual combinations of one of the four chemotherapeutic agents that are widely used in the clinic, and the new peptide, hTS inhibitor, [D-Gln4]LR. This binds hTS allosterically and, unlike classical inhibitors that bind at the catalytic pocket, causes cell growth inhibition without inducing hTS overexpression. The dual drug combinations showed schedule-dependent synergistic antiproliferative and apoptotic effects. We observed that the simultaneous treatment or 24h pre-treatment of OC cells with the peptide followed by either agent produced synergistic effects even in resistant cells. Similar synergistic or antagonistic effects were obtained by delivering the peptide into OC cells either by means of a commercial delivery system (SAINT-PhD) or by pH sensitive PEGylated liposomes. Relative to non-PEGylated liposomes, the latter had been previously characterized and found to allow macrophage escape, thus increasing their chance to reach the tumour tissue. The transition from the SAINT-PhD delivery system to the engineered liposomes represents an advancement towards a more drug-like delivery system and a further step towards the use of peptides for in vivo studies. Overall, the results suggest that the association of standard drugs, such as cDDP and/or 5-FU and/or RTX, with the novel peptidic TS inhibitor encapsulated into PEGylated pH-sensitive liposomes can represent a promising strategy for fighting resistance to cDDP and anti-hTS drugs.
The microRNA-34a-Induced Senescence-Associated Secretory Phenotype (SASP) Favors Vascular Smooth Muscle Cells Calcification
Authors: Zuccolo Estella , Badi Ileana , Scavello Francesco , Gambuzza Irene , Mancinelli Luigi , Macrì Federica , Tedesco Calogero C. , Veglia Fabrizio , Bonfigli Anna Rita , Olivieri Fabiola , Raucci Angela
Published: June 2020

The senescence of vascular smooth muscle cells (VSMCs), characterized by the acquisition of senescence-associated secretory phenotype (SASP), is relevant for VSMCs osteoblastic differentiation and vascular calcification (VC). MicroRNA-34a (miR-34a) is a driver of such phenomena and could play a role in vascular inflammaging. Herein, we analyzed the relationship between miR-34a and the prototypical SASP component IL6 in in vitro and in vivo models. miR-34a and IL6 levels increased and positively correlated in aortas of 21 months-old male C57BL/6J mice and in human aortic smooth muscle cells (HASMCs) isolated from donors of different age and undergone senescence. Lentiviral overexpression of miR-34a in HASMCs enhanced IL6 secretion. HASMCs senescence and calcification accelerated after exposure to conditioned medium of miR-34a-overexpressing cells. Analysis of miR-34a-induced secretome revealed enhancement of several pro-inflammatory cytokines and chemokines, including IL6, pro-senescent growth factors and matrix-degrading molecules. Moreover, induction of aortas medial calcification and concomitant IL6 expression, with an overdose of vitamin D, was reduced in male C57BL/6J Mir34a−/− mice. Finally, a positive correlation was observed between circulating miR-34a and IL6 in healthy subjects of 20-90 years. Hence, the vascular age-associated miR-34a promotes VSMCs SASP activation and contributes to arterial inflammation and dysfunctions such as VC.
Ultrastructural and Photosynthetic Responses of Pod Walls in Alfalfa to Drought Stress
Authors: Wang Hui , Zhou Qingping , Mao Peisheng
Published: June 2020

Increasing photosynthetic ability as a whole is essential for acquiring higher crop yields. Nonleaf green organs (NLGOs) make important contributions to photosynthate formation, especially under stress conditions. However, there is little information on the pod wall in legume forage related to seed development and yield. This experiment is designed for alfalfa (Medicago sativa) under drought stress to explore the photosynthetic responses of pod walls after 5, 10, 15, and 20 days of pollination (DAP5, DAP10, DAP15, and DAP20) based on ultrastructural, physiological and proteomic analyses. Stomata were evidently observed on the outer epidermis of the pod wall. Chloroplasts had intact structures arranged alongside the cell wall, which on DAP5 were already capable of producing photosynthate. The pod wall at the late stage (DAP20) still had photosynthetic ability under well-watered (WW) treatments, while under water-stress (WS), the structure of the chloroplast membrane was damaged and the grana lamella of thylakoids were blurry. The chlorophyll a and chlorophyll b concentrations both decreased with the development of pod walls, and drought stress impeded the synthesis of photosynthetic pigments. Although the activity of ribulose-1,5-bisphosphate carboxylase (RuBisCo) decreased in the pod wall under drought stress, the activity of phosphoenolpyruvate carboxylase (PEPC) increased higher than that of RuBisCo. The proteomic analysis showed that the absorption of light is limited due to the suppression of the synthesis of chlorophyll a/b binding proteins by drought stress. Moreover, proteins involved in photosystem I and photosystem II were downregulated under WW compared with WS. Although the expression of some proteins participating in the regeneration period of RuBisCo was suppressed in the pod wall subjected to drought stress, the synthesis of PEPC was induced. In addition, some proteins, which were involved in the reduction period of RuBisCo, carbohydrate metabolism, and energy metabolism, and related to resistance, including chitinase, heat shock protein 81-2 (Hsp81-2), and lipoxygenases (LOXs), were highly expressed for the protective response to drought stress. It could be suggested that the pod wall in alfalfa is capable of operating photosynthesis and reducing the photosynthetic loss from drought stress through the promotion of the C4 pathway, ATP synthesis, and resistance ability.
An Innovative Therapeutic Option for the Treatment of Skeletal Sarcomas: Elimination of Osteo- and Ewing’s Sarcoma Cells Using Physical Gas Plasma
Authors: Jacoby Josephine M. , Strakeljahn Silas , Nitsch Andreas , Bekeschus Sander , Hinz Peter , Mustea Alexander , Ekkernkamp Axel , Tzvetkov Mladen V. , Haralambiev Lyubomir , Stope Matthias B.
Published: June 2020

Osteosarcoma and Ewing’s sarcoma are the most common malignant bone tumors. Conventional therapies such as polychemotherapy, local surgery, and radiotherapy improve the clinical outcome for patients. However, they are accompanied by acute and chronic side effects that affect the quality of life of patients, motivating novel research lines on therapeutic options for the treatment of sarcomas. Previous experimental work with physical plasma operated at body temperature (cold atmospheric plasma, CAP) demonstrated anti-oncogenic effects on different cancer cell types. This study investigated the anti-cancer effect of CAP on two bone sarcoma entities, osteosarcoma and Ewing’s sarcoma, which were represented by four cell lines (U2-OS, MNNG/HOS, A673, and RD-ES). A time-dependent anti-proliferative effect of CAP on all cell lines was observed. CAP-induced alterations in cell membrane functionality were detected by performing a fluorescein diacetate (FDA) release assay and an ATP release assay. Additionally, modifications of the cell membrane and modifications in the actin cytoskeleton composition were examined using fluorescence microscopy monitoring dextran-uptake assay and G-/F-actin distribution. Furthermore, the CAP-induced induction of apoptosis was determined by TUNEL and active caspases assays. The observations suggest that a single CAP treatment of bone sarcoma cells may have significant anti-oncogenic effects and thus may be a promising extension to existing applications.
Investigation of Termite Attack on Cultural Heritage Buildings: A Case Study in Aceh Province, Indonesia
Authors: Novita Novita , Amiruddin Hasbi , Ibrahim Husaini , Jamil Teuku Muhammad , Syaukani Syaukani , Oguri Emiko , Eguchi Katsuyuki
Published: June 2020

Surveys of the conditions of termite attack were conducted in two regencies, Pidie and Greater Aceh, Aceh Province, Indonesia (40 houses in each location). Interviews were also conducted with home owners to collect data on the building history; culture, such as daily life in the house; the frequency and intensity of termite attacks; and traditional knowledge for avoiding and/or suppressing termite attacks. We found that 51% of traditional houses were infested by two termite species: Coptotermes gestroi and Nasutitermes matangensis. The lower parts of traditional houses were frequently attacked and severely damaged by termites. Previous land use and the ages of the traditional houses affected the intensity of the termite attacks. Several measures for avoiding and/or suppressing termite attacks on cultural heritage buildings are also proposed.
Evaluation of the In Vivo Biocompatibility of Amorphous Calcium Phosphate-Containing Metals
Authors: Moerbeck-Filho Pio , Sartoretto Suelen C. , Uzeda Marcelo J. , Barreto Maurício , Medrado Alena , Alves Adriana , Calasans-Maia Mônica D.
Published: June 2020

Among the biomaterials based on calcium phosphate, hydroxyapatite has been widely used due to its biocompatibility and osteoconduction. The substitution of the phosphate group by the carbonate group associated with the absence of heat treatment and low synthesis temperature leads to the formation of carbonated hydroxyapatite (CHA). The association of CHA with other metals (strontium, zinc, magnesium, iron, and manganese) produces amorphous calcium phosphate-containing metals (ACPMetals), which can optimize their properties and mimic biological apatite. This study aimed to evaluate the biocompatibility and biodegradation of ACPMetals in mice subcutaneous tissue. The materials were physicochemically characterized with Fourier Transform InfraRed (FTIR), X-Ray Diffraction (XRD), and Atomic Absorption Spectrometry (AAS). Balb-C mice (n = 45) were randomly divided into three groups: carbonated hydroxyapatite, CHA (n = 15), ACPMetals (n = 15), and without implantation of material (SHAM, n = 15). The groups were subdivided into three experimental periods (1, 3, and 9 weeks). The samples were processed histologically for descriptive and semiquantitative evaluation of the biological effect of biomaterials according to ISO 10993-6:2016. The ACPMetals group was partially biodegradable; however, it presented a severe irritating reaction after 1 and 3 weeks and moderately irritating after nine weeks. Future studies with other concentrations and other metals should be carried out to mimic biological apatite.
Comparison of Satellite-Based Sea Surface Temperature to In Situ Observations Surrounding Coral Reefs in La Parguera, Puerto Rico
Authors: Gomez Andrea M. , McDonald Kyle C. , Shein Karsten , DeVries Stephanie , Armstrong Roy A. , Hernandez William J. , Carlo Milton
Published: June 2020

Coral reefs are among the most biologically diverse ecosystems on Earth. In the last few decades, a combination of stressors has produced significant declines in reef expanse, with declining reef health attributed largely to thermal stresses. We investigated the correspondence between time-series satellite remote sensing-based sea surface temperature (SST) datasets and ocean temperature monitored in situ at depth in coral reefs near La Parguera, Puerto Rico. In situ temperature data were collected for Cayo Enrique and Cayo Mario, San Cristobal, and Margarita Reef. The three satellite-based SST datasets evaluated were NOAA’s Coral Reef Watch (CoralTemp), the UK Meteorological Office’s Operational SST and Sea Ice Analysis (OSTIA), and NASA’s Jet Propulsion Laboratory (G1SST). All three satellite-based SST datasets assessed displayed a strong positive correlation (>0.91) with the in situ temperature measurements. However, all SST datasets underestimated the temperature, compared with the in situ measurements. A linear regression model using the SST datasets as the predictor for the in situ measurements produced an overall offset of ~1 °C for all three SST datasets. These results support the use of all three SST datasets, after offset correction, to represent the temperature regime at the depth of the corals in La Parguera, Puerto Rico.
Diversification and Fund Performance—An Analysis of Buyout Funds
Authors: Huss Matthias , Steger Daniel
Published: June 2020

This paper studies the relationship between portfolio diversification and fund performance, based on an unexplored, hand-collected dataset of buyout funds. The dataset comprises detailed information at the level of portfolio companies, which allows measuring the concentration of the fund portfolios towards individual companies, industrial, and geographical focus. Our results suggest that diversification within, but not across industries, associates with higher buyout fund performance. We do not find a significant relationship between geographical diversification and performance. These results partly contradict results documented in prior literature.
Land Conversion for Tourism Development under Vietnam’s Ambiguous Property Rights over Land
Authors: T.T. Duong Mai , Samsura D. Ary A. , van der Krabben Erwin
Published: June 2020

The paper aims to explore the process of land conversion for tourism development in Vietnam, under the present ambiguous and insecure property rights system. Four case studies in different geographical areas were selected to analyse land conversion and land compensation for tourism projects before and after the implementation of the new land law in 2013. The findings of this study show that, in the present legal system of land and property rights, the rights of local people are not sufficiently guaranteed due to the decisive role of the State not only in defining compensation prices for land in the case of compulsory land acquisition but also in determining whether tourism projects are in the public’s interest or not (thus deciding the appropriate land conversion approach as well as affecting price negotiations). The research also found that, although a voluntary land conversion approach (when the project is not in the public’s interest), based on the 2013 Land Law, offers land users a better negotiation position and a higher compensation payment, possibly reducing land-related conflicts between the State and land users, ambiguity over property rights in fact increased due to the government’s substantial discretion to choose between ‘public purpose’ and ‘economic purpose.’ The paper concludes with questioning whether the present legal basis for compulsory land acquisition is future proof since urbanisation pressure is likely to increase, which may lead to even more land conflicts in the near future.
Steering Energy Transitions through Landscape Governance: Case of Mathare Informal Settlement, Nairobi, Kenya
Authors: Njoroge Peris , Ambole Amollo , Githira Daniel , Outa George
Published: June 2020

Poor households in urban informal settlements face a big challenge in accessing clean energy for cooking, heating, and lighting. We use Kenya’s Mathare informal settlement as a landscape site to better understand how cross-sector collaboration can enhance access to sustainable energy in informal settlements. We also demonstrate that academics are well-placed in facilitating multi-stakeholder engagements between community members, experts, and policy actors. This is pursued by drawing on the results of two energy research projects (CoDEC and AfriCLP). We employ a landscape governance framework to re-conceptualise the findings from the CoDEC and AfriCLP projects. Specifically, we use the ecological, socio-cultural, and political dimensions of landscape governance to discuss the relationships between energy demands and other landscape issues in the case study. In conclusion, the paper recommends landscape governance as a promising approach for integrating energy issues with other competing landscape interests, while also encouraging cross-sector collaboration.
Optimization of Multilayered Walls for Building Envelopes Including PCM-Based Composites
Authors: Fachinotti Victor D. , Bre Facundo , Mankel Christoph , Koenders Eduardus A. B. , Caggiano Antonio
Published: June 2020

This work proposes a numerical procedure to simulate and optimize the thermal response of a multilayered wallboard system for building envelopes, where each layer can be possibly made of Phase Change Materials (PCM)-based composites to take advantage of their Thermal-Energy Storage (TES) capacity. The simulation step consists in solving the transient heat conduction equation across the whole wallboard using the enthalpy-based finite element method. The weather is described in detail by the Typical Meteorological Year (TMY) of the building location. Taking the TMY as well as the wall azimuth as inputs, EnergyPlusTM is used to define the convective boundary conditions at the external surface of the wall. For each layer, the material is chosen from a predefined vade mecum, including several PCM-based composites developed at the Institut für Werkstoffe im Bauwesen of TU Darmstadt together with standard insulating materials (i.e., EPS or Rockwool). Finally, the optimization step consists in using genetic algorithms to determine the stacking sequence of materials across the wallboard to minimize the undesired heat loads. The current simulation-based optimization procedure is applied to the design of envelopes for minimal undesired heat losses and gains in two locations with considerably different weather conditions, viz. Sauce Viejo in Argentina and Frankfurt in Germany. In general, for each location and all the considered orientations (north, east, south and west), optimal results consist of EPS walls containing a thin layer made of the PCM-based composite with highest TES capacity, placed near the middle of the wall and closer to the internal surface.