bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Toxicity of Nitro-Substituted Benzenes and Zinc to Photobacterium Phosphoreum: Evaluation and QSAR Analysis
Authors: Zhang Shengnan , Su Limin , Zhang Xujia , Li Chao , Qin Weichao , Zhang Dongmei , Liang Xiaoxia , Zhao Yuanhui
Published: March 2019

The single toxicity (IC50) of zinc (Zn) and 11 nitro-substituted benzenes to Photobacterium phosphoreum were determined, respectively. On basis of single toxicity, the joint toxicity of binary mixtures of Zn and 11 nitro-substituted benzenes at different Zn concentrations of 0.2 IC50, 0.5 IC50, and 0.8 IC50 were measured. The joint toxicity was evaluated by toxic unit (TU) and additive index (AI) methods. The results indicated that the joint toxicity was not only depending on the Zn concentrations but also on the substituted groups of nitro-substituted benzenes. The quantitative structure-activity relation (QSAR) equations were developed and the results showed that the toxicity of nitro-substituted benzenes has different joint effect at the different Zn concentrations. At the Zn concentration of 0.2 IC50, the binary joint effects were mainly antagonism and the joint toxicity was negatively related to descriptors called VE2_B(p) and TIC3. At the Zn concentration of 0.5 IC50 and 0.8 IC50, the binary joint effects were mainly antagonism and simple addition, and the joint toxicity was related to the same descriptor Eig06_ AEA(dm). It indicated that the joint toxic actions were similar when combined at the medium and high concentrations of Zn.
Factors Associated with Leptospirosis in Domestic Cattle in Salakphra Wildlife Sanctuary, Thailand
Authors: Yatbantoong Nantawan , Chaiyarat Rattanawat
Published: March 2019

Leptospirosis found in cattle (Bos taurus indicus) has potentially increased in economic impact. The objective was to investigate the factors associated with leptospirosis in cattle in the protected area. We investigated the seroprevalence of leptospirosis in cattle in Salakphra Wildlife Sanctuary, Thailand. Serum was collected to investigate the seroprevalence by agglutination test and their associated factors. From a total of 513 samples, antibodies against Leptospira were detected in 92.2% of samples. Within a total of 42 herds, the serovar with the highest prevalence was L interrogans serovar Tarassovi (92.9%). Most leptospirosis was found in medium-sized herds with the highest concentrations in cattle farms close to cities (52.4%, p < 0.05). Seroprevalence was associated with herd size, raising pattern in the dry and wet seasons, grazing distance, number of years that cattle were kept in the farm, the introduction of new cattle into the farm, and keeping some pets in the farm. The results of the study suggest that keeping cattle in larger herds, raising pattern and distance, keeping period, and introducing new cattle and having pets impart potential risk of increasing leptospirosis exposure. These results indicate that cattle are important hosts of Leptospira in Thailand and may act as sentinels of Leptospira infection for wildlife and people in the protected areas.
Planning of a Health Emergency Disaster Risk Management Programme for a Chinese Ethnic Minority Community
Authors: Tam Greta , Chan Emily Ying Yang , Liu Sida
Published: March 2019

Rural populations living in poverty are the most vulnerable to disaster. Despite this increased risk of recurrent disaster, previous disaster experience is not a good predictor for disaster preparedness in these populations. This was evidenced on 31 August 2012, when a major flood occurred in Sichuan, China. A health needs assessment carried out in December 2012 showed that residents of Hongyan village, a Yi-minority community in Sichuan lacked disaster preparedness. This indicated that measures were necessary to improve Health Emergency Disaster Risk Management (Health-EDRM) in the community. Nutbeam’s planning model for health promotion was used to guide the development of a Health-EDRM programme at Hongyan Village, Liangshan Yi Autonomous Prefecture, Sichuan. Relevant information was obtained from sources such as literature review, household surveys and stakeholder interviews. A team of stakeholders conducted an interactive workshop to train villagers on disaster preparedness in March 2014. Disaster kits and equipment for Oral Rehydration Solution preparation were handed out to villagers.
Measuring the Prevalence of Adverse Childhood Experiences by Survey Research Methods
Authors: Ujhelyi Nagy Anikó , Kuritár Szabó Ildikó , Hann Endre , Kósa Karolina
Published: March 2019

Background: Child maltreatment has been firmly established as a fundamental risk factor for adult health. However, its quantification poses many questions methodologically, psychologically, and culturally alike. We carried out the first nationally representative survey research in Hungary and in Central–Eastern Europe to assess the prevalence of adverse childhood experiences (ACEs) among adults. Methods: Data were collected by an opinion research company using a screening tool of the Adverse Childhood Experiences study. Results: 25% (n = 293) of adults reported any childhood adversity; 5% (n = 59) of them had four or more ACEs. The most prevalent forms of child maltreatment were emotional (5%, n = 59) and physical abuse (5%, n = 59), sexual abuse (1%, n = 12) being the least prevalent. The most frequent dysfunctional household condition was parental divorce or separation (13%, n = 153), followed by household substance abuse (11%, n = 129). Conclusions: Nationally representative surveys on ACEs found a range of overall prevalence of various forms of child maltreatment between 14.1 and 35.2% into which our results fall. Nevertheless, our survey most likely underestimates the prevalence of child maltreatment in Hungary, reflecting the impact of a host of factors influencing awareness. Survey research methods are appropriate to obtain nationally representative data on child maltreatment that not only contribute to designing interventions but can also be used to monitor the effectiveness of interventions to improve child and adult health in the long run.
Factors Shaping Attitudes of Medical Staff towards Acceptance of the Standard Precautions
Authors: Rosiński Jerzy , Różańska Anna , Jarynowski Andrzej , Wójkowska-Mach Jadwiga ,   Polish Society of Hospital Infections Team
Published: March 2019

Standard precautions (SPs) guidelines are the minimum infection prevention practices that apply to all types of patient care, regardless of suspected or confirmed infection status of the patient. They are based on risk assessment, make use of common sense practices and personal protective equipment that protect healthcare providers from infection and prevent the spread of infection from patient to patient. The aim of this study was to determine medical staff’s attitudes towards SPs and analyse the factors shaping these attitudes. The study was conducted using a questionnaire that comprised 25 statements describing the attitudes of medical personnel towards SPs. They were designed to pinpoint the factors that determine these attitudes. There were five factors identified that shape employees’ attitudes towards SPs: assessment of the situation, favourable patterns of behaviour, negative norms, unfavourable patterns of behaviour and rationalising. The study analysed 505 questionnaires filled in by hospital workers from five Polish cities. The majority of the respondents were women (92.1%), nurses (87.5%); the average age was 41.8 and the average seniority was 19.2 years. Over one-third of the respondents worked in non-surgical (36.4%) and surgical (31.6%) wards, 12.3% were employed in intensive care units (ICUs) and 8.9% in emergency departments (EDs). The variable significantly affecting the level of acceptance of SPs was seniority: initially the support was high, then it later decreased, with the greatest decrease occurring between the third and eighth year of work. The staff of medical wards and ICUs demonstrated significantly lower support for SPs and strong environmental impact on SPs perception; low degree of acceptance among medical ward staff correlated negatively with factors from the category “favourable patterns of behaviour”. The substantially strongest support for SPs was found in ED workers. The results indicate the need for continuous education of individual groups of workers concerning the application of SPs, but also the necessity to change the organisational culture in Polish hospitals.
The Evaluation of Organizational Well-Being in An Italian Teaching Hospital Using the ANAC Questionnaire
Authors: Cortese Claudio Giovanni , Emanuel Federica , Colombo Lara , Bonaudo Marco , Politano Gianfranco , Ripa Franco , Avanzato Marilena , Dall’Occo Franca , Rinaudo Antonella , Gianino Maria Michela
Published: March 2019

In Italy, the Italian National Anti-Corruption Authority (Autorità Nazionale Anti-corruzione—ANAC) has developed a questionnaire to assess the organizational well-being of employees within public agencies. The study aimed to explore the relationship among variables in the ANAC questionnaire: Several job resources (lack of discrimination, fairness, career and professional development, job autonomy, and organizational goals’ sharing) and outcomes of well-being at work, such as health and safety at work and sense of belonging. The research was carried out among workers in an Italian hospital in Northwest Italy (N = 1170), through an online self-report questionnaire. Data were grouped into two job categories: Clinical staff (N = 939) and non-clinical staff (N = 231). The hypothesized model was tested across the two groups through multi-group structural equation modeling. Results showed that health and safety at work and sense of belonging had significant positive relationships with the other variables; some differences emerged between the determinants of the two outcomes and among groups. The study aims to identify some reflections and suggestions regarding the assessment of well-being in the health care sector; implications for practice are identified to promote organizational well-being and health in organizations.
The Spatial and Heterogeneity Impacts of Population Urbanization on Fine Particulate (PM2.5) in the Yangtze River Economic Belt, China
Authors: Xie Weiwei , Deng Hongbing , Chong Zhaohui
Published: March 2019

This paper addresses the effect of population urbanization on Fine Particulate (PM2.5) in the Yangtze River Economic Belt in China from 2006 to 2016 by employing PM2.5 remote sensing data and using the Stochastic Impacts by Regression on Population, Affluence and Technology (STIRPAT) model. The study contributes to the growing empirical literature by addressing heterogeneity, spillover, and dynamic effects in the dynamic spatial panel modeling process simultaneously. The empirical results show that population urbanization has a significant impact on PM2.5 with a positive spillover effect and a dynamic effect being detected and controlled. The heterogeneity effects of population urbanization on PM2.5 due to geographical positions show evidence of an obvious inverted U-shaped curve relationship in the upstream area and an increasing function curve in the midstream and downstream areas. The heterogeneity effects due to population urbanization levels show that an inverted N-shape curve relationship exists in low and medium urbanization level areas, while a U-shape curve relationship exists in high urbanization level areas. It is hoped that this study will inform the local governments about the heterogeneity of population urbanization and spillover effects of air pollution when addressing air pollution control.
No Established Link between Repeated Transient Chokes and Chronic Traumatic Encephalopathy Related Effects. Comment on Lim, L.J.H. et al. Dangers of Mixed Martial Arts in the Development of Chronic Traumatic Encephalopathy. Int. J. Environ. Res. Public Health 2019, 16, 254
Authors: Stellpflug Samuel J.
Published: March 2019

This letter to the editor is in response to “Dangers of Mixed Martial Arts in the Development of Chronic Traumatic Encephalopathy” by authors Lim, Ho, and Ho, which was published in the International Journal of Environmental Research and Public Health (2019; 16: 254). This communication clarifies some potentially misleading word choices by the authors and addresses the insinuated, but not established, link between repeated transient choking episodes during martial arts training and a gradual decline in neuropsychiatric testing in the patient presented in the report.
Waste Mismanagement in Developing Countries: A Review of Global Issues
Authors: Ferronato Navarro , Torretta Vincenzo
Published: March 2019

Environmental contamination due to solid waste mismanagement is a global issue. Open dumping and open burning are the main implemented waste treatment and final disposal systems, mainly visible in low-income countries. This paper reviews the main impacts due to waste mismanagement in developing countries, focusing on environmental contamination and social issues. The activity of the informal sector in developing cities was also reviewed, focusing on the main health risks due to waste scavenging. Results reported that the environmental impacts are pervasive worldwide: marine litter, air, soil and water contamination, and the direct interaction of waste pickers with hazardous waste are the most important issues. Many reviews were published in the scientific literature about specific waste streams, in order to quantify its effect on the environment. This narrative literature review assessed global issues due to different waste fractions showing how several sources of pollution are affecting the environment, population health, and sustainable development. The results and case studies presented can be of reference for scholars and stakeholders for quantifying the comprehensive impacts and for planning integrated solid waste collection and treatment systems, for improving sustainability at a global level.
‘It’s Important to Make Changes.’ Insights about Motivators and Enablers of Healthy Lifestyle Modification from Young Aboriginal Men in Western Australia
Authors: Seear Kimberley H. , Lelievre Matthew P. , Atkinson David N. , Marley Julia V.
Published: March 2019

Lifestyle modification can improve the health of people with or at risk of non-communicable diseases; however, initiating and maintaining positive health behaviours including healthy eating and physical activity is challenging. Young remote Aboriginal people who had successfully made significant healthy lifestyle changes were sought out to explore how they achieved this success. Four Aboriginal men aged 20–35 years were identified and consented to participate. Their perceptions of motivation for change, strategies, and facilitators and barriers were explored through in-depth interviews. Themes developed from the interviews included self-efficacy, self-reliance, and increased knowledge and altered health beliefs underpinning change. Participants with diabetes were highly motivated to avoid diabetes complications and had a strong belief that their actions could achieve this. In a setting with high levels of disadvantage, participants had relatively favourable socioeconomic circumstances with solid social supports. These findings highlight that lifestyle modification programs that foster internal motivation, enhance key health knowledge, and modify health beliefs and risk perception are needed. Increasing diabetes awareness among at-risk young people is important, emphasising the largely preventable and potentially reversible nature of the condition. Broad health improvements and individual changes will be facilitated by equitable socioeconomic circumstances and environments that support health.
Impact of OM-85 Given during Two Consecutive Years to Children with a History of Recurrent Respiratory Tract Infections: A Retrospective Study
Authors: Esposito Susanna , Bianchini Sonia , Polinori Ilaria , Principi Nicola
Published: March 2019

In otherwise healthy infants and young children, respiratory tract infections (RTIs) are extremely common. Clinical data have shown that OM-85 could prevent respiratory recurrences in children. However, further studies are needed to explore the true importance of OM-85 in clinical practice. In addition, an unsolved problem is the efficacy of OM-85 when it is administered for two consecutive years. Moreover, another open question is the safety of OM-85 when co-administered with the influenza vaccine. In order to solve these unanswered issues, 200 children aged three to six years with a history of recurrent RTIs, defined as at least six documented episodes of acute RTI in a single year, who had received OM-85 (Broncho-Vaxom®; OM Pharma, a Vifor Pharma Group Company, Geneva, Switzerland) for two consecutive years (3.5 mg once a day for 10 days for 3 months of each year) were selected and matched based on age, sex, and period of evaluation with children with recurrent RTIs who did not receive OM-85. In the group of children treated with OM-85, the number of patients who did not experience any new episode of RTI, as well as the number of RTIs, wheezing episodes, medical visits, and prescribed antibiotic courses, were significantly lower than that in the group not treated with OM-85. The results were similar in the first and second year of OM-85 administration. A minority of patients showed mild adverse events, and the safety profile was overall good, including in the 49 children who received the influenza vaccination within one month from the beginning of the first cycle of OM-85. Our data suggest that OM-85 can effectively and safely reduce the risk of new infective episodes in children with recurrent RTIs and that a second yearly course of lysate administration can be useful to maintain protection, particularly when the diagnosis of recurrent RTIs is made in younger children for whom it is likely that definitive maturation of the immune system still requires a long time.
Cleaning Staff’s Attitudes about Hand Hygiene in a Metropolitan Hospital in Australia: A Qualitative Study
Authors: Sendall Marguerite C. , McCosker Laura K. , Halton Kate
Published: March 2019

Background: In 2009, the National Hand Hygiene Initiative (NHHI) was implemented in hospitals across Australia with the aim of improving hand hygiene practices and reducing healthcare-associated infections. Audits conducted post-implementation showed the lowest rates of compliance with hand hygiene practices are among operational staff including hospital cleaners. There is limited information about hand hygiene issues in hospital cleaners to inform development of evidence-based interventions to improve hand hygiene compliance in this group. Aim: This qualitative study was undertaken to explore the attitudes of hospital cleaning staff regarding hand hygiene and the National Hand Hygiene Initiative. Methodology: Focus groups were conducted with 12 cleaning staff at a large Australian hospital implementing the National Hand Hygiene Initiative. Findings: Hospital cleaners recognise the importance of hand hygiene in preventing healthcare-associated infections. Cleaners cite peer support, leadership, and the recognition and reward of those excelling in hand hygiene as strong motivators. Barriers to optimal hand hygiene practice include the presence of multiple conflicting guidelines, hand hygiene “overload” and a lack of contextualised education programs. This exploratory qualitative study reveals three themes about attitudes of hospital cleaning staff towards hand hygiene. These themes are: (1) “The culture of hand hygiene: It’s drummed into us”; (2) “Reminders and promotion for hand hygiene: We just need a big ‘Please wash your hands’ sign”; and (3) “The personal value of hand hygiene: Like he said, it’s second nature to us”. Conclusion: Hand-hygiene messages and training need to be more consistent and contextualised to achieve improvements in hand hygiene practices in hospital cleaning staff in Australia.
Complementary Role of P2 and Adenosine Receptors in ATP Induced-Anti-Apoptotic Effects Against Hypoxic Injury of HUVECs
Authors: Feliu Catherine , Peyret Hélène , Poitevin Gael , Cazaubon Yoann , Oszust Floriane , Nguyen Philippe , Millart Hervé , Djerada Zoubir
Published: March 2019

Background: Vascular endothelial injury during ischemia generates apoptotic cell death and precedes apoptosis of underlying tissues. We aimed at studying the role of extracellular adenosine triphosphate (ATP) on endothelial cells protection against hypoxia injury. Methods: In a hypoxic model on endothelial cells, we quantified the extracellular concentration of ATP and adenosine. The expression of mRNA (ectonucleotidases, adenosine, and P2 receptors) was measured. Apoptosis was evaluated by the expression of cleaved caspase 3. The involvement of P2 and adenosine receptors and signaling pathways was investigated using selective inhibitors. Results: Hypoxic stress induced a significant increase in extracellular ATP and adenosine. After a 2-h hypoxic injury, an increase of cleaved caspase 3 was observed. ATP anti-apoptotic effect was prevented by suramin, pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), and CGS15943, as well as by selective A2A, A2B, and A3 receptor antagonists. P2 receptor-mediated anti-apoptotic effect of ATP involved phosphoinositide 3-kinase (PI3K), extracellular signal-regulated kinases (ERK1/2), mitoKATP, and nitric oxide synthase (NOS) pathways whereas adenosine receptor-mediated anti-apoptotic effect involved ERK1/2, protein kinase A (PKA), and NOS. Conclusions: These results suggest a complementary role of P2 and adenosine receptors in ATP-induced protective effects against hypoxia injury of endothelial. This could be considered therapeutic targets to limit the development of ischemic injury of organs such as heart, brain, and kidney.
Use of Multifactorial Treatments to Address the Challenge of Translating Experimental Myocardial Infarct Reduction Strategies
Authors: Horton Julie L. , Virag Jitka
Published: March 2019

Myocardial tissue damage that occurs during an ischemic event leads to a spiraling deterioration of cardiac muscle structural and functional integrity. Reperfusion is the only known efficacious strategy and is the most commonly used treatment to reduce injury and prevent remodeling. However, timing is critical, and the procedure is not always feasible for a variety of reasons. The complex molecular basis for cardioprotection has been studied for decades but formulation of a viable therapeutic that can significantly attenuate myocardial injury remains elusive. In this review, we address barriers to the development of a fruitful approach that will substantially improve the prognosis of those suffering from this widespread and largely unmitigated disease. Furthermore, we proffer that ephrinA1, a candidate molecule that satisfies many of the important criteria discussed, possesses robust potential to overcome these hurdles and thus offers protection that surpasses the limitations currently observed.
Effects of Pressure and Temperature on the Atomic Fluctuations of Dihydrofolate Reductase from a Psychropiezophile and a Mesophile
Authors: Huang Qi , Rodgers Jocelyn M. , Hemley Russell J. , Ichiye Toshiko
Published: March 2019

Determining the effects of extreme conditions on proteins from “extremophilic” and mesophilic microbes is important for understanding how life adapts to living at extremes as well as how extreme conditions can be used for sterilization and food preservation. Previous molecular dynamics simulations of dihydrofolate reductase (DHFR) from a psychropiezophile (cold- and pressure-loving), Moritella profunda (Mp), and a mesophile, Escherichia coli (Ec), at various pressures and temperatures indicate that atomic fluctuations, which are important for enzyme function, increase with both temperature and pressure. Here, the factors that cause increases in atomic fluctuations in the simulations are examined. The fluctuations increase with temperature not only because of greater thermal energy and thermal expansion of the protein but also because hydrogen bonds between protein atoms are weakened. However, the increase in fluctuations with pressure cannot be due to thermal energy, which remains constant, nor the compressive effects of pressure, but instead, the hydrogen bonds are also weakened. In addition, increased temperature causes larger increases in fluctuations of the loop regions of MpDHFR than EcDHFR, and increased pressure causes both increases and decreases in fluctuations of the loops, which differ between the two.
The Molecular Mechanism of Vitamin E as a Bone-Protecting Agent: A Review on Current Evidence
Authors: Wong Sok Kuan , Mohamad Nur-Vaizura , Ibrahim Nurul ‘Izzah , Chin Kok-Yong , Shuid Ahmad Nazrun , Ima-Nirwana Soelaiman
Published: March 2019

Bone remodelling is a tightly-coordinated and lifelong process of replacing old damaged bone with newly-synthesized healthy bone. In the bone remodelling cycle, bone resorption is coupled with bone formation to maintain the bone volume and microarchitecture. This process is a result of communication between bone cells (osteoclasts, osteoblasts, and osteocytes) with paracrine and endocrine regulators, such as cytokines, reactive oxygen species, growth factors, and hormones. The essential signalling pathways responsible for osteoclastic bone resorption and osteoblastic bone formation include the receptor activator of nuclear factor kappa-B (RANK)/receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG), Wnt/β-catenin, and oxidative stress signalling. The imbalance between bone formation and degradation, in favour of resorption, leads to the occurrence of osteoporosis. Intriguingly, vitamin E has been extensively reported for its anti-osteoporotic properties using various male and female animal models. Thus, understanding the underlying cellular and molecular mechanisms contributing to the skeletal action of vitamin E is vital to promote its use as a potential bone-protecting agent. This review aims to summarize the current evidence elucidating the molecular actions of vitamin E in regulating the bone remodelling cycle.
Between Innate and Adaptive Immune Responses: NKG2A, NKG2C, and CD8+ T Cell Recognition of HLA-E Restricted Self-Peptides Acquired in the Absence of HLA-Ia
Authors: Pump Wiebke C. , Kraemer Thomas , Huyton Trevor , Hò Gia-Gia T. , Blasczyk Rainer , Bade-Doeding Christina
Published: March 2019

On healthy cells the non-classical HLA class Ib molecule HLA-E displays the cognate ligand for the NK cell receptor NKG2A/CD94 when bound to HLA class I signal peptide sequences. In a pathogenic situation when HLA class I is absent, HLA-E is bound to a diverse set of peptides and enables the stimulatory NKG2C/CD94 receptor to bind. The activation of CD8+ T cells by certain p:HLA-E complexes illustrates the dual role of this low polymorphic HLA molecule in innate and adaptive immunity. Recent studies revealed a shift in the HLA-E peptide repertoire in cells with defects in the peptide loading complex machinery. We recently showed that HLA-E presents a highly diverse set of peptides in the absence of HLA class Ia and revealed a non-protective feature against NK cell cytotoxicity mediated by these peptides. In the present study we have evaluated the molecular basis for the impaired NK cell inhibition by these peptides and determined the cell surface stability of individual p:HLA-E complexes and their binding efficiency to soluble NKG2A/CD94 or NKG2C/CD94 receptors. Additionally, we analyzed the recognition of these p:HLA-E epitopes by CD8+ T cells. We show that non-canonical peptides provide stable cell surface expression of HLA-E, and these p:HLA-E complexes still bind to NKG2/CD94 receptors in a peptide-restricted fashion. Furthermore, individual p:HLA-E complexes elicit activation of CD8+ T cells with an effector memory phenotype. These novel HLA-E epitopes provide new implications for therapies targeting cells with abnormal HLA class I expression.
Change in Renal Glomerular Collagens and Glomerular Filtration Barrier-Related Proteins in a Dextran Sulfate Sodium-Induced Colitis Mouse Model
Authors: Chang Chia-Jung , Wang Pi-Chao , Huang Tzou-Chi , Taniguchi Akiyoshi
Published: March 2019

Renal disease is not rare among patients with inflammatory bowel disease (IBD) and is gaining interest as a target of research. However, related changes in glomerular structural have rarely been investigated. This study was aimed at clarifying the changes in collagens and glomerular filtration barrier (GFB)-related proteins of glomeruli in a dextran sulfate sodium (DSS)-induced colitis mouse model. Acute colitis was induced by administering 3.5% DSS in Slc:ICR strain mice for eight days. Histological changes to glomeruli were examined by periodic acid-Schiff (PAS) and Masson’s trichrome staining. Expressions of glomerular collagens and GFB-related proteins were analyzed by immunofluorescent staining and Western blot analysis. DSS-colitis mice showed an elevated disease activity index (DAI), colon shortening, massive cellular infiltration and colon damage, confirming that DSS-colitis mice can be used as an IBD animal model. DSS-colitis mice showed increased glycoprotein and collagen deposition in glomeruli. Interestingly, we observed significant changes in glomerular collagens, including a decrease in type IV collagen, and an increment in type I and type V collagens. Moreover, declined GFB-related proteins expressions were detected, including synaptopodin, podocalyxin, nephrin and VE-cadherin. These results suggest that renal disease in DSS-colitis mice might be associated with changes in glomerular collagens and GFB-related proteins. These findings are important for further elucidation of the clinical pathological mechanisms underlying IBD-associated renal disease.
A Systematic Review of Phytochemistry, Pharmacology and Pharmacokinetics on Astragali Radix: Implications for Astragali Radix as a Personalized Medicine
Authors: Guo Zhenzhen , Lou Yanmei , Kong Muyan , Luo Qing , Liu Zhongqiu , Wu Jinjun
Published: March 2019

Astragali radix (AR) is one of the most widely used traditional Chinese herbal medicines. Modern pharmacological studies and clinical practices indicate that AR possesses various biological functions, including potent immunomodulation, antioxidant, anti-inflammation and antitumor activities. To date, more than 200 chemical constituents have been isolated and identified from AR. Among them, isoflavonoids, saponins and polysaccharides are the three main types of beneficial compounds responsible for its pharmacological activities and therapeutic efficacy. After ingestion of AR, the metabolism and biotransformation of the bioactive compounds were extensive in vivo. The isoflavonoids and saponins and their metabolites are the major type of constituents absorbed in plasma. The bioavailability barrier (BB), which is mainly composed of efflux transporters and conjugating enzymes, is expected to have a significant impact on the bioavailability of AR. This review summarizes studies on the phytochemistry, pharmacology and pharmacokinetics on AR. Additionally, the use of AR as a personalized medicine based on the BB is also discussed, which may provide beneficial information to achieve a better and more accurate therapeutic response of AR in clinical practice.
Zoledronate Enhances Osteocyte-Mediated Osteoclast Differentiation by IL-6/RANKL Axis
Authors: Kim Hyung Joon , Kim Ha Jin , Choi YunJeong , Bae Moon-Kyoung , Hwang Dae Seok , Shin Sang-Hun , Lee Jae-Yeol
Published: March 2019

Bisphosphonates are one of the most widely used synthetic pyrophosphate analogues for the treatment of bone resorbing diseases such as osteoporosis, multiple myeloma, and bone metastases. Although the therapeutic usefulness of bisphosphonates mainly depends on their anti-osteoclastogenic effect, a severe side-effect of bisphosphonates called bisphosphonate-related osteonecrosis of the jaw (BRONJ) could not be explained by the anti-osteoclastogenic effect of bisphosphonates. In the present study, we have evaluated the changes in osteoclastogenesis- or osteoblastogenesis-supporting activities of osteocytes induced by bisphosphonates. Zoledronate, a nitrogen-containing bisphosphonate, markedly increased both the receptor activator of nuclear factor kB ligand (RANKL) as well as sclerostin in osteocyte-like MLO-Y4 cells, which were functionally revalidated by osteoclast/osteoblast generating activities of the conditioned medium obtained from zoledronate-treated MLO-Y4 cells. Of note, the zoledronate treatment-induced upregulation of the RANKL expression was mediated by autocrine interleukin-6 (IL-6) and subsequent activation of the signal transducer and activator of transcription 3 (STAT3) pathway. These results were evidenced by the blunted RANKL expression in the presence of a Janus activated kinase (JAK2)/STAT3 inhibitor, AG490. Also, the osteoclastogenesis-supporting activity was significantly decreased in zoledronate-treated MLO-Y4 cells in the presence of IL-6 neutralizing IgG compared to that of the control IgG. Thus, our results show previously unanticipated effects of anti-bone resorptive bisphosphonate and suggest a potential clinical importance of osteocytes in BRONJ development.
Caffeic Acid Phenethyl Ester Rescues Pulmonary Arterial Hypertension through the Inhibition of AKT/ERK-Dependent PDGF/HIF-1α In Vitro and In Vivo
Authors: Cheng Chin-Chang , Chi Pei-Ling , Shen Min-Ci , Shu Chih-Wen , Wann Shue-Ren , Liu Chun-Peng , Tseng Ching-Jiunn , Huang Wei-Chun
Published: March 2019

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial proliferation and remodeling, resulting in a specific increase in right ventricle systolic pressure (RVSP) and, ultimately right ventricular failure. Recent studies have demonstrated that caffeic acid phenethyl ester (CAPE) exerts a protective role in NF-κB-mediated inflammatory diseases. However, the effect of CAPE on PAH remains to be elucidated. In this study, monocrotaline (MCT) was used to establish PAH in rats. Two weeks after the induction of PAH by MCT, CAPE was administrated by intraperitoneal injection once a day for two weeks. Pulmonary hemodynamic measurements and pulmonary artery morphological assessments were examined. Our results showed that administration of CAPE significantly suppressed MCT-induced vascular remodeling by decreasing the HIF-1α expression and PDGF-BB production, and improved in vivo RV systolic performance in rats. Furthermore, CAPE inhibits hypoxia- and PDGF-BB-induced HIF-1α expression by decreasing the activation of the AKT/ERK pathway, which results in the inhibition of human pulmonary artery smooth muscle cells (hPASMCs) proliferation and prevention of cells resistant to apoptosis. Overall, our data suggest that HIF-1α is regarded as an alternative target for CAPE in addition to NF-κB, and may represent a promising therapeutic agent for the treatment of PAH diseases.
Transcriptome Analysis Reveals Cotton (Gossypium hirsutum) Genes That Are Differentially Expressed in Cadmium Stress Tolerance
Authors: Han Mingge , Lu Xuke , Yu John , Chen Xiugui , Wang Xiaoge , Malik Waqar Afzal , Wang Junjuan , Wang Delong , Wang Shuai , Guo Lixue , Chen Chao , Cui Ruifeng , Yang Xiaoming , Ye Wuwei
Published: March 2019

High concentrations of heavy metals in the soil should be removed for environmental safety. Cadmium (Cd) is a heavy metal that pollutes the soil when its concentration exceeds 3.4 mg/kg. Although the potential use of cotton to remediate heavy Cd-polluted soils is known, little is understood about the molecular mechanisms of Cd tolerance. In this study, transcriptome analysis was used to identify Cd tolerance genes and their potential mechanisms in cotton. We exposed cotton plants to excess Cd and identified 4627 differentially expressed genes (DEGs) in the root, 3022 DEGs in the stem and 3854 DEGs in the leaves through RNA-Seq analysis. Among these genes were heavy metal transporter coding genes (ABC, CDF, HMA, etc.), annexin genes and heat shock genes (HSP), amongst others. Gene ontology (GO) analysis showed that the DEGs were mainly involved in the oxidation–reduction process and metal ion binding. The DEGs were mainly enriched in two pathways, the influenza A and pyruvate pathway. GhHMAD5, a protein containing a heavy-metal binding domain, was identified in the pathway to transport or to detoxify heavy metal ions. We constructed a GhHMAD5 overexpression system in Arabidopsis thaliana that showed longer roots compared to control plants. GhHMAD5-silenced cotton plants showed more sensitivity to Cd stress. The results indicate that GhHMAD5 is involved in Cd tolerance, which gives a preliminary understanding of the Cd tolerance mechanism in upland cotton. Overall, this study provides valuable information for the use of cotton to remediate soils polluted with Cd and potentially other heavy metals.
Increased Brain-Derived Neurotrophic Factor in Lumbar Dorsal Root Ganglia Contributes to the Enhanced Exercise Pressor Reflex in Heart Failure
Authors: Schiller Alicia M. , Hong Juan , Xia Zhiqiu , Wang Han-Jun
Published: March 2019

An exaggerated exercise pressor reflex (EPR) is associated with excessive sympatho-excitation and exercise intolerance in the chronic heart failure (CHF) state. We hypothesized that brain-derived neurotrophic factor (BDNF) causes the exaggerated EPR via sensitizing muscle mechanosensitive afferents in CHF. Increased BDNF expression was observed in lumbar dorsal root ganglia (DRGs) from CHF rats compared to sham rats. Immunofluorescence data showed a greater increase in the number of BDNF-positive neurons in medium and large-sized DRG subpopulations from CHF rats. Patch clamp data showed that incubation with BDNF for 4–6 h, significantly decreased the current threshold-inducing action potential (AP), threshold potential and the number of APs during current injection in Dil-labeled isolectin B4 (IB4)-negative medium-sized DRG neurons (mainly mechano-sensitive) from sham rats. Compared to sham rats, CHF rats exhibited an increased number of APs during current injection in the same DRG subpopulation, which was significantly attenuated by 4-h incubation with anti-BDNF. Finally, chronic epidural delivery of anti-BDNF attenuated the exaggerated pressor response to either static contraction or passive stretch in CHF rats whereas this intervention had no effect on the pressor response to hindlimb arterial injection of capsaicin. These data suggest that increased BDNF in lumbar DRGs contributes to the exaggerated EPR in CHF.
Trypanosoma brucei Interaction with Host: Mechanism of VSG Release as Target for Drug Discovery for African Trypanosomiasis
Authors: Moreno Cláudia Jassica Gonçalves , Temporão Adriana , Torres Taffarel , Sousa Silva Marcelo
Published: March 2019

The protozoan Trypanosoma brucei, responsible for animal and human trypanosomiasis, has a family of major surface proteases (MSPs) and phospholipase-C (PLC), both involved in some mechanisms of virulence during mammalian infections. During parasitism in the mammalian host, this protozoan is exclusively extracellular and presents a robust mechanism of antigenic variation that allows the persistence of infection. There has been incredible progress in our understanding of how variable surface glycoproteins (VSGs) are organised and expressed, and how expression is switched, particularly through recombination. The objective of this manuscript is to create a reflection about the mechanisms of antigenic variation in T. brucei, more specifically, in the process of variable surface glycoprotein (VSG) release. We firstly explore the mechanism of VSG release as a potential pathway and target for the development of anti-T. brucei drugs.
Microbe-Host Communication by Small RNAs in Extracellular Vesicles: Vehicles for Transkingdom RNA Transportation
Authors: Lee Heon-Jin
Published: March 2019

Extracellular vesicles (EVs) are evolutionary well-conserved nano-sized membranous vesicles that are secreted by both prokaryotic and eukaryotic cells. Recently, they have gained great attention for their proposed roles in cell-to-cell communication, and as biomarkers for human disease. In particular, small RNAs (sRNAs) contained within EVs have been considered as candidate interspecies-communication molecules, due to their demonstrated capacity to modulate gene expression in multiple cell types and species. While research into this field is in its infancy, elucidating the mechanisms that underlie host–microbe interactions and communications promises to impact many fields of biological research, including human health and medicine. Thus, this review discussed the results of recent studies that have examined the ways in which EVs and sRNAs mediate ‘microbe–host’ and ‘host–microbe’ interspecies communication.
Design and Synthesis of a New Soluble Natural β-Carboline Derivative for Preclinical Study by Intravenous Injection
Authors: Marx Sébastien , Bodart Laurie , Tumanov Nikolay , Wouters Johan
Published: March 2019

Harmine is a natural β-carboline compound showing several biological activities, including antiproliferative properties, but this soluble natural molecule lacks selectivity. Harmine derivatives were reported to overcome this problem, but they are usually poorly soluble. Here, we designed and synthesized a new 2, 7, 9-trisubstituted molecule (1-methyl-7-(3-methylbutoxy)-9-propyl-2-[(pyridin-2-yl)methyl]-9H-pyrido[3,4-b]indol-2-ium bromide) with a solubility of 1.87 ± 0.07 mg/mL in a simulated injection vehicle. This compound is stable for at least 72 h in acidic and physiological conditions (pH 1.1 and 7.4) as well as in a simulated injection vehicle (physiological liquid + 0.1% Tween80®). Solubility in those media is 1.06 ± 0.08 mg/mL and 1.62 ± 0.13 mg/mL at pH 7.4 and 1. The synthesized molecule displays a significant activity on five different cancer cell lines (IC50 range from 0.2 to 2 µM on A549, MDA-MB-231, PANC-1, T98G and Hs683 cell lines). This compound is also more active on cancer cells (MDA-MB-231) than on normal cells (MCF-10a) at IC50 concentrations. Due to its high activity at low concentration, such solubility values should be sufficient for further in vivo antitumoral activity evaluation via intravenous injection.
Creating a Multimodal Translation Tool and Testing Machine Translation Integration Using Touch and Voice
Authors: Teixeira Carlos S. C. , Moorkens Joss , Turner Daniel , Vreeke Joris , Way Andy
Published: March 2019

Commercial software tools for translation have, until now, been based on the traditional input modes of keyboard and mouse, latterly with a small amount of speech recognition input becoming popular. In order to test whether a greater variety of input modes might aid translation from scratch, translation using translation memories, or machine translation postediting, we developed a web-based translation editing interface that permits multimodal input via touch-enabled screens and speech recognition in addition to keyboard and mouse. The tool also conforms to web accessibility standards. This article describes the tool and its development process over several iterations. Between these iterations we carried out two usability studies, also reported here. Findings were promising, albeit somewhat inconclusive. Participants liked the tool and the speech recognition functionality. Reports of the touchscreen were mixed, and we consider that it may require further research to incorporate touch into a translation interface in a usable way.
High-Resolution Computed Tomography (HRCT) Reflects Disease Progression in Patients with Idiopathic Pulmonary Fibrosis (IPF): Relationship with Lung Pathology
Authors: Cocconcelli Elisabetta , Balestro Elisabetta , Biondini Davide , Barbiero Giulio , Polverosi Roberta , Calabrese Fiorella , Pezzuto Federica , Lacedonia Donato , Rea Federico , Schiavon Marco , Bazzan Erica , Foschino Barbaro Maria Pia , Turato Graziella , Spagnolo Paolo , Cosio Manuel G. , Saetta Marina
Published: March 2019

High-Resolution Computed Tomography (HRCT) plays a central role in diagnosing Idiopathic Pulmonary Fibrosis (IPF) while its role in monitoring disease progression is not clearly defined. Given the variable clinical course of the disease, we evaluated whether HRCT abnormalities predict disease behavior and correlate with functional decline in untreated IPF patients. Forty-nine patients (with HRCT1) were functionally categorized as rapid or slow progressors. Twenty-one had a second HRCT2. Thirteen patients underwent lung transplantation and pathology was quantified. HRCT Alveolar (AS) and Interstitial Scores (IS) were assessed and correlated with Forced Vital Capacity (FVC) decline between HRCT1 and HRCT2. At baseline, AS was greater in rapids than in slows, while IS was similar in the two groups. In the 21 subjects with HRCT2, IS increased over time in both slows and rapids, while AS increased only in rapids. The IS change from HRCT1 to HRCT2 normalized per month correlated with FVC decline/month in the whole population, but the change in AS did not. In the 13 patients with pathology, the number of total lymphocytes was higher in rapids than in slows and correlated with AS. Quantitative estimation of HRCTs AS and IS reflects the distinct clinical and pathological behavior of slow and rapid decliners. Furthermore, AS, which reflects the immune/inflammatory infiltrate in lung tissue, could be a useful tool to differentiate rapid from slow progressors at presentation.
Uncovering Female Child Sexual Offenders—Needs and Challenges for Practice and Research
Authors: Tozdan Safiye , Briken Peer , Dekker Arne
Published: March 2019

This article provides a short literature overview on female child sexual offenders (FCSO) focusing on the discrepancy between prevalence rates from different sources, characteristics of FCSO and their victims, as well as the societal “culture of denial” surrounding these women. FCSO are a powerful social taboo. Even professionals in the healthcare or justice system were shown to respond inappropriately in cases of child sexual abuse committed by women. As a result, offences of FCSO may be underreported and therefore difficult to research. The lack of scientific data on FSCO lowers the quality of child protection and treatment services. We therefore deem it particularly necessary for professionals in health care to break the social taboo that is FCSO and to further stimulate research on the topic of FCSO. We provide some general implications for professionals in health care systems as well as specific recommendations for researchers. We end with an overall conclusion.
The Extended Use of Eculizumab in Pregnancy and Complement Activation–Associated Diseases Affecting Maternal, Fetal and Neonatal Kidneys—The Future Is Now?
Authors: Stefanovic Vedran
Published: March 2019

Excessive complement activation is involved in the pathogenesis of many diseases and the kidney is an organ with particular susceptibility to complement-mediated injury. Apart from paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), there are several other diseases with clear evidence of complement activation affecting both maternal and fetal kidneys during pregnancy and causing long-term adverse outcomes. Several novel drugs have been recently developed for blocking the complement cascade, including purified plasma proteins, new monoclonal antibodies, recombinant proteins, small molecules, and small interfering RNA agents. Eculizumab, the humanized monoclonal IgG2/4-antibody targeting C5 was approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of two rare diseases: PNH in 2007 and aHUS in 2011. There is an increasing number of publications of successful use of eculizumab for off-label indications, e.g., in pregnant women with antiphospholipid syndrome, sickle-cell anemia, and HELLP syndrome. These severe diseases are associated with both high maternal and fetal morbidity and mortality rate and substantial prematurity. Eculizumab has considerably improved overall outcome of patients with PNH and aHUS, enabling safe pregnancy for many women. Prolongation of pregnancy and the use of eculizumab, even for only a few weeks, may protect not only maternal renal function, but also alleviate acute and long-term renal consequences of prematurity in offspring.