Cadmium induces physiological and behavioral changes associated with 180 kDa NCAM lower expression and higher polysialic acid, in the African clawed Xenopus laevis tadpoles.

Heavy metals are released into the environment in increasing amounts from different natural and anthropogenic sources. Among them, cadmium contaminates aquatic habitats and represents a threat to Amphibians. To assess the risks of exposure to cadmium in the aquatic environment, we studied the survival rate of early tadpoles of Xenopus laevis under exposure to CdCl2 for 6 days in the concentration range between 0.15 and 150 µM of Cd2+. Tadpoles survived and reached stage 45 before feeding at all concentrations tested except 150 µM Cd2+, which significantly induced death. With an exposure of 15 µM Cd2+, tadpoles' mean body length decreased, heart rate increased, fastest swimming speed decreased, and distance traveled was greater compared to unexposed controls. Additionally, a witness of neuronal normal development, the neural cell adhesion molecules (NCAM) expression, was decreased. Moreover, this cell-surface glycoprotein exhibited higher polysialylation, a post-translational modification capable to reduce cell adhesion properties and to affect organ development. Our study highlights the effects of Cd2+ on a series of parameters including morphology, physiology, and behavior. They emphasize the deregulation of molecular NCAM suggesting this effector is an interesting biomarker to detect cadmic toxicity in early tadpoles.

Follicular cells protect Xenopus oocyte from abnormal maturation via integrin signaling downregulation and O-GlcNAcylation control.

Xenopus oocytes are encompassed by a layer of follicular cells that contribute to oocyte growth and meiosis in relation to oocyte maturation. However, the effects of the interaction between follicular cells and the oocyte surface on meiotic processes are unclear. Here, we investigated Xenopus follicular cell function using oocyte signaling and heterologous-expressing capabilities. We found that oocytes deprotected from their surrounding layer of follicular cells and expressing the epidermal growth factor (EGF) receptor (EGFR) and the Grb7 adaptor undergo accelerated prophase I to metaphase II meiosis progression upon stimulation by EGF. This unusual maturation unravels atypical spindle formation but is rescued by inhibiting integrin ß1 or Grb7 binding to the EGFR. In addition, we determined that oocytes surrounded by their follicular cells expressing EGFR-Grb7 exhibit normal meiotic resumption. These oocytes are protected from abnormal meiotic spindle formation through the recruitment of O-GlcNAcylated Grb7, and OGT (O-GlcNAc transferase), the enzyme responsible for O-GlcNAcylation processes, in the integrin ß1-EGFR complex. Folliculated oocytes can be forced to adopt an abnormal phenotype and exclusive Grb7 Y338 and Y188 phosphorylation instead of O-GlcNAcylation under integrin activation. Furthermore, an O-GlcNAcylation increase (by inhibition of O-GlcNAcase), the glycosidase that removes O-GlcNAc moieties, or decrease (by inhibition of OGT) amplifies oocyte spindle defects when follicular cells are absent highlighting a control of the meiotic spindle by the OGT-O-GlcNAcase duo. In summary, our study provides further insight into the role of the follicular cell layer in oocyte meiosis progression.

Diversity of sialic acids and sialoglycoproteins in gametes and at fertilization.

Sialic acids are a family of 9-carbon monosaccharides with particular physicochemical properties. They modulate the biological functions of the molecules that carry them and are involved in several steps of the reproductive process. Sialoglycoproteins participate in the balance between species recognition and specificity, and the mechanisms of these aspects remain an issue in gametes formation and binding in metazoan reproduction. Sialoglycoproteins form a specific coat at the gametes surface and specific polysialylated chains are present on marine species oocytes. Spermatozoa are submitted to critical sialic acid changes in the female reproductive tract facilitating their migration, their survival through the modulation of the female innate immune response, and the final oocyte-binding event. To decipher the role of sialic acids in gametes and at fertilization, the dynamical changes of enzymes involved in their synthesis and removal have to be further considered.

Porphyrin-Loaded Lignin Nanoparticles Against Bacteria: A Photodynamic Antimicrobial Chemotherapy Application.

The need for alternative strategies to fight bacteria is evident from the emergence of antimicrobial resistance. To that respect, photodynamic antimicrobial chemotherapy steadily rises in bacterial eradication by using light, a photosensitizer and oxygen, which generates reactive oxygen species that may kill bacteria. Herein, we report the encapsulation of 5,10,15,20-tetrakis(4-hydroxyphenyl)-21H,23H-porphyrin into acetylated lignin water-dispersible nanoparticles (THPP@AcLi), with characterization of those systems by standard spectroscopic and microscopic techniques. We observed that THPP@AcLi retained porphyrin's photophysical/photochemical properties, including singlet oxygen generation and fluorescence. Besides, the nanoparticles demonstrated enhanced stability on storage and light bleaching. THPP@AcLi were evaluated as photosensitizers against two Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, and against three Gram-positive bacteria, Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis. THPP@AcLi were able to diminish Gram-positive bacterial survival to 0.1% when exposed to low white LED light doses (4.16 J/cm2), requiring concentrations below 5 µM. Nevertheless, the obtained nanoparticles were unable to diminish the survival of Gram-negative bacteria. Through transmission electron microscopy observations, we could demonstrate that nanoparticles did not penetrate inside the bacterial cell, exerting their destructive effect on the bacterial wall; also, a high affinity between acetylated lignin nanoparticles and bacteria was observed, leading to bacterial flocculation. Altogether, these findings allow to establish a photodynamic antimicrobial chemotherapy alternative that can be used effectively against Gram-positive topic infections using the widely available natural polymeric lignin as a drug carrier. Further research, aimed to inhibit the growth and survival of Gram-negative bacteria, is likely to enhance the wideness of acetylated lignin nanoparticle applications.

Effects of Ferrocenyl 4-(Imino)-1,4-Dihydro-quinolines on Xenopus laevis Prophase I - Arrested Oocytes: Survival and Hormonal-Induced M-Phase Entry.

Xenopus oocytes were used as cellular and molecular sentinels to assess the effects of a new class of organometallic compounds called ferrocenyl dihydroquinolines that have been developed as potential anti-cancer agents. One ferrocenyl dihydroquinoline compound exerted deleterious effects on oocyte survival after 48 h of incubation at 100 µM. Two ferrocenyl dihydroquinoline compounds had an inhibitory effect on the resumption of progesterone induced oocyte meiosis, compared to controls without ferrocenyl groups. In these inhibited oocytes, no MPF (Cdk1/cyclin B) activity was detected by western blot analysis as shown by the lack of phosphorylation of histone H3. The dephosphorylation of the inhibitory Y15 residue of Cdk1 occurred but cyclin B was degraded. Moreover, two apoptotic death markers, the active caspase 3 and the phosphorylated histone H2, were detected. Only 7-chloro-1-ferrocenylmethyl-4-(phenylylimino)-1,4-dihydroquinoline (8) did not show any toxicity and allowed the assembly of a histologically normal metaphase II meiotic spindle while inhibiting the proliferation of cancer cell lines with a low IC50, suggesting that this compound appears suitable as an antimitotic agent.

Acetylated lignin nanoparticles as a possible vehicle for photosensitizing molecules.

Lignins are underused and abundant bio-sourced polymers with various potential applications. An attractive one is the development of nanoparticles for bioactive compound delivery. Here, we optimized the synthesis of hydrodispersible nanoparticles of acetylated lignin by comparing different lignin sources, degrees of acetylation and preparation methods. The formation of acetylated lignin nanoparticles in various solvents was probed by both experiments and, for the first time, a molecular dynamics simulation. We showed that dialysis is more suitable to obtain these nanoparticles than anti-solvent addition. The encapsulation of hydrophobic photosensitizing porphyrin in these nanoparticles was also demonstrated and rationalized at the molecular level, together with experiments, docking and molecular dynamics simulations. As acetylated lignin has been demonstrated to exhibit photosensitizing activity, the encapsulation of bioactive compounds in lignin nanoparticles opens the doors to a broad range of potential applications.

Effects of glyphosate and a commercial formulation Roundup® exposures on maturation of Xenopus laevis oocytes.

Pesticides are often found at high concentrations in small ponds near agricultural field where amphibians are used to live and reproduce. Even if there are many studies on the impacts of phytopharmaceutical active ingredients in amphibian toxicology, only a few are interested in the earlier steps of their life cycle. While their populations are highly threatened with extinction. The aim of this work is to characterize the effects of glyphosate and its commercial formulation Roundup® GT Max on the Xenopus laevis oocyte maturation which is an essential preparation for the laying and the fertilization. Glyphosate is an extensively used herbicide, not only known for its effectiveness but also for its indirect impacts on non-target organisms. Our results showed that exposures to both forms of glyphosate delayed this hormone-dependent process and were responsible for spontaneous maturation. Severe and particular morphogenesis abnormalities of the meiotic spindle were also observed. The MAPK pathway and the MPF did not seem to be affected by exposures. The xenopus oocyte is particularly affected by the exposures and appears as a relevant model for assessing the effects of environmental contamination.

Adverse effects of fly ashes used as immobilizing agents for highly metal-contaminated soils on Xenopus laevis oocytes survival and maturation-a study performed in the north of France with field soil extracts.

Amphibians are now recognized as the most endangered group. One of this decline causes is the degradation of their habitat through direct contamination of water, soil leaching, or runoff from surrounding contaminated soils and environments. In the North of France, the extensive industrial activities resulted in massive soil contamination by metal compounds. Mineral amendments were added to soils to decrease trace metal mobility. Because of the large areas to be treated, the use of inexpensive industrial by-products was favored. Two types of fly ashes were both tested in an experimental site with the plantation of trees in 2000. Aim of the present work was to investigate the effects of extracts from metal-contaminated soils treated or not for 10 years with fly ashes on Xenopus laevis oocyte using cell biology approaches. Indeed, our previous studies have shown that the Xenopus oocyte is a relevant model to study the metal ion toxicity. Survival and maturation of oocyte exposed to the soil extracts were evaluated by phenotypic approaches and electrophysiological recordings. An extract derived from a metal-contaminated soil treated for 10 years with sulfo-calcic ashes induced the largest effects. Membrane integrity appeared affected and ion fluxes in exposed oocytes were changed. Thus, it appeared that extracted elements from certain mineral amendments used to prevent the mobility of metals in the case of highly metal-contaminated soils could have a negative impact on X. laevis oocytes.

ApiAppS: A Project to Study and Help Practitioners in Recommending mHealth Apps and Devices to Their Patients.

The ApiAppS ongoing project aims to provide physicians with a decision support system for the prescription / recommendation of mHealth technologies. We describe the context and the components of the project which includes: 1) a technical part on modelling and implementing the decision support system, and 2) a psychosocial investigation part designed to have a better knowledge of general practitioners (GPs) and patients' expectations, beliefs and practices.

Exposures to chemical contaminants: What can we learn from reproduction and development endpoints in the amphibian toxicology literature?

Environmental contamination is one of the major factors or cofactors affecting amphibian populations. Since 2000, the number of studies conducted in laboratory conditions to understand impacts of chemical exposures increased. They aimed to characterize biological effects on amphibians. This review proposes an overview of biological responses reported after exposures to metals, phytopharmaceuticals or emerging organic contaminants and focuses on endpoints relating to reproduction and development. Due to amphibian peculiar features, these periods of their life cycle are especially critical to pollutant exposures. Despite the large range of tested compounds, the same model species are often used as biological models and morphological alterations are the most studied observations. From the results, the laboratory-to-field extrapolation remained uneasy and exposure designs have to be more elaborated to be closer to environmental conditions. Few studies proposed such experimental approaches. Lastly, gametes, embryos and larvae constitute key stages of amphibian life cycle that can be harmed by exposures to freshwater pollutants. Specific efforts have to be intensified on the earliest stages and notably germ cells.

Criteria for assessing the quality of mHealth apps: a systematic review.

Objective: Review the existing studies including an assessment tool/method to assess the quality of mHealth apps; extract their criteria; and provide a classification of the collected criteria. Methods: In accordance with the PRISMA statement, a literature search was conducted in MEDLINE, EMBase, ISI and Scopus for English language citations published from January 1, 2008 to December 22, 2016 for studies including tools or methods for quality assessment of mHealth apps. Two researchers screened the titles and abstracts of all retrieved citations against the inclusion and exclusion criteria. The full text of relevant papers was then individually examined by the same researchers. A senior researcher resolved eventual disagreements and confirmed the relevance of all included papers. The authors, date of publication, subject fields of target mHealth apps, development method, and assessment criteria were extracted from each paper. The extracted assessment criteria were then reviewed, compared, and classified by an expert panel of two medical informatics specialists and two health information management specialists. Results: Twenty-three papers were included in the review. Thirty-eight main classes of assessment criteria were identified. These were reorganized by expert panel into 7 main classes (Design, Information/Content, Usability, Functionality, Ethical Issues, Security and Privacy, and User-perceived value) with 37 sub-classes of criteria. Conclusions: There is a wide heterogeneity in assessment criteria for mHealth apps. It is necessary to define the exact meanings and degree of distinctness of each criterion. This will help to improve the existing tools and may lead to achieve a better comprehensive mHealth app assessment tool.

Maturation of Xenopus laevis oocytes under cadmium and lead exposures: Cell biology investigations.

Since amphibians are recognised as good models to assess the quality of environments, only few studies have dealt with the impacts of chemical contaminants on their gametes, while toxic effects at this stage will alter all the next steps of their life cycle. Therefore, we propose to investigate the oocyte maturation of Xenopus laevis in cadmium- and lead-contaminated conditions. The impacts of cadmium and lead ions were explored on events involved in the hormone-dependent process of maturation. In time-course experiments, cadmium, at the highest concentration, delayed and prevented the germinal vesicle breakdown. Even in the absence of progesterone this ion could also induce it. No such spontaneous maturation was observed after lead exposures. An acceleration of the process at the highest tested concentration of lead (90µM), in presence of progesterone, was recorded. Cytological observations highlighted that cadmium exposures drove severe disturbances of meiotic spindle morphogenesis. At last, cadmium exposures altered the MAPK pathway, regarding the activation of ERK2 and RSK, but also the activation and the activity of the MPF, by disturbing the state of phosphorylation of Cdc2 and histone H3. Xenopus laevis oocytes were affected by these metal ion exposures, notably by Cd2+. Signatures of these metal exposures on the oocyte maturation were detected. This germ cell appeared to be a relevant model to assess the effects of environmental contaminants such as metals.

A Cross-Sectional Study of Prominent US Mobile Health Applications: Evaluating the Current Landscape.

Mobile health (mHealth) could offer unprecedented opportunity to provide medical support closer to the users. We have selected some relevant criteria to describe 100 apps from Google Play store and Apple's App Store's top suggestions in medical category. These characteristics were compared based on the paid or free nature of the apps, the target users: consumers or healthcare professionals, and the platform: Android or iOS. Seventeen provided functionalities and 27 medical subjects covered by these apps were also extracted. Our study shows that even in top rated mHealth apps, a high proportion lacks some basic criteria regarding the quality of the apps including the presence of a privacy policy, describing content sources, participation of the target users in the app development, etc. Paid apps did not ensure better quality compared to free apps. The current mHealth market is not mature enough to be used widely and recommended by healthcare professionals.

A Collaborative Evaluation Framework for Biometric Connected Devices in Healthcare.

A large number of biometric connected devices are currently available with a variety of designs. Healthcare users cannot easily choose the reliable ones that correspond the best to their healthcare problems. The existing evaluation methods do not consider at the same time aspects of connectivity and healthcare usage. In this study, a collaborative evaluation framework for biometric connected devices in healthcare usage is proposed. This framework contains six dimensions: medical validity, technical reliability, usability, ergonomy, legal compliance, and accuracy of measurements. In a first step, these dimensions were assessed by designing a self administered questionnaire answered by the stakeholders (patients, health professionals, payers, and manufacturers). A case study was then carried out in a second step to test this framework in a project of telemonitoring for heart failure patients. The results are in favor of the efficiency of the proposed framework as a decision making tool in healthcare usage.

mHealth Quality: A Process to Seal the Qualified Mobile Health Apps.

A large number of mobile health applications (apps) are currently available with a variety of functionalities. The user ratings in the app stores seem not to be reliable to determine the quality of the apps. The traditional methods of evaluation are not suitable for fast paced nature of mobile technology. In this study, we propose a collaborative multidimensional scale to assess the quality of mHealth apps. During our process, the app quality is assessed in various aspects including medical reliability, legal consistency, ethical consistency, usability aspects, personal data privacy and IT security. A hypothetico-deductive approach was used in various working groups to define the audit criteria based on the various use cases that an app could provide. These criteria were then implemented into a web based self-administered questionnaires and the generation of automatic reports were considered. This method is on the one hand specific to each app because it allows to assess each health app according to its offered functionalities. On the other hand, this method is automatic, transferable to all apps and adapted to the dynamic nature of mobile technology.

Adoption and Use of a Mobile Health Application in Older Adults for Cognitive Stimulation.

Serious games could be used to improve cognitive functions in the elderly. We evaluated the adoption of a new tablet application dedicated to cognitive stimulation in the elderly. The Stim'Art application offers various serious games to work different cognitive functions (memory, attention, concentration, etc.). The usage of fifteen older adults was followed for six months. The type of the game, the number of launches for each game, the time spent on each game, the difficulty level, the success rate and perceived well-being of users have been studied and compared at the end of the first and the sixth months. The participants have played half an hour per day on average. The average time of playing per day in the sixth month was significantly higher than the average time of playing during the first month (p value < 7 * 10(-4)). The same result was found for the average number of game launches per day (p value < 7 * 10(-4)). However, older people seem not to launch more difficult levels in the last month. The success rate at sixth months was significantly higher than the success rate at the end of the first month (p value < 6.4 * 1010(-4)). Generally, seniors have had an improvement in their wellbeing score judged by themselves. Our study showed that the mobile application receives a good admission from users. The results are promising and can pave the way for improving cognitive function in the elderly patients. The use of tablets and the constitution of serious games in close cooperation with health professionals and elderly patients (the end user), are likely to provide satisfactory results to improve healthcare provided for elderly patients suffering from cognitive disorders.

Desenvolvendo indicadores para a gestão sustentável de resíduos sólidos nos municípios de Iranduba, Manacapuru e Novo Airão, Amazonas, Brasil / Developing indicators for sustainable management of solid waste in Iranduba, Manacapuru and Novo Airão municipalities, Amazon, Brazil

RESUMOA gestão dos resíduos sólidos é de forma consensual uma das premissas para a sustentabilidade urbana no mundo. No Brasil, o principal marco legal para o setor é a Política Nacional de Resíduos Sólidos. Instituído em agosto de 2010, o dispositivo estabeleceu diretrizes, planos e metas para todas as unidades da Federação. Considerando a precariedade do saneamento básico no norte do país, o estudo optou por desenvolver uma avaliação dos sistemas de gestão/gerenciamento dos resíduos sólidos em três municipalidades do Amazonas: Iranduba, Manacapuru e Novo Airão. Foram aplicados nove indicadores de sustentabilidade, de natureza predominantemente qualitativa, adaptados a partir de duas pesquisas predecessoras sob mesma abordagem. Como resultado final o estudo concluiu que as três municipalidades apresentaram resultados muito abaixo da média pré-estabelecida e recomendou a adoção de algumas ações prioritárias.

ABSTRACTSolid waste management is by consensus one of the premises for urban sustainability in the world. In Brazil, the main legal framework for this area is the National Solid Waste Policy. Established in August 2010, this policy institutes guidelines, plans and targets for all units of the Federation. Considering the outstanding precarious sanitation in the North of the country, this study chose to develop an assessment of solid waste management systems in three Amazon municipalities: Iranduba, Manacapuru and Novo Airão. For that, were applied nine sustainability indicators, with predominantly qualitative features, adapted from two predecessor researches under the same approach. As a result, the study concluded that the three municipalities had below-average results and recommends some priority actions.

Mobile Health Applications, in the Absence of an Authentic Regulation, Does the Usability Score Correlate with a Better Medical Reliability?

Health-related mobile applications (apps) have been shown to improve the quality of health and patient care. Their use in clinical and health-related environments is becoming more considerable. The number of health-related apps available for download has considerably increased, while the regulatory position of this new industry is not well known. Despite this lack of regulation, measuring the usability score of these apps is not difficult. We compared two samples of twenty health-related applications each. One of the samples contained the apps with top-rated usability scores, and the other contained the apps with lowest-rated usability scores. We found that a good usability score correlates with a better medical reliability of the app's content (p<0.005). In the period in which a valid regulation is still lacking, calculation and attribution of usability scores to mobile applications could be used to identify apps with better medical quality. However, the usability score method ought to be rigorous and should not be rounded off with a simple five stars rating (as is the case in the classic app stores).

Toward a use case based classification of mobile health applications.

Smartphones are growing in number and mobile health applications (apps) are becoming a commonly used way for improving the quality of health and healthcare delivery. Health related apps are mainly centralized in Medical and health&fitness categories in Google and Apple app stores. However, these apps are not easily accessible by the users. We decided to develop a system facilitating the access to these apps, to increase their visibility and usability. Various use cases for 567 health related apps in French were identified and listed incrementally. UML modeling was then used to represent these use cases and their relationships with each other and with the potential users of these apps. Thirty one different use cases were found that were then regrouped into six major categories: consulting medical information references, communicating and/or sharing the information, fulfilling a contextual need, educational tools, managing professional activities, health related management. A classification of this type would highlight the real purpose and functionalities of these apps and offers the user to search for the right app rapidly and to find it in a non-ambiguous context.

Xenopus laevis oocyte maturation is affected by metal chlorides.

Few studies have been conducted using Xenopus laevis germ cells as oocytes, though these cells offer many advantages allowing both electrophysiological studies and morphological examination. Our aim was to investigate the effects of metal (cadmium, lead, cobalt and zinc) exposures using cell biology approaches. First, cell survival was evaluated with both phenotypical and electrophysiological approaches. Secondly, the effect of metals on oocyte maturation was assessed with morphological observations and electrophysiological recordings. From survival experiments, our results showed that metal chlorides did not affect cell morphology but strongly depolarized X. laevis oocyte resting potential. In addition, cadmium chloride was able to inhibit progesterone-induced oocyte maturation. By contrast, zinc, but also to a lesser extent cadmium, cobalt and lead, were able to enhance spontaneous oocyte maturation in the absence of progesterone stimulation. Finally, electrophysiological recordings revealed that some metal chlorides (lead, cadmium) exposures could disturb calcium signaling in X. laevis oocyte by modifying calcium-activated chloride currents. Our results demonstrated the high sensitivity of X. laevis oocytes toward exogenous metals such as lead and cadmium. In addition, the cellular events recorded might have a predictive value of effects occurring later on the ability of oocytes to be fertilized. Together, these results suggest a potential use of this cellular lab model as a tool for ecotoxicological assessment of contaminated fresh waters.