Burns are among the most challenging injuries to manage. Although the great advances in treatment that have been made have arguably been sufficient to address the related medical challenges of the past century, modern society now faces even greater difficulties. These are caused predominantly by increase in population and lifespan, which frequently are not matched by an increased effectiveness in the maintenance of health and quality of life.Because aging people are more prone to illness, keeping people healthy and active, while managing healthcare costs, is an important societal challenge. The ethical and economic dilemma is how to achieve equality in quality of care while simultaneously decreasing the cost of care for an ever-expanding number of people.Burn injuries, leading to significant mortality and morbidity all over the word, are among the most devastating of all injuries, with outcomes varying from physical impairments and disabilities to emotional and mental consequences. The management of burns and their sequelee, even in the well-equipped, modern burn units of advanced and affluent societies, remains demanding and extremely costly.Consequently, considerable effort is needed to define an appropriate strategy for the successful implementation of therapeutic treatments in terms of performance and cost. In the context of these complex needs, biomaterials and related novel technologies may play an important role because it is possible to precisely customize their overall properties.Generally, burns cause significant fluid loss and extensive tissue damage resulting from deep wounds by impairing many of the vital functions performed by the skin. Wound infection, which further exacerbates the local tissue damage, is a common complication, and systemic inflammatory and immunological responses can arise that may lead to a higher predisposition toward life-threatening sepsis and multi-organ failure. In such Regeneration of tissues, andPrevention of tissue deterioration.These considerations suggest an expanded emphasis on the following to satisfy the growing need for effective burn treatment:This note outlines the clinical needs that could be met by innovative bioactive materials in the near future, including the repair and regeneration of soft tissues and the rapid, low-cost analysis of human cell-biomaterial interactions leading to patient-specific diagnoses and treatments using molecularly tailored biomaterials.in situ tissue responses offers the potential to achieve both tissue regeneration and prevention of tissue deterioration. The clinical success of the use of bioactive biomaterials for regeneration provides evidence that this approach is effective; likewise, there is evidence that the prevention of tissue deterioration is also possible.Various therapies that effect wound repair have been proposed over the past few decades. The innovative application of bioactive materials with genetic control of Bioengineered products that can facilitate the healing of chronic ulcers, deep wounds, and burns are in increased demand to improve patients’ quality of life and survival rate. Many different biomaterials have been investigated for the use as dermal substitutes and no me.g., alginate and fibrin) and to bioligand-driven cell-activity control .[etc., have also been studied as wound dressing materials. The article entitled “Pre-clinical evaluation of soybean-based wound dressings and dermal substitute formulations in pig healing and non-healing in vivo models” by Shevchenko and Santin, demonstrates the function of such materials in wound healing and the importance of choosing optimized formulations for different situations.[The clinical performance of wound dressings and dermal substitutes based on synthetic biomaterials is limited by the ability of these polymers to keep the wound environment moist, to protect the wound site from infections, and, in some cases, to encourage cell colonization.,5 Naturaluronan). In this luronan). Natural tuations. However,Initially, raw human or animal skin, either fresh or frozen, was used to cover wounds but immunological reactions were soon observed leading to poor experimental and clinical performances. These demonstrated no rejection upon implantation while providing a solid dermal wound bed for the later application of split-thickness skin grafts. AlthoughA class of therapies is emerging that is based on gene and stem cell therapy. Gene therapy, which was initially developed to treat congenital defects, is a newly viable option for the enhancement of wound repair. Gene encoding for growth factors or cytokines has shown the greatest potential in accelerating wound closure. Most of the gene-delivery systems are on the basis of naked DNA application, high-pressure injection, viral transfection, or liposomal vectors. Stem cell therapy is based on the prolonged capacity of embryonic and adult stem cells that can differentiate into various tissue types. Stem cells isolated from various sources, including bone marrow, umbilical cord blood, peripheral blood, adipose tissue, skin, and hair follicles, have been used to accelerate the wound healing process of acute and chronic wounds.et al. introduce the use of collagen-binding MSC affinity peptide as a scaffold in treating acute full-thickness skin wounds in vivo. The scaffold demonstrated the ability to capture MSCs to injury sites and to accelerate wound healing.[In this issue, Wang  healing. RecentlyThe engineering of dermal substitutes and their application in human patients has come into reality. However,Nanotechnologies and nanomaterials have introduced new therapeutic horizons in medical research, and innovative technologies are rapidly advancing for the development of novel bioactive materials for burn-wound care that are able to mimic the extracellular matrix, including its structure, biological cues, cells, and biofunctionality. Moreover, efforts in the development of novel strategies for modifying the nanotopography of surfaces have recently been applied to the fabrication of new generations of bactericidal biomaterials through surface coatings or surface-chemical modifications.Hydrogels/gels and related composites appear to be optimal biomaterials for burn management that employ both regenerative and reparative strategies. Because of their intrinsic structure, hydrogels and gels prevent the presence of excessive exudates in the wound while also, contributing to the digestion of eschar and necrotic tissue. They enable the following:1. The inclusion of nanofibers to fulfill structural needs;2. The inclusion of nano- and/or microspheres to include biological cues, for both regenerative and therapeutic needs, to induce delivery on demand;3. The inclusion of specific cells for optimal regeneration;4. The modulation of the nano- and microporosity of the materials to promote angiogenesis and reinnervation;5. Surface-chemical modification to achieve anti-adhesive and antimicrobial effects; andet al. in this issue. This review contributes to the understanding of the functions of polymeric hydrogels, as well as the research and application of hydrogels for wound healing.[6. Biodegradability. The use of polymeric hydrogels as advanced skin wound dressings and regenerative templates in wound care is reviewed by Madaghiel  healing.Research and product development should be directed toward specific clinical needs;A knowledge systemic approach should be taken, fostered by the integration of various disciplines based on key enabling technologies; andAppropriate actions should always consider the mental, social, and physical health of the patient.There is considerable potential for hydrogels and polymer-based materials to facilitate the achievement of better treatment for burn injuries without neglecting healthcare needs. However, for the implementation of this approach, several aspects should be considered:


The interrelationship between ionizing radiation and the immune system is complex, multifactorial, and dependent on radiation dose/quality and immune cell type. High-dose radiation usually results in immune suppression. On the contrary, low-dose radiation (LDR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Although the underlying molecular mechanism is not fully understood yet, LDR has been used clinically for the treatment of autoimmune diseases and malignant tumors. These advancements in preclinical and clinical studies suggest that LDR-mediated immune modulation is a well-orchestrated phenomenon with clinical potential. We summarize recent developments in the understanding of LDR-mediated immune modulation, with an emphasis on its potential clinical applications. Over the past several decades, increasing evidence on the effects of low-dose radiation (LDR) has become available. In contrast to high-dose radiation (HDR), LDR is able to promote growth and development, suppress the aging process, enhance immune functions, and delay cancer progression ,2. This The immune system is one of the most important defenses against environmental insults, and is strongly affected by ionizing radiation. LDR modulates a variety of immune response processes and reveals the properties of immune hormesis. In vitro and in vivo studies have confirmed that the regulatory effect of LDR on innate and adaptive immunity depends on many factors, including the status of immune cells, the microenvironment of the immune system, and the interaction of immune cells ,5,6. PreUntil recently, no consistent evidence has existed with reference to the effects of LDR on the different immune cells. What remains unclear is the circumstances under which certain immune cell types are most sensitive to LDR, and how LDR-induced effects on different immune cells can potentially be used in the prevention and therapy of immune-related diseases. Thus, it is worthwhile to further clarify and provide a prospective overview of the potential applications of LDR in immune-related diseases. We review recent developments in the understanding of LDR immune modulation, with emphasis on its potential clinical applications.The human immune system mainly includes innate immunity and adaptive immunity. The innate immune system is the first line of defense for the body, taking immediate action in response to invading pathogens. This system primarily involves natural killer (NK) cells, macrophages, and dendritic cells (DCs). A more evolved adaptive immunity creates immunological memory after an initial response to a specific pathogen and then leads to an enhanced response to that pathogen. This process involves cellular and humoral immune cells (T cells and B cells). It has been demonstrated that LDR enhances the immune response by augmenting the proliferation-reactive response of immune cells to mitogenic stimulation, altering immune cell populations and cytokine release as well as enhancing the interaction of innate and adaptive immune cells ,15,16,17Cells of the innate immune system act as the first line of defense against invading pathogens. The hormetic effect of LDR on innate immunity was mainly reported as the modulation of innate immune cells by LDR. As innate immune effectors, NK cells play a key role in immune surveillance against viral, bacterial, fungal, and protozoan infections . ThroughDespite many reports of LDR-induced activation of NK cells, the molecular mechanisms driving this phenomenon remain obscure and controversial. Sonn et al. reported that enhancement of NK cytotoxicity induced by LDR was not due to changes in the rate of early or late apoptosis of NK cells or alterations in NK-activating receptors  . HoweverMacrophages are traditional innate immune cells that play critical roles in the clearance of pathogens and the maintenance of tissue homeostasis ,27,28. S+) M1 macrophages that orchestrate cytotoxic T cell recruitment into and killing within solid tumors [It has been described that LDR programs the differentiation of inducible nitric oxide synthase  are the most effective and professional antigen-presenting cells (APC) in the innate immune system, which initiates the adaptive immune response . The immSo far, it indicates that LDR may stimulate innate immunity cells, which further activate the cells of adaptive immunity, leading to the enhancement of the immune response. However, in light of the inconsistencies in present reports, which may be caused by inter-laboratory variations in irradiation dose, dose rate, and irradiation time, further studies are required to confirm the effects and mechanisms of LDR on DCs.Alongside the innate immune system, adaptive immunity is a major system that creates immunological memory after an initial response to a specific pathogen. This memory leads to an enhanced response to subsequent encounters with the pathogen. The adaptive immunity includes both cell-mediated immunity components and humoral immunity components, which mainly involve T cells and B cells, respectively. The T cell plays a central role in cell-mediated immunity. There are three broad categories of T cells. In vitro and in vivo experiments confirmed that LDR could increase the subpopulations and enhance the response of CD4+ T cells ,45,46,47Some studies also show that the number and function of regulatory T cells (Tregs) were markedly decreased in mice or rats following treatment with LDR , which eOn the contrary, in an animal model of autoimmune disease, it was observed that LDR could stimulate a selective retention/expansion of Tregs capable of producing immunosuppressive activity to control autoimmune disease . ObviousB cells are the major cells involved in the production of antibodies that circulate in blood plasma and lymph; this process is known as humoral immunity. Reportedly, LDR can affect many aspects of B cell behavior. At the same time, the molecular mechanisms underlying the effect of LDR on B cells have also been explored. LDR could enhance B lymphoblast proliferation by elevation of cyclin E and cyclin-dependent kinase 2 (CDK2), as well as elevation of the phosphorylation level of Ikaros protein, a member of the zinc finger-containing transcription factor family . LDR canAbove all, LDR-induced immune hormesis occurs mainly via alterations in innate and adaptive immune cells . These eMany human diseases have causes related to immune dysfunction. The immune function decline occurs when the immune system is not as strong as normal, resulting in malignant tumors or life-threatening infections. On the contrary, autoimmune disease results from a hyperactive immune system attacking normal tissue. At present, the therapeutic drugs for these immune-related diseases are limited. Most of these drugs are designed to regulate one of the multiple steps in the process of the immune response, thereby leading to other adverse reactions associated with immune disorders.In contrast with these traditional therapeutic drugs, the regulatory effect of LDR on the immune system depends on the immune microenvironment of the body. In different immune-related diseases, the integrated regulation of LDR on the immune system enables the immune system to achieve balance, thereby treating the disease. In recent decades, researchers have systematically investigated the effects of LDR on animal models of these diseases; these efforts are contributing to a theoretical basis for the clinical application of low-dose radiotherapy.In recent years, a large number of studies in vitro and in vivo have demonstrated that LDR has the potential to be used in the clinical treatment of autoimmune diseases. For instance, it has been observed that repeated LDR significantly inhibited osteoclastic activity and subsequent bone resorption in patients with rheumatoid arthritis ,67,68. ISince inflammation is an important pathophysiological process of autoimmune disease, the anti-inflammatory effect of LDR plays a key role in the mechanism by which LDR treats autoimmune disease ,71,72. LHowever, LDR could also reduce the Treg population, which is associated with anti-tumor immunity, in mice with tumors ,76. A diOverall, LDR seems to exert diverse hormetic effects on immune cells. Since the human immune system is complex, it remains unclear which LDR effects act on immune cells for particular autoimmune diseases. Further experimental studies on the molecular mechanisms underlying the effects of LDR on the immune system are necessary for effectively using LDR as an autoimmune disease treatment. In addition, based on the current linear no-threshold (LNT) theory for the risk of radiation carcinogenesis that is extrapolated from observations of effects at high or moderate doses, there is concern about whether LDR can increase cancer risk, which significantly impedes the further validation and acceptance of LDR for benign autoimmune illnesses However, most epidemiology studies performed on nuclear plant workers exposed to LDR do not have adequate statistical power regarding an increased risk of cancer ,79. TherThe development and establishment of tumor cells in the body can suppress the immune system, while activation of both innate and adaptive immunity has been shown to boost anticancer activity. Conventional radiotherapy and chemotherapy are well-established and effective forms of cancer treatment. However, the success of radiotherapy and chemotherapy is limited by systemic and normal tissue toxicity, including the inhibition of immune function. Therefore, upregulation of immune surveillance by LDR offers an anticancer therapeutic strategy.Epidemiological and experimental results indicate that LDR can inhibit tumor growth, metastasis, and occurrence by enhancing the immune response . For exaThese results support the use of LDR as a regimen for cancer prevention and clinical treatment. Nonetheless, the issue of whether LDR could also induce the same hormesis in cancer cells warrants discussion. This information will be important since exposure times and doses of LDR can be manipulated to favor anti-cancer effects. Our group has demonstrated, for the first time, that LDR-induced proliferative effects are absent in cancer cells, including leukemia and solid tumor cells, in vitro and in vivo . The mecIn addition, other studies demonstrate that the lack of hormesis induced by LDR has been observed in cancer cells ,91,92. HThe literature increasingly indicates that LDR modulates a variety of immune responses, including innate and adaptive immunity. At the same time, LDR has shown dual effects in the regulation of immune hormesis , dependiIt should be mentioned that cancer and autoimmune diseases are fundamentally different. In autoimmune diseases, the immune response hyperactivates against a self-antigen, leading to tissue injury, while in cancer it is suppressed and unable to eradicate the transformed self-cells. Therefore we have to further explore the effects of LDR on the immune system. Using the proper dose of ionizing radiation can be part of immunotherapy in future treatment of both benign autoimmune diseases and malignant tumors. Compared with the traditional treatment of these two types of diseases, low-dose radiotherapy is simple, convenient, and easy to implement for most medical institutions.However, unresolved questions, e.g., the optimal dose and timing of LDR therapy for different diseases, motivate further investigation. In addition, the pathogenesis of various diseases is complex and diverse. The effect of LDR on immune cells in vitro will be different from that on the body’s immune system. The therapeutic effects of LDR on a disease will be affected by both the disease itself and the microenvironment of the body.Therefore, to maximize the effectiveness of the immune response to LDR we need additional clinical trials with appropriate design and statistical analysis. To establish optimal protocols we need to maximize the magnitude and duration of immune response along with minimal marrow radiation via reducing irradiated body volume. We also need proper clinical trials to define the effectiveness of LDR immune stimulation in patients who have other disease-related immune responses.


During the past decade, new directions of modern research, broadly defined as nanoscale science and technology have emerged. Nanotechnology is not a separate scientific field, it is a complex platform for the existing disciplines of chemistry, physics, biology, medicine, neurology, information technology, and engineering, a new multidisciplinary scientific research area. In recent years, the nanotechnology has attract a great deal of attention in both synthesis methodologies and wide applications of medicine, energy, environmental, electronics etc. Despite of significant progress in nanotechnology and rise of many commercialized products involving nanomaterials, nanoscience, and technology are still facing many new challenges, especially in the areas of great concern to the public: energy and health.As versatile components of optoelectronic devices, the nanostructured materials attracted a great deal of attention due to its unique ability to manipulate light and control energy flow at nearly the atomic level  to make sure the stabilization of the colloidal stabilization, (ii) provide facile and stable charge transportation between the nanocrystals, and (iii) constructively supplement the properties of the nanocrystal solid.While the new generation of photovoltaic cells  exhibit great promise in the applications, it also presents challenges in the practical application. The challenges can be addressed in the following directions: (1) a simple fabrication processing with low manufacturing complexities and costs. Solution-based deposition and processing by using the nanoparticles inks is an appealing route. It has attracted a great deal of attention in the energy conversion, due to its unique properties including atmospheric pressure and low temperature processing, compatibility for the flexible substrates and large-area, high throughput, and so on. In addition, these approaches can be readily adapted for patterning materials without any subsequent processing steps. (2) One-dimensional nanomaterials can also offered new opportunities to design more efficient solar cells for enhancing solar cell efficiencies. By facilitating electron collection, transport and photon absorption, the one-dimensional nanostructures, including nanorods, nanotubes, nanowires etc. provide significant opportunities for improving solar cell efficiency. (3) The development of new materials with not only high photon absorption, electron transport, etc. but also heavy metal free is much more important for the practical application, because the many of the present energy conversion nanomaterial, such as perovskites, CdTe share a common disadvantage of environmentally hazardous heavy metal, which hinder the commercialization of them.Beside the energy conversion, the energy economical consumption is also very important for the energy sustainable development. Among the straightforward successes of nanotechnology familiar to consumers, the light emitting devices (LED) with high electron to light conversion efficiency have been well developed in the past decade. The high luminescence efficiency and uniquely size-tunable color of solution processable semiconducting colloidal quantum dots (QDs) highlight the potential of QDLEDs for use in energy-efficient, solid state lighting and high color quality thin-film display. The key advantages of using quantum dots QDs in display and lighting applications, including their color purity, stability, and solution processability. From a device efficiency perspective, the three key challenges facing by QDLEDs are QDs photoluminescence quenching, poor photon outcoupling, and a limited understanding of the fundamental operating mechanisms of QDLEDs. Additionally, if the QDLED are to become a broad commercial reality, the operational lifetime and cost of QDLEDs must be addressed in the further research.Besides the high efficient conversion of the solar energy, the storage of the converted energy is also critical desired, because the night or cloudy weather can interrupt solar energy's steadiness. We should capture and store the solar energy for the usage during the interruptions of the sun light. So, energy storage is very important for the efficient consumption of energy sources. As one of the most important constituent part, the nanomaterials are closely related to the energy conversion and storage. Owing to the innovation and advancement of materials science, the energy storage nanotechnologies have also been well-developed in the decades, especially the researches on hydrogen storage and Li-ion batteries.4 nanoparticles. With the decrease of particle size from 1–10 mm to 2–10 nm, the active energy can be successively reduced from 116 to 58 kJ mol−1 H2  with surface area as high as 3,200 m2/g and narrow pore size distribution below 1 nm exhibit a high hydrogen binging energy of 8.2 kJ/mol (Yang et al., Efficient hydrogen storage is regarded as the key challenge in large-scale applications of hydrogen energy. Hydrogen storage materials are the core technology for the storage of hydrogen sources with efficient and safe manner. To meet the stringent requirements of application of hydrogen energy, people has devoted many efforts to develop the potential materials for hydrogen storage (Liu et al., Li-ion batteries is one of the most important and widely used secondary batteries for the energy storage. The higher power/energy density, high speed recharge/discharge, and longer cycling life is much important for the newly emerging electronic devices, advanced communication and transportation facilities. In the past decades, many efforts were devoted to the development of the electrode materials with desirable electrochemical properties, including larger Li storage capacity, better cycling performance, and higher rate capability (Chen and Cheng, Theranostics is a term derived from therapy and imaging, which provide an integrated platform for the personalized medicine to meet the challenges in modern health care (Chen et al., The nano-theranostics will face a series of biological barriers during circulation in living subjects which will influence the nanoparticle delivery efficacy: the nanoparticles firstly should cross blood vessels, then escape the entrapment of organs and removal of phagocytic cells, finally reach the specific target (Kievit and Zhang, It has been demonstrated that the circulation and metabolism in living subjects are profoundly effected by the Size (Tang et al., The structure-activity relationship between the nanomaterials and applications should be built firstly, which is critical for the design of the nanomaterials. A good performance in the application is our ultimate aim, so we should know what kind of materials are good for the improvement of the capability.As the core components of nanotechnology, nanomaterials provides basic building blocks for fabricating complex devices with abundant functions. To better service for building up of the structure-activity relationship, the controllable targeting synthesis is another criterion in the nanoscience research.Exploring synthetic routes to large-scale production with low cost is very important for the wide spread promotion of the new nanotechnology.Last but not least, systemically evaluation on the toxicity and environmental risks of nanomaterials is essential.In the past decade, various nanostructures have been fabricated to address the significant material and applications challenges that exist in energy, environment, and health. Although, there are diverse specific requirements for nanomaterials in different applications, many commonality criterions for the research in the nanoscience can be built and summarized as following:The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Web-based typed exchanges are increasingly used by professionals to provide emotional support to patients. Although some empirical evidence exists to suggest that various strategies may be used to convey emotion during Web-based text communication, there has been no critical review of these data in patients with chronic conditions.The objective of this review was to identify the techniques used to convey emotion in written or typed Web-based communication and assess the empirical evidence regarding impact on communication and psychological outcomes.An electronic search of databases, including MEDLINE, CINAHL, PsycINFO, EMBASE, and the Cochrane Library was conducted to identify literature published from 1990 to 2016. Searches were also conducted using Google Scholar, manual searching of reference lists of identified papers and manual searching of tables of contents for selected relevant journals. Data extraction and coding were completed by 2 reviewers . Publications were assessed against the eligibility criteria and excluded if they were duplicates, were not published in English, were published before 1990, referenced animal or nonhuman subjects, did not describe original research, were not journal papers, or did not empirically test the effect of one or more nonverbal communication techniques  as part of Web-based or typed communication on communication-related variables, including message interpretation, social presence, the nature of the interaction , patient perceptions of the interaction , or psychological outcomes, including depression, anxiety, and distress.A total of 6902 unique publications were identified. Of these, six publications met the eligibility criteria and were included in a narrative synthesis. All six studies addressed the effect of smileys or emoticons on participant responses, message interpretation, or social presence of the writer. None of these studies specifically targeted chronic conditions. It was found that emoticons were more effective in influencing the emotional impact of a message than no cue and that smileys and emoticons were able to convey a limited amount of emotion. No studies addressed other techniques for conveying emotion in written communication. No studies addressed the effects of any techniques on the nature of the interaction , patient perceptions of the interaction , or psychological outcomes .There is a need for greater empirical attention to the effects of the various proposed techniques for conveying emotion in Web-based typed communications to inform health service providers regarding best-practice communication skills in this setting. The majority of people with chronic disease may experience some level of psychological distress in their lifetime ,2. CompaVarious forms of psychological support have been found to improve physical and psychological outcomes in patients with chronic conditions ,5,6. AppThe advantages of Web-based or computer-mediated communication over face-to-face or telephone-based methods of providing psychological support include fewer limitations related to geographical location, staffing, resources, and timing of service provision, as well as anonymity for the patient . It has Whereas telehealth has been highlighted as having potential relevance to this review, it is not considered to be directly applicable as it is outside the scope of the research question. Despite some definitions of telehealth, including broad concepts such as text-based communication between a health care professional and a patient without the presence of videoconferencing contact, the literature largely focuses on patient outcomes rather than conveyance of emotion. Furthermore, the literature regarding health care professional and patient relationships with respect to the provision of telehealth services seems to relate to emotional communication transmitted by tone of voice, posture, gaze, and eye contact, which is irrelevant to the explicit focus of this review (communication methods in Web-based text-only interactions).Although some empirical evidence exists to suggest that Web-based or typed communication techniques have the ability to convey emotion  and are The review aims to critically examine original research to identify experimental studies regarding Web-based communication methods to describe the following:The number of empirical studies of techniques used to convey emotion in written or typed Web-based communication .The effect of the identified techniques on communication-related variables, including message interpretation, social presence, the nature of the interaction , and patient perceptions of the interaction .The impact of the identified techniques on patient psychological outcomes, including depression, anxiety, and distress.An electronic search of databases, including MEDLINE, CINAHL, PsycINFO, EMBASE, and the Cochrane Library was conducted to identify literature published from 1990 to 2016. Searches were also conducted using Google Scholar, manual searching of reference lists of identified papers, and manual searching of tables of contents for selected relevant journals.professional-patient relations, therapeutic alliance, computer, cyber, email*, web, online, internet, and instant mess*. Strategies suggested by the first medical librarian, which were integrated into the final search strategy, included implementation of the adj5 function to search for 5 words or fewer apart from counsel and therap, explosion of certain medical subject headings or MeSH terms (emotion), and confirmation of the decision to exclude Sociological Abstracts from the list of databases searched because of the largely irrelevant results it yielded. The second medical librarian reviewed the final search strategy as a quality assurance exercise and ran an alternative approach to the search. The results of the alternative search strategy were exported into an EndNote X7.3.1 database and compared with the results of the original search strategy. This comparison demonstrated that the alternative search strategy did not yield any additional relevant content. The search terms utilized for each database is provided in Two medical librarians provided expert guidance on the development of the review’s search strategy. The initial search strategy was developed and tested by the research team and forwarded to the first medical librarian for review regarding search terms and appropriate databases. There was significant overlap of search terms in the original and alternative search strategies, including The search was limited to papers published from January 1, 1990 to December 31, 2016. The year 1990 was chosen as the starting point of the literature search strategy period as the availability of Web-based technology was greatly accelerated during the 1990s.The inclusion criteria were developed to isolate studies that identified the effects of communication techniques used in typewritten Web-based communication. Variables that were only relevant to audiovisual communication were not sought. All eligible abstracts were examined for relevance following removal of duplicates. The full-text papers of potentially relevant original research studies were obtained and examined. A coding template was used to extract relevant data from the included publications. Publications were excluded if they were duplicates, were not published in English, were published before 1990, referenced animal or nonhuman subjects, did not describe original research, were not journal papers, or did not empirically test the effect of one or more nonverbal communication techniques  in adults as part of Web-based, Web-based or typed communication on communication-related variables, including, for example, message interpretation, social presence, the nature of the interaction , patient perceptions of the interaction (such as participant satisfaction), or psychological outcomes, including depression, anxiety, and distress.Article abstracts were initially assessed against the eligibility criteria by MC and excluded if the study did not meet the inclusion criteria. A random subsample (10.0%) of included studies were categorized by 2 other authors (CP and HS) and compared with the coding of MC. An initial agreement of 83.0% was achieved, with any discrepancies resolved via discussion and recoded as necessary.All publications which met the eligibility criteria were coded by CP, and 10.0% were independently coded by another author  to determine the papers that focused on the following:Techniques used to convey emotion in written or typed Web-based communication: publications that reported techniques used ; communication modality ; format of communication delivery ; and one of the following:The effect of the identified techniques on message interpretation and social presence: publications that reported effect on mood or perception of writer’s commitment, perceived extraversion or sociality of writer, and perception of message .The effect of the identified techniques on the nature of the interaction: publications that reported effect on therapeutic alliance or working alliance.The effect of the identified techniques on patient perceptions of the interaction: publications that reported effect on participant satisfaction.The impact of the identified techniques on patient psychological outcomes: publications that reported effect on psychological outcomes, including depression, anxiety, and distress.The full-text of intervention studies was then assessed independently by 2 reviewers (MC and CP) regarding whether those studies met the minimum design criteria for classification as any one of a randomized controlled trial (RCT), a non-RCT, a controlled before and after study, or an interrupted time series study using the Cochrane Effective Practice and Organization of Care risk of bias criteria. There was perfect agreement (100.0%) between the 2 reviewers.To assess intervention effectiveness, data on each of the following variables were extracted by 2 authors (CP and DR) using an extraction coding table: author and year of publication, study setting; study design, sample characteristics , assessment based on inclusion and exclusion criteria, outcome measures, and study findings. An agreement of 96% was achieved (a single error was identified and corrected).A total of 6902 publications were identified using the search strategy , patient perceptions of the interaction , or psychological outcomes .Four of the included studies found that the use of a smiley or emoticon is more effective than no cue in influencing the perceived emotion of an interaction ,20-22. WWalter and D'Addario  observedhappy emoticons and the observer’s assessment of qualities of agreeableness, conscientiousness, and openness.Lo , GansterVery few experimental studies have explored the effects of typed strategies to assist conveyance of emotion in text-only forms of communication. Although there are many studies of the efficacy of computer-mediated psychotherapeutic interventions, there were no studies exploring the impact of communication techniques for conveying emotion on the nature, perception, or outcomes of such interactions. The studies excluded at the full-text stage either described computer-mediated interventions without addressing the effect of communication techniques or were observational (described the use of rather than tested the effects of such techniques). No studies regarding communication techniques other than smileys and emoticons were identified. These two aspects of computer-mediated communication highlight important gaps in the evidence base regarding the delivery of supportive or therapeutic typed Web-based communication.The six experimental studies identified indicate that smileys and emoticons do strengthen the perceived emotion in text-only messages. The work of Comesana et al  suggestsThere appear to be some caveats on what smileys and emoticons can achieve as techniques for conveying emotion: positively valenced emoticons cannot counteract a negatively worded message, and there appears to be a particular sensitivity to negative smileys such that they may need to be utilized sparingly . FurtherCurrent literature indicates that therapeutic interventions delivered Web-based can be as successful as the face-to-face versions ,10, suggIt is important to acknowledge that the identified studies have been conducted with young and healthy nonclinical populations, rather than patient populations. This significantly limits the ability to generalize the findings to older people or to patient populations. For older people and patient populations, there is perhaps a greater need for sensitivity in conveying emotion in a text-only setting ,29. TherThis review suggests that the use of a limited range of easily recognized smileys and emoticons could be cautiously encouraged in text-only therapeutic interactions for people in younger age groups. There is a need for further research on how to use communication techniques, including emoticons and smileys, effectively in text-only interactions across a diverse range of ages and to inform evidence-based practice of therapists working in the Web-based domain. Furthermore, there is a need for research focused on the communication of emotion in text-only Web-based interactions in a therapeutic clinical setting.


To date, the etiology and pathogenesis of Crohn's disease (CD) have not been fully elucidated. It is widely accepted that genetic, immune, and environment factors are closely related to the development of CD. As an important defensive line for human body against the environment, intestinal mucosa is able to protect the homeostasis of gut bacteria and alleviate the intestinal inflammatory and immune response. It is evident that the dysfunction of intestinal mucosa barriers plays a crucial role in CD initiation and development. Yet researches are insufficient on intestinal mucosal barrier's action in the prevention of CD onset. This article summarizes the research advances about the correlations between the disorders of intestinal mucosal barriers and CD. CD and ulcerative colitis (UC) are inflammatory bowel disease (IBD). As a chronic, nonspecific, and granulomatous bowel disease, CD often occurs in the whole layer of intestinal wall, and, mostly, its lesions are segmentally and asymmetrically distributed. It may appear in any part of the gastrointestinal tract, especially in terminal ileum and adjacent colon . CD has Intestinal mucosal barrier is composed of mechanical barrier, chemical barrier, immune barrier and biological barrier, constituting a defensive barrier between the human body and the surrounding environment. The mechanical barrier mainly consists of intestinal epithelial cells and epithelial tight junctions. Tight junction (TJ) is the main connection form between intestinal mucosal epithelial cells, and it also plays an important role in maintaining the integrity of structure and normal function of intestinal mucosal barrier. Chemical barrier is made up of many chemicals such as digestive acid secreted by gastrointestinal, digestive enzymes, lysozyme, mucopolysaccharides, glycoproteins, and glycolipids. Therefore, it is involved in the process of bacteriolysis to inhibit the invasion of pathogenic bacteria. Gut-associated lymphoid tissue (GALT) and secretory immunoglobulin A (SIgA) as well as some special cells  constitute the immune barrier, which is an important guarantee for the intestinal immunity homeostasis via identifying the autoantigens and exogenous antigens to regulate the immune response. Actually, biological barrier is a mutually dependent and interrelated microecosystem. It is mainly composed of the resident intestinal flora, among which obligate anaerobe is the dominant bacterial community. Intestinal mucosal barrier is a barrier constituted between the organism and the surrounding environment. Those four barriers have distinguished structures and regulatory mechanism and each plays a different role in biological function. Intestinal mucosal barrier can effectively maintain the balance between pro- and anti-inflammatory factors and prevent pathogenic microorganism from entering into the tissues to keep the body healthy –15. An iThe intestinal epithelial tight junction (TJ) is an important part of the intestinal mechanical barrier, and it is indeed the most essential structure to maintain the function of mechanical barrier. TJ is mainly composed of occludin, claudin, junction adhesion molecules (JAMs), and ZOs –18, amon in vitro [The mucus secreted by gastrointestinal tract together with various other substances forms the intestinal mucosal chemical barrier, which is the key component of the body's natural immune system. Among all these substances, mucus is the most effective one in protecting the surface of intestinal mucosa. Intestinal mucous layer consisting of goblet cells and mucin (MUC) secreted by intestinal epithelial cells is the first defensive line to resist against extraneous pathogen through protecting and lubricating intestine. The intestinal mucous layer can be divided into external mucous layer which provided a suitable symbiotic environment for the gut microbiota and the internal mucous layer which protected the integrity of intestinal mucosal barrier by preventing microorganism from invading intestinal epithelium. Normally, only when the body is in a disease state caused by some abnormal factors could the bacteria penetrate the internal mucous layer and destroy the intestinal epithelium subsequently. MUC is not only the main component of the intestinal mucous layer but also the most important functional unit in mucus . The mucin vitro , 29. Stuin vitro , 31 havein vitro .The immunological factor has been considered to be the key factor in the occurrence and development of CD. Intestinal mucosal immune barrier is essential for maintaining intestinal immune homeostasis. GALT is made up of lymphoid nodule, free lymphoid tissue, plasma cells, and the intestine-related tissue composed of lymphocyte in the epithelium. GALT is an important immune organ to maintain the integrity of intestinal mucosal barrier. SIgA secreted immune globulin with diverse functions and is a main antibody that plays an important role in effects of anti-infection and immunomodulation in defense system of mucosa. A related study  found th Bifidobacterium and Lactobacillus are the probiotics. On one hand, they could restrict the pathogenic bacteria; on the other hand, they could repair the damaged mucosal barrier by adjusting the level of inflammatory cytokines. A study had demonstrated that lactic acid bacteria could decrease the levels of IL-6, TNF-alpha, toll-like receptor 4 (TLR4), and NF- kappaB mRNA and increase the level of IL-10 mRNA observably at the same time [ bacteroid, Bacillus, and Streptococcus were increased, while the amount of Bifidobacterium was decreased [The biological barrier is constituted by normal flora and deposited in intestinal mucosa to maintain the integrity of the intestinal mucosal barrier. Normally, the microecological environment in intestine maintains homeostasis through the interdependence and mutual restrictions between probiotics and pathogenic bacteria. IBD is accompanied with alteration of intestinal flora, which could induce intestinal infection when body is affected by abnormal factors –61. Bothame time . In the ecreased . Prebiotecreased , 65. Stuecreased –69 have The mechanical, chemical, immune, and biological barriers play important role in protecting the gut against bacteria homeostasis, regulating the intestinal immune response and reducing the inflammatory response. Yet the comprehensive and systematic researches are insufficient on intestinal mucosal barrier's action in the prevention of CD onset. Therefore, it is of great significance to conduct more thorough studies and randomized controlled trials with largescale, multicentre, and high-quality. In addition, interventions by which to maintain the structural integrity and proper function of intestinal mucosal barrier are expected to be a rational and reliable approach in the prevention of CD in the future.


Anopheles mosquitoes interferes with mosquito infection by Plasmodium and influences mosquito fitness, therefore affecting vectorial capacity. This natural barrier to malaria transmission has been regarded with growing interest in the last 20 years, as it may be a source of new transmission-blocking strategies. The last decade has seen tremendous progress in the functional characterisation of the tripartite interactions between the mosquito, its microbiota and Plasmodium parasites. In this review, we provide insights into the effects of the mosquito microbiota on Plasmodium infection and on mosquito physiology, and on how these aspects together influence vectorial capacity. We also discuss three current challenges in the field, namely the need for a more relevant microbiota composition in experimental mosquitoes involved in vector biology studies, for a better characterisation of the non-bacterial microbiota, and for further functional studies of the microbiota present outside the gut.The microbiota of  Plasmodium malaria parasites are transmitted by Anopheles mosquitoes. Female mosquitoes become infected after taking a blood meal on humans carrying Plasmodium pre-sexual stages. Upon entering the gut lumen, parasites undergo sexual reproduction and differentiate into motile forms, ookinetes, within 24 hours. After crossing the gut epithelium, the ookinete develops into an oocyst which undergoes mitoses in the following week and releases sporozoites in the hemolymph. About 10–14 days after the infected blood meal, sporozoites reach the salivary glands. The mosquito then becomes infectious and will inject parasites to humans with its saliva during subsequent bites for the rest of its life.Plasmodium colonisation in the gut and by affecting different aspects of mosquito physiology, notably its lifespan.Ingestion of an infectious blood meal will only result in malaria transmission if the parasite makes it through bottlenecks in the gut and salivary glands and if the mosquito bites humans after the extrinsic incubation period, the time needed for parasites to become infectious. The gut, salivary glands and reproductive organs are colonised by a dynamic microbial community composed by bacteria, viruses and fungi, of which the bacterial part is the best characterised –3. This Plasmodium infection rates, either via natural competition mechanisms -glycine radiolabelled Pseudomonas isolated from the Anopheles microbiota, radioactivity is detectable not only in the whole mosquito body, but also in P. berghei oocysts and in disseminated sporozoites [Finally, the microbiota is also reported to contribute to the nutrition of the mosquito and rozoites . This maPlasmodium , Acetobacteraceae (Acetobacter and Asaia) and Flavobacteriaceae (Elizabethkingia and Chryseobacterium) . On theiewed in . This suAnopheles reared in laboratory conditions showed a reduced bacterial diversity in their midgut with respect to field-collected ones, although the majority of bacteria found in laboratory mosquitoes were present in wild mosquitoes [Plasmodium have mostly been conducted on mosquitoes reared under controlled laboratory conditions  abundance in An. gambiae after experimental infection of adults derived from field-collected larvae. These data point out the need for more appropriate microbiota models to perform functional studies on the tripartite relationship between the mosquito, the microbiota and Plasmodium. Several experimental setups may be favoured and are shown in Fig. Remarkably, squitoes , 36, 43.ns Table . The micf et al.  found anAnopheles [Despite the high number of studies on the midgut microbiota, our knowledge of its non-bacterial components is still poor. Metagenomic data on total mosquito RNA detected several viruses associated with wild-caught nopheles , 51. Simnopheles , but cos18S rRNA sequencing is in part complicated by the amplification of DNA from the mosquito or from the blood source [Candida, Pichia and Penicillium were isolated from Anopheles larvae and adults through standard microbiological techniques [Plasmodium infectiveness either negatively [Plasmodium.The analysis of the eukaryotic microbiota by d source . Severalchniques –55. Two gatively  or positgatively . HoweverAnaplasma phagocytophilum infects the tick Ixodes scapularis, it induces significant variations in the composition of the host gut microbial community. This correlates with pathogen-dependent induction of the Ixodes Antifreeze Glycoprotein IAFGP, which reduces biofilm formation and impairs the integrity of the peritrophic matrix, facilitating penetration of the pathogen into the tick body cavity [Anopheles-microbiota-Plasmodium system, further studies are required to clarify the role of the parasite in influencing the microbiota and host immunity.Along these lines, the parasite itself may be considered as part of the microbial community, or pathobiome , harboury cavity . Since sPlasmodium transmission and mosquito ecology. Microorganisms present in the salivary glands are prone to interact with the parasite when the mosquito is becoming infectious and thus they might affect transmission efficiency, while microbes colonising the Anopheles genitalia may impact reproductive success, immunity, lifespan and microbiota composition of the offspring. The endosymbiont Wolbachia is found in half of the insect species, but had not been detected in any Anopheles species until recently. When artificially introduced in an An. stephensi strain, Wolbachia persists in mosquito ovaries, is vertically transmitted and increases the resistance against P. falciparum in laboratory conditions [Wolbachia has now been found associated with around 10% of Anopheles in a wild population in Burkina Faso [Ae. albopictus where Wolbachia was found to account for 99% of the 16S rRNA reads in whole mosquitoes [Asaia, interfere with Wolbachia colonisation and thus reduce its possible use against malaria [The microbial communities colonising the mosquito salivary glands and reproductive organs are as relevant as those in the midgut for several aspects concerning nditions . Wolbachina Faso . Its loasquitoes , 61–63.  malaria , 65.Anopheles mosquitoes in few metagenomics studies [The microbiota of the ovaries and salivary glands has been investigated in  studies , 63, 66.Plasmodium transmission and mosquito ecology. Moreover, the isolation of bacteria able to colonise the body of the mosquito without affecting its lifespan and to be efficiently vertically transmitted will identify new paratransgenesis candidates able to spread efficiently in the mosquito population. Recently, Serratia was identified in both ovaries and salivary glands of Anopheles mosquitoes and proposed for malaria control [Functional studies on the role of the microorganisms colonising other tissues beyond the midgut will help to clarify several aspects of  control , 8.Plasmodium infection and transmission has gradually emerged. However, the tripartite interaction between the mosquito, its microbiota and the parasite is a complex relationship that still needs further investigation. In general, the microbiota was found to reduce Plasmodium infection and to impact several physiological aspects of the mosquito, notably affecting its lifespan. Surprisingly, these effects induced by the microbiota were consistent almost irrespective of the Anopheles and Plasmodium species, suggesting that this tripartite interaction is a stable system in which each component plays a role. Although our knowledge on the mosquito microbiota is continuously expanding, several aspects have not been completely elucidated yet and represent the current challenges of this field. In particular, the non-bacterial component of the mosquito microbiota has not been investigated as extensively as the bacterial one, although viruses and eukaryotes might be as relevant as prokaryotes in limiting Plasmodium infection. Moreover, it is not clear whether the microbiota of the reproductive track or salivary glands impacts parasite transmission or mosquito fitness. Finally, most of the functional studies conducted on the mosquito microbiota have been carried out on laboratory-reared insects, which are known to possess a different microbial community from that of field mosquitoes. Depending on the desired levels of control on experimental conditions and of relevance of microbiota composition, several experimental set ups may be used to improve the study of the mosquito microbiota.In the past 20 years, the pivotal role of the mosquito microbiota in shaping


A large and convincing body of evidence demonstrated that aging is characterized by a progressive decline in the efficiency of physiological functions due to the consequence of free radical-induced damage to cellular macromolecules. Moreover, the age-dependent inability to counterbalance these changes by endogenous antioxidant defenses can further contribute to the oxidative damages.Many recent concepts of biology or medicine have underlined the importance of nutrition for the maintenance of “physiological” changes during aging or insults stemming from various degenerative diseases. The role of a balanced nutrition to human health is now well documented in different fields such as neuroscience.Epidemiological analysis of the relations between nutrient consumption and neurodegeneration is complex and it is highly unlikely that a single component might play a major role. In addition, since multiple factors across the human lifespan might influence the brain function in adulthood and in the elderly, multidomain interventions might be more promising in the prevention of the neurodegeneration.The interactions between lifestyle and brain health have been widely demonstrated, and recent studies have demonstrated the important role of antioxidants and vitamins in the antiaging process and in neurodegenerative disorders, such as Alzheimer's disease (AD) and Parkinson's disease (PD). Moreover, it has been demonstrated that caloric restriction could increase the functional and maximal lifespan, and accumulating evidence demonstrated that the selection of appropriate whole foods or the addition of antioxidants into the diet might be beneficial to increase the functional lifespan, if not the maximal lifespan. One could then argue that caloric selection may be as important as caloric restriction.Along this line, the current special issue provides appreciable evidence showing that nutritional and pharmacological interventions based on their antioxidant properties might be particularly relevant for the onset and progression of neurodegenerative disorders.The present volume, at which contributed eminent scholars, includes 10 original research articles and was organized in the attempt to cover the whole field of the interrelationship between oxidative stress, nutritional/pharmacological interventions, and neurodegenerative disorders.To this regard, an interestingly cross-sectional analysis conducted by L. K. Mischley and colleagues on 1053 individuals affected by idiopathic PD demonstrated that a reduced rate of PD progression is associated to the consumption of different foods, including fresh vegetables, fresh fruit, nuts and seeds, nonfried fish, olive oil, wine, coconut oil, fresh herbs, and spices.Studies have demonstrated that an altered arginine metabolism is involved in aging and neurodegenerative processes. M. Mazlan and colleagues found a chemical- and region-specific age-related alteration of L-arginine metabolism in the brain of old rats. Moreover, the authors reported that a three-month oral supplementation with vitamin E, in the form of a tocotrienol-rich fraction, had beneficial effects on memory and motor function in old rats. The authors suggested that such effect was related to a reversion of age-associated changes in arginine metabolites in the entorhinal cortex and cerebellum.Many efforts and resources have been spent in the last years to find new therapeutic strategies for the treatment of neurodegenerative disorders. Since most of these disorders have oxidative and inflammatory components, studies are geared in the finding of strategies to dampen these processes.It is widely accepted that the main hallmarks of AD are not only senile plaques and neurofibrillary tangles, but also reactive astrogliosis, which contributes to neuronal loss depriving neurons of the homeostatic support. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide, belonging to the class of nuclear factor agonists. PEA has been demonstrated to bind a nuclear receptor and to exert a great variety of biological functions. PEA has been shown to have anti-inflammatory, antinociceptive, neuroprotective, and anticonvulsant properties. M. R. Bronzuoli and colleagues found that PEA is able to dampen reactive astrogliosis and to promote the glial neuro supportive function, thus furnishing an alternative treatment approach for innovative therapeutic strategy against AD.Armillaria mellea, an edible fungus. In particular, AMPS reduced the apoptosis rate, amyloid beta (Aβ) deposition, oxidative damage, and phospho-Tau aggregations in the hippocampus of a murine model of AD. Moreover, AMPS enhanced horizontal movements in an autonomic activity test, improved endurance times in a rotarod test, and decreased escape latency time in a water maze test.The study by S. An and colleagues described in a mouse model of AD the neuroprotective effects of mycelium polysaccharides (AMPS) obtained from de novo GSH synthesis since the neuroprotection was blocked by the inhibition of γ-glutamyl-cysteine ligase, the first enzyme of the cellular eliminate GSH biosynthetic pathway.In the study by A. N. Winter and colleagues, the authors demonstrated that a whey protein supplement significantly protects neurons against diverse inducers of oxidative stress, providing the cystine for the synthesis of the endogenous antioxidant glutathione (GSH). The effect of the supplement was dependent on Furthermore, D. Vergara and colleagues reported that resveratrol treatment led to a significant increase of GSH level and a reduction of GSSG/GSH ratio, as well as of reduced free thiol content in fibroblasts from parkin-mutant early-onset PD patients.P. Priore and colleagues reported that oleic acid (OA) and hydroxytyrosol (HTyr), two different components of extra virgin olive oil, could affect lipid synthesis in C6 glioma cells. In particular, OA and HTyr inhibited both de novo fatty acid and cholesterol synthesis without affecting cell viability. Interestingly, the effect on lipid synthesis was more pronounced when OA and HTyr were coadministered to cells, suggesting a synergistic effect.In the study by Z. Hou and colleagues, an edible bird's nest (EBN), traditionally used for general well-being, was used to improve the cognitive decline in ovariectomized rats compared to estrogen-treated rats. The results indicated that 12-week treatment with EBN was able to improve learning and memory in ovariectomized female rats without inducing liver toxicity, a side effect observed in the estrogen-treated group. The latter results suggest that EBN might be an effective alternative to estrogen therapy for menopause-induced aging-related memory loss.It should be considered that the chronic use of drugs, approved to alleviate the symptoms of several neurodegenerative diseases, is often associated with debilitating side effects. Moreover, none of these drugs seems to stop the progression of the degenerative process. In keeping with this, the finding of new natural molecules useful for the treatment/preventions of neurodegenerative disorders acquires considerable significance. From this special issue, it appears evident that many studies are devoted to the finding of natural molecules directed at improving the symptoms of neurodegenerative diseases. In conclusion, the articles in this special issue offer tantalizing hints at the potential for new prevention strategies and treatments for people with neurodegenerative diseases, encompassing a wide variety of techniques and methods. We hope that these studies will inspire new and useful ideas to fill the gaps that remain in this critical area.Anna Maria GiudettiMichel SalzetTommaso Cassano


Heart failure and frailty are clinical syndromes that present with overlapping phenotypic characteristics. Importantly, their co-presence is associated with increased mortality and morbidity. While mechanical and electrical device therapies for heart failure are vital for select patients with advanced stage disease, the majority of patients and especially those with undiagnosed heart failure would benefit from early disease detection and prompt initiation of guideline-directed medical therapies. In this article, we review the problematic interactions between heart failure and frailty, introduce a focused cardiac screening program for community-living elderly initiated by a mobile communication device app leading to the Undiagnosed heart Failure in frail Older individuals (UFO) study, and discuss how the knowledge of pre-frailty and frailty status could be exploited for the detection of previously undiagnosed heart failure or advanced cardiac disease. The widespread use of mobile devices coupled with increasing availability of novel, effective medical and minimally invasive therapies have incentivized new approaches to heart failure case finding and disease management. In consecutively recruited study subjects, the mean prevalence was 43.5% (median 49.6%) Table , ischemiTo date, two cross-sectional studies from the Netherlands have provided some clues on the scale of undiagnosed HF in patients with suggestive symptoms. Although those studies did not include frailty assessment and recruited subjects based on symptoms , HF was diagnosed by cardiologists and verified by echocardiography and other investigations. Oudejans et al. evaluated 206 elderly patients (mean age 82 years) referred to geriatric outpatient clinics for assessment of HF symptoms and diagnosed HF in 46% of study subjects  projectIt is noteworthy that HF in older individuals may present with atypical symptoms other than exertional dyspnea, reduced exercise tolerance or lack of energy. The questions embedded in the FRAIL  scale . Frail geriatric patients discharged from hospitals may serve as a benchmark for the high-risk frail group. The study attempts to encompass and recruit as diverse a community-dwelling elderly population as possible, with different health and socioeconomic status in order to minimize bias. However, real-world recruitment bias may be impossible to eliminate; for instance, the frail elderly living and struggling in the community may be less likely or interested to come forth for the study recruitment. Nevertheless, the pre-frail older individuals may be an especially important group to study, given the increasingly available interventional options and the possibility of a successful intervention on preventing progression into the frail state. In this study, apart from clinical assessment, echocardiography and NT-proBNP levels, we will also measure physical fitness , and compare patients' medication inventory, cardiovascular history and risk profiles, and social determinants of health among different frail/non-frail states.n = 2,539 Hong Kong Chinese respondents, median age band of 70–79 years). Aside from minor differences in the frailty assessment instrument used , it is unclear whether social, cultural and/or ethnic factors might be explanatory.Recently, investigators of the biracial (white and African American) Atherosclerosis Risk in Communities (ARIC) study have reported an association between frailty and cardiac abnormalities  in older adults  with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Declaration of Helsinki. The protocol was approved by the CUHK-NTEC CREC.The described study is being carried out under the oversight of the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (CUHK-NTEC CREC, EF: conceived the framework and contents of the paper, collected the data and performed data analysis, wrote the draft, performed editing and is the corresponding author; EH: critically reviewed the manuscript and contributed to the editing of the manuscript; XY: performed data analysis, and contributed to editing; LL, KC, QL, YF, DS, BM, JL, and AL: critically reviewed the manuscript and contributed to editing; JW: contributed to drafting of the manuscript, critically reviewed it and contributed to editing.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The aim of this study was to characterize the influence of functionalization of synthetic poly-(L-lactic acid) (PLLA) nanofibers on mechanical properties such as maximum load, elongation, and Young's modulus. Furthermore, the impact of osteoblast growth on the various nanofiber scaffolds stability was determined. Nanofiber matrices composed of PLLA, PLLA-collagen, or BMP-2–incorporated PLLA were produced from different solvents by electrospinning. Standardized test samples of each nanofiber scaffold were subjected to failure protocol before or after incubation in the presence of osteoblasts over a period of 22 days under osteoinductive conditions. PLLA nanofibers electrospun from hexafluoroisopropanol (HFIP) showed a higher strain and tended to have increased maximum loads and Young's modulus compared to PLLA fibers spun from dichloromethane. In addition, they had a higher resistance during incubation in the presence of cells. Functionalization by incorporation of growth factors increased Young's modulus, independent of the solvent used. However, the incorporation of growth factors using the HFIP system resulted in a loss of strain. Similar results were observed when PLLA was blended with different ratios of collagen. Summarizing the results, this study indicates that different functionalization strategies influence the mechanical stability of PLLA nanofibers. Therefore, an optimization of nanofibers should not only account for the optimization of biological effects on cells, but also has to consider the stability of the scaffold.


Recent reform of medical education highlights the growing concerns about the capability of the current educational model to equip medical school students with essential skills for future career development. In the field of ophthalmology, although many attempts have been made to address the problem of the decreasing teaching time and the increasing load of course content, a growing body of literature indicates the need to reform the current ophthalmology teaching strategies. Flipped classroom is a new pedagogical model in which students develop a basic understanding of the course materials before class, and use in-class time for learner-centered activities, such as group discussion and presentation. However, few studies have evaluated the effectiveness of the flipped classroom in ophthalmology education. This study, for the first time, assesses the use of flipped classroom in ophthalmology, specifically glaucoma and ocular trauma clerkship teaching. A total number of 44 international medical school students from diverse background were enrolled in this study, and randomly divided into two groups. One group took the flipped glaucoma classroom and lecture-based ocular trauma classroom, while the other group took the flipped ocular trauma classroom and lecture-based glaucoma classroom. In the traditional lecture-based classroom, students attended the didactic lecture and did the homework after class. In the flipped classroom, students were asked to watch the prerecorded lectures before the class, and use the class time for homework discussion. Both the teachers and students were asked to complete feedback questionnaires after the classroom. We found that the two groups did not show differences in the final exam scores. However, the flipped classroom helped students to develop skills in problem solving, creative thinking and team working. Also, compared to the lecture-based classroom, both teachers and students were more satisfied with the flipped classroom. Interestingly, students had a more positive attitude towards the flipped ocular trauma classroom than the flipped glaucoma classroom regarding the teaching process, the course materials, and the value of the classroom. Therefore, the flipped classroom model in ophthalmology teaching showed promise as an effective approach to promote active learning. As our understanding of the pathophysiology of diseases keeps on expanding, and new treatment technology continuously emerges, the limitations of the traditional lecture-based teaching becomes obvious. First, the increasing load of course content and a decreasing teaching time due to the competing service demands pose a big challenge to the instructors. Second,Previous studies have shown that content comprehension and knowledge retention can be greatly enhanced if students are actively participated into the learning process , 5. MediThe modality of flipped classroom has long been applied in non-science education, and recent development of video recording and internet capability expand this approach into teaching medical courses. JohnathOphthalmic clinical skill training is essential to all medical practitioners, as the visual system interacts with other bodily systems, and ophthalmic abnormalities can be key clues for systemic disease diagnosis. Concurrent with the increasing need for ophthalmic care providers, ophthalmology education, however, has been marginalized worldwide as a consequence of decreasing curriculum time. This reIn this study, we for the first time evaluated the effectiveness and acceptability of the flipped classroom curriculum versus lecture-based curriculum of glaucoma and ocular trauma delivering to the international medical school students at Zhongshan Ophthalmic Center (ZOC) of Sun Yat-sen University in the spring of 2016.ZOC is the first western-style hospital in China., 25.24,


The signals that determine the choice between phagocytosis and the generation of NETs are still poorly characterized. Neutrophils that had phagocytosed bulky particulate substrates, such as apoptotic cells and activated platelets, appear to be “poised” in an unresponsive state. Environmental conditions, the metabolic, adhesive and activation state of the phagocyte, and the size of and signals associated with the tethered phagocytic cargo influence the choice of the neutrophils, prompting either phagocytic clearance or the generation of NETs. The choice is dichotomic and apparently irreversible. Defects in phagocytosis may foster the intravascular generation of NETs, thus promoting vascular inflammation and morbidities associated with diseases characterized by defective phagocytic clearance, such as systemic lupus erythematosus. There is a strong potential for novel treatments based on new knowledge of the events determining the inflammatory and pro-thrombotic function of inflammatory leukocytes.Neutrophils recognize particulate substrates of microbial or endogenous origin and react by sequestering the cargo  The release of neutrophil extracellular traps (NETs) vicariates frustrated or ineffective phagocytosis. It enhances the efficacy of the innate response coping with invading microbes. Moreover, NETs counterbalance microbial strategies to evade the immune response. NETs are large macromolecular structures that comprise neutrophil DNA, citrullinated histones, and an array of active proteases  , 26. Iniironment .Indeed cytokines and other signals important in phagocyte biology, including the growth factor, GM-CSF, are known to enhance the ability of neutrophils in the fluid phase to recognize and to internalize apoptotic cells –32. ConvNeutrophils and platelets frequently and extensively interact in the peripheral blood and at sites of inflammation. Their cross-talk is important in the maintenance of the homeostasis. Platelets scan the vascular surface and collect deposited bacteria, boosting neutrophil activities such as NET generation , while tin vitro and in vivo on platelet P-selectin interaction with the PSGL1 receptor on leukocytes . The direct or indirect recognition of PS on the prey can result in the rearrangement of actin-based cytoskeleton and the internalization of the tethered platelet by professional and non-professional phagocytes, such as endothelial cells , 68, 69.Third, the firm interaction between neutrophils and tethered PS-expressing phagocytic substrates is a potent inducer of NETs (see below). Indeed, regulation of the overall charge of the phagocytic substrate, like it occurs during apoptosis when glycosylated epitopes undergo caspase-dependent desialylation, influences the interaction between phagocyte and prey and the efficacy of the clearance .2+ concentration sharply increases, interfering with the translocase action and causing the rapid, patchy, potentially transient exposure of PS , highlighting the link of systemic autoimmunity, defective neutrophil function, and the recognition of PS  signal, suggesting that remission might be associated with a block of the ability to activate autophagy and to release inflammatory NETs  still uncharacterized signals activating the P2Y6 purinergic receptor/store-operated calcium entry/IL-8 axis  and (ii)ory NETs .via macrophage inflammasomes plays a critical role in atherosclerosis, and cholesterol crystals prompt in vivo NET generation. Macrophages exposed to NETs respond by activating the TH17 cell-dependent pathway that amplifies and sustains the recruitment of neutrophils within the atherosclerotic plaque  urate aggregates are a normal finding in the fluids of patients with hyperuricemia and only a fraction of these subjects develops acute gouty arthritis. Microaggregate clearance by blood neutrophils and monocytes prevents the actual precipitation of crystals, their frustrated phagocytosis, and the generation of NETs . PhagocyMicroparticles also trigger NETs generation, playing a role in the pathogenesis of diseases characterized by extensive vascular damage, such as lupus nephritis, systemic sclerosis, and preeclampsia , 157–160The size of the particulate dramatically influences the outcome of its interaction with neutrophils , 171. Ne(i)via a pathway dependent on the ability of elastase to cleave histones but independent of the enzymatic activity of myeloperoxidase in vitro and in vivo for NETs generation (Conversely, the integrity of the cytoskeleton is required to phagocytose particulate substrates. Neutrophils dismantle to generate NETs, the actin-based cytoskeleton, and are not competent anymore to phagocytose particulates. Small Rac GTPases, components of the NADPH oxidase NOX2 complex and required for the generation of NETs, regulate the cytoskeleton dynamics and adhesion , 176, prneration .Myeloperoxidase, elastase, and ROS are in parallel key signals in the generation of NETs. In this case, signals that activate neutrophils lead to an oxidative burst and to the generation of ROS in the absence of a competent phagolysome. Thus, ROS cannot promote the focused release of neutrophil enzyme within the vesicle, contributing to dismantle the internalized cargo. ROS promote the release of the azurosome complex, which contains among other components myeloperoxidase and elastase, from the membrane of azurophilic granules into the cytosol. The complex then binds to and degrades the actin-based cytoskeleton. This event is a critical checkpoint.NADPH oxidase activity is optimal at an intracellular pH of 7.5. An acute, transient drop in intracellular pH, dependent on H+ ions generated as a consequence of the NADPH oxidase activity, ensues the phagocytosis of opsonized bulky particulates  and acidPathways leading to NET generation differ in terms of dependence on oxygen species, of kinetics of the process, and of the fate of the involved neutrophils, which can either die or survive after NET generation conserving at least some of their biological function , 180–182The nucleus is not a passive target of the action of granular and cytosolic enzymes. At least two signals normally involved in chromatin architecture and function, DEK and HMGB1, actively regulate NET generation. Both molecules have a “double life.” Besides their action in the nucleus, they can be extruded or actively released in the extracellular environment where they regulate the inflammatory response. DEK, a highly conserved phosphoprotein involved in the control of genomic stability, is both an autoantigen and a chemoattractant signal whose role has been so far only partially characterized . Neutropvia NET induction—favoring a prothrombotic state in tumor-bearing patients (HMGB1 is as well a non-histone protein with an architectural function in the living cells [see above and , 190–192patients . HMGB1 ipatients –203. It in vivo, eventually leading to the termination of the apoptotic meal, i.e., to the failure of phagocytes that have internalized/are processing the prey to phagocytose further particulate substrates (noxa. Conversely, the systemic inflammatory response and enhanced thromboembolic risk, which are hallmarks of diseases associated with the failure of the phagocytic ability of neutrophils or macrophages, such as SLE, might thus reflect among other causes the lack of the calming effects of the phagocytic meal.Other mechanisms probably concur to explain the dichotomic nature of the neutrophil choice between phagocytosis and NET generation. Phagocytosis implies the sudden increase of the cell actual content depending on the ingestion of the phagocytic cargo with its own lipids, nucleic acids, proteins, etc. The metabolic pathways that allow the phagocyte to handle the further burden of internalized material have been only partially elucidated , 205. Thbstrates . A similAll authors listed have made substantial, direct, and intellectual contribution to the work and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.