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This study was conducted through a mixed-methods approach to determine whether implementing online collaborative learning (OCL) strategies in English-speaking classes had an effect on developing English-speaking skills and exploring the opinions of Myanmar migrant students in Thailand. A purposive sample group of 20 participants was chosen from the estimated 250 enrollments in the third semester of 2023 at the Bawaalin Myanmar Vocational Training Center in Thailand. The sample group was taught through OCL settings for a month. Its effectiveness was assessed using the three data collection instruments. The quantitative data acquired from English-speaking skills tests were evaluated using a paired sample t-test based on the mean, standard deviation, and significant value. The examination of the English-speaking skills test score revealed a significant mean difference of 14.14 (35.34%) between the pretest mean ([mu] = 13.50) and the posttest mean ([mu] = 27.64). The significance value was 0.000. The students' opinion questionnaires had a result of [alpha].90, indicating the excellent level of their opinions toward the method. The qualitative data obtained from a one-on-one student's opinion interview revealed that online collaborative learning has a positive impact on the overall opinions of Myanmar migrant students. The findings demonstrated that the English-speaking skills of Myanmar migrant students were developed, and their opinions toward the applied method were also at a high level. Therefore, online collaborative learning was strongly recommended for making a choice forteaching all subjects and skills in order to attain similar goals.

Based on well-known concepts, including organizational creativity, inclusive leadership theories as well as the input-process-output and its extended version, the current study investigated the effects an inclusive leadership style had on creative teaching through the mediating roles of intra-school knowledge sharing and innovative climate. A questionnaire using a convenience sampling method was conducted among 490 high school teachers in Vietnam, with a return rate of 95.5% (468 respondents) and 446 valid datasets for purposes of analysis. The study indicated that an inclusive leadership style has a positive effect on knowledge sharing, innovative climate, and creative teaching. The mediating role of knowledge sharing and innovative climate were also established in relation to inclusive leadership style and creative teaching. Theoretical and practical implications from our research include recommendations for governments, educators, and policymakers.

This study proposes a new model for integrating the protection motivation theory (PMT) with the technology acceptance model (TAM) to explore factors affecting students' intention to attend e-learning courses during the COVID-19 pandemic. A total of 432 valid responses to an online questionnaire were received from freshmen students studying in universities in Vietnam and Taiwan. Structural equation modeling was used to evaluate the proposed research model and test the hypotheses, and model evaluation reflected a good fit between the data and the proposed research model. Differences between perceived vulnerability, perceived severity, and intention to take e-learning courses across two countries were also established, suggesting that both the TAM and the PMT should be considered for use in studies related to technology adoption in the pandemic context. The factors influencing students' intentions to take online courses can be quite varied when different educational settings are considered; therefore, a more contextual understanding of students' e-learning intentions during pandemic times should be carefully examined. Suggestions for governments and policy makers are also proposed.

This study focused on evaluating the project on vocational training for rural laborers in Vietnam with respect to its effectiveness in employment creation and poverty reduction among rural laborers. The investigation took the form of a case study; official policy statistics, a survey of 300 project participants and interviews with eight vocational teachers were collected to triangulate the data. Our findings found that while the project met its initial objectives of increasing the trained laborer rate, creating jobs, and reducing poverty, Vietnam's traditional culture in addition to a lack of funding and vocational training poses potential obstacles to further increases in rural laborers' income and industrial transformation. In contrast to previous work, this study incorporated multidimensional poverty criteria with three sources of data from different stakeholders' perspectives to provide a more comprehensive and realistic picture of the long-term poverty reduction effect of the vocational training policy. Further implication for policy practice and policy evaluation method were discussed.

This study explored the gaming principles that fitted well in the theory of learning in good computer games and attempted to incorporate those principles into mathematics education. A qualitative dominant mixed methods approach was employed, in which qualitative interviews [eight students, six teachers and eight parents] and quantitative surveys [students, n = 174] were administered concurrently to explore the participants' thoughts and beliefs about mathematics education and computer games. Initially, gaming principles were identified and compared with the existing mathematics classroom setting. Then, a gamified approach was proposed. Data collected has indicated that the current mathematics education tends to be exam-oriented, predominantly product-focused, emphasizes drill-and-practice, without instant feedback, where mistakes are not welcomed and there is an absence of story. On the other hand, students learn differently when playing computer games. Gameplay is process-focused and involves problem-based learning, where instant feedback is provided. Computer games work on the principle of failing forward and often include stories. By applying the gaming principles into mathematics education, the authors propose mathematics education to be process-focused, problem-based, and promote an attitude of learning from mistakes, and suggest an introduction of storytelling into classroom activities.

Wikis are a supporting tool for pupils' learning and collaboration. Tasks such as cooperative authoring, joined workbooks creation, document review, group assignments, reflection notes and others have been tried out using wikis as a facilitating tool [1]. However, few studies have reported how students actually perceive some well-claimed benefits. This study investigated the perception of learning activities facilitated by wikis, and the effectiveness of several roles wikis might play in constructive and collaborative learning. This study tried to answer the following questions. How do students perceive a wiki as a learning tool? How does a wiki support constructive learning skills? How does a wiki support student's collaborative learning skills? How does collaboration in wiki facilitate students' content learning and project work? The study was conducted using a survey method to examine the perception of wiki usage and collaborative and constructive learning. In the reported study, a questionnaire was used to gather data from 92 graduate students. The results suggest that using wikis were perceived to enhance collaborative knowledge building among students, but it did not contribute much to learning the subject matter although students were more involved in the learning process than with conventional teaching methods. In other words, it indicates that students may not obtain better return of investment on the time spent in using wiki as a learning tool. While wiki did contribute to enrich the learning experience, further study is needed to investigate how to link the learning process with learning outcomes using this type of collaboration tools. (Contains 8 tables and 1 figure.)

The current project brings together academic and governmental specialists from Cambodia, Laos, and Viet Nam (CLV), in a collaborative study of the prospects for distance education (DE) in those countries. The study's overall objectives are to: (1) survey and take stock of existing educational scenarios and problems in CLV; (2) document the policies and research relating to DE practices in CLV and beyond; (3) discuss these policies and practices with national core groups, policy and decision makers; (4) initiate strategies for networked collaboration among CLV's educational institutions; (5) build DE capacity by "training the trainers" in a variety of distance teaching and learning skills; and (6) formulate recommendations for the development of detailed DE initiatives in the three nations. This article reports on the early stages of this project: the implementation of a stakeholder survey in the three countries, and a study of existing policies and practices. The project is funded in 2005-2008 by the International Development Research Centre (IDRC), whose PANdora model provides a collaborative basis to assist the teams in developing a common research strategy and in avoiding duplication of effort. (Contains 2 tables.)

This paper examines the state of physics teaching and learning in the Pacific Island nations. How have things changed in teaching physics? We believe that some of the goals and many of the challenges faced today have changed very little over the years. This paper is purely based upon the authors' experiences in teaching physics at the first-year level at the University of the South Pacific (USP). USP is a typical medium-sized teaching and research university as compared to universities internationally. In the Pacific, it is the biggest university and is effectively serving the 12 Pacific Island nations. Consequently, the findings described here should represent the overall situation for the Pacific region. Perhaps some of our results will resonate with readers in other locations as well. Worldwide, university students often find studying physics to be very challenging, and only a small fraction of them choose physics as a major for their degree or as a career. Students at USP are not an exception, and here we describe the severity of the problem.

Background: Current anti-obesity medications suffer from limited efficacy and side-effects because they act indirectly on either the central nervous system or gastrointestinal system. Herein, this work aims to introduce a transdermal photothermal and nanocatalytic therapy enabled by Prussian blue nanoparticles, which directly act on obese subcutaneous white adipose tissue (sWAT) to induce its beneficial remodeling including stimulation of browning, lipolysis, secretion of adiponectin, as well as reduction of oxidative stress, hypoxia, and inflammation. Methods: Prussian blue nanoparticles were synthesized and incorporated into silk fibroin hydrogel for sustained retention. The efficacy of mild photothermal (808 nm, 0.4 W/cm 2 , 5 min) and nanocatalytic therapy (mPTT-NCT) was assessed both in vitro (3T3-L1 adipocytes) and in vivo (obese mice). The underlying signaling pathways are carefully revealed. Additionally, biosafety studies were conducted to further validate the potential of this therapy for practical application. Results: On 3T3-L1 adipocytes, mPTT-NCT was able to induce browning, enhance lipolysis, and alleviate oxidative stress. On obese mice model, the synergistic treatment led to not only large mass reduction of the targeted sWAT (53.95%) but also significant improvement of whole-body metabolism as evidenced by the substantial decrease of visceral fat (65.37%), body weight (9.78%), hyperlipidemia, and systemic inflammation, as well as total relief of type 2 diabetes. Conclusions: By directly targeting obese sWAT to induce its beneficial remodeling, this synergistic therapy leads to significant improvements in whole-body metabolism and the alleviation of obesity-related conditions, including type 2 diabetes. The elucidation of underlying signaling pathways provides fundamental insights and shall inspire new strategies to combat obesity and its associated diseases., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Although aversive responses to sensory stimuli are common in autism spectrum disorder (ASD), it remains unknown whether the social relevance of aversive sensory inputs affects their processing. We used functional magnetic resonance imaging (fMRI) to investigate neural responses to mildly aversive nonsocial and social sensory stimuli as well as how sensory over-responsivity (SOR) severity relates to these responses. Participants included 21 ASD and 25 typically-developing (TD) youth, aged 8.6-18.0 years. Results showed that TD youth exhibited significant neural discrimination of socially relevant versus irrelevant aversive sensory stimuli, particularly in the amygdala and orbitofrontal cortex (OFC), regions that are crucial for sensory and social processing. In contrast, ASD youth showed reduced neural discrimination of social versus nonsocial stimuli in the amygdala and OFC, as well as overall greater neural responses to nonsocial compared with social stimuli. Moreover, higher SOR in ASD was associated with heightened responses in sensory-motor regions to socially-relevant stimuli. These findings further our understanding of the relationship between sensory and social processing in ASD, suggesting limited attention to the social relevance compared with aversiveness level of sensory input in ASD versus TD youth, particularly in ASD youth with higher SOR., (© 2024 The Author(s). Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Implementation of evidence-based practice (EBP) is essential for ensuring high-quality nursing care. In Portugal, nurses are responsible for care delivery to patients who require peripheral intravenous access. However, recent authors emphasized the predominance of a culture based on outdated professional vascular access practices in Portuguese clinical settings. Thus, the aim of this study was to map the studies conducted in Portugal on peripheral intravenous catheterization. A scoping review was conducted based on the Joanna Briggs Institute recommendations, with a strategy adapted to different scientific databases/registers. Independent reviewers selected, extracted, and synthesized the data. Of the 2128 studies found, 26 were included in this review, published between 2010 and 2022. Previous research shows that Portuguese nurses' implementation of EBP was found to be relatively low overall, while most studies did not attempt to embed EBP change into routine care. Although nurses are responsible for implementing EBP at an individual patient level, the studies conducted in Portugal report nonstandardized practices among professionals, with significant deviations from recent evidence. This reality, combined with Portugal's absence of government-endorsed evidence-based standards for peripheral intravenous catheter (PIVC) insertion and treatment and vascular access teams, may explain the country's unacceptably high incidence of PIVC-related complications reported over the last decade., (Copyright © 2023 Infusion Nurses Society.)

Background: This study aimed to (1) investigate the association of prognostic awareness with psychological (distress level and emotional well-being) and spiritual well-being among patients with heart failure, and (2) assess the main and moderating effects of illness acceptance on the relationship between prognostic awareness and psychological and spiritual well-being., Methods and Results: This study used baseline data of a Singapore cohort of patients with heart failure (N = 245) who had New York Heart Association class 3 or 4 symptoms. Patients reported their awareness of prognosis and extent of illness acceptance. Multivariable linear regressions were used to investigate the associations. Prognostic awareness was not significantly associated with psychological and spiritual well-being. Illness acceptance was associated with lower levels of distress (β [SE] = -0.9 [0.2], P < .001), higher emotional well-being (β [SE] = 2.2 [0.4], P < .001), and higher spiritual well-being (β [SE] = 5.4 [0.7], P < .001). Illness acceptance did not moderate the associations of prognostic awareness with psychological and spiritual well-being., Conclusions: This study suggests that illness acceptance could be a key factor in improving patient well-being. Illness acceptance should be regularly assessed and interventions to enhance illness acceptance should be considered for those with poor acceptance., Competing Interests: Disclosure The authors declare that they have no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Context: The Good Health & Great Hair program was developed by Kaiser Permanente in partnership with a network of trusted neighborhood barbershops and beauty salons in West Baltimore, Maryland., Program: The initiative aimed to increase health awareness and knowledge and reduce health disparities by making no-cost health care services available beyond traditional health care settings in predominantly Black, historically redlined neighborhoods in West Baltimore., Implementation: This initiative, established by an integrated health care system, is the first to utilize mobile health clinics into a holistic community health outreach program in partnership with barbershops and beauty salons to provide medical and social services to underserved populations. In addition to the mobile health clinics, key features of this program included lay first responder trainings on topics of physical and behavioral health, on-site medical and social services offered by community partners, and culturally relevant mental health programming. The majority of participants (n = 1823) were male (58%), Black (86%), and between the ages of 45 and 64 years (51%)., Evaluation: Data presented include the number of clinical and social services provided. More than 8000 clinical and social services were provided between September 2016 and March 2020. Blood pressure (n = 2317), diabetes (n = 469), tobacco (n = 448), and cholesterol (n = 443) were the most accessed clinical screening services. The median number of clinical services provided per client was 2. Fitness (n = 1496), job search support (n = 1123), mental health (n = 603), and health insurance (n = 455) were the most accessed social services., Discussion: The initiative delivered critical health and social support services through a partnership with an established integrated health care system, community barbershops and beauty salons, a mobile health team, and social supports. This novel program utilized a mobile health clinic to provide extensive clinical services complemented by on-site social services. Patterns of service utilization and lessons learned could inform the design of similar programs., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Despite the increasing prevalence of obesity, the current medications, which act indirectly on the central nervous system to suppress appetite or on the gastrointestinal tract to inhibit fat absorption, suffer from poor effectiveness and side effects. Here, we developed a transdermal mild photothermal therapy directly acting on the root of evil (subcutaneous white adipose depot) to induce its ameliorating remodeling (browning, lipolysis, and apoptosis), based on the injectable thermoresponsive hydrogel encapsulated with copper sulfide nanodots. Further, combining pharmaceutical therapy with codelivery of mirabegron leads to a strong therapeutic synergy. This method not only ensures high effectiveness and low side effects due to localized and targeted application but also remotely creates significant improvements in systemic metabolism. Specifically, as compared to the untreated group, it totally inhibits obesity development in high-fat-diet fed mice (15% less in body weight) with decreased masses of both subcutaneous (40%) and visceral fats (54%), reduced serum levels of cholesterol (54%)/triglyceride (18%)/insulin (74%)/glucose (45%), and improved insulin sensitivity (65% less in insulin resistance index). This self-administrable method is amenable for long-term home-based treatment. Finally, multiple interconnected signaling pathways are revealed, providing mechanistic insights to develop effective strategies to combat obesity and associated metabolic disorders.

Teprotumumab was the first and only medication approved by the US Food and Drug Administration for the treatment of thyroid eye disease in January 2020. Thyroid eye disease is a complex autoimmune inflammatory disease that can be sight-threatening, debilitating, and disfiguring to affected patients. Although biologic therapies are a preferred treatment option for many complex immunologic and oncologic conditions, their use in ophthalmology and endocrinology may be more novel. The goals of this article are to introduce this new therapeutic option; discuss its mechanism of action, indications for use, administration protocol, infusion precautions, and informed consent; and review common side effects and management., Competing Interests: K. Cockerham and R. Douglas are on the Horizon Therapeutics Medical Advisory Board. A. Kossler is a consultant for Horizon Therapeutics. J. Kang, M. Lechuga, and J. Braun have no conflicts of interest to disclose., (Copyright © 2021 Infusion Nurses Society.)

Cell therapies for the treatment of skin disorders could benefit from simple, safe and efficient technology for the transdermal delivery of therapeutic cells. Conventional cell delivery by hypodermic-needle injection is associated with poor patient compliance, requires trained personnel, generates waste and has non-negligible risks of injury and infection. Here, we report the design and proof-of-concept application of cryogenic microneedle patches for the transdermal delivery of living cells. The microneedles are fabricated by stepwise cryogenic micromoulding of cryogenic medium with pre-suspended cells, and can be easily inserted into porcine skin and dissolve after deployment of the cells. In mice, cells delivered by the cryomicroneedles retained their viability and proliferative capability. In mice with subcutaneous melanoma tumours, the delivery of ovalbumin-pulsed dendritic cells via the cryomicroneedles elicited higher antigen-specific immune responses and led to slower tumour growth than intravenous and subcutaneous injections of the cells. Biocompatible cryomicroneedles may facilitate minimally invasive cell delivery for a range of cell therapies., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

The commensal microbiota is a key modulator of animal fitness, but little is known about the extent to which the parental microbiota influences fitness-related traits of future generations. We addressed this gap by manipulating the parental microbiota of a polyphagous fruit fly ( Bactrocera tryoni ) and measuring offspring developmental traits, body composition, and fecundity. We generated three parental microbiota treatments where parents had a microbiota that was non-manipulated (control), removed (axenic), or removed-and-reintroduced (reinoculation). We found that the percentage of egg hatching, of pupal production, and body weight of larvae and adult females were lower in offspring of axenic parents compared to that of non-axenic parents. The percentage of partially emerged adults was higher, and fecundity of adult females was lower in offspring of axenic parents relative to offspring of control and reinoculated parents. There was no significant effect of parental microbiota manipulation on offspring developmental time or lipid reserve. Our results reveal transgenerational effects of the parental commensal microbiota on different aspects of offspring life-history traits, thereby providing a better understanding of the long-lasting effects of host-microbe interactions.

Obesity is a serious epidemic health problem that can cause many other diseases including type 2 diabetes and cardiovascular diseases. Current approaches to combat obesity suffer from low effectiveness and adverse side effects. Here, a new self-administrable and minimally invasive transdermal drug delivery strategy for home-based long-term treatment of obesity and other diseases is developed. Specifically, ultrathin, core-shelled, and lance-shaped polymeric drug reservoirs (micro-lances [MLs]) are readily fabricated by a thermal pressing molding method and totally implanted into subcutaneous fat by lancing through the skin. Using a diet-induced obese mouse model, it is shown that the development of obesity and associated metabolic disorders is effectively inhibited by applying therapeutic core-shelled MLs once every 2 weeks. The outstanding therapeutic effects are attributable to highly localized and biphasic drug release, as well as combination therapy based on browning transformation of white fat and enhanced insulin sensitivity., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The emergence and spread of drug resistance is a problem hindering malaria elimination in Southeast Asia. In this study, genetic variations in drug resistance markers of Plasmodium falciparum were determined in parasites from asymptomatic populations located in three geographically dispersed townships of Myanmar by PCR and sequencing. Mutations in dihydrofolate reductase ( pfdhfr ), dihydropteroate synthase ( pfdhps ), chloroquine resistance transporter ( pfcrt ), multidrug resistance protein 1 ( pfmdr1 ), multidrug resistance-associated protein 1 ( pfmrp1 ), and Kelch protein 13 ( k13 ) were present in 92.3%, 97.6%, 84.0%, 98.8%, and 68.3% of the parasites, respectively. The pfcrt K76T, pfmdr1 N86Y, pfmdr1 I185K, and pfmrp1 I876V mutations were present in 82.7%, 2.5%, 87.5%, and 59.8% isolates, respectively. The most prevalent haplotypes for pfdhfr, pfdhps, pfcrt and pfmdr1 were 51I/59R/108N/164L, 436A/437G/540E/581A, 74I/75E/76T/220S/271E/326N/356T/371I, and 86N/130E/184Y/185K/1225V, respectively. In addition, 57 isolates had three different point mutations (K191T, F446I, and P574L) and three types of N-terminal insertions (N, NN, NNN) in the k13 gene. In total, 43 distinct haplotypes potentially associated with multidrug resistance were identified. These findings demonstrate a high prevalence of multidrug-resistant P. falciparum in asymptomatic infections from diverse townships in Myanmar, emphasizing the importance of targeting asymptomatic infections to prevent the spread of drug-resistant P. falciparum .

This paper describes novel tobacco control laws passed in New York City in 2017. These laws are designed to improve the city's strategy of using price to decrease tobacco consumption, and over time, change the city's landscape by making tobacco less accessible.

In holometabolous insects, adult fitness depends on the quantity and quality of resource acquired at the larval stage. Diverse ecological factors can influence larval resource acquisition, but little is known about how these factors in the larval environment interact to modulate larval development and adult traits.Here, we addressed this gap by considering how key ecological factors of larval density, diet nutritional composition, and microbial growth interact to modulate pupal and adult traits in a polyphagous tephritid fruit fly, Bactrocera tryoni (aka "Queensland fruit fly").Larvae were allowed to develop at two larval densities (low and high), on diets that were protein-rich, standard, or sugar-rich and prepared with or without preservatives to inhibit or encourage microbial growth, respectively.Percentage of adult emergence and adult sex ratio were not affected by the interaction between diet composition, larval density, and preservative treatments, although low preservative content increased adult emergence in sugar-rich diets but decreased adult emergence in protein-rich and standard diets.Pupal weight, male and female adult dry weight, and female (but not male) body energetic reserves were affected by a strong three-way interaction between diet composition, larval density, and preservative treatment, whereby in general, low preservative content increased pupal weight and female lipid storage in sugar-rich diets particularly at low-larval density and differentially modulated the decrease in adult body weight caused by larval density across diets.Our findings provide insights into the ecological factors modulating larval development of a polyphagous fly species and shed light into the ecological complexity of the larval developmental environment in frugivorous insects., Competing Interests: None to declare.

Background: The malaria burden of Myanmar still remains high within the Greater Mekong Subregion of Southeast Asia. An important indicator of progress towards malaria elimination is the prevalence of parasite infections in endemic populations. Information about malaria epidemiology is mostly derived from reports of confirmed acute malaria cases through passive case detection, whereas the prevalence of baseline subclinical malaria infections is much less known., Methods: In this study, cross-sectional surveys were conducted during the rainy season of 2017 in four townships (Bilin, Thabeikkyin, Banmauk and Paletwa) of Myanmar with divergent annual malaria incidences. A total of 1991 volunteers were recruited from local villages and Plasmodium subclinical infections were estimated by light microscopy (LM), rapid diagnostic tests (RDTs) and nested PCR. The nested PCR analysis was performed with a modified pooling strategy that was optimized based on an initial estimate the infection prevalence., Results: The overall malaria infection prevalence based on all methods was 13.9% (277/1991) and it differed drastically among the townships, with Paletwa in the western border having the highest infection rate (22.9%) and Thabeikkyin in central Myanmar having the lowest (3.9%). As expected, nested PCR was the most sensitive and identified 226 (11.4%) individuals with parasite infections. Among the parasite species, Plasmodium vivax was the most prevalent in all locations, while Plasmodium falciparum also accounted for 32% of infections in the western township Paletwa. Two RDTs based on the detection of the hrp2 antigen detected a total of 103 P. falciparum infections, and the ultrasensitive RDT detected 20% more P. falciparum infections than the conventional RDT. In contrast, LM missed the majority of the subclinical infections and only identified 14 Plasmodium infections., Conclusions: Cross-sectional surveys identified considerable levels of asymptomatic Plasmodium infections in endemic populations of Myanmar with P. vivax becoming the predominant parasite species. Geographical heterogeneity of subclinical infections calls for active surveillance of parasite infections in endemic areas. The pooling scheme designed for nested PCR analysis offers a more practical strategy for large-scale epidemiological studies of parasite prevalence. Such information is important for decision-makers to put forward a more realistic action plan for malaria elimination.

Bradykinin mediated angioedema (BK-AE) can be associated either with C1Inhibitor deficiency (hereditary and acquired forms), either with normal C1Inh (hereditary form and drug induced AE as angiotensin converting enzyme inhibitors…). In case of high clinical suspicion of BK-AE, C1Inh exploration must be done at first: C1Inh function and antigenemy as well as C4 concentration. C1Inh deficiency is significant if the tests are below 50 % of the normal values and controlled a second time. In case of C1Inh deficiency, you have to identify hereditary from acquired forms. C1q and anti-C1Inh antibody tests are useful for acquired BK-AE. SERPING1 gene screening must be done if a hereditary angioedema is suspected, even if there is no family context (de novo mutation 15 %). If a hereditary BK-AE with normal C1Inh is suspected, F12 and PLG gene screening is suitable., (Copyright © 2018. Published by Elsevier Masson SAS.)

Eye diseases and injuries impose a significant clinical problem worldwide. Safe and effective ocular drug delivery is, however, challenging due to the presence of ocular barriers. Here we report a strategy using an eye patch equipped with an array of detachable microneedles. These microneedles can penetrate the ocular surface tissue, and serve as implanted micro-reservoirs for controlled drug delivery. The biphasic drug release kinetics enabled by the double-layered micro-reservoirs largely enhances therapeutic efficacy. Using corneal neovascularization as the disease model, we show that delivery of an anti-angiogenic monoclonal antibody (DC101) by such eye patch produces ~90% reduction of neovascular area. Furthermore, quick release of an anti-inflammatory compound (diclofenac) followed by a sustained release of DC101 provides synergistic therapeutic outcome. The eye patch application is easy and minimally invasive to ensure good patient compliance. Such intraocular drug delivery strategy promises effective home-based treatment of many eye diseases.

[This corrects the article DOI: 10.1038/sigtrans.2017.22.].

Hydrogen sulfide (H2S), being an important gaseous signaling molecule, has been gaining increasing attention for its involvement in a wide range of physiological processes. Herein, we developed a novel fluorescence turn-on nanoprobe for selective and sensitive detection of H2S based on graphene quantum dots (GQDs) conjugated with (2,4-dinitrophenoxy)tyrosine (DNPTYR). Taking advantage of its high fluorescence quantum yield, biocompatibility, photostability, and ease to be uptaken by cells, the GQD-based fluorescence probe was further employed for real-time monitoring of the triggered dynamic change of the intracellular H2S level in live cells.

Skin interstitial fluid (ISF) is an emerging source of biomarkers for disease diagnosis and prognosis. Microneedle (MN) patch has been identified as an ideal platform to extract ISF from the skin due to its pain-free and easy-to-administrated properties. However, long sampling time is still a serious problem which impedes timely metabolic analysis. In this study, a swellable MN patch that can rapidly extract ISF is developed. The MN patch is made of methacrylated hyaluronic acid (MeHA) and further crosslinked through UV irradiation. Owing to the supreme water affinity of MeHA, this MN patch can extract sufficient ISF in a short time without the assistance of extra devices, which remarkably facilitates timely metabolic analysis. Due to covalent crosslinked network, the MN patch maintains the structure integrity in the swelling hydrated state without leaving residues in skin after usage. More importantly, the extracted ISF metabolites can be efficiently recovered from MN patch by centrifugation for the subsequent offline analysis of metabolites such as glucose and cholesterol. Given the recent trend of easy-to-use point-of-care devices for personal healthcare monitoring, this study opens a new avenue for the development of MN-based microdevices for sampling ISF and minimally invasive metabolic detection., (© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Brown adipose tissue dissipates energy in the form of heat. Recent studies have shown that adult humans possess both classical brown and beige adipocytes (brown-like adipocytes in white adipose tissue, WAT), and stimulating brown and beige adipocyte formation can be a new avenue to treat obesity. Angiotensin II (AngII) is a peptide hormone that plays important roles in energy metabolism via its angiotensin type 1 or type 2 receptors (AT1R and AT2R). Adipose tissue is a major source of AngII and expresses both types of its receptors, implying the autocrine and paracrine role of AngII in regulating adipose functions and self-remodeling. Here, based on the in vitro studies on primary cultures of mouse white adipocytes, we report that, AT2R activation, either by AngII or AT2R agonist (C21), induces white adipocyte browning, by increasing PPARγ expression, at least in part, via ERK1/2, PI3kinase/Akt and AMPK signaling pathways. It is also found that AngII-AT2R enhances brown adipogenesis. In the in vivo studies on mice, administration of AT1R antagonist (ZD7155) or AT2R agonist (C21) leads to the increase of WAT browning, body temperature and serum adiponectin, as well as the decrease of WAT mass and the serum levels of TNFα, triglycerides and free fatty acids. In addition, AT2R-induced browning effect is also observed in human white adipocytes, as evidenced by the increased UCP1 expression and oxygen consumption. Finally, we provide evidence that AT2R plays important roles in hormone T3-induced white adipose browning. This study, for the first time, reveals the browning and brown adipogenic effects of AT2R and suggests a potential therapeutic target to combat obesity and related metabolic disorders., Competing Interests: The authors declare no conflict of interest.

Monitoring cellular redox homeostasis is critical to the understanding of many physiological functions ranging from immune reactions to metabolism, as well as to the understanding of pathological development ranging from tumorigenesis to aging. Nevertheless, there is currently a lack of appropriate probes for this ambition, which should be reversibly, sensitively, and promptly responsive to a wide range of physiological oxidants and reductants. In this work, a redox-sensitive fluorescence-switchable probe is designed based on graphene quantum dots (GQDs) functionalized with a chelated redox Fe 2+ /Fe 3+ couple. The underlying mechanism is investigated and discussed. The high sensitivity and fast response are attributable to the fact that the GQD's photoluminescence is highly sensitive to photon-induced electron transfer because of its ultrasmall size and associated prominent quantum confinement effect. Also taking advantages of GQDs' excellent photostability, biocompatibility, and readiness for cell uptake, our reversibly tunable fluorescence probe is employed to monitor in real time the triggered dynamic change of the intracellular redox state. This addition to the limited arsenal of available redox probes shall be useful to the still poorly understood redox biology, as well as for monitoring environment or chemical processes involving redox reactions.

Acid-base homeostasis is essential to normal function of the human body. Even slight alterations can significantly alter physiologic processes at the tissue and cellular levels. To optimally care for patients, nurses must be able to recognize signs and symptoms that indicate deviations from normal. Nurses who provide infusions to patients-whether in acute care, home care, or infusion center settings-have a responsibility to be able to recognize the laboratory value changes that occur with the imbalance and appreciate the treatment options, including intravenous infusions.

Graphene quantum dots (GQDs) are emerging fluorescence reporters attractive for optical sensing, owing to their high photostability, highly tunable photoluminescence, molecular size, atomically thin structure, biocompatibility, and ease of functionalization. Herein, we present a fluorometric sensing platform based on tyramine-functionalized GQDs, which is able to detect a spectrum of metabolites with high sensitivity and specificity. Furthermore, multiparametric blood analysis (glucose, cholesterol, L-lactate, and xanthine) is demonstrated. This convenient metabolite profiling technique could be instrumental for diagnosis, study, and management of metabolic disorders and associated diseases, such as diabetes, obesity, lactic acidosis, gout, and hypertension.

Background: Behaviour change communication (BCC) can improve malaria prevention and treatment behaviour. As a one of the activities under Myanmar Artemisinin Resistance Containment (MARC) programme, BCC have been conducting. This study aimed to evaluate the effectiveness of the behaviour change communication and community mobilization activities in MARC zones in Myanmar., Methods: A cross sectional descriptive survey was conducted in randomly selected 16 townships in Tier I and II areas of MARC zones by quantitative and qualitative approaches., Results: In 832 households resided by 4664 people, there were 3797 bed nets. Around 54% were untreated while 45.6% were insecticide-treated nets (ITN) and 36.2% were long-lasting insecticide-treated nets (LLINs). Proportion of households with at least one ITN was 625 (75.12%), proportion of households with at least one ITN for every two peoples was 487 (58.53%), and proportion of existing ITNs used in previous night was 1225 (70.65%) respectively. Nearly 23% of households had old nets while 52% had new and unused extra bed nets reflecting the adequacy. Interestingly, 38% could not mention the benefit of the use of ITN/LLINs. Although 88.2% knew the disease "malaria", 11.9% could not be able to mention the symptoms. More than 80% provided correct responses that mosquito bite can cause malaria while only 36.9% could mention the blood test for malaria diagnosis. Only 36.6% received malaria information within previous year but nearly 15% could not recognize it. Mostly, 80% of fever episodes were treated at rural health centers (38.24%) followed by drug shops (17.65%) and private clinics (16.18%) respectively., Conclusions: Efforts should focus on correcting misconceptions about malaria transmission, prevention and universal use of ITN/LLINs. Although BCC activities have been documented, it is still necessary to intensify community mobilization through all accessible multiple channels in MARC areas.

Brown adipose tissue expends energy in the form of heat via the mitochondrial uncoupling protein UCP1. Recent studies showed that brown adipose tissue is present in adult humans and may be exploited for its anti-obesity and anti-diabetes actions. Apelin is an adipocyte-derived hormone that plays important roles in energy metabolism. Here, we report that apelin-APJ signaling promotes brown adipocyte differentiation by increasing the expressions of brown adipogenic and thermogenic transcriptional factors via the PI3K/Akt and AMPK signaling pathways. It is also found that apelin relieves the TNFα inhibition on brown adipogenesis. In addition, apelin increases the basal activity of brown adipocytes, as evidenced by the increased PGC1α and UCP1 expressions, mitochondrial biogenesis, and oxygen consumption. Finally, we provide both in vitro and in vivo evidence that apelin is able to increase the brown-like characteristics in white adipocytes. This study, for the first time, reveals the brown adipogenic and browning effects of apelin and suggests a potential therapeutic route to combat obesity and related metabolic disorders., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Graphene quantum dots (GQDs) are emerging zero-dimensional materials promising a wide spectrum of applications, particularly, as superior fluorescent reporters for bio-imaging and optical sensing. Heteroatom doping can endow GQDs with new or improved photoluminescence properties. Here, we demonstrate a simple strategy for the synthesis of nitrogen and phosphorus co-doped GQDs from a single biomolecule precursor (adenosine triphosphate - ATP). Such ATP-GQDs exhibit high fluorescence quantum yield, strong two-photon upconversion, small molecular weight, high photostability, and good biocompatibility. Furthermore, transferrin conjugated ATP-GQDs have been used for imaging and real-time tracking of transferrin receptors in live cells.

The purpose of this article is to describe how the concept of infusion nursing was incorporated into orientation for new graduate nurses at an academic medical center in the Midwest. Strategies were identified based on their unique learning needs and a desire to instill safe infusion practices early in their nursing careers. (A Supplemental Video Abstract for this article is available at http://links.lww.com/JIN/A64.).

Objective: Tumors of the jugular foramen are notably rare, and the majority of them arise from the glomic tissue of the jugular vein. There are other tumors that do not originate from that tissue, and these are called the nonglomic tumors. This report includes a series of patients with nonglomic tumors of the jugular foramen to analyze their biological and radiological behavior and the clinical outcomes of patients., Methods: Patients with tumors of the jugular foramen other than chemodectomas were included for the present series. All of the patients were subjected to a protocol that included imaging studies and a complete clinical evaluation. Surgery was planned and performed by a multidisciplinary team using the following approaches: retrosigmoid, infratemporal fossa, and zygomatic-transmandibular. Depending on the precise diagnosis and surgical outcomes, radiotherapy or radiosurgery were indicated. The average follow-up period was 5 years., Results: Thirty patients with nonglomic tumors were included: 18 schwannomas, 6 meningiomas, 5 chordomas, and 1 metastatic carcinoma. The patients with chordomas had the most severe clinical manifestations, and the chordomas were the largest and most invasive tumors that destroyed the jugular foramen contour on imaging studies. Schwannomas presented a more benign clinical evolution and enlarged (but did not destroy) the jugular foramen contour. Two patients died (chordomas) during the follow-up because of tumor activity., Conclusions: The most common nonglomic tumor of the jugular foramen was the schwannoma, which was the lesion with the best surgical prognosis. Chordoma is a rare and highly destructive tumor that has a notably high recurrence index., (Copyright © 2014 Elsevier Inc. All rights reserved.)

It has been recently recognized that the increased oxidative stress (ROS overproduction) in obese condition is a key contributor to the pathogenesis of obesity-associated metabolic diseases. Apelin is an adipocytokine secreted by adipocytes, and known for its anti-obesity and anti-diabetic properties. In obesity, both oxidative stress and plasma level of apelin are increased. However, the regulatory roles of apelin on oxidative stress in adipocytes remain unknown. In the present study, we provide evidence that apelin, through its interaction with apelin receptor (APJ), suppresses production and release of reactive oxygen species (ROS) in adipocytes. This is further supported by the observations that apelin promotes the expression of anti-oxidant enzymes via MAPK kinase/ERK and AMPK pathways, and suppresses the expression of pro-oxidant enzyme via AMPK pathway. We further demonstrate that apelin is able to relieve oxidative stress-induced dysregulations of the expression of anti- and pro-oxidant enzymes, mitochondrial biogenesis and function, as well as release of pro- and anti-inflammatory adipocytokines. This study, for the first time, reveals the antioxidant properties of apelin in adipocytes, and suggests its potential as a novel therapeutic target for metabolic diseases.

The thermal oxidation of carbon nanotubes in air is investigated by in situ Raman spectroscopy. Etching rates are directly seen to be diameter, chirality, and type dependent. We directly track the evolution of bundled nanotube networks that undergo air etching from 300 to 600 °C. Some species are more robust than others. Changes to radial breathing mode (RBM) and G- peak structures suggest that metallic species etch away more rapidly, with smaller diameter semiconducting species etching more slowly and large diameter nanotubes, including semiconductors, etching last. The decay in integrated G and D band intensities is tracked and fit reasonably well with biexponential decay. The RBM evolution is better represented by a single exponential. All bands are fit to activation plots with RBMs showing significantly different rates.

Graphene quantum dots (GQDs) hold great promise as a new class of fluorophores for bioimaging, owing to their remarkable physicochemical properties including tunable photoluminescence, excellent photostability, and biocompatibility. Despite their highly anticipated potentials, GQDs have yet to be used to specifically label and track molecular targets involved in dynamic cellular processes in live cells. Here, we demonstrate that GQDs can serve as universal fluorophores for bioimaging because they can be readily conjugated with a wide range of biomolecules while preserving their functionalities. As a proof-of-concept demonstration, insulin-conjugated GQDs have been synthesized and utilized for specific labeling and dynamic tracking of insulin receptors in 3T3-L1 adipocytes. Our experiments reveal, for the first time, that the internalization and recycling of insulin receptors in adipocytes are oppositely regulated by apelin and TNFα, which may contribute to the regulations of these two cytokines in insulin sensitivity.

Biofuel cells (BFCs), which use enzymes as catalysts to harvest energy from green and sustainable fuels abundantly producible from biological systems, are promising next-generation energy devices. However, the poor stability and high specificity to only one fuel type of these bio-catalysts largely limits the practical use of current BFCs. In this contribution, we demonstrate a unique fuel cell which, equipped with two identical enzyme-free electrodes based on Co3O4 coated 3D graphene, is able to efficiently harvest electricity from various sweet biofuels (glucose, sucrose, or lactose). Taking advantage of the dual catalytic ability of nanostructured Co3O4 for both glucose oxidation and oxygen reduction as well as the exceptional electrical and structural properties of 3D graphene, our glucose-powered fuel cell, with good long-term stability, offers high open circuit voltage (~1.1 V) and power density output (2.38 ± 0.17 mW cm(-2)).

Angiotensin II (AngII), a peptide hormone released by adipocytes, can be catabolized by adipose angiotensin-converting enzyme 2 (ACE2) to form Ang(1-7). Co-expression of AngII receptors (AT1 and AT2) and Ang(1-7) receptors (Mas) in adipocytes implies the autocrine regulation of the local angiotensin system upon adipocyte functions, through yet unknown interactive mechanisms. In the present study, we reveal the adipogenic effects of Ang(1-7) through activation of Mas receptor and its subtle interplays with the antiadipogenic AngII-AT1 signaling pathways. Specifically, in human and 3T3-L1 preadipocytes, Ang(1-7)-Mas signaling promotes adipogenesis via activation of PI3K/Akt and inhibition of MAPK kinase/ERK pathways, and Ang(1-7)-Mas antagonizes the antiadipogenic effect of AngII-AT1 by inhibiting the AngII-AT1-triggered MAPK kinase/ERK pathway. The autocrine regulation of the AngII/AT1-ACE2-Ang(1-7)/Mas axis upon adipogenesis has also been revealed. This study suggests the importance of the local regulation of the delicately balanced angiotensin system upon adipogenesis and its potential as a novel therapeutic target for obesity and related metabolic disorders.

Apelin is an adipokine secreted by adipocytes. Co-expression of apelin and apelin receptor (APJ) in adipocytes implies the autocrine regulations of apelin on adipocyte functions through yet unknown molecular mechanisms. In the present study, we provide evidence that apelin, through its interaction with APJ receptor, inhibits adipogenesis of pre-adipocytes and lipolysis in mature adipocytes. The detailed molecular pathways underlying apelin signaling is proposed based on our experimental observations. Specifically, we show that apelin suppresses adipogenesis through MAPK kinase/ERK dependent pathways. And by preventing lipid droplet fragmentation, apelin inhibits basal lipolysis through AMP kinase dependent enhancement of perilipin expression and inhibits hormone-stimulated acute lipolysis through decreasing perilipin phosphorylation. Apelin induced decrease of free fatty acid release can be attributed to its dual inhibition on adipogenesis and lipolysis. This study suggests that the autocrine signaling of apelin may serve as a novel therapeutic target for obesity and other metabolic disorders., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Adipocytes play pivotal roles in regulating metabolism through secretion of a variety of adipokines, which in turn is regulated by other metabolic factors (e.g., insulin). Understanding the regulations of adipokine secretion is important because adipokines are implicated with metabolic disorders, such as, obesity and diabetes mellitus. Here, we investigated the regulatory roles of angiotensin II (AngII) on the secretion of apelin in 3T3-L1 adipocytes, and distinct signaling pathways mediated by AngII receptor type 1 (AT₁) and type 2 (AT₂) were revealed. It was found that activation of AT₁ receptors stimulates apelin secretion in Ca²⁺, protein kinase C, and MAPK kinase dependent ways while activation of AT₂ receptors inhibits apelin secretion through cAMP and cGMP dependent pathways. Furthermore, we demonstrate that the expression of apelin receptor (APJ) is also similarly regulated by AT₁ and AT₂ receptors. Finally, a detailed AngII signaling map is proposed., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Secretory phospholipase A(2) (sPLA(2)) isoforms are widely expressed in the brain and spinal cord. Group IIA sPLA(2) (sPLA(2)-IIA) has been shown to stimulate exocytosis and release of neurotransmitters in neuroendocrine PC12 cells and neurons, suggesting a role of the enzyme in neuronal signaling and synaptic transmission. However, the mechanisms by which sPLA(2) is itself released, and a possible relation between glutamate receptors and sPLA(2) exocytosis, are unknown. This study was carried out to elucidate the effects of glutamate receptor agonists on exocytosis of sPLA(2)-IIA in transfected SH-SY5Y neuroblastoma cells. sPLA(2)-IIA enzyme was packaged in fusion-competent vesicles and released constitutively or upon stimulation, suggesting regulated secretion. The signal peptide of sPLA(2)-IIA is required for its vesicular localization and exocytosis. External application of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate (KA) induced vesicular exocytosis and release of sPLA(2)-IIA. UBP 302, a GluR5-specific KA receptor antagonist, abolished the effect of KA, confirming the role of KA receptors in mediating sPLA(2)-IIA secretion. Moreover, KA-induced sPLA(2)-IIA secretion is dependent on Ca(2+) and protein kinase C. Together, these findings provide evidence of a link between glutamate receptors and regulated sPLA(2) secretion in neurons that may play an important role in synaptic plasticity, pain transmission and neurodegenerative diseases., (Copyright © 2011 S. Karger AG, Basel.)

Adipocytes, which secrete a spectrum of adipokines, play an integral role in metabolism via communications with other endocrine cells. In the present work, we have studied the interplays between adipokines and catecholamines, using 3T3-L1 adipocytes and PC12 cells as the cell models and an integrative experimental platform. We demonstrate that all catecholamines inhibit vesicle trafficking and secretion of leptin and resistin through β-adrenergic receptors, while leptin and resistin enhance the vesicle trafficking and secretion of catecholamines through PKC, PKA, MAPK kinase and Ca(2+) dependent pathways. The crosstalks between adipokines and catecholamines were further corroborated by co-culturing 3T3-L1 adipocytes and PC12 cells. Our findings highlight the importance of adipo-adrenal axis in energy metabolism and the intricate interactions between metabolic hormones., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Adipose tissue is a highly active endocrine organ secreting a variety of signaling molecules called adipokines. Leptin and resistin are two adipokines critically involved in metabolic homeostasis. Nevertheless, the secretory pathways of these adipokines and their interplays are poorly elucidated. In this work, we have comparatively studied several key aspects of leptin and resistin secretion from 3T3-L1 adipocytes. It was found that leptin and resistin molecules are compartmentalized into different secretory vesicles. The trafficking of leptin and resistin vesicles, and the secretion of leptin and resistin are oppositely regulated by insulin/glycolytic substrates and cAMP/protein kinase A. Interestingly, these two adipokines adversely influence each other on secretion and vesicle trafficking. Finally, we demonstrated that both leptin and resistin secretion are Ca(2+) dependent.