Antimicrobial resistance is an important global issue facing society. Healthcare workers need to be engaged in solving this problem, as advocates for rational antimicrobial use, stewards of sustainable effectiveness, and educators of their patients. To fulfill this role, healthcare workers need access to training and educational resources on antimicrobial resistance.To better understand the resources available to healthcare workers, we undertook a global environmental scan of educational programs and resources targeting healthcare workers on the topic of antimicrobial resistance and antimicrobial stewardship. Programs were identified through contact with key experts, web searching, and academic literature searching. We summarized programs in tabular form, including participating organizations, region, and intended audience. We developed a coding system to classify programs by program type and participating organization type, assigning multiple codes as necessary and creating summary charts for program types, organization types, and intended audience to illustrate the breadth of available resources.We identified 94 educational initiatives related to antimicrobial resistance and antimicrobial stewardship, which represent a diverse array of programs including courses, workshops, conferences, guidelines, public outreach materials, and online-resource websites. These resources were developed by a combination of government bodies, professional societies, universities, non-profit and community organizations, hospitals and healthcare centers, and insurance companies and industry. Most programs either targeted healthcare workers collectively or specifically targeted physicians. A smaller number of programs were aimed at other healthcare worker groups including pharmacists, nurses, midwives, and healthcare students.Our environmental scan shows that there are many organizations working to develop and share educational resources for healthcare workers on antimicrobial resistance and antimicrobial stewardship. Governments, hospitals, and professional societies appear to be driving action on this front, sometimes working with other types of organizations. A broad range of resources have been made freely available; however, we have noted several opportunities for action, including increased engagement with students, improvements to pre-service education, recognition of antimicrobial resistance courses as continuing medical education, and better platforms for resource-sharing online. Antimicrobial resistance (AMR) is a looming global health problem; misuse and overuse of antimicrobials in the past 50 years has accelerated the development of resistance to antibiotics and other antimicrobial drugs . With feChanging HCW and patient habits will require substantial effort to ensure that all prescribers and patients are aware of the challenges associated with AMR. Surveys suggest that many HCWs receive too little training on AMR and rational antibiotic use. In Saudi Arabia, nearly half of surveyed physicians felt that they had inadequate knowledge of antibiotic prescribing . The InfThe WHO Global Action Plan on Antimicrobial Resistance expresses a need for all countries to include antibiotic resistance as a core component of both HCW training and continuing education . To bettWe sought to identify AMR educational programs targeting HCWs. For breadth, programs were identified through multiple methods, including contact with key experts, web searching, and academic literature searching. An initial literature search in August and September 2016 identified educational programs and key academic researchers who had published in the field over the previous decade. We emailed these and other key experts identified by WHO regional office contacts to request information on AMR and AMS-related educational programs. Additional experts were identified via a snowball strategy and web-searching. Experts were asked to identify recent or ongoing educational programs on AMR/AMS.We further identified educational programs through online web-searching. We hand-searched the websites of several relevant organizations to identify past and current educational initiatives. We also conducted a non-systematic web search using combinations of a range of search-terms including “antimicrobial resistance”, “antibiotic resistance”, “antimicrobial stewardship,” “antibiotic stewardship”, “education”, “course”, “curriculum”, and “workshop” and region or country in September and October 2016. Relevant articles, project reports, course flyers, and other resources were reviewed to identify programs. We examined national action plans concerning AMR in search of references to educational initiatives. Once identified, these programs were followed up with additional online research as necessary.We summarized the identified programs in tabular form, including participating organizations, program types, region, and intended audience. We created codes to classify programs by program type, organization type, and WHO region. Programs that were not associated with any specific region  were classified as “global”. Multiple program codes were assigned as necessary. Program type and organization codes were developed and updated iteratively as programs were identified to identify commonalities between initiatives.In total, we identified 94 educational initiatives related to AMR/AMS. The 94 initiatives represent a diverse array of programs including formal courses, workshops, conferences, guidelines, public outreach materials, and online-resource websites. The complete list of initiatives is presented in Table We identified 24 multi-component umbrella programs, which typically included web-based resources, videos, references to guidelines, and promotional materials, such as posters, pamphlets, or infographics. Programs that incorporated four or more program types were defined as umbrella programs. Umbrella programs tended to have broader target audiences and wider scopes; in many cases, their awareness campaign materials were targeted towards a general audience, while online reading and guidelines were more often aimed at HCWs. Many umbrella programs targeted their messaging at HCWs—including physicians, pharmacists, and sometimes nurses—as a group, rather than targeting professions or specialties individually.Of the programs identified see Fig. , the mosOther teaching resources available online included videos, webinars, and lecture slides. Online courses, including massive open online courses (MOOCs), are becoming common and often incorporate online videos and discussion boards to engage participants. In Fall 2016, there were two MOOCs on the FutureLearn platform (see Initiatives #44 and #90). The MOOC run by the University of Dundee and British Society for Antimicrobial Chemotherapy (Initiative #90) has gained global popularity. Several experts referenced this course as a resource used in their country; the course has been offered three times to date and participants have come from more than 41 countries.Figure Professional societies, particularly those with a strong tie to AMR, were heavily involved in the creation and provision of resources for HCWs. Three examples are the British Society for Antimicrobial Chemotherapy, which has been involved in the creation of resource websites (Initiative #48), coordination of a MOOC (Initiative #90), and provision of funding for AMR education; the European Society of Clinical Microbiology and Infectious Diseases, which runs a study group on antimicrobial resistance, develops and coordinates courses, and carries out collaborative academic research; and the Infection Control Africa Network which organized a free distance learning course for HCWs in Africa in 2014. Many professional bodies with broader mandates, for example, medical associations and pediatric societies, have partnered with others to support larger projects, but were rarely the lead organization in the projects that we identified. For example, the NPSMedicineWise project (Initiative #82) in Australia engaged the Australian College of Nursing, Australian Association of Consultant Pharmacy, the Australian College of Rural & Remote Medicine, and the Australian Nursing and Midwifery Federation and many others alongside government bodies to produce resources and course content for the website.University-led projects were typically related to online or in-person courses or to resource websites. Many of these sites provide lecture slides, or recorded video lectures (e.g. Initiative #16), as well as information on guidelines and policies (e.g. Initiative #35). Other types of organization were engaged in a wide variety of projects. Hospitals and healthcare centers, for example, engaged with umbrella programs, courses and workshops, intervention studies, and resource guides.Most programs targeted HCWs as a broadly defined group. Figure We identified programs from around the world, though, as expected, the programs were unequally distributed between countries and regions, with a larger share of the programs from North America and Europe. Figure Our environmental scan shows that many organizations are working to develop and share course content and educational resources for HCW training and continuing education around the world. We identified several types of resources, from traditional in-person courses to workshops and conferences, to MOOCs, to online campaign materials, to handbooks, and to workbooks. Governments, hospitals, and professional societies appear to be driving action on this front, and these three types of organization have successfully built partnerships with others including non-profits, insurance companies, and WHO regional offices.This level of collaborative work is promising; however, we have identified opportunities for action on several fronts. First, there is an opportunity for the development of better resources and training opportunities for students in the healthcare professions. Early engagement can provide a strong foundation of AMR knowledge that students draw upon as they progress through their careers as prescribers and patient educators. Second, it appears that training for current HCWs is probably under-recognized by professional development and continuing education programs. HCWs need to have their AMR learning efforts formally recognized, as they may lack incentives to engage in substantial additional training on a purely volunteer basis. Below we discuss how addressing these two elements of training, both pre-service and continuing education, can improve the content, delivery, uptake, and scale-up of AMR/AMS education, and identify programs that are interesting models for development of further resources.We identified a small number resources for students in healthcare disciplines, though research suggests that medical students in Europe and the USA have a desire for increasing training on AMR , 12. ResWe found that many excellent courses already exist, and several are available online at low or no cost. As content is already available, improving roll-out is a matter of ensuring that these courses can run repeatedly; preparing a course for a single session is likely a waste of resources. Another way to improve roll-out is to facilitate translation of course materials to other languages. Consulted experts noted that translating available content, such as a MOOC, from English into other languages is a slow and difficult process. Beyond the translation of lecture slides, there is a need to obtain other resources, such as academic articles and video content, in the foreign language. Creation of a database that brings together resources on AMR/AMS in other languages would facilitate the adaptation of courses between languages.Improving uptake of existing educational opportunities is also key. We note that among the resources identified, very few are accredited as continuing professional education. This is probably a major oversight—and opportunity—as evidence suggests that HCWs are not receiving enough training on AMR/AMS . HCWs woMany of the programs that we identified made their content freely available online. In addition to courses, we found lecture slides, video lectures, case studies, facilitator guides, handbooks, posters, and other campaign materials online. The presence of these many high-quality resources online suggests that it is not necessary for new educational campaigns and courses to reinvent the wheel; a large amount of information is already available. However, much of this content is scattered across the web. It would be very useful to develop a resource site or database of good AMR content. Collecting this content would allow educators to build off of existing educational materials and focus their efforts on developing course content specific to the local context. The ReAct Toolbox (Initiative #94) is an excellent model, providing basic information on several aspects of AMR/AMS and links to other online resources that are relevant to both LMICs and high-income countries. The main limitation of the site, and many of the other educational resources that we have identified, is that many resources are only available in English.This project is the first attempt that we know of to map educational resources for HCWs around the world. We contacted more than 50 experts and identified educational resources and projects in all WHO regions. By identifying and classifying programs, we can see the breadth of resources already available for training HCWs on AMR/AMS.As we relied extensively on web searching in addition to expert advice, it is likely that we identified more of some types of resource than others. Therefore, the quantity of identified programs of this type should not be interpreted as proof that these resources are the most common program type. We paired our web searching with expert input to identify those other resources that are more difficult to identify online. We recognize that some web resources, such as guidelines, are more likely to endure on the internet than others, such as advertisements for courses and conferences. We included mobile apps specific to antibiotic resistance if they were identified by experts or identified in web searches. However, it was beyond the scope of the study to search within existing medical apps to locate AMR/AMS content; this has been done elsewhere by Goff et al. .We conducted our web and academic searching in English and relied upon on expert contacts to provide information on educational programs in other languages. We identified and reviewed some educational programs where the detailed information online was in French, but did not translate articles from other languages, and therefore likely missed other educational resources posted online that are only available in other languages.Finally, we note that longevity of resources on the internet is an issue. We found many broken links, where program information could no longer be obtained. We identified many courses through course advertisements posted to the web; however, the limitations of our search strategy make it likely that we mainly identified recent courses. Further, for most courses, we cannot comment as to whether the course content has been archived on the web. While much of the content from a larger course, such as a MOOC, is likely to remain on the web, it is unlikely that the course content of shorter, in-person courses will be retained in the same way. Resource sites must monitor content to ensure it remains up to date. To facilitate the sharing of resources between countries, it will also be important to find a mechanism such that content does not become inaccessible after removal from the website.In mapping the available educational programs on AMR/AMS for HCWs, we have identified 94 existing programs and resources, and several opportunities for improvement and expansion on the existing resources. Many high-quality educational campaigns already exist and there are many opportunities to adapt these programs to meet educational needs in other contexts. But gaps exist, particularly when it comes to resources for healthcare students, and provision of accredited training for current HCWs. National and international stakeholders should advocate for increased accreditation, the creation of a series of competencies for undergraduate curricula, and support resource sharing platforms. Action on these fronts would support both the goals laid out in many national AMR action plans and the desires of many HCWs to ensure that all HCWs receive sufficient training on AMR and AMS.


In situ polymerization was used to prepare indium oxide/polyaniline (In2O3/PANI) composite nanofibers with different mass ratios of In2O3 to aniline. The structure and morphology of In(NO3)3/PVP, In2O3/PANI composite nanofibers and pure PANI were investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM) and current–voltage (I–V) measurements. The gas sensing properties of these materials towards NH3 vapor (100 to 1000 ppm) were measured at room temperature. The results revealed that the gas sensing abilities of In2O3/PANI composite nanofibers were better than pure PANI. In addition, the mass ratio of In2O3 to aniline and the p–n heterostructure between In2O3 and PANI influences the sensing performance of the In2O3/PANI composite nanofibers. In this paper, In2O3/PANI composite nanofibers with a mass ratio of 1:2 exhibited the highest response values, excellent selectivity, good repeatability and reversibility.Indium nitrate/polyvinyl pyrrolidone (In(NO Ammonis NO2 [2 , acetones NO2 [2  and forms NO2 [2 . Howevers NO2 [2 . Compares NO2 [2 –20. Becas NO2 [2 –22. To cs NO2 [2 ,23–27.2O3/PANI composite nanofibers were prepared by the combination of electrospinning technique, calcination method and in situ polymerization. This study presents the improved response capabilities of gas sensors based on In2O3/PANI composite nanofibers, which were synthesized with different ratios between In2O3 and aniline during the in situ polymerization. All sensors were tested at room temperature in a concentration range of NH3 from 100 to 1000 ppm.In this paper, InMw = 1.3 × 106 g/mol) was purchased from Bo Di Industrial Co. Ltd of Tianjin. Indium nitrate hydrate, N,N-dimethylformamide (DMF), ethyl alcohol, aniline monomer (An), ammonium persulfate (APS), hydrochloric acid , ammonium hydroxide (NH4OH) and m-cresol were obtained from Sinopharm Chemical Reagent Co., Ltd. . All chemicals and reagents were used as received, expect for aniline monomer. Distilled aniline monomer and deionized water were used in this study.Polyvinylpyrrolidone-K90 3/PVP composite nanofibers were fabricated via single-nozzle electrospinning. In(NO3)3·4.5H2O (1.059 g) and PVP (3.529 g) were added into 10 mL ethyl alcohol and 10 mL DMF. The mixture was stirred at 65 °C until all the solutes were fully dissolved. The precursor solution was poured into the syringe for electrospinning. The parameters of the electrospinning were: a needle-to-collector distance of 16 cm, a voltage of 16 kV, and a feed rate of 0.5 mL/h. Then the In2O3 nanofibers were synthesized by annealing the precursor composite nanofibers at 800 °C for 3 h after heating from room temperature at a rate of 0.5 °C/min.The In were prepared. Correspondingly, the four sensors were denoted as PANI sensor, In2O3/PANI-1 nanofibers sensor, In2O3/PANI-2 nanofibers sensor and In2O3/PANI-3 nanofibers sensor.The ground In2O3 nanofibers was characterized by X-ray diffraction  in a 2θ region of 3–90° with Cu Kα radiation. The morphologies and structures of the In2O3 nanofibers, PANI and PANI/In2O3 composite nanofibers were examined by field emission scanning electron microscopy , transmission electron microscopy , and Fourier transform infrared (FTIR) spectroscopy in the range of 4000–400 cm−1 with a 4 cm−1 spectral resolution . I–V measurements were carried out on a CHI 660E electrochemical workstation  with a three-electrode system.The crystal structure of In2O3/PANI nanofibers was measured using a custom-built static state gas sensing test system at room temperature (25 ± 1 °C) with a relative humidity of 60 ± 1%. During the gas measurement, the aqueous ammonia was injected into the test chamber using a syringe through a rubber plug. The volume of ammonia injected into chamber were 1.3468 μL, 4.0404 μL, 6.734 μL, 10.7744 μL and 13.468 μL resulting in ammonia vapor with concentrations of 100, 300, 500, 800 and 1000 ppm, respectively. The gas response value (S) is defined as a ratio of (Ri − R0)/R0, in which Ri and R0 are the resistance of the sensor in testing gas and air, respectively. Each result was the average value of five tests.The gas sensing performance of the prepared In3)3/PVP composite nanofibers at 800 °C are shown in 2O3, and the diffraction peak of 30.56° was indexed to the (222) crystal plane of the cubic structure of In2O3. This result confirmed that the final product of calcination was In2O3.The XRD patterns of the nanofibers obtained by annealing In3/PVP composite nanofibers exhibits a broad characteristic band around 3382 cm−1, which is related to the O–H stretching vibration. It could be the result of absorbing moisture from air. The –CH2 stretching vibration and bending vibration of PVP are attributed to the peaks of around 2951 cm−1 and 1423 cm−1. The peaks at 1647 cm−1 and 1292 cm−1 were assigned to the C=O stretching vibration and C≡N antisymmetrical stretching vibration, respectively, in the ring skeleton of PVP. But the characteristic peaks of In(NO3)3 could not be found in the FTIR spectra. In the spectrum of In2O3 nanofibers 3 was converted into In2O3 during annealing.The chemical structure of the precursor nanofibers, Innofibers , the cha2O3, PANI and In2O3/PANI nanofibers. The characteristic peaks around 1558 cm−1 originating from C=C stretching vibration in the quinoid ring of PANI can be seen. The characteristic bands of 1300 cm−1 and 1116 cm−1 were attributed to the C–N stretching vibration in the benzenoid ring and the bending vibration plane of C–H bonds in the quinoid ring, respectively. By comparison, the characteristic peaks of In2O3 also exist in the spectrum of In2O3/PANI nanofibers. This demonstrated that PANI was coated on the surface of the In2O3 nanofibers by in situ polymerization. But for In2O3/PANI-3 nanofibers, the peaks of In2O3 and PANI showed a significantly decrease which may be caused by the excess of PANI covering.3)3/PVP composite nanofibers and In2O3 nanofibers, respectively. From 3)3/PVP composite nanofibers was relatively smooth and no beads and droplets appeared. The diameter distribution of In(NO3)3/PVP nanofibers were mostly in the range of 700–1000 nm. The In2O3 nanofibers were relatively uniform with diameters of 150–220 nm. These results show that the In2O3 nanofibers were much rougher and smaller than the precursor nanofibers. In addition, it shows that some nanofibers adhered together in 2O3 nanofibers were gradually formed, but the bonded nanofibers would not segregate during this process, leading to some nanofibers connected along each other.2O3 nanofibers. In 2O3 nanofibers consited of small grains and the hollow structure can be clearly observed. The hollow structure of In2O3 nanofibers was synthesized by a template-assisted method. PVP as the supporting material of precursor nanofibers was decomposed during the annealing process, and the In(NO3)3 was transformed into crystalline In2O3. During calcination, PVP decomposed and gases diffused from the interior to the exterior of the composite nanofibers, leading to crystalline In2O3 grains constantly moving and tending to be regularly arrayed [2O3 nanofibers was formed during the annealing process.The cross-sectional image and the TEM image show the detailed structure of In arrayed . As a reI–V) measurements of PANI, In2O3/PANI-1, In2O3/PANI-2 and In2O3/PANI-3 nanofibers were carried out at room temperature. As shown in I–V characteristics of all In2O3/PANI nanofibers clearly exhibit a nonlinear behavior and it can be observed the rectifying behavior in 2O3 [2O3/PANI showed exponential rise at low voltage and then almost linear rise at high voltages. But for pure PANI, the current showed nearly linear behavior in the forward region, which is attributed to raidply forming polarons and bipolarons in PANI. As some researches mentioned [2O3. Compared with pure PANI, the In2O3/PANI nanofibers reach a higher current due to the smaller width of the depletion layer between PANI and In2O3. Moreover, the addition of PANI reduced the width of the depletion layer at the interface and was helpful to form a typical ohmic system [2O3 had been formed.Current–voltage , the responses to NH3 decreased.The response values of pure PANI and these three In2O3 to aniline had an obvious influence on the NH3 sensing performance of the composite nanofibers. Comparing the sensitivity of three In2O3/PANI nanofibers sensors, it can be found that the In2O3/PANI-2 nanofibers sensor delivers the best performance. Therefore, In2O3/PANI-2 was selected to further investigate the sensing properties.These results revealed that the mass ratio of In3 will cause harm to human health. Accordingly, the response of the In2O3/PANI-2 sensor to 50 ppm, 30 ppm and 10 ppm were investigated. As shown in 2O3/PANI-2 sensor to low concentration (10–50 ppm) NH3 was 0.12, 0.48 and 0.94, respectively. Thus it can be seen the In2O3/PANI-2 sensor had good response performance towards low concentrations of NH3.As mentioned in the Introduction section, 50 ppm NH2O3/PANI-2 nanofibers sensor. 2O3/PANI-2 nanofibers sensor to methanol, ethanol, acetone and ammonia at a concentration of 1000 ppm. It is obvious that the In2O3/PANI-2 nanofibers sensor was almost insensitive to methanol, ethanol and acetone vapors. According to the test results, it can be concluded that In2O3/PANI-2 nanofibers sensor exhibited unique selectivity to ammonia. A possible mechanism for the selectivity to NH3 is the chemisorption of NH3 on PANI in In2O3/PANI-2 forming ammonium [2O3/PANI-2 nanofibers to different gases may be explained by this.The cross-response test was used to evaluate the selectivity of Inammonium . Besidesammonium , and the2O3/PANI-2 nanofibers sensor was exposed to 1000 ppm ammonia for five times to investigate the repeatability and reversibility. As shown in 2O3/PANI-2 nanofibers sensor could not fully return to the initial state, and there was a baseline drift of 4% after the first exposure to NH3. This bias was smaller than the results in other reports [2O3/PANI-2 nanofibers sensor showed good repeatability and reversibility.In reports –36. On t3 resulting in the transformation of PANI from emeraldine salt to emeraldine base by dedoping. The reaction between PANI and NH3 can be described as follows:It is well known that the chemical sensors are composed of two parts, an active part and a transduction part, whose function is sensitive to gas analytes and produces a signal that is related to the concentration . In this3 caused the deprotonation of the N–H+ site of the emeraldine salt, leading to a significantly increased resistance [3 atmosphere, the resistance of the PANI-based sensor maintained a constant value. When the sensor was exposed to air, NH3 is volatilized and the resistance of the PANI composite nanofibers is reduced. Therefore, due to the unique mechanism, PANI  based sensors exhibited a great selectivity to NH3.The absorption of NHsistance –38. WhenI–V characteristics show, it is confirmed that p–n heterojunctions had been formed between PANI and In2O3 nanofibers, in which PANI is a p-type semiconductor and In2O3 nanofibers presents as an n-type semiconductor [3, the protons from PANI are transferred to the NH3 molecules, which results in a widening of the depletion layer in the PANI section [2O3 region and on the p–n junction. The electrons of In2O3 and holes of PANI move in opposite directions until the new Fermi level (EF-NH3) reaches equilibrium. In this process, the electron transfer between the n-type In2O3 and p-type PANI is obstructed due to the potential barrier. Thus the depletion layer between PANI and In2O3 becomes wider and the resistance of the material increases [S = (Ri − R0)/R0), the increase in resistance attributed to the p–n junction increases the sensitivity of composite nanofibers sensors. In addition, the sensitivity of the composite gas sensor materials is also connected to the mass ratio of In2O3 and aniline.As the onductor ,27,34. Tonductor . With lo section . Simultancreases –42. Acco2O3/PANI-1 gas sensor showed a lower sensitivity. However, for the In2O3/PANI-3 gas sensor, the external surface of In2O3 nanofibers was coated with excess polyaniline, yielding a gas sensing perfomance similar to that of pure PANI. Even the response of In2O3/PANI-3 to 100 ppm and 500 ppm NH3 was less than that of pure PANI. The p–n junction of In2O3 and PANI in In2O3/PANI-3 does not work efficiently. In general, the characteristic of the gas sensitive material response was discrete instead of ideally linear [2O3/PANI-3 and pure PANI, the characteristic responses were similar. Therefore, it was possible that the response of In2O3/PANI-3 were less than that of pure PANI, especially towards lower concentrations of NH3. In this study, when the mass ratio of In2O3 to aniline was 1:2, the gas sensor material exhibited optimum performance in detecting NH3.Because of the smaller amount of polyaniline, which acts as active material in this composite system, the Iny linear ,36,43. F2O3/PANI nanofibers with reliable sensing properties towards NH3 were synthesized by electrospinning, calcination and in situ polymerization. The gas sensors based on In2O3/PANI nanofibers exhibited a higher sensitivity than pure PANI. The In2O3/PANI-2 nanofiber sensor exhibited the best sensitivity to NH3 vapor at room temperature, and this sensor was further investigated for its selectivity by interfering with methanol, ethanol and acetone vapors. The results indicated that the In2O3/PANI-2 nanofiber sensor had excellent selectivity, good repeatability and reversibility. The enhancement of gas sensing performance of In2O3/PANI nanofiber sensor may be attributed to formation of a p–n junction between In2O3 and PANI, which existence is confirmed by the I–V characteristics.In


FERMT1. This gene encodes kindlin-1, a focal adhesion protein involved in activation of the integrin family of extracellular matrix receptors. Most cases of KS show a marked reduction or complete absence of the kindlin-1 protein in keratinocytes, resulting in defective cell adhesion and migration. Electric fields also act as intrinsic regulators of adhesion and migration in the skin, but the molecular mechanisms by which this occurs are poorly understood. Here we show that keratinocytes derived from KS patients are unable to undergo electrotaxis, and this defect is restored by overexpression of wild-type kindlin-1 but not a W612A mutation that prevents kindlin-integrin binding. Moreover, deletion of the pleckstrin homology domain of kindlin-1 also failed to rescue electrotaxis in KS cells, indicating that both integrin and lipid binding are required for this function. Kindlin-1 was also required for the maintenance of lamellipodial protrusions during electrotaxis via electric field-activated β1 integrin. Indeed, inhibition of β1 integrins also leads to loss of electrotaxis in keratinocytes. Our data suggest that loss of kindlin-1 function may therefore result in epithelial insensitivity to electric fields and contribute to KS disease pathology.Kindler syndrome (KS) is an autosomal recessive blistering skin disease resulting from pathogenic mutations in  Kindlin-1 is predominantly expressed in epithelial tissues such as skin and intestine. Loss-of-function mutations in kindlin-1 causes Kindler syndrome (KS), which is characterized by skin blistering, fragility, and photosensitivity . KeratinKindlin-1 has been shown to bind to β1, β3, and β6 integrin cytoplasmic domains and enhance focal adhesion formation . The intIn this study, we describe a mechanism by which kindlin-1 mediates efficient keratinocyte electrotaxis through activation of β1 integrins. Our data show that kindlin-1 regulates the distribution and maintenance of lamellipodial protrusions and integrin activation through association with phospholipids and that this is required for polarization and directed electrotaxis. These data provide the evidence that specific focal adhesion proteins are required for optimal cell sensing of electric gradients and further suggest that a potential defect in this pathway in KS patients may contribute to disease pathology.Kindlin-1 has previously been shown to be required for efficient migration of keratinocytes and loss or reduced levels of this protein in KS leads to defective adhesion assembly and migration . To deteKindlin-1 has been shown to associate directly with integrin cytoplasmic domains and is required for full activation of β1 integrins and, subsequently, cell adhesion and migration . Recent The formation of F-actin containing lamellipodia and filopodia is critical for directional migration and requires the interaction of external guidance cues, adhesion receptors, and cytoplasmic adaptors . AnalysiThe higher probability and longer maintenance of protrusion in a certain direction, the higher the possibility that cells migrate in that direction persistently . We usedIntegrins have been reported to be important in mediating EF-induced migration of keratinocytes . To deteTo further verify that activation of β1 integrins is required for EF-induced directional migration, we assessed the electrotactic response of NHK cells pretreated with β1 integrin function-blocking antibody P5D2. Integrin inhibition in NHK resulted in the loss of persistent pseudopods facing the cathode  online aPI(3)K and downstream effector PIP3 have been reported to control electrotactic responses of several cell types . KindlinIn this study, we showed a role for kindlin-1 in regulating pseudopod protrusion and maintaining directed cell migration in electrotaxis. We report that KS cells are defective in EF-mediated directional migration because of loss of function of kindlin-1. Previous work has shown that kindlin-1 is required for keratinocyte adhesion and spreading, and we show that kindlin-1 acts to maintain EF-induced asymmetric redistribution of pseudopod protrusions and polarized β1 integrin activation, which is in turn required for cathodal migration in response to EF. Our findings that re-expression of wild-type, but not W612A-kindlin-1, rescued the deficient electrotactic response of KS cells, strongly implies that kindlin-integrin association is required for efficient keratinocyte electrotaxis. Phospholipid signaling is a potential upstream regulator of kindlin-1–regulated electrotaxis, because we also showed that kindlin-1 lacking the PH domain failed to rescue the electrotactic response in KS cells. Our study reveals the role of kindlin-1 in mediating the directed migration response of keratinocytes to EFs and suggests that the membrane environment may be crucial to establishing an adhesion-dependent polarized guidance cue in response to EF stimulation.Skin wounds generate endogenous EFs ranging from 70 to 200 mV/mm/ with variation across different species of animals and humans . The wou2+/calmodulin-dependent protein kinase, and myosin light chain kinase do not reduce either migration velocity or directedness significantly; however, both protein kinase A and PI(3)K inhibitors can effectively reduce cell responses to EF K decreases EF-induced directional migration in epithelial cells. Similarly, deleting phosphatase and tensin homolog in mice, human skin fibroblasts, and neuronal stem cells increases electrotactic responses . HoweverIn conclusion, we describe a role for kindlin-1 in sustaining directional migration of keratinocytes in response to EFs and show that the interaction of kindlin-1 with β1 integrins is important to maintain lamellipodia at the leading edge and achieve EF-mediated directional migration. Thus, kindlin-1 may act to relay local signals, via PI(3)K, to fully activate β1 integrins to stabilize the newly formed lamellipodia in the direction of the applied EF. Studying the function of kindlin-1 in electrotaxis will improve our understanding not only of skin integrity in KS patients but also the mechanisms of directional sensing and migration that are required for other biological processes such as embryonic development, inflammation, and tumor cell metastasis.The following antibodies were used: anti-integrin β1  and anti-integrin β1 . The following secondary antibodies were purchased from Invitrogen : Alexa Fluor 488 goat anti-mouse and Alexa Fluor 488 goat anti-rabbit.FERMT1 mutations were used for this study .A total of 1 × 10Cells were fixed with 4% paraformaldehyde for 10 minutes at room temperature and blocked with 5% fetal bovine serum (Invitrogen) in phosphate buffered saline, followed by primary antibody incubation overnight at 4 °C. The secondary antibody was incubated for 1 hour at 37 °C. The fixed coverslips were analyzed with a DeltaVision Imaging system (Imsol). Analysis of intensity of integrin staining was performed in ImageJ .Pseudopod dynamics analysis was conducted with the Quimp3 algorithm following a previous description . BrieflyThe authors state no conflict of interest.This study was funded by European Research Council StG grant 243261 and the British Council Global Innovation Initiative Award (to BS), the British Skin Foundation and the UK National Institute for Health Research Biomedical Research Centre based at Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London (MP and JAM), and Grants of Innovative Research Teams of Liaoning Province, China (LT2011012 to XHG). The views expressed are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, or the UK Department of Health.BS, MP & GZ designed the study and wrote the paper. GZ, YG & RB conducted the experiments and data analysis. HDC, XHG & JAM contributed to the data analysis, discussion and paper writing. BS led the study regarding electric stimulation and cell migration analysis. MP created KS and NHK cell lines and constructed plasmids. BS, XHG and MP provided financial support to the project.


We are faced with a worldwide opiate/opioid epidemic that is devastating. According to the Centers for Disease Control and Prevention (CDC), at least 127 people, young and old, are dying every day in America due to narcotic overdose. The Food and Drug Administration (FDA) has approved Medication-Assisted Treatments (MATs) for opiate/opioids as well as alcohol and nicotine. The mechanism of action of most MATS favors either blocking of dopaminergic function or a form of Opiate Substitution Therapy (OST). These treatment options are adequate for short-term treatment of the symptoms of addiction and harm reduction but fail long-term to deal with the cause or lead to recovery. There is a need to continue to seek better treatment options. This mini-review is the history of the development of one such treatment; a glutaminergic-dopaminergic optimization complex called KB220. Growing evidence indicates that brain reward circuitry controls drug addiction, in conjunction with “anti-reward systems” as the “anti-reward systems” can be affected by both glutaminergic and dopaminergic transmission. KB220 may likely alter the function of these regions and provide for the possible eventual balancing the brain reward system and the induction of “dopamine homeostasis.” Many of these concepts have been reported elsewhere and have become an integral part of the addiction science literature. However, the concise review may encourage readership to reconsider these facts and stimulate further research focused on the impact that the induction of “dopamine homeostasis” may have on recovery and relapse prevention. The most recent variant of KB220 includes the following ingredients: Thiamine, 15 mg ; Vitamin B6, 10 mg (500%); Chromium poly nicotinate 200 mcg (166%); a fixed dose combination of amino acids and herbs called Synaptose. Synaptose contains DL-phenylalanine, L-tyrosine, Passion flower extract; L-glutamine; 5-hydroxytryptophan (5-HTP); Thiamine hydrochloride; Pyroxidal-5-phosphate; Pyridoxine HCl and a composite containing Arabinogalactans, N-acetylglucosamine, Astragalus, Aloe vera, Frankincense resin, White pine bark extract, N-acetyl-cysteine (NAC) and Rhodiola.Firstly, regarding the mechanism of action, KB220 ingredients provide some interesting properties which can assist in the induction of “dopamine homeostasis.” To appreciate this, familiarity with the ideas related to reward processing especially the Brain Reward Cascade (BRC) is essential . The prePrimarily KB220 relies on the benefits of the precursor aminio-acids and it behooves us to present bioavailability and elimination information. Parameters differ for transporting precursor amino-acids like L-glutamate and L-tryptophan across the Blood Brain Barrier (BBB), a low–capacity independent carrier system  that focus on both spirituality and fellowship . The eviSAMHSA has been responsible for most of the public funding of drug addiction treatment and has recently changed the language of its grant applications to push the treatment industry away from the previously accepted abstinence model. From the days of (AA) in 1935 to current thinking, some still believe that the abstinence model, which promotes complete restraint from substances including medications prescribed for addiction, is the only acceptable recovery method.However, a recent initiative has spurred new policies. Within the block grant application for the fiscal years 2016–2017 ($1.8 million was awarded in 2015), SAMHSA now encourages the rejection of the abstinence policy and requires the option of Medication-Assisted Treatment (MAT) in clinical settings. Buprenorphine/naloxone combinations for opioid addicts have been approved by the FDA the short-term treatment with continued restrictions on patients per practitioner. However, the vast majority of rehabilitation facilities across America do not offer such care. While the FDA has approved MAT for alcoholism, opioid dependence, and even nicotine abuse, there is no approved MAT for cocaine and marijuana abuse. Even NIDA and NIAAA understand that MAT alone is not optimal and continue their efforts to find even better treatments.America is in the middle of a tremendous heroin and prescription opioid epidemic that is targeting youth both white and colored and debilitating future generations. Notably, heroin-related overdose deaths almost quadrupled between 2002 and 2013, according to The Centers for Disease Control and Prevention (CDC). In fact, National Drug Control Policy Director Michael Botticelli stated that the U.S. government would make drug court funding conditional on states’ adherence to scientifically-supported treatment rather than ideologically motivated treatment exemplified by the abstinence model. However, Christie/Trump model targeting borders and reducing insurance coverage for the treatment of SUD could be diasatorious. Instead targeting pharmaceutical prescription abuse (297 million in 2016) seems more parsonomuous.Indeed, progress in scientifically proven treatments may pave the way for even better long-term less aversive therapies. However, we do know that most FDA approved drugs favor blocking dopamine (are predominantly dopamine antagonists). There is also some evidence that when long-term treatment with buprenorphine/naloxone combinations is compared to short-term treatment, no significant benefit in their resultant clinical outcomes is observed. Studies using fMRI reveal almost 98% saturation of Mu opiate receptors with 16mg of Buprenorphine , 70 and Over years of research, many including Nora D. Volkow (Director of NIDA), George Koob (Director of NIAAA) and our group have argued that “Dopamine Function” is an important cornerstone for a healthy and happy life . If we aWhile there is no magic solution, Mark Gold and associates came close when they proposed the use of Bromocriptine, a robust D2 agonist, to treat cocaine addiction . This neSo while it is important to consider short-term dopamine antagonistic therapy as espoused by FDA approval of MAT drugs, long-term use cannot be recommended. Understandably, while many of the proponents of current MAT would argue against this premise, we are looking for ways to normalize dopamine regulation. Imagine a solution that could provide regulation or “normalization” of dopaminergic function leading to what has been called “dopamine homeostasis?” In this way, balancing the brain’s neurotransmitter signaling should work best regardless of whether the trait or state is hyperdopaminergic or hypodopaminergic .In fact, only a small percentage of treatment centers currently embrace this concept by offering dopamine-boosting modalities. Practices like meditation and yoga exercise, sound and music therapy, brain spotting and behavioral, cognitive therapy, trauma therapy, and adhering to a dopamine-friendly diet are dopamine boosting. Holistic approaches require investigation for direct evidence for dopamine enhancement effects, however, the literature shows a 65% increase in neuronal dopamine with practices like Yoga and Mediation  and certThe first statistical analysis showing both compliance to FDA-approved MAT and abstinence from drugs of abuse during treatment used data from Comprehensive Analysis of Reported Drugs (CARD) provided by Dominion Diagnostics. The study involved urine drug screens from thousands of patients in Chemical Dependency Programs from six states was published in PLoS One . The conRegarding relapse vulnerability, there is evidence of an increased risk for relapse to carriers of the A1 form of the of the DRD2 gene have  and if tAlong these lines glutaminergic–dopaminergic optimization complex therapy (KB220), has been well-researched; in many clinical trials. KB220Z has been shown to provide gentle activation of dopamine across the brain reward circuitry in abstinent heroin and abstinent psychostimulant addicts . SignifiThis summary of the research results provides substantial scientific support for the use of KB220 formulations based on almost 40 years of research. Indeed, we have recently demonstrated increased resting state functional connectivity and induction of physiological changes in the brain (neuroplasticity) .Moreover, along with millions of recovering addicts here in the United States, low dopamine function may be prevalent in the general non-addicted population in part because of either their genetics or environmental pressure (stress). Notably, low dopamine function has been definitively linked in studies to reduced cognition (164) decision making (45) and exercise activity (73); excessive cravings (241); reduced performance (291) and loss of memory (199) aging (218); vulnerability to stress (374); overeating (162) sadness (257); poor relationships (36); and lack of well-being (984).GARS;Drug urine monitoring for both Compliance to MAT and Abstinence from psychoactive drugs;Long-term use of glutaminergic-dopaminergic optimization complex therapy to induce dopamine homeostasis;Polymorphic DNA-directed mRNA genetic expression profiling.The proposed “Reward Deficiency System Solution” includes:One frequent question concerning the use of KB220 in the treatment and prevention of relapse for all RDS behaviors is; “Will KB220 be required to be taken life-long- to maintain the balance in the brain reward system?” The answer has two parts. Genetically induced RDS like genetically induced diabetes which is a life-long condition will require lifelong treatment. However, although RDS can be caused by inheritable factors like having the A1 allele of the DRD2 gene amongst other reward gene polymorphisms, it can also be caused by epigenetic effects like stress (anti-reward) as well as the toxic effects of substances. Epigenetic effects can last up two generations , althougThe hope is that leading minds in addiction medicine, clinics, and interested scientists will come to recognize that to boost (or modulate), rather than blocking dopamine function will eventually lead to better quality of life for all. Relapse prevention and long-term treatment with dopamine regulation may provide a more comprehensive and humane way of treating addiction disorders. The scientific and medical community is challenged here to admit that our current treatment protocols are severely ineffective (locking people into addiction rather than treating the root cause). It is clear that addiction treatment requires a more comprehensive solution. These challenges in no way negate the enormous efforts of countless people who have unselfishly given so much to the field. While the FDA’s push for MAT and the use of off-label Gabapentin, Topiramate, Ketamine and other drugs to alter the brain reward circuitry is understood, the potential for reducing further, needed dopamine with these pharmaceuticals in the chronic treatment of RDS behaviors, is indeed counter-intuitive. The message is to activate , not block, dopamine function in the reward circuitry of the brain in the long-term . We are . In fact, the Obama selection of the former US Surgeon General has encouraged physicians across the United States to curtail the prescription of powerful narcotic pharmaceuticals and find new ways to screen for a predisposition to high addiction risk before treating pain with these narcotic agents. The conception of screening for addiction risk using a panel of reward genes such as the GARS would be one intervention that might be useful in averting some of the pain involved in the prevention and treatment of this opioid epidemic [Lastly, in addressing the concern about “An American Opioid Epidemic” the recent restrictions on prescription opioid use in chronic pain conditions by the Center for Disease Control  are appropriateepidemic  leading


Solution blow spinning (SBS) is an innovative process for spinning micro/nanofibers. In this paper, polyamic acid (PAA) nanofibers were fabricated via a SBS apparatus and then imidized into polyimide (PI) nanofibers via thermal process. The morphology and diameter distributions of PAA nanofibers were determined by scanning electron microscope (SEM) and Image Tool software, the processing parameters, including PAA concentration, solution feeding rate, gas pressure, nozzle size, and receiving distance were investigated in details. The fourier transform infrared spectroscopy (FTIR) was used to characterize the chemical changes in the nanofibers after thermal imidization. The results showed that the solution concentration exhibited a notable correlation with spinnability, and the formation of bead defects in PAA nanofibers. Solution feeding rate, gas pressure, nozzle size, and receiving distance affected nanofiber production efficiency and diameter distribution. The average diameters of fibers produced ranged from 129.6 to 197.7 nm by varying SBS parameters. Precisely, PAA nanofibers with good morphology were obtained and the average diameter of nanofibers was 178.2 nm with optimum process parameter. After thermal imidization, the PI nanofibers exhibited obvious adhesion morphology among interconnected fibers, with an increased average diameter of 209.1 nm. The tensile strength of resultant PI nanofiber mat was 12.95 MPa. Novel nanofiber techniques have gained wide interest, since nanofibers possess extraordinary structure features, novel performance, and exhibit tremendously potential application . ElectroThe next-generation nano-manufacturing techniques will be toward high yields and processing security, as the nanofibers market is growing. For this purpose, emerging technologies have been employed, for instance, forcespinning (FS), which uses centrifugal force to process a polymer solution or polymer melt into nanofibers with the capability for mass production ,8,9. FS Over the last few years, SBS has been successfully employed to produce micro/nanofibers of many polymers, including cellulose , polyacrIn the present work, we adopt the facile SBS method to fabricate PAA nanofibers. The processing parameters are optimized, the effects of polymer concentration, solution feeding rate, gas pressure, nozzle inner diameter, and receiving distance on the nanofibers morphology and diameter distribution of resultant PAA nanofibers are systematically evaluated by means of SEM and image tool analysis software. Afterwards, PI nanofibers are produced via thermal imidization process from as-spun PAA nanofibers. The chemical and morphological changes in the nanofibers before and after imidization are analyzed. To the best of our knowledge, this is the first comprehensive study of fabricating PAA nanofibers via the SBS process, and this work will help to show the future applicability in large-scale production of PI nanofibers.The polymer concentration, solution feeding rate, gas pressure, nozzle size, and receiving distance during SBS process are important factors affecting the morphology and diameter distributions of solution blown PAA nanofibers.Concentration of polymer solution is the primary key factor affecting the spinnability in SBS process that it has to be properly controlled. Changing the concentration could alter the solution viscosity . It is nThe effect of solution feeding rate (varied from 0.8 to 3.2 mL/h) on the morphology and diameter distributions of PAA nanofibers was evaluated at a fixed PAA concentration, gas pressure, inner nozzle diameter, and receiving distance of 8 wt %, 0.08 MPa, 0.4 mm and 20 cm, respectively. The results shown in In the case of SBS, high velocity gas flow has the function of evaporating the solvent, deforming the solution streams, and solidifying them into the fibers. To evaluate the effect of spinneret nozzle size on nanofiber morphology and diameters, four different coaxial nozzles were adopted by varying inner nozzle diameters from 0.3 to 0.6 mm at fixed outer nozzle size and SBS parameters. SEM micrographs and fiber diameter distributions of PAA nanofibers were presented in The so-called receiving distance in SBS process generally means the distance from the nozzle orifice to the surface of the receiving drum, it determines the volatilization time of solvent and the moving distance of the solution jet before it become solidified. Following the optimization of polymer concentration, solution feeding rate, gas pressure, and nozzle size, the effect of receiving distances variable from 10 to 25 cm was discussed in our experiment. As demonstrated in −1, which were attributed to the C=C stretching and C–H bending vibration in benzene ring of PAA and PI, respectively. The most obvious difference in the FTIR spectrums was the disappearance of the broad absorption peak at 2900–3600 cm−1 after thermal imidization, which was attributed to the stretching vibration of carboxyl groups and amide groups of PAA. Meanwhile, the characteristic absorption peak at 1651 cm−1 (C=O stretching vibration in –CONH– and –COOH– groups) and 1604 cm−1 (N–H bending vibration in –CONH–) of PAA also vanished in PI spectrum, while new characteristic absorption peaks appeared at 1773, 1715, and 1355 cm−1 of the PI spectrum, which were accounted for the C=O asymmetric stretching, C=O symmetrical stretching, and C–N stretching in the imide ring, respectively. The above information demonstrated that the PAA nanofibers had been effectively converted to the corresponding PI nanofibers by the thermal imidization process. Furthermore, the absorption peak at 1244 cm−1 that appeared in both spectrums was attributed to the stretching of C–O–C, which verified the existence of flexible 4,4′-oxydianiline (ODA) units in the polyamide acid and polyimide molecular chain [To accurately confirm the conversion from PAA to PI, FTIR was used to characterize the chemical structures of the nanofibers before and after thermal imidization. As presented in ar chain .θ = 24.7°, indicating that a certain ordered crystalline structure has been formed during the solidifying and imidizing process of PAA. The degree of crystallinity of PI nanofibers was 23.56%, which was higher than that of most as-spun PI fibers [Wide angle X-ray diffraction (XRD) was performed for examining the crystallization in the nanofibers (nonwoven membrane made up of PI nanofibers), and the XRD pattern was shown in I fibers  due to tThe imidization of PAA is considered to be chemical change accompanied by a molecular chain self-ordering process. As shown in N,N-Dimethylformamide (DMF) with analytical grade was provided by Shanghai Ling Feng Chemicals Co., Ltd.,  and stored over 4 Å activated molecular sieves for at least a week prior to use.3,3′,4,4′-Biphenyltetracarboxylic dianhydride  and 4, 4′-oxydianiline  were supplied by Changzhou Sunlight Pharmaceutical Co., Ltd., . p-Phenylenediamine (PDA) was purchased from Sigma-Aldrich . PAA for spinning was synthesized from BPDA/PDA/ODA with molar ratio of 2:1:1. The synthesis process was as follows: 1.080 g (0.01 mol) PDA and 2.002 g (0.01 mol) ODA were first dispersed in DMF within a three-neck flask under dry nitrogen gas. After the diamine was almost dissolved, 5.94 g (0.02 mol) BPDA was gradually added with four batches in an hour. The polycondensation process was performed with intense stirring at 0 °C for 24 h. A pristine PAA solution with a concentration of 13 wt % was obtained eventually. The inherent viscosity of PAA solution was measured to be 3.56 dL/g by diluting a bit precisely weighted amount of the as-synthesized PAA solution with DMF. The obtained PAA solution was stored in refrigerator for later use.A special-designed SBS apparatus used for the experiments was schematically shown in The as-prepared PAA solution was diluted to different concentrations with a calculated amount of DMF; they were magnetically stirred for 10 h to ensure homogeneity. SBS process was carried out as follows: the homogeneous PAA solution was loaded into a 20 mL disposable syringe that was connected with the coaxial nozzle, and was extruded through the inner nozzle by a syringe pump at a certain rate (varied from 0.8 to 3.2 mL/h). The pressurized gas source was controlled with a pressure regulator, and the gas pressure varied according to experiment design. The inner nozzle was protruded 4.5 mm beyond the concentric outer nozzle. The blow-spun PAA nanofibers were deposited on a rotating drum as a collector, which was covered with aluminum foil, the drum was positioned at a fixed distance from the nozzle and the rotational speed of the collector was maintained at 150 rpm. After being spun for a certain time, the collected PAA nanofiber mat was peeled off carefully from the foil, and was subsequently dried in a vacuum oven at 60 °C overnight to volatilize the residual solvent.The thermal imidization of the as-spun PAA nanofibers was performed in a high temperature pipe furnace under argon atmosphere. The procedure was set as follows: heating up to 250 °C at a rate of 5 °C /min and annealing for 1 h, then heating up to 340 °C at a rate of 1 °C/min and annealing for 1 h, and finally cooling down to room temperature. The molecular structural formula of PAA and PI was shown in −1 with the resolution of 0.09 cm−1. A wide angle X-ray diffractometer  with a CuKα (λ = 1.5406 Å) was used to confirm the crystallographic structure of the sample. The diffraction angle 2θ was recorded from 5° to 60°. The tensile tests of as-prepared membranes were performed on a tensile tester  at a crosshead speed of 10 mm/min in ambient condition. The gauge length was 10 mm and the dimensions of test specimens were 3 mm wide and 25 μm thick. Every series of samples were measured ten times.Surface morphological observations of solution blown PAA were performed with a field emission scanning electron microscope  after sputter-coated with 5–10 nm of gold. Fiber diameters were determined using Image Tool software  by randomly selecting 100 individual fibers per specimen from at least five different SEM images with 5000× magnification. The structure of the PAA and PI membrane were confirmed by fourier transform infrared spectroscopy  with the attenuated total reflectance (ATR) mode. All spectra were run in 32 scan per spectrum in the range of 4000–600 cmIn summary, we succeeded in fabricating PAA nanofibers by a novel solution blow spinning method and then imidized them into PI nanofibers. The effect of solution blow spinning parameters on the morphology and diameter distributions of PAA nanofibers was discussed. It was found that solution concentration exhibited a notable correlation with spinnability and the formation of bead defects in PAA nanofibers. Accordingly, other parameters, including solution feeding rate, gas pressure, nozzle size, and receiving distance influenced the morphology and diameter distribution of PAA nanofibers. It was revealed that uniform PAA nanofibers were got under the optimum process parameters of 8 wt % PAA concentration, 2.4 mL/h solution feeding rate, 0.08 MPa gas pressure, 0.4 mm inner nozzle, and the receiving distance of 20 cm. The diameters of resultant PAA nanofibers distributed from 130 to 210 nm with an average value of 178.2 nm. FTIR confirmed that PAA nanofibers were effectively converted to PI nanofibers by the thermal imidization process. Furthermore, the XRD pattern indicated the degree of crystallinity of PI nanofibers was 23.56%, which contributed to the nanofibers’ strong mechanical properties. The PI nanofibers exhibited obvious adhesion morphology among interconnected fibers, along with the average diameter of 209.1 nm and tensile strength of 12.95 MPa, which was increased significantly when compared to that of PAA nanofiber mat (2.60 MPa). This research provides a novel and effective method to fabricate PI nanofiber mats.


The objective of this study was to compare the adsorption/desorption of target compounds on homemade electrospun nanofibers, polystyrene (PS) nanofibers, acrylic resin (AR) nanofibers and PS-AR composite nanofibers with Tenax TA. Ten volatile organic compounds (VOCs) were analyzed by preconcentration onto different sorbents followed by desorption  and analysis by capillary gas chromatography. In comparison to Tenax TA, the electrospun nanofibers displayed a significant advantage in desorption efficiency and adsorption selectivity. Stability studies were conducted as a comparative experiment between PS-AR nanofibers and Tenax TA using toluene as the model compound. No stability problems were observed upon storage of toluene on both PS-AR nanofibers and Tenax TA over 60 hours period when maintained in an ultra-freezer (−80°C). The nanofibers provided slightly better stability for the adsorbed analytes than Tenax TA under other storage conditions. In addition, the nanofibers also provided slightly better precision than Tenax TA. The quantitative adsorption of PS-AR nanofibers exhibited a good linearity, as evidenced by the 0.988–0.999 range of regression coefficients (R). These results suggest that for VOCs sampling the electrospun nanofibers can be a potential ideal adsorbent. Sample pre-treatment is the key segment of chemical analysis. When volatile organic compounds (VOCs) often as low as ppbV to pptV are to be determined, pre-concentration becomes the most crucial step. Solid Phase Extraction (SPE), for any type of sampling, it is possible to make choices in the type of adsorbent material used, sampling method (pumped or diffusive), the method by which the trapped vapours are removed (or not) from the adsorbent for analysis . Usually6–C30) [Tenax TA, a porous polymer of poly-2, 6-diphenyl-p-phenylene oxide, since the mid-1980s has been utilized for sampling VOCs. Though adsorbed loss of semi-volatiles has been related with stainless steel Tenax tubes, the hydrophobicity nature of Tenax TA avoids water-derived analytical issues experienced with multi-bed or carbon materials while still retaining a wide range of compound capture (C6–C30) –6. Howev6–C30) . It is vSPE and Solid Phase Micro Extraction (SPME) are well developed techniques in VOCs sampling and analysis, and every method has advantages and limitations . The metAs we known, electrospinning is a straightforward and versatile method for producing thin fibers, with diameters in the ranges of micrometre and nanometre, in the one-step formation of two- or three-dimensional nanofiber network assemblies composed of a broad spectrum of molecules, such as inorganic molecules as well as synthetic and biological polymers . A s a rIn this work, we performed a comparative study of the adsorption/desorption performance of VOCs for homemade electrospun nanofibers and commercial adsorbent Tenax TA, including the characterization, adsorption amount and selectivity, desorption efficiency, precision, stability, quantitative adsorption studies. In order to gain probe into the adsorption of VOCs on polymeric nanofibers, we displayed experimental results for adsorption of typical VOCs on three structurally dissimilar polymeric adsorbents, PS nanofibers, and acrylic resin (AR) nanofibers, and PS-AR co-spinning nanofibers, which is consistent with nanofiber adsorbent in previous study . And theAll of the solvents were of analytical grade and obtained from Lingfeng Chemical Reagent Co., Ltd, Shanghai, China. Polystyrene (PS) and acrylic resin (AR) were purchased from Shanghai Chemical Agents Institute, Shanghai, China. Tenax TA (60/80 mesh) was obtained from Buchem BV .The equipment referred in this research for the analysis of all target VOCs consisted of a gas chromatography-flame ionization detector (GC-FID) system . The target VOCs were separated on a HP-5 column (0.32 mm × 30 m × 0.25 μm). A high-voltage power supply  and syringe pump  were used for electrospinning. The nanofibers were examined using a field emission scanning electron microscope  and a specific surface and porosity analyzer . A headspace sampler  was used for thermal desorption.PS, AR and PS-AR electrospun nanofibers were fabricated as following: PS of 10% (w/v) was dissolved in a mixture of dimethylformamide (DMF) and tetrahydrofuran (THF) . AR of 10% (w/v) was dissolved in a mixture of DMF and ethanol . 10% (w/v) of PS-AR  was dissolved in the mixture of DMF and THF . Next, before electrospinning these solutions were stirred for 8 h at room temperature.Then every solution was loaded into the glass syringe which was fitted to a steel needle with a tip diameter of 0.5 mm. Electrospinning, shown in Before experiments, the tested materials were thermally conditioned to remove any residual components as follows: electrospun nanofibers were heated at 80°C for 2 hours with a nitrogen flow; Tenax TA was conditioned by thermal cleaning  under a nitrogen flow at 100 mL/min.As Then turned on the vacuum pump , No. 1, In preliminary experiments, we probed into the time of blowing gas. After 1 min, 3 min and 5 min of blowing gas, the initial peak areas of every VOC were consistent, so we chose the most convenient 1 min as the optimal time of blowing gas. Thus, after 1 min, the sealing clip was closed. The sample flask was always tightly sealed with the rubber plug. To ensure uniform distribution of the gas in the sample flask, a magnetic stirrer , No. 10 To verify the sample flask containing ten VOCs at the same time, the initial peak areas of ten VOCs were obtained by GC analysis of 1ml of injected sample. The tests were conducted in triplicate for every flask to indicate that every peak area variation was less than ± 5% and the process of blowing gas was prepared well.According to the recent study on adsorption equilibration time , after 3The sample components of desorption were determined using external standard quantitation. External standard calibration curves for samples were set up by preparing standards in methanol or in a mixture of acetone/hexane 1:1 (v/v) in a concentration range of 1–100 μg/mL. Then, 1 μL of the liquid was injected into GC for analysis. The determination was performed in triplicate for each sample.The desorbed VOCs were analyzed by GC-FID. The column oven temperature of GC was programmed to increase from an initial 40°C, which was maintained for 3 min, followed by an increase to 120°C at 5°C/min and a second increase to 250°C at 20°C/min, which was maintained for 5 min. The injection temperature and detection temperature were 250°C and 280°C respectively. Nitrogen was selected as carrier gas with flow rate of 0.5 mL/min. All injections were conducted in the split mode with the split ratio of 19:1.The surface characteristics of tested materials were studied utilizing SEM. As The textural property data of PS-AR nanofibers and Tenax, including the BET surface area, pore volume and pore size, was listed in 2/g, 0.025 cm3/g and 5.05 nm. However, the surface area and pore size of Tenax particle that the BET surface area, pore size and pore volume is 35 m2/g, 2.4 cm3/g and 200 nm respectively, much larger than that of PS-AR nanofibers. As these textural property data shown, the BET surface area data displayed no much difference between two materials, but their pore volume exhibited a differential of approximately one hundred times and pore size showed twenty times, which suggests the pore density of nanofibers is much higher than that of Tenax particle. Due to much smaller diameter of nanofibers, all this maybe signifies pores into nanofibers are dense and shallow. These dense and shallow pores contribute to adsorbates to arrive at adsorption site more easily, that is easier adsorption and desorption, as analogous presentation in a recent report [The analysis of surface area and pore size shows that the BET surface area, pore volume, pore size of representative PS-AR composite nanofibers are 19.52 mt report .In this paper, desorption procedure was conducted in two ways, thermal desorption and solvent desorption in sequence. The adsorption amount was expressed as the sum of the mass of the targets (μg/5 mg for the sorbent) desorbed from the solid phase using two methods. The adsorption amount was shown in Tenax TA is one of the most widely used adsorbents for the preconcentration of VOCs even though it does not exhibit satisfactory behavior for very volatile organic compounds , which is primarily due to the displacement of the adsorbed volatile and polar compounds by non-polar high-molecular weight compounds . As showPS nanofibers exhibit a higher adsorption amount for toluene and chlorobenzene because the interaction between the adsorbates and adsorbent is favored by similar chemical behavior of the polymer backbone and adsorbates . TherefoAn interesting phenomenon was discovered for the PS-AR nanofibers, which exhibit an integrated adsorption behavior of PS and AR nanofibers and adsorb nearly all of the tested compounds with a broad spectrum of moderate retention. The adsorption amount of the PS-AR nanofibers for VOCs is intermediate between those of PS and AR nanofibers. This phenomenon is obviously highly dependent upon the formation of composites, which could exhibit multifunctionality, such as the π-π interactions, hydrogen bonding, polar functional groups, etc. The interaction mechanism is partly analogous to extraction of polar targets from serum, urine and other biological samples using electrospun nanofibers –23. One An ideal sorbent for preconcentrating VOCs should have not only infinite adsorption amount for interesting compounds but also exhibit complete desorption of these compounds at moderate temperatures. During sampling the lack of retention is not the problem generally, yet polar analytes are strongly retained on most sorbents, which needs long residence times of the analytes on hot and active sorbent surface during desorption might resulting in reactions of the analytes, or reactions of the analytes with the surface itself, or reactions of the analytes with other adsorbed species. These reactions can cause permanent adsorption or/and artifact formation which is clearly undesirable effects . TherefoFrom Comparative results show that the nanofibers have a high or comparative adsorption amount and efficient thermal desorption. The reasons may be the gaseous adsorption/desorption occurs at the surface of nanofibers, while for Tenax TA, adsorbed mass has to diffuse through micropores, mesopores and macropores, the diffusion path is long and intricate, which slows the rate of adsorption and desorption.A precision study was conducted by the consecutive analysis of 5 samples executing adsorption/desorption. PS-AR nanofibers were selected in this experiment due to its broad-spectrum adsorption nature. 5 pieces of PS-AR nanofibers samples weighing 5 mg were placed in five separate sample boxes. Then, the boxes were placed into a vial filled with ten VOCs (conducted as mentioned in Experiment procedures of Adsorption and desorption). After adsorption for 2 hours, the nanofibers were desorbed with two methods including thermal desorption at 80°C and solvent desorption using 0.5 mL of methanol individually. Tenax TA was tested with the same procedure except that solvent desorption was performed with 0.5 mL of acetone/hexane 1:1 (v/v). Three replicate measurements of desorption samples were performed to obtain the peak area values, and only one measurement for thermal desorption. The precision was calculated as relative standard deviation (RSD) of the values.As shown in Stability study was conducted between PS-AR nanofibers and Tenax TA using toluene as a model compound (conducted as mentioned above in adsorption and desorption). After adsorption for 2 hours, PS-AR nanofibers and Tenax TA were stored in a sealed Pyrex glass tube respectively. The tubes were respectively stored under the following conditions: room temperature at 20°C, refrigerator at 4°C, conventional freezer at -20°C and ultra-freezer at −80°C. After a specific period of time, four sets of six samples were collected at different store times to yield a total of 24 samples for each adsorbent. Then, the adsorbents were desorbed in the proper solvent as described above. Three replicate measurements of the solvent desorption liquid were performed to obtain the peak area values. The amount of toluene recovered from the adsorbents analyzed at a storage time of zero was used as the baseline for the measurement of stability. As shown in The experimental device was shown in After 5 hours, the test materials were desorbed for 30 min in a headspace sampler at 80°C, and 1 mL of the gas sample was injected into GC for analysis.As shown in It is also shown that an anomalous adsorption with a narrow linear range or a larger intercept of the fitted line was observed for some VOCs. The reason is maybe that in the closed adsorption space containing ten VOCs, the interaction and interference existed between theseVOC molecules, andcompetitive adsorption and displace adsorption occurred in the adsorption sites on fibers till a dynamic adsorption equilibrium was reached.The adsorption/desorption performance of three types of nanofibers compared to that of Tenax TA, the most popular sampling material, for several VOCs was investigated. In comparison to the conventional adsorbent Tenax TA, electrospun nanofibers performed better or comparably well as the adsorbents for the VOCs tested. The electrospun nanofibers markedly displayed two special advantages. The ability to facilely fabricate selective or broad-spectrum nanofiber sorbents by pre- and post-electrospinning modification processes have been demonstrated. Additionally, the electrospun nanofibers also exhibited higher thermal desorption rates for most VOCs in the smaller empty vial at the lower temperature. These two characteristics are useful for improving the selectivity and sensitivity during VOCs sampling and determination. And the characteristics provided slightly better precision and stability of adsorbed analytes than Tenax TA. The electrospun nanofibers have been clearly suggested being a viable alternative to be the adsorbents for VOCs sampling.


Objectives: The pharmacotherapy of Parkinson’s disease (PD) is often challenging as clinicians have to find a favourable balance between the efficacy on motor symptoms and side effect profiles of different dopaminergic medications. We aimed to assess the available evidence on the role of dopamine agonist monotherapy as an alternative to Levodopa in the treatment of motor symptoms of PD, along with the role of dopamine antagonists in the treatment of PD-related psychosis.Methods: We performed a systematic literature review using the databases MEDLINE, EMBASE, PsycINFO and the Cochrane Library Central register of controlled trials. Two searches were performed, ‘Search 1’ extracting trials on dopamine agonists, and ‘Search 2’ on atypical antipsychotics. Eligible studies were Double-blind Randomised Controlled Trials (RCTs) using the Unified Parkinson’s Disease Rating Scale (UPDRS) and the Brief Psychiatric Rating Scale (BPRS) as outcome measures for Search 1 and 2, respectively.Results: 16 relevant RCTs were extracted from the search results. Overall, dopamine agonists were shown to significantly improve UPDRS scores, with a mean percentage improvement of 14.4% compared to −1.9% in the control arm However, their side effect profile illustrated they were associated with twice the incidence of psychotic symptoms in comparison to the controls. The results on the efficacy of atypical antipsychotics for the treatment of PD-related psychosis werenot significant.Conclusions: This evidence-based review confirmed that dopamine agonists can be an effective and safe treatment as monotherapy in PD, however psychotic symptoms remain a significant side effect. Atypical antipsychotics may not be relied upon for the correction of these symptoms due to inconsistent results about their efficacy.