Rapid urbanization has led to expansion of peri-urban fringes, where intensive, industry-style livestock rearing has led to emerging vulnerabilities at the human-animal-environment interface. This study was undertaken to understand the health system and farm-level factors that influenced the risk of transmission of bovine Tuberculosis (bTB) in animals and humans in peri-urban smallholder dairy farms of India.Thematic guides were developing through literature review and expert consultation. In-depth interviews were conducted till attainment of saturation. Identification of core themes was followed by etiological enquiry and generation of a conceptual model.Veterinarians were consulted as a last resort after home-remedies and quacks had failed. Damage control measures, especially with respect to- selling or abandoning sick animals, added to the risk of disease transmission. Although civic authorities believed in the adequacy of a functioning laboratory network, end users were aggrieved at the lack of services. Despite the presence of extension services, knowledge and awareness was limited, promoting risky behaviour. The absence of cogent policies in dealing with bTB was a significant barrier. Stakeholders did not consider bTB to be a major concern. It is possible that they underestimate the problem.The current study helps to identify gaps which need to be addressed through collaborative research, and OneHealth interventions to build community awareness.The online version of this article (10.1186/s12889-019-6634-3) contains supplementary material, which is available to authorized users. Mycobacterium bovis, the cause of bovine tuberculosis, has been identified in humans in most countries where isolates of mycobacteria from human patients have been fully characterized. The incidence of pulmonary tuberculosis caused by M. bovis is higher in occupationally exposed individuals such as farm and slaughterhouse workers than in urban inhabitants [M. bovis to humans via milk and its products is eliminated by the pasteurization of milk. Btb has been included in the list of notifiable terrestrial and aquatic animal diseases as given by OIE [M. tuberculosis) and animal (M. bovis) origin [M. bovis, in difference to meaning any tuberculosis occurring in bovines. A recent systematic review by Muller and colleagues has highlighted the existing gaps in basic epidemiological data relating to Btb globally with special emphasis to South East Asian region [Bovine tuberculosis (Btb) is a disease of infectious nature that occurs in cattle and can spread to humans by aerosol inhalation or ingestion of unpasteurized milk , 2. Mycoabitants . The tran by OIE . In deven by OIE , little ) origin . Both myn region . Reporten region –9. With n region . ConsideThe current study is part of larger initiative with a focus on periurban smallholder dairy farms. Smallholder dairy farming, typical of periurban ecosystems, suffers from lack of support and quality control of dairy farming as well as the absence of an organized system of farm inspection or screening of animals for disease . AgriculThis qualitative inquiry was undertaken among smallholding dairy farmers in peri-urban areas of three cities of India i.e. Guwahati, Ludhiana and Bangalore. In general, periurban zones of a typical city comprise a wide range of activities, including harvesting, animal husbandry, real estate investments, housing development and waste dumping etc. . DescripRespondents were identified through purposive sampling with the help of officials at local veterinary colleges and Non-Government Organization (NGO) partners. Snowballing technique was used to identify and ascertain stakeholder relevant for the study . No new The interviews were conducted by MSG  and ASC . Both interviewers were practicing public health investigators with significant experience in community processes, participatory methods and field level qualitative data collection methods. Interviewers held postgraduate degrees in public health with specialisation in qualitative field data collection methods. Face-to-face interviews with identified stakeholders were conducted at a place convenient to them. Partnering NGOs assisted setting up of schedules for interaction at a time convenient to the respective stakeholder. Most interviews with community level stakeholders were done in their respective local languages and most health systems and policy level officials were interviewed in English. On average, an IDI lasted nearly for 1 h. All interviews were tape-recorded, transcribed and translated from local language into English by professional agency, and double-checked against original tape recordings.Content analyses was used to undertake the data analysis. Software package AtlasTi 7.2® was used to code the transcripts, utilizing a reflexive and inductive approach to allow codes and categories to emerge from within the data. Coding was done by two investigators (MSG and ASC) and disagreements were addressed in discussion with senior investigators (MK and DG).An iterative process ensured that the data collected was grounded and have rich details related to the topic of inquiry .Interviews were conducted by qualified researchers. Interviews were scrutinised for completeness, correctness, and transcription and translation of responses with proper tagging of recordings. About 30% of the interviews from every study site were randomly verified for their correct transcription and translation. Due to inherent limitations of interpretation of qualitative data from culturally diverse as well from different farming systems, the data collection team undertook regular meetings with the steering group . The stuDetails of the stakeholders interviewed under this study is provided under Table Knowledge and practices related to BtbLimited system support for prevention and control of BtbLack of effective policies and programmatic direction in the context of BtbThe results are categorised as three core themes:Core theme are further divided into themes and sub-themes. These are listed in Table Systems concept allowed to study the associations and interplay between the sub-themes and core themes that functions at different levels. Levels are explained in detail in a previous publication associated with the larger initiative .Limited knowledge and practices related to Btb, especially among farmers, emerged as an important core theme. This was further determined by lack of understanding of disease causation, transmission, prevention and control, animal and public health impacts; availability of limited evidence to support attention by local stakeholders which reflected in absence of screening of cattle for Btb.Farmers could only relate the word ‘tuberculosis’ to human. A strong construct of ‘Tb only in human’ was reflected from the interviews. Farmers were mainly aware about the clean milk production and prevention & control of mastitis, brucellosis and foot & mouth disease. Due to lack of awareness about the possibility of cattle suffering from Btb, knowledge related to prevention and control was universally absent. Interestingly, few farmers could also tell about treatment of human tuberculosis. Nearly half the farmers were aware about brucellosis and its zoonotic potential. Among those who were aware, they knew that brucellosis can transmit between animal-animal and human-animal.Veterinarians demonstrated good understanding of Btb, its zoonotic potential, symptoms and, prevention and control measures. However, veterinary field assistants at all three sites had limited understanding of Btb. Most were aware about tuberculosis in cattle but not sure about zoonotic potential.Veterinary official’s perspective: According to state officials and veterinarians there is absence of estimates on burden of Btb in cattle population. As a result, the disease holds less importance for policy makers due to absence of evidence. Many veterinarians reported having come across clinical symptoms of Btb in cattle during their field visits. Few veterinarians also reported signs of tuberculosis infection during post mortem examination of cattle. One pathologist reported that he had recently come across cases of tuberculosis in cattle while conducting autopsies in one of the sites. He felt that this could potentially be an important area to study as nothing is known about the extent of the problem.goshalas, where older cattle are kept. All the six cases I came across last year were from a goshala and they did not know it was tuberculosis. It was only when post mortem was done did we come across nodules suggestive of M. bovis infection.” Pathologist - Government“I think bTB is of great importance now but we don’t have much data on it. Maybe you can study this especially in “We generally go to the fair and observe the physical characteristics of the animals on sale and how it walks how it stands etc. Based on that we decide whether to buy the animal or not.” Dairy farmerVeterinarians also admitted that in general, farmers did not screen animals before buying them and that the practice of routine screening of animals to detect any infections was practically non-existent. Similarly, sick cattle are often sold in cattle fairs.Screening of animals for diseases is almost universally done only by visual inspection. Farmers have been taught traditionally that the gait of the animal and its posture helps identify which animal is healthy and which is diseased. However, farmers also admitted pitfalls of this approach and the fact that there were occasions when they had managed to sell their animals that were sick at fairs.“Actually, we don’t have any policy to screen for TB in animals. Nothing has been done in this regard. Sometimes when there are studies carried out we have found cases, but there was no policy on what to do so it was left at that.” VeterinarianLimited systems support, outreach and oversight for prevention and control of Btb emerged as a core theme at the veterinary health systems level. This core theme could be further explained based on the following factors: inadequate support of extension services, lack of laboratory support to diagnose Btb and make informed decision for prevention and control and lack of technical and operational guidance on disposal of infected and dead animals.Officials from the animal husbandry department reported operationally functional labs and diagnostic support services to the field veterinarians. However, when asked specifically about Btb, very few veterinarians mentioned about the skin testing facility being available at the army farms or progressive dairy farms having large holdings. Routine screening as well as diagnostic facility for bovine tuberculosis in cattle for smallholder dairy farms was reported to be universally absent.“If the lab is in working condition we don’t have a microbiologist, if the microbiologist is there then there is no proper equipment. So how do I make use of it? On paper it is all there but practically it is not possible. If I need a lab report, then I ask them to go to the university or to some private labs to get a report.” VeterinarianVeterinarians reported that they are not dependant on laboratory results to treat cattle in the field. Treatment is mostly based on case history and symptomatic assessments. Veterinarians mentioned that in most of the cases the farmers seeks veterinarian’s consultation when cattle is critically ill after being all self-treatment and drug administration is tried, and resulted in no improvement.. Veterinarian immediately has to attend the cattle to prevent the loss of life. Secondly, according to the field veterinarians, the laboratories are not fully equipped nor completely functional. Therefore, even if they want to access the services, they do not receive the desired response both in terms of timeliness and quality. No veterinarian reported to have ever accessed laboratory facilities for testing Btb.“Look we treat primarily from the case history of the sick animal and after some years of experience you know that this animal is in this condition means it is suffering from this problem and this is the treatment. Other than that not much.” Veterinarian“What services are you talking about? There is such a big college here and they can’t even provide us with proper semen.” Dairy farmer union officialIt’s noteworthy that none of the dairy farmers in the study locations mentioned being benefitting from the extension services and all perceived them as substandard quality both in terms of content and delivery. They also reported that the extension services were undertaken as field level training to the university students. None of the farmers mentioned about any information being given specifically on Btb.“No we do not get anything from the department or college.” Dairy farmer“The department does organise activities from time to time when they want to train their students. Other than that, such activities are not focused on small farmers and their farms.” Dairy farmerExtension units are working efficiently and offers services to local dairy farmers on a consistent basis. Most of these extension services were presented free of charge so that all dairy farmers in these areas could avail them. Across the study locations, information being given to dairy farmers on farm hygiene and clean milk production was reported. None of the officials mentioned about any information session mentioning Btb.“Regular meetings are organized by the department and we have sessions taken by experts to give them the latest know-how on various issues related to management of a dairy farm.” Senior Extension department officialMany veterinarians reported that majority of the small holding dairy farmers do not to join the workshops organised by extension department. According to them, this is due to the farmers’ confidence on traditional knowledge which they receive via Intergenerational transfer of knowledge and practices in context to animal husbandry. On the other hand, new progressive farmers are relatively keen for learning the latest methods and developments in the field of dairy farming, and also receptive to the behavioural modifications.“If any of our animals die then we have to pay to get someone to come and remove the body (carcass) and take it away. We don’t get any support for this from anyone. So we don’t keep very sick animals here.” Dairy farmerThe farmers reported not receiving any regular formal support for disposal of dead animals. Disposal was organized by the farmers themselves which came at a cost and added to losses incurred on account of treatment as well as loss of productivity. As a result, farmers preferred selling animals when sick and not responsive to treatment.Dairy farmers referred to a specific community of people who visited farms and took sick animals away. In some sites they were referred to as ‘Mohammadeans’. Members of this community visit dairy farms on a regular basis, eyeing cattle, which showed signs and symptoms of any illness and offering prices based on the condition and age of the cows or buffaloes. While we did not get the opportunity to meet with any member of this community, dairy farmers across the three sites considered them as their allies  as they helped in easy disposal of sick animals. However, farmers remained unaware about the fate of this cattle.Lack of effective policies and programmatic direction in the context of Btb emerged as the core theme at policy level. The policy context of Btb could be further explained based on three sub themes that emerged inductively, namely limited focus on Btb under current livestock health programs, lack of Btb specific surveillance and response system and limited guidance on treatment protocol/procedure to deal with Btb.Assistance to States for Control of Animal Diseases (ASCAD) as a federally funded program provides provision for inclusion of diseases deemed important by the state. However, senior officials reported that there is no separate initiative to address Btb including, under ASCAD. It was also reported that limited screening of animals, as a diagnostic procedure, is done in veterinary colleges or on request by farmers in a more organized dairy farming set up.“When we had an outbreak of FMD then they came to screen all the animals. Otherwise nothing” Veterinarian“We do not have any data and that is our biggest problem. First of all, we need to collect proper data on the animals that we have without that we can’t progress.” Senior government officialRoutine surveillance was reported to be universally absent and no systems were in place to obtain any data in this regard. It was only during outbreaks when animal husbandry department and other officials got involved in collecting information about various cattle in the area and if any of them were infected with the particular disease of interest that had caused the outbreak . Efforts are primarily centred on outbreak and once the issue had settled down surveillance and screening of animals also tended to stop. However, it has never been done for Btb.Extension department officials in one of the sites pointed out that some years ago cases were found in animals held at the local veterinary university but there was no policy regarding what was to be done after that. A senior official pointed out that there was neither a policy about what to do with Btb nor adequate facilities to test samples.“Actually we don’t have any policy to screen for TB in animals. Nothing has been done in this regard. Sometimes when there are studies carried out we have found cases, but there was no policy on what to do, so it was left at that.” Veterinarian“See I am able to detect and find brucellosis why because there is support under a national programme. It is only after that I am able to test many samples and find out otherwise it is very difficult to do this work. So for TB so far we have nothing.” Senior official, Government LabFarmers were unaware of Btb as a disease that affected cattle and had marked impact on health and productivity of animals. However, as elicited in disease management practices, once some unsuccessful attempts have been made to treat the animals, a sick cow is often sold to minimize losses. This should include cows suffering from Btb which typically results in disease signs/symptoms such as cough, wasting and loss of productivity in cows.There is a significant variation between the three selected study sites in context to dairy farming systems. Guwahati dairy farming system is unregulated and mainly dominated by traders. In contrast, Bangalore and Ludhiana are fairly under influence of cooperative unions which are relatively active in providing information services etc. related to disease transmission and animal health. Dairy system could potentially be a driving force affecting farm level disease dynamics and non-prescribed usage of veterinary antimicrobials.A conceptual model was developed to present the findings of the study. The potential drivers contributing to the transmission of Btb in periurban small holding dairy farms are categorized into community, health system and policy level. This was done considering the level there are operating in. Additionally, interplay of these drivers within and across the categories is demonstrated in the model Fig. .Fig. 1CoDairy farming sector in India has seen a major turnaround in the last few decades. As a result of the “white revolution”, India now has the distinction of being the largest milk producer in the world with 53.77 million tonnes in year 2017–18 . InteresKnowledge of good animal husbandry practices, farm hygiene and clean milk production are critical for safe and sustainable milk production. Extension services are supposed to play an important role in imparting this knowledge on a regular basis. Similarly, organized systems of milk procurement and supply such as cooperatives can be an important source of knowledge and oversight of good practices. India, however, fails on both these accounts. Evidence suggests that public sector extension system is a source of information for about 10% farmers, with 33rd schedule of NSSO’s ‘Situation Assessment Survey of Framers’ revealing that 60% of farmer households in India had not accessed any information on modern technology in past 1 year . SimilarThis qualitative enquiry studied dairy farming practices in peri-urban small holder farms in three cities in India, each characterized by a different trading system, in the context of vulnerability to Btb. Btb is a zoonoses that has been widely underreported and understudied but is believed to be a significant contributor to animal and human losses in India , 21. MajAt the system level, efforts directed at prevention and control of Btb were found to be grossly inadequate. Btb was not perceived as a problem and as result there was no system for regular screening of animals, except for voluntary testing by farmers or in more organized systems such as military and university farms. Expectedly, skin testing for Btb was found to be more of an academic exercise in university departments rather than a regular program feature. Efforts to increase awareness among farmers through outreach activities were also found to be absent. For example, few farmers in Bangalore reported that although they had attended seminars and workshop, tuberculosis was never discussed on these platforms. The Assistance to States for Control of Animal Diseases (ASCAD) programme provides a framework wherein states are free to choose the disease which, according to them, are important to their respective state . CurrentLimited appreciation of Btb as a problem could be the consequence of overall policy neglect, largely driven by lack of evidence. Qualitative narrative and the literature review show that bovine tuberculosis among cattle is one of the least studied disease with limited epidemiological evidences to support the decision making in India. Studies from South-East Asia reported animal level prevalence of bovine tuberculosis up to 24.7% , 30. A rLimited specific technical options available to policy makers and program managers for control of Btb, such as test and slaughter or test and isolation, could also explain the policy neglect. In India, cattle are considered sacred and slaughtering is constitutionally banned . In lighIntensification of dairy production in the peri-urban fringes could potentially be helpful in alleviating the poverty among the dairy farmers which could further address the issue of risk practices like selling sick cattle for slaughtering through unregulated channels as well as in cattle fairs. Better economic condition would further enhance capacity to pay for veterinary consultations, medications etc. Improved feeding, especially better use of concentrate feed, well-developed marketing systems with processing infrastructure, improving genetic quality of the herd through support to private or co-operative-based AI services are some of the potential options for successful intensification of dairy sector in India , 34.While a synergy emerged among the stakeholders as reflected in general lack of knowledge and appreciation of Btb as a problem, interesting divergent perspectives that are equally important in informing next steps, were worth noting. The animal husbandry department indicated towards an element of secrecy, over-reliance on traditional knowledge and avoidance of formal health care services on part of the farmers in the event of sickness in the herd. On the other hand, the health care system was perceived as severely constrained by the farmers in terms of providing knowledge, technical support, economic support and access in general. As a result, they had to rely on more predictable sources of information such as traditional knowledge, peers and private practitioners. Any efforts at system strengthening should therefore address the trust and credibility deficit for program impact.A very small number of state-level civic officials were involved in this study. Notwithstanding this, the limited number provided rich and meaningful data as the respondents who participated had decades of experience in animal husbandry and veterinary medicine. IDI with dairy farmers were performed in the local languages and then translated into English. Despite the rigorous verification process, some subtle nuances might have been missed during the verbatim transcribing.There are serious knowledge deficits and lack of appreciation of Btb as an animal and public health problem. While investments have lacked at the program and policy level, a large part could be attributed to lack of evidence and focus by the research community. The evidence is needed not only about the burden and risks, but also on possible options for control applied in the local Indian setting. Meanwhile, there is preliminary evidence that can at least inform initiation of awareness about the problem of Btb in animals, its health and economic impact in animals and zoonotic potential in humans. The response has to be initiated from both animal and human health sectors.Additional file 1:Thematic Guides. Thematic guides used for formal In-Depth Interviews of the stakeholders under the study. (PDF 251 kb)


The diagnosis of idiopathic interstitial pneumonias (IIPs) involves amultidisciplinary scenario in which the radiologist assumes a key role. Thelatest (2013) update of the IIP classification by the American ThoracicSociety/European Respiratory Society proposed some important changes to theoriginal classification of 2002. The novelties include the addition of a newdisease  and the subdivision of theIIPs into four main groups: chronic fibrosing IIPs ; smoking-related IIPs; acute or subacute IIPs ; rare IIPs ; and the so-called“unclassifiable” IIPs. In this study, we review the main clinical, tomographic,and pathological characteristics of each IIP. The integrated approach notwithstanding, the finalclassification and definitive diagnosis might not be achieved in all cases. Somecases do not meet the criteria for classification into any of the classicinterstitial lung disease categories and are therefore designated “unclassifiable”.Such cases continue to pose a challenge for the entire multidisciplinary team.Idiopathic interstitial pneumonias (IIPs) are part of a broad, heterogeneous group ofinterstitial lung diseases that encompasses more than 200 acute or chronic diseaseswith varying degrees of inflammation or fibrosis. Given the innumerable clinical,radiological, and pathological aspects, as well as the constant need to analyze thecourse of IIPs, it is essential that the diagnosis and follow-up of these diseasesbe conducted within a multidisciplinary scenario in which the radiologist assumes afundamental role. High-resolution computed tomography of the chest has been thesubject of recent publications in the radiology literature of Brazil,9 proposes some important changes inrelation to the original (2002) classification. Notable among those changes are thesubdivision of IIPs into four main groups  and the addition of a new disease: idiopathicpleuroparenchymal fibroelastosis.The most recent (2013) update of the American Thoracic Society/European RespiratorySociety IIP classificationIn this study, we provide a brief clinical description of each of these four IIPgroups, as well as presenting their main radiological characteristics , includi, idiopathicpulmonary fibrosis is the most common; it is an interstitial lung disease ofunknown cause, characterized histologically by the usual interstitial pneumoniapattern,12, with dispersed fibroblasticfoci and heterogeneous involvement of the parenchyma, areas of tissuepreservation being interspersed with areas of interstitial inflammation andhoneycombing. It occurs mainly in adults over 50 years of age who are smokers orformer smokers, typically manifesting as progressive dyspnea and dry cough. Ingeneral, it has a poor prognosis, with an estimated survival of less than fiveyears after the diagnosis. Patients usually have fewer acute exacerbations whentreated with cyclosporine combined with corticosteroids, and most are consideredcandidates for lung transplantation. In an appropriate clinical setting , the diagnosis of idiopathic pulmonary fibrosis canbe established without the need for biopsy.Among all IIPs: cellular (less common andwith a better prognosis); fibrotic (with a worse prognosis); or mixed.Nonspecific interstitial pneumonia can be idiopathic, although it most oftenmanifests as pulmonary symptoms associated with connective tissue diseases, hypersensitivity pneumonia, drug reactions, or diffusealveolar damage. It typically occurs in women between 40 and 50 years of age,with symptoms similar to, although usually milder than, those of idiopathicpulmonary fibrosis. Treatment is directed to the underlying disease and caninclude the use of a combination of systemic corticosteroids and cytotoxicdrugs, which is successful in most cases. Although the tomographic findings of idiopathicpulmonary fibrosis and nonspecific interstitial pneumonia are oftensimilar, anexperienced radiologist knows the main differences between them , mainly affecting previously healthy patients between 50 and 60 yearsof age, with severe sudden-onset dyspnea (occurring within the first threeweeks), typically progressing to the need for mechanical ventilation. Itmainly affects women between 50 and 70 years of age, with nonspecific symptomsof chronic coughing and dyspnea . Theresponse to corticosteroid therapy is unpredictable.In the vast majority of patients, lymphocytic interstitial pneumonia isassociated with systemic autoimmune or immunodeficiency disorders, includingconnective tissue diseases . In its idiopathic form, it isconsidered extremely rare. Histologically, it is characterized by diffuseinfiltration of the interstitium by polyclonal lymphocytes, histiocytes, andvariable numbers of plasma cells, as well as reactive lymphoid folliclesdistributed throughout the peribronchovascular regions, accompanied by intenseinflammation. With a little more than 40 cases describedin the literature to date, this entity has been associated with infections, bonemarrow transplantation, autoimmune diseases, and genetic predisposition. Itssymptoms are nonspecific (dry cough and dyspnea), and it is believed to progressslowly (over the course of 10-20 years), with few therapeutic options other thanlung transplantation.Idiopathic pleuroparenchymal fibroelastosis is a rare disease affecting thepleura and lungs. It is characterized histologically by homogeneous subpleuralfibrosis and abundant elastic fibers, with variable inflammation and lymphoidaggregates. Currently, there is no consensus regarding its diagnostic criteriaor regarding the fact that it is a new entityThe correct diagnosis and classification of IIPs involves a broad multidisciplinarydebate, with many gaps. Given the similarity of the clinical and pathologicalfindings, together with the complexity of the differential diagnoses and the needfor constant follow-up, high-resolution computed tomography plays a fundamental rolein the diagnostic assessment of these diseases.


Antimicrobial resistance (AMR) has become an emerging issue in the developing countries as well as in Bangladesh. AMR is aggravated by irrational use of antimicrobials in a largely unregulated pluralistic health system. This review presents a ‘snap shot’ of the current situation including existing policies and practices to address AMR, and the challenges and barriers associated with their implementation.Google Scholar, Pubmed, and Biomed Central databases for searching peer-reviewed literature in human, animal and environment sectors during January 2010-August 2019, and Google for grey materials from the institutional and journal websites. Two members of the study team independently reviewed these documents for inclusion in the analysis. We used a ‘mixed studies review’ method for synthesizing evidences from different studies.A systematic approach was adopted for identifying, screening, and selecting relevant literature on AMR situation in Bangladesh. We used Of the final 47 articles, 35 were primary research, nine laboratory-based research, two review papers and one situation analysis report. Nineteen articles on human health dealt with prescribing and/or use of antimicrobials, five on self-medication, two on non-compliance of dosage, and 10 on the sensitivity and resistance patterns of antibiotics. Four papers focused on the use of antimicrobials in food animals and seven on environmental contamination. Findings reveal widespread availability of antimicrobials without prescription in the country including rise in its irrational use across sectors and consequent contamination of environment and spread of resistance. The development and transmission of AMR is deep-rooted in various supply and demand side factors. Implementation of existing policies and strategies remains a challenge due to poor awareness, inadequate resources and absence of national surveillance.AMR is a multi-dimensional problem involving different sectors, disciplines and stakeholders requiring a One Health comprehensive approach for containment. The world is on the verge of sliding back to ‘pre-antibiotic era’ due to evolving resistance against life-saving antimicrobial drugs, with fundamental effect on individual and public health . To combThe southeast Asia is considered to have the highest risk of AMR among all the WHO regions . Most ofIn many of these countries, antimicrobials are widely available as over-the-counter (OTC) drug, Bangladesh is no exception . The prePolicies and regulations that support appropriate and rational use of antimicrobials are essential for effective interventions to contain the development and spread of AMR. Bangladesh has recently approved a National Action Plan (NAP) for containing AMR, in alignment with the WHO GAP guidelines . For impGoogle for unpublished/grey materials; Google Scholar, PubMed, and BioMed Central for peer-reviewed articles)  . We handrticles) . A PRISMrticles) .We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach for selection of articles on current AMR situation and relevant policies and practices to be included in the analysis .We used a ‘mixed studies review’ method for synthesizing evidence from qualitative, quantitative and mixed method studies which are useful in understanding complex public health interventions and programmes . A data We used Google, Google Scholar, Pubmed, and BiomedCentral databases for searching relevant literature from Bangladesh. Ultimately, 47 articles  were included for analysis. Of these, 35 were primary research, nine laboratory-based research, two review papers and one situation analysis report. Again, 19 of the articles on human health dealt with antimicrobial prescribing and/or use, five with self-medication, two on non-compliance of dosage, and 10 were on antibiotics sensitivity and resistance patterns. For AMR scenario in animals and environment, five papers focused on use in animals and six papers on environmental contamination. Besides, current health and drug-related policies and strategies for both humans and animals, and national action plan for containment of AMR in Bangladesh were included through hand search and grey literature search using Google. The findings from the review are described below according to key themes of the study.Several small-scale studies reported on antimicrobial prescribing and its use, varying by factors such as age and sex. For example, children (66%) were prescribed more antimicrobials than adults (44%) , and thePatients’ non-compliance with scheduled dosage, and consequently facilitating the emergence of AMR, was a common phenomenon found in the literature reviewed ,28,32,33The prevalence of self-treatment  in the reviewed studies was found to be quite high –38. It wE. coli, and S. typhi to be resistant to low-cost and commonly used antibiotics [S. typhi to be resistant to multiple antibiotics. Another study conducted in three tertiary level hospitals in Dhaka shows resistance against older and commonly used antimicrobials in E. coli, S. aureus, Pseudomonas and Klebsiella infections in 50% of the cases [E. coli in 84% of cases, which was resistant to amoxicillin in 82% of cases [E. coli against amoxicillin were also observed in another study involving isolates from public and private hospitals, and clinics and diagnostic centres in Dhaka city [Ten papers reported on antibiotic susceptibility testing and resistance patterns. Resistance against antibiotics like imipenem was found in uropathogens . Susceptibiotics –43. Mannibiotics  collectehe cases . In 70% of cases . SimilarSalmonella typhi was found sensitive to amikacin (70%), azithromycin (73%), ceftazidime (63%), ceftriaxone (67%) and ciprofloxacin (87%). Another study (2017) found E. coli in 86% of urine samples collected from a private medical college hospital in Dhaka which was highly resistant to amoxicillin (95%) [E. coli [In a recent study, Tarana et al  reportedin (95%) . More thin (95%) . Antibio[E. coli . A revie[E. coli .Pangas fish samples from Sylhet Sadar [E. coli in the water [E.coli in Buffalo faeces [A high percentage of poultry meat and eggs meant for human consumption were found to have antimicrobial residues such as tetracycline, ciprofloxacin, enrofloxacin and amoxicillin ,50. The et Sadar . This haet Sadar –57. The et Sadar . Besideset Sadar . Around et Sadar . The hoshe water . This eno faeces .Quite a number of policies, guidelines, ordinances and laws relevant to containment of AMR in human, food animal, and environment sectors currently exist in Bangladesh . Of thesSince the updated National Drug Policy 2016 , the govst and 2nd lines of choice of antibiotics for specific infecting organisms. Banning the general use of antibiotics as a growth factor is emphasized in documents pertaining to the animal sector. To prevent contamination of the environment, specific guidelines are advised for waste management e.g., Guideline for Assessment of Effluent Treatment Plant 2008, Medical Waste Management and Processing Rule 2008, and Environment Protection Act 1995. Interestingly, none of these made any specific reference to the problem of AMR  formulated the National Livestock Development Policy where they highlighted inadequate veterinary services and weak implementation of regulatory frameworks as barriers to address AMR in this sector . Specifim of AMR .Finally, a National Action Plan 2017–2022 for containing AMR in Bangladesh has been prepared by the Disease Control Unit of the Director General of Health Services, MoHFW with a road map for its implementation in alignment with the global plan . The docThis scoping review revealed widespread availability of antimicrobials without prescription in Bangladesh, a rising trend in its irrational use in humans and food animals and fisheries, and consequent spread of resistant strains through environmental contamination. The policies and strategies to contain AMR are at an early stage of development in the country and implementation remains a major challenge. This is due to poor awareness about AMR among the policy makers and practitioners, inadequate resources to implement measures to contain AMR, and absence of a comprehensive national surveillance system to monitor the emergence of AMR. The implications of these findings in the context of the emerging ‘One Health’ movement in the country is discussed, including some recommendations for tackling the problem urgently.It is obvious from the findings that the factors underlying irrational and inappropriate use of antimicrobials, and consequent emergence of AMR in Bangladesh, have both supply and demand side perspectives. On the supply side, all categories of the allopathic practitioners whether qualified or not, are prone to use ‘excess’ antimicrobials due to poor awareness regarding its rational use. Other factors contributing to the emergence of AMR include lack of diagnostic facilities, burgeoning private practice and unreasonable demand for antibiotics from patients and ‘caregivers’, especially for children. Besides, there are aggressive marketing strategies of the pharmaceutical companies specifically aimed at generating prescriptions at the cost of patients. This scenario is not unlike that found in other countries of the region such as India , IndonesEncouragingly, attempts have been made to overcome the ‘gaps’ in knowledge and use of antimicrobials by these countries which have implication for Bangladesh. For example, the Indian Council of Medical Research (ICMR) brought a qualified group of prescribers in a workshop to enhance their knowledge on AMR and related issues, and involved them in preparing guidelines for rational prescription of antimicrobials . GARP-NeIn the demand side, rising trend of antimicrobials use resulting from poor consumer awareness on dangers of inappropriate use, use as a stop-gap measure, non-compliance with dosage, and self-medication as observed in Bangladesh are also common in India –71, Sri In this review, we found a large proportion of medical practitioners and students in Bangladesh unaware about the guidelines on the use of antimicrobials. The urgency of including this in the graduate curriculum cannot be overemphasized. Coupled with stringent implementation of regulatory measures in the production and distribution of antimicrobials, with appropriate incentives (‘carrot and stick’ approach), will go a long way in mitigating the AMR problem.There is no dearth of policies and strategies especially since 2014, but operationalization of these remains a challenge which is true for implementing any public policy in general in Bangladesh , includiE. coli [The importance of building awareness among the policy-makers for coordinated action across the sectors, updating medical and allied health sciences curriculum for rational use of medicines including antimicrobials, and adequate resourcing with budget and human resources cannot be overemphasized. Again, for the very fundamental task of infection prevention and control in LMICs like Bangladesh, the implementation of WASH activities has an important role to play by reducing the transmission of resistant strains in the environment –84. ThisE. coli . The sitE. coli . This shThe problem of AMR is multi-sectoral, multi-disciplinary, and multi-institutional and thus need a coordinated response of the three sectors, adopting a comprehensive approach such as that of One Health. The outbreak of avian influenza in Bangladesh in 2007 exposed the vulnerability of the country to transmission of infection from animals and environment. In 2008, stakeholders in the human, animal and environmental sectors came together to promote the concept of ‘One Health’ in Bangladesh . As a coIn this scoping review of AMR situation in Bangladesh, we tried to gather maximum available information. However, due to restricted access to some of the databases, the search may not be exhaustive. Besides, there was dearth of published materials on this topic in general, and particularly in some sectors such as the contribution of environmental contamination in initiating and propagating AMR. The included articles were critically appraised but the weighted ratings were not done.The factors for the development and transmission of AMR in Bangladesh are deep-rooted in various supply and demand side factors. However, irrational use of antimicrobials in, and beyond, human health sector  is aggravating the situation and posing a threat to human health. To address this comprehensively, multi-sectoral and multi-stakeholder efforts are needed based on the strategy of ‘One Health.’ For this, critical awareness of the problem across the sectors and professionals, high level political commitment, intra and inter-ministerial coordination among relevant sectors, and enforcement of regulatory regime are urgently warranted.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.


Especially under 308 nm UVB-LED pumping, the total emission spectral power of supramolecular Tb-complexes/PAN nanofibers are identified to be 2.88 µW and the total emission photon number reaches to 7.94 × 1012 cps which are nearly six times higher than those of the binary complex ones in the visible region, respectively. By modifying the sorts of organic ligands, the luminous flux and luminous efficacy of multi-ligand Tb-complexes/PAN nanofibers are up to 1553.42 μlm and 13.72 mlm/W, respectively. Efficient photon-releasing and intense green-emission demonstrate that the polymer-capped multi-component terbium-complexes fibers have potential prospects for making designable flexible optoelectronic devices.Multivariate terbium-complexes were incorporated into polyacrylonitrile (PAN) and electrospun into flexible multifunctional nanofibers with a uniform diameter of ~200 nm. Fluorescence comparison in multi-ligand-binding nanofibers under ultraviolet (UV) radiation verifies that the differentiated β-diketone ligands with dual functions are the primary cause of the spectral fluctuation, adequately illustrating the available methods for the quantification of intermolecular reciprocities between organic ligands and central Tb Particularly, more remarks in challenge of 1D organic-inorganic composites lie in integrating the flexibility and processability of the organic materials into the thermal stability and chemical resistance of the inorganic materials8. So far, electrospinning is considered as a relatively straightforward method for producing 1D luminescent nanomaterials with high porosity, favorable flexibility and large surface, such as nanofibers, nanowires, nanotubes, nanorods, nanobelts and so forth13. The electrospun setup for fabricating the nanofibers is shown in Fig. 18.Growing interest is being devoted to exploring novel luminescent materials with assembling one-dimensional 1D) nanostructures in view of their unique properties and intriguing applications in light-emitting devices and color displayD nanostr22. Among the trivalent lanthanide compounds with visible light emission, the investigations are mainly focused on the europium and terbium complexes which possess long-lived intense red and green luminescence with high quantum efficiency26. In addition, as a result of the absent dense energy level, the probability of non-radiative transition is greatly reduced between the triplet and ground states of ligands, thus the introduction of RE into β-diketone ligands with large absorption cross-section has attracted extensive attention29. At the same time, in order to improve inferior optical properties and poor thermal stability of pure complexes, RE-complexes are usually incorporated into polymer matrixes to embody excellent characteristics of both the complexes and the polymers and apply to various new technologies34. Although some RE-complexes doped polymer nanofibers have been investigated37, the systematic correlation on the fluctuation of photon-releasing with differentiated organic ligands in electrospun nanofibers is still worth exploring in making optoelectronic devices.Considering that rare earth (RE) complexes have sharp and strong emission lines under ultraviolet (UV) irradiation through effective intramolecular energy transfer from the coordinated ligands to the RE-ions, the affinity can be improved by selecting or synthesizing organic groups3+ ions is chief factor which determines the luminescence performance of the swatches. Spectroscopic intensity parameters of multivariate nanofibers are derived from spectral power and photon number, as well as the luminous flux is also deducted under 308 nm UVB light emitting diode (UVB-LED) excitation, revealing the appropriate organic ligands are conducive to improving the efficiency of photon-conversion. The flexible polymeric nanofibrous membrane containing β-diketone ligands can be adopted as a developed prototype with characteristic of bending, stretching and even twisting and no negative effect on photon emission, these facilitate the development of the flexible wearable electronic devices.Our work has focused on the use of multifunctional ligands to capture the energy and transfer to the rare-earth-metal-ions in PAN-capped electrospun nanofiber membranes, among which the multivariate terbium-complexes nanofibers have adopted organic ligands including acetylacetone (acac), benzoic acid (BA) and 1,10-phenanthroline (Phen). Asystematic microstructural and spectroscopic characterization of poly-ligand Tb-complexes/PAN nanofibers are presented by SEM, FT-IR, fluorescence spectra, absolute spectral distributions and DSC-TGA thermodynamic investigation, which provide the evidence of excellent performance for composite fibers. Differentiated responses to short-wave radiation in these nanofibers are revealed and the energies involved in noncovalent interactions are proposed, confirming that the energy difference between the lowest triplet state energy of ligands and the resonant emissive energy of Tb3 (curve 1), Tb(acac)3Phen (curve 2), Tb(BA)3Phen (curve 3) and Tb(acac)2(BA)Phen (curve 4) precursor powders have been carried out in the frequency range of 4000−400 cm−1 and shown in Fig. −1 are associated to the enol-keto tautomers of the β-diketone corresponding to the C=O stretching vibration of keto and the C=C stretching vibration of enol, respectively, which indicates that the carboxylic acid takes off the proton to coordinate with the Tb3+ ions by the acid radical40. As expected, a broadband peaked at 3435 cm−1 may be because of the presence of external water molecule. As compared with the spectrum of curve 1, the peaks of curve 2, curve 3 and curve 4 around 1600 cm−1 left shift slightly corresponding to the non-characteristic absorption −N=C− stretching vibration of Phen. Meanwhile, the regions of 835–853 and 718–733 cm−1 in curve 2 are attributed to N–H vibration, and it is noticed that the complexation spectra at 3428 cm−1 appear a shift of the δ(N–H) absorption band to a higher frequency (Δδ = 7 cm−1) after the introduction of Phen, indicating that the chelating action from nitrogen atoms to Tb3+ ions has produced42. In curves 3 and 4, the peaks at 1556 and 1421 cm−1 are the C=O and C=C stretching vibration of β-diketone which left shift (1464 cm−1) due to the substitution of one or two acetylacetone by BA groups during the dissolution process43. Moreover, the frequency signal about 534 cm−1 provided valuable information about ligand-metal vibrations, which can be ascribed to the interactions of Tb–O coordination. The above spectra data fully demonstrate the formation of the multi-ligand binary (Tb(acac)3), ternary (Tb(acac)3Phen and Tb(BA)3Phen) and quarternary (Tb(acac)2(BA)Phen) complexes. β-diketone rare-earth-metal complexes not only exhibit good coordination and fine sensitization function but also possess a variety of conjugate structures44. In addition, the high electron cloud density of β-diketonate ligand will enable the RE-complexes to have strong photo-absorption and energy transfer ability.In order to explore the effect of different organic ligands on the properties of composite materials, the intensive research is carried out on terbium-complex/PAN nanofibers. Figure 3/PAN (A), Tb(acac)3Phen/PAN (B), Tb(BA)3Phen/PAN (C) and Tb(acac)2(BA)Phen/PAN (D) nanofibers with favorable morphologies are obtained as shown in Fig. In order to further understand the micro/macro-structure of the PAN loaded Tb-complexes nanofiber membranes, the Tb(acac)46. Furthermore, the 1D cross-link-mesh-like superfine nanofiber also exhibits larger surface to volume ratios with a positive effect in absorbing ultraviolet (UV) and shortwave radiation, demonstrating that ordered nanoscale arrays could serve as building blocks to fabricate complex wearable optoelectronic devices and systems.To further confirm and demonstrate the dispersion of precursor powders in nanofibers, the internal constructions of A, B, C and D electrospun nanofibers are clearly exhibited by TEM images in Fig. 3+ ion chelated complexes exhibit lanthanide characteristic emissions and the luminescence of the A, B, C and D nanofibers are demonstrated by the emission spectra in Fig. ∗ transition of ligands and emission lines of Tb3+ 5D4 → 7FJ  are obtained with the hypersensitive transition 5D4 → 7F4 (545 nm) green emission as the most prominent group50. However, the emission intensity is quite different for each complex, this difference originates from the various coordination environments caused by the diverse neutral ligands.Tb53. Bright green fluorescence is observed and the effect of Phen is confirmed upon enhanced emission, indicating the effectiveness of photon-conversion from UV to visible region. For C nanofiber, the strongest fluorescence emission is revealed under 239 and 327 nm excitations, which confirms the optimum of excitation wavelengths in the BA and Phen coexistence system. In D nanofiber, since the excited state energy of Phen is close to that of acac and lower than that of BA, the energy transfer from BA to acac and Phen leads to the decreases of the energy received and the fluorescence release of Tb3+ ions54. The variation of ligands disturbs the surrounding environment of the center Tb3+ ions and causes the distorted complex structure to some extent, resulting in the change of the center ion symmetry and further modified forbidden effect of f-f transition, all of which cause the discrepancy of luminescent properties in the composites.The luminescence properties change dramatically compared with the corresponding binary complexes after the second and third ligands introducing in ternary and quaternary complexes systems. Compared of fluorescence performances between A and B nanofibers, the luminescence emission intensity is influenced greatly when Phen is introduced as a synergistic screening ligand for acac, which can explain by the difference of triplet state energies and the existence of the intermolecular reciprocity between carboxylic acids and Phen56. Except for A nanofibers, other excitation spectra monitoring the green emission of Tb3+ at 545 nm are dominated by a broad band centered at 276 and 296 nm, respectively, which is consistent with the emissions in all of them and indicates that the energy transfer exists between ligands and central Tb3+ ions. Apparently, the excitation bands of B nanofibers become wider and blue shift compared with those of the other complex nanofibers, which further demonstrates the excellent fluorescence properties in B nanofibers. However, the excitability is relatively low in case of BA, acac and Phen coexisting, which imply the radiation intensity of Tb3+ is subject to limitations due to the variation of energy transfer efficiency and the intermolecular interaction from the ligands to the central Tb3+. As the token of the increased ligand types, the absorption competition among ligands predominate, and the fluorescence intensity of the system decreases. Therefore, altering the kinds of organic ligands could change the relative intensity of Tb-complex emission to obtain strong green fluorescence under UV radiation, which further testifies that Tb3+ ion is suitable as the emission source of photoelectric devices.As shown in Fig. 3+ ions in binary, ternary and quaternary complex systems and the efficient emission photos of the nanofibers under UV exposure are portrayed in Fig. 3+ ions, while the Phen stabilizes the molecular structure of ternary complex system and decreases the non-radiative channels , which reveals the existence of Phen contributes to the enhancement of fluorescence intensity57. While in quaternary composite system, as the species of the ligands further increases, the reciprocities between ligand and ligand become more complicated and the energy loss increases, resulting in a decrease in the photon acceptability of the central Tb ions.Interaction mechanism of ligand-ligand and ligand-Tb58. Subsequently, a pre-carbonization process is further performed after 450 °C to achieve enough intermolecular cyclization. Among them, a few physical cross-links formed among the PAN molecules due to the coordination of the PAN and the Tb-complex, which plays a pivotal role in the heat resistance of the PAN-based composite nanofibers. Further, given that the operating temperature of LEDs is less than 150 °C, the macromolecular polymer-based Tb-complex nanofibers with good thermal stability are sufficient for the manufacture of LEDs60.The thermal behavior of the materials involved can be further supplemented by DSC–TGA curves, and the nanofibers are put into an alumina crucible where all materials are measured in identical conditions. As can be seen from Fig. 5D4 level in A, B, C and D nanofibers excited at 276 nm and monitored at 545 nm are presented in Fig. τexp-avg) of 5D4 level is derived from the fluorescence decay curves using the following equationI(t) is the emission intensity at time t. Besides, the related results are calculated and listed in Table 3+ is varied slightly in the complexes, from which the luminescence lifetime is determined to be 1.43, 1.55, 1.37 and 1.50 ms in A, B, C and D, respectively. The fluorescence lifetime is varied with the β-diketone ligands for Tb-complexes in organized molecular nanofibers, which can be put down to the dual functions of ligands for the Tb3+ ions.For further comparison and clarity, the fluorescence decay curves of 3+ fluorescence decay in nanofibers, the fluorescence lifetime t of 5D4 can be expressed by the following form k1 is radiation rate constant, k2 and k3 are non-radiative energy transfer and the back-donation rate constants to the ground states and to the triplet of the ligands, respectively. Among them, the resonance energy level and the rate constants k1 and k2 of Tb3+ are relatively stable, while the k3 could be modified with the adjustable of β-diketone ligands61. The longest and weakest t are revealed in the B and C nanofibers, which can be understood by investigating the intramolecular energy transfer process in Tb-complexes. Additionally, the t is also relevant to the energy transfer rate constant k3 which originates from 5D4 to the triplet of β-diketone ligands. In B nanofibers, k3 may be the smallest among those in Tb-complexes nanofibers, resulting in the longest fluorescence lifetime. Along with the introduction of BA, the fluorescence time shows a descending trend due to the triplet energy level of BA (21200 cm−1) is lower than those of acac (25280 cm−1) and Phen (22075 cm−1), and it is similar to the 5D4 energy level (21000 cm−1) of Tb3+ ions, causing the poor intramolecular resonance energy transfer between BA and Tb ions64. As a result, the fluorescence of Tb(acac)3(BA)Phen/PAN nanofiber is the weakest.To further investigate the effects of ligands on Tb5D4→7FJ  transitions with the strongest emission at 545 nm as shown in Fig. 66. In the meantime, the spectra are reshaped gradually and the emitting light of composite nanofibers is tuned by modifying the class of β-diketone ligands in Tb-complexes. Besides, the total emission powers of A, B, C and D nanofibers are identified to be 0.47, 2.88, 2.04 and 1.10 µW, respectively. In view of the increasing interest in systems capable of generating photon fields containing a preset number of photons, it chiefly provides basic information and related applications in the field of optics. Furthermore, the photon distribution can be given by the following formulaλ, ν, h and c represent wavelength, wavenumber, Planck’s constant and vacuum light velocity, respectively. The total emission photon numbers are derived to be 1.29 × 1012, 7.94 × 1012, 5.61 × 1012 and 3.03 × 1012 cps for A, B, C and D nanofibers, respectively, and the photon distribution curves are presented in Fig. 3+ ions in B nanofibers.For a better understanding of the optical properties in these complexes, the absolute spectral parameters from those used in interiors and for which almost all data on visual performance have been accumulated. Intense green light scattering is captured in PAN-capped Tb-complexes and spectral power distributions of A, B, C and D nanofibers are recorded using an integrating sphere with a 308 nm UVB-LED as the pump source, which consists of a weak broadband and four major luminescent peaks centering at 480, 545, 584 and 621 nm originate from the * transition of β-diketonate ligand, and another absorption band at 274 nm is attributed to the π → π* transition of the non-bonded electrons involving the oxygen atoms. The absorption peak for B, C and D nanofibers at 270 nm is primarily ascribed to the superimposition of n → π* transition of C=N in Phen and the π → π* electron transition of the benzene ring67. Moreover, an obvious blue shift is observed in the spectra after the addition of Phen owing to a large resonance effect of the substituent between the carboxylate groups and N atoms and an increase of electron conjugation in lanthanide metal centers, which increases the π* level to a higher extent than the n rank68. These results show a maximum photo-absorption capacity of polymer-Tb composite nanofiber and confirm the existence of intramolecular interaction and sensitization effect, further demonstrating that the fibrous membranes could be well excited at the short-wavelength UV region.Besides, UV absorption of RE-complexes is mainly determined by ligands. When the RE-ions bond with ligands, the light absorptivity increases due to the enhance of electron delocalization and oxygen atoms conjugation and the decrease of the system energy. Here, the UV-Vis absorption spectra of A, B, C and D nanofibers are presented in Fig. 70. Therefore, an efficient energy transfer (ET) mechanism among the ligands is also discussed in this part. Taking the dominance of ligand radiation under 276 and 296 nm excitations as examples, the ligand absorbs energy from the ground state (S0) to the excited singlet state (S1), then inter-system crossing (ISC) to the excited triplet state (T1) and then releases FL. In addition, the neutral ligands may compete with the central ligands to absorb energy in the presence of multiple neutral ligands. Therefore, compared with binary and ternary complexes, the reduced luminescence intensity in the quaternary complex nanofibers is due to the disturbed energy absorption process and the lost energy between different ligands. Afterward the ET occurs from the ligands to the resonantly excited 5D3 level of Tb3+ ions, and the excited ions decay to the energetically 5D4 states through multi-phonon relaxation and then the characteristic fluorescence is released via the non-radiative relaxation (NRR)72. When it comes to color displays, the CIE-1931 chromaticity coordinates of the green color shift from  to ,  and  with the amelioration of ligands in A, B, C and D nanofibers with the introduction of more components and the CIE diagram is represented in Fig. Energy transfer efficiency is primarily determined by the matching degree between the triplet state of the ligands and the excited state of RE-ions. Figure 73. Under the 308 nm UVB-LED excitation, the total luminous flux Φv of A, B, C and D nanofibers can be defined by the following expressionV(λ) and Km are the relative eye sensitivity and the maximum luminous efficacy at 555 nm (683 lm/W), respectively. All of the emission spectra offer very high luminous efficacy as illustrated in Fig. v and the luminous efficacy are exposed in Table Luminous efficacy provides a relation between daylight and solar radiation, which reflects valuable insight into the spectral quality of incident radiation, in other words, it is helpful information for the research of optoelectronic materialsmentclass2pt{minim3+ ions. Therefore, the polymer-based Tb-complex nanofibers provide an orientation for the systematic design and development of advanced functional materials by ligand optimization and electrospun fibrosis.Under the 308 nm UVB-LED excitation with the exciting electric power of 113.2 mW, the total luminous flux and the luminous efficacy of B nanofibers reach to the maximum 1553.42 μlm and 13.72 mlm/W, respectively, which surpass those of other nanofibers with an accordance in fluorescence spectra. Meanwhile, the brightness parameter of B is higher than that of A, C and D nanofibers, which is mainly owing to the better interactivity between ligands and RE ions, further indicating that the B nanofibers possess stronger sensitivity of the intramolecular energy transfer between the triplet state energy of ligands and the resonant emissive energy of central Tb3+ ions and the lowest triplet states of the ligands. The total emission powers of Tb(acac)3, Tb(acac)3Phen, Tb(BA)3Phen and Tb(acac)2(BA)Phen doped PAN nanofibers are identified to be 0.47, 2.88, 2.04 and 1.10 µW, and the total emission photon numbers are up to 1.29 × 1012, 7.94 × 1012, 5.61 × 1012 and 3.03 × 1012 cps under the excitation of 308 nm UVB-LED, respectively. Furthermore, the luminous fluxes and the fluorescence lifetimes are recorded under short-wavelength radiation, revealing the intramolecular interaction and sensitization of ligands have great influence on the photon-conversion of Tb-complexes/PAN nanofibers. Efficient photon releasing and positive emission behavior for polymer-based Tb-complex composites provide a positive role for promoting the development of the advanced flexible photoelectronic devices.Superfine and uniform multivariate β-diketone terbium-complexes integrated polyacrylonitrile (PAN) nanofibers are prepared via electrospun with a diameter of ~200 nm and bright green emission is obtained under ultraviolet excitation. Fluctuated photon releasing with multi-component β-diketone ligands compounds is attributed to the suitable energy matching between the resonance energy levels of the central Tb3, Tb(acac)3Phen, Tb(BA)3Phen and Tb(acac)2(BA)Phen were synthesized with acetylacetone (acac), benzoic acid (BA) and 1,10-phenanthroline monohydrate (Phen) as ligands, respectively. For instance, according to Tb(acac)2(BA)Phen chemical formula, TbCl3·6H2O, acac, BA and Phen were dissolved in 40 mL 99.7% ethanol in a molar ratio of 1:2:1:1, and then sodium hydroxide (NaOH) was added to adjust the PH to 6–7. Subsequently, polyacrylonitrile (PAN) were dissolved in N, N-Dimethylformamide (DMF) solutions with Tb(acac)3, Tb(acac)3Phen, Tb(BA)3Phen and Tb(acac)2(BA)Phen precursors concentration occupied 1 wt% of PAN weight and then labeled as A, B, C and D, respectively. All the Tb-complex/PAN electrospinning solutions were magnetically stirred until uniform and transparent at room temperature. During the electrospinning process, a 19.5 kV voltage was provided by a variable high DC voltage power and the 20 cm distance was setup between the nozzle and the collector.Precursor powders of Terbium-complexes Tb(acac)−1 using KBr pellets. Field-emission scanning electron microscope  was employed to observe the surface morphologies of the terbium-complexes doped PAN nanofibrous membranes at 5 kV accelerating voltage. Transmission electron microscopy  was studied to confirm dispersion of composite precursors in nanofibers. Photoluminescence spectra and fluorescence decay curves were recorded with a Hitachi F-7000 fluorescence spectrophotometer, using a R928 photomultiplier (PMT) tube as the detector and a commercial Xe-lamp as the excitation source. Differential scanning calorimetry (DSC) and the thermogravimetric analysis (TGA) were carried out to study the thermal performance by an American TA company SDT 600 under N2 atmosphere with a heating rate of 20 °C/min. The absorption spectra were conducted by a Perkin-Elmer UV/VIS/NIR Lambda 950 double-beam spectrophotometer. Absolute spectral parameters of the samples were obtained in an integrating sphere (Labsphere) with an internal diameter of 25 cm equipped a QEP01780 standard CCD detector (Ocean Optics) with a core wire of 600 μm. Under 308 nm UVB-LED excitation, the excited current was fixed at 20 mA and the referenced voltage was 5.66 V. A standard halogen lamp  was used to calibrate the measurement system and the nanofibers were placed on the top of the LED.The transmission spectra of Tb-complex precursors were investigated by a Perkin-Elmer FTIR/NIR Spectrometer (FT-IR), which reflected the functional groups in complexes for wavenumbers of 4000–400 cm


Important approaches such as high-throughput screening (HTS) have increasingly been used in combination with emerging strategies relying on genomics, chemical biology and molecular modeling  with a combination of experimental techniques  connects recent applications of LBDD and SBDD with the study of drug activity, as well as drug absorption, distribution, metabolism, excretion (ADME) and toxicity. We were able to collect 31 articles connecting more than 200 scientists from all around the world. Molecular modeling strategies for different conditions such as cancer, leishmaniasis, malaria, coronary heart disease, diabetes, and Alzheimer's disease are addressed. A broad variety of topics including the development of scoring functions, nuclear magnetic resonance (NMR)-assisted molecular docking, and the interplay between molecular docking and molecular dynamics are covered. In addition, this RT highlights the use of natural products as inhibitors of molecular targets such as the epidermal growth factor receptor (EGFR) and tumor necrosis factors (TNFs). New ligands targeting protein arginine methyltransferases, Kirsten rat sarcoma viral oncogene homolog (KRAS), G protein-coupled receptors (GPCRs), matrix metalloproteinases, heat shock proteins (HSPs), and mammalian Disheveled, are also considered. The design and implementation of online platforms for the prediction of It is our aim that the high-quality material enclosed in this RT contributes to the dissemination of outstanding science across the worldwide research community dedicated to the fascinating universe of drug discovery.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Oryzias melastigma and saltwater Rhodeus ocellatus, which led to their death. The occurrence of the intracellular assembly of SeNVs was observed in the roots and leaves of corn Zea mays, but not in those of Limnobium laevigatum. SeNVs led to the death of Z. mays but caused chronic toxicity in L. laevigatum. SeNVs should be a system or structure that dissipates the intracellular redox gradients of the host cells, with simple information consisting Se–O, Se–N, or Se–S bond, that would ensure elemental Se ligand binding with nearly specific biomolecules in host cells, thereby maintaining their composition and stabilizing their structure. The multiple toxic effects of Se, therefore, could be the consequence of increase of entropy in the host cells caused by the intracellular assembly of SeNVs. This study may provide an insight into the underlying mechanism of Se in environmental toxicology and its applications in human health.Selenium (Se) is an essential micronutrient in living organisms, having a narrow margin between essential and potentially toxic intake/exposure. Thus, the biochemistry of Se in living organisms must be studied in-depth to determine the underlying mechanism of Se cytotoxicity. In this study, we report the emergence of selenium nanovirus (SeNVs) in selenite-exposed fish  and plants (dryland) and its toxicity in them. SeNVs were found in both the abdomen and tail of  •Intracellularly assembly of SeNPs has been considered as a new interpretation of selenium cytotoxicity.•We provide the concept of SeNVs, which should be a system/structure that dissipates the redox gradients of host cells.•The toxic effect of selenium could be the consequence of structural and functional disorder in the host cell caused by SeNVs.•The concept of SeNVs will be beneficial for understanding the toxicology of selenium. HoweverThe intracellular assembly of SeNPs have been found in bacteria, archaea, and fungi . The acuIn the present study, our operational hypothesis was that the intracellular biogenic SeNPs are nanovirus (SeNVs) and are a process rather than a live system . Althoug22.1Chlamydomonas reinhardtii that revealed no requirement for Se [Z. mays  [The results of TEM analyses showed that exposure to high concentrations of selenite led to acute toxicity in medaka, Chinese bitterling, and corn with 100% mortality occurring after 24 and 96 h . A high t for Se ,34. In t[Z. mays . Corn Z.diagram) .Table 1ML. laevigatum, but found different toxicities between smooth frogbit L. laevigatum and corn Z. mays. Smooth frogbit L. laevigatum was more resistant to selenite than corn Z. mays, perhaps because there is no SeNVs emergence in smooth frogbit L. laevigatum  was cultured in 5.0-L aquaria with fresh water, using the same freshwater quality and selenite treatment employed for the Chinese bitterling. Selenite was diluted with a stock solution (10 mg/mL), and was randomly administered to the plants (8 per group) to the final concentration of 10 mg/L. Corn (Zea mays) was cultivated in pots during the kharif season in 2017 in the net house of Ningbo Urban Environment Observation and Research Station, Chinese Academy of Sciences. The soil used in the pot for the experiment was collected from an agricultural farm, air-dried, ground, and sieved through a 2-mm sieve. The sieved soil (0.5 kg) was used to fill each pot. The experimental design was laid out in triplicate. Each pot had two baby corn plants and were treated with selenite (10 mg/kg) to the final concentration of 10 mg/kg after 20 days of cultivation. A batch of adult salinity-tolerant medaka (Oryzias melastigma) and freshwater Chinese bitterling (Rhodeus ocellatus) were used in this study. The fish were cultured in 5.0-L aquaria. All fish were fed an artificial pellet diet twice a day. For acute toxicity study, three separate trials were performed using the same batch. Sodium selenite (10 mg/mL) was randomly administered to adult fish (8 per group) to the final concentration of 10 mg/L [Smooth frogbit  at 4 °C. The tissue samples were then fixed in 1% osmium tetroxide buffered with veronal for 1 h. The samples were then dehydrated in an alcohol series  and embedded in Epon 812 . Ultrathin sections were cut perpendicular to the plane of the monolayer and double stained with lead citrate and uranyl acetate. Electron microscopy and measurement of precipitated Se with electron microscopy-based energy dispersive X-ray (EDX) spectrometric analysis were conducted using TEM equipped with scanning and point EDX capability.Tissue samples for TEM  were first washed with phosphate-buffered saline solution, fixed overnight The authors declare no competing interests.


In principle, excitation of surface plasmons by molecular tunnel junctions can be controlled at the molecular level. Stable electrical excitation sources of surface plasmons are therefore desirable. Herein, molecular junctions are reported where tunneling charge carriers excite surface plasmons in the gold bottom electrodes via inelastic tunneling and it is shown that the intermittent light emission (blinking) originates from conformational dynamics of the molecules. The blinking rates, in turn, are controlled by changing the rigidity of the molecular backbone. Power spectral density analysis shows that molecular junctions with flexible aliphatic molecules blink, while junctions with rigid aromatic molecules do not. In molecular tunnel junctions, plasmons are excited via inelastic tunneling where the charge carriers tunnel through molecular bonds. These junctions blink due to molecular vibrations and conformational changes. This article shows that the light emission is unstable for junctions with flexible aliphatic backbones while junctions with rigid molecular backbones do not blink paving the way for stable molecular plasmon sources. We characterized the on‐time (P(ton)) and off‐time (P(toff)) probability densities of the intermittent light emission (blinking) in the STJs and found that the P(ton) and P(toff) probability densities follow a power‐lawRecently, we have demonstrated on‐chip electrically driven plasmon sources using self‐assembled monolayer (SAM)‐based tunnel junctions (STJs) and showed the control over the plasmonic properties  by the chemistry of the molecules in the STJs.J (the current density) for the same molecule incorporated in different types of junctions.In molecular electronics, a challenge is to rationalize the large spread of eight orders of magnitude in the measured values of We believe that the intermittent light emission of molecular electronic plasmon (MEP) sources can be explained by the fluctuating barrier model associated with the conformational changes of the molecules in response to inelastic tunneling where charge carriers interact with the vibrational modes of the molecule resulting in conformational changes of the molecules.ton and toff that characterize the length of each state ranging from microseconds to minutes.P(ton) and P(toff) follow an inverse power law, P(ton)∝t−mon and P(toff)∝t−moff, where mon and moff range from 1 to 2.P and t.S(f).P(t) analysis, S(f) is in the frequency domain and is the Fourier transform of the autocorrelation of the emission intensity time trace I(t).P(t), the distributions of S(f) follow a power law in the form of S(f  ) ∝ f−α where α is between 1 and 2.S(f) behavior is often modeled with Equation A and B are the amplitudes of the 1/f  and the 1/f  2 components, f0 is the characteristic frequency of the 1/f  2 component and can be characterized by the inflection point in S(f), and the constant C does not depend on frequency and is an offset representing the white noise floor.Under continuous excitation, point sources, such as quantum dots and single molecules, emit light irregularly, and often switch between “on” and “off” states with the times −3–100 Hz) studied here. These observations suggest that conformational changes of the molecules play a major role in the blinking of MEP sources. This work also highlights that the electrical contact between the electrode and the barrier molecules is highly heterogenous and varies from junction to junction depending on the chemical nature of the molecules. In addition, the electrical contact points along which tunneling occurs change within the junctions resulting in time‐dependent changes in the junction properties.In this work, we experimentally demonstrate the control of the intermittent light emission of the MEP sources by the rigidity of the molecular backbone. With stiff aromatic molecular backbones, the blinking is almost eliminated, while the opposite is true for flexible aliphatic molecular backbones over the range of frequencies , which is well‐established and generates high‐quality molecular junctions in high yields of working devices.2.12, which, e.g., can have gauche conformations which are not possible for SC‐PEP. Consequently, an SC12 molecule can be in contact with both electrodes when in an all‐trans conformation but the contact with the top‐electrode will be lost when a Gauche defect is present. In the former case, the tunneling barrier width (d0) and height and the corresponding tunneling decay coefficient (β1) are defined by the molecule  a second component is presently defined by the air gap d2 and associated tunneling decay coefficient β2  measurementsFigure J(V) characteristics of the two types of STJs were recorded using the Keithley 6430 source meter and a home‐made Labview program, with electrical bias applied between −1.8 and +1.8 V in steps of 90 mV. FigureJ(V) curves (averaged over 150 traces) of the two types of STJs. We note that the two SAMs have a similar molecular length (1.8 nm for SC12 and 1.6 nm for SC‐PEP), thus junctions with SC‐PEP SAMs with the aromatic molecular backbone, in theory, should have higher J values than junctions with SC12 SAMs because aromatic molecules have smaller tunneling decay coefficients (0.2–0.4 Å−1) than aliphatic molecules (0.8 Å−1),FigureThe 12 SAM  curves and clear molecular effects are resolved as in our experiments the top‐electrodes were fabricated always in exactly the same manner. We have shown elsewhere that the 0.7 nm thin GaOx layer shows metallic behavior and only has a minor contribution to the contact resistance.To record the light emission from the STJs in real‐time, we used a wide‐field inverted optical microscope equipped with an electron‐multiplying charge coupled device and a 100 × oil immersion objective with the numerical aperture NA = 1.49 (see the Supporting Information). Figure S(f) analysis of the intermittent light emission from individual emission spots for both types of STJs . Figure S(f) analysis. The I(t) of the STJ with SC12 SAMs , the S(f) of the SC12 junction . In contrast, the S(f) of the SC‐PEP junction . Here, the 1/f component results from intensity fluctuations that occur randomly in the on state and do not have a measurable repetition period. While in the case of SC12 junctions, the 1/f component is mainly due to the random intensity fluctuations of the off states. The extra 1/f  2 component with the characteristic frequency f0 = 0.1 Hz corresponds to the pronounced intensity fluctuations (the blinking) between the on and off states with a repetition period of around 10 s. It is important to note that although the time scale for the molecular conformational change can be very fast, the conformational changes in SAM are very slow due to steric hindrance between neighboring molecules and favorable packing energies. Previous STM experimentsp‐phenyleneethynylene) molecules in SAMs keep their conformations stable over prolonged periods of time up to hours.To quantify the blinking dynamics, we performed s Figure a shows cs Figure b remainsn Figure c decreasS(f) of the SC12 junctions at −1.8, −2.0, and −2.2 V. Figure S(f) analysis. For each applied bias, we analyzed 40–50 individual blinking spots to determine f0 and Figure f0 with a Gaussian fit  to these histograms to determine the Gaussian mean value of f0. The value of f0 increases from 0.09 Hz at −1.8 V to 0.15 Hz at −2.2 V showing that the blinking rate increases with bias. These observations agree with inelastic tunneling: with increasing bias both the tunneling electron energy and the tunneling electron rate increase, thus the possibility for the conformational change increases, which explains the near doubling of f0. For SC‐PEP junctions, we also observed an increase in the blinking rate with increasing bias, however, the 1/f component dominates in the measured bias range .It has been reported before that the rate of conformational changes induced by inelastic tunneling increases with increasing applied bias.S(f) analysis of the time traces of the tunneling current. Figure12 SAMs and SC‐PEP SAMs with the current sampling time 0.13 s . For both types of STJs, the tunneling current fluctuations are smaller than 20% and only show the 1/f component. This cannot account for the 1/f  2 blinking behavior of the SC12 junction. We note that the recorded tunneling current represents the current flowing across all spots in the entire STJ. As shown in Figure C represents the thermal noise of the tunnel junctions. For both types of junctions, the current is at the same level (within a factor 2–4) and the term C of 5 × 10−5 is also very similar J = J2 is the tunneling decay coefficient of air (since our experiments are conducted in ambient conditions). Since the value of β2 of air is 2.9 Å−1 and β1 is 0.8 Å−1 for aliphatic SAMs,d2 of 1.1 Å (which is roughly the length of one CH2 unit) results in a factor of 10 decrease in the value of J. Such a small gap can be easily obtained by bending of the molecule and  rotation of molecular segments around C‐C bonds. For aromatic SAMs, β1 is 0.2–0.4 Å−1,d2 of 0.9 Å is sufficient to reduce the local current by a factor of 10, and, as mentioned above, changes in the dihedral angle of the two phenyl groups can also induce changes in the current. However, our results show that the SC‐PEP molecules have significantly reduced blinking events than the SC12 case in the measured frequency range. Therefore, we conclude that changes in the dihedral angle fall out of the measured frequency window.The tunnel barrier can be described as a double barrier junction by Equation S(f) analysis was performed in the frequency range of 0.1–106 Hz, and the fluctuation of the tunneling current was attributed to changes in the molecule–electrode (Au‐S) bond,S(f) analysis of the light emission from large‐area STJs (in the frequency range of 10−3 to 1 Hz) which provides a new way to visualize and examine the local current fluctuations within a large‐area STJ, which is not possible with noise spectroscopy based on the tunnel current measured across the whole junction.We note that others have performed noise spectroscopy of current time traces of single molecule junctions.V < 0.3 V), the J(V) curves are linear from which we determined a conductance of the SC12 and SC‐PEP junctions of 1.2 × 10−7G0 and 8.2 × 10−7G0, respectively (G0 is the quantum conductance of 7.75 × 10−5 S). Considering the number of emitting spots (the spot number at −2.0 V), that is 42 ± 5 for SC12 and 8 ± 3 for SC‐PEP junctions , the conductance of each emitting spot is 2.9 × 10−9 and 1.0 × 10−7G0, respectively. These conductance values are similar (within one order of magnitude) to previously reported values obtained from junctions . We believe that this difference can be explained by the different stiffness of the molecules as molecules with a large conformational degree of freedom can form a better conformal contact with the top electrode than stiff molecules. For techniques that require spin coating of top‐electrodes or protective barriers (that are placed between the SAM and the top electrode), such as organic semiconductorsOur results also reveal that the top electrode forms a 5.2 times more efficient contact with the SC3f behavior, while STJs with aliphatic molecules show an extra 1/f  2 component representing the blinking induced by the conformational changes of the molecules. In addition, our methods allow for direct visualization and quantification of the effective electrical contact area making quantitative comparisons to single molecule experiments possible and dynamic characteristics of the molecule–electrode interfaces of molecular tunnel junctions in operando. Thus, we disentangled two sources of heterogeneity—spatial and temporal—and showed that rigidity of the molecules—an inherent property of all molecules—within the junction directly influences the light emission during electron tunneling at the electrical contact areas.In conclusion, we demonstrate control over the intermittent light emission of STJ‐based plasmon sources by changing the flexibility of the molecular backbones. Stable light emission (originating from radiative decay of surface plasmons) is obtained for junctions with stiff conjugated molecules, in contrast to the same junctions but with aliphatic molecules. We found that light emission from STJs with aromatic molecules follows a 1/We believe that our results are important for future studies where, for instance, strong intermolecular interactions could be explored to reduce blinking, or how molecular dipoles or charging of the SAMs via redox reactions could affect the molecule–electrode interactions and consequently the blinking dynamics.The authors declare no conflict of interest.SupplementaryClick here for additional data file.SupplementaryClick here for additional data file.SupplementaryClick here for additional data file.