Kenji Shibuya and coauthors discuss the potential contribution of East Asian countries to global health in the light of COVID-19. East Asia, comprising the 10 ASEAN countries, China, Japan, and the countries of the Korean peninsula, has achieved comparatively good outcomes during the ongoing Coronavirus Disease 2019 (COVID-19) pandemic.This can be explained by sociological imprinting of and learning from past outbreaks, as well as competent governance.Concomitantly, East Asian nations have also been expanding capacity in global health development and diplomatic outreach, although there is as yet no coherent regional bloc vision, shared strategy, or a common set of operating principles, thus limiting synergistic impact.We believe that concrete next steps to bolster cooperation and extend influence could include the establishment of an East Asian Center for Disease Control, joint work in health and human security by the Asian Development Bank (ADB) and Asian Infrastructure and Investment Bank, and a region-wide research funding programme.Much, however, depends on evolving geopolitics writ large, notably the instability and reorientation of global alliances, which have the potential to adversely affect relations between neighbouring East Asian member states.Health diplomacy for global human security has the potential to become a stabilising influence and can be a topic around which all actors can more comfortably rally.While the constituent countries of East Asia share common elements of history and culture, there is great diversity and rapid transition in social systems, economic development, demography, and epidemiological profiles . These fHere, in the light of Coronavirus Disease 2019 (COVID-19), we discuss East Asia’s experience in this and past major outbreaks, its capacity and willingness to share best practice and support global health development, and the regional bloc’s potential in reshaping the global architecture for human security.Geographically and ethnoculturally, East Asia has conventionally referred to the region comprising China, Japan, Republic of Korea (South Korea), Democratic People’s Republic of Korea (North Korea), and Mongolia. More recently, the term has been broadened to encompass Southeast Asia , largely due to expanded regional economic cooperation and latterly for geopolitical reasons.COVID-19 has prompted reflections on how the world has come to the present state of the ongoing pandemic, drawing lessons from the past century of global outbreaks since the defining 1918 influenza pandemic [Therefore, East Asia may possess certain ecological and environmental characteristics that could have facilitated the emergence of novel respiratory viruses. The propensity for zoonotic spillovers is one major factor. For example, poultry supply chains in major producing nations, notably China and Vietnam in East Asia, as well as neighbouring Indonesia, still feature the long-entrenched live poultry market trade that remains responsible for half of all birds consumed in those countries. From farm production , to transport over long distances reaching wholesale markets, thence distribution to retail outlets, there are plenty of opportunities for virus amplification among the flocks and zoonotic events crossing the avian–human interface . With reIn addition, the sociological imprints of multiple, repeated major emergence events might well have influenced population readiness and behaviour as well as governments’ predisposition to preparedness and response. In particular, SARS in 2002 to 2003 had left a deep impression on the collective psyche of East Asian countries that were affected: mainland China, Taiwan, Hong Kong Special Administrative Region, and Singapore. These and other East Asian governments revamped their surveillance and response infrastructure, built additional hospital isolation wards, and invested in workforce training, just as many European and American counterparts retrenched and pulled back funding support for these critical public health functions ,6. For eAt the individual level, personal hygiene practices and perception of what might be deemed appropriate and acceptable behaviour changed. Take mask wearing as an example: whether to don face masks or facial covering to prevent community spread has perhaps been one of the most argued and divisive issues in COVID-19, initially between East Asia and the West and later along partisan fissures within Western countries. Even the World Health Organization (WHO) had prevaricated on the issue during the initial months of the pandemic until it finally advised governments to “encourage the general public to wear masks in specific situations and settings as part of a comprehensive approach to suppress SARS-CoV-2 transmission” in its June 2020 guidance ,11.Comparing the COVID-19 responses in China, Hong Kong Special Administrative Region, Singapore, South Korea, and Taiwan, we identify 4 main East Asian characteristics that may be relevant to improving global preparedness and response to future outbreaks ,12,13.Chief among these is the critical importance of maintaining high levels of preparedness and the willingness and ability to respond swiftly and robustly to suppress an epidemic very early in its course. This has allowed for the policy goal of “near elimination” or “zero COVID” in all of these places. Crucial corequisites include sustained prior investment in strengthening public health infrastructure and capabilities; coordinated public health emergency management systems; clear structures to liaise across multiple agencies; a strong science base; effective testing, contact tracing, and isolation capabilities; stockpiling of personal protective equipment, medical supplies, and equipment; and good public communications built around comprehensive and transparently shared data. Countries that have not placed similar emphases, including those highly rated for epidemic preparedness before COVID-19 , have doA second learning point from the East Asian COVID-19 response is the need to swiftly adapt strategies and innovate as more becomes known about the virus and how it spreads. For example, South Korea showed that very big outbreaks can be controlled or prevented through rapid high-volume testing of large numbers of potentially exposed individuals, obviating the need for a full national lockdown . The iniThird, East Asia demonstrated how the extensive application of technology, data fusion, and analytics can substantially contribute to suppressing the spread of this highly infectious virus. For example, South Korea rapidly developed the 3-T scientific system of testing, tracing contacts, and treating in isolation, by leveraging “a walk-through testing system” that allows minimal contact with potentially infected people, tracing contacts based on artificial intelligence (AI)-based analysis of mobile big data and card transactions, and treating patients based on AI-driven analysis of clinical data . Taiwan Fourth, the COVID-19 pandemic has highlighted the importance of strong political leadership, coupled with a collective societal receptiveness to adhering to wide-ranging public health measures. The acceptance of universal masking in mainland China, Hong Kong, South Korea, and Japan exemplifies this, especially as this was widely practiced before the importance of masking as source control to reduce asymptomatic spread, was broadly accepted  Fig 2)..Fig 2). Notwithstanding these relative successes, lessons from East Asia should be understood in context. In addition to experiential learning through sociological imprinting by past outbreaks, East Asian societies tend to value collective well-being sometimes at the expense of individual liberties. Preexisting social structures to enforce mass lockdowns are difficult to replicate elsewhere. Taking the mainland Chinese example, containment had been greatly facilitated by neighbourhood-level organisations that monitored home quarantine and self-medical surveillance. It was further buttressed by the ubiquitous penetration of social and payment apps that had been quickly adapted for contact tracing purposes and as mobility passports. Finally, while a “zero COVID” approach might have saved tens or even hundreds of thousands of lives in 2020, this success may have paradoxically retarded vaccine acceptance despite adequate access and poses an ongoing conundrum of how best to reopen society.Until the 1990s, Japan had been the only major donor in East Asia, and the majority of East Asian economies had been recipients of development assistance for health (DAH). This has changed substantially and rapidly since the mid-2000s, where China and South Korea have been increasing the size and scope of DAH . This trBeyond aid, it would be important to consider the overall global health architecture, defined as “the relationship between the many different actors engaged in global health and the processes through which they work together” . In receTo date, DAH in East Asia has primarily been driven by government-controlled, Overseas Development Aid (ODA)-focused development agencies such as the Japan International Cooperation Agency (JICA), Korea International Cooperation Agency (KOICA), and latterly China International Development Cooperation Agency (CIDCA) since 2018. Regional multilaterals, primarily led by seconded officials from Japan and South Korea, such as WHO’s Western Pacific Regional Office and the Asian Development Bank (ADB) also play an important role . China lIn terms of support, Japan’s ODA is guided by the view of assistance as part of a partnership with recipient countries. Japan has prioritised its health ODA in capacity building and sustainability, which is unique among major donors . With feGlobal health has also been a priority issue in South Korea’s development policy since its inclusion in the second Strategic Plan for International Development Cooperation for 2016 to 2020. Its goal is to contribute to the achievement of universal health objectives by improving access to quality health and medical services and care for all . South KIn 2013, China launched the Belt and Road Initiative (BRI) to promote trade, infrastructure, and commercial relations with 65 countries in Asia, Africa, and Europe. This initiative contains important health components. China’s DAH has so far been primarily deployed to develop infrastructure, dispatch medical personal, and provide medical supplies to Africa and Asia . In receAs a group, however, thus far there has been little regional coherence, or tendency to foster such, among the bigger players in North East Asia  nor within ASEAN, let alone region wide. Where bilateral actions currently predominate, there remains much room to bring synergistic impact through multilateralism, perhaps in a different way than the post-WWII institutions currently operating. However, a shared vision that can be operationalised through a set of common principles and goals would be prerequisites.Of course, it would be naive to understand DAH in isolation from any country’s foreign policy, projection of its soft power, and geopolitics writ large. The increasingly patent bipolar reorientation of global alliances around China  and the US Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 TableDAH, development assistance for health.(DOCX)Click here for additional data file.


Engineered 3D tissues with central nervous system (CNS) identity are often developed from human pluripotent stem cells (hPSCs). Based on a variety of established culturing protocols, these 3D structures can be generated with an orderly cellular organization that not only contains essential cell components implicated in CNS development but incorporates complex cell-cell interactions. Indeed, they provide a novel platform for modeling CNS diseases and therapeutic cell replacement. With support of the revolutionary cellular reprogramming technology, complex 3D cellular structures derived from patients made a great leap forward in realizing personalized medicine for neurological disorders and injuries. This Research Topic aimed to collect and highlight recent advances and discoveries in the research arena of using hPSC-derived 3D cultures composed of various CNS cellular elements for disease modeling and cell therapy. This special issue includes six articles, three reviews, and three original research articles from excellent researchers in the field which covers some of the most recent and exciting findings in advancement of the human 3D CNS tissue engineering, as well as its applications in translational medicine.Three-dimensional (3D) culture of bioengineered tissues can be referred to as micro-tissues  and biomechanical (Matrigel) changes made to the PSC protocols and how it has revolutionized the field. They also strengthen their stance on introducing bioelectricity as the next revolutionary change to have a better physiologically accurate organoid. A thorough literature review is made on the potential of bioelectricity and modulation of endogenous electric field on development and differentiation, cell viability and proliferation, and other molecular mechanisms. Nevertheless, this review also highlights that the lack of bioelectric components in the current protocols is due to the knowledge gap in mapping the electric network of the body and the strength and duration of electric field used for stimulation. In all, the authors elucidate the advantage of using bioelectricity to generate physiologically relevant CNS organoids for developmental studies and disease modeling.The review article by Iyer and Ashton entitled “Bioengineering the human spinal cord” aims to elucidate the nature of stem cell derived spinal organoids in the context of spinal cord neurodevelopment, particularly as it pertains to patterning along the rostrocaudal and dorsoventral axes. Rostrocaudal identity, which is mainly characterized by HOX profiles, can be tuned by manipulating organoid exposure to and timing of SMAD inhibitors with shorter exposures leading to more caudal identities, and can be further enhanced through patterning with FGF, WNT, GDF11, and RA. Dorsoventral patterning on the other hand relies on local concentration-dependent SHH and BMP signaling, which promotes the emergence of region specific progenitors that will then mature into organized neuronal domains. Limitations of generating human spinal organoids are also discussed as lack of standardized hiPSC culturing methods which results in limited cell diversity and organization, inconsistent reproducibility, and restricted culture durations. Current bioengineering strategies are proposed to leverage biomaterial-supported constructs, microfluidics gradients, and genetic engineering to overcome some of these limitations by providing a more dynamic range of environmental cues, including mechanoregulation, complex morphogenetic gradients, and spatially localized optogenetic signaling. Nevertheless, the authors summarize the standardization of culture techniques and further innovation of bioengineering strategies will continue to develop human spinal cord organoids as a useful system for studying patient-specific neurodegenerative diseases and will enable finding appropriate translational solutions.The minireview article by in-vitro neurological systems” Elder et al. review cellular reprogramming strategies for disease modeling and cell therapies. The authors highlight two distinct strategies to generate neurons from human PSCs–directed and transcription factor induced differentiation. Directed differentiation mimics the developmental process of neurogenesis by employing exogenous stimulations, whereas transcription factor induction utilizes genetic and epigenetic engineering tools to manipulate the activation and inactivation of master regulators in neurogenesis for various neuronal phenotypes. Some major limitations discussed by the authors include differentiating region-specific cell types and difficulty in maintaining their functionality over time to accurately model neurological diseases. However, with the expansion in cellular engineering, stem cell technology, and our understanding of the human brain, more hybrid approaches that combine aspects of directed and induced differentiation, co-culture, and organoids can overcome some of the limitations and prove beneficial in a technical and clinical setting.In “Diseased, differentiated and difficult: Strategies for improved engineering of Miranda et al. entitled “A Dynamic 3D Aggregate-Based System for the Successful Expansion and Neural Induction of Human Pluripotent Stem Cells” depicts novel methods of expanding phenotypically stable hiPSCs in 3D cultures and effective differentiation of neural progenitors with specific region identities on a large scale. The authors discovered that with the help of orbital shakers or vertical-wheel bioreactors, hiPSC aggregates cultured in Gibco StemScale PSC medium exponentially expanded within a few passages. Furthermore, these hiPSC aggregates can be robustly differentiated into neural progenitor cells when cultured in either Neural Induction Medium (NIM) or N2B27 medium supplemented with dual SMA inhibition, but with somewhat different outcomes. For example, N2B27 aggregates display a larger size; and NIM yielded similar proportions of the three cell types , whereas N2B27 promoted mostly neurons and immature neurons along with much fewer astrocytes. Interestingly, the single-cell calcium imaging which is to evaluate the functionality of the cells shows cells cultured in NIM were more responsive than cells cultured in N2B27. Lastly, the authors validated their protocols of generating neural progenitor cells with region identities. In conclusion, these methods are important for scaling up the hiPSC and their neuronal derivatives which potentially can be used in the clinical that depends on the scalability such as cellular therapies and drug screening.The original research article by Yates et al. report novel results from experiments utilizing hiPSCs derived from Veterans with and without Gulf War Illness (GWI) to establish cerebral organoids for disease modeling. In “Veteran-derived cerebral organoids display multifaceted pathological defects in studies on Gulf War Illness”, characterizing organoids after exposure to Gulf War toxicants revealed increased astrocytic reactivity, enhanced phosphorylation of tau proteins, decreased microtubule stability, and impaired neurogenesis were identified. Interestingly, some of these phenotypes were more pronounced in the organoids derived from the GWI Veterans, potentially indicating a susceptibility in these patients. In all, these results suggest that GW Veteran-derived human cerebral organoids not only can be used as an innovative human model to uncover the cellular responses to GW toxicants but can also serve as a platform for developing personalized medicine approaches for the veterans.Romero et al. entitled “Oligodendrogenesis and myelination tracing in CRISPR/Cas9-engineered brain organoids” puts forward an efficient approach to study the processes of oligodendrogenesis and myelination using CRISPR/Cas9 gene editing to knock in a fluorescent protein at the stop codon of PLP1, which is a marker for oligodendrocytes, thus creating a fusion protein to track the differentiation, migration, and maturation of OL cells in cerebral organoids. The authors demonstrated the efficacy of reverse knock-in when compared to forward knock-in when transfecting cells and performed quality control steps such as off-target screening and chromosome aberration assays to ensure high knock-in cell fidelity and minimal genetic aberration. This methodology in this article has the potential to be used for high-fidelity insertion of fluorescent tags into hiPSCs to study the development of certain cell types. The authors also validated the applicability of their model to effective drug screening by using cuprizone (CPZ), which is known to cause demyelination in vivo.The original research article by Overall, this Research Topic summarizes and highlights important findings related to the studies using human induced pluripotent stem cells for translational medicine and provides prospective advances in its application. Bioengineered human 3D cellular tissues have great potential in meeting growing need for more advanced disease modeling platforms and therapeutic cellular resources. Organoids, assembloids, circuitoids, and organ-on-a-chip systems are several modeling strategies that allow for great flexibility and ingenuity in mechanistic studying for organ development, as well as fostering personalized medicine disease treatment.LQ wrote this editorial. MAL, CAD, OR, and IF edited this editorial. All authors have approved it for publication.


Data archiving and distribution are essential to scientific rigor and reproducibility of research. The National Center for Biotechnology Information’s Database of Genotypes and Phenotypes (dbGaP) is a public repository for scientific data sharing. To support curation of thousands of complex data sets, dbGaP has detailed submission instructions that investigators must follow when archiving their data.https://CRAN.R-project.org/package=dbGaPCheckup) and developed on GitHub (https://github.com/lwheinsberg/dbGaPCheckup).We developed dbGaPCheckup, an R package which implements a series of check, awareness, reporting, and utility functions to support data integrity and proper formatting of the subject phenotype data set and data dictionary prior to dbGaP submission. For example, as a tool, dbGaPCheckup ensures that the data dictionary contains all fields required by dbGaP, and additional fields required by dbGaPCheckup; the number and names of variables match between the data set and data dictionary; there are no duplicated variable names or descriptions; observed data values are not more extreme than the logical minimum and maximum values stated in the data dictionary; and more. The package also includes functions that implement a series of minor/scalable fixes when errors are detected . Finally, we also include reporting functions that produce graphical and textual descriptives of the data to further reduce the likelihood of data integrity issues. The dbGaPCheckup R package is available on CRAN (dbGaPCheckup is an innovative assistive and timesaving tool that fills an important gap for researchers by making dbGaP submission of large and complex data sets less error prone.The online version contains supplementary material available at 10.1186/s12859-023-05200-8. In recent years, many major funding agencies, including the National Institutes of Health (NIH), have moved toward requiring data sharing across scientific disciplines. A variety of publicly available data repositories exist to facilitate this, including the Database of Genotypes and Phenotypes (dbGaP) , 2 whichThis package focuses on two required dbGaP subject phenotype files: (1) the data set, which contains the study data for participants, with each row representing a participant, and each column representing a phenotype variable; and (2) the corresponding data dictionary, which contains descriptions of the variables in the data set with each row representing a unique variable (corresponding to the columns in the data set) and each column representing information about that variable . For the data dictionary, specifically, dbGaP submission requirements state that, at a minimum, the variable name (VARNAME), description (VARDESC), units (UNITS), and value = meaning (VALUES) columns  must be present to facilitate public use of a data set. The dbGaPCheckup package expands on this by requiring additional fields of variable type (TYPE), logical minimum value (MIN), and logical maximum values (MAX) be present to facilitate a series of additional checks.https://lwheinsberg.github.io/dbGaPCheckup/index.html. To initiate the package, users simply load the data set and data dictionary and call the check_report function  to make their data publicly available as of January 2023 , we beliAdditional file 1. is a PDF file adapted from the dbGaPCheckup vignette. It contains additional information about dbGaP subject phenotype files and submission instructions, how dbGaPCheckup can be used as a curation tool during the pre-submission phase, and detailed applied examples of dbGaPCheckup including discussion of function input, output, and interpretation.


Several patients undergoing physical therapy have nutritional problems. Knowledge of nutrition is necessary for addressing nutritional problems, such as malnutrition, sarcopenia, frailty, and cachexia. However, the relationship between physical therapy and nutrition is not fully understood. Physical therapy plays an important role in nutritional management, and evaluations, such as muscle strength and muscle mass evaluations, play an important role in nutritional screening and diagnosis. Exercise, as the core of physical therapy, is essential for nutritional interventions. Several recent studies have suggested that a combination of nutrition and physical therapy interventions can maximize the function, activity, participation, and quality of life of patients. The combination of nutrition and physical therapy interventions is key to addressing the needs of modern and diverse populations. This position paper was developed by the Physical Therapist Section of the Japanese Association of Rehabilitation Nutrition in consultation with the Japanese Society of Nutrition and Swallowing Physical Therapy. In recent years, there has been an increase in focus on the role of physical therapy in nutritional management because several patients undergoing physical therapy have nutritional problems. In Japan, the aging population is rapidly increasing, and several older patients undergoing physical therapy have nutritional problems, such as undernutrition, sarcopenia, and frailty. Knowledge of nutrition is, therefore, necessary for physical therapy for obesity in midlife, cachexia caused by chronic wasting disease, and athletes in the sports field. Several studies have suggested that these nutritional problems negatively affect the effectiveness of physical therapy. Thus, nutritional management is essential to maximizing the effectiveness of physical therapy.Physical therapy plays an important role in nutritional management. However, its role in nutrition remains unclear. Clarifying the relationship between physical therapy and nutrition helps all medical professionals involved in physical therapy share common understanding and maximize function, activity, participation, and quality of life (QOL). We hope that this paper provides common understanding among all medical professionals in physical therapy and a basis for administering physical therapy to improve the outcomes of patients with nutritional problems.(1). However, there is no dedicated physical therapy system for nutrition, there is insufficient education and training on providing advice on the best foods for the nutritional and health statuses of a patient, and there is no official nutrition section for the physical therapy community in Japan. A certified nutritional physical therapy (CNPTⓇ) system has been established to improve the knowledge and skills of nutrition advisors in the United States (2). To be certified as a CNPTⓇ, physical therapists must complete all three of the APTA-approved education courses and must pass the certification exam. Physical therapists need to develop skills in nutritional screening and provide information to patients for appropriate feeding (3), and the scope of teaching regarding feeding and nutrition that should be carried out by physical therapists needs to be clarified and standardized (4). Thus, it has been emphasized that physical therapists should know regarding nutrition and feeding in the United States.The American Physical Therapy Association (APTA) has identified the involvement of physical therapists in nutrition and food intake as important for public health and beneficial to patients (5). However, all of these reports were based on small samples, and there have been no systematic reviews or clinical guidelines. To date, a system combining nutrition and physical therapy has not been established. In the future, it is expected that the concept of nutritional physical therapy based on rehabilitation nutrition will be globalized.However, this is inconsistent with the perspectives of “physical therapy in consideration of nutrition” and “nutrition in consideration of physical therapy” found in “Rehabilitation Nutrition” in Japan. Nutritional knowledge has been highlighted among the recommended skills that a physical therapist should have. However, there are no indications on how to tailor physical therapy interventions based on nutritional status. The synergistic effects of physical therapy and nutrition on sarcopenia have been demonstrated in Europe and other countries, and there have been several reports of improved physical function, especially in patients with advanced cancer (6). For the national examination for physical therapists, questions that require knowledge of nutrition and geriatric nutritional problems such as sarcopenia and frailty are increasing. Physical therapists can obtain certifications, such as the Japanese Association of Rehabilitation Nutrition (JARN) certified rehabilitation nutritionist (7) and the Japan Society of Clinical Nutrition and Metabolism (JSPEN) certified Nutrition Support Team (NST) therapist. Physical therapists can also obtain certifications as rehabilitation nutrition instructors certified by the JARN and as NST specialists certified by the Japanese Society of Clinical Nutrition and Metabolism (8). Physical therapists are participating in the NST and are increasingly involved in nutritional management. Interventions based on both nutrition and physical therapy play an important role in meeting the varying needs of patients.In Japan, it has become important for physical therapists to be involved in nutritional management. The Japan Physical Therapy Association (JPTA) has been developing an educational system for nutrition . The JPT(9) has facilitated the coexistence of nutrition and physical therapy in Japan. Rehabilitation nutrition is closely related to physical therapy, in that it is based on the International Classification of Functioning, Disability, and Health (ICF). Goal setting based on the consideration of nutritional disorders, sarcopenia, and excessive or inadequate nutritional intake has been accepted in administering physical therapy regardless of the disease. With the widespread adoption of rehabilitation nutrition, the effectiveness of interventions that combine rehabilitation and nutrition has been reported (11). The importance of nutritional management in rehabilitation has also been reflected in the 2018 revision of medical fees, and the participation of dietitians in the rehabilitation plan is mandatory in rehabilitation wards in Japan (12). The JARN has published medical guidelines in an international journal (13) and initiated total nutrition therapy rehabilitation to contribute to the development of academic culture and the improvement of medicine and healthcare. Thus, to clarify the effect of physical therapy on nutrition, it is necessary to understand the concept of rehabilitation nutrition.Rehabilitation nutrition (14).Rehabilitation nutrition is “nutrition from the perspective of rehabilitation” or “rehabilitation from the perspective of nutrition” to improve nutritional status, sarcopenia, nutrient intake, and frailty of disabled and frail older patients and to maximize their function, activity, participation, and QOL after holistic evaluation based on ICF, assessment of the presence and causes of nutritional disorders, sarcopenia, and excess or deficient nutrient intake, diagnosis, and goal setting The effect of physical therapy on nutrition can be considered based on rehabilitation nutrition. Physical therapy can be involved in all aspects of rehabilitation nutrition. In addition to rehabilitation nutrition assessment and diagnoses, physical therapy evaluation plays a major role in rehabilitation nutrition monitoring. Physical therapists need to be involved in setting specific and achievable goals in collaboration with other medical professionals. Exercise, as the core of physical therapy, is an indispensable component of rehabilitation nutrition intervention. It is necessary for all medical professionals involved in physical therapy to share common understanding of its role in the rehabilitation nutrition care process.(15). In the practice of nutritional physical therapy, it is important to have the viewpoint of both “physical therapy in consideration of nutritional status” and “nutrition care management that can maximize the effect of physical therapy”  therapy” . Nutrititherapy” . The two(18). Regardless of patients receiving physical therapy often have these nutritional problems, they can be overlooked. Nutrition screening by physical therapists can identify patients with nutritional disorders (20). The validated nutritional screening tools are the Mini Nutritional Assessment Short-Form (MNAⓇ-SF), Malnutrition Universal Screening Tool, and Malnutrition Screening Tool. Physical therapists can use these nutritional screening tools to screen for nutritional status. If malnutrition is suspected, physical therapists should consult a nutrition professional  to further evaluate nutritional status and consider appropriate nutritional care management. Multimodal nutritional interventions may reduce morbidity and mortality associated with nutritional disorders and may improve the outcomes of patients (20).Physical therapists need to assess the nutritional status of patients. Nutritional disorders, sarcopenia, and inadequate energy intake adversely affect the recovery of physical function (24). The diagnostic criteria for malnutrition by the American Society for Parenteral and Enteral Nutrition and the American Dietitians Association (AND) include decreased muscle mass and function based on grip strength (25). The Global Leadership Initiative on Malnutrition (GLIM) criteria also recommend that functional assessments based on hand grip strength provide a supportive measure of muscle mass (26). Muscle strength tests include grip strength, knee extensor strength, and peak expiratory flow (24). Muscle function tests include walking speed, short physical performance battery, and timed up and go test (24). Muscle strength and function respond more sensitively to nutritional status than body composition and can be used to monitor nutritional management (21). In addition, ADL assessment should be used as a nutritional monitoring and outcome measure because ADL impairment results from muscle weakness (23). These assessments have been professionally assessed by physical therapists and can be used for nutritional assessment. Thus, it is important to share physical therapy evaluations with dietitians, nurses, and clinicians, which leads to appropriate nutritional management.Nutritional status is associated with muscle mass and strength, physical function, and ADL. These functional measurements are increasingly important for nutritional assessment  (21), (2(9). In addition, adequate protein intake and resistance training (RT) should be combined to increase skeletal muscle mass, which is an important objective of nutritional management (27). For overnutrition and sarcopenic obesity, it is useful to combine RT and aerobic exercise instead of energy restriction alone (28). Thus, exercise is an essential component of the nutritional management of patients requiring physical therapy, and physical therapy plays an important role in multimodal nutritional management.Nutritional management enhances the effectiveness of physical therapy, and the effectiveness of nutritional management is enhanced by physical therapy. Physical therapy combined with nutritional management may improve function, activity, and participation (29). In addition, muscle strength is considered a better predictor of negative health outcomes than skeletal muscle mass (30). Therefore, muscle strength, including the entire neuromuscular function, is recognized as a biomarker that determines the well-being of older adults (31). On the other hand, skeletal muscle mass directly reflects nutritional status. For example, in chronic inflammatory diseases, such as chronic obstructive pulmonary disease, loss of skeletal muscle mass may be more apparent than muscle weakness, but there is no clear evidence. The response to RT is also different between muscle strength and skeletal muscle mass. The increase in skeletal muscle mass due to RT appears later than the increase in muscle strength (32). In a study of older adults who were followed up for 3 months after hospitalization, muscle strength and physical function recovered to the same level or even higher than that at the time of hospitalization. However, skeletal muscle mass did not recover during hospitalization (33). Therefore, we believe that long-term nutritional physical therapy is necessary to improve skeletal muscle mass.To implement effective nutritional physical therapy, we need to understand that age-related loss of skeletal muscle mass and muscle weakness are not exactly parallel. Previous studies have reported that age-related muscle weakness appears earlier than the loss of skeletal muscle mass Physical therapy should be performed depending on nutritional status. Adequate nutrient intake leads to improvement and maintenance of physical function, physical activity, participation, and QOL . Gender-(34), older patients should prevent frailty and sarcopenia, even if they are well nourished. The effect of branched-chain amino acid intake in combination with RT improves muscle protein synthesis and muscle strength in athletes (35). Similarly, branched-chain amino acid intake combined with exercise can improve the skeletal muscle mass, muscle strength, and physical function of older patients (36).In well-nourished patients, the goal of physical therapy is to improve or maintain muscle mass, muscle strength, and physical function according to the health status and objectives of the patient. As skeletal muscle mass decreases with aging (37). However, the energy expenditure associated with leaving the bed is negligible (38), and leaving the bed should be actively practiced to prevent disuse syndrome. As metabolism shifts to anabolism, skeletal muscle mass is expected to increase, and active nutritional management and physical therapy should be performed to improve nutritional status and physical function. In the case of undernutrition due to lack of nutrient intake, high-intensity exercise during starvation may accelerate muscle breakdown, but rest and calorie-restricted conditions lead to further reductions in muscle mass. Hence, medical staff should pay attention to avoid unnecessary bed rest. The exercise load should be gradually increased in parallel with improvements in nutritional status through nutritional management.For cases of undernutrition, physical therapy should be administered depending on the cause. If undernutrition is caused by severe invasion, the goal of physical therapy is to maintain ADL and QOL as much as possible because excessive loads lead to muscle breakdown. Highly invasive cases and nutritional disorders are more severe because of hyperglycemia and accelerated muscle breakdown (39). For sarcopenic obesity, which increases the risk of developing cardiovascular and metabolic chronic diseases, a comprehensive approach, including nutritional therapy (moderate low energy diet and high protein intake of at least 1.2 g/kg/day) and RT, is recommended (28)．Resting may lead to obesity and overnutrition; physical therapy is mainly aerobic taking into account carbohydrate and lipid metabolism (40), and this response is not exclusive to older adults (41). Regarding nutritional quality, it has been reported that β-hydroxy-β-methylbutyrate (HMB), in addition to leucine, which is the most potent branched-chain amino acid that stimulates muscle protein synthesis (42), is effective in increasing muscle mass in older adults (43), but the results are not consistent (44). The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend a protein intake of at least 1 g/kg/day for older adults (45). The PROT-AGE Study Group position paper recommends a protein intake of 1.2-1.5 g/kg/day for older adults with acute and chronic diseases and 2.0 g/kg/day for critically ill, traumatized, or malnourished patients with consideration of renal function (46). For patients receiving RT, adding nutritional intake with appropriate timing, quality, and quantity can maximize the effect of RT. The combined use of amino acid-based nutrition and exercise has been reported to be effective in a study of older patients with sarcopenia during hospitalization (47). This suggests that combined physical therapy and nutritional interventions are effective for hospitalized older adults with sarcopenia. Oral nutrition supplements are recommended depending on the patient’s general condition and swallowing ability. Previous studies have shown that leucine-rich jelly-type supplements (10) or powdered supplements dissolved in water (47) effectively increase skeletal muscle mass and muscle strength and improve ADL in older patients with sarcopenia undergoing rehabilitation.“Nutritional management in consideration of physical therapy” means the adjustment of the nutrient intake of energy, protein, and lipid due to exercise in consultation with multidisciplinary medical professionals. Considerations of the timing, quality, and quantity of nutrient intake are necessary when implementing RT. The promotion of muscle protein synthesis after RT should be considered, and optimal intake of protein and amino acids will improve the muscle strength and muscle mass of the patient. It has been reported that muscle protein synthesis is more enhanced after RT and nutrient intake than after nutrition intervention alone or RT alone (48). The energy expenditure for activities for a certain period is calculated by considering the energy expenditure during the activity, in addition to the energy expenditure at rest. The total energy expenditure of hospitalized patients undergoing physical therapy should be evaluated with considerations of the amount of energy expenditure during physical therapy. The rationale for setting activity factors according to the intensity of physical therapy is unclear, but a guideline is 1.3 as an activity factor for 20 minutes of physical therapy, 1.3-1.7 for ≥1 hour, and 1.5-2.0 for ≥2 hours (49). In addition, accurate assessments of abnormal muscle tone and involuntary movements caused by cerebrovascular and neurodegenerative diseases will lead to appropriate nutritional management. It has been reported that oxygen consumption during exercise is higher in patients with Parkinson’s disease than in healthy people (50), and deep stimulation of the subthalamic nucleus increases body weight and BMI (51). In addition, it has been reported that energy expenditure is higher in patients with cerebellar ataxia than in healthy people because of decreased coordination during walking (52). Appropriate physical therapy evaluation based on disease characteristics is necessary to prevent the deterioration of nutritional status due to increased energy expenditure.Accurate assessment of energy metabolism resulting from exercise can lead to appropriate nutritional management. Nutritional status deteriorates if nutritional management does not consider the energy metabolism resulting from exercise. Exercise-induced energy metabolism was calculated using metabolic equivalents (METs) This position paper, which is the first to assess the synergistic effects of nutrition and physical therapy, provides insights into the effects of physical therapy on nutrition and vice versa based on domestic and international trends. Regardless of the disease or stage of the disease, it is necessary to focus on nutrition and physical therapy to appropriately address nutritional problems and to maintain and improve function, activity, participation, and QOL, which are the original objectives of physical therapy. On the other hand, systematic clinical practice based on an interactive perspective of nutrition and physical therapy has not been adequately implemented. In addition, it needs to simplify nutritional evaluation to perform rapid and effective intervention in any environment. Further clinical practice and research are required.(59).”This is the secondary English version of the original Japanese manuscript for “Nutrition and physical therapy: A position paper by the physical therapist section of the Japanese Association of Rehabilitation Nutrition NoneWe would like to thank the Japanese Society of Nutrition and Swallowing Physical Therapy for their advice in developing this position paper. We are also grateful for public comments on this paper.Substantial contributions to the conception or design of the work: Tatsuro Inoue, Yuki Iida, Kohei Takahashi, Kengo Shirado, Fumihiko Nagano, Shinjiro Miyazaki, Izumi Takeuchi, Yoshihiro Yoshimura, Ryo Momosaki, Keisuke Maeda, and Hidetaka WakabayashiDrafting the work: Tatsuro Inoue, Yuki Iida, Kohei Takahashi, Kengo Shirado, Fumihiko Nagano, Shinjiro Miyazaki, Izumi Takeuchi, Yoshihiro Yoshimura, Ryo Momosaki, Keisuke Maeda, and Hidetaka WakabayashiFinal approval of the version to be published: Tatsuro Inoue, Yuki Iida, Kohei Takahashi, Kengo Shirado, Fumihiko Nagano, Shinjiro Miyazaki, Izumi Takeuchi, Yoshihiro Yoshimura, Ryo Momosaki, Keisuke Maeda, and Hidetaka WakabayashiAgreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: Tatsuro Inoue, Yuki Iida, Kohei Takahashi, Kengo Shirado, Fumihiko Nagano, Shinjiro Miyazaki, Izumi Takeuchi, Yoshihiro Yoshimura, Ryo Momosaki, Keisuke Maeda, and Hidetaka WakabayashiNot applicable.* The editor-in-chiefs of the Journal of the Japanese Association of Rehabilitation Nutrition and JMA Journal have given permission for secondary publication of this position paper.(59)* This article is based on a study first reported in the Journal of the Japanese Association of Rehabilitation Nutrition. 2021;5(2):226-234 (Japanese) Journal articles published ahead of issue (print): Inoue T et al. Nutrition and physical therapy: a position paper by the physical therapist section of the Japanese Association of Rehabilitation Nutrition. The Journal of the Japanese Association of Rehabilitation Nutrition. 2021.https://sites.google.com/site/jsrhnt/ポジションペーパー?authuser=0.* The original version is available at


Global Health Security (GHS) is a state of freedom from the scourge of infectious diseases irrespective of their origin or source. As the COVID-19 pandemic has shown, however, it can only be achieved and maintained through concerted, cooperative action at all levels—from local communities to the international system—when acting in solidarity, informed by equity.We reaffirm the Sydney Statement on GHS’s seven core principles (The seven principles are: (1) That interventions must be inclusive, equitable and data driven; (2) Prevention, detection and response capabilities are critical and must be linked with universal health coverage and health system strengthening; (3) Governments must comply with the International Health Regulations and other associated agreements; (4) GHS requires action and engagement from all sectors; (5) GHS must embrace a One Health approach; (6) Countries with resources have a duty to partner with those with lower capacity to strengthen capabilities; and (7) Sustainable, comprehensive funding is critical.). These principles, agreed prior to the pandemic, are only more salient now. COVID-19 has highlighted the urgent need for strengthening and maintaining global, regional, national, and local preparedness and response capacities, even as we also must prepare for known and hitherto unforeseen challenges emerging from a changing climate, microbially resistant microorganisms, existing pathogens and future zoonotic spillover events. We must embrace the fact we live together on one planet, deeply connected to each other and our natural environment.To that end, we declare:GHS is made sustainable only when embedded within universal health systems that ensure equitable access to services and treatment, irrespective of socioeconomic status or means to pay, and delivered by an appropriately trained and remunerated health workforce.Health emergency planning, preparedness and response workforces must be strengthened and proactively expanded to include multisectoral, interdisciplinary expertise. To foster these workforces, inclusive, lifelong training must be encouraged, readily accessible and linked to professional advancement.Preventing future unintended disease events requires enhanced surveillance of animal and environmental conditions, including in urban settings, and the adoption of policies and standards that proscribe activities that harm the natural environment.Governments must sustainably finance, build, strengthen, maintain and regularly practice preparedness and response capabilities that respect human rights, are inclusive, context specific, and adhere to relevant international law such as the International Health Regulations.Preparedness and response must strengthen and maintain not only technical but also social, economic and political measures for reducing harm arising from disease events. This includes taking practical steps to improve health literacy across communities to mitigate misinformation and disinformation, and the development of new social, economic and political preparedness indicators to enhance resilience.Achieving GHS, strengthening health systems and improving population health around the world requires a sustained commitment at all levels of government and across all sectors of society.


Mage = 13.54 years, SD = 1.04; 55.60% boys) completed a survey assessing optimism and pessimism, the habitual use of reappraisal and acceptance strategies, life satisfaction, and depression. The results from dominance analysis revealed that the presence of optimism was more powerful than the absence of pessimism in predicting adolescent life satisfaction, while the absence of pessimism was more powerful than the presence of optimism in predicting adolescent depression. Moreover, mediation models showed that reappraisal and acceptance mediated both the link between optimism and life satisfaction and the link between pessimism and depression. These findings suggest possible avenues for intervening in different aspects of adolescent subjective well-being.Prior research has found the differential strength of optimism and pessimism in predicting physical health. However, whether similar findings would be obtained in predicting subjective well-being and the possible underlying mechanisms are still unclear. This study examined the relative strength of optimism and pessimism in predicting adolescent life satisfaction and depression, and further explored the possible mediating mechanisms from the perspective of emotion regulation. A sample of 2672 adolescents ( The personality dimension dispositional optimism (expectancies regarding future outcomes) has been widely proven to show strong associations with markers of physical health and subjective well-being across ages and nations ,2,3,4. EMost of the studies cited used the Life Orientation Test (LOT)  or its rTracing the theoretical root of dispositional optimism, optimism and pessimism are also related to different motivational processes . The conSince optimism and pessimism are relatively independent, we may wonder whether the presence of optimism or the absence of pessimism is more prominent in predicting important adaptive outcomes. Answering this question could help us to specify the relative contributions of optimism and pessimism to the prediction of life outcomes, which may prove profitable both practically and theoretically . HoweverN = 33) [Several previous studies explored the relative strength of optimism and pessimism in subjective well-being, but they mainly focused on adults and yielded inconsistent results ,31,32. SN = 33) ,33. TherAdolescence is accompanied by various physiological, psychological, and social challenges, including increased potential for conflict with parents, more body image concerns, and an increase in the developmental tasks of identity formation and autonomy ,35. AdolAs an important personality trait related to motivational processes , disposiAlthough, according to our first hypothesis, optimism and pessimism would be related distinctively to adolescent subjective well-being, the underlying mechanisms of these associations are still unclear. The top-down model of personality, coping, and emotional outcomes  may lendQuite a few empirical studies speak directly to the relationship between dispositional optimism and ER. The available evidence consistently indicates that a higher level of optimism is linked to more habitual use of adaptive strategies to regulate emotions, such as reappraisal and acceptance, while a higher level of pessimism is linked to less habitual use of adaptive ER ,45. ReapTo summarize, this study aimed to explore the differences in the predictive power of optimism and pessimism on positive and negative aspects of adolescents’ subjective well-being , as well as the possible mediating roles of reappraisal and acceptance. Based on the literature review, the present study tested the following three hypotheses: (1) optimism would be a stronger predictor for adolescents’ life satisfaction than pessimism, and pessimism would be a stronger predictor for adolescents’ depression than optimism; (2) reappraisal and acceptance would mediate the relationship between optimism and adolescents’ life satisfaction; and (3) reappraisal and acceptance would mediate the relationship between pessimism and adolescents’ depression.Mage = 13.54 years, SD = 1.04, 1486 boys (55.60%)) recruited from two middle schools in central and southwest China. No participants reported any records of using psychiatric medication. There was less than 1% missing data, and the missing data were estimated with the Expectation Maximization (EM) procedure in SPSS 25.0 .Participants included 2672 adolescents . Combined with the results of CFA and other previous studies [Optimism and pessimism were assessed by the Chinese version of the Life Orientation Test-Revised (CLOT-R) , which c studies ,25, it sReappraisal is measured by six items  selected from the Emotion Regulation Questionnaire (ERQ) , which iAcceptance was assessed by the Chinese version of Acceptance and Action Questionnaire II (AAQ-II), which has been used among Chinese adolescents with good internal consistency and validity . It inclAdolescents’ subjective well-being in this study was indicated by life satisfaction and depression. Life satisfaction was assessed by the Satisfaction with Life Scale (SWLS) . It inclAdolescents’ depression was measured by the Chinese version of the Center for Epidemiologic Studies Depression Scale (CES-D) , which iBesides the above scales, adolescents also completed a questionnaire soliciting information about sex, age, and family socioeconomic status (SES). Family SES was assessed by the Family Affluence Scale (FAS), which is well established with moderate internal consistency and good validity and widely used among adolescents both in China and in Western countries ,63. FAS R2 values for all possible subset models [To address the study’s first aim (determining the relative contributions of optimism and pessimism to explaining variances in adolescents’ life satisfaction and depression), we conducted dominance analyses to identify the relative importance of predictors in multiple regression based on an examination of the t models ,65.To address the study’s second aim (exploring how adolescents’ optimism or pessimism predict their life satisfaction and depression), mediation models were tested by PROCESS macro for SPSS  , which hTo avoid common method bias, we performed Harman’s single-factor test on all items of the current study before data analysis . The resDescriptive statistics and correlations among variables in this study are displayed in As k = 0 (indicating that there were only control variables in the regression model), 0.214 > 0.093; k = 1 (indicating that the regression model included a predictor in addition to control variables), 0.131 > 0.010). Consequently, optimism completely dominated pessimism in predicting adolescents’ life satisfaction.In this stage, we performed a series of hierarchical regression analyses, with control variables entered in the first step and optimism or pessimism of interest in the second or third step (method = enter). As shown in k = 0 (indicating that there were only control variables in the regression model), 0.296 > 0.246; k = 1 (indicating that the regression model included a predictor in addition to control variables), 0.125 > 0.074). Consequently, pessimism completely dominated optimism in predicting adolescents’ depression.As seen in The results of dominance analysis show that optimism completely dominated pessimism in predicting adolescents’ life satisfaction, while pessimism completely dominated optimism in predicting adolescents’ depression. In this stage, through testing mediation models with reappraisal and acceptance as mediators, we further explored how optimism predicted life satisfaction when controlling pessimism and how pessimism predicted depression when controlling optimism.In The findings of multiple mediation model analysis to predict depression from pessimism, reappraisal, and acceptance are presented in N = 2672) and robust dominance analysis, examined the relative strength of optimism and pessimism in contributing to associations with adolescents’ subjective well-being . It further explored the mediating roles of reappraisal and acceptance in these associations based on the top-down model of personality, coping, and emotional outcomes [The current study, using a large sample of normal adolescents (outcomes . Many proutcomes , but mosFirst, consistent with our hypothesis, we found that the presence of optimism was more powerful than the absence of pessimism in predicting adolescent life satisfaction, while the absence of pessimism was more powerful than the presence of optimism in predicting adolescent depression. These findings are congruent with the theoretical grounding that optimism and pessimism are related to different motivational processes and may show differential effects on life outcomes ,27,28, aSecond, consistent with the top-down model of personality, coping, and emotional outcomes  as well Another interesting result in this study is that the mediating effect of acceptance was significantly greater than that of reappraisal in the relationship between pessimism and adolescent depression, while there was no significant difference in the mediating effects of acceptance and reappraisal in the relationship between optimism and adolescent life satisfaction. This may be related to the characteristics of reappraisal and acceptance strategies and the cognitive characteristics of optimistic and pessimistic adolescents. For adolescents, the ability to regulate emotions is a pivotal skill for both their physical health and subjective well-being . There aThe current study has several limitations that should be highlighted. First, the cross-sectional design of this exploratory study can provide valuable information for the research questions, but we should bear in mind that the findings are based on correlational data, which cannot support causal inferences. Future longitudinal or experimental studies may be needed to clarify causal directions. Second, life satisfaction and depression were chosen as indicators of positive and negative aspects of subjective well-being, which cannot cover all the aspects of subjective well-being. Future studies could test the relative contributions of optimism and pessimism to the prediction of other important adaptive indicators, providing the basis for targeted interventions. Third, the variable-centered approach used in this study cannot allow for exploring how optimism and pessimism, two separate but related traits, are integrated within an individual and what the adaptive outcomes of individuals with different combinations of optimism–pessimism levels are. Blasco-Belled et al.  adopted Our study shows that the presence of optimism is more powerful than the absence of pessimism in predicting adolescent life satisfaction, while the absence of pessimism is more powerful than the presence of optimism in predicting adolescent depression. Moreover, reappraisal and acceptance mediated both the link between optimism and life satisfaction and the link between pessimism and depression. The mediating effect of acceptance is significantly greater than that of reappraisal in the relationship between pessimism and adolescent depression. These findings tease apart the nuances of optimism and pessimism in predicting adolescent life satisfaction and depression and provide insights into how to intervene for different aspects of adolescents’ subjective well-being.


There are 670 million people at risk of contracting lymphatic filariasis (LF) in India, which bears 40% of the global burden of the disease. The National Program to Eliminate LF was launched in 2004 first with a single-drug therapy—diethylcarbamazine (DEC), followed by a two-drug therapy—DEC + albendazole (DA). In 2017, following successful drug trials, World Health Organization endorsed a new triple-drug therapy to fight LF using ivermectin with DEC and albendazole (IDA). Sushruta Samhita, and in the seventh century AD, Madhava-kara described signs and symptoms of the disease in his treatise, Madhava Nidhana.Lymphatic filariasis (LF), or elephantiasis, is a mosquito-borne disease that disfigures and disables those who become infected. The disease was recorded in India as early as the sixth century BC by Sushruta in his book, India’s National Health Policy 2002 set a goal to eliminate LF as a public health problem in India by 2015, which was later extended to 2017. The goal set by the Global Program to Eliminate Lymphatic Filariasis was to eliminate LF by 2020. The global goal was subsequently revised to eliminate LF by 2030. National goals across endemic countries have aligned to meet that target.India launched the National Program to Eliminate Lymphatic Filariasis in 2004. As part of the program, an annual single dose of diethylcarbamazine (DEC) administered through mass drug administration (MDA) was introduced in 202 of the 256 endemic districts in India. By 2007, the MDA program had scaled up to cover 256 districts and included the administration of two drugs—DEC and albendazole (DA). In 2020, based on the remapping data, National Vector Borne Diseases Control Program (NVBDCP) added 16 new districts, making it a total of 272 LF endemic districts in the country. As of the start of 2021, 174 districts are still undergoing MDA, and 98 have stopped MDA and are undergoing various stages of transmission assessment surveys, which determine whether the transmission levels of LF are low enough to stop MDA ,Most of the 174 districts undergoing MDA (not including 16 newly added LF endemic districts) have implemented roughly 8–10 rounds of MDA in the last 15 years. In addition to poor community participation and low compliance, the program has faced multiple implementation challenges at a higher level. For years, the program suffered from a seeming impasse in which LF elimination was not a major part of the national public health agenda, few champions publicly voiced support for accelerating elimination efforts, little public discussion existed on the impact of LF on communities living in endemic regions, and national decision-making was slow in regard to adopting innovations to improve program efficiency. Frequent leadership transitions and postponement of technical advisory committee meetings also contributed to delays.At the implementation level, delays in scheduling MDA rounds in endemic districts resulted in other management problems including delays in drug inventory projections, lack of availability of family registers for health staff, delays in development of district microplans, delays in training plans, and inaccurate counts of community members in urban and rural areas. The program also suffered from poor uptake of preventive drugs among community members during MDA due to deep-rooted systemic mistrust issues that were not addressed in a timely manner, leading to poor community participation and poor compliance with MDA. Limited external partner support in funding and technical assistance to help the states and districts successfully implement MDA further contributed to implementation challenges.As a result of these challenges, the WHO country office for India expanded its technical support and shared strategies to address them through routine monitoring reports. The reports for 2017–2019 showed that over a period of 3 years, there was a significant decline in the number of “missed areas,” defined as areas where houses were missed and drugs were not offered. For the same time period, they showed a gradual improvement in the compliance among the population who received the drugs . The expert group declared that IDA was a safe mass treatment regimen for LF elimination.Global trials in five countries including India between October 2016 and November 2017 showed that a single dose of triple-drug treatment—ivermectin with DEC and albendazole (IDA)—is superior to the double-drug combination of DEC and albendazole (DA).After assessing the results of the multicountry IDA trials, WHO updated its MDA guidelines by providing guidance to introduce IDA in selected geographies based on inclusion criterion. At the same time, the Mectizan Donation Program committed to providing 100 million treatments per year of ivermectin for IDA introduction globally until 2025.Renewing India’s commitment to accelerate LF elimination, the former Union Health Minister Shri. J. P. Nadda launched the Accelerated Plan for Elimination of Lymphatic Filariasis at the Global Alliance to Eliminate Lymphatic Filariasis meeting in June 2018 in New Delhi, India. The Ministry of Health and Family Welfare decided to introduce IDA initially in five districts of the country. The National Vector Borne Disease Control Program (NVBDCP) collaborated with partners—WHO, Bill & Melinda Gates Foundation, Project Concern International, PATH, and Global Health Strategies—to facilitate the rollout process at national, state, and district levels.A technical committee was created under the chairmanship of the Directorate General of Health Services, and co-chaired by Dr. N. K. Ganguly, former Director General of Indian Council of Medical Research, with members from NVBDCP and WHO. The committee explored introduction of IDA in the LF MDA campaign in India. The committee was responsible for framing technical guidelines and policies, providing guidance for IDA implementation to states, overseeing adherence to safety protocols, and monitoring results of ground-level activities.•Implementing units (administrative units such as blocks and districts) that have not yet started or have had fewer than four effective MDA rounds of DA.•Implementing units that have not met appropriate epidemiological targets in sentinel and spot-check site surveys or that have failed transmission assessment surveys (or pre-Transmission Assessment Survey [TAS] surveys), despite meeting drug coverage targets during MDAs.•Communities where post-MDA or postvalidation surveillance identified infection, which suggests local transmission.According to WHO recommendations, annual triple-drug IDA—rather than the double-drug combination—should be implemented in the following settings:With these recommendations in mind, the technical committee used the following criteria to identify districts for inclusion in the study: 1) districts that have failed transmission assessment surveys—two with predominantly rural areas and two with large urban areas; and 2) a district that has never undertaken MDA, but where LF transmission has been identified.The technical committee selected Arwal district in Bihar and Simdega district in Jharkhand as the two small rural areas , and Nagpur district in Maharashtra and Varanasi district in Uttar Pradesh as the two large urban areas. The fifth district was Yadgir in Karnataka where IDA was previously administered as part of the global study for more than 6,000 people during the drug clinical trial. Whereas Simdega was to conduct MDA for the first time, the other four districts had failed transmission assessment surveys despite conducting more than five MDA rounds. IDA was rolled out in a staggered approach so that smaller areas could be targeted before moving on to larger areas. IDA implementation began in December 2018 and was completed in all five districts by the end of November 2019, thus making India the first country in Southeast Asia to roll out the innovative, WHO-approved triple-drug IDA regimen to accelerate LF elimination efforts.https://www.aninews.in/news/national/general-news/health-ministry-plans-to-introduce-mass-drug-administration-programme-in-yadgir-district-karnataka20190920165052/; Accessed July 13, 2021). Reported increases in drug compliance within communities encouraged national program managers to scale up innovations to accelerate LF elimination efforts. This paved the way for sustained scale-up of IDA in the country.The Government of India submitted a proposal to the Mectizan Donation Program, which works with ministries of health and partners by donating ivermectin for neglected tropical diseases through WHO. India’s proposal was to facilitate donation and delivery of ivermectin for close to 10.7 million people. Through WHO, the Mectizan Donation Program provided 31.27 million tablets of ivermectin during IDA rollout in the initial five districts. After successful introduction, the program further committed to providing 50 million doses of ivermectin for India annually until 2022 , availability of drugs, and willingness of the states. Of the 21 newly identified districts, 17 were able to complete their first round of IDA by 2020. The second round of IDA in these districts were delayed due to the COVID-19 pandemic and is scheduled for the second half of 2021.Among these 17 IDA scale-up districts, the WHO independent monitoring coverage data for the first round of IDA in 12 districts ranged from 25% to 84% as shown in Table In a comparison of IDA rounds 1 and 2 coverage data, we found a remarkable improvement in overall coverage in the initial four districts during the second round Figure . Good coKey stakeholders, including the central government, state government, district, and block-level health officials, adopted tailored approaches to rolling out IDA. Efforts focused on advocacy, information, education, and communication (IEC) efforts to build awareness, social mobilization, deployment of more teams to administer drugs, and supervision and monitoring. The partners’ role in filling gaps worked as a catalytic support for ensuring effective implementation of the rounds of IDA MDA. Strategies and approaches that contributed to the successful implementation of IDA rollout in India are described in more detail as follows.As an immediate outcome of advocacy efforts during the Global Alliance to Eliminate Lymphatic Filariasis meeting in June 2018, J. P. Nadda, former Union Minister, chaired a review meeting with the state health ministers and principal secretaries of health from seven endemic states to prioritize LF elimination. Subsequently, the state health ministers of Bihar and Maharashtra undertook review meetings of their respective state LF elimination programs. A total of 17 members of parliament and members of the legislative assembly actively supported IDA rollout in the initial pilot districts.Sustained involvement of bureaucratic leadership at the national and state levels ensured that the district level prioritized IDA rollout as an important public health priority. This was achieved through well-coordinated efforts under the leadership of NVBDCP and strong coordination with neglected tropical disease partners, state officials, and districts officials. Joint action plans were developed and agreed upon to effectively plan and implement activities before, during, and after MDA rounds.The state, district, and block task forces were composed of staff from the Ministry of Health and Family Welfare, other government departments, and partners. Existing training processes were modified according to IDA guidelines and were simplified in Hindi, the local language. Social mobilization and interpersonal communication sessions for frontline workers were incorporated in all trainings, including the state-level training of trainers, district-level training of trainers, and drug administrator training. The number of days allotted to conduct the MDA campaign were increased to ensure complete coverage and compliance of the target population.Enhanced training of medical officers, frontline workers, supervisors, and drug administrators before the MDA rounds covered aspects such as the proper use of dose poles, clarity on IDA dosages, and training on key messages for community members on the benefits of IDA. Drug administrators were well equipped with newly designed IEC tools to engage with the community effectively.The MDA campaigns used innovative approaches that focused on supervised administration at single-day booths in schools , Anganwadi centers, and health facilities. These innovative strategies were implemented in combination with door-to-door administration and mop-up rounds. Additionally, finger marking using marker pens was adopted to indicate who had already received IDA, including school children covered at booths. NVBDCP, in close coordination with partners, developed an innovative color-marked dose pole to determine the required dosage of ivermectin based on the height of the individual, according to WHO guidelines Figure . Finger Supervisors and drug administrators received training to improve the quality of microplanning for rural and urban areas. Good-quality microplans were of great help in reducing missed areas. Training at each level emphasized the importance of good-quality microplanning for effective implementation.•Community mobilizers were deployed at the block level to facilitate mobilization.•All existing platforms available in the districts were activated, such as schools, leaders of panchayat , local leaders, and women’s collectives.•Advance notice to communities was ensured. Community members received information about possible side effects and reasons for occurrence and how to report any adverse effects to community health workers, Anganwadi or health workers at booths, or the nearest subcenter or primary health center.•In coordination with the education department, a special school awareness program called Bhag Filaria Bhag  was initiated in all schools 15 days before MDA rounds began. Essay and drawing competitions were also organized in schools with winners receiving certificates of appreciation.•Sensitization of block-level public representatives and faith-based organizations was conducted.•Awareness rallies and wall writing also contributed to enhancing community reach and awareness.IEC materials including billboards, banners, posters, wall paintings, brochures, handbills, and newspaper advertisements were developed and shared in sufficient numbers well in advance of IDA rounds in the select districts. In addition to media engagement and crisis communications, branding and brand ambassadors, digital communications, and high profile launch events (detailed below), the following initiatives for community mobilization and awareness generation were also adopted:Media workshops were organized 2 days before the launch ceremony of IDA to disseminate key messages on the benefits of IDA and promote the dates of IDA rounds through print, broadcast, and digital channels. Crisis communication plans were developed to engage with the media in case of any serious adverse event to ensure a high level of trust among community members and preparedness to address misinformation.A logo and tagline were developed to enhance brand recognition and community acceptance for the program. The logo includes two hands—the first hand signifies the health worker offering the IDA treatment and the second hand indicates the community member accepting the treatment. The tagline is “safe drug, assurance for better health” Figure .State governments were supported to officially recruit a popular actor and youth icon as the brand ambassador for LF elimination in the state of Maharashtra where IDA was to be piloted in Nagpur District, which includes over 2 million people in urban areas. The actor’s engagement to support IDA introduction ranged from developing audio and video messages, authoring media articles, and leveraging his vast social media network to popularize the importance of addressing LF as a public health problem and acceptance of IDA by the community.Facebook and Twitter campaigns (#IndiaWillEndLF) promoting the elimination of LF were used to amplify the digital reach of communication messages about triple-drug MDA rounds. Social media messages were customized and shared through WhatsApp groups and widely disseminated through the networks of state, district, and community government officials, technical experts, and frontline workers.To increase the visibility of IDA rollout, launch events included the participation of elected representatives, popular celebrities, technical experts, state- and district-level officials , and the media.Effective supervision with one supervisor for every five booths or teams and a system of daily reporting from the supervisor to the block level by each evening was implemented. Simple formats facilitated daily reporting from booths to supervisors, supervisors to block levels, blocks to district headquarters, and districts to state headquarters. Rapid response teams headed by a medical officer with mobility support were identified in each block. In blocks with larger populations, two rapid response teams were identified. All adverse events were immediately attended to, while those with serious adverse events were hospitalized and adequately managed.Designated medical colleges carried out the post-MDA assessment according to established guidelines within 15 days after completion of MDA. A team formed by the state- and the district-level officials and one representative from NVBDCP conducted the post-MDA evaluation. Partner organizations including the WHO and Project Concern International also conducted independent small sample size data collection for post-MDA monitoring. Low coverage areas were followed up with additional “mop up” activities to cover the left-out populations.Partner support was vital for the successful implementation of IDA. WHO provided country support by developing standardized technical guidelines and training materials, operational research, and logistical support for drugs. Project Concern International supported social mobilization in selected states; PATH provided technical support for developing guidelines and tools; and Global Health Strategies undertook national-, state-, and district-level advocacy and communications.•The Drug Controller General of India had not approved ivermectin for human use in India, so the technical committee decided to seek approval, which required additional time and effort by NVBDCP to secure necessary approvals.•The supply of drugs was delayed due to administrative challenges and dates of MDA had to be revised.•During IDA rollout in Bihar, there was a local strike of accredited social health activists . Alternatively, other cadres such as Anganwadi workers were involved and booths were established in Anganwadi centers and schools. MDA was initiated but was interrupted after 2 weeks when Anganwadi workers also joined the strike.•Because MDA had never been undertaken in urban parts of Nagpur district or Simdega district, a lot of preparatory work was required, including mapping, developing microplans, and setting up systems as well as work to promote community awareness and conduct outreach activities.•In Varanasi district, IDA had to be conducted in February 2019. However, the Kumbh Mela (an elaborate religious gathering of pilgrims) took place at the same time and most of the government machinery was deployed for the event. Postponing IDA was not an option because general elections were scheduled for April 2019, which would have further delayed the rollout of IDA. Elections impact the overall reach to community members because health staff are deployed for election duties.•The delay in fabricating and dispatching dose poles from the central level led to the recommendation that dose poles should be developed at the local level. This helped prevent implementation delays.•Because of low coverage rates, the “mop-up” activity, which normally took from 7 to 10 days, to reach people who were missed during the initial efforts was extended to 2 or 3 weeks in some areas, which led to additional time and effort by drug administrators (without increasing the budget).•Lessons learned from India’s Polio Eradication Program were optimally applied for the successful introduction of IDA. Polio eradication principles were followed in all aspects of IDA rollout, including microplanning, training, social mobilization, engaging with the media, developing a logo and tagline, recruiting a brand ambassador, using finger marking and house marking, monitoring, strengthening data quality, and conducting program reviews at all levels. State and district administrators and partners easily understood the connection and were successful in their efforts.•For securing approval of the new drug combination, past experiences from introducing the Japanese encephalitis vaccination in campaign in India were helpful. Getting the right stakeholders at the table was a crucial step learned in the previous decade. Being cautious and honest about the possibilities of adverse events after the introduction of a new vaccine/drug and ensuring awareness of a strong rapid response mechanism inspired confidence among Indian stakeholders in regard to introducing and scaling up IDA.•Districts with a large urban population required detailed mapping of areas to be covered and advance planning to engage all existing resources. Engaging with municipal corporations yielded good results. Urban health units need to be sensitized to increase ownership of the campaign.•Convincing apparently healthy and asymptomatic adults to consume eight tablets at a time is a challenge. There is a need for targeted and enhanced communications and social mobilization to effectively reach out to communities.•Migrant people, particularly labor-intensive populations from LF endemic states, move frequently in search of work and livelihood. This demands a convergent approach to engage allied departments to cover these migratory populations.•Greater involvement of local-level panchayat and functionaries enhances efforts to reach out to communities. Advance preparation for advocacy, IEC, and social mobilization efforts is greatly beneficial.•Increased number of booths for administering drugs, along with household visits, helped increase program reach. Household members who were absent during door-to-door campaigns were visited subsequently during mop-up activities to ensure drug consumption. This helped redesign and improved microplans for further IDA rounds.•A daily monitoring system, reporting of adverse events, and arranging for the treatment of those with adverse effects should be in place for the duration of MDA rounds and until 4–5 days after completion of the rounds.Because India has a huge population to be covered during MDA campaigns, the greatest need is domestic procurement of ivermectin to scale up IDA in persistently endemic implementation units. Ultimately, 50 million treatments donated by the Mectizan Donation Program per year will not be sufficient for the 430 million people who can benefit by receiving the more effective triple-drug IDA regimen to accelerate elimination goals in India. Ensuring a good-quality drug supply from domestic manufacturers is an area of concern for India.To improve program implementation and targeted community compliance during MDA rounds, there is a need to reduce the size of implementation units. Focusing on blocks as the implementing unit and evaluating transmission at the block level can help in identifying blocks with ongoing transmission versus blocks that have achieved transmission interruption. Targeting and scaling up IDA in identified blocks in known endemic districts can play a major role in curbing ongoing transmission and enabling other blocks to move to post-MDA surveillance activities.The Government of India received additional support from partners to strengthen not only the introduction of triple-drug IDA but also double-drug DA campaigns. There was a significant improvement in overall program performance from those districts as well Figure . The proWhile reviewing subnational data, significant improvements were observed at the district level. An example of district-level data for the state of Uttar Pradesh is shown in Figure The current strategy is to strengthen the program in all geographies, irrespective of whether MDAs have been carried out using double-drug or triple-drug regimens Figure .•Public funding and budget allocation for triple-drug MDA rounds should be revised as rates that were fixed a decade ago by the Ministry of Health are insufficient for achieving desired results. This will ensure orientation of health staff, involvement of allied health department, and the alignment of IEC, and social mobilization to the needs of each area.•Urban areas need more attention as the health system doesn’t have sufficient govt./accountable drug administrators/supervisors and there is a lack of updated population registery for all individuals. Officer goers, shopkeepers, and private schools will need extra efforts for optimal coverage. Microplanning will need adjustments to administer drugs at institutions and to plan revisits when most residents are expected to be at home. Resident welfare associations and Multistorey building management will have to cooperate with drug administrators for better coverage. Improved and innovative social media usage will help in awareness generation and acceptance of drugs.•IDA should be given to migrant populations of daily wage workers if they are in large cluster groups from LF endemic areas working in various industries such as mines and factories located in other mosquito-endemic geographies.•Strong monitoring and evaluation system will be required to measure the success and provide evidence for corrective action.The following measures will assist in the rapid scale-up of IDA in India and further improve compliance among communities to sustain reductions in LF transmission during the post-IDA period:Proper documentation will be required for WHO validation of elimination in the future.Supplemental materials


Louisa et al. from the University of Indonesia have performed a systematic review on the role of Moringa oleifera Lam [Moringaceae] in cardiovascular or metabolic disorders, in addition to its high nutritional value. Moringa oleifera Lam. is a native plant of several Asian countries and is reported to provide potential benefits against oxidative stress and inflammation, modulating glucose and lipid metabolism and preventing end-organ damage. They have also covered the importance of altering the gut microbiota in metabolic syndrome in addition to the supporting data for the role of Moringa oleifera Lam. on various signaling pathways activated during inflammation and oxidative stress. Liu et al. have studied the molecular basis of the effect of ShenLian extract on atherosclerotic plaques in vitro and in vivo. By using the co-culture model, macrophage and smooth muscle cell (SMC) interactions were studied and reported the necessary role of transforming growth factor (TGF)-β in the cross-talk between macrophages and SMC in stabilizing the atherosclerotic plaques. They have reported that ShenLian extract  could stabilize the vulnerable plaques by increasing plaque collagen and functionally reconstruct the extracellular matrix via increasing TGF-β expression and regulating the STAT3/SOCS3 pathway. Liu et al. and her team reported that the monocyte locomotion inhibitory factor (MLIF), a heat-stable pentapeptide from Entamoeba histolytica, promoted microglia transition toward the M2 phenotype, which contributes to neuronal survival and tissue repair, in vivo and in vitro ischemic stroke model via regulation of eEF1A1/NFκB signaling pathway. They have suggested that MLIF might be a useful pharmacological agent for ischemic stroke. Zhang et al. have performed a meta-analysis on the systematic evaluation of TCM in the treatment of ventricular remodeling after acute MI. They have analyzed various parameters of myocardial function, ventricular remodeling, and serum levels of BNP and CRP from forty randomized clinical trials involving 3,659 participants and proved that a combination of TCM or TCM preparations with conventional Western medicine could prevent and reverse ventricular remodeling in post-acute MI (AMI). They have concluded that the combination of TCM and Western medicine can alleviate ventricular remodeling, enhance cardiac function, and reduce the incidence of major adverse cardiac events in AMI patients. Though fewer articles are available on this topic, we hope that this Research Topic provides readers with the importance of ethnopharmacology and traditional medicine system in the treatment of cardiometabolic diseases, initiates new ideas, and enhances future research to advance the field.Aging is a normal physiological process altering cell function largely through cellular senescence, but sometimes accelerated aging and/or excess accumulation of senescent cells in individuals may lead to several complications affecting the quality of life. One such complication is cardiometabolic disease, which is commonly seen in the elderly and is a global burden, causing health and economic problems. Though various treatment strategies are made available to manage the cardiometabolic diseases such as atherosclerosis, angina pectoris, and myocardial infarction (MI), etc., traditional systems of medicine play a major role in their treatment in various countries, such as Ayurveda, traditional Chinese medicine (TCM), Japanese Kampo medicine, Homoeopathy, Unani, and Siddha, etc. The lack of evidence for their beneficial effects as well as their molecular effects urged us to choose this topic.