Assessment of the Implementation of Pakistan's National Action Plan on Antimicrobial Resistance in the Agriculture and Food Sectors.

The agriculture and food (agrifood) sectors play key roles in the emergence, spread, and containment of antimicrobial resistance (AMR). Pakistan's first National Action Plan (NAP) on AMR was developed to guide One Health interventions to combat AMR through 2017-2022. To improve subsequent iterations, we assessed the implementation of Pakistan's NAP in the agrifood sectors (NAPag) in October 2022, using the Progressive Management Pathway on AMR tool developed by the Food and Agriculture Organization of the United Nations (FAO). The assessment tool addressed four crucial focus areas of the NAPag: governance, awareness, evidence, and practices. Each focus area contains multiple topics, which involve four sequential stages of activities to progressively achieve systematic management of AMR risk in the agrifood sectors. High-level representatives of the NAPag stakeholders provided information for the assessment through pre-event documentary review and workshop discussions. The assessment results showed that Pakistan's NAPag had an overall moderate coverage (59%) of the anticipated activities. Gaps were particularly notable in strengthening governance, good practices, and interventions in non-livestock sectors. Furthermore, only 12% of the evaluated activities were fully executed and documented, consistently remaining at the planning and piloting stages in the livestock sector across all the examined topics. Insufficient attention to non-livestock sectors, inadequate regulation and enforcement capacity, and resource constraints have hindered scalable and sustainable interventions under the current plan. This assessment provides valuable insights to strengthen the inclusiveness and contribution of the agrifood sectors in the next NAP iteration. In the short-to-medium term, strategic prioritization is necessary to optimize the use of limited resources and target the most critical gaps, such as improving awareness among key stakeholders and fortifying regulations for prudent antimicrobial use. In the long term, integration of AMR into the country's broader health, development, and agricultural transformation agendas will be needed to generate sustainable benefits.

Study on the Properties and Synergistic Antioxidant Effects of Novel Bifunctional Fusion Proteins Expressed Using the UTuT6 System.

Important antioxidant enzymes, glutathione peroxidase (GPx) and superoxide dismutase (SOD), are involved in maintaining redox balance. They can protect each other and result in more efficiently removing excessive reactive oxygen species (ROS), protecting cells against injury, and maintaining the normal metabolism of ROS. In this study, human cytosolic GPx (hGPx1) and human phospholipid hydroperoxide GPx (hGPx4) genes were integrated into the same open reading frame with human extracellular SOD active site (SOD3-72P) genes, respectively, and several novel fusion proteins were obtained by using the UTuT6 expression system for the first time. Among them, Se-hGPx1UAG-L4-SOD3-72P is the bifunctional fusion protein with the highest GPx activity and the best anti-hydrogen peroxide inactivation ability thus far. The Se-hGPx4UAG-L3-SOD3-72P fusion protein exhibits the strongest alkali and high temperature resistance and a greater protective effect against lipoprotein peroxidation damage. Se-hGPx1UAG-L4-SOD3-72P and Se-hGPx4UAG-L3-SOD3-72P fusion proteins both have good synergistic and antioxidant abilities in H2O2-induced RBCs and liver damage models. We believe that this research will help with the development of novel bifunctional fusion proteins and the investigation of the synergistic and catalytic mechanisms of GPx and SOD, which are important in creating novel protein therapeutics.

Global prioritization of endemic zoonotic diseases for conducting surveillance in domestic animals to protect public health.

Zoonotic diseases (zoonoses) originating from domestic animals pose a significant risk to people's health and livelihoods, in addition to jeopardizing animal health and production. Effective surveillance of endemic zoonoses at the animal level is crucial to assessing the disease burden and risk, and providing early warning to prevent epidemics in animals and spillover to humans. Here we aimed to prioritize and characterize zoonoses for which surveillance in domestic animals is important to prevent human infections at a global scale. A multi-criteria qualitative approach was used, where disease-specific information was obtained across literature of the leading international health organizations. Thirty-two zoonoses were prioritized, all of which have multi-regional spread, cause unexceptional human infections and have domestic animal hosts as important sources or sentinels of zoonotic infections. Most diseases involve multiple animal hosts and/or modes of zoonotic transmission, where a lack of specific clinical signs in animals further complicates surveillance. We discuss the challenges of animal health surveillance in endemic and resource-limited settings, as well as potential avenues for improvement such as the multi-disease, multi-sectoral and digital surveillance approaches. Our study will support global capacity-building efforts to strengthen the surveillance and control of endemic zoonoses at their animal sources. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

One health systems strengthening in countries: Tripartite tools and approaches at the human-animal-environment interface.

Unexpected pathogen transmission between animals, humans and their shared environments can impact all aspects of society. The Tripartite organisations-the Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the World Organisation for Animal Health (WOAH)-have been collaborating for over two decades. The inclusion of the United Nations Environment Program (UNEP) with the Tripartite, forming the 'Quadripartite' in 2021, creates a new and important avenue to engage environment sectors in the development of additional tools and resources for One Health coordination and improved health security globally. Beginning formally in 2010, the Tripartite set out strategic directions for the coordination of global activities to address health risks at the human-animal-environment interface. This paper highlights the historical background of this collaboration in the specific area of health security, using country examples to demonstrate lessons learnt and the evolution and pairing of Tripartite programmes and processes to jointly develop and deliver capacity strengthening tools to countries and strengthen performance for iterative evaluations. Evaluation frameworks, such as the International Health Regulations (IHR) Monitoring and Evaluation Framework, the WOAH Performance of Veterinary Services (PVS) Pathway and the FAO multisectoral evaluation tools for epidemiology and surveillance, support a shared global vision for health security, ultimately serving to inform decision making and provide a systematic approach for improved One Health capacity strengthening in countries. Supported by the IHR-PVS National Bridging Workshops and the development of the Tripartite Zoonoses Guide and related operational tools, the Tripartite and now Quadripartite, are working alongside countries to address critical gaps at the human-animal-environment interface.

Consideration of COVID-19 beyond the human-centred approach of prevention and control: the ONE-HEALTH perspective.

Most of the new emerging and re-emerging zoonotic virus outbreaks in recent years stem from close interaction with dead or alive infected animals. Since late 2019, the coronavirus disease 2019 (COVID-19) has spread into 221 countries and territories resulting in close to 300 million known infections and 5.4 million deaths in addition to a huge impact on both public health and the world economy. This paper reviews the COVID-19 prevalence in animals, raise concerns about animal welfare and discusses the role of environment in the transmission of COVID-19. Attention is drawn to the One Health concept as it emphasizes the environment in connection with the risk of transmission and establishment of diseases shared between animals and humans. Considering the importance of One Health for an effective response to the dissemination of infections of pandemic character, some unsettled issues with respect to COVID-19 are highlighted.

Achieving Antimicrobial Stewardship on the Global Scale: Challenges and Opportunities.

Antimicrobial resistance (AMR) has been clearly identified as a major global health challenge. It is a leading cause of human deaths and also has a toll on animals, plants, and the environment. Despite the considerable socio-economic impacts, the level of awareness of the problem remains woefully inadequate, and antimicrobials are not generally recognized as a global common good, one that everyone has a role and responsibility to conserve. It is imperative for antimicrobial stewardship to be more widely implemented to achieve better control of the AMR phenomenon. The Food and Agriculture Organization (FAO) of the United Nations plays an important role in promoting and facilitating antimicrobial stewardship. The specific needs to be addressed and barriers to be overcome, in particular, in low- and middle-income countries in order to implement antimicrobial stewardship practices in agrifood systems are being identified. As a global community, it is essential that we now move beyond discussing the AMR problem and focus on implementing solutions. Thus, FAO provides multi-pronged support for nations to improve antimicrobial stewardship through programs to strengthen governance, increase awareness, develop and enhance AMR surveillance, and implement best practices related to antimicrobial resistance in agrifood systems. For example, FAO is developing a platform to collect data on AMR in animals and antimicrobial use (AMU) in plants (InFARM), working on a campaign to reduce the need to use antimicrobials, studying the use of alternatives to the use of antimicrobials (especially those used for growth promotion) and actively promoting the implementation of the Codex Alimentarius AMR standards. Together, these will contribute to the control of AMR and also bring us closer to the achievement of multiple sustainable development goals.

Unpacking the Emotional Experiences of Learners in a Blended Learning Context.

Understanding the relationship between emotion and learning behavior is conducive to learners' well-being and effective learning. However, previous studies only regarded emotion as an additional variable, and there lacked specific research on academic emotion in the blended learning (BL) context. BL is characterized by systematic integration of online and face-to-face (F2F) learning, hence leading to special emotional experiences. What is the emotional experience of learners in online learning? What is it like face-to-face? Does the connection between the two have an impact on learners' emotional experience? In order to address these questions and explore the emotional profiles of learners in BL context, this study constructs a typical BL context in a Chinese university, and conducts questionnaire and focus group interviews with 89 participants at the end of the semester. Data analysis showed that learners' emotions of face-to-face classes are more intense than those of online learning, both positive and negative. As to positive emotions, paired-sample t-test shows that mean values of feeling of challenge, comfort, sense of community, satisfaction, enthusiasm and interest in F2F are significantly higher than those of online learning. About negative emotions, stress, embarrassment, tension and frustration of F2F are significantly stronger than those of online learning, while boredom and disappointment of online learning are more intense than those for F2F section. Theme analysis identified 11 influencing factors of academic emotions, among which degree of difficulty, readiness before class, workload, and interaction are unique to BL and deserve special attention. These findings help form a picture of learners' academic emotions in BL context. It also provides practical reference for BL course design, so as to inspire emotions which are conducive to effective and in-depth learning.

Towards a global One Health index: a potential assessment tool for One Health performance.

BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8-65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI-subject to rigorous validation-would represent the world's first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge.

United Against Rabies Forum: The One Health Concept at Work.

Human deaths from rabies are preventable and can be eliminated by applying a systematic One Health approach. However, this ancient disease still threatens the lives of millions of people in up to 150 countries and kills an estimated 59, 000 people every year. Rabies today is largely a disease of poverty, almost always linked to dog bites, with most deaths occurring in neglected communities in Africa and Asia. The disease places an immense economic burden on its victims, a cost that far outweighs the investment needed to control it. A global framework for rabies elimination in humans is set out in Zero by 30: The Global Strategic Plan to end human deaths from dog-mediated rabies by 2030. Despite the existence of proven control strategies and agreement on the path to eliminating human rabies deaths, mortality numbers from rabies remain high, and COVID-19 has set back efforts even further. But COVID-19 has also highlighted the value of a One Health approach to zoonotic disease and pandemic prevention. Rabies control programs offer a practical route to building One Health capacities that can also address other zoonotic threats, including those with pandemic potential. The United Against Rabies Forum aims to accelerate progress on rabies elimination while applying a One Health approach. The Forum promotes cross-sector collaboration among stakeholders and supports countries in their rabies elimination efforts. Increased political engagement and resource mobilization, both internationally and nationally, will be needed to achieve global rabies goals and can also make One Health implementation a reality.

A systematic approach toward progressive improvement of national antimicrobial resistance surveillance systems in food and agriculture sectors.

The first Food and Agriculture Organization of the United Nations (FAO) Action Plan on antimicrobial resistance (AMR), published in 2016, identified the need to develop capacity for AMR surveillance and monitoring in food and agriculture sectors. As part of this effort, FAO has developed the "Assessment Tool for Laboratories and AMR Surveillance Systems" (FAO-ATLASS) to assist countries in systematically assessing their AMR surveillance system in food and agriculture. FAO-ATLASS includes two different modules for surveillance and laboratory assessment. Each module includes two questionnaires that collect either qualitative or semi-quantitative data to describe and score the performance of national AMR surveillance system data production network, data collection and analysis, governance, communication and overall sustainability in a standardized manner. Based on information captured in the questionnaire by trained assessors (1) tables and figures describing the outputs of the surveillance system are automatically generated (2) a Progressive Improvement Pathway (PIP) stage, ranging from "1-limited" to "5-sustainable", is assigned to each laboratory assessed in the country, each area of the surveillance system and also to the overarching national AMR surveillance system. FAO-ATLASS allows national authorities to implement a strategic stepwise approach to improving their AMR surveillance systems via the FAO-ATLASS PIP system and provides an evidence base for actions and advocacy. The implementation of FAO-ATLASS at regional and global levels can contribute to harmonize and better coordinate strategies aimed at implementing an integrated AMR surveillance system under the One Health approach.

Effect of Hypothermia on Serum Myelin Basic Protein and Tumor Necrosis Factor-α in Neonatal Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: Multiple randomized controlled trials have shown that hypothermia is a safe and effective treatment for neonatal moderate or severe hypoxic-ischemic encephalopathy (HIE). The neuroprotective mechanisms of hypothermia need further study. The aim of this study was to investigate the effect of hypothermia on the serum levels of myelin basic protein (MBP) and tumor necrosis factor-α (TNF-α) as well as neurodevelopmental outcomes in neonatal HIE. STUDY DESIGN: Eighty-five neonates with moderate-to-severe HIE were divided into a hypothermia group (n = 49) and a control group (n = 36). Serum levels of MBP and TNF-α within 6 hours after birth and after 3 days of treatment were determined by enzyme-linked immunosorbent assay, and neurodevelopmental outcome at the age of 12 to 15 months was assessed by using the Gesell development scale. RESULTS: After 3 days of treatment, serum levels of MBP and TNF-α in the control group were not significantly different from levels before treatment (p > 0.05), and serum levels of MBP and TNF-α in the hypothermia group were significantly lower than levels before treatment (p < 0.05). Serum levels of MBP and TNF-α were significantly negatively correlated with developmental quotient (DQ; r = - 0.7945, p = 0.0000; r = - 0.7035, p = 0.0000, respectively). Serum levels of MBP and TNF-α in neurodevelopmentally impaired infants were significantly higher than those in infants with suspected neurodevelopmental impairment and those in neurodevelopmentally normal infants (both p < 0.01). The rate of reduction of neurodevelopmental impairment was higher among infants in the hypothermia group than among those in the control group (χ2 = 16.3900, p < 0.05). CONCLUSION: Hypothermia can reduce serum levels of MBP and TNF-α in neonates with HIE. Inhibiting the release of TNF-α may be one of the mechanisms by which hypothermia protects the myelin sheath. KEY POINTS: · Hypothermia can reduce serum levels of MBP and TNF-α in neonatal HIE.. · Hypothermia improves neurodevelopmental outcomes and reduces the rate of neurodevelopmental impairment.. · Hypothermia is a feasible and effective treatment for neonates with moderate or severe HIE..

Governance Processes and Challenges for Reservation of Antimicrobials Exclusively for Human Use and Restriction of Antimicrobial Use in Animals.

The majority of antimicrobials that are produced are administered to animals, particularly food animals. While the overall impact of antimicrobial use in animals on antimicrobial resistance in humans and the environment is unclear, it undeniably has a role. Yet, some degree of antimicrobial use in animals is necessary for animal health and welfare purposes. Balancing the benefits and risks of antimicrobial use in animals is challenging because of the complexity of the problem and limitations in available data. However, a range of measures can be implemented to reduce, refine and optimize antimicrobial use in animals, with a goal of minimizing the impact on human and environmental health while maintaining necessary therapeutic use in animals. A pandemic instrument can provide the necessary foundation for the whole-of-society and whole-of government One Health approach that is required to strengthen surveillance, communication, collaboration, and action.

Advances in the Molecular Genetics of Catecholaminergic Polymorphic Ventricular Tachycardia.

Catecholaminergic polymorphic ventricular tachycardia is a primary arrhythmogenic syndrome with genetic features most commonly seen in adolescents, with syncope and sudden death following exercise or agitation as the main clinical manifestations. The mechanism of its occurrence is related to the aberrant release of Ca2+ from cardiomyocytes caused by abnormal RyR2 channels or CASQ2 proteins under conditions of sympathetic excitation, thus inducing a delayed posterior exertional pole, manifested by sympathetic excitation inducing adrenaline secretion, resulting in bidirectional or polymorphic ventricular tachycardia. The mortality rate of the disease is high, but patients usually do not have organic heart disease, the clinical manifestations may not be obvious, and no significant abnormal changes in the QT interval are often observed on electrocardiography. Therefore, the disease is often easily missed and misdiagnosed. A number of genetic mutations have been linked to the development of this disease, and the mechanisms are different. In this paper, we would like to summarize the possible genes related to catecholaminergic polymorphic ventricular tachycardia in order to review the genetic tests currently performed, and to further promote the development of genetic testing techniques and deepen the research on the molecular level of this disease.

Non-coding RNAs and Pathological Cardiac Hypertrophy.

Cardiovascular disease (CVD) is a common disease which poses a serious threat to human health and it is characterized by high prevalence, high disability and high mortality. Myocardial hypertrophy (MH) is a common pathological process of various cardiovascular diseases and is considered as an independent risk factor for increased cardiovascular morbidity and mortality. Therefore, it is particularly important to understand its pathological mechanism and treatment. In recent years, it has been found that many non-coding RNAs (ncRNAs) play key regulatory roles in humans' various pathophysiological processes. Abnormal expression of ncRNAs in different types of cardiac cells is associated with pathological cardiac hypertrophy. Understanding the relationship between various ncRNAs and intercellular communication through extracellular vesicles (EV) can identify the key ncRNAs which are the accurate targets of precise therapy in this network of action, it also can potentially be a marker for clinical disease diagnosis, which will reflect the progress of the disease earlier and more accurately. There are many factors that regulate the occurrence and development of cardiac hypertrophy, ncRNAs are only a part of them. There are also mutual promotion or inhibition between ncRNAs and other molecules. It will be helpful for us to comprehend the mechanism of cardiac hypertrophy better and provide a sufficient theoretical basis for clinical diagnosis and treatment by defining these relationships.