Striated muscle exists in two types, skeletal and cardiac. They share numerous operational and structural characteristics, including sarcomere organization, with repeating functional units that confer the typical striated appearance observed in microscopic images of this tissue. Striated muscle is a highly adaptive and critically important metabolic tissue with intrinsic roles in health and disease. Striated muscle contraction supports various crucial physiological processes, including respiration, locomotion, posture , and pumping blood throughout the vascular system (cardiac muscle). Striated muscles are affected by many acquired and genetic pathophysiological conditions, which represent significant health and economic burden for modern society. Cardiac disorders, including ischemia and arrhythmias, are among the leading cause of death worldwide. Loss of skeletal muscle mass and strength is an indicator of neuromuscular genetic pathologies, aging, cancer, and a variety of chronic or acute conditions that are systemic or primarily affecting different tissues.This Research Topic aims to describe new technical approaches and critically discuss existing methods and protocols applicable to the study of striated muscle physiology. The goal is to provide investigators with novel reliable tools: 1) to understand the fundamental mechanisms controlling striated muscle biology, 2) to characterize and diagnose striated muscle degenerative conditions, and 3) to identify innovative therapeutic strategies to preserve skeletal and cardiac muscle homeostasis and function.ex vivo molecular analysis or cellular and histological characterization. This is particularly critical if the donors of the biopsies are in a particularly fragile category, such as old people or individuals presenting coagulation defects, such as patients with chronic liver diseases. The Bergström biopsy is the gold-standard technique for sampling skeletal muscle and is used worldwide. This approach relies on collecting 25–125 mg of tissue with a 3–5 mm needle. Quinlan et al. report the results obtained with cohorts of patients affected by end-stage liver disease and non-cirrhotic non-alcoholic fatty liver disease undergoing percutaneous vastus lateralis biopsies with a Bergström needle. They report 90% of successful biopsies in over 71 attempts and only one adverse event (hematoma). This study also identifies the presence of subcutaneous adipose tissue as a critical aspect hindering productive sampling, indicating that appropriate patient selection and good technique mitigate against potential risks. An alternative to Bergström biopsy is microbiopsy, obtained with a needle of smaller diameter  and therefore characterized by decreased invasiveness. The size of tissue biopsy is generally smaller, ranging from 14 to 22 mg. Hester et al. show that percutaneous microbiopsy can be successfully performed in old individuals, and sufficient material is obtained for histological characterization of fiber types. This observation supports the idea that microbiopsies may be a valuable muscle sampling alternative to the Bergström technique, particularly for categories of fragile patients.One of the major limitations of the study of striated muscle characteristics for both basic research and diagnostic purposes is obtaining and preparing tissue for subsequent ex vivo investigation are also challenging for cardiac muscle. Cultivation of ventricular slices is increasingly used in basic and translational studies investigating mechanisms of ventricular dysfunction that lead to heart failure. Palmer and Bell describe, in the rat model, methods for removing and preparing cardiac papillary muscles and provide instruction for preparing cardiac slices for functional analyses. Klumm et al. describe a methodology that allows for long-term (up to 3 weeks) cultivation and functional analysis of beating human atrial myocardium. The possibility of establishing multicellular models of atrial myocardium expands the possibility of study beyond ventricular pathophysiology to discern atrial biology and atrial dysfunction.The obtainment and preparation of tissues for in vitro investigation in cardiac biology is disclosed by the methodological study reported by Krstic et al. They performed a visual characterization of beat-to-beat mitochondrial calcium fluxes in rat cardiomyocytes. For this purpose, they modify the fluorescent membrane-permeable Ca2+ indicator Rhod-2 by reducing it to di-hydroRhod-2, which is non-fluorescent unless it reaches the oxidative environment of mitochondria. This study highlights the need for optimized protocols to comprehend the complex mechanism underlying the contraction of striated muscle cells.The power of 2+ governs striated muscle contraction and relaxation at the myofilament level via conformational modulations of the troponin complex. Rasmussen and Jin developed an approach using site-specific monoclonal antibodies as probes to monitor conformational changes of proteins. They applied this technique to study the Ca2+-binding subunit and the tropomyosin-binding/thin filament-anchoring subunits of troponin. Measurements at the sub-cellular level are instrumental in investigating striated skeletal and cardiac muscle contractility. In his manuscript, Marston reviews the current methods for measuring force production at the subcellular level, including single myofibril and single myofilament techniques. Herzog further critically discusses this area of expertise, particularly focusing on the isolation and testing of single sarcomeres. Also focused on sarcomeres is the publication by Adkins et al. that reports a quantification of the variability of in vivo sarcomere length measures obtained in human upper limb skeletal muscle with second harmonic generation microendoscopy. This state-of-the-art technique allows minimally invasive measures of sarcomere length. The assessment of the natural variability associated with this approach guides the development of robust experimental design and the interpretation of in vivo analyses of sarcomere length.Calcium dynamics drive ATP production in the mitochondrial matrix, and play a critical role in the cytosol where CaFlorio et al. disclose the potential use of electro-enhanced DNA transfer to murine skeletal muscle to investigate the characteristics of these mononucleated cells. Importantly, this approach can be applied not only to the study of healthy muscle but also to the investigation of alterations of the phenotypic properties that have been associated with defective repair and fibrosis in aging and dystrophic tissues.Skeletal muscle is not only composed of contractile syncytial muscle fibers but also other mononucleated cellular types, such as muscle stem cells, immune cells, interstitial and stromal progenitors, all reportedly playing a crucial role during muscle regeneration. Sarvazyan in a review centered on valveless pumping based on the Liebau mechanism is particularly intriguing. Here, the author describes the biological occurrence of Liebau pumps, highlights the differences between Liebau pumping and the peristaltic flow, and discusses the potential uses and body sites that can benefit from implantable Liebau-type pumps.The overarching theme of this Research Topic is to better understand striated tissue biology and uncover new diagnostic and therapeutic approaches to treat striated muscle disease. In this light, the discussion put forward by Methods and applications in striated muscle physiology incorporates novel original techniques and reviews of methodological approaches that can be used by investigators operating in the field of skeletal or cardiac muscle biology.In conclusion, this Research Topic on


An implementation gap exists between the evidence supporting physical activity in the prevention and management of long-term medical conditions and clinical practice. Person-centred conversations, i.e. focussing on the values, preferences and aspirations of each individual, are required from healthcare professionals. However, many currently lack the capability, opportunity, and motivation to have these conversations. This study uses the Behaviour Change Wheel (BCW) to inform the development of practical and educational resources to help bridge this gap.The BCW provides a theoretical approach to enable the systematic development of behaviour change interventions. Authors followed the described eight-step process, considered results from a scoping review, consulted clinical working groups, tested and developed ideas across clinical pathways, and agreed on solutions to each stage by consensus.The behavioural diagnosis identified healthcare professionals’ initiation of person-centred conversations on physical activity at all appropriate opportunities in routine medical care as a suitable primary target for interventions. Six intervention functions and five policy categories met the APEASE criteria. We mapped 17 Behavioural Change Techniques onto BCW intervention functions to define intervention strategies.This study uses the BCW to outline a coherent approach for intervention development to improve healthcare professionals’ frequency and quality of conversations on physical activity across clinical practice. Time-sensitive and role-specific resources might help healthcare professionals understand the focus of their intervention. Educational resources aimed at healthcare professionals and patients could have mutual benefit, should fit into existing care pathways and support professional development. A trusted information source with single-point access via the internet is likely to improve accessibility. Future evaluation of resources built and coded using this framework is required to establish the effectiveness of this approach and help improve understanding of what works to change conversations around physical activity in clinical practice. In keeping with global trends, Non-Communicable Disease (NCD) dominates morbidity and mortality in the UK . This poPhysical inactivity is responsible for almost 10% of the major NCDs, including heart disease, type 2 diabetes, and breast and colon cancers . People In keeping with the UK’s ‘Make Every Contact Count’ initiative , the NatEncouragingly, most healthcare professionals perceive conversations about physical activity to be important  our clinical networks across two regional meetings involving 70 multidisciplinary professionals and patients from community and hospital rheumatology and musculoskeletal services and (2) service managers, multidisciplinary leads and patients across three inpatient and one community pathway in the active hospital project . We met In step 3, we explored the nature and characteristics of the target behaviours defined in step 2 in more detail and considered the context in which each behaviour occurs. Questions we addressed as a group included who needed to undertake the behaviour, what they needed to do, and where and when they might do it. If we were unclear about the application of the target behaviour, we spent time exploring contrasting clinical pathways to identify common characteristics. This step helped generate discrete target areas for influencing behaviour.We identified the capability, motivation and opportunity factors required to change the identified target behaviours based on the scoping review of the literature, feedback from clinical groups, departmental meetings with clinical service leaders, and discussions with inpatients involved in the active hospital project. We subsequently used the theoretical domains framework to add context to each behavioural target by working the targets through diverse clinical pathways and identifying areas of commonality. This process helped us generate discrete targets with a theoretical rationale to change practitioner behaviour successfully.In a paper exercise, we mapped COM-B components from the behavioural diagnosis onto intervention functions according to the BCW. First, we met as a group to discuss and assess each intervention function using the APEASE criteria – Affordability, Practicability, Effectiveness and cost-effectiveness, Acceptability, Side effects and safety and Equity . FollowiWe identified policy categories reported in the literature and those highlighted by healthcare professionals during active hospital pathway development. As with intervention functions, we met to assess policy categories according to the APEASE criteria and mapped relevant policy categories onto behavioural domains defined in the BCW .BCTs form the active ingredients of interventions and enable coherent approaches to evaluation . The BCWThe final step of the BCW is to develop a delivery framework based on a recognised taxonomy of delivery modes . A revieWhat is the behaviour? Healthcare professionals initiating person-centred conversations on physical activity at all appropriate opportunities in routine medical careWhere does the behaviour occur? Across the spectrum of healthcare provision for managing and treating people living with long-term medical conditions. Delivery will range from community and primary care settings to hospital inpatients in secondary and tertiary care facilities. Settings may include clinic rooms, wards, day rooms and all other environments delivering healthcare services, including remote or telehealth consultations.Who is involved in performing the behaviour? All healthcare professionals.What are common barriers to performing the behaviour? Consistent barriers to physical activity conversations in clinical practice are reported amongst a range of healthcare professionals practising in various clinical domains across numerous countries. Table We agreed on the following answers to the questions posed in step 1:Following analysis of the potential behavioural targets, we agreed on the initiation of conversations on physical activity by healthcare professionals as the primary target behaviour. This discrete and tangible target can be easily measured and, if achieved, is likely to prompt healthcare professionals to develop their skills. Furthermore, once initiating conversations becomes a part of healthcare professionals’ routine consulting practice, they are likely to influence others’ practice positively. Table After specifying the primary and secondary target populations and behaviours, we specified the behavioural target regarding who, what, where and when the behaviour is performed. This helped us generate the discrete target areas for influencing behaviour outlined in Table The behavioural diagnosis identified barriers and facilitators to all six core components of the COM-B model. Expanding each domain using the theoretical domains framework helped us define tangible targets for intervention design, as demonstrated in Table In total, we selected six out of nine intervention functions. We deemed incentivisation not affordable or practical, coercion not practical or acceptable, and restriction not practical for implementation in general clinical environments. Table We selected 5 out of 7 policy categories, although regulation relies on external bodies for practicability. Despite this, we agreed to include regulation because service leaders in clinical pathways we were developing in the active hospital project were keen to change the systems regulating practice by healthcare professionals in their pathways, for instance, through the electronic records system. Fiscal and legislative policy categories were deemed impracticable and unacceptable. Table We identified 17 promising BCTs and mapped these onto BCW intervention functions, as demonstrated in Table We focused on population-level delivery approaches to make a resource accessible to as many healthcare professionals as possible. In addition, Digital channels predominate to make the project affordable and broaden its reach. Table This study uses the BCW to outline a coherent approach for intervention development to improve the frequency and quality of conversations on physical activity by healthcare professionals managing long-term conditions. Time-sensitive and role-specific resources will help healthcare professionals understand the focus of their intervention. Educational resources aimed at healthcare professionals and patients will have mutual benefit, should fit into existing care pathways and support professional development. A trusted information source with single-point access via the internet will improve accessibility and provide an ideal delivery mechanism for a wide range of resources, including an avenue for distributing free promotional information.Our concurrent clinical activity in the development of three inpatient and one community clinical physical activity pathway in the Active Hospital pilot provided an ideal environment to explore and test promising ideas from published literature. We balanced our behavioural analysis across community and hospital environments. However, we recognise there is a risk of a bias toward understanding the implementation landscape in a hospital environment, potentially limiting the applicability of our findings to interventions in other settings, such as primary care. Although our clinical backgrounds positively impact the clinical relevance of this study, the quality of our work is potentially limited by the lack of a robust academic background in behaviour change amongst the healthcare professionals in our team. This impacted some of our decision-making; for instance, we included modifying patient behaviour as a secondary behavioural target due to promising literature suggesting the benefits from this approach without behavioural analysis of patients themselves. We identified the risk of our academic limitations at the outset, which informed our decision to use the BCW due to its straightforward and step-wise guidance. As others have reported, we discovered that following the BCW system is an exacting challenge . SystemaA growing body of evidence demonstrates the potential of time-efficient behavioural change approaches in clinical practice , 112. PeWhilst education and training alone are insufficient to change healthcare professional behaviour, embedding education and training opportunities into a practical structure to support routine practice improves practitioner engagement and increases the likelihood of behavioural change . HealthcAs well as prompting habit formation, building educational resources into routine care by supporting real-time decision-making and providing point-of-care prompts for best practice can enhance professional development . Such edwww.movingmedicine.ac.uk and call upon researchers to focus on improving our understanding of what works to improve conversations on physical activity across clinical practice.Future research may include understanding how to leverage the influence of patients on healthcare professional behaviour and improve habituation within complex communication skills. Greater understanding is required of how healthcare systems and the professionals within them can best balance the fundamental medical requirements of long-term condition management with individualised and person-centred behavioural change support. Designing interventions with evaluation in mind is critical to help understand the optimal approach to increasing the frequency and quality of conversations on physical activity across clinical practice. To this end, the findings of this study have informed the development of a hybrid online resource combining educational material with conversational guidance coded with BCTs to support evaluation , 59. We We have iteratively developed a framework using the BCW to improve healthcare professionals’ capability, opportunity and motivation to have person-centred conversations on physical activity. The framework is grounded in the priorities of busy healthcare professionals addressing a range of barriers, including time, knowledge, skills and system support. At the heart of a successful intervention lies the principles of person-centred care and an approach that may be unfamiliar to healthcare professionals trained in a didactic consultation style. Resources need to be time-sensitive and role-specific, whilst educational resources aimed at healthcare professionals and patients will have mutual benefit, should fit into existing care pathways and support professional development. A trusted information source with single-point access via the internet will improve accessibility and provide an acceptable delivery mechanism for a wide range of resources. All healthcare team members have a role in delivering constructive physical activity support.Building practical resources based on this framework will improve efficacy, integrate the principles of behaviour change and provide a platform to inform future research and develop clinical physical activity services. Therefore, we encourage open evaluation of resources built using this framework to help improve understanding and implementation of what works.


This study explores accelerated internationalization among inexperienced digital entrepreneurs who lack resources such as prior experience, knowledge, and networks, which previous research regards as prerequisites for such growth. Following an in-depth qualitative research methodology, the findings reveal three theoretical mechanisms through which inexperienced entrepreneurs can make international commitment decisions with regard to the internationalization of their digital firms. The first is a novel mindset-based approach through which an entrepreneur can make an affective commitment to the international stakeholders within a digital community. Entrepreneurs do that by applying pull-based tools in digital communication to build interest among potential network contacts. The second mechanism is a means-based approach following effectuation logic resulting in an effectual form of commitment to international stakeholders in the digital community. The mechanism relies on applying push-based tools for digital communication to facilitate interactions with known network contacts. The third mechanism is continuance commitment to international business that entrepreneurs can foster over time in tandem with accumulated international experiential knowledge. This research provides an entrepreneurial decision-making model that extends effectuation theory and integrates it with extant research. The resulting holistic entrepreneurial decision-making model explains the accelerated internationalization of digital firms. Digital technologies enable entrepreneurial activity that incorporates novel technology and creates new business ventures. Consequently, there has recently been additional room for accelerated internationalization, particularly during the COVID-19 pandemic . Interestingly, the literature reviewed revealed that there is one stream of research under label entrepreneurs’ decision-making logic that covers research dealing with use of effectuation logic and networking. Moreover, there is another stream of research that can be labeled as digital entrepreneurship, which provides insights into how entrepreneurial firms can internationalize within the digital community. However, there is no mention in the literature about how entrepreneurial decision-making logic and related networking applies to digital entrepreneurship in the context of accelerated internationalization. The following sections review earlier research and draw conclusions based on those studies; we present our positioning against the identified key articles in Table Our conceptual foundation is based on a systematic literature search of the most relevant journals related to studies investigating effectuation, networking, and digital entrepreneurship. We used Reuter’s Web of Science database and EBSCOhost (multiple databases) to perform an advanced search within relevant journals publishing international entrepreneurship research, such as Entrepreneurship Theory and Practice, Journal of the Academy of Marketing Science, Journal of Business Research, Journal of Business Venturing, Journal of International Business Studies, Journal of International Entrepreneurship, Journal of Marketing, Journal of Marketing Research, Journal of World Business, Management International Review, and Small Business Economics. We considered articles published up until 2021. We searched for the keywords Experiential knowledge can only be learned through personal experience. With experiential knowledge, emphasis is placed on the change in the services the human resources can supply which arises from their activity… experience itself can never be transmitted, it produces a change – frequently a subtle change – in individuals and cannot be separated from them (p. 53).Earlier research suggests that international experiential knowledge exerts a key influence on accelerated internationalization, such that prior knowledge of foreign markets can enhance the speed with which an entrepreneurial team perceives opportunities  and international market conditions  can cause uncertainty for entrepreneurial firms expanding internationally relatively soon after their foundation , entrepreneurs may amend their perceptions of their firm’s mission, vision, or strategy. The effectuation process may also become one based more on causal decision-making. In causation, the entrepreneur focuses on the target, which involves asking what should be done using underutilized network relationships and with partners that could confer benefits  where those processes are conducted .We conducted eight interviews applying the ontological, epistemological, and methodological assumptions of our study. The interviewees had been central to Alpha’s development and included the firm’s founders, chief executive officers (CEOs), a chief technical officer (CTO), and a chief marketing officer (CMO) . Because of their self-learned skills as amateur talents in mobile-game development, they believed in themselves and wanted to show their competence (what I know). However, regarding their international experiential knowledge, the entrepreneurs lacked the resources, dense social networks, and previous international management and industry expertise to facilitate the process of establishing a new venture with an international orientation.The Alpha founders were university students whose lack of international experiential knowledge was compensated for by their favoring an effectuation approach. They had a dream of becoming global, well-respected talents in digital programming . By these means, they attracted more interest, creating a pull factor in digital networks. As a result, the young entrepreneurs were recognized as new digital talents among game developers in the mobile gaming industry network, which encouraged them to establish a new venture.In 2003, their success at new means) and instigated close collaboration with them. This effectual commitment included an investment from the Alpha side into research and development work in order to meet Beta’s expectations. The collaboration set the Alpha entrepreneurs up with a new insider position and provided access to the global digital community, which spurred the firm’s accelerated internationalization. The Alpha staff described their relationship with Beta as active and beneficial, and Beta invested considerable resources into the partnership and, thus, shared the risk of the new venture. Although Beta gave Alpha significant autonomy in the collaboration, the Alpha entrepreneurs recognized the need to become more independent in their digital entrepreneurship.Although the entrepreneurs lacked international experiential knowledge, their capabilities in mobile-game development and digital communication  facilitated access to Beta, a multinational corporation (MNC) digital games publisher, in 2004. Because Beta management had identified the entrepreneurs behind Alpha as potential partners, the young entrepreneurs made an effectual commitment to the MNC game developer ((as new means) in mobile-game development was the foundation of their self-efficacy. The perspective led to them adopting an effectual approach as a decision-making logic. Such entrepreneurial behavior enabled increasingly greater effectual commitment in global game development collaborations with several multinational corporations, and they felt able to bypass Beta, their MNC distributor. Alpha’s management created a push through digital communication  by interacting with key players in the digital community – an example of employing effectual logic. Subsequently, the Alpha entrepreneurs committed to subcontract arrangements with several direct MNC customers in the digital mobile-game industry, which led them to invest the money received from an angel investor into rebranding the firm as Alpha Ltd. Such collaborations particularly helped the Alpha entrepreneurs recognize that they needed to gain brand visibility among consumers of the digital community . To reduce the firm’s dependence on any single relationship and to pursue rapid international growth, Alpha sold its own mobile games to operators, which triggered a staff expansion in 2006.The Alpha entrepreneurs’ initial international experiential knowledge combined with the danger of overdependence and enhanced digital capability a digital artifact). The game deliberately targeted consumers globally and, in time, proved an enormous success. The innovative touch-screen technology exposed the game to new consumers in the digital mobile-game industry and was enabled by the emerging digital global marketplaces or digital platforms.Owing to the entrepreneurs’ very limited experience of building a profitable business partnership, the expansion was unsuccessful. The entrepreneurs almost lost their financial independence and the firm failed to realize its international sales forecasts. However, Alpha’s entrepreneurs learned more about the game development industry and used that knowledge to develop new and better games. The entrepreneurs’ digital capability, which now included analytical skills and a specific understanding of the global mobile-game industry, prompted the move toward a causation-based strategic decision to commercialize their first mobile game . Therefore, they targeted several franchising opportunities and quickly built partnerships with global consumer brands outside of the digital community. These new collaborations brought Alpha’s management team closer to the retail markets and pushed the firm toward new growth opportunities flowing from the expansion into highly diversified global consumer markets. The strong digital brand also led to unexpected contacts from various fields interested in associating their products with digitalization and gaming (new means).what I can do) can compensate for a lack of international experience in a new field. Alpha leveraged its strong brand to push through effectual commitments in new avenues to foster brand extension, and the entrepreneurs also formed an innovative collaboration with a world-leading global film studio. In May 2016, the computer-animated Alpha movie was released and enjoyed substantial worldwide success. This success was extremely important for the future of Alpha and its brand; it strengthened its global network position, and as a result, industry leaders sought to collaborate with Alpha. The discourses of the Alpha management informants reveal they view effectuation as an important decision-making tool that enables the firm to remain agile to exploit new digital business opportunities through innovative product development.However, the new strategy was unsuccessful and led to the fragmentation of Alpha’s businesses. The entrepreneurs’ extensive international experiential knowledge meant they recognized that their brand would deteriorate rapidly if Alpha relied only on leveraging the brand through international consumer firms. Consequently, the entrepreneurs began to explore developing a new digital business area. However, as they were unaware of the precise new direction it would take, the entrepreneurs applied a means-based approach. Having dispatched one of the entrepreneurs to the United States to explore possible avenues, the entrepreneurs used effectual networking to identify the digital movie industry as a potential area of expansion. They accordingly sought to collaborate with a leading global film studio and mutual commitments were made to develop a new movie based on the Alpha brand. The movie deal is an example of how a means-based effectuation approach  During accelerated internationalization, entrepreneurs can follow (a) an initial global mindset-based approach leading to affective commitment, or (b) an entrepreneurial means-based approach leading to effectual commitment to the stakeholders within the digital community.Whom I know) and enabled the subsequent means-based effectuation process.The empirical evidence suggests that following the effectuation process by relying on either a mindset- or a means-based approach may involve adopting new means or setting new goals. A new finding pertaining to Sarasvathy’s  model isWhat can I do.” Hence, we offer the following synthesis:In the next event, effectual decision-making resulted in the entrepreneurs acquiring new international experiential knowledge relating to the constraints of being dependent on a single partner. The situation persuaded Alpha to increase the number of partners involved in subsequent key events. This evidenced a converging cycle of constraints on the transformation of the new digital artifact that brought the firm back to adopting a means-based effectual approach and asking, “Synthesis 2: An entrepreneur that has established mutual commitment with the stakeholders within the digital community can embark on a repeated process of effectuation based on learning by following either (a) an expanding cycle of resources or (b) a converging cycle of constraints on the transformation of new digital artifacts.Recording the changes to the discourses over time enabled us to see beyond the initial choice between effectual decision-making and causal networking  partners. The new goals cycle was applied when the company realized that the strategy was depleting its brand value, forcing it to return to applying the effectuation process during its next iteration into film production. Therefore, our entrepreneurial decision-making and networking model of accelerated internationalization see Fig.  extends Synthesis 4: As internationalization advances in a digital firm and the entrepreneurs engage in causal decision-making to attain continuance commitment, they may temporarily (a) return to effectuation by following the expanding cycle of resources or (b) the converging cycle of constraints on the transformation of the new digital artifacts.The context for this study is that of entrepreneurs’ decision-making and networking within the digital community when engaging in accelerated internationalization, doing so successfully, despite lacking experiential knowledge. This phenomenon was investigated by focusing on two literature streams: entrepreneurial decision-making and digital entrepreneurship. An examination of qualitative research identified three entrepreneurial decision-making and networking paths for entrepreneurs to adopt in the course of accelerated internationalization see Fig. .This research contributes to the international entrepreneurship research field in the following ways. First, in terms of originality (Corley & Gioia, Second, this study adds scientific utility (Corley & Gioia, Third, the current research incrementally extends the international entrepreneurship research field (Corley & Gioia, Following Corley and Gioia , our finMoreover, the entrepreneurial decision-making model for accelerated internationalization presented in our research could prove very useful in entrepreneurial education, particularly as there is a strong demand across society to promote digital entrepreneurship, as evident, for instance, in universities being expected to produce more science-based entrepreneurs, but there being few initiatives to ensure those often inexperienced graduates can select the most viable path to follow in their internationalization.


Bradyrhizobium in natural populations. Studying rhizobia from the perspective of their mobile genetic elements, which have their own transmission modes and fitness interests, reveals novel mechanisms for the generation and maintenance of diversity in natural populations of these ecologically and economically important mutualisms.Despite decades of research, we are only just beginning to understand the forces maintaining variation in the nitrogen-fixing symbiosis between rhizobial bacteria and leguminous plants. In their recent work, Alexandra Weisberg and colleagues use genomics to document the breadth of mobile element diversity that carries the symbiosis genes of  We are witnessing a sea change in the way evolutionary biologists think and write about the mutualism between rhizobia and their legume hosts. While variation in these large and complex bacterial genomes and its impact on plant growth and fitness has been of interest for a long time, the “mobile genetic element’s (MGE)-eye view”  is makinBradyrhizobium genomes: symbiosis (sym) genes embedded within sym integrative and conjugative elements (symICEs), which in turn are embedded within Bradyrhizobium chromosomes. Importantly, sym genes can be shuffled across different ICE (or even plasmid!) backbones via recombination, while ICEs are transferred among Bradyrhizobium strains via excision and interbacterial conjugation. When in symbiosis, sym genes reside on and interact with these MGEs , which interact with bacterial chromosomes in the bacterial cell, all of which reside within the symbiotic nodules on plant roots, resulting in a series of nested interactions reminiscent of a Ukrainian nesting doll  to be evolving in a complex ensemble of nested genomic populations rather than in a vacuum: populations of MGEs evolve within the context of populations of bacterial chromosomes, whereby the population size, mutation rates, and even geographic structure of one population does not necessarily reflect the structure of the other  could infect the roots of other potential hosts, though only a single strain displayed a beneficial effect. This strain largely contained the core genes required for effective symbiosis but had a varied organization of the associated symbiosis MGEs compared to others of its subtype (–Finally, Weisberg’s MGE-eye’s view helps reveal how less-beneficial rhizobia on a focal plant species might be maintained in part through effective symbiosis with alternative host species. Although we often study this symbiosis as a pairwise interaction in experimental work, rhizobia and their legume hosts do not exist in a vacuum, devoid of other species and interactions in nature. Indeed, rhizobia exist in more complex microbial communities while in their soil-dwelling phase , includi subtype . Togethe subtype . Thus, u subtype –31, intrsubtype –, 33, andsubtype –, 34.As we continue to make sense of how legumes and rhizobia evolve in the context of diverse and complex natural ecosystems, a synthesis of the MGE-eye’s view across systems will be critical. Together with ecological genetic work focused on measuring natural selection and phenotypic variation as well as increasingly community-aware perspectives on evolution, this synthesis will move us toward a predictive understanding of how N-fixing symbiosis evolves in the wild and improve our ability to manage symbiotic outcomes toward conservation and sustainable agriculture goals.


Overall, the articles in this Research Topic highlight a spectrum of research encompassing the importance of pursuing work to explore new ways of treating multidrug resistant bacteria. Despite the availability of a range of antimicrobials, multidrug resistant (MDR) bacterial infections continue to have a significant impact, contributing to the burden on the public health sector of various countries . The disTangsawad et al. who reported the results of a retrospective review of the incidence of carbapenem resistant Enterobacterales in Siriraj Hospital, Bangkok, Thailand between January 2015 and December 2019. The data from this retrospective cohort study found 420 cases of CRE over this period of time, with 90.48% of these being carbapenem-resistant Klebsiella pneumoniae; 26.9% of the patients were critically ill with the median length of hospitalization being 31 days, and the all-cause in-hospital mortality rate was 68.33%. The median hospitalization cost per admission was US$10,435, giving a strong indication of the burden placed on society by multidrug resistant organisms and highlighting how important it is to begin to take concrete steps to address this problem.The burden of MDR organisms on the healthcare system in Thailand is clearly illustrated by Gomez et al. sought to decipher the role these pumps play in mediating resistance of the subsets of carbapenem resistant organisms which are also resistant to drug combinations used to target these organisms. They studied the role of these efflux systems on the baseline susceptibility to ceftazidime/avibactam (CZA) and ceftolozane/tazobactam (C/T) in clinical isolates of non-carbapenemase-producing carbapenem-resistant Pseudomonas aeruginosa and re-evaluated this in the presence of an RND pump inhibitor. Their conclusion was that RND efflux pumps do participate in baseline resistance to CZA and even more to C/T; however, the genomic diversity of the clinical isolates requires more in-depth analysis to determine the elements directly involved.One of the key virulence factors mediating antibiotic resistance in Gram-negative bacteria are resistance-nodulation-division (RND) multidrug efflux pumps . ContrerStaphylococcus aureus virulence inhibitor)  and ticagrelor  against Staphylococcus aureus in prosthetic joint infections (PJIs), which represents a significant clinical concern. Savirin is a low molecular weight, lipophilic, synthetic molecule, while ticagrelor is a P2Y12 platelet inhibitor. Their work was able to show that in an animal model of biofilm-related S. aureus PJI, both these substances, alone and also in combination with cefazolin, were able to reduce bacterial concentrations on implants compared with controls. Ticagrelor and savirin both also reduced bacterial dissemination to periprosthetic tissue. Savirin also downregulated several key biofilm related genes. These results clearly demonstrate the potential of these agents to be potentially viable adjuvants to conventional antibiotics to improve outcomes of prosthetic joint surgery.In two separate articles, Narayan Pant and his team explore the antibacterial and antibiofilm properties of savirin  against Klebsiella pneumoniae both in vitro and in vivo . Compound 666–15, was originally synthesized in an effort to create potent cyclic adenosine monophosphate response element-binding protein (CREB) inhibitors , a traditional Chinese medicine formulation, in treating pelvic inflammatory disease (PID) in a rat model . PID was induced using a bacterial suspension containing Staphylococcus aureus and Escherichia coli, and the results of the work demonstrated that KFXYs lowered the rectal temperature and white blood cell counts in acute illness as well as alleviating uterine inflammatory cell infiltration. The KFXYs also significantly improved the effectiveness of levofloxacin. KFXYs is believed to have mediated these effects through inhibition of NF-κB activation by decreasing phosphorylation of p65, demonstrating the potential value of exploring traditional remedies with modern methods.Exploration of traditional medications was carried out by Lv et al. propose a novel solution through the creation of their Antibiotic Combination DataBase (ACDB) which represents an easily explored resource of current information available about existing antibiotics, providing a means to simplify the process of predicting successful antibiotic combinations .Given the urgent need to discover new drugs and therapeutics that may provide us with a lifeline to treat these problematic organisms, and the fact that combinations of drugs may yield better results, a new problem for researchers can be trying to select the optimal combination of drugs to experiment with. In summary, this Research Topic has brought together a spectrum of research highlighting the importance of pursuing work to explore new ways of treating multidrug resistant bacteria; a crucial effort now given the increasing recognition of multidrug resistant organisms as an impending healthcare crisis, even having been highlighted as such by the WHO. The work highlighted here provides hope that there are as yet undiscovered mechanisms that may provide novel means to overcome these MDR organisms. Although a true solution to this will go beyond the laboratory, requiring input and effort in healthcare policy and patient education to reduce indiscriminate antibiotic usage, as well as improved prophylactic strategies, the ongoing research on a global scale is key to providing hope that we can overcome this crisis.


Chronic pelvic pain syndrome (CPPS) is a functional pain disorder characterized by ongoing pain in the apparent absence of clinically identifiable causes. The prevalence of functional pain disorders demonstrates the importance of adequate management of ongoing symptomatology, but due to the uncertain etiology and myriad patient presentation phenotypes, reliable treatment options are difficult to implement. New interventions involving non-pharmacological approaches to pain management have been investigated across a spectrum of clinical and pre-clinical studies. Given that conservative care such as exercise, counseling, and musculoskeletal therapy is widely recommended as first-line treatment for CPPS, an updated review of these and related methodologies are needed. Familiarizing physicians and the public with the newest evidence for complementary and alternative medicine (CAM) and other conservative care treatments will assist with the promotion of evidence-based practices in a safe and reliable manner. This review aimed to summarize the current evidence and proposed mechanisms for non-pharmacological treatment specific to CAM and management of chronic pelvic pain centered on neuromusculoskeletal focused intervention such as acupuncture, auriculotherapy, manipulation, manual therapy, myofascial release, and phototherapy. The discussion suggests that reported improvements in pelvic pain or related symptomatology may be attributed to changes in the peripheral inflammasome and somatic origins of peripheral sensitization. Robustness of the included clinical studies is discussed throughout the review, and attention is paid to delineating inclusion criteria of formally diagnosed CPPS compared to general pelvic or abdominal pain. Overall, this review consolidates the current state of evidence regarding the utilization of non-traditional interventions using CAM techniques for the management of chronic pelvic pain and recommends a future direction for the field. Chronic pelvic pain syndrome (CPPS) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are conditions acknowledged worldwide, affecting up to 16% of females and 10% of males, respectively . DespiteAs a diagnosis of exclusion and given the vast array of presentations and patient history, outcomes from the standard approaches to managing pain are quite variable. The most resistant cases are often emotionally, physically, and financially frustrating for the patient and the physician. Treatment options can deteriorate into a trial and error approach aiming to manage the most deleterious of symptoms that may never resolve. Therefore, investigating additional multi-modal approaches to treating CPPS is urgently needed. The National Institute of Health (NIH) defines complementary and alternative medicine (CAM) as the replacement or supplementation of conventional medicine with non-mainstream approaches . TypicalA major limitation of the treatment of CPPS is physician familiarity with this complex, multimodal disorder. In 2009, the results from a query of 289 primary care physicians showed a wide range of familiarity with CPPS . Among tThe purpose of this review was to summarize the CAM approach to the treatment and management of CPPS and include methods less frequently reviewed elsewhere. Each section describes a current snapshot of the clinical atmosphere surrounding the approach as well as a discussion on clinical or preclinical insight into proposed mechanisms underlying any demonstrable efficacy. We discuss the quality and scope of evidence-based studies and the areas of continued. Ultimately, the review updates the current state of knowledge related to clinical relevance, proposed mechanisms, and discussion pertinent to the management of this difficult condition.MethodsThe online biomedical journal databases PubMed and EBSCOhost were queried between April 1, 2021, and August 1, 2021. Searches were carried out using the following combinations of keywords and Boolean operators : ({chronic pelvic pain syndrome} OR {CPPS} OR {chronic prostatitis chronic pelvic pain syndrome} OR {CP/CPPS} OR {pelvic pain}) AND . Results were indexed and duplicates were removed. Articles were reviewed if the full text was available in English. Otherwise, non-English articles were evaluated if there was an English-available abstract containing sufficient information. Any non-English full-text publications referenced in the final review are denoted as such. Only human studies designed in the prospective, retrospective, or randomized clinical trials were included. Case studies were excluded. Records were grouped according to the type of intervention and analyzed for inclusion criteria, number of subjects enrolled, and outcome measurements and presented in the following narrative review.Manipulative therapyIn 1989, Browning published a study that demonstrated improvement in low back pain among six patients that met the criteria for a generic pelvic pain disorder following sacral nerve root decompression . This stOsteopathic manipulative therapy (OMT) focusing on pelvic girdle biomechanics, abnormal tension and somatic dysfunction at the pubic symphysis has been suggested as a potential intervention for CPPS . A cliniMyofascial releaseAnother key area where manipulative therapy providers receive training is advanced anatomical understanding of the human body and the ability to palpate impaired or altered muscular, fascial, skeletal, or lymphatic mechanics. These altered systems are commonly referred to as somatic dysfunctions and arise due to homeostatic imbalances . SomaticManual therapy targeting myofascial trigger points in the pelvic floor for interstitial cystitis and urgency frequency syndrome, which are common components of CPPS showed promising results . The stuThese findings suggest some degree of pelvic peripheral sensitization and the neuromodulation therapies that seek to diagnose and ultimately treat these changes have been consolidated into a field of study preliminarily termed neuropelveology, a discipline seeking to gain traction among mainstream pain researchers and clinicians . While tA multimodal musculoskeletal approach to treating general pelvic floor dysfunction, including internal myofascial release, physical therapy, biofeedback, and strengthening exercises improved urinary and pain symptoms among males with CPPS . SimilarElectromyography biofeedback and electromagnetic therapyBiofeedback that incorporates electromyography (EMG) instrumentation is a neuromodulation technique that combines two concepts. The first is biofeedback, which educates the patient about their condition for the purposes of increasing self-awareness and control. The second concept is the visual or audible mapping of neuromuscular electrical activity. Upon interpretation by a skilled practitioner, the electrical activity is scored and analyzed for proper levels similar to the interpretation of any electrophysiological technique. Dysfunction may be due to pathological firing patterns, but the most common finding is quantified signal intensity reflecting a presumed level of hyper- or hypotonic muscle tension . Then thThe utilization of EMG techniques to improve outcomes related to musculoskeletal pain is a logical treatment modality. Less commonly known, EMG biofeedback training has also been used for pelvic floor rehabilitation particularly targeting dysfunction in the pelvic diaphragm, levator ani, pubococcygeus, puborectalis, iliococcygeus, and the obturator internus muscle . For theThe therapeutic effect by which EMG biofeedback exerts beneficial benefit is not known, but three mechanisms may be derived from the literature on sacral nerve stimulation for the treatment of urinary symptoms associated with pelvic pain . They inPhotobiomodulation therapyLow-level laser therapy (LLLT), also known as cold laser and photobiomodulation therapy, is a light source treatment that is thought to act via photochemical or non-thermal reactions in mammalian cells. Cold laser therapy differentiates itself from hot lasers by its power output. Hot lasers have power output above 500 milliwatts whereas cold lasers have a power output at or below 500 milliwatts . Cold laExtracorporeal shock wave therapy (ESWT) is distinct subtype of low-level phototherapy that utilizes many of the same principles through the introduction of a pressure wave of short duration (approximately 10 μs) at a frequency of 16-20 MHz . The lowHuman studies of CPPS patients have demonstrated improved quality of life, pain reports, and urinary symptoms following ESWT therapy. Two recent meta-analyses ,58 have Acupuncture Acupuncture is thought to have originated in China around approximately 2500 BC. Not surprisingly, the therapeutic mechanism of acupuncture was heavily influenced by culture during that era . AcupuncEvidence continues to emerge that acupuncture would be effective for chronic pelvic pain in both males and females. A study in 2015 with 100 patients using a "sham acupuncture" comparison group concluded that the real acupuncture treatment reduced symptoms in males with chronic prostatitis . This stAcupuncture has been shown to alleviate pregnancy-related and endometriosis-related pelvic pain, but specific studies evaluating acupuncture intervention for females with CPPS are lacking ,69. A meBattlefield acupunctureBattlefield acupuncture (BFA), a type of auriculotherapy, is a protocol used in the military for rapid pain relief . DespiteTwo clinical trials suggest that auriculotherapy has a potential benefit for patients with chronic pelvic pain. The first comes from a pediatric gastroenterology practice featuring a randomized clinical trial of adolescent population of patients with functional gastrointestinal disorders lacking a known organic cause. This study demonstrated high levels of tolerance to the therapy and significant decreases in abdominal pain scores following three weeks of treatment. The decreased report of painful events persisted for an extended time period after the treatment concluded . Second,An overview of articles included in the review is reported in Table Mechanistic themes with relevant clinical examples that summarize the neuromusculoskeletal approaches in relation to complementary and alternative medicine are shown in Figure Adding to the complexity of CPPS is the inclusion of an array of comorbid pain conditions affecting non-pelvic organs. Chronic pain conditions are often comorbid and treating one may or may not improve the symptoms associated with another. First-line treatment of CPPS is the administration of non-steroidal anti-inflammatory drugs and muscle relaxants, but for the complex case, these initial approaches provide inadequate relief. Subsequent management is based on the dominant symptom if one can be identified. For the non-specific or multimodal complaint, neuromodulators may be prescribed in a trial and error fashion that is thought to target an unknown neurotransmitter “imbalance.” Anticonvulsants, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors have shown some benefit for CPPS patients, but there is a wide variation of individual pain responses to these medications. The focus of this paper was to review a variety of neuromusculoskeletal complementary and alternative interventions for the management of CPPS.Pain management specialists working with treatment-resistant cases of CPPS may consider implementing an alternative treatment either as a stand-alone therapy or in combination with traditional pharmacological options. As many of the complementary and alternative interventions described in this review reported well-tolerability and minimal deleterious effects, their implementation into the overall management plan should at least be taken into consideration. There are some clinical trials or preclinical studies that demonstrate at least minimal benefit to many of the described approaches in this review. However, there will consistently remain a group of patients who are minimally or fully unresponsive to a given intervention. This is likely due to the wide variety of underlying pathologies contributing to likely disparate disorders that are manifesting in a constellation of patient presentation experiences ultimately diagnosed as CPPS. The next era of this research should consider clinical or preclinical trials that combine traditional pharmacological treatments with additional integrated interventions, such as studying anti-inflammatories along with acupuncture, biofeedback techniques that incorporate electromyography instrumentation, and physical therapy, or antidepressants in combination with cognitive behavioral therapy or supplement management and exercise. Bidirectional research needs to take place that combines multimodal approaches to management and simultaneously categorize the CPPS phenotypes either through biomarkers, genetic factors, and relevant histories or triggers. This sort of personalized medicine will someday efficiently connect patients with the combination of interventions that may be best poised to help them.


Piglet facial and sow teat lesions are the main reported reasons why pig producers routinely practice teeth resection. This is a painful procedure performed on piglets, where their needle teeth are clipped or ground to resect the pointed tip. The practice raises welfare concerns. In contrast to other procedures, such as tail docking, we know little about the risk factors for these two types of lesions.We employed two methods to answer these questions: (1) reviewing the literature to identify potential risk factors, and (2) surveying pig production stakeholders worldwide to identify the occurrence of these lesions and the strategies used in practice that enable pig producers to manage or prevent these lesions while avoiding teeth resection. For the literature review, we used Google Scholar to include peer-reviewed publications and gray literature. We distributed the survey using convenience sampling and documented information on the current situation regarding teeth resection, including the methods, frequencies, and reasons for resecting piglets' teeth, the occurrence of piglet facial and sow teat lesions, and measures used to prevent and control these lesions.The literature review identified six major risk factors for both lesions, including the presence or absence of teeth resection, housing system, litter size, piglet management, environmental enrichment, milk production and other piglet management practices. However, most studies focused on the effects of the first two factors with very few studies investigating the other risk factors. There were 75 responses to the survey from 17 countries. The survey showed that half of the respondents practiced teeth resection with many recognizing that facial and teat lesions are the main reasons behind this practice. However, many producers used other interventions rather than teeth resection to prevent these lesions. These interventions focused on improving milk production of the sow, managing large litters, and providing environmental enrichment.More research is needed to validate these interventions and more science-based advice is needed to bridge the gap between research and practice to help more producers further understand the cause of piglet facial and sow teat lesions to transition toward the cessation of routine teeth resection. Piglets are born with eight fully erupted needle teeth . At birth, the needle teeth are orientated outwards  and lateDuring the fights and displacements that occur to establish the teat order, piglets can inflict injuries to the faces of litter mates with their needle teeth . PigletsAs well as injuries to littermates, competition for access to milk can lead to injuries to sows' teats although these can also be caused by external factors such as sharp edges in the environment . AlthougIn some commercial pig production systems, piglets' needle teeth are resected (reduced) to minimize facial lesions in piglets and teat lesions in sows. The two main methods to resect needle teeth are clipping and grinding . ClippinWe need a better understanding on the current scientific evidence on the risk factors behind piglet facial and sow teat lesions, information on the occurrence of these lesions, and the proportion of producers and other relevant stakeholders that carry out teeth resection or that use alternative methods to minimize these lesions. This is important to promote better practices and to improve pig welfare globally. Therefore, the first aim of this paper was to review the literature on the risk factors for both piglet facial and sow teat lesions, identifying possible knowledge gaps. Secondly, we collected information on the occurrence of these issues, their perceived causes and the practice of teeth resection as conducted on commercial farms by surveying pig producers and other relevant stakeholders through an online global survey. Finally, we highlighted practical alternatives to teeth resection to support management to prevent piglet facial and sow teat lesions and provided suggestions for future research on under-researched risk factors.A literature search was conducted using Google Scholar, assisted by Web of Science to cover both peer-reviewed and non-peer-reviewed gray literature. The search terms used for piglet facial lesions were: (sows OR pigs OR swine OR piglets),  (lesions OR injuries OR damage OR laceration OR wound OR abrasion) in addition to each of the risk factors. Similarly, for sow teat lesions the search terms used were (sows OR pigs OR swine), (teat OR udder), (lesions OR injuries OR damage OR laceration OR wound OR abrasion) with each risk factor. A detailed list of search terms used is available in We screened relevant literature for inclusion manually. The inclusion criteria for peer-reviewed literature were (i) either piglet facial or sow teat lesions should be included as the outcome measure, or (ii) the risk factors of either piglet facial or sow teat lesions should be discussed. For gray literature, the topic should be on observational or anecdotal description of possible risk factors causing lesions to piglets' faces or sows' teats.The risk factors were categorized into six sections for both lesions: (a) presence or absence of teeth resection, (b) housing system, (c) litter size, (d) piglet management, (e) lack of environmental enrichment, (f) milk production and other miscellaneous risk factors.An online piglet teeth reduction survey was designed in Google Forms with versions in English, Dutch, French, German, Italian, Portuguese and Spanish, and a version in Chinese was created using the online platform WJX. The survey included 20 questions in five sections . All respondents were involved in pig farm management at some stage during the production chain.Convenience sampling was used to reach as many potential respondents as possible without any specific inclusion criteria. A link to the survey was shared on social media  and sent to colleagues P < 0.05 and tendencies discussed (P < 0.1).The survey responses to the French, German, Italian, Portuguese, Spanish, and Chinese versions were transferred into the English version of the survey in Google forms for data analysis in English. Responses were then downloaded from Google Forms into Excel and imported to R (version 4.0.5) for analysis . All sumn = 75).Correlations between the reported severity of piglet facial lesions with sow teat lesions were analyzed using Spearman's rank correlation (using the “spearman.test” function). Chi-square tests were used to analyse the use of enrichment, litter size, farrowing system and flooring, as well as the responses to why teeth reduction is practiced, the reported reasons for facial and teat lesions and the measures used to resolve the lesions by whether or not teeth reduction was practiced. The frequencies were cross-tabulated and analyzed using a homogeneity test for contingency tables (chi-square tests implemented in the chisq.test function in the “stats” package). Multiple answers were allowed for responses on why teeth reduction is practiced, the reported reasons for facial and teat lesions and the measures used to resolve the lesions and therefore the sample size in the Chi-square model can be larger than the number of respondents  Sow farrowing management training topics: learning about sow farrowing behavior; checking sow more regularly before farrowing; assisting farrowing; counting number of teats; feed/nutrition adjustment; checking water flowrate or consumption; and checking sow milk productionvia milk cups or similar)ii) Types of piglet management strategies used: cross-fostering; split suckling; use of nurse sows; artificial rearing ; milk supplementation (iii) The main reported reasons for the occurrence of face and teat lesions: piglets' teeth are clipped or ground; piglets' teeth are NOT clipped or ground; large litter size; using conventional farrowing crates; using free farrowing pens; outdoor farrowing; flooring in the farrowing accommodation; poor milk production of sows; not enough cross-fostering; too much cross-fostering; lack of environmental enrichment/nesting materialiv) The measures tried to resolve facial and teat lesions: only used teeth reduction; avoid large litter size ; select for sows with good mother traits; improve sow nutrition at farrowing; check on sows more frequently; increase sow water intake; provide early supplementary piglet nutrition; frequent cross-fostering; split suckling; use nurse sows; artificial rearing; provide nesting material/enrichment in the farrowing crate/pen)v) The measures reported to have worked to resolve the lesions (same options as previous)P-values were corrected for multiple testing using the Bonferroni correction.These new numeric variables were analyzed for differences between those who practice teeth reduction or not and by the reported severity of facial and teat lesions using non-parametric tests for group differences . Finally, the non-parametric Kruskal Wallis test  was conducted with the reported severity of piglet facial and sow teat lesions as the dependent variables with the following as explanatory variables: litter size, farrowing system, floor type and material, the use of enrichment, farm size and whether or not teeth reduction is practiced. In total, 51 articles matched the search criteria . The majority of research focussed on the effects of the presence or absence of teeth resection, different methods of teeth resection, followed by the housing systems  . Some stn = 48) of respondents were based in Europe, 66.7% (n = 50) were male, 38.7% (n = 29) were farm owners and 48.0% (n = 36) worked on medium-sized farms (100–999 sows). Of note, while attempts were made to engage pig industry participants from across the globe, two large segments of world pig production  are not proportionately represented; therefore, the authors acknowledge that findings may not be indicative of production characteristics and efficacy of strategies outside of the countries more heavily represented.Seventy-five respondents from 17 countries answered the survey providing valid responses. Although somewhat limited in the total quantity of responses, detailed demographics of the respondents including respondents' country, age, gender and role on the farm, and the farm size are provided in s) = 0.727, P < 0.001; Respondents were asked to indicate the severity of piglet facial and sow teat lesions on their farms . More thThe main reasons reported for the occurrence of piglet facial lesions, sow teat lesions or both lesion types are shown in When asked what intervention measures were tried to solve the issues of piglet facial and sow teat lesions, as well as whether the measures worked or not, respondents showed a range of responses .A more detailed breakdown of the survey results will be presented hereafter in accordance with each risk factor.Teeth resection was the subject of most of the retrieved scientific studies related to the occurrence of piglet facial lesions. As early as 1975, Fraser , only a small percentage of facial lesions was reported . TherefoAlthough teeth resection can decrease the risk of piglet facial lesions, it is worth noting that the procedure itself can cause significant lesions in the piglets' mouth and on their teeth , 29. It In gray literature, a consensus continues to exist in the veterinary and producer advisory circles that teeth clipping should be practiced in order to reduce lacerations on piglets' faces , 31–33 aFu et al.  recordedBy contrast, a Swedish study showed that either clipping or grinding piglets' needle teeth increased the risk of mastitis in sows, which could be due to bacteria introduced by infection in the pulp cavity following teeth resection procedures , althougSimilar to piglet facial lesions, the advisory resources to producers from gray literature commonly recognized that teat lesions can be prevented by resecting piglets' teeth , 32, 36,ad-hoc whenever they see a problem occurring. Thirteen (35.1%) individuals reported performing the procedure on all litters and all piglets, fourteen (37.8%) reported reducing the teeth of all litters but avoiding the small piglets, five (13.5%) reduced the teeth of most litters and all piglets within a litter, and a small number  reported resection on most litters but avoiding small piglets. Two (5.4%) respondents occasionally perform teeth reduction when they see a problem.Contrary to the focus found in the literature, just over half  of the respondents indicated that they did not practice teeth reduction on their farm, and just under half  practiced the procedure. For those performing teeth reduction, the majority only used grinding , while some used clipping  and two respondents reported using both methods (5.4%). Almost all performed the procedure within 48 h after piglets were born , while five performed it between piglets' age of daya 3–7 and one did it P < 0.001) between those who practice teeth reduction and those who do not, as fewer respondents who practice teeth reduction never saw piglet facial lesions, whereas more respondents who practice teeth reduction reported that they needed to adjust management practices to keep lesions manageable , was proven by research” and “Dramatic increase in Greasy Pig disease especially in gilt litters”. Including only the main options (not the “other” options) for why the procedure is performed, there was no difference between the reasons reported by those who practice or do not practice teeth reduction.The reported reasons why respondents practice or used to practice teeth reduction, or their opinion on why this procedure is performed, are shown in Similarly, there was no difference in the respondents' opinions about the causes of piglet facial and sow teat lesions between those who practice teeth reduction and those who do not. However, those who do not practice teeth reduction considered “large litters” as the top cause, whereas those who practice teeth reduction considered “teeth not reduced” as the main cause of the lesions . The repThe total number of answers selected by respondents for  trainingIn summary, the literature review indicated a positive effect of teeth resection to control piglet facial and sow teat lesions, although some studies found the difference in lesions was most apparent in the initial days during suckling. The gray literature almost unanimously indicates that teeth resection is the necessary procedure to prevent piglet facial and sow teat lesions. The survey showed that only about half of the respondents use teeth reduction to control these lesions. The respondents that do resect piglets' needle teeth considered the issues of lesions more severe. They consider them only controllable by teeth reduction, which is why they were still practicing it, but this is only numerically different.The risk factors for piglet facial lesions and sow teat lesions associated with housing system include farrowing system and flooring. These factors can be the direct cause of such injuries or may indirectly influence teat order fights of piglets.There are indications of an effect of the suckling environment on piglet facial lesions . In a stCompared to literature on piglet facial lesions, there are more studies that examined the impacts of housing on sow teat and udder injuries and there appears to be consensus that systems with increased space or freedom of movement for the sow, offer protective effects. This is presumably by enabling the sow to protect her udder from unwanted attention from her piglets. Sows housed in conventional crates compared with crates that open  or indiv2 and found that sows in the two smaller pen sizes showed significantly more lesions on udder and teats than sows in the largest pen size. Studies comparing single pen lactation with group lactation  found fewer teat and udder lesions in the group housed sows  and flooring type  as more of those with alternative farrowing systems never see these lesions or reported they were manageable without changing management practices (The farrowing system and flooring used on the farms of the survey respondents is shown in ractices .Some respondents reported flooring as a reason for the presence of sow teat (14.7%) and piglet facial (8%) lesions, and a few reported using specific farrowing systems as a reason, with crates  reported more often than free farrowing pens  and outdoor farrowing  . AlthougIn summary, literature shows that farrowing systems which give sows more freedom of movement and more space may reduce the risk of sow teat lesions, as sows have more control over nursing, whereas the effect of flooring material is less clear. In accordance with the literature review, the survey also showed that the issue of lesions was less severe on farms not using conventional farrowing crates, and numerically fewer respondents reported practising teeth reduction in alternative farrowing systems.The teat order is established as soon as possible after birth. As failure to secure a teat may result in the unsuccessful piglets potentially starving to death, competition for teat access occurs even if the number of functional teats is sufficient for all littermates . In largSome studies show that litter size influences the number and severity of teat wounds in sows. The risk of having at least one teat wound and the number of teat wounds per sow increased significantly with an increase in litter size at weaning . This waThe average litter size  in the responding farms is shown in When asked to select the reasons for the occurrence of piglet face and sow teat lesions, “large litters” was the third most selected option, after “teeth not being reduced” and “poor milk production”, as 46.7 and 38.7% selected this option for piglet facial and sow teat lesions, respectively . For thoThirty-four respondents reported “avoiding large litters (keep litter size at around/below 12–13 piglets)” as a measure that they employed to tackle problems with piglet face and sow teat lesions . Of thosIn summary, there is some evidence that large litter sizes increase the incidence of fighting to establish teat order and also the risk for piglet facial lesions. Additionally, sows with larger litters have more teat wounds, which can negatively affect sow welfare due to acute or chronic mastitis. This agrees with the survey results, with many respondents acknowledging large litters as a risk factor for these lesions and one of the top-rated measures taken to alleviate these issues, especially for those who do not practise teeth reduction.Cross-fostering was traditionally performed to improve the survivability chances of low-birth-weight piglets  but is iNurse sow strategies are also applied to manage large litters. A nurse sow is a lactating sow given younger foster piglets, when her own piglets are transferred to another sow or weaned. Two main types of strategies are used ; the nurEarly socialisation can be achieved by exposing piglets to unfamiliar piglets in other litters between conventional farrowing crates while still suckling their dam . This isSchmitt et al.  found a Similar to the results on piglet facial lesions, Camerlink et al.  found thRespondents reported that they use or have used several management strategies on suckling piglets. The most common were the use of cross-fostering , nurse sows , split suckling  and milk supplementation . Fewer respondents reported using artificial rearing  and some reported using none of the listed management strategies . The use of piglet management strategies did not differ by whether or not teeth reduction was used (data not shown).When asked to select the reasons for the occurrence of piglet facial and sow teat lesions, too much cross-fostering , and low cross-fostering  were both selected by more respondents for piglet facial lesions than sow teat lesions.The measures related to management strategies reported to solve the issue of piglet facial and sow teat lesions included early piglet nutrition , using nurse sows , split suckling , frequent cross-fostering  and artificial rearing  .In summary, most literature studies reviewed showed that cross-fostering increased piglet facial lesions but were less conclusive for facial lesions across nurse sow strategies presented in the literature. Early socialisation is beneficial for piglets to reduce aggression and stress later on but may increase the risk of piglet facial and sow teat lesions. The survey respondents indicated many management strategies to help alleviate these lesions, especially the provision of early piglet nutrition supplementation and cross-fostering, but also expressed ambivalence in terms of how much cross-fostering would be beneficial.via the sow and the farrowing system, as well as how the sow is managed (see sections Risk factor 2: Housing system and Risk factor 4: Piglet management).The literature on how environmental enrichment influences piglet facial or sow teat lesions is sparse. Most relevant studies reported on the possible indirect influences, e.g., Very few studies focussed on effects of varying the piglets' environment on facial or teat lesions. Early work  found thBuilding on these findings, Lewis et al.  evaluateThe respondents' use of nesting materials and environmental enrichment is reported in Several respondents perceived the lack of enrichment as a reason for the presence of piglet face (28.0%) and sow teat (17.3%) lesions, which was the fourth highest reason reported, after teeth not being reduced, poor milk production and larger litters . Thirty-In summary, early work found a benefit of providing piglets with opportunities to chew so that they did not redirect this behaviour to littermates or the sow; however, this does not appear to be studied (or reported) in later investigations on piglet facial and sow teat lesions. Interestingly, several survey respondents applied the use of enrichment to manage these lesions and that several of those reported that this works. This warrants further exploration also with a view to provide adequate environmental enrichment for pigs, which is essential to improve their welfare in general .Anecdotal evidence suggests that poor milk production causes hungry and distressed piglets to fight for access to a teat and thereby potentially causes not only facial lesions but also injuries to the sows' teats. The vocalisations of the fighting piglets further disturb the sows, causing them to lie on their bellies or to dog sit  and ther“Poor milk production” was almost equally reported as the top reason for the presence of piglet facial and sow teat lesions , with reported percentages nearly equal to those that reported “teeth not reduced” . However, when asked the rationale for teeth reduction, only six respondents 8.0%,  selectedIn terms of the training of staff on farrowing management, respondents selected a median of 5  training topics. The frequency of the training options selected is shown in In summary, poor milk production was recognized as an important risk factor behind piglet facial and sow teat lesions by the respondents who expressed the necessity to monitor and maintain sow milk production to prevent the lesions. However, we could not find scientific literature on this subject, and only few studies indirectly showed evidence that milk supplementation for piglets could reduce piglet facial lesions.Poor health in sows and their piglets affects sow teat and piglet facial lesions through several indirect routes such as those relating to milk production outlined in section Risk factor 6: Milk production. However, pathogens may directly cause piglet facial and sow teat lesions. Swinepox Virus (SWPV) is a pathogen that can cause cutaneous lesions on the piglets' face and also on sows' teats , 72. OthBased on the survey results, the reported severity of piglet face and sow teat lesions did not differ with farm size (data not shown).This paper presented the findings of a literature review on the risk factors for piglet facial and sow teat lesions, the two conventional rationales for routine teeth resection in piglets. We integrated these findings with those of the first global online survey on piglet teeth reduction practices in which we collected information on lesion occurrence and the risk factors considered important by pig producers and other relevant stakeholders.Six main risk factors were identified in the literature, namely teeth resection and housing (farrowing system and flooring), along with litter size, piglet management , environmental enrichment and milk production. Most studies found a protective effect of teeth resection to reduce piglet facial lesions but some reported minor and transient effects. The effect of teeth resection on sow teat lesions was less evident. Housing sows in farrowing crates appears to increase the risk of these lesions, so does a large litter size. Some studies looked at the effect of piglet management strategies, but the scarce literature showed inconsistent results. Milk supplementation for piglets can reduce their facial lesions, but our literature review did not find other studies investigating the link between milk production and lesions. Even fewer studies examined the effects of providing environmental enrichment on the lesions.The survey results showed that half of the respondents practise teeth resection to manage piglet facial lesions and sow teat lesions. When asked about the main reasons for the occurrence of these lesions, leaving piglet teeth intact was closely followed by poor milk production, large litter sizes and a lack of environmental enrichment. In addition, many respondents mentioned other reasons for the occurrence of piglet facial and sow teat lesions, including some of the risk factors mentioned in the literature: management strategies used to manage large litters (cross-fostering: too much or too little) and features of the environment (flooring and farrowing system). These were also indicated as measures that were tried by the respondents to manage these lesions. The responses suggest that there is a gap between the current scientific evidence on the risk factors for piglet facial and sow teat lesions and the practical knowledge of those working in pig farming, who are aware of different risk factors other than those associated with piglets' intact teeth.Most studies to date investigated the effect of teeth resection or different methods of teeth resection on piglet facial and sow teat lesions. The survey results also showed that leaving piglets with intact teeth was identified as one of the main causes of these lesions, and such lesions, in turn, were the main justification for practicing teeth resection. As these lesions are the collateral damage during fighting for access to teats, it is understandable that resecting piglets' teeth can have a preventive effect when piglets' natural defences are made less damaging.However, the survey results also showed a tendency that when teeth resection is practised, other potentially effective measures  that could help manage these lesions may be more likely either not used or not considered useful. It is possible that producers tried all other measures to control these lesions but to no avail and decided to resect piglets' teeth as a last resort, which would be in the spirit of the EU legislation. More likely, is that teeth resection became habitual thereby discouraging efforts to try alternative means of addressing the roots of the problem. Many respondents stated that the reason for practising teeth resection was that it had become a “standard procedure”. There is an analogy with tail docking, which is routinely carried out to prevent tail biting, whereas tail docking only masks the underlying issues that cause pigs to tail bite : the rouPiglets struggled more during teeth resection compared to those undergoing sham-processes, and some studies found that piglets performed more oral behaviours and spent less time playing and fighting after the procedure [as reviewed by ]. There Most survey respondents used farrowing crates and of those who practised teeth reduction, more were using farrowing crates than alternative farrowing systems . The literature showed that both piglet facial and sow teat lesions were more frequent in crates than in pens, which may explain why a higher proportion of those producers using crates may see this as a problem and may practise teeth reduction. Alternatively, producers using alternative systems may be more likely to practise higher welfare husbandry and not carry out what they see as unnecessary painful procedures. Worker safety may also be a factor, with the caretaker at higher risk of injury from maternally protective sows in open farrowing systems when attempting to carry out piglet processing procedures .per se impacts piglet facial lesions, but there is some evidence that solid flooring can have a beneficial impact on sow teat lesions, if it is straw-bedded. Where solid and partly slatted floors are used, the producers may have the option to use straw, which serves the needs of the sow for nest building and provides an outlet for chewing needs of the piglets , and we asked for explicit consent before respondents could continue to the survey stating, you agree that you're at least 18 years of age and the information you provided will be used for research purposes only.The survey was distributed by J-YC, EN, TH, HW, LB, and SI. All authors contributed to the conceptualisation, writing, reading and approval of the final manuscript.This project was an output from the 3Ts Alliance, which is a non-profit voluntary stakeholder group. The publication fee was funded by World Animal Protection.HW was employed by Cerebrus Associates Ltd. SI was employed by World Animal Protection International. 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