Cannabis sativa (Cannabis) is one of the world’s most well-known, yet maligned plant species. However, significant recent research is starting to unveil the potential of Cannabis to produce secondary compounds that may offer a suite of medical benefits, elevating this unique plant species from its illicit narcotic status into a genuine biopharmaceutical. This review summarises the lengthy history of Cannabis and details the molecular pathways that underpin the production of key secondary metabolites that may confer medical efficacy. We also provide an up-to-date summary of the molecular targets and potential of the relatively unknown minor compounds offered by the Cannabis plant. Furthermore, we detail the recent advances in plant science, as well as synthetic biology, and the pharmacology surrounding Cannabis. Given the relative infancy of Cannabis research, we go on to highlight the parallels to previous research conducted in another medically relevant and versatile plant, Papaver somniferum (opium poppy), as an indicator of the possible future direction of Cannabis plant biology. Overall, this review highlights the future directions of cannabis research outside of the medical biology aspects of its well-characterised constituents and explores additional avenues for the potential improvement of the medical potential of the Cannabis plant. Cannabis sativa (Cannabis) is arguably one of the world’s most versatile crops. While the genetic origin and evolution of Cannabis is a long-standing and heavily debated topic - to [R]-reticuline) locus led to the development of high noscapine Papaver varieties with a non-functioning cytochrome P450-oxidoreductase fusion protein, inhibiting the [S]-reticuline conversion to [R]-reticuline necessary for completion of the morphinan pathway [Papaver [Papaver beyond narcotics, varieties with high food value have been established through EMS and gamma ray mutagenesis breeding programs to produce increased seed yield (5.66 g/capsule versus the 3.39 g/capsule of control plants) with elevated levels of unsaturated seed oil and no narcotic production [Papaver varieties, the long-standing and successful development of Papaver varieties with superior phenotypic and/or chemotypic traits of interest certainly provides a reference for guiding Cannabis research strategies, which at present are comparatively in their infancy. Development of varieties producing high levels of alkaloid biosynthetic pathway intermediates is a promising indicator for the potential production of Cannabis varieties that reliably produce high levels of minor cannabinoids or intermediates in the cannabinoid biosynthesis pathway.Given the multitude of efficacious compounds produced by morphine . Similarubstrate ,482,483. Papaver . Generatectively . The ide pathway ,487,488. pathway . An RNA [Papaver . In the oduction . While tCannabis research field. Emerging research has begun to reveal the pharmacology and molecular targets of the minor cannabinoids. Due to the wide spectrum of molecular effects involved with cannabinoid consumption, it is clear that there are a range of medical ailments that could be addressed through endocannabinoid augmentation using secondary metabolites of Cannabis. Here, we have illustrated that via the utilisation of specific minor cannabinoids, which share some, but not all targets of THC and CBD, the medical reach of cannabinoid-containing pharmaceuticals could potentially be broadened. However, there are many challenges that currently impede this possibility, even outside of the international legal environment. Firstly, there is further room for significant characterisation of minor cannabinoid pharmacology, and currently, disease-orientated preclinical and clinical trials are lacking. Critically, techniques for producing cannabinoid isolates—even CBD and THC—are still in their infancy, and this remains a clear barrier to large-scale commercialisation of pharmaceutical cannabinoids. Here, we have reviewed the currently available literature which covers the processes involved in the biosynthesis of cannabinoids, as well as the techniques involved in the production of novel Cannabis chemotypes, including methods of improving yield that might be adopted from historically similar cases, such as the opioid industry. Based on this historical example, and the existing literature, it is likely that a molecular genetic modification approach will be applied to Cannabis to generate new opportunities for the improved yield of specific minor and major cannabinoids in the near future. In conclusion, there are multiple enticing and potentially profitable opportunities for commercial and academic growth in the Cannabis market outside of THC and CBD, and here, we highlight some of the most important current perspectives of this growing industry.In summary, we have reviewed the current literature of several important aspects of cannabinoid research outside of THC and CBD, which dominate discussion in the


Parkinson's disease (PD) management requires the involvement of movement disorders experts, other medical specialists, and allied health professionals. Traditionally, multispecialty care has been implemented in the form of a multidisciplinary center, with an inconsistent clinical benefit and health economic impact. With the current capabilities of digital technologies, multispecialty care can be reshaped to reach a broader community of people with PD in their home and community. Digital technologies have the potential to connect patients with the care team beyond the traditional sparse clinical visit, fostering care continuity and accessibility. For example, video conferencing systems can enable the remote delivery of multispecialty care. With big data analyses, wearable and non-wearable technologies using artificial intelligence can enable the remote assessment of patients' conditions in their natural home environment, promoting a more comprehensive clinical evaluation and empowering patients to monitor their disease. These advances have been defined as technology-enabled care (TEC). We present examples of TEC under development and describe the potential challenges to achieve a full integration of technology to address complex care needs in PD. Parkinson's disease (PD) is a neurodegenerative disorder with motor and non-motor clinical manifestations (NMS) that dictate the accrual of loss of autonomy and increasing complexity of care. The increase in life expectancy and expected doubling of PD prevalence in coming years  further The organization of healthcare teams dedicated to care delivery for people living with PD (PwP) is an active research field. The vast majority of system-based approaches consist of care delivery models centered in a PD tertiary center either in the form of an all-in-one multidisciplinary clinic or as a hub of a care network articulated with regional healthcare centers.The use of technology in PD has gathered great interest. The potential to generate a more continuous and remote health monitoring and the enhancement of patient care communication are bound to deliver a revolution in PD care.In this review, we first introduce concepts and state-of-the-art knowledge about the use of technology in PD evaluation, the approaches to multidisciplinary care, and the concept of technology-enabled care (TEC). We provide real-world scenarios on how these three concepts can be implemented jointly in a digital revolution for care today and in the future.In the last decades, there has been a growing interest in improving health-related outcomes using technology. In PD, technology-based solutions have been developed mainly with the aim of generating an accurate, objective, and reproducible measurement of motor function. Novel sensor-based and wearable technologies enable a shift of the evaluation of PD from the traditional clinical examination and clinical scales to one based on more objective health monitoring of daily function in an everyday-life naturalistic environment. For example, the detailed analyses of movement patterns in the home are expected to provide greater insight on patients' clinical status and their response to treatment.The most relevant new technologies supporting this paradigm change are inertial measurement units (IMUs). Most IMUs have a triaxial accelerometer and gyroscope, although a magnetometer is frequently included. IMU-based devices are based on the same general principles: (a) preprocessing of the signal generated by the IMU, (b) extraction of the essential characteristics of the movement signal, and (c) creation of a summary variable of the pattern of movement . Other eIMUs have been embedded in devices worn by the patient  in the clinic and, for remote monitoring, in the home setting. As such, wearable technology may more realistically portray motor function for clinical and research purposes. Currently, technologies developed for the management and treatment of PwP have enabled measurement of variations in movement parameters, such as frequency and amplitude that have moderate to high agreement with traditional motor standards such as the Movement Disorders Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) , 4. ThesUltimately, the development of sensor-based and wearable technologies and the growing internet-enabled access to information and mass data storage would facilitate the integration of these technologies in a multisensor/multidomain healthcare framework that we describe below (see the Technology-Enabled Care section).Currently, allied health interventions are carried out most commonly in isolation, with insufficient collaboration and communication with other disciplines involved in PD care , 7. The Technology can play a significant role in care delivery in PD as it is designed to increase the engagement of people in their healthcare and foster self-management in a highly personalized way. The term TEC has been adopted to express the transformative potential of different technological solutions such as telemedicine, online coaching, and self-care apps for care. TEC aims to cover the following goals in the PD care paradigm: (i) assess and measure a wide range of symptoms to capture subtle changes at the prodromal stage and document clinical progression, (ii) support therapeutic choices especially in the presence of multimorbidity, (iii) facilitate rehabilitation and physical activity, and (iv) facilitate remote care.There are two critical gaps in the care of PwP that technology can help overcome. First, most commonly, each specialty provides care in a silo. Second, with few exceptions, the patient's current assessment is restricted to the hospital or clinic setting. Three main technological breakthroughs can enable care integration supported by technology. One is the digitalization of medicine, which permits patients' connectivity with the hospital from the home environment and the connection between specialists ; second An important aspect to highlight is that not all systems bear the same degree of development. Like drug trials, where the different phases reflect how close a new drug is from being approved for medical use, in technology, the maturity or “readiness level” reflects how close a system is to being validated for use in routine care. The Technology Readiness Level (TRL) scale developed by NASA in the 1970s is a scale commonly used for this purpose . We willDigital health technologies, namely, telemedicine, telehealth, and health information technologies, have the potential to reduce the burden of care by connecting patients with the specialist and deliver personalized health services directly to the home , supportDigitalization is also characterized by the progressive use of electronic health records (EHRs), which in the last decade has been an essential advance for the efficient transformation of medical care institutions. EHRs have proven essential for preventing medical errors, improving efficiency and quality, increasing costumers' trust, improving medical care, and cutting down on healthcare costs . ElectroThe SARS-CoV2 pandemic has amplified the need to adopt digital healthcare . Both heAnother key element of TEC is the sensing of different health-related phenomena at “home,” more specifically, the natural environment of the patient. Wearable devices enable the remote assessment of patients' conditions in their natural settings  and measAs mentioned earlier, IMUs represent the most widely used technology used in PD and may well-serve the goal of providing data meaningful for healthcare. Over time, IMU-based sensors have become more refined and portable, allowing for unobtrusive monitoring of PD in the home environment. Currently, the main applications of these sensors include (i) the accurate evaluation of cardinal motor features (mainly for bradykinesia and tremor) , 19 and The collection of wearable sensor data at home requires increased computing power, mass data storage capacities, and widespread internet access, which imply that the digitalization of medicine is enabled. The integration of multiple devices within the home environment may have a two-fold impact, allowing for a more comprehensive clinical assessment and empowering patients to monitor their disease in a delivery of highly personalized care . In the The field of neurorehabilitation is an ideal example of how technology could be implemented to support medical care. VR and augmented reality (AR) have become more popular recently in this field to enable remote care. A virtual environment established by a computer is used in VR, while in AR, the experience of a real environment is enhanced by computer-generated perceptual information. Since 2008, VR research in PD has been conducted with the first studies of gait evaluation using VR  Another In addition, commercial video games (VGs) like video games, exergames, serious gaming, PlayStation, Nintendo, Wii, Wii Fit, Xbox, or Kinect have shown positive results in combination with traditional physical therapy. VGs seem to be effective for treating gait, balance, and strength PD symptoms . NeuroreVGs let patients interact in a two-dimensional environment real time and may represent a strategy to engage both mental and motor functions at the same time, possibly enhancing several PD cognitive domains . ExergamApart from that of cognitive functions, technological implementation for rehabilitation of other clinical manifestations such as speech and language is unfortunately limited. However, communication and swallowing problems, together with hypomimia, are highly prevalent in PD . A limitExoskeletons and robotic devices are one of the technological advances in the field of neurorehabilitation. To date, several systems have been developed like the Lokomat, ReoAmbulator, Lower Extremity Powered ExoSkeleton (LOPES), and Anklebot . AlthougAll the technologies described in the previous section and others not described here have the potential to reformulate PD management routines. Current standards for PD clinical care rely on assessment using clinical scales such as the MDS-UPDRS, Hoehn and Yahr staging, the Schwab and England rating of activities of daily living, and self-reported patient diaries . AlthougTraditional models of care focused on the management of a single chronic condition do not fit the paradigm of care required for PwP characterized by multimorbidity and frailty. In most healthcare systems, the “interface” between inpatient and outpatient management remains unsatisfactory and fragmented, which often leads to PwP receiving suboptimal care. Although elderly PwP will have other chronic diseases, most clinical guidelines focus almost exclusively on motor manifestations and neglect clinical heterogeneity , 47. OnlWearable sensors, accelerometers, gyroscopes, and non-wearable devices have been tested as ambulatory devices to assess motor parameters such as gait, kinematic features, sway, physical activity, tremor, and bradykinesia , 50. TheThere are significant challenges in the implementation of technology objective measures in day-to-day clinical practice. PD is a progressive disorder, with a significant compromise of functional independence, self-care, and QoL. Moreover, it is frequently associated with multimorbidity, requiring a considerable number of clinical visits and hospital care, resulting in high medical and economic burden –57. The The current technological development offers the opportunity to achieve an eHealth environment, where gaps of current care models are overcome and a more effective model of care is established. The foundational steps include implementing patient-operated digital platforms integrated with sensors and clinical and non-clinical applications, information sharing  among patients and caregivers and healthcare providers, to complement face-to-face visits and enhance standard care pathways. The design of this technology needs to ensure engagement and effective use in real life. Suitable systems will be defined and used to support sensible and appropriate healthcare usage going beyond the traditional “telehealth” approach. The objective is to develop a system where multidisciplinary care managers and empowered patients operate and enable timely and coordinated access to healthcare providers.Thanks to the advances described above, new models of care delivery in PD begin to emerge, profiting from the advances in telecommunications (and technology at large), that enable the emerging generation of digitalization of medicine at “home.” Yet few of these models are integrated widely into PD management. Emerging care modalities require the unification of multispecialty teams and the migration of patient necessities into their home or community. In this context, PD-Pal, a multicenter European medical project, proposes an innovative approach to the care and management of PwP in the most advanced stages. At this stage, symptoms are complex, and treatment is challenging, with a severe compromise of QoL of patients and family members. Moreover, in this advanced PD stage, patient care necessities change frequently, which makes management difficult and leads to a high number of clinical visits. By integrating electronic tools to monitor movement and cognitive functions at home, for example, and defining the standards for an integrated multidisciplinary path, it will be possible to validate this approach. To achieve this goal, the project will incorporate the integration of a new wearable technology system, PDMonitor®, for remote patient monitoring in their natural environments. This device will inform the management of advanced PD patients overcoming architectural barriers and social isolation. The PD-Pal project could successfully shape multidisciplinary palliative care in PD, integrating technology at home and defining new European standards for care pathways in the advanced stages of PD .The multinational consortium iCARE-PD is another example of technology integration for care delivery. iCARE-PD aims to develop an innovative, pragmatic healthcare model that shifts the hub of care from outpatient care to home-based community across a wider spectrum of disease stages in PD. This model consists of an integrated care network supported by a digital platform shaped as a virtual PD coach that incorporates principles of integrated care, self-management support, and TEC and integrates various eHealth solutions for PwP using co-design , 63. Co-Another example is the vCare European project. vCare stands for virtual coaching activities for rehabilitation in the elderly and aims at improving rehabilitation for people as they age. vCare will develop and validate new information and communications technology based on a virtual coaching approach for empowering and motivating people with chronic diseases like PD. vCare proposes to support the recovery to an active and independent life at home, providing rehabilitation guidance and guaranteeing the continuity of care in the home environment. This project has the following aims: (i) coaching activities based on the underlying care pathway system; (ii) integration of a semantic layer enabling technologies such as reasoning, machine learning, behavioral models, and predictive analytics; and (iii) a continuous personalization regarding the cognitive, physical, and social conditions with seamless context integration and non-obtrusiveness in a home environment using open platforms like FIWARE . TherefoA final example of integrative PD management is a stand-alone technological integrated solution, the PD-manager. The PD-manager uses a set of mobile and wearable devices such as a smartwatch, smartphone, and sensor insoles for monitoring and collection of adherence data. The core of the system is a cloud system that provides all the necessary functionality for users and services communication, along with computing power for data processing and storage. This mHealth platform is accessible through the patients' mobile application and can be shared to clinicians to perform a clinical evaluation using a dedicated medical mobile application. Among the functionalities of the PD-manager, there is a pillbox to optimize medication intake, a dedicated nutritional study, game-based physiotherapy at home, and personalized management suggestions through education.The current landscape of technology applied to PD evaluation and care is full of potential. The integration of technology in PD care is not a matter of possibility but how to fulfill the promise. For a successful implementation of TEC, it is urgent to create standards of validation for the intended clinical use of each technological modality and for their integration in a manner that is usable by patients. Ongoing and future collaborative projects will inform how the future eHealth environment will emerge to reduce care inequities and provide a more comprehensive care for empowered patients.TM, AA, and Á-SF developed the structure and topic of revision. TM provided critique and review to the initial draft. All authors contributed to the initial draft.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The Achilles tendon is the largest and strongest tendon in the human body and is essential for storing elastic energy and positioning the foot for walking and running. Recent research into Achilles tendon anatomy and mechanics has revealed the importance of the Achilles subtendons, which are unique and semi-independent structures arising from each of the three muscular heads of the triceps surae. Of particular importance is the ability for the subtendons to slide, the role that this has in healthy tendons, and the alteration of this property in aging and disease. In this work, we discuss technical approaches that have led to the current understanding of Achilles subtendons, particularly imaging and computational modeling. We introduce a 3D geometrical model of the Achilles subtendons, built from dual-echo UTE MRI. We revisit and discuss computational models of Achilles subtendon twisting suggesting that optimal twist reduces both rupture loads and stress concentrations by distributing stresses. Second harmonic generation imaging shows collagenous subtendons within a rabbit Achilles tendon; a clear absence of signal between the subtendons indicates an inter-subtendon region on the order of 30 μm in our rabbit animal model. Entry of wheat germ agglutinin in both the inter-fascicular and the inter-subtendon regions suggests a glycoprotein-containing inter-subtendon matrix which may facilitate low friction sliding of the subtendons in healthy mammals. Lastly, we present a new computational model coupled with human exercise trials to demonstrate the magnitude of Achilles subtendon sliding which occurs during rehabilitation exercises for Achilles tendinopathy, and shows that specific exercise can maximize subtendon sliding and interface strains, without maximizing subtendon strains. This work demonstrates the value of imaging and computational modeling for probing tendon structure-function relationships and may serve to inform and develop treatments for Achilles tendinopathy. In the last decade, research has expanded rapidly in the areas of Achilles tendon structure and mechanics. One particularly exciting research direction pertains to the Achilles subtendons, the presence and behavior of which have only recently been reported  MRI, for instance, allows for in-depth human tendon modeling and subject-specific analysis of tendon structure and mechanics. Imaging of animal models with second harmonic generation (SHG) imaging  imaging is a label-free microscopy method that utilizes a non-linear optical effect to visualize certain molecular structures, such as collagen fibers  using a water immersion objective  and a pulsed laser . Collagen was visualized by SHG imaging microscopy using the 920 nm laser line for excitation and a small detection window centered at 460 nm. The fluorescence of WGA-Alexa Fluor 555 was imaged in two-photon fluorescence excitation using the 1,045 nm laser line and a detection window from 577 to 633 nm. 3D imaging was performed by recording z-stacks . In order to image over 2–4 mm in x- and y-direction, several z-stacks were recorded in tile scanning mode. Stitching and image processing was done in Leica LAS-X (Leica Microsystems).in silico experiments in various aspects of tendon fascicle twist angles. The finite element (FE) mesh of the human Achilles tendon was developed using the Visible Human dataset . Sensitivity analyses were performed to comparatively characterize the influence of the following factors on tendon strength: (1) fascicle twist angles, (2) cross sectional area (CSA), and (3) tendon stiffness. Parameters were varied according to means and standard deviations reported in the literature . Using resting and 70% MVIC value, we found optimum parameters for the following three terms in the material model—the stiffness of ground substance, rate of collagen fiber loading, and Young's modulus of straightened fibers. Values used were the average from eight participants involved in the aforementioned study.The material model used here was based on a transversely isotropic hyperelastic material model that treats the tendon as a composite of collagen fascicles embedded in a matrix of ground substance  performed rehabilitation exercises based on Alfredson's protocol , the computational framework developed as a part of the International Union of Physiological Society (IUPS) Physiome Project .The FE analysis was performed using CMISS  MRI is an effective technique for imaging tendons in the human body and, in this study, was used to acquire 3D images of the Achilles tendon. While UTE uses an echo short enough to obtain signal from tendon and other collagenous tissues, similar signal intensity may concomitantly be obtained from surrounding tissues, especially muscle. To eliminate this unwanted signal and create high-signal-high-contrast images of the Achilles tendon, we performed dual echo UTE, where the second echo was acquired at a conventional short TE. Our final images were produced by subtracting the second echo from the first. Other imaging approaches have been used in the past to acquire tendon images, for instance ultrasound and magic angle imaging .GH organized the team, wrote the bulk of the document, planned the section contributions, revised and prepared the document, and was the primary researcher on the MRI, geometrical modeling, and the SHG portion of the work. JG contributed to the development and data collection of the SHG portion of the work, and proofread, edited, and wrote sections of the document. JM conducted the technical aspects of the SHG work, oversaw data collection, and contributed sections to the document. ER-Z contributed to the experimental aspect of the SHG portion of this manuscript, oversaw sample preparation, interpreted results, proofread, and edited the document. EH and BV contributed technical aspects of the rehabilitation exercise portion of this work including data collection and analysis, contributed sections, proofread, and edited document. VS co-led the organization of this work, performed the continuum modeling portion of this work, wrote sections of the document, proofread, and edited.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Atherosclerosis is one of the most common diseases of the cardiovascular system that leads to the development of life-threatening conditions, such as heart attack and stroke. Arthrosclerosis affects various arteries in the human body, but is especially dangerous in the arteries alimenting heart and brain, aorta, and arteries of the lower limbs. By its pathophysiology, atherosclerosis is an inflammatory disease. During the pathological process, lesions of arterial intima in the form of focal thickening are observed, which form atherosclerotic plaques as the disease progresses further. Given the significance of atherosclerosis for the global health, the search for novel effective therapies is highly prioritized. However, despite the constant progress, our understanding of the mechanisms of atherogenesis is still incomplete. One of the remaining puzzles in atherosclerosis development is the focal distribution of atherosclerotic lesions in the arterial wall. It implies the existence of certain mosaicism within the tissue, with some areas more susceptible to disease development than others, which may prove to be important for novel therapy development. There are many hypotheses explaining this phenomenon, for example, the influence of viruses, and the spread in the endothelium of the vessel multinucleated giant endothelial cells. We suggest the local variations of the mitochondrial genome as a possible explanation of this mosaicism. In this review, we discuss the role of genetic variations in the nuclear and mitochondrial genomes that influence the development of atherosclerosis. Changes in the mitochondrial and nuclear genome have been identified as independent factors for the development of the disease, as well as potential diagnostic markers. Atherosclerosis is a multifactorial disease with a complex pathogenesis. Multiple factors were shown to be involved in atherosclerotic lesion formation, and many knowledge gaps still remain. Atherosclerotic lesions can develop in any artery, but are especially dangerous in large vessels that aliment the heart, brain, and other vital organs. Macroscopically, the lesions are seen as local accumulation of fat in the arterial wall , which is followed by local thickening of the innermost arterial wall layer called intima. At the advanced stages, the plaques acquire a thick fibrous cap, which separates them from the vessel lumen and circulating blood. Currently, several key factors in atherosclerotic lesion formation are considered. There is no doubt that impaired endothelial function and increased permeability plays an important role, especially at the initial stages of the lesion development . AlteratNumerous genetic studies were conducted to establish risk factors for the development of atherosclerosis . ResearcAtherosclerotic lesion development takes place in the intimal layer of the arterial wall. Adult intima is a rather thick formation with complex architecture and heterogeneous cellular composition. The intima is separated from the lumen of the vessel by a monolayer of endothelial cells. Endothelium plays a key role in the transport of cells and non-cellular components of blood from the arterial bed to the vascular wall . EndotheUnder the basal membrane, intima is populated by different types of cells . Immune Cellular composition of the arterial wall undergoes profound changes in atherosclerotic lesion areas . Lesion in vitro experiments, such as oxidized LDL. Atherogenic modification of LDL begins with desialylation, and continues with changes of the lipoprotein particle size, density, and electric charge resulting in the formation of small dense and electronegative LDL fraction. Oxidation is likely to occur at later stages of atherogenic LDL modification. LDL atherogenicity is enhanced by the formation of self-associates and circulating immune complexes containing modified LDL and anti-LDL autoantibodies (The primary source of lipids that accumulate in foam cells is atherogenic modified low density lipoprotein (LDL). Particles of LDL circulate in the blood and undergo chemical modifications affecting the glycoconjugate, lipid, and protein moieties . Notewortibodies .Native (unmodified) LDL does not cause the accumulation of intracellular lipids in cultured cells, because LDL binds to a specialized LDL receptor (LDLR), and undergoes degradation through the receptor-mediated pathway . The excAssociates of modified LDL stimulate the phagocytic activity of subendothelial macrophages and pericytes. Following phagocytosis, inflammatory cytokines are secreted, which attracts monocytes and other immune cells to the emerging site of inflammation. Inflammatory cytokines contribute to further accumulation of intracellular lipids induced by modified atherogenic LDL. Moreover, in some cases, lipid accumulation induction is observed even in absence of modified LDL , tumor necrosis factor alpha (TNF-α), chemokines monocyte chemoattractant factor 1 (MCP-1), growth factors, such as platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF), and adhesion molecules. This leads to the increased recruitment and adhesion of circulating immune cells that interact with the endothelium and penetrate into the subendothelial space. During this process, circulating monocytes become activated and differentiate into macrophages. This further increases the pro-inflammatory signaling at the emerging lesion site. Macrophages are specialized phagocytes that actively participate in lipid uptake within the lesion and are an important source of foam cells .An increase in the concentration of pro-inflammatory cytokines leads to endoplasmic reticulum stress in the arterial wall cells, which in turn can lead to the initiation of apoptosis . CytokinIt is plausible that atherosclerotic lesion development occurs when the inflammatory process cannot be resolved in a regular way and becomes chronic . Thus, tIt is generally believed that in rare cases, single nucleotide substitute in nuclear genome may greatly affect the clinical phenotype. On the opposite, as a rule, it is impossible to establish a causal relationship between a certain variant of the nuclear genome and a phenotypic manifestation of this change. This is also true for detecting genetic predisposition to chronic pathologies like atherosclerosis and related cardiovascular diseases. In the last decade, the genome-wide associations study (GWAS) approach came into play and was widely applied. In general, this is a targeted search for associations between genomic variants and phenotypic traits, i.e. for the search of associations between single nucleotide polymorphisms (SNPs) and diseases. Such studies provide a great bulk of information, which, however, can hardly be implemented into practical healthcare. On the other hand, systematic approach to the search for such associations is necessary to assess the quality of the results of numerous studies in this area and to identify the most promising sets of markers for further detailed research .AIP, DRAP1, POLR2I, and PQBP1 genes) in the RGN of the arterial wall with cross-species verification, including RNA processor genes. This RGN was re-identified in THP-1 foam cells and independently in blood-derived monocytes of CAD patients and macrophages from carotid atherosclerotic lesions. Such studies can help to better identify the candidate genes critical for the development of CAD identified in the framework of GWAS, and this is only the beginning of the path to achieving the goals of personalized medicine , that are longer than 200 nucleotides, can regulate the expression of neighboring genes. Recent evidence suggests the role of lncRNAs expression on proliferation of vascular smooth muscle cells and apoptosis, and, consequently, on the risk of aortic aneurysm and atherosclerosis . The likferation . Importadiabetes .LOX, which encodes for lysyl oxidase, a protein responsible for cross-linking of collagen and elastin molecules during the formation of regular collagen fibers. LOX is important for mechanical integrity of the arterial wall, and missense mutations in this gene were shown to cause aneurysm formation and aortic dissection due to insufficient crosslinking of elastin and collagen in the aortic wall. The study that linked LOX to aneurism formation offered an algorithm that could be used to search mutational changes associated with the development of coronary heart disease (One of the genes implicated in aneurism formation is  disease .LDLR), its ligand apolipoprotein B (APOB), or the proprotein convertase subtilisin/kexin type 9 (PCSK9), which takes part in the regulation of cholesterol metabolism. Binding of PCSK9 to EGF-A (extra-cellular domain of LDLR) leads to degradation of the receptor. A decrease in LDLR causes a decreased LDL metabolism, which can lead to hypercholesterolemia. The PCSK9 is synthesized in a soluble inactive form of proenzyme, which can be activated spontaneously during intramolecular processing in the endoplasmic reticulum (APOE) and the signal-transducing adaptor family member 1 (STAP1)  . The mod (STAP1) . HoweverAccumulating evidence indicates that mtDNA mutations play a role in atherosclerosis development alongside with nuclear genome polymorphisms. An important part of mitochondrial proteins that are indispensable for proper functioning of the respiratory chain and energy production are encoded by mtDNA. Therefore, mtDNA mutations can lead to serious consequences, such as altered energy homeostasis, impaired glucose and fat metabolism, elevated oxidative stress and, ultimately, cell damage and death. These processes are tightly implicated in atherosclerotic lesion development .The main function of mitochondria in the eukaryotic cell is oxidation of organic compounds and the use of the released energy for ATP synthesis and thermogenesis . The sizMitochondrial reactive oxygen species (ROS) generated by dysfunctional mitochondria not only contribute to cell damage during oxidative stress, but also act as intermediate signals, which are modulators of gene expression associated with the development of atherosclerosis. Mutational changes in the mitochondrial genome can partially explain the focal nature of the vascular wall damage in atherosclerosis. Cells of different sections of the vascular wall can vary significantly by the level of heteroplasmy, which leads to differences in cellular metabolism. Therefore, due to the development of mitochondrial dysfunction, and some cells become more susceptible to various pathological influences triggering the atherosclerotic process .Previous studies have revealed several atherosclerosis-associated mtDNA mutations, including m.3256C > T, m.3336T > C, m.5178C > A, m.12315G > A, m.14459G > A, m.15059G > A, and m.13513G > A. It was found that a certain spectrum of pro- and anti-atherogenic mtDNA mutations is characteristic for various types of atherosclerotic lesions of the human aortic intima .PPARGC1A gene in muscle and liver tissue. It was shown that the suppression of the synthesis of PGC1a protein  impacted mitochondrial biogenesis and contributed to the induction of insulin resistance  play an important role in this process. These factors regulate the expression of the transcription factor of the mitochondrial genome (Tfam) and many other mitochondrial genes involved in oxidative phosphorylation. Recent studies demonstrated a link between mitochondrial dysfunction and insulin resistance through altered expression of the sistance . The funsistance .Thr m.15927G> mutation revealed its association with coronary heart disease. The m.15927G > A mutation hindered the highly conserved base-pairing (28C-42G) of anticodon stem of tRNAThr. Molecular modeling study demonstrated that the m.15927G > A mutation resulted in an unstable tRNAThr structure. The study conducted on cybrid lines bearing mitochondria with the m.15927G > A mutation showed a significant decrease in the efficiency of aminoacylation, which led to a decrease in the number of polypeptides encoded by mtDNA, respiratory failure, a decrease in membrane potential, and an increase of ROS production. The increased release of cytochrome c into the cytosol and caspase 3, 7, 9 and PARP proteins indicated that the presence of this mutation contributes to the development of apoptosis. These observations confirm the data published by different groups supporting the important effect of mitochondrial mutations on the pathophysiology of coronary heart disease .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The regulation of energy balance requires the complex integration of homeostatic and hedonic pathways, but sensory inputs from the gastrointestinal (GI) tract are increasingly recognized as playing critical roles. The stomach and small intestine relay sensory information to the central nervous system (CNS) via the sensory afferent vagus nerve. This vast volume of complex sensory information is received by neurons of the nucleus of the tractus solitarius (NTS) and is integrated with responses to circulating factors as well as descending inputs from the brainstem, midbrain, and forebrain nuclei involved in autonomic regulation. The integrated signal is relayed to the adjacent dorsal motor nucleus of the vagus (DMV), which supplies the motor output response via the efferent vagus nerve to regulate and modulate gastric motility, tone, secretion, and emptying, as well as intestinal motility and transit; the precise coordination of these responses is essential for the control of meal size, meal termination, and nutrient absorption. The interconnectivity of the NTS implies that many other CNS areas are capable of modulating vagal efferent output, emphasized by the many CNS disorders associated with dysregulated GI functions including feeding. This review will summarize the role of major CNS centers to gut-related inputs in the regulation of gastric function with specific reference to the regulation of food intake. Sensory information from the gastrointestinal (GI) tract is relayed centrally via neural and humoral pathways; the central nervous system (CNS) integrates this large volume of sensory afferent information and coordinates a precise series of efferent responses to regulate food and caloric intake including the modulation of gastric motility, tone, and emptying, as well as intestinal motility, transit, secretion and absorption. This efferent output is regulated meticulously in order to maintain homeostasis based on current energy needs and visceral sensory stimuli. The advent of novel and emerging molecular and genetic labeling techniques implies that, as a field, we are in a better position to be able to potentially delineate the exact phenotype of neurons involved in distinct aspects of nutrient signaling, and to interrogate and manipulate those neurocircuits with spatial and temporal precision. Characterizing the central neurocircuits involved following activation of gut inputs, including their phenotypes, activation characteristics, and connectomes, will be important to understand the physiology and pathophysiology of food intake.GI sensory information is relayed centrally via both vagal and spinal afferents. Spinal afferents, particularly those within the splanchnic nerves, relay low- or high-threshold mechanical and chemical information centrally and are considered primarily to be involved in nociceptive processing ,2. In coGastric vagal afferents can be distinguished on the basis of their preferred response modality; mechanosensitive afferents, for example, innervate the GI smooth muscle and are activated by distention and stretch in response to food ingestion (reviewed in ). RecentGpr65-expressing neurons that display extensive innervation of the duodenal mucosa and are unresponsive to mechanical distention. Mucosal afferents are in close contact with enteroendocrine cells (EEC), and are respond to released gut endocrine peptides to induce an appropriate response in the vagal afferent neurons, and, subsequently, within the NTS, DMV, and the arcuate nucleus of the hypothalamus, . In. In81]. The cerebellum, located posterior to and heavily connected with the brainstem, is canonically thought to be involved in motor control. Several lines of evidence, however, show that cerebellum also plays a critical role in the regulation of feeding behavior. Cerebellar lesions have been shown to alter feeding behavior and dysregulate blood glucose and body weight . AlthougThe hypothalamus lies rostral to the brainstem, making up the floor of the third ventricle. Composed of many subnuclei, the hypothalamus has pivotal roles in the autonomic control of thirst, temperature, biological rhythms as well as feeding and glycemic regulation. Focusing on its role in the integration of sensory gut inputs and the regulation of feeding patterns, the hypothalamus receives ascending gut-related projections from the NTS as well as responding directly to circulating feeding-related factors.Located in the basal hypothalamus adjacent to the arcuate (ARC) nucleus, the median eminence is a circumventricular organ ,42 that Beyond exposure to circulating factors, the ARC receives input from other hypothalamic nuclei as well as the NTS, the locus ceruleus, reticular formation, and bed nucleus of the stria terminalis . PeriphA subpopulation of the LH, composed of orexin/hypocretin neurons, has been shown to form synaptic connections with NTS neurons and modulate food intake . This prBeyond autonomic and homeostatic control, feeding is also regulated by higher cognitive centers. The memory of recent meals can control initiation, frequency, and size of future meals, as well as encoding information regarding where food was available. The hippocampus, split anatomically into dorsal and ventral regions, is known to be involved in these memory formations, placing it as a potentially critical central region for controlling food intake. Indeed, hippocampal neurons are activated by gastric distention  in additThe amygdala, located in the temporal lobe, lies adjacent to the inferior horn of the lateral ventricle and medial to the hypothalamus. The amygdala can be broken down into substructures that include the central amygdala (CeA) and the extended amygdala that includes the bed nucleus of the stria terminalis (BNST). The CeA receives projections from the PBN and the PVN and sends descending projections to the hypothalamus and brainstem in order to mediate physiological responses to fear and anxiety  125]. T. T125]. Several studies have highlighted changes in vagal afferent responsiveness and signaling following high fat diet (HFD) exposure and diet-induced obesity (DIO), including a decreased vagal afferent response to mechanical stretch of the stomach and neuroendocrine peptides including CKK, GLP-1, leptin, and serotonin, as well as impaired responses to glucose ,127,128.Another interesting phenomenon, well documented by Levin and colleagues, has shown that HFD-fed male Sprague-Dawley rats separate into two populations, one that become hyperphagic and obese, and another that maintain their eating patterns and resist weight gain . Of noteA receptors subunit composition that alters the channel kinetics and subsequently increases inhibitory drive from the NTS that is associated with decreased gastric motility [Central feeding circuits develop during the embryonic period, but are subject to significant development maturation in the early postnatal period. In rodents, descending autonomic inputs from the hypothalamus, CeA, BNST, and cortex reach the DVC in the first postnatal week, marking this as a critical window during which early life experiences can shape the connectivity of these central feeding nuclei . Severalmotility , althougmotility . Elevatemotility , possiblmotility ,142. Posmotility ,144. TakBecause of the extensive interconnectivity of brainstem, midbrain, and higher CNS centers with the DVC and brainstem neurocircuitry involved in the regulation of GI functions, several neurological, developmental, and behavioral disorders are associated with alterations in gut functions, including those involved in the regulation of food intake and energy balance.Stress has been defined as a stimulus or event that challenges the physiological and psychological homeostatic state of an individual ,146,147.Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral disturbances such as repetitive behaviors and impaired social behaviors. Beyond changes to social behavior, these patients also exhibit altered eating patterns where children with ASD are considered very selective eaters (picky eaters), with aversions to particular food colors, smells, and textures, amongst other characteristics ,152. An Parkinson’s disease (PD) is a neurodegenerative disorder characterized by severe degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). It is considered a movement disorder marked by bradykinesia, rigidity, tremor, and gait/posture disorders. However, PD patients also experience a wide array of prodromal symptoms that include sleep disorders, orthostatic hypotension, and GI dysfunction ,161,162.The regulation of food intake is a result of a coordinated and intricate series of short- and long-term responses to peripheral and central nervous system signals. Although circulating factors can modulate the activity of circumventricular nuclei directly, sensory inputs from the gut are relayed centrally via the afferent vagus nerve, terminating in a pathway-specific manner predominately within the NTS. Because of its reciprocal connections with other brainstem, midbrain, and forebrain nuclei, the NTS plays a major role in consolidating responses from across the CNS and relaying an integrated signal to the adjacent DMV to control the vagal motor output to the GI tract. This interconnectivity has led to the increased appreciation that many disorders of the CNS are accompanied by dysregulated central control of GI dysfunction, including disruptions in feeding, metabolism, and energy balance which significantly affects many patient’s quality of life.The advent of novel and emerging molecular and genetic techniques has allowed identification of discrete gut–brain neurocircuits involved in particular GI responses, and affirmed that many such neurocircuits are exquisitely specialized as per their physiological response. Using a multi-functional approach, the gut–brain axis has been shown to determine preference for sugar  via post-ingestive mechanisms involving afferent vagus nerve-mediated activation of the caudal NTS . While tMany challenges and barriers still exist to understanding the mechanisms by which central neurociruits regulate food intake in response to gut inputs. The central connectome of the gut–brain axis has yet to be fully elucidated, particularly in regard to pathway-specific neurocircuits. While studies from several groups have provided a great deal of information regarding vagal efferent control of GI functions in both physiological and pathophysiological conditions, there is surprisingly little phenotypic characterization of vagal efferent neurons involved in different visceral functions. Questions still remain regarding the validity of many animal models used to investigate complex human physiologial systems; while the use of transgenic animals has clearly pushed our understanding of nutrition, feeding and the role of the gut–brain axis forward, using such a reductionist approach to answer polygenic pathophysiological problems is not without translational difficulties. Little is known about how the gut–brain axis or the responsiveness of central neurocircuits to visceral inputs vary across the life span or during ageing and, despite strong clinical evidence that the perinatal envionment is critically important to offspring outcomes, few studies have investigated how early life events alter the development of feeding related neurocircuits. Nevertheless, increasing awareness of the crucial role that the CNS plays in modulating GI sensory and motor functions should encourage continued investigations into the reciprocal ‘big brain–little brain’ partnership.


Raw materials have played significant role in all industrial revolutions. Iron, steel, advanced machinery, cutting-edge tools, and structured factories have instigated the first industrial revolution in the UK. At its core, the production of steel has paved the way for the industry to flourish and built up the foundations for new era world and globalization. Owing to its strength, ease in designing, and reliability, steel proved to be an extremely useful utility in healthcare. Improvements in manufacturing and better standardization have resulted in the occurrence of second industrial revolution in the late nineteenth century up to the early twentieth century. Electricity, petroleum, and rubber-based materials were developed during this period, with wide applications in the medical and health fields. This was accompanied by regulations and standardizations which improved health care infrastructure and infection control systems. During that period, economic interdependence was evolving, and socio-economic systems around the world were being transformed. Globalization continued to grow exponentially throughout the third and fourth industrial revolutions, and technology played a major role in developing society and fulfilling global needs. The uniqueness of the fourth industrial revolution (Industry 4.0) is not to be solely attributed to the advancement in manufacturing and digital systems, but also to the convenience of transportation between geological borders and the relaxation of national boundaries.Although the effects of globalization have been positive in most respects, this has arguably not been the case when it comes to global pandemics. Disease outbreaks have occurred several times during the past few decades, showcasing rapid evolution and spread. Despite the progress in medicine, globalization has raised other risks and consequences in disease outbreaks which can undermine public health systems, economies, and overall social behavior. With these socio-economic transformations and the nature of genetically modified strains of viruses, the outbreaks may become more frequent and lethal. Therefore, governments around the world should be well prepared for possible health crises.https://www.who.int/emergencies/diseases/novel-coronavirus-2019), updated on April 9, 2020, there is an overall of 1,395,136 confirmed cases and total deaths of 81,580 worldwide.In December 2019, the World Health Organization (WHO) announced the outbreak of an emergent infectious disease due to a specific strain of corona virus called SARS-CoV-2. The novel coronavirus disease (COVID-19) was declared by the WHO as a pandemic on March 11, 2020. According to WHO . The question of the moment is that what roles can industry 4.0 and its emergent materials can play in mitigating the harms of disease outbreaks as a whole, and COVID-19 in particular. Emergent materials are playing a central role in improving the health systems and in facing the consequences of the ongoing pandemic.The detection of diseases is done through specific biomarkers in saliva, blood, or tissue samples. New devices based on nanomaterials can perform fast, inexpensive, and sensitive detections. Biosensors are common in the detection process. These sensors can be customized using new tailored nanomaterials for improved electrochemical and optical sensors. Such materials are used for their customized properties, specifically their conductivity, mechanical stability, and easy processing techniques. Some of the prime examples include quantum dots, nanofibers, nanowires, magnetic beads, metal-based nanoparticles, and nanocomposites.The application of these materials in infectious disease analytical tests requires improvement in sensitivity, lowering both the cost and complexity process. Collaboration between researchers in materials science and industry can lead to a new effective way in improving the detection of epidemics through the reduction of the needed workflow and speedup the diagnostic procedures.Building smaller and smarter testing systems is highly required as it will be easier to test the samples on the site where possible patients are expected. Emergent materials with nanotechnology are contributing through reducing the size of these systems. The application of emergent tailored nanomaterials will lead to usage of less quantities of the needed samples and chemicals used for testing, meanwhile also making the over-all process more practical.Emergent materials can also play a role in antiviral activities. Well-known examples of such materials include graphene oxide and reduced graphene oxide. Their antiviral activities are attributed to their structure (single layer) and to the presence of a negative charge.Moreover, emergent materials within Industry 4.0 are also contributing in supporting fatigued health systems during the current pandemic. For instance, some materials are improving the robotic systems and sensor abilities for sterilization and the detection of crowded areas. This is done through improving sensing materials which eventually lead to increase in the battery life. Additionally, the 3D printing of different types of polymers and composites is now a well-established technique providing much needed medical parts and custom components which are in short supply. Recent and present examples of such materials include face masks, shields, ventilator parts, etc.Further research in different types of emergent materials and nanomaterials can be tested and tailored for better protection, analysis, and curing of pandemic diseases, including COVID-19. The Emergent Materials journal supports the development of materials in improving human welfare worldwide and welcomes contributions in advancing healthcare and technology systems with advanced emerging materials to combat and prevent disease outbreaks.


Old age, hypertension, obesity and diabetes are the major risk factors for severe disease with COVID 19. However, snoring and obstructive sleep apnoea (OSA), unrecognised, or under reported , and is Aspiration during sleep is among several pathways by which snoring, and sleep apnoea increases vulnerability to pneumonia . The proWhile some have recommended suspending the use of nasal positive pressure therapy (CPAP) and non-invasive positive pressure ventilation (NIV) because of the risk of viral spread , CPAP wiHowever, another, perhaps more important benefit of CPAP use in sleep, is preventing aspiration, by stopping snoring and apnoea. In the time window between the initial viral infection in the nasopharynx and the onset of the lung disease, unrecognised snoring and sleep apnoea may be significant mechanisms increasing aspiration during sleep and exposing the lungs to high levels of viral inoculates. Rather than waiting for the patient to develop lung changes, early use of nasal CPAP in sleep might offer a safe method of helping to reduce the progression to potentially fatal COVID 19 pneumonia. The report by Oranger et al.  supports


Although benefiting from an unprecedented technological evolution, contemporary endodontics is still characterized by the recurrence of retreatments, due to the need to solve quite frequent incidents, accidents, or even failures of primary endodontic treatment. This survey aims to assess both the etiology and the prevention methods of one of the most troublesome endodontic iatrogenies: instrument separation during root canal shaping. The multifactorial nature of this occurrence entails identifying and taking into account all the causal and contributing factors. Their significant number and the possible involvement of any of them, starting with the complexity and variability of the root canals and ending with the technical specifications concerning the nickel-titanium rotary instrumentation system being used, highlight the necessity to develop valid guidelines to avert the occurring of such an upsetting situation. Present-day endodontics witnesses a plethora of developments as the result of continuous scientific evolution and advancements in technologies, methods, and materials. These materialize in every aspect of root canal treatment, from diagnostic imaging investigations, designing and kinematics of instrumentation, to different materials and techniques concerning root canal filling. The results make it possible to approach treatment options for complex clinical situations, with the outcome of healed teeth, i.e., “functional, asymptomatic teeth with no or minimal radiographic periradicular pathosis” .However, endodontic procedures may frequently be challenging, with an important number of issues having consequences on the degree of difficulty and the risks involved by the treatment option required. In turn, these must be correctly evaluated, beginning with an accurate diagnosis and a reasonable prognosis to achieve a comprehensive treatment plan. Aspects that are unique to each case have to be considered, such as the complexity of the root canal anatomy. Evidence provided by thorough clinical examination and diagnostic imaging enables a correct appraisal of preoperative diagnosis and treatment planning in endodontics .However, a significant number of incidents or accidents may occur during endodontic treatment. Since 2002, these are considered to be “unfortunate occurrences that happen during treatment, some owing to inattention to detail, others totally unpredictable” . Such acEndodontic mishaps are numerous and diverse and are usually classified according to:•John Ingle: access-related, instrumentation-related, obturation-related and miscellaneous mishaps;•Walton & Torabinejad: procedural accidents during access preparation, accidents during cleaning and shaping, accidents during obturation and accidents during post space preparation;•Leif Tronstad: incomplete analgesia, access cavity, perforations from the pulp chamber, root perforations, obliterated root canal, fracture of an instrument, adverse reactions to medicaments, overfilling of the root canal and vertical root fractures .It is hard to evaluate the real frequency of occurrence of these mishaps rigorously. A significant number of clinical cases is suspected to be overlooked, either by not observing or not reporting them.All of the above-mentioned possible mishaps include fracture of an instrument, also known as instrument separation.The fracture of an instrument is a very disturbing situation, a barrier being thus raised in front of further shaping and filling that particular root canal. Apical access to that obstruction is denied, and root canal treatment cannot be completely performed.Depending on both the moment during the endodontic treatment when the accident happened, and the level of the root canal where the instrument broke, proper shaping and filling of the root canal is more or less prevented. This leads to possible complications and may even endanger the positive outcome of the entire endodontic treatment. Starting with Strindberg in 1956, an important number of surveys approached the matter from both clinical and statistical viewpoints [Research has shown that the incidence of endodontic files separation is extremely variable, strongly depending on some factors influencing how statistics surveys was performed -10, suchIt is important to note that any endodontic instrument may fracture during its use: endodontic probes, Gates Glidden drills, stainless steel files, nickel-titanium files, irrigation tips, ultrasonic tips, spreaders, pluggers, and others. The most common situations involve endodontic files separated during root canal shaping. It is interesting to mention that the fracture incidence of rotary nickel-titanium (Ni-Ti) instruments was significantly greater during root canal re-treatment than root canal treatment, mainly with small instruments and in the apical third of the canal .From a statistical perspective, the incidence concerning the fracture of an endodontic instrument is mainly influenced by the way in which these studies are carried out; thus, a wide range of values could be encountered:•Stainless steel files: 0.7 - 7.4%;•NiTi rotary files driven by continuous rotation: 0.4 - 5%;•NiTi rotary files driven by reciprocation: 0.14%;•SAF (Self Adjusting File): 0.6%.This reveals that the frequency of nickel-titanium rotary instruments fracture is comparable to that of stainless-steel endodontic files, although the metallurgical and mechanical properties of nickel-titanium alloy are definitely superior, mainly due to its superelasticity. Even more, there are studies suggesting a higher incidence of fracture for NiTi rotary instruments compared with stainless steel files.It should also be noted that, unlike NiTi instruments, the stainless-steel ones could present some “warnings” of imminent breakage, represented by plastic deformations of the file: unwidening, overwidening or angulations at sharp angles.However, the fracture mechanisms are different for the two different kinds of endodontic instruments: excessive amounts of torque for stainless-steel files and mainly torsion overload and cyclic fatigue for the nickel-titanium ones .The fracture of the endodontic instrument has a multifactorial etiology, being influenced by diverse elements , 14 suchThe endodontic access cavity must allow a direct view of all root canal orifices and straight-line access to the first curvature of each root canal, considering the root canal is accessible over its entire working length.The absence of complete removal of the ceiling of the pulp chamber, as well as a restriction of straight-line access, constitute the main reasons for higher stress of the rotary file resulting in an increased risk of fracture.Endodontic instrumentation, currently exclusively based on nickel-titanium rotary systems, benefits from the illumination and magnification provided by the endodontic operating microscope, which also allows the implementation of the concept of minimally invasive access cavities. Studies conducted in this respect do not indicate an increase in the incidence of endodontic instrument fracture, which shows that root canal shaping can also be performed with minimal risks under the specific conditions of minimally invasive dentistry under the conditions offered by endodontic specialists and current treatment options -16.The importance of root canal anatomy is evident because the risk of instrument fracture increases directly proportional to the complexity of the endodontic system. Most cases occur in both upper and lower molars, and more precisely, in their mesiobuccal root canals . The expEach curvature is described by two parameters: its angle and its radius, and the two elements are independent of each other. At the same angulation, two root canals may have different radii of curvature. The smaller the radius, the sharper the curvature. The rotating file is subjected to repeated stress cycles - exerted on its external curvature - and compression cycles - on its internal curvature. With the increase of the angulation and the reduction of the radius, the instrument is increasingly stressed by the increasing torsional values. From this perspective, the dimensions of the radius of curvature seem to be more important.The succession of these cycles, in the conditions of tight curvatures, or even several successive curvatures along the root canal, causes an increase of the fracture risk of the instrument. Consequently, the main recommendation is to use a continuous axial movement of the instrument during its rotation, thus avoiding the concentration of the stresses only in certain places of the file. The cross-section of root canals also plays an important role . On the In any type of rotation, there are two parameters in inverse proportionality: rotational speed and torque , 19. TheEffective and safe instrumentation is mainly dependent on correct endodontic irrigation, in order to allow the removal of debris and to continuously lubricate the root canal.Another essential parameter concerning the etiology of an endodontic instrument separation is the number of sterilization cycles to which it has been subjected, which is often indicated by the manufacturer.The cumulative stress an endodontic file undergoes is dependent both quantitatively (the number of uses) and qualitatively . All the studies conducted in this regard demonstrate the direct proportionality between the number of uses of endodontic instruments and the incidence of their fracture.There are also situations in which, considering that the mechanical stresses to which the instruments were subjected were very important, these should be discarded after their first use, otherwise significantly increasing the risk of fracture when reused.In relation to the above mentioned, the preventive elements regarding the endodontic instruments fracture can be summed up as follows:•achieving an endodontic approach as close as possible to the right line, avoiding the excessive curvature of the instrument;•verifying the access of the root canals throughout the entire working length;•obtaining a sliding path that allows torque to be maximally effective;•endodontic irrigation present throughout the instrumentation, with the help of effective systems, which allow removal of the debris throughout the length of the root canal ;•the use of current rotary systems with minimal engagement and minimal “screw-in” effect in dentin;•observing the speed and torque values indicated by the manufacturer for each specific type of rotary system;•minimizing the number of uses of endodontic files or implementing rotary systems that allow a single use of an instrument - “One Endo file”.Though any endodontic instrument may break in any given case, an accurate assessment of the clinical and imaging diagnosis, comprehensive knowledge concerning the instruments being used, as well as consistently relying on the operating microscope can provide significant means in order to avoid a troublesome experience and perform the best endodontic treatment possible.The authors declare that there is no conflict of interest.


In addition to the regulation of blood pressure, the renin-angiotensin system (RAS) also plays a key role in the onset and development of insulin resistance, which is central to metabolic syndrome (MetS). Due to the interplay between RAS and insulin resistance, antihypertensive compounds may exert beneficial effects in the management of MetS. Food-derived bioactive peptides with RAS blocking properties can potentially improve adipose tissue dysfunction, glucose intolerance, and insulin resistance involved in the pathogenesis of MetS. This review discusses the pathophysiology of hypertension and the association between RAS and pathogenesis of the MetS. The effects of bioactive peptides with RAS modulating effects on other components of the MetS are discussed. While the in vivo reports on the effectiveness of antihypertensive peptides against MetS are encouraging, the exact mechanism by which these peptides infer their effects on glucose and lipid handling is mostly unknown. Therefore, careful design of experiments along with standardized physiological models to study the effect of antihypertensive peptides on insulin resistance and obesity could help to clarify this relationship. Metabolic syndrome (MetS) is a cluster of several risk factors for cardiovascular disease (CVD), coronary heart disease, and type-2 diabetes . AccordiAs a classical feature of the MetS, high blood pressure levels are strongly associated with visceral obesity and insulin resistance, the main pathophysiologic features of MetS . It has Treatment of MetS requires improvement in lifestyle, engagement in physical activity, and a balanced low-energy diet . AdherenFood protein-derived bioactive peptides have great potential for the development of functional foods and/or nutraceuticals for the prevention and management of MetS and hypertension ,18,19. BThe underlying mechanisms for development of hypertension and MetS are complicated and have not yet been completely defined. Visceral obesity, insulin resistance, sympathetic overactivity, oxidative stress, endothelial dysfunction, activated RAS, and inflammation have been suggested as the potential mechanisms ,22. A nuBlood pressure is controlled by several different interacting biochemical pathways. Systemic RAS, identified as a hormone-based pathway, plays an important role in regulating arterial pressure. Low blood pressure is one of the stimulants of RAS where it triggers the secretion of enzyme renin from the kidneys to the blood stream. Renin hydrolyzes angiotensinogen secreted from the liver to angiotensin I (Ang I). Angiotensin converting enzyme (ACE) is membrane-bound glycoprotein generated by and resident in the lungs, the endothelial cells of the vasculature, and cell membranes of a number of organs in the body . ACE cleThe cardiovascular risk factors such as hypercholesterolemia and diabetes mellitus are closely related to overexpression and increased activation of AT1Rs in the vascular wall . Ang II 2+ or reduced sensitivity to this ion [Abnormalities in the structure and function of blood vessels in terms of endothelial dysfunction, oxidative stress, and vascular remodeling can lead to the development of hypertension. The endothelium, a monolayer of cells lining the lumen of blood vessels, is the key regulator of vascular homeostasis. The healthy endothelium responds to physical and chemical signals by producing various factors that regulate vascular tone, cellular adhesion, smooth muscle cell proliferation, and vessel wall inflammation . Endothethis ion ,39. Reduthis ion .Impaired glucose metabolism, obesity, dyslipidemia, and hypertension are all associated with endothelial dysfunction. Endothelial injury, oxidative stress, inflammation, and disruption of NO function and bioavailability are the mechanisms by which these risk factors affect endothelial function in MetS.Metabolic actions of insulin on promoting glucose disposal are augmented by vascular actions of insulin on endothelium to stimulate NO production with vasodilatory properties. The pathway involved in the production of NO in the endothelium shares noticeable similarities with the pathways in skeletal muscle promoting glucose uptake . ActivatOxidative stress, resulting from the excessive and/or dysregulated generation of reactive oxygen or nitrogen species , is a major contributor to disease pathologies . Being c−) generation. Peroxynitrite is a highly reactive molecule causing nitration at the tyrosine residues of various proteins resulting in endothelial inflammation and cell death. Increased formation of peroxynitrite also inactivates prostacyclin synthase, leading to the accumulation of inflammatory and prothrombotic eicosanoids [osanoids .Hypertension linked to the decreased NO bioavailability and/or plasma FFA-mediated ROS exaggeration is considered a primary risk factor for MetS . ObesityIn summary, regulation of ROS/RNS levels for maintaining normal physiological functions is critical. Antioxidant therapies have shown potential benefits in minimizing vascular injury and prevention or treatment of hypertension ,60. The Inflammation, the body’s response to non-lethal injury, is an essential component of the immune response for resisting microbial infection and wound healing. However, excessive and uncontrolled inflammatory changes often lead to the development of vascular disease, atherosclerosis, and its complications. The vascular endothelium plays a key role by acting as a gatekeeper for the extravasation of leukocytes, which is a hallmark of inflammation. The interactions between a variety of inflammatory cells, the extracellular matrix, endothelial cells, and vascular smooth muscle cells are involved in the vascular inflammatory response . When enInsulin resistance, hyperinsulinemia, and blood pressure have been correlated in both obese and lean hypertensive subjects . High baThe overproduction of the RAS, including Ang II, activation of the AT1R, and increased production of aldosterone, impairs insulin signaling, further exacerbating insulin resistance ,82. An eRAS components expressed in various tissues in the body including but not limited to the kidneys, heart, brain, and adipose tissue are referred to as the tissue or local RAS. Local RAS involves in physiological  and pathophysiological  conditions in the body . StudiesPharmacological treatments for RAS blockade are, however, associated with side effects, which has led to a shift toward the development of naturally derived alternatives to synthetic drugs in recent decades. Food proteins containing bioactive peptides with a wide variety of biological activities including antioxidant, antihypertensive, antilipidemic, antimicrobial properties and among others have great potential to be used as alternatives to synthetic drugs ,19,113. Bioactive peptides are specific protein fragments that are encrypted in proteins. These peptides can only show their biological effects once they are released from their parent proteins. The diverse physiological effects of bioactive peptides from plant or animal sources have been examined extensively in the literature ,116,117.ACE inhibitory peptides with potential antihypertensive properties have been identified from both animal and plant sources ,123. VPPEgg proteins are other sources to produce anti-hypertensive peptides ,137,138.IRW, IQW and LKP are the ovotransferrin-derived tripeptides initially identified as ACE inhibitors  and lateGW is a novel di-peptide derived from ovotransferrin hydrolysate with antioxidant and anti-inflammatory effects in human umbilical vein endothelial cells . Both GlMarine proteins contain peptides with various biological activities including antihypertensive, antiobesity, antioxidant, antimicrobial, immunomodulatory, and anticancer properties ,159,160.MY is an ACE inhibitory dipeptide with antihypertensive effects derived from sardine muscle hydrolysate . This diHemp seed meal protein hydrolysate has been reported to prevent and treat hypertension in young and adult SHRs, respectively . This trA close link between the high prevalence of the non-communicable diseases such as MetS and hypertension globally and dietary habit has prompted interest in unlocking the potential of food bioactives that can be used to improve health or reduce the risk of diseases. One example is bioactive peptides derived from food proteins. Emerging research findings so far have shown the potential effects of antihypertensive peptides in alleviating several complications of the MetS including adipose tissue dysfunction and insulin resistance. Due to the interplay of pathophysiology between the RAS and insulin resistance, there is a great potential for ACE inhibitors to alleviate other complications of the MetS. Understanding the mechanism(s) of action may be challenging due to the multifunctional characteristics of many bioactive peptides where several pathways are involved for their attributed biological effects. Nevertheless, in the case of protein hydrolysates containing a complex array of peptides, assigning the mechanism of action to a single peptide is impossible unless the peptides responsible for that particular biological effect are identified. While the results obtained from these in vitro and in vivo studies are encouraging, studies on humans are scarce. Therefore, clinical trials are necessary to confirm the effectiveness of these peptides and their safety.


Cultural limitations are identified in the traditional use of qualitative approaches at the expense of quantitative measurement-based monitoring methods to design and assess ergonomic interventions and train operators. To bridge the gap between the return-to-work rehabilitation and other disciplines, several teaching courses, accompanied by further electrodes and instrumentations development, should be designed at all Bachelor, Master and PhD of Science levels to enhance the best skills available among physiotherapists, occupational health and safety technicians and ergonomists.Patients affected by neurological pathologies with motor disorders when they are of working age have to cope with problems related to employability, difficulties in working, and premature work interruption. It has been demonstrated that suitable job accommodation plans play a beneficial role in the overall quality of life of pathological subjects. A well-designed return-to-work program should consider several recent innovations in the clinical and ergonomic fields. One of the instrument-based methods used to monitor the effectiveness of ergonomic interventions is surface electromyography (sEMG), a multi-channel, non-invasive, wireless, wearable tool, which allows in-depth analysis of motor coordination mechanisms. Although the scientific literature in this field is extensive, its use remains significantly underexploited and the state-of-the-art technology lags expectations. This is mainly attributable to technical and methodological  and cultural limitations. The technical  Bipolar and multi-channel (high-density) surface electromyography (sEMG and HDsEMG) represent non-invasive physiological approaches, which enable greater comprehension of the upper limb, lower limb, and trunk muscle behaviors during the execution of movement –4. Diffe° maximum,° averaged rectified value,° root mean square, and- amplitude indices , 6° max- muscle activation timings .Furthermore, sEMG-based algorithms enable greater in-depth comprehension of the muscle coordination mechanisms adopted by the central nervous system (CNS) by estimating the following:- simultaneous activation of several muscles or muscle groups (co-activation), a mechanism adopted by the CNS to stabilize joints, upper and lower limbs, and the spine –11,- myoelectric manifestation of muscle fatigue, estimated by measuring the decrease in fiber conduction velocity , 13, whi- locomotor coordination –26, analHigh-density sEMG recordings are performed using high-density surface grids placed on the skin to evaluate the online spatial distribution of the sEMG activity and estimate the discharge times of several motor units by using decomposition algorithms , 31.Despite the many advantages of sEMG and HDsEMG, these instrumental tools are largely underexploited and their application lags expectations in the fields of ergonomics and occupational medicine. These tools have begun to be applied in the prevention of work-related musculoskeletal disorders, a set of painful inflammatory and degenerative conditions affecting the joints, spinal dizcs, cartilage, muscles, tendons, ligaments and peripheral nerves, caused by manual lifting, pushing and pulling, repetitive movements, and patients handling activities –39. Howeoccupational health and safety technicians and ergonomists which should operate in a multidisciplinary team also constituted by neurologists, occupational physicians, physiatrists, biomedical engineers and movement scientists. We believe that no new professions should be created.People affected by neurological pathologies need to be integrated/reintegrated into their workplaces because their motor disease symptoms appeared when they were of working age, reducing their working capacity , 41 and Occupational health and safety technicians have an academic degree offered at Bachelor of Science level in the same field of physiotherapists . Instead, professionals from different disciplines, for example occupational physicians, who aspire to practice the profession of ergonomist, need a degree that is not conferred by universities. In Europe, the Center for the Registration of the European Ergonomists (CREE) is the professional certification supported by European ergonomics associations and recognized by the International Ergonomics Association (IEA) which provides the title of “Eur.Erg.” and allows to practice the profession of ergonomist in 47 countries.The above premise serves as a rationale for identifying and discussing the barriers to the coherent and widespread use of sEMG in work integration/reintegration.This article represents the perspective, under the aegis of the SOPHIA project, of the Laboratory of Ergonomics and Physiology of the Italian Institute for Insurance against Accidents at Work (INAIL), a public non-profit entity aimed at facilitating the return-to-work of people with motor disorders.Ethical review and approval and written informed consent were not required for the study because no human participants were recruited in the study and in accordance with the local legislation and institutional requirements.Degenerative and acquired neurological diseases, including neuropathies, multiple sclerosis, stroke, spastic paraplegia, cerebellar ataxia, dystonia, traumatic spine and brain lesions, and encephalitis, are disorders, which can affect the motor function during working age and severely limit the autonomy and efficiency of workers , 54–58. Combined with kinematic and kinetic measurements, sEMG is currently widely used in research laboratories by movement scientists and still little in clinical routine by health operators to classify quantitatively the nature and degree of motor dysfunction, analyze the complex relationship between the primary deficit and the adaptive and compensatory mechanisms, categorize patients based on their specific neurological disease, and finally monitor pre-post-treatment. Importantly, as sEMG essentially investigates the final output of motor commands, it can quantify the residual motor function, which can theoretically be monitored continuously in workplace adaptation and integrated into HRC technologies.When a worker affected by a neurological pathology with motor disorders is reintegrated at work, an exhaustive assessment of his/her residual motor function is of primary importance to design and/or adapt his/her workplace well. Additionally, it is necessary to verify and monitor the efficacy of these ergonomic interventions over time.Although no consistent studies have specifically investigated the sEMG of patients with neurological disorders in the workplace context, there are several reports on the residual muscle function assessment of patients with neurological disorders [, for revSome long-lasting degenerative neurological diseases, such as cerebellar ataxia and spastic paraplegia, often begin at a young age and can persist for the entire duration of a subject's working life. This is of interest in the context of work-related rehabilitation because the majority of patients consider themselves capable of working, and approximately 78% of non-working patients seek employment . FurtherThe use of sEMG analysis in patients with degenerative cerebellar ataxia  reveals a series of muscle activation abnormalities . SpecifiIt has been reported that patients with degenerative spastic paraplegia  show increased global  and segmHuman-robot collaborative technologies, particularly exoskeletons, have proven significantly useful in the rehabilitation programs of patients affected by neurological diseases. Physiological parameters with sEMG play a key role in monitoring muscle activation amplitude and fatigue in the design of innovative active exoskeleton controller systems and assessment of their effectiveness on motor performance .Recent improvements in the measurement and real-time classification of myoelectric signals have already facilitated the use of sEMG in man-machine interfaces for controlling prostheses and orthoses among other devices –76.Very recently, human-exoskeleton interfaces were developed for the purpose of rehabilitation to support physically weak and disabled people in performing several motor activities of daily living, such as walking. These interfaces were developed based on new technical and mathematical approaches, including new sEMG signal-processing procedures –82.The performance of these man-machine interfaces is quickly improving owing to neuro-musculoskeletal models driven by neural information obtained from the decomposition of HDsEMG .methodological and cultural limitations. The technical issues are attributable to both monitoring and control functions. With regard to monitoring, the most critical technical aspects are strongly associated with the sEMG technique:The critical issues hindering the widespread adoption of sEMG in return-to-work programs are mainly attributable to technical, - electrode-skin impedance, noise, and electrode contact stability;while the methodological aspects are associated to:- - problems linked to electrode location, size, configuration, and distance;- presence of crosstalk signals .- placement of sEMG electrodes for long hours;- selection of the right sensor setup on the base of the neurological pathology and manual handling activity to be investigated;- management the sEMG amplitude normalization;- definition of appropriate sEMG-related outcomes and normative data.and methodological limitations of the sEMG approach can be minimized and do not justify its non-usage in return-to-work rehabilitation plans. In addition, new wearable sensors and electronic smart devices such as smartphones and tablets allow simple monitoring of the worker at the workplace. Wearable sensors do not interfere with the typical movements performed by workers owing to their miniaturization and wireless communication protocols. In addition, multi-channel sEMG systems are available in wireless versions despite their high number of channels and high data rate. The combination of sensor networks and intelligent work environments provides real-time estimation of physiological parameters, enabling direct feedback to workers who are monitored directly and constantly at the workplace. Real-time monitoring is additionally useful for providing acoustic, visual, and vibro-tactile stimuli to workers  with a significant involvement of erector spinae and rectus abdominus muscles, while handling low loads at high frequency imply neck and upper limbs muscles fatigue. For this reason the choice of channels and the rationale for selecting them should be task-guided.The criticisms related to the use of sEMG to control collaborative wearable trunk and upper limb devices designed to assist people with neurological disabilities are attributable to the algorithms used in human-robot interfaces. These algorithms are used for pattern recognition and classification of patients' movement intentions. Only a few years ago, the performance of sEMG-based interfaces had not reached accuracies acceptable for widespread commercial use . AccuracAnother technical limitation of sEMG-based interfaces for use in HRC technology control is the fact that most wearable assistive devices use traditional control tools, such as bipolar sEMG, to record antagonist muscle activities. This low spatial sampling implies that a maximum of one degree of freedom (DoF) can be controlled. Furthermore, managing up to two DoFs requires slow, sequential, and unintuitive control. The related limited functionality in conjunction with the extensive training required of neurological subjects led to the high rejection rates of these technologies . Currenthas so far been disregarded, owing to cultural barriers, which lead to a preference for qualitative approaches.Without doubt, in job integration/reintegration, the sEMG approach has yet to be adopted and the critical issues associated with it are managed with difficulty. In fact, while reasonable workplace accommodation and disability employment issues are being historically and widely addressed by the governments of the industrialized world, the adoption of instrument-based quantitative assessments of ergonomic interventions A clear testimony of the presence of this educational gap is the worldwide social policies for persons with disabilities , 91, sucThe lack of quantitative approaches suggests that, except in rare cases, sEMG is not taught in the Ph.D. programs of universities and occupational medicine specialization schools. Furthermore, the domestic and international chapters of the Human Factors and Ergonomics Society do not actively promote meetings, conferences, and events to address the challenges of sEMG use. Finally, the reference society for sEMG, the International Society of Electrophysiology and Kinesiology, has thus far not dedicated specific training programs regarding job accommodation. All the above mentioned training activities would typically be successful to address methodological issues, as increased knowledge alone cannot overcome technical limitations.The enormous potential of the sEMG and HDsEMG approaches and their very limited use in return-to-work programs represent a real paradox. It is difficult to determine why sEMG is underused. Perhaps, the most likely reason is that the training provided to professionals is based on more qualitative rather than quantitative approaches, and the transition from one approach to the other is evidently difficult. Professionals in the field have to be trained to understand the extremely variable abnormalities of workers suffering from neurological pathologies and to associate an appropriate return-to-work plan with them.Although sEMG is considered the most informative instrument for muscle monitoring when wearable robots are used, its use poses a number of challenges.One such challenge, which we believe is on the verge of being addressed, pertains to the use of exoskeletons for active rehabilitation therapies. It pertains to the optimization of appropriate smart algorithms to detect patients' intentions and allow exoskeletons to act in synergy with them , 94. TheMyocontrol should be increasingly based on HDsEMG to increase spatial resolution with respect to low-density sEMG and to improve the accuracy of motor workers' intentions recognition. Moreover, machine learning approaches such as artificial neural networks should be used to evaluate the capacity of workers with neurological diseases for myocontrol.In a recent study , HDsEMG occupational health and safety technicians, physiotherapists, ergonomists, occupational physicians, rehabilitation engineers and movement scientists) that has always reached the maximum allowed limit (30 in the case of training courses). The authors of this article begin to observe a first positive impact of these initiatives on the need that operators in the field have in using the sEMG approach.To bridge the gap between the return-to-work concept and other disciplines, several educational activities should be developed to enhance and apply the best skills available in rehabilitation engineering, physiotherapy, occupational therapy, and ergonomics. For a few years, INAIL has been promoting a Ph.D. program together with the Sapienza University of Roma titled “Kinematic, Kinetic, and Electromyographic Characterization of Motor Disabilities and Biomechanical Overload Risk Management for Job Reintegration,” a Masters' course titled “New Methodologies for the Evaluation and Management of Biomechanical Risk and Criteria and Methods for the Adaptation of Workplaces,” and several training courses regarding the role of sEMG in occupational medicine and ergonomics. The participation, although the events were not free and not recognized as continuing education, has always been conspicuous with a number of participants  results in altered motor unit recruitment and decreased maximal voluntary motor unit firing rate that can be detected by sEMG monitoring. A specific scenario could be to adapt the workplace and to modify the work-task according to the subjects' abnormal fatiguing performance, by assisting the workers with devices and/or reducing the amount and the duration of the work-related activity. Furthermore, an individualized rehabilitative program could be planned to improve the impact of the work-task on the fatigability in a long-term period.The abnormal muscle co-activation is another example of common problem identifiable by sEMG in several neurological disorders  which can be detected by measuring the simultaneous time-varying sEMG signal in many muscles. It is known that patients with balance disorders increase the muscle co-activation to control their walking instability in the attempt to stiffen the body segments. Unfortunately, this compensatory mechanism has some negative effects, such as increased metabolic cost and risk of cartilage degeneration. A specific scenario for these workers is to plan an appropriate workplace rehabilitation to improve their balance, to stabilize the body segments and to reduce the need to increase the muscle co-activation.In conclusion, sEMG should be used in job integration plans to:- classify the nature and degree of residual motor function in order to design/adapt the workplace;- assess the efficacy of work-task rehabilitation and ergonomic interventions;- control new assistive technologies such as collaborative robots;- evaluate the biomechanical risk during the execution of manual handling activities;- plan a preventive rehabilitation program to prevent injury.Including the sEMG approach in work integration/reintegration offers the possibility of designing programs based on the residual motor abilities of the worker and adapting his/her workplace. This allows to consider a wide range of workers with several neurological pathologies and different levels of severity but without a complete inability to perform activities of daily life.To make this possible, Bachelor, Master and PhD programs should be promoted, or at least, supervised and monitored, by scientific societies in the fields of physiotherapy, ergonomics, occupational medicine, biomechanics, electrophysiology and kinesiology, and should include continuing education courses on the use of sEMG specifically oriented to teachers in these fields.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval and written informed consent were not required for the study as per local legislation and institutional requirements.AR, MS, and FD planned the manuscript, performed the literature searches, wrote the text and revised the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.