The blood–brain barrier (BBB) plays a crucial role in maintaining the specialized microenvironment of the central nervous system (CNS). In aging, the stability of the BBB declines and the permeability increases. The list of CNS pathologies involving BBB dysfunction is growing. The opening of the BBB and subsequent infiltration of serum components to the brain can lead to a host of processes resulting in progressive synaptic, neuronal dysfunction, and detrimental neuroinflammatory changes. Such processes have been implicated in different diseases, including vascular dementia, stroke, Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, hypoxia, ischemia, and diabetes mellitus. The BBB damage is also observed in tauopathies that lack amyloid-β overproduction, suggesting a role for tau in BBB damage. Tauopathies represent a heterogeneous group of around 20 different neurodegenerative diseases characterized by abnormal deposition of the MAPT in cells of the nervous system. Neuropathology of tauopathies is defined as intracellular accumulation of neurofibrillary tangles (NFTs) consisting of aggregated hyper- and abnormal phosphorylation of tau protein and neuroinflammation. Disruption of the BBB found in tauopathies is driven by chronic neuroinflammation. Production of pro-inflammatory signaling molecules such as cytokines, chemokines, and adhesion molecules by glial cells, neurons, and endothelial cells determine the integrity of the BBB and migration of immune cells into the brain. The inflammatory processes promote structural changes in capillaries such as fragmentation, thickening, atrophy of pericytes, accumulation of laminin in the basement membrane, and increased permeability of blood vessels to plasma proteins. Here, we summarize the knowledge about the role of tau protein in BBB structural and functional changes. Tau proteins are the most frequent microtubule-associated proteins in the brain and are characterized as intrinsically disordered proteins. They are abundant in the neurons of the central nervous system (CNS) and have roles primarily in maintaining the stability of microtubules in axons. They are also less expressed in brain-resident immune cells: astrocytes and oligodendrocytes , and vascular PSP. In case of PSP, GGTs, and aging-related tau astrogliopathy, a few reports describing functional changes of NVU exists. For other tauopathies, there are no reports dealing with vascular or NVU changes , but also late-onset cases have been described  function at the BBB using [11C]-verapamil PET in PSP patients revealed increased [11C]-verapamil uptake in basal ganglia and frontal regions, suggesting decreased function of the transporter in these areas. Even if these results were not significant, they showed differences between the patients in various stages of the disease. These results are consistent with regionally decreased P-gp function with the progression of the disease  have been reported. Koga et al.  have invIn the past, CTE was referred to as dementia pugilistica. The recent studies have shown neuropathological evidence of CTE in retired American football players, professional wrestlers, professional hockey or soccer players, as well as in nonathletes. CTE may have different causes, such as falls, motor vehicle accidents, assaults, epileptic seizures, or military combat /CT studies suggest that in about 16% of analyzed AD cases, BBB dysfunction may be present, and this pattern is related to a worse metabolic pattern (Chiaravalloti et al., Clinical studies suggest that the NVU changes may represent an early biomarker of human cognitive dysfunction (Nation et al., However, major questions remain, such as how tau-induced NVU changes are presented at the clinical level and whether early biomarkers of these processes could help in more focused therapeutic intervention in the future.AM, PM, and AK wrote the manuscript. All authors read and approved the final draft of 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.


In recent years, there has been an increased interest observed concerning the relationship between the consumption of highly processed foods and health impact. The growing incidence of chronic diseases in modern society has become a relevant and current topic. Therefore, it is necessary to consider how to reverse the trend of the increased consumption of ready-to-eat and convenient food and return to the well-established eating patterns based on minimally processed foods and freshly prepared meals.The results of numerous studies support the claim that the orientation of global food supply towards ultra-processed foods may partly explain the growing trends in the incidence of chronic non-communicable diseases and an overall higher mortality risk ,2,3,4. TIt should be noted that an increasingly industrialized food system is highly effective in terms of large-scale production and low prices, and it is difficult to replace it as it offers attractive prices and convenience, a long shelf-life, microbiological safety, and thus proper nutritional value . TherefoAccording to Monteiro et al. ,11, ultrParticularly interesting and unique results were presented by Rauber and her team . They prIn sum, average consumption in the UK is alarmingly high, reflecting the prevalence of ultra-processed products on the food market and their aggressive promotion. That situation results in excessive consumption, leading to obesity and other diet-related chronic non-communicable diseases. Therefore, broad-based action of governments to promote consumption of less processed foods with a healthier nutrient profile is becoming critical.Those extensive studies were also followed by other research. Leite et al.  assessedHall et al.  investigIt is impossible to overestimate the fact that governments and public health experts have noticed the necessity of taking action in order to play a greater role in preventive nutrition and health promotion. Such action includes recommendations to limit the amount of salt added to processed foods, remove trans-fatty acids from food, and to order schools to stop supplying unhealthy food to students .In conclusion, recent years have presented observations regarding considerable interest in diet composition in relation to its beneficial nutritional value and health implications. Numerous studies suggest that increasing the consumption of freshly prepared, unprocessed or minimally processed foods with a simultaneous reduction in the share of highly processed foods in the diet would definitely have beneficial effects. The published research  presents


Toward the same path, the possibility to directly induce conversion of fibroblasts into CMs has recently emerged as a promising area for in situ cardiac regeneration. In this review we provide an up-to-date overview of the latest advancements in the application of pluripotent stem cells and tissue-engineering for therapeutically relevant cardiac regenerative approaches, aiming to highlight outcomes, limitations and future perspectives for their clinical translation.Cardiovascular diseases represent the major cause of morbidity and mortality worldwide. Multiple studies have been conducted so far in order to develop treatments able to prevent the progression of these pathologies. Despite progress made in the last decade, current therapies are still hampered by poor translation into actual clinical applications. The major drawback of such strategies is represented by the limited regenerative capacity of the cardiac tissue. Indeed, after an ischaemic insult, the formation of fibrotic scar takes place, interfering with mechanical and electrical functions of the heart. Hence, the ability of the heart to recover after ischaemic injury depends on several molecular and cellular pathways, and the imbalance between them results into adverse remodeling, culminating in heart failure. In this complex scenario, a new chapter of regenerative medicine has been opened over the past 20 years with the discovery of induced pluripotent stem cells (iPSCs). These cells share the same characteristic of embryonic stem cells (ESCs), but are generated from patient-specific somatic cells, overcoming the ethical limitations related to ESC use and providing an autologous source of human cells. Similarly to ESCs, iPSCs are able to efficiently differentiate into cardiomyocytes (CMs), and thus hold a real regenerative potential for future clinical applications. However, cell-based therapies are subjected to poor grafting and may cause adverse effects in the failing heart. Thus, over the last years, bioengineering technologies focused their attention on the improvement of both survival and functionality of iPSC-derived CMs. The combination of these two fields of study has burst the development of cell-based three-dimensional (3D) structures and organoids which mimic, more realistically, the  Myocardial infarction (MI) is associated with necrosis of the cardiac tissue due to the occlusion of the coronary arteries, a condition that irrevocably diminishes oxygen and nutrient delivery to the heart . While ein vivo  or to diIn this review, we will particularly focus on those cell replacement therapies based on the use of pluripotent stem cells (PSCs), either embryonic (ESCs – embryonic stem cells) or induced from somatic cells (iPSCs – induced pluripotent stem cells). Indeed, over the last 15 years, the discovery of iPSCs has opened a new chapter in the field of regenerative medicine for the treatment of degenerative disorders, including HF . SimilarPluripotent stem cell-based therapy has already demonstrated some beneficial effects, including the promotion of cell angiogenesis, increased vascularization, attenuation of cardiac cells apoptosis and the reduction of myocardial fibrosis .in vivo, together with the poor grafting of these cells into the heart after transplantation, are still major unsolved problems linked to the use of PSC-CMs for cell replacement therapy  and the related arrhythmogenic potential  therapy . Over thThis review aims to provide an updated overview on cell-based therapies and tissue-engineering, elucidating current applications and limitations, with a focus on future perspectives for their actual application in the clinics.in vivo in preclinical models of HF (There are two different types of pluripotent stem cells (PSCs): embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). ESCs were first isolated in 1981  from thels of HF . Howeverin vitro  and metabolism . Furthermore, hPSC-CMs exhibit distinct electrophysiological characteristics  and reduced force of contraction, due to an abnormal excitation-contraction coupling and calcium handling. In fact, in hPSC-CMs diverse components of calcium dynamic processes are missing, such as transverse tubules (T-tubules), invagination of the membrane in which channels and receptors key for impulse propagation and contraction are located . A comprIn the context of tissue repair, this immature state may lead to lethal arrhythmia after hPSC-CMs transplantation . Thus, sin vivo has not been irrefutably determined  or at later stages  post intervention . In partHowever, despite the fact that many different types of stem cells and derivatives have been proposed as valuable candidates for regeneration of the myocardium, a general consensus on which cell type should be considered the gold standard for cell replacement therapy of the heart, remains elusive. This issue mostly arises from the complex structure of the cardiac muscle, that is formed by different types of cells , all contributing to the proper functionality of the heart. By now, the majority of preclinical studies have been conducted in two-dimensional culture systems, a condition that does not take into account the multiple interactions occurring in a three-dimensional structure, like the heart: this is among the major issues still limiting the application of cell therapy approaches into the clinics. Thus, in the last years, many studies have directed their efforts to identify the optimal structural and environmental conditions for the development of a three-dimensional (3D) structure able to functionally resemble the cardiac tissue and suitable for heart transplantation. Thanks to the combination of bioengineering methods and the advances in the cardiovascular stem cell biology field, in particular in the protocols for generating CMs from PSCs, significant progress has been made in the development of 3D-cardiac tissue-like structures and their application to cardiac regeneration. The intent of this review is to provide an up-to-date overview of the available technologies and the recent advancements in the field, particularly in relation to their potential applicability for clinical purposes.in vitro should be able to replicate the complex interactions occurring between extracellular environment, cells and specialized tissues within the organ itself, as well as their specific functions. In particular, the cardiac tissue is composed by contractile and non-contractile cells , that are organized as a complex 3D structure. The tightly regulated interaction among these diverse cell types plays a central role in the heart’s function. Although 2D-cell cultures have been – and still are – widely used in cardiovascular research, 3D cell-based systems have the potential to add a layer of complexity and to generate cardiac-like structures which faithfully recapitulate cellular interactions as those in vivo. Furthermore, 3D systems may also integrate scaffolds and biomaterials, mimicking the properties of the extracellular matrix present in the human heart. Thus, in the last years, 3D cell cultures are emerging as a new tool for both drug discovery and regenerative medicine applications. Indeed, the increased knowledge in the cardiovascular biology field boosted the development of 3D cellular systems, that progressively and faithfully reproduce the morphological and functional features of cardiac tissue, overcoming the maturation-related limitations of 2D cultures. A growing number of studies have indeed demonstrated that hPSC-CMs differentiated in 3D systems acquire structural, metabolic and functional properties similar to their adult counterparts , with an engraftment rate exceeding 25%, significantly improving cardiac function  with a central lumen and an epithelium containing microvilli structures  and CFs is highly desirable. On this regard, However, while the self-organization property of the organoids allows generation of a high level of tissue organization, one that cannot be reached by the current tissue engineering approaches with the only requirements of external cues and growth factors cocktails, this characteristic also represents the main weakness of this approach. In fact, the self-assembly process is not subjected to pre-defined extrinsic patterning instructions, but is instead a stochastic event, leading to heterogeneity in shape, size and cell composition . In addiTissue engineering is an emerging and multidisciplinary field which aims at developing functional tissue substitutes for medical purposes, mainly replacement of damaged tissues/organs or drug screening applications. Tissue engineering involves the combinatorial use of cells, materials, biochemical and/or physical factors and engineering methodologies, and has thus far been applied to a large variety of human tissues . The bioin vivo. Therefore, such complexity is not easy to achieve due to several limitations, mainly represented by the response of the host to biomaterials used to build the supports and the limited sources of suitable human cells.The first engineered-based approaches simply implied the addition of cells to natural or synthetic biomaterials, that should mimic extracellular matrix providing mechanical support to the cells. The choice of the biomaterial is indeed key for developing effective cardiac regenerative strategies; biomaterials can indeed have different impacts on survival, proliferation and differentiation of a specific cell type, and allow specific scaffold anchoring to generate a functional tissue. Biomaterials used in tissue engineering can be either natural  or synthetic ; both types of polymers may represent an optimal choice for fabrication of tissue-like cardiac structures and, depending on the specific application, have been alternatively employed to develop engineered constructs for cardiac regenerative purposes .in vivo. However, despite the reported beneficial effects, collagen is a stiff material and this characteristic can impede its mechanical integration into the heart. To overcome this problem, several strategies have been proposed and demonstrated the ability to tune its mechanical properties; among these, Collagen is probably the most important “biomechanical” protein of the human body and it represents one of the most relevant natural polymers used in the field of cardiac regeneration. Indeed, due to its abundance in the ECM, collagen provides an optimal support for cell attachment and growth, and several studies in rodents have demonstrated positive effects of collagen-based scaffolds . ResearcAlginate is another natural material suitable for tissue engineering applications. It is an anionic polymer obtained from brown seaweed and it has been employed for numerous biomedical applications. In fact, alginate possess several characteristics – such as biocompatibility and low toxicity - that made it an ideal candidate for its medical use . AlginatAnother natural biomaterial with some applicability in regenerative therapy is fibrin, an insoluble protein formed from fibrinogen. Use of fibrin has been reported to improve cardiac function by reducing infarct size . Howevertrans-endocardial injection of the hydrogel.The use of a decellularized extracellular matrix (dECM) directly isolated from tissues represents another option to build scaffolds for cardiac tissue engineering and has been applied in several conditions, from myocardial infarction to orthopedic injures . dECM coin vivo. With respect to the cardiovascular field, the most popular synthetic polymers are represented by poly(ethylene glycol), poly(ε-caprolactone), poly(propylene), poly, poly(N-isopropylacrylamide), poly(glycerol sebacate), poly(ester urethane)s s . The autethane)s . In addiethane)s , nanowirethane)s , carbon ethane)s , and polethane)s . Electroethane)s  and polyethane)s  could beethane)s . Differeethane)s . Howeverethane)s . Indeed,pro and cons.A valid alternative option is represented by polythiophene polymers, that are biocompatible and highly soluble in water . In partin vitro by combining bioprinting techniques and human cardiac progenitor cells (hCPCs), demonstrating the applicability of bioprinting in this area of research. Specifically, they demonstrated that hCPCs can be printed in a scaffold containing alginate without affecting cell proliferation and viability; additionally they showed an improvement in the cardiac commitment of the “printed” cells, that exhibited a significant increase of the expression of both, early  and late  cardiac-specific markers  of different polymers by hydrogen bonds and hydrophobic or electrostatic interactions represents one of the proposed approaches to produce natural biomaterials . This te markers . More re markers . By finein vivo. As already mentioned above, the choice of the biomaterial utilized for developing engineered cardiac constructs is one crucial aspect, since this material will constitute the support for the cells, and should guarantee the optimal conditions for their growth, differentiation and survival. Another important parameter to be considered is represented by the “structure” (or “shape”) of the engineered supports, which provide the geometrical patterned for cell organization and for the establishment of cell-cell communication and 3D-microenvironment. Although there is no clear distinction between the different types of engineered-based constructs, based on their geometry and the methodology used for cell assembly, we can mainly identify cell sheets, cardiac patches and actual 3D-engineered cardiac tissue models.However, regardless of the employed strategy, generation of tissue-like engineered structures suitable for regenerative medicine applications needs further considerations, specifically in relation to some aspects that may be critical for their efficacy and potential undesired effects One of the first examples of a tissue-like structure obtained through engineering-based methodologies is represented by cell sheets. Cell sheets are generated by detachment of monolayers of cells, grown at confluency, from the culture surface. Functional tissues can be then fabricated by layering the recovered cell sheets without the need of any scaffold or complicated manipulation. Cell sheets are also used to produce engineered cardiac patches containing aligned CMs. Compared to cell sheets, cardiac patches are thicker engineered supports, which recreate a functioning piece of “heart tissue” and can be used to replace the damaged area of a patient’s heart, to maintain its contractile properties.in vitro; when transplanted in vivo, they were functional and electrically coupled with the recipient myocardium  (PIPAAm), which is temperature-responsive polymer. Under normal culture conditions (37°C), the surface of the dishes is relatively hydrophobic and cells efficiently attach and proliferate. In turn, when temperature decreases to about 32°C , the polymer becomes hydrophilic and a hydration layer forms between the surface of dishes and the cells, leading to their detachment from the culturing surface as an intact sheet, with no need of enzymatic treatments. Using the same approach, in vivo, and demonstrated their ability to drive functional recovery after MI. More recently, in vivo, the generated cardiac sheets led to a significant reduction of the fibrotic area and an increase of the capillarity density in the border zone. However, the cell sheet layering methods still present some limitations mainly related to the number of cell layers that can be superimposed before incurring the decrease in oxygen and nutrients supply to the cells and thus leading to the necrosis of the transplanted patch after its implantation. On this regard, the recent work from in vitro studies and in vivo experiments will certainly establish the therapeutic potential of such cardiac constructs.In terms of technology, detachment of intact cell sheets from the culture surface may be achieved using different approaches. On this regard, in vivo. In fact, engineered cardiac tissue models are generated with the aim of recreating the heart environment, and to provide the proper electrical and mechanical support to the cell for their delivery into the heart. in vivo (in vivo (over 8 weeks after implantation). Similar results were obtained by Engineered cardiac tissue models have recently emerged as promising approaches to repair damaged cardiac tissue as well as suitable platforms for drug/toxicity testing and disease modeling . Through in vivo . However in vivo . To givein vitro. One of the first evidence supporting the maturation of CMs in 3D-engineered constructs is given by the study from The improvement of protocols for differentiation of PSCs toward the cardiac lineage made the production of large amounts of human CMs feasible, bursting the development of human heart surrogates for disease modeling, drug testing and autologous cell therapy applications. On this regard, embedding CMs derived from PSCs into engineered structures has been shown to positively impact cell maturation to different extents, depending on the specific characteristics of the generated 3D-constructs. In fact, even if improved over time, use of both human iPSCs and ESCs still deals with an important issue of cell maturation following cardiac induction On this regard, the recent work from in vitro study of human cardiac functions, in terms of the force, pacemaking activity, contractile properties and electrophysiological parameters  toward CMs in vivo through different strategies   and JAK inhibition. The “newly” generated CMs showed sarcomere organization and expressed cardiomyocyte-specific genes. At the functional level, the authors reported calcium transient and mechanical contraction  . Synthes(miRNAs) . Jayawartraction . LikewisESRRG and MESP1 genes was able to increase cardiac reprogramming from human cells, and to generate CMs showing sarcomere formation and cardiac-specific gene expression. Despite the low efficiency of the current protocols and the need of further studies to develop new and optimized direct reprogramming strategies, these reports are encouraging about the possibility to apply cardiac reprogramming to regenerative medicine in the future.In addition to that, we should consider that cardiac reprogramming of human cells is more difficult – and therefore less efficient – compared to the murine counterpart. Although different types of stem cells have been proposed as potential candidates for cardiac regenerative medicine, there is no consensus about which represents the best choice. Given the complexity of cardiac tissue, which is composed by diverse cell types, human PSCs – mostly iPSCs – are certainly among the most relevant sources. In particular, CMs differentiated from iPSC may represent a realistic option for the regeneration of the injured heart. During the last few decades, researchers have made substantial progress in generating iPSC-CMs which have led to a general better understanding the biology of these cells and, to the definition of highly efficient differentiation protocols. A significant number of different cell therapy strategies that employ iPSC-CMs have been proposed to restore cardiac function, ranging from injection of cells alone, to their combination with ECM-like biomaterials, and to more complicated engineered-based strategies, which aim to faithfully recreate the myocardium. The majority of these approaches have shown – at least to some extent – success in mimicking heart cells and improving cardiac function, providing new hope for the replacement of CMs after the irreversible loss of heart tissue occurring during myocardial infarction . NotablyMore recently, iPSC-based therapies are taking over ESCs, offering a solution that overcomes ethical issues related to the use of embryo-derived material and offering a source of autologous cells for transplantation. Few clinical studies using iPSC-derived cells have already started to treat patients suffering from different diseases, such as neovascular age-related macular degeneration and Parkinson disease . Some prIn this scenario, tissue engineering has emerged in the last years as a new field of research applied to cardiac tissue repair for developing improved strategies to treat cardiac dysfunctions after injury. Advantages of tissue-engineering based methodologies rely on the possibility to provide CMs with the biological environment mimicking that of the heart tissue: tissue engineering allows the creation of suitable three-dimensional matrices resembling the physico-chemical properties of the myocardium in which cells are maintained viable and functional, and therefore with a higher chance to positively act on cardiac regeneration .in vivo in the infarcted heart has emerged as potential option for cardiac regeneration. However, despite the promising results obtained by preclinical research, the approach is still rather immature for its clinical translation and further investigations are needed to develop effective and more efficient strategies to achieve cardiac regeneration in vivo.The progress made by tissue engineering technologies has been encouraging. Indeed, with currently available methodologies, it is feasible to create bio-supports able to incorporate the cells needed for the regeneration of cardiac tissue. However, besides the milestones reached thus far, significant improvements are still mandatory before we could consider their routine use in the clinical field for treatment of patients suffering from myocardial diseases. These improvements mainly regard scaffold production, through the careful analysis of biocompatibility and mechanical properties of the engineered constructs developed for the clinics. Also, further investigations on the interaction occurring between cells and the ECM and vascular integration with the host are highly desirable in order to further ameliorate tissue engineering-based supports, hopefully opening new doors for cardiac regeneration therapy via tissue engineering strategies. In this scenario, the possibility to directly convert fibroblast into CMs MM performed the bibliographic search and wrote the manuscript. ED wrote and revised the manuscript and provided funding.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.


Age-related sarcopenia probably leads to chronic systemic inflammation and plays a vital role in the development of the complications of the disease. Gut microbiota, an environmental factor, is the medium of nutritional support to muscle cells, having significant impact on sarcopenia. Consequently, a significant amount of studies explored and showed the presence of gut microbiome–muscle axis (gut–muscle axis for short), which was possibly considered as the disease interventional target of age-related sarcopenia. However, a variety of nutrients probably affect the changes of the gut–muscle axis so as to affect the healthy balance of skeletal muscle. Therefore, it is necessary to study the mechanism of intestinal–muscle axis, and nutrients play a role in the treatment of senile sarcopenia through this mechanism. This review summarizes the available literature on mechanisms and specific pathways of gut–muscle axis and discusses the potential role and therapeutic feasibility of gut microbiota in age-related sarcopenia to understand the development of age-related sarcopenia and figure out the novel perspective of the potential therapeutic interventional targets. The dynamic balance symbiosis system composed of gut microbiome and the human body is destroyed in CKD state, and the resulting intestinal microecological imbalance can accelerate the progress of sarcopenia . TherefoAt present, the role of the gut–muscle axis in regulating age-related muscle health has been confirmed by animal models and human studies, while its mechanisms have not been systematically understood. We will systematically introduce the mechanisms probably involved, including protein metabolism, systemic chronic inflammation and metabolic resistance, mitochondrial dysfunction, and modulation of host gene expression .de novo, such as tryptophan, which represents the fundamental substrates for muscle protein anabolism  is involved in the development of sarcopenia . The chaIt is suggested that age-related sarcopenia is closely associated with metabolic resistance . There iAtopobium parvulum was the most prominent microbe associated with mitochondrial dysfunction and the relative abundance of A. parvulum correlates negatively with both the level of butyrate producers and the mitochondrial protein expression. Besides, the loss of butyrate producers will cause decreased butyrate production that in turn will impair mitochondrial functions  and folate, which may prevent reduction of muscle function through improving muscle anabolism, as well as preventing both hyperhomocysteinemia-induced oxidative stress and endothelial damage  of a limited number of bacteria, are non-digestible carbohydrates and therefore have healthy effects on the host . There arebiotic , and morrebiotic . Cani etrebiotic . Probiote amount . Sarcopeleukemia . Besideslantarum . Treatme in mice . As for  in mice . Interesr people . Howeverr people . Moreover people , which mr people .Fecal microbiota transplantation (FMT) is the infusion of a solution of donor feces to patients . Many stPrevotella, some Firmicutes, and SCFAs are significantly associated with consumption of a Mediterranean diet (During aging, most of gut microbiota alterations due to diet, in other words, gut microbiota composition, depends heavily on diet composition . It is sean diet . In factean diet . In thisean diet . We willA study shows that protein consumption is correlated positively with gut microbiota diversity , and theBifidobacterium (Bifidobacterium in the adolescent group and Bifidobacterium longum in the lycopene-treated middle-aged group increases and is accompanied by dose-dependent changes in blood, liver metabolism, and skeletal muscle and skin parameters. Additionally, RSV, a polyphenol found in walnuts, berries, and grapes, is capable of improving muscle performance in mature aged mice (Recently, an animal study shows that feeding a mixture of SCFAs to GF mice was able to improve muscle strength . In addiacterium . Melatonacterium . It possacterium . The relged mice . After 4ged mice . DietaryThere are no pharmacologic agents for the treatment of sarcopenia, and the main treatment of sarcopenia is physical therapy for muscle strengthening and gait training . ExercisIn conclusion, gut microbiota plays a highly important role in skeletal muscle, and chronic inflammation is the main pathogenic mechanism of sarcopenia. In fact, systemic chronic inflammation also represents the substrate of aging and a significantly important risk factor for both morbidity and mortality in older people . HoweverAll the authors listed have made a rational and substantial contribution to the work and approved the publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Understanding consumers’ food choices and the psychological processes involved in their preferences is crucial to promote more mindful eating regulation and guide food design. Fortifying foods minimizing the oral dryness, rough, and puckering associated with many functional ingredients has been attracting interest in understanding oral astringency over the years. A variety of studies have explored the sensorial mechanisms and the food properties determining astringency perception. The present review provides a deeper understanding of astringency, a general view of the oral mechanisms involved, and the exciting variety of the latest methods used to direct and indirectly quantify and simulate the astringency perception and the specific mechanisms involved. The human being consciously interacts with the surrounding environment through its five senses, which determines the sensory perception. Perception is defined in the Oxford dictionary as “the awareness through the senses interpreted in the light of experience”. In other words, sensorial perception is the consciousness arising through a single sense or a combination of multiple senses with personal factors. The oral perception of food is the result of food features interacting in the mouth and immediately interpreted by the brain . The senGiven the recent trend to fortify consumables with functional ingredients and simultaneously minimize their sometimes undesired mouthfeel, the mechanisms of oral development of astringency have attracted more interest . Astringad stringere, which means “to bind”. It was once considered a basic taste modality in ancient Indian culture. However, since then, it was understood as a tactile sensation due to the mechanical effect of the decreased salivary lubrication [Astringency has Latin origin from the word rication . In the rication  suggesterication , who advrication  also defrication  reportedrication .The astringency perception arises from the interaction of astringents with the oral cavity, e.g., tissues, cell membrane proteins, epithelial cells, mechano, and chemo-receptors. Consequently, many mechanisms, beyond simple lubrication, drive this mouthfeel .The oral cavity is coated and lubricated with a salivary film, which is significantly impaired by the consumption of food and beverages . The filDespite the proposed general events, a more in-depth understanding of the continuity and properties of the salivary pellicle and its disruption by the astringents is still needed in order to validate this holistic point of view ,16.The most studied mechanism of astringency is the interaction between salivary proteins  and the food compounds. Several works have shown good correlations between the perceived astringency  and the As mentioned previously, astringency is a complex phenomenon in which multiple events might occur. Different mechanisms can be involved in phenol-protein interaction. This interaction can consequently be affected by the type of noncovalent interactions implicated in the bounding, e.g., hydrophobic effect and hydrogen bonds . It is gThe report mentioned above corroborated a previous model for tannins . The modchorda tympani and glossopharyngeal nerves to tannic acid (an astringent) were described [In the past, the electrophysiological responses of rat escribed . The cheescribed ,27. Receescribed . The mecescribed . Concernescribed .When it comes to the molecular phenomenon of astringency, this topic has become more popular, mainly on studying the interaction of different types of proteins present in saliva with polyphenols . HoweverOther studies also defend the existence of a relationship between the astringency and the oral production of salivary PRP, which can be affected by the consumption of dietary fibers or tannins ,34,35.Numerous and powerful health benefits of some astringent, such as polyphenolic compounds, were reported. However, the ingestion of polyphenol-rich foods and beverages is frequently associated with a tactile dryness and roughness, and constriction perceived throughout the oral cavity. Moreover, tannins can have antinutritional effects, generally attributed to the inhibition of the digestion of dietary proteins, later one having negative impacts on the flavor perception. Even though positive impacts are reported, some authors also point out that certain polyphenolic compounds can difficult the digestion of plant proteins and further impact the digestive mucosa ,36,37.Some examples of astringent foods are red wine, tea, chocolate, and a variety of fruits and nuts. In the case of red wine, an extremely consumed drink in the world, a balanced level of astringency, to make it a desirable product, is required. By wine writers, astringency adds flavors to red wines and extends the finish. Indeed, the renowned winemaker Emile Peynaud states that the effects of harmony, balance, and elegance of astringency, correspond to great red wines ,38. The The complexity of astringency hinders its individualization from other oral sensations. For instance, Lee and Lawless suggested that astringency and bitterness could be confused since certain compounds can induce both . AnotherGreen et al.  proposedMoreover, Fleming et al.  reportedDespite being primarily perceived as a disagreeable oral sensation, especially when intense, astringency is under certain circumstances a desirable feature, that can provide the pleasant sensation of “cleanness” in the mouth, removing after-tastes and fatty mouth coating sensations, as corroborates Des Gachons et al. . For insSeveral factors influence the perception of astringencies, such as saliva composition, oral pH and temperature, surface properties of the oral cavity, and composition in the oral fluid . The following The astringency of the phenolic compounds increases with the presence of added acid or lowered pH of the foods . DecreasThe actual oral pH will depend on the amount and buffering capacity of saliva on the initial pH of the food. Therefore, a protein-based astringency should consider the pH, concentration, buffering capacity, and pH-related aggregation and how that alters physiological processes occurring in the mouth.The mouth is a highly vascularized region whose temperature quickly returns to typical values after consumption of hot or cold foods or beverages. Therefore, to study the actual influence of temperature on food perception can be a complex process. Temperature can affect hydrogen bonds and trigger the formation of hydrophobic bonds, and consequently, it is an essential parameter in protein–phenolic interactions. Moreover, polyphenols bind strongly to proteins at a higher temperature according to a model protein system .However, the effect of temperature also depends on the type of astringent compound in question. For temperatures of 7 °C or 18 °C, the intensity of astringency in the water of tannic acid or catechin does not differ significantly . CranberSaliva is the most crucial component defining the surface chemistry of the human mouth when it is fully covered. It consists of approximately 98% water and a variety of electrolytes and proteins, such as proline-rich proteins (PRPs), statherin, P-B peptide, cystatins, mucins, histatins, urea, ammonia, uric acid, glucose, cholesterol, and fatty acids . The salSalivary PRPs are considered the leading family of salivary proteins associated with astringency . They coMucin-glycoproteins, or mucins, are responsible for the viscoelastic properties of all mucosal secretions and also play a role in astringency perception. Two of the most essential MG1 (MUC5B) and MG2 (MUC7) salivary mucins are secreted by the submandibular and sublingual glands, as well as some smaller salivary glands . The intThe influence and interaction of saliva are addressed in several studies providing insightful information about the perceived astringency. Beecher et al.  showed tThe high viscoelasticity and fluid properties of the salivary film and its lubrication regime alter with foods and beverages consumption . A reducThe incorporation of polysaccharides in foods can modify the texture and flavor perception, which consequently can determine their acceptance ,78. The Currently, there is no technique able to replicate the whole complexity and accurately quantify the sequence of events involved in the oral development of astringency. A wide array of different techniques is needed to cover the behavior of the individual components and their interactions, to further correlate with the food properties.Astringency has been measured with direct and indirect methodologies and by simulating molecular interactions of compounds of interests. They will be discussed in the following sections.Textural and sensorial evaluation is often an essential step in developing new food products and optimizing processing techniques. Currently, sensory analysis is one of the most used methods to evaluate astringency. The sensory analysis uses the human senses, i.e., vision, smell, touch, taste, and hearing, to assess the attributes of a product and measure human responses to foods .Many attribute the conception of sensory science to the 1940s with the development of consumer or hedonic food acceptance methodologies by the US Army Corps of Engineers . By thatThe descriptive sensory models, which are the most sophisticated tools in the arsenal of the sensory scientist, detect and describe the qualitative and quantitative sensory components of a consumer product by trained panels of judges . This teThe selection phase is essential to motivate and understand how committed each panelist is. The panel should be selected, taking into account a series of factors, such as health status, allergies, personality, education, dietary habits, verbal creativity, previous experience, medication, sensitivity, and use of products. Panelists are then trained to implement a common language and scale. The descriptive language should be precisely defined and contain enough terms to include all attributes of interest, but it should not be overwhelming. The system adopted during training will depend on the approach of the method chosen, available time, and on the products under test . Various evaluation methods are available, including the flavor profile method, texture profile method, quantitative descriptive analysis, spectrum method, quantitative flavor profiling, and free-choice profiling . As theiUntil a few years ago, animal models for astringency had not been reported. Animals offer the chance of a more straightforward evaluation of astringency. They can, for instance, lend direct or indirect support to an association between tannin interactions with salivary proteins and astringency perception, according to their expressed preferences in analyzing the relevant actions on taste and aversion .Three requirements must be met to consider an animal as a sensory model: (a) the sensitivity for the tested substance should be comparable to that of humans, (b) should be genetically homogeneous, and (c) must respond a behavioral paradigm that can be associated with a direct phenomenon linked to astringency . MoreoveA genetically homogeneous naive mouse model has already been used to study the influence of tannic acid drink intake by observing competitiveness/averseness as an astringent indicator. The animal preference index proposed is based on the two-bottle preference test . The tasSpectroscopic methods and techniques have been very successful for the routine analysis, quality control, and bioprocess monitoring of food production. They allow real-time and simultaneous monitoring of multiple compounds  and to dThe usage of UV spectroscopy to predict astringency in wine by tannin quantification was first suggested by Ribéreau-Gayon . Since tThe analytical method of sodium dodecyl sulfate-page (SDS-Page) is widely used for the detection and authentication of species present in food products. It uses the principle of electrophoresis separation of proteins based on molecular weight differences using SDS .Sarni-Manchado et al.  have expSince then, this technique arose as a useful tool to investigate the behavior of salivary proteins involved in astringency and their interactions . Such knThe Saliva Precipitation Index (SPI) is an index evaluating the precipitation abilities of phenolic or other astringent compounds with saliva, which makes use of SDS-Page. SPI is frequently used in the wine industry to analyze selected salivary proteins precipitated after reaction with wine polyphenols. SPI analysis comprises five stages: (1) preparation of resting saliva and stimulated saliva, (2) Binding assays, (3) SDS–PAGE electrophoresis, (4) Densitometry, and (5) SPI  . ConductQuantification of the protein precipitation is an alternative technique to indirectly measure the perception of astringency against the standard estimation procedure of the gelatin index. The gelatin index is an in vitro method, which uses gelatin to reduce astringency and improve clarity . In geneThere has been a growing interest in multivariate processing of sensor signals to extract relevant information such as quality parameters, sample condition, state of a process, and expected human food perception . The eleThe e-tongue and e-nose have been mostly used to analyze the astringency of tea and red wine. For example, Costa and co-works quantified total phenolics and different phenolic fractions in wine and predicted the perceived astringency. They used e-tongues based on potentiometric and voltammetric sensors . More reThe Surface Plasmon Resonance (SPR) phenomenon occurs due to charge-density oscillation that exists at the interface of two media with dielectric constants of opposite signs, for instance, a metal and a dielectric material . SensingLocalized surface plasmon resonance (LSPR) emerged as an effective nano-based technique for the quantitative detection of chemical and biological targets . For exaThe food industry is always searching for new rapid, reliable, and non-destructive techniques. A promising route is based on the use of optical methods, namely the hyperspectral imaging (HSI) technique. This emerging technique integrates conventional imaging and spectroscopy to acquire both sample spatial and spectral information. It allows visualizing the biochemical constituents in the area of the sample .2 concentration treatments (95–98%) promoted anaerobic respiration in the fruit, making tannins insoluble at the end of the treatment and astringency to be no longer detected. The HSI blueprints showed that the tannins distributed similarly in the internal part of the fruit and near the surface. Despite the limitation on the penetration depth of the HSI, it presents great potential.Munera and co-workers have been evaluating the effectiveness of de-astringency treatments by HSI . It has The recently suggested one-component model (OC) approach could determine rice sweetness, acidity, and astringency through sensor measurement, sensory evaluation, chemical analysis, and data processing . The OC Quartz Crystal Microbalance (QCM) is a shear mode device that consists of an extremely sensitive mass balance capable of measuring nanogram to microgram level changes in mass per unit area. Astringent measurement methods, including QCM, precisely measure the interaction of polyphenols with peptides on the quartz crystal surface ,120.Throughout the years, with the application of this technology in fields like biology and biotechnology, the quartz crystal microbalance with dissipation (QCM-D) technique has gained increasing relevance. The QCM-D apparatus determines the changes of mass and viscoelastic properties of surface-bound molecules and is an ideal method for studying biological surface in situ and in real-time. Yan et al.  studied 2, hydroxyapatite, and Teflon (PTFE) modified quartz crystals. Those alterations of the salivary pellicle may be part of the complex sensations of oral astringency [Therefore, QCM-D can be used to monitor salivary events such as alterations at the proteinaceous pellicle, influenced by astringents or salivary proteins. The films can be formed on several materials such as SiOringency .Voltammetric methods are being progressively used in the assessment of polyphenols in foodstuff. Cyclic voltammetry (CV) involves the application of an electric potential to a working electrode, immersed in a solution containing the electroactive compound of interest. The potential is cycled linearly and the resulting current measured.Studies on the influence of sulfur dioxide, glutathione, and ascorbic acid on polyphenol oxidation processes, using CV were relevant to measure wine oxidation and to correlate an analytical response to sensory characteristics such as astringency ,124.More recently, Vilas-Boas et al.  observedThe concept of tribology was enunciated in 1966 by the Department of Education and Science in the UK . It is aThe tribometer includes a cell to test conditions such as the nature of tribo-pairs surfaces, behavior, and speed of the sliding or rotating support plate, lubrication regimes , and solvent composition  . In the Initially, Breslin et al.  validateA minimal number of studies are available hitherto on the application of oral tribology to astringency perception. However, the outcomes have shown the enormous potential of this approach to establish relationships between tribological parameters and the perceived texture and mouthfeel attributes. Shewan et al.  recent rThrough the years, many methods, such as nuclear magnetic resonance (NMR) and X-ray diffraction (XRD), have been extensively used to understand protein structure and the relation to its functionality. However, to fully understand the mechanism of the interactions between processing conditions and proteins, it is increasingly important to explore and comprehend the effect on properties at the molecular or even atomic level .The technique of molecular dynamics (MD) studies atomic and molecular interactions employing the numerical integration of Newton’s equations of motion and choice of adequate force fields to model atoms and molecules interactions. This technique has been widely used to create innovative drug systems in the field of pharmaceutical sciences . HoweverThe emergence of nanotribology and biotribology has led to some studies that could quantify the astringency phenomenon, in particular, the interactions between phenolic compounds and proteins as mechanisms that could explain the perception of astringency in wines. In 2017, Ramos-Pineda et al.  conducteTo understand some astringency mechanisms, in particular, to evaluate the structural characterization of some substances, Nuclear Magnetic Resonance (NMR) is a powerful tool. Researches focus on chemical shift variations, diffusion-ordered spectroscopy, and saturation transfer diffusion. This method has been applied to study PRP-tannin interaction , aggregaMass spectrometry approach, coupled with synchrotron radiation, has helped to better understand the molecular mechanisms involved in this astringency phenomenon, mainly in the determination of the binding site of tannin-PRP interaction. Synchrotron radiation was used to study the photochemical fragmentation of an intrinsically disordered protein and compared it to mass spectrometry data .Polyphenols contribute to the astringency of certain foods and beverages. Those compounds interact with salivary constituents, such as mucins (MUC5B and MUC7). Imaging analysis through Atomic Force Microscopy (AFM) permits the observations of the structural alterations resulting from their interaction .The immunocytochemistry (ICC) is used to visualize cellular molecules under the microscope by conjugation with specific reporters . In the oral context, the mucosal pellicle structure and properties can be analyzed immunostaining the salivary MUC5B. The use of this technique on the mucosal pellicle structure contributes to the understanding of the loss of lubrication and the typical dry and rough feeling of astringency .The present review article reported on how sensory perception plays an essential role in food intake, by describing the several oral mechanisms involved and the techniques to study the interactions between food and the oral processing with emphasis on the astringency mouthfeel.It was possible to conclude that oral astringency is a very complex phenomenon, which has received some research attention, nonetheless, lacking further developments to achieve a proper understanding. Astringency perception arises from the signals resulting from the interaction of astringents with the oral cavity, e.g., saliva, cell membrane proteins, epithelial cells, mechano- and chemoreceptors, that rely on the individual’s characteristics . The brain interprets those signals in conjugation with another simultaneous occurring mouthfeel that can influence the perception. Therefore, many mechanisms, beyond simple lubrication, drive this mouthfeel.A considerable amount of compounds provoke it , and a multitude of factors influence the oral perception . Astringency is approached at many different levels of methods, in particular: direct , indirect detection of salivary complexes  or monitoring the interaction , analyzing the lubrication alteration  or predicting compounds interactions . They are well documented and accessible, with some gaps still existing; nonetheless, they are capable of quantifying the perceived astringency or some property that can be correlated with it.Research limitations have left space to future guidelines that could ensure that consumer expectations are in agreement with the sensory experience of the product consumed. Moreover, indirect methods that could accurately and quickly predict the mouthfeel to aid the design of foods and their personalization for particular consumer groups are still needed.


While the clinical, laboratory and epidemiological investigation results of the Ebola outbreak in Likati Health Zone, Democratic Republic of the Congo (DRC) in May 2017 have been previously reported, we provide novel commentary on the contextual, social, and epidemiological characteristics of the epidemic. As first responders with the outbreak Surveillance Team, we explain the procedures that led to a successful epidemiological investigation and ultimately a rapid end to the epidemic. We discuss the role that several factors played in the trajectory of the epidemic, including traditional healers, insufficient knowledge of epidemiological case definitions, a lack of community-based surveillance systems and tools, and remote geography. We also demonstrate how a collaborative Rapid Response Team and implementation of community-based surveillance methods helped counter contextual challenges during the Likati epidemic and aid in identifying and reporting suspected cases and contacts in remote and rural settings. Understanding these factors can hinder or help in the rapid detection, notification, and response to future epidemics in the DRC. In April 2017 , the ProThe DRC is the second largest and fourth most populated country in Africa and has an environment favorable to zoonotic disease outbreaks such as yellow fever, monkeypox, EVD, and other viral hemorrhagic fevers , 8. TropThe Bas Uélé province—which houses the Likati Health Zone where the May-June 2017 EVD outbreak occurred—is situated in the northern part of the country on the border with the Central African Republic. Likati is a heavily forested, rural area   ~140 km In the 2017 Likati EVD outbreak, the MOH's National Coordination Committee was responsible for managing outbreak response activities, coordinating with national and international partners to develop the outbreak response plan and assembling a multi-sectoral Rapid Response Team , which wWe visited remote villages throughout the Likati Health Zone to interview case contacts, health workers, traditional healers, community and family members who transported patients, and local authorities to determine how and when the outbreak began. We reviewed health records, investigated unexplained deaths and illnesses in humans and animals, and investigated evidence of animal-to-human transmission of EVD. A standard case investigation form was used to record demographic characteristics; determine methods of exposure; document illness onset and signs and symptoms; and identify potentially exposed contacts of suspect, confirmed and probable cases.To improve the early detection of suspected cases, we established a community alert system and trained community health workers to rapidly report and effectively manage community alert cases. Based on the outbreak-specific case definitions , all aleTM Viral Hemorrhagic Fever (VHF) application, version 0.9.60  was identified. Surveillance Team members traveling in the remote health areas and health center personnel were trained to report based on the definition of a suspected case, and would then notify the Rapid Response Team to either transport the patient to receive appropriate medical care or to collect and safely despose of the human remains. Notifications of both alert and suspected cases prompted Surveillance Team investigation; based on the investigation results, alert and suspected cases received a final classification as a probable, confirmed, or non-case according to the specified definitions (Standard case definitions from the 2011 Integrated Disease Surveillance and Response (IDSR) Technical Guide  were adainitions .As previously reported, the outbreak resulted in eight cases, five of which were laboratory confirmed [two by RT-PCR and three by enzyme-linked immunosorbent assay (ELISA)] , 18, andAll contacts completed the 21-day monitoring period by June 2, 2017, with no additional cases identified. The WHO officially declared the EVD outbreak over on July 2, 2017, 42 days after the last confirmed case tested Ebola virus-negative the second time; this period, which is twice the maximum incubation period for Ebola virus, is used to confirm the end of human-to-human transmission .Data suggest that all confirmed and probable cases originated from a single EVD case with bushmeat exposure, and all subsequent cases resulted from human-to-human transmission . The epiThe epidemiological investigation found that the index case became symptomatic  on March 27, 2017, within the incubation period after exposure to bushmeat on March 15, 2017. The index case was treated at a private health facility for ~6 days. The index case experienced hematemesis on April 2, 2017; believing it to be a sign of poisoning, the index case's family brought them to a traditional healer. Showing no signs of improvement after 2 days, the traditional healer referred the patient to a private health center, and upon arrival their temperature was 103.1 degrees Fahrenheit (39.5 degrees Celsius). Symptoms did not improve, and after 1 day of observation they were advised to transfer to the Likati General Reference Hospital. The index case died en route on April 5, 2017, 9 days after symptom onset. Transportation to the hospital was via motorcycle, with a driver and a person assisting with transport. The driver, who later died, was classified as a probable case. The person assisting with transport was classified a confirmed case (serology), and was initially believed to be the index case until the epidemiological investigation, instead, identified them as a contact.Standardizing case definitions, establishing the community alert system, and training community health workers helped to detect, report, and effectively manage community alerts. Coordination with the Communication and Social Mobilization Team  was crucThe epidemiological investigation discovered a limited understanding of EVD among community health workers and healthcare facility staff in Likati. In response to this observed gap, we trained 98 community health workers in seven health areas of Likati Health Zone on the EVD community case definition to identify community alerts, case contact identification, data collection and follow-up procedures, and collection of body temperature.In DRC, previous experience with EVD outbreaks has contributed to improved national preparedness to swiftly coordinate and manage an outbreak response. Decades of experience has led to successful containment strategies that involve both formal health workers, traditional healers, and village social and religious leaders, and substantial efforts have been made in the DRC for capacity-building in epidemiology, laboratory analysis, and patient care, resulting in readily available local expertise that can quickly respond to outbreaks . These pUnderstanding the contextual factors that contribute to notification delays may allow for targeted improvement of the surveillance system in DRC in preparation for future EVD outbreaks. In the 2017 Likati EVD outbreak, first responders identified several factors that contributed to the delays in detection and reporting: the use of traditional healers as first-line healthcare and treatment, insufficient knowledge of EVD case definitions at the health center and among community health workers, lack of community-based surveillance systems and tools, and remote rural geographic characteristics.Interviews with key informants during the epidemiological investigation found that EVD cases—including the index case—received care from traditional healers, which can result in delayed detection of a potential epidemic and the coordinated response necessary to halt viral transmission . TraditiDespite treatment at two local healthcare facilities and a traditional healer, the index case was not properly diagnosed with EVD, leading to a substantial delay in notification of the case. This points to the importance of health workers and communities' ability to recognize the signs and symptoms of EVD. The Surveillance Team observed a limited understanding of EVD among facility-based and community-based health workers in remote health areas of Likati Health Zone; as care seeking from traditional healers or religious leaders often replaces or precedes the formal healthcare system, community health workers should be routinely trained to detect unusual health events in their communities (including suspected EVD cases) and report these events to health authorities. The Surveillance Team's knowledge of this factor led to targeted training of community health workers during the Likati epidemic, emphasizing the important role of community-surveillance systems in remote and rural settings.The Likati epidemic demonstrated the important role of communities in contributing to EVD response efforts. Training and equipping community and facility-based health workers with the tools to collect, manage, and properly report community alerts and suspected cases in line with national and international surveillance rules and regulations is critical to containing epidemics. Tools such as low-literacy flip charts and posters with visual depictions of case definitions and data collection and reporting forms, should be standardized and available for use in both the informal and formal healthcare system to bridge the gap between event- and indicator-based surveillance systems . To be mLikati's remote and rural geography presented challenges that impacted the ability to conduct outbreak investigation and response activities. Impassable roads and poor network coverage affected timely and accurate communication and reporting from remote health areas. Limited transportation infrastructure between Likati and the general reference laboratory in Kinshasa slowed the diagnosis of initial suspected cases until a mobile laboratory unit could be deployed. To address these challenges, Rapid Response Teams  used canThe context in which an EVD outbreak occurs can contribute delays in detection, notification, and rapid response. The 2017 Likati outbreak response was a success; despite delays in notification, the Rapid Response Team successfully worked together to contain the EVD outbreak. Case investigation and contact tracing efforts provided important information about how and when the outbreak began, confirmed the true index case, and developed a comprehensive chain of transmission. The investigation also highlighted epidemiological characteristics that can hinder rapid response efforts; understanding these factors that contribute to notification delays allows for targeted improvement of the DRC's surveillance system to best prepare for future EVD outbreaks. Ongoing efforts to identify gaps, and the motivation of the MOH and international community to implement sustainable solutions, may support improved response to and prevent morbidity and mortality from infectious disease epidemics in the DRC and the wider global community.The data analyzed in this study was obtained from the Directorate of Disease Control, Ministry of Public Health, Kinshasa, and Democratic Republic of the Congo. The following licenses/restrictions apply: all data requested related to the Likati EVD outbreak investigation will be deidentified prior to sharing. Requests to access these datasets should be directed to Dr. Benoit Kebela Ilunga, kebelailunga@gmail.com.BN, LL, MM, and AO were members of the Rapid Response Surveillance Team responsible for developing the epidemiological investigation plan, conducting the investigation, collecting and analyzing epidemiological data, and establishing the chain of transmission. BI provided technical oversight to the Rapid Response Ream and contributed to the design of the outbreak epidemiological surveillance strategy. KG, KS, JH-F, and PM provided technical assistance for surveillance activities during the outbreak and compiled the findings of the epidemiological investigation for the manuscript. KG wrote the first draft of the manuscript and steadily improved based on comments from KS, JH-F, and PM. All authors reviewed and approved the final manuscript.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.


In particular, infected individuals, their relatives, and medical staff face an increased risk of high psychological distress as a result of the ongoing pandemic. Thus, structured psychosocial emergency concepts are needed. The University hospital of Essen has taken up this challenge by creating the PEC concept to reduce psychosocial long-term consequences for infected patients, relatives, and medical staff at the university hospital. The concept includes professional medical as well as psychological support to convey constructive coping strategies and the provision of adequate tools such as the low-threshold online training program (CoPE It), which is accessible via the webpage  Since the beginning of the year, the SARS CoV-2 virus COVID-19) had a significant impact on the lives of the majority of people all around the world (Zhu et al. 9 had a sAs a first step, infected patients, relatives, and medical staff of the Essen University Hospital can contact the coordinating office by telephone either anonymously or not anonymously if required. After primary assessment and the allocation trough the coordinating office, the person who called is subsequently contacted by an expert, a psychologist or physician specialized in psychosomatic medicine. Appointments are held via telephone or video calls. These initial assessments aim to capture the extent and scope of the issue leading to the indicated need. The required number of professionals is then activated. For patients and relatives, the intervention consists predominantly of psychotherapeutic care to achieve stability through psycho-education, mindfulness, and cognitive behavioral skills. It also aims at providing help with topics such as stabilizing interventions, resource activation, relaxation techniques, and coping strategies. For medical staff, recommendations are given to deal with periods of high mental stress, including optional external moderation for highly stressed teams and managers.Additionally, self- and third-party risks are examined at the current time and in case of an emergency, first aid can be activated. If necessary, further treatment in regular psychological care is discussed. Each call is documented pseudonymously to record the content of the telephone calls. Subsequently, feedback is given to the coordinating office, to allow adaptions of the offers to the needs of the individuals seeking help. The coordinating office has the opportunity to involve additional resources. As an additional strategy for low-threshold crisis intervention, there is also the possibility of using a new online intervention, which was developed to reduce psychological distress and worries and improve the feeling of control during the pandemic by supporting burdened individuals in a self-help manner named CoPE It (Bäuerle et al.


The goal of this Research Topic was to explore the myriad ways that researchers conceptualize and study the phenomenon of “talking to oneself” and associated experiences of intrapersonal communication. It is clear that people show wide variations in what kinds of intrapersonal communication they experience, how frequently they engage in it, and what functions it serves. In this Research Topic, the contributors explore a range of explanations for how and why people differ in their inner speech, self-talk, or internal dialogue. Our nine contributors examine the phenomenology of intrapersonal communication, its development in childhood, personality and individual differences in the phenomenon, and its occurrence and use in sport contexts.Variations in intrapersonal communication have been studied using multiple methods, including questionnaires, open-ended self-reports, thinking aloud protocols, imaging techniques, and descriptive experience sampling. Researchers have also started to examine ways that inner speech can be manipulated and the effects of those manipulations on thoughts, emotions, and behavior.Interest in inner speech (covert self-communication) and private speech  has a long history. However, only recently have researchers begun in earnest to explore the wide range of features of intrapersonal communication. For example, research on various aspects of the neuroanatomy of inner speech and the development of inner speech is very active. Recent work also examines individual and personality differences in the nature, content, and frequency of intrapersonal communication. There is also substantial interest in applied work with self-talk in the domain of sport and athletic performance. This Research Topic highlights work in these areas.Grandchamp et al. present a neurocognitive predictive control framework of the condensation, dialogical, and intentionality dimensions of inner speech. They illustrate how the form and syntax of inner speech can be condensed or abbreviated, how inner speech can include monologic and dialogic forms involving the self and others, and how it can be produced both spontaneously and willfully. Through an fMRI protocol, they provide neuroanatomical evidence for the intentionality and dialogicality dimensions and how they work together to produce intrapersonal communication.What is inner speech and how does it occur? With the ConDialInt Model, Geva and Fernyhough highlight the neuro-development of children's inner speech. They show how the dorsal language stream  supports the development and phenomenon of inner speech. Their review of pediatric and adult studies of the dorsal language stream supports the idea that there are parallels between the neuro-anatomical and psychological development of inner speech. This overlap suggests that the maturation of the dorsal language pathway is closely linked to the development of inner speech in childhood.Fernyhough et al. report two studies of the relations among imaginary companions, inner speech, and auditory verbal hallucinations. Noting that imaginary companions in childhood are associated with a variety of positive development outcomes, they compare those with and without such experiences with “hearing voices” and other aspects of inner experience in adulthood. The results showed that, compared to those without a history of imaginary companions, people with such a history reported more frequent auditory verbal hallucinations and higher scores on social-related inner speech. The authors propose that imaginary companions represent a hallucination-like experience that is closely linked to the development of inner speech.Brinthaupt reviews research on individual differences in self-talk frequency according to social isolation and cognitive disruption hypotheses. Individuals who show high levels of experiences of social isolation are expected to show higher levels of self-talk and those with experiences of cognitive disruption  should also show increased levels of self-talk frequency. Research provides moderate support for the social isolation and strong support for the cognitive disruption hypotheses.Several contributors examined personality and individual differences in intrapersonal communication. For example. Oleś et al.. They define inner dialogues as intrapersonal communication characterized by different voices and mutual expressions representing self and a wide variety of others and self-talk as self-referent or self-directed speech. Comparing two multidimensional measures of inner dialogue and self-talk among a sample of Polish and US participants, their results show a significant degree of common variance between these two modes of intrapersonal communication. They suggest that inner dialogues appear to serve contemplative or reflective functions of intrapersonal communication, whereas self-talk may serve dynamic, active processing functions.The relations between inner dialogue types and self-talk functions is the focus of Łysiak examines the relations between inner dialogues, self-talk, and pathological personality traits, using the DSM-5's new hybrid personality disorder system. She finds that people who report more ruminative and confronting inner dialogues also report higher levels of unusual beliefs, psychoticism, and negative affectivity . However, specific self-talk facets were unrelated to DSM-5 pathological personality traits. Łysiak suggests that inner dialogues and self-talk are complementary, relating to different aspects of intrapersonal communication.Heavey et al. provide a more expansive view of individual differences in intrapersonal communication with the development and validation of their Nevada Inner Experience Questionnaire. The authors show how intrapersonal communication in the form of inner speech is one of several kinds of inner experience, including inner seeing, thinking without symbols, and feelings or emotional experiences. They discuss possible reasons for the relative frequency of these experiences and ways that researchers can increase participants' understanding and awareness of these experiences.Finally, Van Raalte et al. explore how Dialogical Self Theory and the method of Descriptive Experience Sampling (DES) can be used to enhance our understanding of inner experience and self-talk in many sports. They argue that focusing on the dialogical aspects of athlete experiences  open new avenues for theory and research in sport psychology. DES can provide the tools to assess these theoretical ideas and insights into the phenomenon of athlete self-talk.Two contributions focused specifically on the role of self-talk in the sport domain. Latinjak et al. describe an innovative reflexive self-talk online intervention that targets goal-directed self-talk. During the 4-week program, the researchers encouraged participants to describe challenging scenarios in training or competition, examine how they use self-talk in those situations, determine its effectiveness, and explore alternative kinds of self-talk that they could use in the future. Results showed enhanced awareness of self-talk use and content refinements that appeared to benefit the emotions, motivation, and confidence of the participants. The authors discuss several implications for sport psychologists and other applied practitioners.In summary, intrapersonal communication is a complex phenomenon, covering concepts such as inner and private speech, self-talk, inner dialogue, and imaginary companions. This topic is an attempt to exemplify the variety of approaches to studying this multi-faceted phenomenon. At the same time, it represents a first step toward a needed synthesis of knowledge about intrapersonal communication. Several unexplored questions remain to be explored, such as whether non-human animals engage in forms of intrapersonal communication and what are the similarities and differences between adaptive and dysfunctional intrapersonal communication. We hope that this selection of articles provides a useful jumping-off point for future intrapersonal communication theorists, researchers, and practitioners.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


This review is focused on the recent developments of nanocomposite materials that combine a thermoplastic matrix with different forms of graphene or graphene oxide nanofillers. In all cases, the manufacturing method of the composite materials has been melt-processing, in particular, twin-screw extrusion, which can then be followed by injection molding. The advantages of this processing route with respect to other alternative methods will be highlighted. The results point to an increasing interest in biodegradable matrices such as polylactic acid (PLA) and graphene oxide or reduced graphene oxide, rather than graphene. The reasons for this will also be discussed. The fabrication of nanocomposites by the incorporation of nanofillers into polymer matrices originates materials with new functional properties while the excellent processing and manufacturing abilities are retained due to the flexibility in polymer matrices . In receIndustrial thermoplastic polymers and composites are usually melt-processed by extrusion followed by injection molding. The extrusion step combines the application of high temperature and high specific mechanical energy in a short time interval. The optimization of extrusion parameters plays a fundamental role on the final properties of the material. Extrusion elements configuration and parameters such as residence time, screw speed, temperature and energy are even more critical when nanocomposites are concerned ,11. The The original definition of graphene  is that Solvent processing. The use of conventional solvents causes serious health and environmental problems which prevent the large-scale usage of these procedures.In situ polymerization. This is an effective method to obtain small quantities of materials for laboratory research applications but not for industrial scale.Melt blending. Several thermoplastic matrices have been modified by melt blending addition of different forms of graphene oxide (GO) and reduced graphene oxide (rGO) nanofillers. However, this process might cause defects in the GO structure, from wrinkles and rolling, to modification of the initial aspect ratio.Methods for achieving the dispersion of graphene in polymer matrices  usually Methods using a solvent need the previous modification of graphene surface in order to disperse it. In situ polymerization can be more efficient. However, both methods are not readily scaled to industrial processing. In contrast with solvent dispersion and in-situ polymerization processes, melt processing, that is, the direct dispersion of graphene nanophases into molten polymer is a cleaner process that can be readily scaled up for industrial applications. However, in order to achieve uniform graphene dispersion into highly viscous polymers, it is still necessary to modify the surface of graphene flakes. Although this modification can be made by chemical functionalization, with the formation of new covalent bonds , it can Melt-processing is usually performed by twin-screw extrusion, which is an environmentally-friendly method immediately applicable to the industrial scale manufacturing of final parts. The versatility of this process allows tailoring the extrusion parameters for each material and application. This method is widely used for the processing of nanocomposites, since the mixing action is based on an elongational flow. Shear and elongation stresses are as the material is transported through the space between screws  .2, the order of magnitude of the force necessary to exfoliate the graphite is about 300 nN/mm2 [Another advantage of extrusion could be the alignment of planar nanostructures such as those of graphene nanomaterials in one preferential direction. Kim et al.  have dis0 nN/mm2 ,26,27, wResearch interest in nanocomposite materials containing graphene has been present for more than a decade , as it b2 hybridization. As it is depicted in As it is mentioned above, there are several kinds of carbon nanofiller that are commonly called graphene. The basic structure of the different graphenic nanomaterials is graphene . This na3 hybrid carbon atoms with functional groups such as hydroxyl and epoxy groups in the surface and carboxylic groups at the edges [One of the most widely used graphene derivatives is graphene oxide. The structure of this nanomaterial consists in graphene sheets with stoppages of sphe edges ,40,41. The edges ,43. Othehe edges ,45,46. IIn this section we have summarized the recent publications on thermoplastic matrix composites modified by addition of graphene-derived nanofillers, modified graphene nanofillers or blends with other nanomaterials. These new nanocomposites have been obtained by extrusion, in most cases twin-screw extrusion, which can be followed by injection molding.The effect of graphene nanoplatelets (GnP) size on PP nanocomposites processed by twin-screw extrusion and injection molding has been studied  to find Recently, the combination of several nanofillers has demonstrated a useful strategy to obtain new nanocomposites with special properties. Synergy between graphene (G) and synthetic graphite (SG) was studied by Altay et al. , when adIn any case, agglomeration is an impasse in the development of PP-based nanocomposites . During Although PP and PLA (see below) are the most widely studied matrices for graphene nanocomposites, many other thermoplastic materials have also been modified to obtain graphene nanocomposites  21,64,6,92,93,94Polyethylene (PE) and different types of polyethylene-derived materials such as linear low-density polyethylene (LLDPE), high density polyethylene (HDPE), or polyfluorinated ethylene propylene and polyethylene naphthalate (PEN) have been studied as matrices ,67,68,69Polyamides (PA) are another commonly used base polymer for the processing of graphene containing nanocomposites ,75,76,772 processed by using twin-screw extrusion [Other widely used thermoplastics include polystyrene (PS), thermoplastic polyurethane (TPU) or poly (methylmethacrylate) (PMMA) matrices ,78,79. Ixtrusion  have beextrusion  to reducxtrusion . ABS  , PPS  of PLA has been explored ,109,110.Biodegradable nanocomposites have been obtained by different approaches, such as thermal reduction of GO during processing of PLA-PBS (polybutylene succinate)-rGO nanocomposites , and theco-3-hydroxyvalerate)), the selected fillers are a combination of rGO and ZnO nanoparticles [In the case of the biodegradable and biocompatible plastics, different mixtures of graphene and other materials are used as fillers to preserve the sustainability of the composites. Manufacturing of biodegradable plastics can reduce the environmental impact and favor renewable resources. However, some properties of biodegradable polymers cannot often be comparable with petroleum-based plastics and the addition of fillers may enhance the physical, chemical and mechanical properties ,115. Bioarticles , to mainThe present work is an overview on very recent developments in the field of graphene-thermoplastic nanocomposites melt processed by extrusion methods. A wide range of matrices have been studied, from commodity polymers to high resistant engineering polymers. Special attention is being paid at the development of biodegradable and biocompatible nanocomposites.Extrusion is readily scalable to industrial manufacturing of final products; however, in most cases, obtaining homogeneous graphene dispersions within the polymer matrix is not a simple task. Segregation and agglomeration of the nanophases are responsible for the lack of improvement in the thermal, mechanical and electrical properties with respect to the unmodified matrix materials.The results of this review denote that the most widely used techniques to improve the dispersion of graphenic nanofillers are sonication, surface modification and the application of a coating layer of graphene on the polymer surface. However, another promising technique that is beginning to yield positive results is the use of ionic liquids, which should be explored more thoroughly. Other strategies are focused on the modification of the extrusion process, the use of masterbatches and the combination of graphene with other materials as hybrid nanophases.The main factors that affect the characteristics and attributes of these nanocomposites are the nanofiller size and concentration. It has been stated that larger sizes of nanofillers result in a reduction of the mechanical properties but an increase of other functional properties, such as electrical conductivity. However, the effect of graphene concentration is not so well defined, and more studies are necessary.A relevant field, which has received limited consideration until the present moment, is that of the influence of the additives on the deformation and fracture modes and on the resistance to degradation of the final materials.Finally, another line of work that is starting to receive attention is the tribological performance of extruded nanocomposites as a function of extrusion parameters, polymer structure, nanofiller orientation and surface modification.


This paper introduces the special issue on race, child welfare, and child well-being. In doing so, I summarize the evidence of racial/ethnic disparities in child well-being after the onset of the COVID-19 pandemic. Recent findings demonstrate that, compared to white children, black and Latino children are more likely to have experienced poverty and food insufficiency, to have had parents lose their jobs, and to be exposed to distance learning and school closures during the pandemic. I argue that though COVID-19 has indeed worsened racial/ethnic disparities in child well-being, it has also served to place a spotlight on the American welfare state’s historical mistreatment of low-income families and black and Latino families in particular. Consider that around three-fourths of black and Latino children facing food insufficiency during the pandemic also experienced food insufficiency prior to the onset of the pandemic. Moving forward, analyses of racial/ethnic disparities in child well-being during the pandemic, I argue, must not only consider the economic shock and high unemployment rates of 2020, but the failure of the American welfare state to adequately support jobless parents, and black and Latino parents in particular, long before the COVID-19 pandemic arrived. In late 2019, when we began working on this Special Issue related to racial inequalities in child welfare and child well-being, we knew well that racial injustice was deeply entrenched into the public institutions of the United States. Black families, in particular, were more likely to encounter a child welfare system, criminal justice apparatus, education system, and a welfare state that each offered more hurdles and less support than for comparable white families. We had little idea at the time, however, of how the events of 2020 would only magnify and exacerbate those injustices. In spring of 2020, the COVID-19 pandemic prompted record levels of unemployment in the USA, hundreds of thousands of deaths, and widespread economic despair. And as with most crises in the USA, the socio-economic consequences of the pandemic did not hit evenly across race and ethnicity.Consider that black and Latino children were much more likely than white children to experience poverty and/or economic hardship in the initial months after the pandemic  systems. The UI system is not simple to navigate: a mountain of administrative hurdles, particularly in states trying to reduce UI caseloads, contribute to a burdensome application process that many unemployed adults choose, at least in pre-pandemic times, to avoid altogether  peers in navigating the American welfare state, calls for its overhaul have gained more traction. While such calls are welcome, families experiencing poverty and hardship prior to the onset of the pandemic would be right to question why, only now, their needs are deemed worthy of adequately addressing.Consider the following. Before the onset of the pandemic, black and Latino children were around twice as likely as white children to live in poverty Fox . In factThese racial/ethnic inequalities cannot be detached from the role of racism itself in influencing the comparative weakness of the American welfare state. A number of studies have documented the role of race and racism in reducing levels of income support for jobless adults  families, expanded access to unemployment benefits, and included a $600 per week unemployment supplement for those who could access unemployment benefits. The benefits were short-lived: the $600 supplements expired at the end of July 2020. Nonetheless, the Congressional Budget Office projected that the new income transfers would amount to more than $450 billion—more than the country spent on all direct income transfers combined in 2019  and Child Tax Credit (CTC). Dr. Curran reveals that The final three papers of the special issue turn attention toward the child welfare system.Dr. Megan Feely and Dr. Emily Adlin Bosk investigate the need to bring a structural risk perspective to reduce racial disproportionality in child welfare. Specifically, the authors confront standardized decision-making procedures that aim to control for implicit or explicit bias in child protective systems (CPS). In doing so, they question how structural factors are accounted for in assessment of risk within CPS, and the consequences of leaving structural factors out of risk assessments procedures. The authors demonstrate that structural racism has been overlooked as an important cause of disproportionality in CPS and offer a revisioning of assessment of risk within child welfare that acknowledges the social determinants of CPS involvement.Dr. Darcey Merritt uses data collected from qualitative research to highlight the lived experience of racism among families involved with the child welfare system. Her work directly incorporates the voices of black and Latino families, revealing how perceptions of race-based mistreatment generates feelings of disrespect, mistrust, and fear, particularly during the oversight and surveillance processes of the child welfare system.The sixth paper in the special issue focuses on racial disparities in the juvenile justice system. Dr. Laura Abrams, Dr. Elizabeth S. Barnert, and Dr. Matthew Mizel apply a mixed-methods approach to examine rates of disproportionality among younger children in the California juvenile justice system. The authors find that at each stage of the juvenile justice system, the overrepresentation of black youth increases relative to white youth. The stakeholders they interview attribute this problem to early phases of the system  where more discretion is applied. The authors conclude that minimum age laws that uniformly exclude younger children from the juvenile justice system altogether would mark a useful step toward reducing disparities in the juvenile justice system.Together, these six studies confront systemic racial inequalities embedded into the American welfare state, child welfare system, and juvenile justice systems. The researchers offer findings that contribute to academic knowledge in their respective fields, but more importantly, they have offered concrete evidence and roadmaps toward reducing racial injustices in the USA I warmly invite policymakers, advocates, and fellow researchers who are concerned with racial inequalities in child welfare and child well-being to engage with, learn from, and act upon each of the papers included in this collection.