Mechanical and Thermal Characterization of Bamboo and Interlaminar Hybrid Bamboo/Synthetic Fibre-Reinforced Epoxy Composites.

The main objective of this study was to investigate the mechanical and thermal properties of bamboo, as well as interlaminar hybrid composites reinforced with both bamboo and synthetic fibres in an epoxy matrix. Bamboo and glass, aramid, and carbon bidirectional fabrics were used with a bi-component epoxy matrix to fabricate the composite materials using the vacuum bagging process. The synthetic fabrics were placed on the outer layers, while the bamboo fabrics were used as the core of the hybrid composites. The developed composites were characterized and compared in terms of morphological, physical, and mechanical properties. Further, thermogravimetric (TGA) analysis was used to measure and compare the degradation temperature of the composites studied. Finally, a Scanning Electron Microscopy (SEM) analysis was performed in order to examine the fracture surfaces of the specimens tested. It was found that the fibre hybridization technique significantly improved the general mechanical properties. TGA analysis showed an increase in the thermal stability of the composites obtained by incorporating the synthetic fibres, confirming the effect of hybridization and efficient fibre matrix interfacial adhesion. The results from this work showed that the use of synthetic fibre reinforcements can help to significantly improve the mechanical and thermal properties of bamboo fibre-reinforced composites.

Extracellular Sombrero Vesicles are Hallmarks of Eosinophilic Cytolytic Degranulation in Tissue Sites of Human Diseases.

Eosinophil sombrero vesicles (EoSVs) are large tubular carriers resident in the cytoplasm of human eosinophils, identifiable by transmission electron microscopy (TEM), and important for immune mediator transport. Increased EoSV formation occurs in activated eosinophils in vitro and in vivo. In tissue sites of eosinophilic cytolytic inflammation, extracellular EoSVs are noted, but their frequency and significance in eosinophil-associated diseases (EADs) remain unclear. Here, we performed comprehensive quantitative TEM analyses and electron tomography to investigate the numbers, density, integrity, and three-dimensional (3D) structure of EoSVs in different biopsy tissues from five prototypic EADs (eosinophilic chronic rhinosinusitis/nasal sinuses, ulcerative colitis/intestines, hypereosinophilic syndrome/skin, dermatitis/skin, and schistosomiasis/rectum). The morphology of extracellular EoSVs was also compared with that of cytoplasmic EoSVs, isolated by subcellular fractionation from peripheral blood eosinophils. We demonstrated that: i) eosinophil cytolysis, releasing intact EoSVs and membrane-bound granules, is a consistent event in all EADs; ii) EoSVs persist intact even after complete disintegration of all cell organelles, except granules (late cytolysis); iii) the EoSV population, composed of elongated, curved, and typical sombreros, and the EoSV 3D architecture, diameter, and density remain unchanged in the extracellular matrix; iv) free EoSVs closely associate with extracellular granules; and v) free EoSVs also associate with externalized chromatin during eosinophil ETosis. Remarkably, EoSVs appeared on the surface of other cells like plasma cells. Thus, eosinophil cytolysis/ETosis can secrete intact EoSVs, alongside granules, in inflamed tissues of EADs, potentially serving as propagators of eosinophil immune responses post-cell death.

Repurposing Metformin for periodontal disease management as a form of oral-systemic preventive medicine.

BACKGROUND: Despite the improvements in treatment over the last decades, periodontal disease (PD) affects millions of people around the world and the only treatment available is based on controlling microbial load. Diabetes is known to increase the risk of PD establishment and progression, and recently, glucose metabolism modulation by pharmaceutical or dietarian means has been emphasised as a significant modulator of non-communicable disease development. METHODS: The impact of pharmaceutically controlling glucose metabolism in non-diabetic animals and humans (REBEC, UTN code: U1111-1276-1942) was investigated by repurposing Metformin, as a mean to manage periodontal disease and its associated systemic risk factors. RESULTS: We found that glucose metabolism control via use of Metformin aimed at PD management resulted in significant prevention of bone loss during induced periodontal disease and age-related bone loss in vivo. Metformin also influenced the bacterial species present in the oral environment and impacted the metabolic epithelial and stromal responses to bacterial dysbiosis at a single cell level. Systemically, Metformin controlled blood glucose levels and age-related weight gain when used long-term. Translationally, our pilot randomized control trial indicated that systemic Metformin was safe to use in non-diabetic patients and affected the periodontal tissues. During the medication window, patients showed stable levels of systemic blood glucose, lower circulating hsCRP and lower insulin levels after periodontal treatment when compared to placebo. Finally, patients treated with Metformin had improved periodontal parameters when compared to placebo treated patients. CONCLUSION: This is the first study to demonstrate that systemic interventions using Metformin in non-diabetic individuals aimed at PD prevention have oral-systemic effects constituting a possible novel form of preventive medicine for oral-systemic disease management.

Schistosomiasis Mansoni-Recruited Eosinophils: An Overview in the Granuloma Context.

Eosinophils are remarkably recruited during schistosomiasis mansoni, one of the most common parasitic diseases worldwide. These cells actively migrate and accumulate at sites of granulomatous inflammation termed granulomas, the main pathological feature of this disease. Eosinophils colonize granulomas as a robust cell population and establish complex interactions with other immune cells and with the granuloma microenvironment. Eosinophils are the most abundant cells in granulomas induced by Schistosoma mansoni infection, but their functions during this disease remain unclear and even controversial. Here, we explore the current information on eosinophils as components of Schistosoma mansoni granulomas in both humans and natural and experimental models and their potential significance as central cells triggered by this infection.

In Vivo ETosis of Human Eosinophils: The Ultrastructural Signature Captured by TEM in Eosinophilic Diseases.

Eosinophilic diseases, also termed eosinophil-associated diseases (EADs), are characterized by eosinophil-rich inflammatory infiltrates and extensive eosinophil degranulation with clinically relevant organ pathology. Recent evidence shows that eosinophil cytolytic degranulation, that is, the release of intact, membrane-delimited granules that arises from the eosinophil cytolysis, occurs mainly through ETosis, meaning death with a cytolytic profile and extrusion of nucleus-originated DNA extracellular traps (ETs). The ultrastructural features of eosinophil ETosis (EETosis) have been studied mostly in vitro after stimulation, but are still poorly understood in vivo. Here, we investigated in detail, by transmission electron microscopy (TEM), the ultrastructure of EETosis in selected human EADs affecting several tissues and organ systems. Biopsies of patients diagnosed with eosinophilic chronic rhinosinusitis/ECRS (frontal sinus), ulcerative colitis/UC (intestine), and hypereosinophilic syndrome/HES (skin) were processed for conventional TEM. First, we found that a large proportion of tissue-infiltrated eosinophils in all diseases (~45-65% of all eosinophils) were undergoing cytolysis with release of free extracellular granules (FEGs). Second, we compared the morphology of tissue inflammatory eosinophils with that shown by in vitro ETosis-stimulated eosinophils. By applying single-cell imaging analysis, we sought typical early and late EETosis events: chromatin decondensation; nuclear delobulation and rounding; expanded nuclear area; nuclear envelope alterations and disruption; and extracellular decondensed chromatin spread as ETs. We detected that 53% (ECRS), 37% (UC), and 82% (HES) of all tissue cytolytic eosinophils had ultrastructural features of ETosis in different degrees. Eosinophils in early ETosis significantly increased their nuclear area compared to non-cytolytic eosinophils due to excessive chromatin decondensation and expansion observed before nuclear envelope disruption. ETosis led not only to the deposition of intact granules, but also to the release of eosinophil sombrero vesicles (EoSVs) and Charcot-Leyden crystals (CLCs). Free intact EoSVs and CLCs were associated with FEGs and extracellular DNA nets. Interestingly, not all cytolytic eosinophils in the same microenvironment exhibited ultrastructure of ETosis, thus indicating that different populations of eosinophils might be selectively activated into this pathway. Altogether, our findings captured an ultrastructural signature of EETosis in vivo in prototypic EADs highlighting the importance of this event as a form of eosinophil degranulation and release of inflammatory markers (EoSVs and CLCs).

Pancreatic Cancer From the Patient Perspective: The Time to Act is Now.

Pancreatic cancer is a disease requiring urgent attention from governments and policymakers. Recently, a state of emergency has been declared for this cancer-being the fourth most common cause of cancer deaths in the European Union, it has the lowest survival rate of all common cancers. One of the major reasons pancreatic cancer is associated with such poor outcomes is because it is usually diagnosed at a late stage. Also, investment in research for effective targeted therapies is lacking. This is the perspective of a white paper developed by Digestive Cancers Europe, an umbrella organisation representing European patient organisations. It has been developed after consultation with pancreatic cancer patients, representatives of cancer patient organisations and leading pancreatic cancer healthcare professionals. The purpose of the paper is to highlight the key urgent unmet needs in pancreatic cancer from the patient perspective, ultimately with a view to improve patient care and outcomes in this very challenging disease.

Mitochondrial Population in Mouse Eosinophils: Ultrastructural Dynamics in Cell Differentiation and Inflammatory Diseases.

Mitochondria are multifunctional organelles of which ultrastructure is tightly linked to cell physiology. Accumulating evidence shows that mitochondrial remodeling has an impact on immune responses, but our current understanding of the mitochondrial architecture, interactions, and morphological changes in immune cells, mainly in eosinophils, is still poorly known. Here, we applied transmission electron microscopy (TEM), single-cell imaging analysis, and electron tomography, a technique that provides three-dimensional (3D) views at high resolution, to investigate mitochondrial dynamics in mouse eosinophils developing in cultures as well as in the context of inflammatory diseases characterized by recruitment and activation of these cells (mouse models of asthma, H1N1 influenza A virus (IAV) infection, and schistosomiasis mansoni). First, quantitative analyses showed that the mitochondrial area decrease 70% during eosinophil development (from undifferentiated precursor cells to mature eosinophils). Mitophagy, a consistent process revealed by TEM in immature but not in mature eosinophils, is likely operating in mitochondrial clearance during eosinophilopoiesis. Events of mitochondria interaction (inter-organelle membrane contacts) were also detected and quantitated within developing eosinophils and included mitochondria-endoplasmic reticulum, mitochondria-mitochondria, and mitochondria-secretory granules, all of them significantly higher in numbers in immature compared to mature cells. Moreover, single-mitochondrion analyses revealed that as the eosinophil matures, mitochondria cristae significantly increase in number and reshape to lamellar morphology. Eosinophils did not change (asthma) or reduced (IAV and Schistosoma infections) their mitochondrial mass in response to inflammatory diseases. However, asthma and schistosomiasis, but not IAV infection, induced amplification of both cristae numbers and volume in individual mitochondria. Mitochondrial cristae remodeling occurred in all inflammatory conditions with the proportions of mitochondria containing only lamellar or tubular, or mixed cristae (an ultrastructural aspect seen just in tissue eosinophils) depending on the tissue/disease microenvironment. The ability of mitochondria to interact with granules, mainly mobilized ones, was remarkably captured by TEM in eosinophils participating in all inflammatory diseases. Altogether, we demonstrate that the processes of eosinophilopoiesis and inflammation-induced activation interfere with the mitochondrial dynamics within mouse eosinophils leading to cristae remodeling and inter-organelle contacts. The understanding of how mitochondrial dynamics contribute to eosinophil immune functions is an open interesting field to be explored.

Validation of the Grace Risk Score to Predict In-Hospital and 6-Month Post-Discharge Mortality in Patients with Acute Coronary Syndrome

Abstract Background The wide range of clinical presentations of acute coronary syndrome (ACS) makes it indispensible to use tools for risk stratification and for appropriate risks management; thus, the use of prognosis scores is recommended in the immediat clinical decision-making. Objective To validate the Global Registry of Acute Coronary Events (GRACE) score as a predictor of in-hospital and 6-month post-discharge mortality in a population diagnosed with ACS. Methods This is a prospective cohort study of consecutive patients diagnosed with ACS between May and December 2018. GRACE scores were calculated, as well as their predictive value for in-hospital and 6-month post-discharge mortality. The validity of the model was assessed by two techniques: discriminative power using the area under the receiver operating characteristic curve (AUC) and goodness-of-fit, using the Hosmer-Lemeshow (HL) test, at the 5% level of significance. Results A total of 160 patients were included, mean age 64 (±10.9) years; of which 60% were men. The risk model showed to have satisfactory ability to predict both in-hospital mortality, with an area under the curve (AUC) of 0.76 (95% confidence interval [CI], 0.57-0.95; p = 0.014), and 6-month post-discharge mortality, with AUC of 0.78 (95%CI, 0.62-0.94), p = 0.002. The HL test indicated good-fit for both models of the GRACE score. Conclusion In this study, the GRACE risk score for predicting mortality was appropriately validated in patients with ACS, with good discriminative power and goodness-of-fit. The results suggest that the GRACE score is appropriate for clinical use in our setting.

Beyond oral hygiene, are capacity-altering, biologically based interventions within the moral domain of dentistry?

Oral diseases such as dental caries (DC) and periodontitis are widely prevalent, and existing approaches to managing these conditions have only a limited effect. Accordingly, there is growing interest in the development of novel biological interventions (including, among others, CRISPR-Cas9) that might, in the future, be used to prevent the development of or cure these conditions. However, in addition to familiar concerns about using biological interventions in children who cannot provide valid consent, it is not clear whether the provision of these interventions would fall within the proper domain of dentistry. In this opinion paper, we defend the view that the provision of reasonably safe and effective novel biological interventions aimed at preventing DC and periodontitis should be understood to fall within the proper domain of dentistry. To do so, we first argue that their use would be consistent with existing practice in dentistry. We then argue that: i) they may substantially increase the recipient's wellbeing and future autonomy; and ii) that their use could constitute a form of indirect preventative medicine by addressing a threat to systemic health.

Incidence of injuries in soccer players - mappingfoot: a prospective cohort study / Incidencia de lesiones en jugadores de fútbol - mappingfoot: un estudio de cohorte prospectivo / Incidência de lesões em jogadores de futebol - mappingfoot: um estudo de coorte prospectivo

ABSTRACT Introduction: Although the positive effects of physical activity on global health are well documented, sports practice is associated with a greater risk of injury; in professional soccer in particular, the risk is substantial. Objective: The primary objective of this study was to investigate the incidence of injuries among male athletes competing in the regional soccer championship. The secondary objective was to determine the prevalence of injuries. Methods: In this prospective cohort study, level of evidence II, the incidence and prevalence of injuries were assessed using an adapted version of the UEFA Champions League Study questionnaire. Results: This study included 310 male athletes from ten teams, aged 26.53±4.75 years, height 180.93±6.49 cm, and weight 79.32±8.29 kg, with a 4-month follow-up. Ninety-two injuries were recorded, representing a prevalence of 29.68% injuries. The body part most frequently injured was the lower limbs (86.9%). The main types of injuries were muscle tear/strain (37.0%), sprain/ligament (19.6%), and other injuries (14.1%). The injuries were mainly caused during run/sprint (33.7%), kick (12.0%) and jumping/landing (6.5%). The incidences of injuries were 15.88±8.57, 2.04±1.09, and 3.65±1.50 injuries/1000h of exposure during matches, training, and matches/training, respectively. Time-loss over the season was between 1 and 50 days, and the severity of the injuries was as follows: light (25%), minor (22.8%), moderate (43.5%) and severe (8.7%). Conclusion: This study suggests that there is a higher incidence of injuries during matches compared to training, among male regional soccer championship players. The lower limbs are the body part most affected, with a higher prevalence of rupture/strain in the thigh region, during running/sprinting. Level of evidence II; Prospective Cohort Study .

RESUMEN Introducción: Aunque los efectos positivos de la actividad física en la salud global estén bien documentados, la práctica deportiva está asociada a un riesgo mayor de lesiones; especialmente en el fútbol profesional, el riesgo es sustancial. Objetivo: El objetivo primario de este estudio fue investigar la incidencia de lesiones en atletas del sexo masculino que compiten en campeonatos regionales de fútbol. El resultado secundario fue determinar la prevalencia de lesiones. Métodos: En este estudio de cohorte prospectivo, nivel de evidencia II, la incidencia y la prevalencia de lesiones fueron evaluadas usando una versión adaptada del cuestionario de estudio de la Liga de Campeones de la UEFA. Resultados: Este estudio incluyó a 310 atletas del sexo masculino de 10 equipos, edad 26,53 ± 4,75 años, estatura 180,93 ± 6,49 cm y peso 79,32 ± 8,29 kg, durante 4 meses de acompañamiento. Se registraron 92 lesiones, lo que representa una prevalencia de 29,68%. La parte del cuerpo que tuvo lesiones más frecuentes fueron los miembros inferiores (86,9%). Los principales tipos de lesión fueron rotura/distensión muscular (37,0%), esguince/ligamento (19,6%) y otras lesiones (14,1%). Las lesiones fueron causadas principalmente durante carrera/sprint (33,7%), puntapié (12,0%) y salto/aterrizaje (6,5%). La incidencia de lesiones fue de 15,88 ± 8,57, 2,04 ± 1,09 y 3,65 ± 1,50 lesiones/1000 horas de exposición durante partidos, entrenamientos y partidos/entrenamientos, respectivamente. El tiempo de alejamiento en la temporada varió de 1 a 50 días, y la gravedad de las lesiones fue la siguiente: leve (25%), menor (22,8%), moderada (43,5%) y grave (8,7%). Conclusión: El presente estudio sugiere que existe mayor incidencia de lesiones durante los partidos en comparación con los entrenamientos entre jugadores del sexo masculino en campeonatos regionales de fútbol. Los miembros inferiores son la región más acometida, con mayor prevalencia de rotura/distensión en la región del muslo durante la carrera/sprint. Nivel de evidencia II, Estudio de cohorte prospectivo .

RESUMO Introdução: Embora os efeitos positivos da atividade física na saúde global sejam bem documentados, a prática esportiva está associada a um risco maior de lesões; especialmente no futebol profissional, o risco é substancial. Objetivo: O objetivo primário deste estudo foi investigar a incidência de lesões em atletas do sexo masculino que competem em campeonatos regionais de futebol. O objetivo secundário foi determinar a prevalência de lesões. Métodos: Neste estudo de coorte prospectivo, nível de evidência II, a incidência e a prevalência de lesões foram avaliados usando uma versão adaptada do questionário de estudo da Liga dos Campeões da UEFA. Resultados: Este estudo incluiu 310 atletas do sexo masculino de 10 equipes, com idade 26,53 ± 4,75 anos, estatura 180,93 ± 6,49 cm e peso 79,32 ± 8,29 kg, durante 4 meses de acompanhamento. Foram registradas 92 lesões, o que representa uma prevalência de 29,68%. A parte do corpo que teve lesões mais frequentes foram os membros inferiores (86,9%). Os principais tipos de lesão foram ruptura/distensão muscular (37,0%), entorse/ligamento (19,6%) e outras lesões (14,1%). As lesões foram causadas principalmente durante corrida/sprint (33,7%), chute (12,0%) e salto/aterrissagem (6,5%). A incidência de lesões foi de 15,88 ± 8,57, 2,04 ± 1,09 e 3,65 ± 1,50 lesões/1.000 horas de exposição durante jogos, treinamento e jogos/treinamento, respectivamente. O tempo de afastamento na temporada variou de 1 a 50 dias e a gravidade das lesões foi a seguinte: leve (25%), menor (22,8%), moderada (43,5%) e grave (8,7%). Conclusão: O presente estudo sugere que existe maior incidência de lesões durante os jogos em comparação com os treinos entre jogadores do sexo masculino em campeonatos regionais de futebol. Os membros inferiores são a região mais acometida, com maior prevalência de ruptura/distensão na região da coxa durante a corrida/sprint. Nível de evidência II; Estudo de coorte prospectivo .

Changing our view of the Schistosoma granuloma to an ecological standpoint.

Schistosomiasis, a neglected parasitic tropical disease that has plagued humans for centuries, remains a major public health burden. A primary challenge to understanding schistosomiasis is deciphering the most remarkable pathological feature of this disease, the granuloma - a highly dynamic and self-organized structure formed by both host and parasite components. Granulomas are considered a remarkable example of how parasites evolved with their hosts to establish complex and intimate associations. However, much remains unclear regarding life within the granuloma, and strategies to restrain its development are still lacking. Here we explore current information on the hepatic Schistosoma mansoni granuloma in the light of Ecology and propose that this intricate structure acts as a real ecosystem. The schistosomal granuloma is formed by cells (biotic component), protein scaffolds, fibres, and chemical compounds (abiotic components) with inputs/outputs of energy and matter, as complex as in classical ecosystems. We review the distinct cell populations ('species') within the granuloma and examine how they integrate with each other and interact with their microenvironment to form a multifaceted cell community in different space-time frames. The colonization of the hepatic tissue to form granulomas is explained from the point of view of an ecological succession whereby a community is able to modify its physical environment, creating conditions and resources for ecosystem construction. Remarkably, the granuloma represents a dynamic evolutionary system that undergoes progressive changes in the 'species' that compose its community over time. In line with ecological concepts, we examine the granuloma not only as a place where a community of cells is settled (spatial niche or habitat) but also as a site in which the functional activities of these combined populations occur in an orchestrated way in response to microenvironmental gradients such as cytokines and egg antigens. Finally, we assert how the levels of organization of cellular components in a granuloma as conventionally defined by Cell Biology can fit perfectly into a hierarchical structure of biological systems as defined by Ecology. By rethinking the granuloma as an integrating and evolving ecosystem, we draw attention to the inner workings of this structure that are central to the understanding of schistosomiasis and could guide its future treatment.

Macrophage modulation of dental pulp stem cell activity during tertiary dentinogenesis.

The interaction between immune cells and stem cells is important during tissue repair. Macrophages have been described as being crucial for limb regeneration and in certain circumstances have been shown to affect stem cell differentiation in vivo. Dentine is susceptible to damage as a result of caries, pulp infection and inflammation all of which are major problems in tooth restoration. Characterising the interplay between immune cells and stem cells is crucial to understand how to improve natural repair mechanisms. In this study, we used an in vivo damage model, associated with a macrophage and neutrophil depletion model to investigate the role of immune cells in reparative dentine formation. In addition, we investigated the effect of elevating the Wnt/ß-catenin pathway to understand how this might regulate macrophages and impact upon Wnt receiving pulp stem cells during repair. Our results show that macrophages are required for dental pulp stem cell activation and appropriate reparative dentine formation. In addition, pharmacological stimulation of the Wnt/ß-catenin pathway via GSK-3ß inhibitor small molecules polarises macrophages to an anti-inflammatory state faster than inert calcium silicate-based materials thereby accelerating stem cell activation and repair. Wnt/ß-catenin signalling thus has a dual role in promoting reparative dentine formation by activating pulp stem cells and promoting an anti-inflammatory macrophage response.

Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth.

Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation.

A new perspective to push forward a stagnated dental world.

Despite the major improvements in clinical dentistry, resulting from dental science efforts to shape current clinical dentistry, it has been almost forty years since a new therapy has reached dental practice. The focused scientific effort on evolving dental materials and equipment to facilitate their use has overshadowed the most important aim for developing new dental techniques: human biology. This opinion piece argues a new mindset in dentistry is crucial for the birthing of innovative treatments. It also discusses the path for a new era of dentistry that welcomes new biologically based approaches, including whole dental pulp and bioengineered tooth regeneration, currently being tested in cutting-edge laboratories around the world. Suggestions will be made to justify the reason clinicians must be educated in molecular biology and how universities and the General Dental Council need to prepare in-qualification or qualified dentists. A new biologically-based era of dentistry is around the corner and dentistry as we know it is changing forever.

Whole Slide Imaging and Its Applications to Histopathological Studies of Liver Disorders.

Histological analysis of hepatic tissue specimens is essential for evaluating the pathology of several liver disorders such as chronic liver diseases, hepatocellular carcinomas, liver steatosis, and infectious liver diseases. Manual examination of histological slides on the microscope is a classically used method to study these disorders. However, it is considered time-consuming, limited, and associated with intra- and inter-observer variability. Emerging technologies such as whole slide imaging (WSI), also termed virtual microscopy, have increasingly been used to improve the assessment of histological features with applications in both clinical and research laboratories. WSI enables the acquisition of the tissue morphology/pathology from glass slides and translates it into a digital form comparable to a conventional microscope, but with several advantages such as easy image accessibility and storage, portability, sharing, annotation, qualitative and quantitative image analysis, and use for educational purposes. WSI-generated images simultaneously provide high resolution and a wide field of observation that can cover the entire section, extending any single field of view. In this review, we summarize current knowledge on the application of WSI to histopathological analyses of liver disorders as well as to understand liver biology. We address how WSI may improve the assessment and quantification of multiple histological parameters in the liver, and help diagnose several hepatic conditions with important clinical implications. The WSI technical limitations are also discussed.

Tooth Repair and Regeneration.

PURPOSE OF REVIEW: Current dental treatments are based on conservative approaches, using inorganic materials and appliances.This report explores and discusses the newest achievements in the field of "regenerative dentistry," based on the concept of biological repair as an alternative to the current conservative approach. RECENT FINDINGS: The review covers and critically analyzes three main approaches of tooth repair: the re-mineralization of the enamel, the biological repair of dentin, and whole tooth engineering. SUMMARY: The development of a concept of biological repair based on the role of the Wnt signaling pathway in reparative dentin formation offers a new translational approach into development of future clinical dental treatments.In the field of bio-tooth engineering, the current focus of the researchers remains the establishment of odontogenic cell-sources that would be viable and easily accessible for future bio-tooth engineering.

Axin2-expressing cells differentiate into reparative odontoblasts via autocrine Wnt/ß-catenin signaling in response to tooth damage.

In non-growing teeth, such as mouse and human molars, primary odontoblasts are long-lived post-mitotic cells that secrete dentine throughout the life of the tooth. New odontoblast-like cells are only produced in response to a damage or trauma. Little is known about the molecular events that initiate mesenchymal stem cells to proliferate and differentiate into odontoblast-like cells in response to dentine damage. The reparative and regenerative capacity of multiple mammalian tissues depends on the activation of Wnt/ß-catenin signaling pathway. In this study, we investigated the molecular role of Wnt/ß-catenin signaling pathway in reparative dentinogenesis using an in vivo mouse tooth damage model. We found that Axin2 is rapidly upregulated in response to tooth damage and that these Axin2-expressing cells differentiate into new odontoblast-like cells that secrete reparative dentine. In addition, the Axin2-expressing cells produce a source of Wnt that acts in an autocrine manner to modulate reparative dentinogenesis.

Promotion of natural tooth repair by small molecule GSK3 antagonists.

The restoration of dentine lost in deep caries lesions in teeth is a routine and common treatment that involves the use of inorganic cements based on calcium or silicon-based mineral aggregates. Such cements remain in the tooth and fail to degrade and thus normal mineral volume is never completely restored. Here we describe a novel, biological approach to dentine restoration that stimulates the natural formation of reparative dentine via the mobilisation of resident stem cells in the tooth pulp. Biodegradable, clinically-approved collagen sponges are used to deliver low doses of small molecule glycogen synthase kinase (GSK-3) antagonists that promote the natural processes of reparative dentine formation to completely restore dentine. Since the carrier sponge is degraded over time, dentine replaces the degraded sponge leading to a complete, effective natural repair. This simple, rapid natural tooth repair process could thus potentially provide a new approach to clinical tooth restoration.