Both animal model and human studies indicate that commensal bacteria may modify type 1 diabetes (T1D) development. However, the underlying mechanisms by which gut microbes could trigger or protect ...from diabetes are not fully understood, especially the interaction of commensal bacteria with pathogenic CD8 T cells. In this study, using islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)-reactive CD8 T cell receptor NY8.3 transgenic nonobese diabetic mice, we demonstrated that MyD88 strongly modulates CD8(+) T cell-mediated T1D development via the gut microbiota. Some microbial protein peptides share significant homology with IGRP. Both the microbial peptide mimic of Fusobacteria and the bacteria directly activate IGRP-specific NY8.3 T cells and promote diabetes development. Thus, we provide evidence of molecular mimicry between microbial antigens and an islet autoantigen and a novel mechanism by which the diabetogenicity of CD8(+) T cells can be regulated by innate immunity and the gut microbiota.
Diabetes is a group of metabolic disorders characterized by persistent hyperglycemia and has become a major public health concern. Autoimmune type 1 diabetes (T1D) and insulin resistant type 2 ...diabetes (T2D) are the two main types. A combination of genetic and environmental factors contributes to the development of these diseases. Gut microbiota have emerged recently as an essential player in the development of T1D, T2D and obesity. Altered gut microbiota have been strongly linked to disease in both rodent models and humans. Both classic 16S rRNA sequencing and shot-gun metagenomic pyrosequencing analysis have been successfully applied to explore the gut microbiota composition and functionality. This review focuses on the association between gut microbiota and diabetes and discusses the potential mechanisms by which gut microbiota regulate disease development in T1D, T2D and obesity.
Aim
To update the existing European Academy of Paediatric Dentistry (EAPD) 2010 policy document on the ‘Best Clinical Practice guidance for clinicians dealing with children presenting with ...Molar-Incisor-Hypomineralisation (MIH).’
Methods
Experts, assigned the EAPD, worked on two different topics: (A) Aetiological factors involved in MIH, and (B) Treatment options for the clinical management of MIH. The group prepared two detailed systematic reviews of the existing literature relevant to the topics and following a consensus process produced the updated EAPD policy document on the ‘Best Clinical Practice guidance for clinicians dealing with children presenting with molar-incisor-hypomineralisation (MIH).’ The GRADE system was used to assess the quality of evidence regarding aetiology and treatment which was judged as HIGH, MODERATE, LOW or VERY LOW, while the GRADE criteria were used to indicate the strength of recommendation regarding treatment options as STRONG or WEAK/CONDITIONAL.
Results
(A) Regarding aetiology, it is confirmed that MIH has a multifactorial aetiology with the duration, strength and timing of occurrence of the aetiological factors being responsible for the variable clinical characteristics of the defect. Perinatal hypoxia, prematurity and other hypoxia related perinatal problems, including caesarean section, appear to increase the risk of having MIH, while certain infant and childhood illnesses are also linked with MIH. In addition, genetic predisposition and the role of epigenetic influences are becoming clearer following twin studies and genome and single-nucleotide polymorphisms analyses in patients and families. Missing genetic information might be the final key to truly understand MIH aetiology. (B) Regarding treatment options, composite restorations, preformed metal crowns and laboratory indirect restorations provide high success rates for the posterior teeth in appropriate cases, while scheduled extractions provide an established alternative option in severe cases. There is great need for further clinical and laboratory studies evaluating new materials and non-invasive/micro-invasive techniques for anterior teeth, especially when aesthetic and oral health related quality of life (OHRQoL) issues are concerned.
Conclusions
MIH has been studied more extensively in the last decade. Its aetiology follows the multifactorial model, involving systemic medical and genetic factors. Further focused laboratory research and prospective clinical studies are needed to elucidate any additional factors and refine the model. Successful preventive and treatment options have been studied and established. The appropriate choice depends on the severity of the defects and the age of the patient. EAPD encourages the use of all available treatment options, whilst in severe cases, scheduled extractions should be considered.
Infantile hemangioma (IH) is the most common pediatric vascular tumor. Its pathogenesis is poorly understood but thought to represent an aberrant response of pluripotent stem cells to stimuli such as ...hypoxia and the renin-angiotensin system. IH usually appears during the first few weeks of life and follows a characteristic natural trajectory of proliferation and involution. Their clinical appearance depends on their depth and distribution. Classification comprises superficial, mixed, and deep IH as well as IH with minimal or arrested growth. Multifocal IHs are more likely to be associated with infantile hepatic hemangioma and, although the need for screening based on a specific number of IH has been recently debated, 5 remains the most widely acceptable cutoff point. Large facial IHs warrant investigation for posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects or aortic coarctation and eye anomalies (PHACE) syndrome. Lumbar IHs warrant investigation for lower body IH and other cutaneous defects, urogenital anomalies, ulceration, myelopathy, bony deformity, anorectal malformations, arterial anomalies, and renal anomalies (LUMBAR) syndrome. Complications of IH include ulceration, obstruction or functional impairment, hypothyroidism, and cosmetic sequelae. Differential diagnoses mostly consist of other vascular tumors and vascular malformations, although IH may sometimes mimic nonvascular tumors or developmental anomalies. Diagnosis is usually clinical and biopsy is rarely indicated. High-frequency ultrasonography may help with the differential diagnosis, particularly with subcutaneous lesions. Referral to other specialists may be required in specific cases.
The main purpose of this research is to investigate and estimate the spillover effects in inbound and domestic tourism flows to 341 cities in mainland China. In conjunction with this, the key ...determinants of tourism flows are also studied in the spatial econometric model. The results confirm the existence of spillover effects in both inbound and domestic tourism flows, and suggest that physical infrastructure factors, tourist attractions, and the SARS outbreak are significant determinants of inbound and domestic tourism flows. In addition, it is found that although the degree of openness to inbound tourists is important for inbound tourism flows, a city’s income is the key to enhancing domestic tourism flows. Significant differences in spillover effects and determinants of tourism flows are also discovered between cities in different regions.
Abstract Type 1 Diabetes (T1D) is an autoimmune disease characterized by the pancreatic infiltration of immune cells resulting in T cell-mediated destruction of the insulin-producing beta cells. The ...successes of the Non-Obese Diabetic (NOD) mouse model have come in multiple forms including identifying key genetic and environmental risk factors e.g. Idd loci and effects of microorganisms including the gut microbiota, respectively, and how they may contribute to disease susceptibility and pathogenesis. Furthermore, the NOD model also provides insights into the roles of the innate immune cells as well as the B cells in contributing to the T cell-mediated disease. Unlike many autoimmune disease models, the NOD mouse develops spontaneous disease and has many similarities to human T1D. Through exploiting these similarities many targets have been identified for immune-intervention strategies. Although many of these immunotherapies did not have a significant impact on human T1D, they have been shown to be effective in the NOD mouse in early stage disease, which is not equivalent to trials in newly-diagnosed patients with diabetes. However, the continued development of humanized NOD mice would enable further clinical developments, bringing T1D research to a new translational level. Therefore, it is the aim of this review to discuss the importance of the NOD model in identifying the roles of the innate immune system and the interaction with the gut microbiota in modifying diabetes susceptibility. In addition, the role of the B cells will also be discussed with new insights gained through B cell depletion experiments and the impact on translational developments. Finally, this review will also discuss the future of the NOD mouse and the development of humanized NOD mice, providing novel insights into human T1D.
Despite an increase in emphasis on psychosocial care in cancer nursing, time constraints and nurses' lack of knowledge in skilled communication continue to be challenges.
To examine how cancer care ...nurses view their communication with patients and how they deal with the psychosocial needs of patients in busy wards.
A qualitative interview study.
Focus groups and individual interviews were conducted with eleven hospital-based cancer nurses in Hong Kong from July 2, 2017 to January 2, 2018.
A qualitative thematic analysis of the data identified three themes: 1. Intentional and unintentional psychosocial care that is secondary in focus; 2. Managing an emotionally challenged environment; 3. Mentoring and learning.
Oncology settings are time-constrained, emotionally charged environments for nurses, and providing psychosocial care for patients is a secondary concern. While proactive strategies can be used to avert patient complaints, being open and attending to the individual needs of patients is equally important to avoid blocking in nurse-patient communication. Despite emotional entanglement and tensions, the positive follow-up strategies used by nurses to manage the patients' emotions and provide psychosocial care reflect good practices. Leadership and support are needed to deal with the nurses' perception that their communication training has been ineffective and their ability to manage strong emotions deficient. Communication skills, honed by making continuous opportunities to communicate available, as well as an understanding of emotional labour, need to be integrated with mindfulness in the nurses' care of themselves and their patients. Notwithstanding the importance of experience in oncology care for junior nurses, it is necessary for both junior and senior nurses to learn about and reflect upon the different forms of emotional labour if value-based care is to be provided. In addition, it is essential for junior nurses to receive continuous coaching and mentoring, and to engage in reflective learning from each clinical encounter with oncology patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity and death. The key cell that prevents albuminuria is the terminally ...differentiated glomerular podocyte. Here we report the evolutionary importance of the enzyme Glycogen Synthase Kinase 3 (GSK3) for maintaining podocyte function in mice and the equivalent nephrocyte cell in Drosophila. Developmental deletion of both GSK3 isoforms (α and β) in murine podocytes causes late neonatal death associated with massive albuminuria and renal failure. Similarly, silencing GSK3 in nephrocytes is developmentally lethal for this cell. Mature genetic or pharmacological podocyte/nephrocyte GSK3 inhibition is also detrimental; producing albuminuric kidney disease in mice and nephrocyte depletion in Drosophila. Mechanistically, GSK3 loss causes differentiated podocytes to re-enter the cell cycle and undergo mitotic catastrophe, modulated via the Hippo pathway but independent of Wnt-β-catenin. This work clearly identifies GSK3 as a critical regulator of podocyte and hence kidney function.
The aim of this study was to characterize the ion release, pH changes and apatite formation ability of two potentially bioactive composites Cention N (CN) and Activa (ACT). Ion release and apatite ...formation was investigated in three different immersion media: Tris buffer pH 7.3 (TB), Artificial Saliva pH 4 (AS4) and Artificial Saliva pH 7 (AS7) in order to mimic the conditions present in the mouth. Fluoride release was followed using an ion selective electrode, whilst all other ions were determined by inductively coupled plasma optical emission spectroscopy. Apatite formation was followed by FTIR and XRD. SEM was used to follow glass degradation and apatite formation on both polished cross-sections and surfaces of the composites.
ACT released very few ions including fluoride upon immersion in TB and AS7, but released more ions including significant quantities of Al in AS4. This would suggest the glasses in ACT are acid degradable fluoro-alumino-silicate glasses similar to the glasses used in glass ionomer cements. There was no evidence of any apatite formation with ACT.
CN released more ions in TB and AS7 than ACT and formed an apatite like phase in AS7. The calcium fluoro-silicate glass in CN was observed to degrade significantly in AS4. CN has bioactive properties that may explain the low incidence of secondary caries found clinically with this composite.
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