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Actas Dermo-sifiliograficas 2020Recurrent aphthous stomatitis is a chronic inflammatory disease of the oral mucosa. It is characterized by painful mouth ulcers that cannot be explained by an underlying... (Review)
Review
Recurrent aphthous stomatitis is a chronic inflammatory disease of the oral mucosa. It is characterized by painful mouth ulcers that cannot be explained by an underlying disease. Recurrent oral mucosal ulcers require a proper differential diagnosis to rule out other possible causes before recurrent aphthous stomatitis is diagnosed. The condition is common, with prevalence rates ranging from 5 to 60% in different series. Its pathogenesis is unknown, but multiple factors are considered to play a part. There are no standardized treatments for this condition and none of the treatments are curative. The goal of any treatment should be to alleviate pain, reduce the duration of ulcers, and prevent recurrence.
Topics: Humans; Mouth Mucosa; Oral Ulcer; Pain; Recurrence; Stomatitis, Aphthous
PubMed: 32451064
DOI: 10.1016/j.ad.2019.09.004 -
Cell Mar 2022Fungal communities (the mycobiota) are an integral part of the gut microbiota, and the disruption of their integrity contributes to local and gut-distal pathologies....
Fungal communities (the mycobiota) are an integral part of the gut microbiota, and the disruption of their integrity contributes to local and gut-distal pathologies. Yet, the mechanisms by which intestinal fungi promote homeostasis remain unclear. We characterized the mycobiota biogeography along the gastrointestinal tract and identified a subset of fungi associated with the intestinal mucosa of mice and humans. Mucosa-associated fungi (MAF) reinforced intestinal epithelial function and protected mice against intestinal injury and bacterial infection. Notably, intestinal colonization with a defined consortium of MAF promoted social behavior in mice. The gut-local effects on barrier function were dependent on IL-22 production by CD4 T helper cells, whereas the effects on social behavior were mediated through IL-17R-dependent signaling in neurons. Thus, the spatial organization of the gut mycobiota is associated with host-protective immunity and epithelial barrier function and might be a driver of the neuroimmune modulation of mouse behavior through complementary Type 17 immune mechanisms.
Topics: Animals; Fungi; Gastrointestinal Microbiome; Immunity, Mucosal; Intestinal Mucosa; Mice; Mucous Membrane; Mycobiome; Receptors, Interleukin-17; Social Behavior
PubMed: 35176228
DOI: 10.1016/j.cell.2022.01.017 -
Journal Der Deutschen Dermatologischen... Jun 2021Lichen planus (LP) is a chronic lichenoid inflammatory disorder of the skin, mucosa and of the appendages. LP is classically characterized by the presence of a rich...
Lichen planus (LP) is a chronic lichenoid inflammatory disorder of the skin, mucosa and of the appendages. LP is classically characterized by the presence of a rich infiltration of inflammatory T cells, which migrate in the upper part of the dermis, arranged in a band-like pattern. Different sub types of the disease have been so far described. Albeit LP is clinically well defined, the disease still represents a therapeutic enigma. Especially with regard to mucosal or scalp affecting LP types, which often present a recalcitrant and treatment unresponsive course, efficacious therapeutic options are still lacking. Thus, LP represents a disease with a high psychosocial burden. Yet, development in the deciphering of LP pathogenesis reveals possible new druggable targets, thus paving the way for future therapeutic options. In this clinical guide, we summarize the current clinical knowledge and therapeutic standards and discuss the future perspective for the management of LP.
Topics: Alopecia; Chronic Disease; Humans; Lichen Planus; Mucous Membrane; Skin
PubMed: 34096678
DOI: 10.1111/ddg.14565 -
Journal of the European Academy of... Sep 2021This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and...
This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course.
Topics: Autoantibodies; Autoantigens; Dermatology; Humans; Mucous Membrane; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous; Quality of Life; Systematic Reviews as Topic; Venereology
PubMed: 34245180
DOI: 10.1111/jdv.17397 -
Journal of the European Academy of... Oct 2021This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all...
This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10-25% of patients laminin 332 is recognized. In 25-30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials.
Topics: Autoantibodies; Autoantigens; Dermatology; Humans; Mucous Membrane; Pemphigoid, Benign Mucous Membrane; Pemphigoid, Bullous; Venereology
PubMed: 34309078
DOI: 10.1111/jdv.17395 -
Cell Stem Cell Jan 2022The high turnover and regenerative capacity of the adult intestine relies on resident stem cells located at the bottom of the crypt. The enteric nervous system consists...
The high turnover and regenerative capacity of the adult intestine relies on resident stem cells located at the bottom of the crypt. The enteric nervous system consists of an abundant network of enteric glial cells (EGCs) and neurons. Despite the close proximity of EGCs to stem cells, their in vivo role as a stem cell niche is still unclear. By analyzing the mouse and human intestinal mucosa transcriptomes at the single-cell level, we defined the regulation of EGC heterogeneity in homeostasis and chronic inflammatory bowel disease. Ablation of EGC subpopulations revealed that the repair potential of intestinal stem cells (ISCs) is regulated by a specific subset of glial fibrillary acidic protein (GFAP) EGCs. Mechanistically, injury induces expansion of GFAP EGCs, which express several WNT ligands to promote LGR5 ISC self-renewal. Our work reveals the dynamically regulated heterogeneity of EGCs as a key part of the intestinal stem cell niche in regeneration and disease.
Topics: Animals; Enteric Nervous System; Intestinal Mucosa; Intestines; Mice; Neuroglia; Stem Cell Niche
PubMed: 34727519
DOI: 10.1016/j.stem.2021.10.004 -
Cell Stem Cell Oct 2020Epidermal growth factor (EGF) maintains intestinal stem cell (ISC) proliferation and is a key component of organoid growth media yet is dispensable for intestinal...
Epidermal growth factor (EGF) maintains intestinal stem cell (ISC) proliferation and is a key component of organoid growth media yet is dispensable for intestinal homeostasis, suggesting roles for multiple EGF family ligands in ISC function. Here, we identified neuregulin 1 (NRG1) as a key EGF family ligand that drives tissue repair following injury. NRG1, but not EGF, is upregulated upon damage and is expressed in mesenchymal stromal cells, macrophages, and Paneth cells. NRG1 deletion reduces proliferation in intestinal crypts and compromises regeneration capacity. NRG1 robustly stimulates proliferation in crypts and induces budding in organoids, in part through elevated and sustained activation of mitogen-activated protein kinase (MAPK) and AKT. Consistently, NRG1 treatment induces a proliferative gene signature and promotes organoid formation from progenitor cells and enhances regeneration following injury. These data suggest mesenchymal-derived NRG1 is a potent mediator of tissue regeneration and may inform the development of therapies for enhancing intestinal repair after injury.
Topics: Cell Proliferation; Epithelium; Intestines; Neuregulin-1; Paneth Cells
PubMed: 32693086
DOI: 10.1016/j.stem.2020.06.021 -
Peritoneal Dialysis International :... Jul 2021A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing...
GUIDELINE 1
A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing individualized dialysis or when planning modality transfer (e.g. to automated peritoneal dialysis (PD) or haemodialysis) in the context of shared and informed decision-making with the person on PD, taking individual circumstances and treatment goals into account. ().
GUIDELINE 2A
It is recommended that the PSTR is determined from a 4-h peritoneal equilibration test (PET), using either 2.5%/2.27% or 4.25%/3.86% dextrose/glucose concentration and creatinine as the index solute. () This should be done early in the course dialysis treatment (between 6 weeks and 12 weeks) () and subsequently when clinically indicated. ().
GUIDELINE 2B
A faster PSTR is associated with lower survival on PD. () This risk is in part due to the lower ultrafiltration (UF) and increased net fluid reabsorption that occurs when the PSTR is above the average value. The resulting lower net UF can be avoided by shortening glucose-based exchanges, using a polyglucose solution (icodextrin), and/or prescribing higher glucose concentrations. () Compared to glucose, use of icodextrin can translate into improved fluid status and fewer episodes of fluid overload. () Use of automated PD and icodextrin may mitigate the mortality risk associated with fast PSTR. ().
GUIDELINE 3
UF This is easy to measure and a valuable screening test. Insufficient UF should be suspected when either (a) the net UF from a 4-h PET is <400 ml (3.86% glucose/4.25% dextrose) or <100 ml (2.27% glucose /2.5% dextrose), () and/or (b) the daily UF is insufficient to maintain adequate fluid status. () Besides membrane dysfunction, low UF capacity can also result from mechanical problems, leaks or increased fluid absorption across the peritoneal membrane not explained by fast PSTR.
GUIDELINE 4A
Diagnosing intrinsic membrane dysfunction (manifesting as low osmotic conductance to glucose) as a cause of UF insufficiency: When insufficient UF is suspected, the 4-h PET should be supplemented by measurement of the sodium dip at 1 h using a 3.86% glucose/4.25% dextrose exchange for diagnostic purposes. A sodium dip ≤5 mmol/L and/or a sodium sieving ratio ≤0.03 at 1 h indicates UF insufficiency. ().
GUIDELINE 4B
in the absence of residual kidney function, this is likely to necessitate the use of hypertonic glucose exchanges and possible transfer to haemodialysis. Acquired membrane injury, especially in the context of prolonged time on treatment, should prompt discussions about the risk of encapsulating peritoneal sclerosis. ().
GUIDELINE 5
measures of peritoneal protein loss, intraperitoneal pressure and more complex tests that estimate osmotic conductance and 'lymphatic' reabsorption are not recommended for routine clinical practice but remain valuable research methods. ().
GUIDELINE 6
When resource constraints prevent the use of routine tests, consideration of membrane function should still be part of the clinical management and may be inferred from the daily UF in response to the prescription. ().
Topics: Adult; Dialysis Solutions; Glucans; Glucose; Humans; Icodextrin; Peritoneal Dialysis; Peritoneum; Sodium; Ultrafiltration
PubMed: 33563110
DOI: 10.1177/0896860820982218 -
Otolaryngologic Clinics of North America Oct 2016The fibrocartilaginous eustachian tube is part of a system of contiguous organs including the nose, palate, rhinopharynx, and middle ear cleft. The middle ear cleft... (Review)
Review
The fibrocartilaginous eustachian tube is part of a system of contiguous organs including the nose, palate, rhinopharynx, and middle ear cleft. The middle ear cleft consists of the tympanic cavity, which includes the bony eustachian tube (protympanum) and the mastoid gas cells system. The tympanic cavity and mastoid gas cells are interconnected and allow gaseous exchange and pressure regulation. The fibrocartilaginous eustachian tube is a complex organ consisting of a dynamic conduit with its mucosa, cartilage, surrounding soft tissue, peritubal muscles (ie, tensor and levator veli palatine, salpingopharyngeus and tensor tympani), and superior bony support (the sphenoid sulcus).
Topics: Argon; Carbon Dioxide; Central Nervous System; Ear, Middle; Eustachian Tube; Humans; Mucous Membrane; Nitrogen; Oxygen; Peripheral Nervous System; Pressure
PubMed: 27468632
DOI: 10.1016/j.otc.2016.05.003 -
Pathologie (Heidelberg, Germany) Mar 2023Non-neoplastic kidney diseases represent a broad spectrum of diseases. Although their pathogenesis differs, the histological findings may be similar in terms of... (Review)
Review
Non-neoplastic kidney diseases represent a broad spectrum of diseases. Although their pathogenesis differs, the histological findings may be similar in terms of conventional morphology. A precise classification of these diseases is a prerequisite for correct therapy and prognostic assessment. In the diagnostic process, the magnification achieved by electron microscopy is essential and cannot be replaced by any other technique. The most frequent diagnostic questions addressed by ultrastructural studies represent (1) alterations of podocytes (e.g., minimal-change disease), (2) changes of the thickness and structure of the glomerular basement membrane (e.g., diabetic glomerulosclerosis or Alport disease), (3) the presence, characteristics and exact localisation of immune complexes (e.g., membranous glomerulonephritis or lupus nephritis), (4) alterations of endothelial cells and capillaries (e.g., thrombotic microangiopathy) and (5) diseases of the tubular cells (e.g., light-chain nephropathy or toxic effects). Therefore, ultrastructural investigations are-together with conventional microscopy and immunohistochemistry (or immunofluorescence)-an integral part of the so-called triple-diagnostics in routine nephropathology.
Topics: Humans; Endothelial Cells; Kidney; Microscopy, Electron; Lupus Nephritis; Glomerular Basement Membrane
PubMed: 36480038
DOI: 10.1007/s00292-022-01164-3