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The permeability of the oral or nasal mucosa is higher than that of the skin. Mucosa permeability depends mainly on the thickness and keratinization degree of the tissues. Their permeability barrier is conditioned by the presence of certain lipids. This work has the main aim of reinforcing the barrier effect of oral mucosa with a series of formulations to reduce permeation. Transmembrane water loss of different formulations was evaluated, and three of them were selected to be tested on the sublingual mucosa permeation of drugs. Caffeine, ibuprofen, dexamethasone, and ivermectin were applied on porcine skin, mucosa, and modified mucosa in order to compare the effectiveness of the formulations. A similar permeation profile was obtained in the different membranes: caffeine > ibuprofen~dexamethasone > ivermectin. The most efficient formulation was a liposomal formulation composed of lipids that are present in the skin stratum corneum. Impermeability provided by this formulation was notable mainly for the low-molecular-weight compounds, decreasing their permeability coefficient by between 40 and 80%. The reinforcement of the barrier function of mucosa provides a reduction or prevention of the permeation of different actives, which could be extrapolated to toxic compounds such as viruses, contaminants, toxins, etc.

This study aimed to determine the effects of Zn sources, used with potato fiber (PF) or lignocellulose (LC), on electrolyte concentration and the mucus layer in the large intestine of pigs. The experiment involved 24 barrows with an initial body weight of 10.8 ± 0.82 kg, divided into four groups fed the following diets: LC and ZnSO4, LC and Zn glycinate (ZnGly), PF and ZnSO4, or PF and ZnGly. Fiber supplements provided 10 g crude fiber/kg diet, while Zn additives introduced 120 mg Zn/kg diet. After four weeks of feeding, the pigs were sacrificed and digesta and tissue samples were taken from the cecum and colon. PF increased the water content and decreased the phosphorus concentration in the large intestine in comparison with LC. PF also increased calcium, iron, and chloride concentrations in the descending colon. Mucus layer thickness and histological parameters of the large intestine were not affected. ZnGly diets increased MUC12 expression in the cecum as compared to the LC-ZnSO4 group. In the ascending colon, the PF-ZnGly diet increased MUC5AC expression, while both PF groups had greater MUC20 expression in comparison with the LC-ZnSO4 group. In the transverse colon, the LC-ZnGly group and both PF groups had higher MUC5AC expression in comparison with the LC-ZnSO4 group, and both ZnGly groups had higher MUC20 expression than ZnSO4 groups. PF and ZnGly increased MUC4 and MUC5AC expression in the descending colon. PF and ZnGly may exert a beneficial effect on colon health in pigs by upregulating the expression of the MUC5AC and MUC20 genes and are more effective than LC and ZnSO4.

The conjunctiva-associated lymphoid tissue (CALT) has been used as a target site for mucosal vaccinations in several animals. In this study, we compared the morphological features of CALT in the eyelid and third eyelid between Holstein calves and adult cows. In the eyelids, CALTs in the form of diffused lymphoid tissue (DLT) and lymphatic follicles (LF) were observed, where DLTs were dominant and LFs were scarce. The CALTs of cows comprised T-, B-cells, macrophages, and antigen-presenting cells (APCs). In particular, B-cells were dominant except in the eyelids of the calves. The epithelial layer covering the CALT is often discontinuous and lacks goblet cells. Cytokeratin18 is strongly expressed in the epithelial layer covering the CALT, except in the third eyelids of adult cows. IgA-positive cells were diffusely distributed in the lamina propria of the conjunctiva of the eyelids and third eyelids. The eyelid CALT area in calves was lower than that in adult cows. Furthermore, the CALT of calves had a lower cellularity of B-cells and a higher cellularity of macrophages than that of adult cows. These histological characteristics indicate that CALT plays a role in the mucosal immune-inductive and effector sites. Furthermore, lower cellularity of B-cells in the CALT of calves indicates that the function of CALT as a mucosal immune induction site is less developed in calves than in adult cows.

We have designed a new compound from the non-steroidal anti-inflammatory drug (NSAID) ketoprofen (Ket) and 2-amino-2-(hydroxymethyl)-1,3-propanediol (Tris) precursors, with the aim to reduce the gastrointestinal (GI) side effects of NSAID therapies. We investigated mucosal reactions in a standard rat model of colitis together with methane generation as a possible indicator of pro-inflammatory activation under this condition (approval number: V./148/2013). Whole-body methane production (photoacoustic spectroscopy) and serosal microcirculation (intravital videomicroscopy) were measured, and mucosal damage was assessed (conventional histology; in vivo laser-scanning endomicroscopy). Inflammatory markers were measured from tissue and blood samples. Colitis induced an inflammatory response, morphological colonic damage and increased methane output. Ket treatment lowered inflammatory activation and colonic mucosal injury, but macroscopic gastric bleeding and increased methane output were present. Ket-Tris reduced inflammatory activation, methane emission and colonic mucosal damage, without inducing gastric injury. Conjugation with Tris reduces the GI side effects of Ket and still decreases the inflammatory response in experimental colitis. Methane output correlates with the mucosal inflammatory response and non-invasively demonstrates the effects of anti-inflammatory treatments.

Abstract Background Allergic rhinitis (AR) is a complex disease involving both mucosal and systemic immune compartments. Greater understanding of the immune networks underpinning AR pathophysiology may assist with further refining disease‐specific biomarkers. Objective To compare immune gene expression profiles in nasal mucosa and peripheral blood samples between adults with AR and controls without AR. Methods This cross‐sectional study included 45 adults with moderate‐severe and persistent AR (37.6 ± 12.8 years; mean ± SD) and 24 adults without AR (36.6 ± 10.2). Gene expression analysis was performed using the NanoString nCounter PanCancer Immune profiling panel (n = 730 immune genes) in combination with the panel plus probe set (n = 30 allergy‐related genes) with purified RNA from peripheral blood and cell lysates prepared from combined nasal lavage and nasal brushing. Results One hundred and thirteen genes were significantly differentially expressed in peripheral blood samples between groups (p

Background: Lip lentigines are benign pigmentations often raising concerns to physicians and patients for fear of malignancy. Specific dermoscopic patterns of lip (mucosal) lentigines have not been clearly defined in the literature when compared to common facial (nonmucosal) lentigines. Objectives: This study aimed to define key dermoscopic features of lip lentigines to help diagnose these benign lesions more efficiently by calculating the specificity, sensitivity, and positive and negative predictive values (PPV and NPV) of dermoscopic patterns in lip and nonlip facial lentigines. Methods: A retrospective observational study was conducted at a medical center in Southern Taiwan. Dermoscopic images of 12 patients with lip lentigines and seven patients with 12 facial nonlip lentigines were inspected. Pattern recognition was performed via blind review by three clinicians. Dermoscopic images were assessed side by side with 12 published dermoscopic patterns of pigmented lesions, to see whether the patterns were presented. Results: Four dermoscopic patterns (hyphal, overlapping vessels, parallel lines, and fish-scale-like) showed very high specificity and PPV (all 100%) in lip lentigines when compared to facial nonlip lentigines. The sensitivity of these four patterns was 83%, 83%, 67%, and 58% and their NPV was 86%, 86%, 75%, and 71%, accordingly. Interrater consistency analysis from pattern recognition showed good consistency (Cronbach's alpha = 0.814) among reviewers. Conclusion: Hyphal, overlapping vessels, parallel lines, and fish-scale-like patterns are specific and sensitive dermoscopic patterns of lip lentigines when compared to facial nonlip lentigines. This knowledge of site-specific dermoscopic patterns could be used in characterizing benign and malignant pigmented lesions of the lip in future studies.

IntroductionHypoxia inducible factors (HIF) are widely researched in human medicine for their role in different disease processes. The aim of this study was to investigate the expression and distribution of HIF in experimental small intestinal ischemia in the horse.MethodsIn 14 horses under general anesthesia, segmental jejunal ischemia with 90% reduction in blood flow was induced. The horses were randomly divided into two groups of seven horses, one subjected to ischemic postconditioning (IPoC) by delayed reperfusion, and a control group (group C) undergoing undelayed reperfusion. Intestinal samples were taken pre-ischemia, after ischemia and after reperfusion. Following immunohistochemical staining for HIF1α and -2α, the immunoreactivity pattern in the small intestine was evaluated by light microscopy, and the mucosal enterocyte and muscularis staining were semi-quantitatively scored. Additionally, mucosal HIF1α protein levels were determined by an Enzyme Linked Immunosorbent Assay (ELISA), and mRNA levels of HIF1α and its target genes by a two-step real-time Reverse Transcriptase Polymerase Chain Reaction. Statistical comparison was performed between the groups and time points using parametric and non-parametric tests (p < 0.05).ResultsAll cell types exhibited cytoplasmic and nuclear immunoreactivity for HIF1α. After reperfusion, the cytoplasmic staining of the crypt and villus enterocytes as well as the villus nuclear staining significantly increased, whereas the perinuclear granules in the crypts decreased. The protein levels showed a significant decrease in group C at reperfusion, with lower HIF1α levels in group C compared to group IPoC during ischemia and reperfusion. No other group differences could be detected. In the HIF2α stained slides, mild to moderate cytoplasmic staining yet no nuclear immunoreactivity of the enterocytes was observed, and no significant changes over time were noted.Discussionthe changes in HIF1α immunoreactivity pattern and expression over time suggest that this transcription factor plays a role in the intestinal response to ischemia in horses. However, the current study could not identify an effect of IPoC on HIF distribution or expression.

ObjectiveA vibratory vocal fold replacement would introduce a new treatment paradigm for structural vocal fold diseases such as scarring and lamina propria loss. This work implants a tissue-engineered replacement for vocal fold lamina propria and epithelium in rabbits and compares histology and function to injured controls and orthotopic transplants. Hypotheses were that the cell-based implant would engraft and control the wound response, reducing fibrosis and restoring vibration.Study designTranslational research.MethodsRabbit adipose-derived mesenchymal stem cells (ASC) were embedded within a three-dimensional fibrin gel, forming the cell-based outer vocal fold replacement (COVR). Sixteen rabbits underwent unilateral resection of vocal fold epithelium and lamina propria, as well as reconstruction with one of three treatments: fibrin glue alone with healing by secondary intention, replantation of autologous resected vocal fold cover, or COVR implantation. After 4 weeks, larynges were examined histologically and with phonation.ResultsFifteen rabbits survived. All tissues incorporated well after implantation. After 1 month, both graft types improved histology and vibration relative to injured controls. Extracellular matrix (ECM) of the replanted mucosa was disrupted, and ECM of the COVR implants remained immature. Immune reaction was evident when male cells were implanted into female rabbits. Best histologic and short-term vibratory outcomes were achieved with COVR implants containing male cells implanted into male rabbits.ConclusionVocal fold cover replacement with a stem cell-based tissue-engineered construct is feasible and beneficial in acute rabbit implantation. Wound-modifying behavior of the COVR implant is judged to be an important factor in preventing fibrosis.Level of evidenceNA. Laryngoscope, 128:153-159, 2018.

The key side effects of antiplatelet therapy are associated with the damage of the upper gastrointestinal tract (GIT) mucous that can lead to erosions or ulcers and specifically complicated by bleeding. Aim. To assess the upper gastrointestinal mucosal condition by endoscopic and histological methods in patients with stable coronary arteries disease receiving long-term antiplatelet therapy with gastrointestinal bleeding (GIB) history or with high risk of this complication. Materials and methods.The study included patients from the single-center prospective registry of long-term antithrombotic therapy REGATTA-1. The gastric mucosa endoscopic examination with biopsy was performed in 20 patients with gastrointestinal bleeding history less than 1 year ago and in 24 patients without GIB, which have concomitant risk factors such as erosions and ulcers history and/or persistent dyspepsia clinical signs. The mucosal condition (erosions and ulcers) was estimated using a modified Lanz scale. The presence of Helicobacter pylori was determined by Histological verification. The inflammatory process characteristics were evaluated according to the modified Sydney classification. All participants received antithrombotic therapy at the time of esophagogastroduodenoscopy; 81.8% of patients received proton pump inhibitors. Results. Chronic inflammation (93.2%), atrophy (59.1%), multiple erosions (45.5%) or ulcers (18.2%) were the most frequent endoscopic finding. H. pylori infection, found in mucosal samples in 90.9% of patients was one of the most important pathogenesis mechanism, which support the gastrointestinal mucosa damage. Conclusion. Mucosal damage endoscopic signs remains despite long-term proton pump inhibitors therapy in patients with coronary arteries disease and concomitant GIB risk factors, receiving antithrombotic therapy. H. pylori contamination may be the cause of these changes. Therefore, its active screening and eradication is necessary in such patients.

Abstract Background: Carbonated beverages include soft drinks or sodas which contain carbondioxide and that when ingested for prolonged period of time lowers the intra-esophageal pH and can lead to histopathological changes in the mucosa. Objective: To study the effects of prolonged intake of carbonated drinks on the oesophagus of albino rats. Method: This experimental study was carried out at Shaheed Mohtarma Benazir Bhutto Medical College for a period of six months. Seventy five rats of wistar strain (gender non specific) were divided into ‘control groups ‘A1 n=10, A2 n=10, A3 n=10 & ‘exposed groups’ B n=15, C n=15 and D n=15.The controls and the exposed animals were fed the same balanced diet, prepared at the lab’s kitchen. The fluid intake of exposed animals was restricted to carbonated drinks only, whereas, the controls were fed water.At the end of the first, third and sixth months, groups A1&B, A2&C and A3&D were sacrificed and histological section of oesophagus were obtained for histomorphological studies. Results: On micrometry, width of the oesophagus of the exposed animals for one month;Group B was higher (17.87) than those of Group A1 (5.70). Those rats sacrificed at the end of the third month; Group C had significantly enlarged wall thickness of the oesophagus compared to A2 group. The average oesophageal wall thickness 13.60?m was found to be more in the exposed group ‘D’, as compared to 4.50?m measured in Control Group A3 (p

Abstract The morphology of the small intestinal mucosa is reflected by the degree of stimuli. Previous studies have come to different conclusion about whether the mucosa is equally symmetrical. The aim of the study is to investigate whether there are structural differences in the mesenteric versus antimesenteric mucosa in mice, rats, and humans. Jejunal biopsies from mice and rats were saved. Samples from human small intestine were obtained from patients undergoing Roux‐en‐Y gastric bypass surgery. Fixed samples were used to morphologically evaluate villus height and enlargement factor due to villi. The number of goblet cells, mast cells, enteroendocrine cells, and Paneth cells were histologically analyzed in the villus structure. Cell turnover was analyzed by Ki‐67 staining. There was a significant increased villi height and villus enlargement factor antimesenterically in mice, rats, and human small intestines. The distribution of goblet cells, mast cells, and Paneth cells were equal while the number of enteroendocrine cells was increased antimesenteric in the human samples. The crypt mitotic activity was almost 20% higher in the antimesenteric part of jejunum. In summary we found longer villi, greater surface enlargement, and increased number of enteroendocrine cells as well as increased cell turnover antimesenterically. These differences may be of importance in understanding normal gastrointestinal physiology in health and disease.

This Perspective presents the potential of the Small Intestinal Axis, a subdivision of the Gut-immune Axis, to modulate systemic inflammation based on sensing contents of the gut lumen. Gut mucosal immunity regulates tolerance to food and gut contents and is a significant factor in maintaining systemic homeostasis without compromising immunity to pathogens. This is achieved through anatomical structures and signaling pathways that link the tolerogenic potential of the proximal small intestine to systemic immunity. Non-live preparations of microbes isolated from human small intestinal mucosa, and the extracellular vesicles (EVs) which they shed, can resolve systemic inflammation without systemic exposure after oral delivery. The mechanism involves primary interactions with pattern recognition receptors followed by trafficking of immune cells through mesenteric lymph nodes. This generates in the periphery a population of circulating CD4+ T cells which have regulatory function but an atypical FoxP3- phenotype. There is no modification of the resident gut microbiome. Discoveries using this novel approach of targeting mucosal microbial elements to the tolerogenic proximal regions of the small intestine are revealing some of the mysteries of the relationship between the gut and immune system. [ABSTRACT FROM AUTHOR]

This study aimed to assess the reliability of two intraoral surface scanners for the representation of the alveolar process in vivo. Complete maxillary scans (CS 3600, Carestream and TRIOS 3, 3Shape) were repeatedly obtained from 13 fully dentate individuals. Scanner precision and agreement were tested using 3D surface superimpositions on the following reference areas: the buccal front teeth area, the entire dental arch, the entire alveolar process, or single teeth by applying an iterative closest point algorithm. Following each superimposition, the mean absolute distance (MAD) between predefined 3D model surfaces was calculated. Outcomes were analyzed through non-parametric statistics and the visualization of color-coded distance maps. When superimpositions were performed on the alveolar process, the median scanner precision was below 0.05 mm, with statistically significant but negligible differences between scanners. The agreement between the scanners was approximately 0.06 mm. When single-tooth superimpositions were used to assess the precision of adjacent alveolar soft-tissue surfaces, the median error was 0.028 mm, and there was higher agreement between the scanners. The in vivo reliability of the intraoral scanners in the alveolar surface area was high overall. Single-tooth superimpositions should be preferred for the optimal assessment of neighboring alveolar surface areas relative to the dentition. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of cold atmospheric plasma (CAP) treatment combined with adhesive filling therapy on rat dental pulps. Cavities were prepared in the first maxillary molars of 20 Sprague Dawley rats. The first molar and the unprepared second molar of one randomly selected maxillary quadrant were treated with CAP. The prepared cavities were filled with composite. After 24 h and 28 days, 10 rats each were killed. Teeth were demineralized and embedded in paraffin and histological sections were stained with hematoxylin–eosin and chloracetatesterase. None of the pulps displayed necrosis. Plasma treatment caused no additional alteration to the dental pulp in combination with adhesive filling therapy. These findings indicate that plasma treatment is compatible with the regenerative potential of the pulp. [ABSTRACT FROM AUTHOR]

Background: The morphology of the epithelium of oral lips comprised of keratinized external epithelium (anteriorly) and non-keratinized or sometimes parakeratinized mucous membrane epithelium (posteriorly). Aims and Objectives: Knowledge of morphometry of lip lining helps in deciding the best site for choosing graft for its better uptake during several dermal grafting procedures following trauma or tumor excision following craniofacial cancers or cosmetic procedures. It also proves useful in dermatopharmacokinetics, in which we monitor the effect of drugs acting on connective tissue by trans labial route and lip augmentation surgeries (esthetic surgery), where care is to be given for dermal fillers not to be injected in muscle core of lip. Materials and Methods: Ten human male cadavers were procured in the Department of Anatomy, King George Medical University, Lucknow, Uttar Pradesh. The rectangle-shaped skin specimen through lower lip which included skin, mucocutaneous junction, and mucosa was stained with hematoxylin and eosin stain. Total of 30 slides were prepared. Thus, readings were obtained for three regions, respectively, with the help of CatCam E-series HD cameras which were installed in light microscope. The following conclusions were drawn for various parameters. Results: Thickness of skin (epidermis+dermis) of lip ranged from 880 μm to 1171 μm among males. Epidermal thickness increases on moving from cutaneous region to mucosa region of lip. Lowest contribution of stratum corneum in thickness of epidermis was observed in vermillion region, while highest contribution was observed in skin region. It was found to be absent in mucosa region of lip. Rete pegs at dermo epidermal junction was found to be maximum in vermillion region and minimum in skin region. Its depth increased as we move from skin to mucosa region of lip. Pattern of rete pegs also showed a characteristic feature in every region of lip. In cutaneous part of lip, rete pegs were shorter and blunt. In vermillion region, they were narrow, long, and slender, while they were longest with blunt end in mucosa region. Depth of dermis was found to be maximum in skin region while minimum in vermillion region. It ranged between 707 μm and 1100 μm. Conclusion: Care should be taken while using dermal fillers in lip augmentation surgeries, especially in vermillion region due to its close proximity to musculature in core of lip. [ABSTRACT FROM AUTHOR]

Intestinal complications are common after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, only scarce data concern herpesvirus incidence in the colonic mucosa post-HSCT. Our purpose was to assess the frequency and clinical significance of cytomegalovirus (CMV), Epstein–Barr virus (EBV), human herpesvirus type 6 (HHV6), and herpes simplex virus (HSV) in the colonic mucosa post-HSCT. The study group included 119 patients of different ages, mostly with leukemias and lymphomas, subjected to allo-HSCT from haploidentical related (48%) or HLA-compatible donors (52%). In total, 155 forceps biopsies of the colonic mucosa were taken in cases of severe therapy-resistant intestinal syndrome post-HSCT. Most samples were taken from the descending, sigmoid, and transverse colon. Intestinal GVHD or local infections were assessed clinically and by histology. EBV, CMV, HSV, and HHV6 were tested in colonic mucosal lysates with commercial PCR assays. HSV was found in <8% of colonic samples, along with high HHV6 and CMV positivity (up to 62% and 35%, respectively) and a higher EBV incidence at 5–6 months post-HSCT (35%). For CMV and EBV, significant correlations were revealed between their rates of detection in blood and colonic mucosa (r = 0.489 and r = 0.583; p < 0.05). No significant relationships were found between the presence of herpesviruses and most patients' characteristics. EBV positivity in colonic samples was correlated with delayed leukocyte and platelet recovery post-HSCT. Higher EBV frequency in the colonic mucosa was found in deceased patients (56% versus 21%, p = 0.02). The correlations among EBV positivity in the colon, lethality rates and delayed hematopoietic reconstitution suggest some relationship with systemic and local EBV reactivation post-transplant. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic inflammation of the gut is a multifactorial, incurable condition that involves interactions between our immune cells and the cells that line the surface layer of gut, known as the epithelium. Interleukin-10, a protein well known to be released by our immune cells, has a protective role in countering inflammation, partly due to the fact that it can block the NFκB pathway, a signalling pathway within cells that promotes genes involved in inflammatory responses. However, we recently showed that laboratory cultures of gut epithelial cells can also synthesise interleukin-10, which acts as a positive regulator of the NFκB pathway to support gut health. In this study here, we investigated further the impact of the role of interleukin-10 on the NFκB pathway and its targets within the gut using a whole animal approach, and confirmed that NFκB activation is indeed positively regulated by interleukin-10, affecting the expression of downstream target genes and their encoded proteins. This strengthens the importance of the interleukin-10/NFκB signalling pathway axis in maintenance of gut health and response to damage, inflammation, and infection. Understanding cell-specific biological roles of interleukin-10 and its interactions with NFκB could prove useful for future therapeutic intervention for interleukin-10 regulated inflammatory conditions. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has a major protective role against intestinal inflammation. We recently revealed that intestinal epithelial cells in vitro regulate NFκB-driven transcriptional responses to TNF via an autocrine mechanism dependent on IL-10 secretion. Here in this study, we investigated the impact of IL-10 deficiency on the NFκB pathway and its downstream targets in the small intestinal mucosa in vivo. We observed dysregulation of TNF, IκBα, and A20 gene and protein expression in the small intestine of steady-state or TNF-injected Il10−/− mice, compared to wild-type C57BL6/J counterparts. Upon TNF injection, tissue from the small intestine showed upregulation of NFκB p65[RelA] activity, which was totally diminished in Il10−/− mice and correlated with reduced levels of TNF, IκBα, and A20 expression. In serum, whilst IgA levels were noted to be markedly downregulated in IL-10-deficient- mice, normal levels of mucosal IgA were seen in intestine mucosa. Importantly, dysregulated cytokine/chemokine levels were observed in both serum and intestinal tissue lysates from naïve, as well as TNF-injected Il10−/− mice. These data further support the importance of the IL-10-canonical NFκB signaling pathway axis in regulating intestinal mucosa homeostasis and response to inflammatory triggers in vivo. [ABSTRACT FROM AUTHOR]

The skin is an endocrine organ and a major target of hormones such as estrogens, androgens and cortisol. Besides vasomotor symptoms (VMS), skin and hair symptoms often receive less attention than other menopausal symptoms despite having a significant negative effect on quality of life. Skin and mucosal menopausal symptoms include dryness and pruritus, thinning and atrophy, wrinkles and sagging, poor wound healing and reduced vascularity, whereas skin premalignant and malignant lesions and skin aging signs are almost exclusively caused by environmental factors, especially solar radiation. Hair menopausal symptoms include reduced hair growth and density on the scalp (diffuse effluvium due to follicular rarefication and/or androgenetic alopecia of female pattern), altered hair quality and structure, and increased unwanted hair growth on facial areas. Hormone replacement therapy (HRT) is not indicated for skin and hair symptoms alone due to the risk–benefit balance, but wider potential benefits of HRT (beyond estrogen's effect on VMS, bone, breast, heart and blood vessels) to include skin, hair and mucosal benefits should be discussed with women so that they will be able to make the best possible informed decisions on how to prevent or manage their menopausal symptoms. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this multicenter retrospective study was to investigate the demographic characteristics and treatment outcomes of patients with mucosal malignant melanoma (MM) of the oral cavity. Materials and methods: This was a multicenter study involving 8 Japanese universities. The medical records of 69 patients who were diagnosed with primary oral MM between January 2000 and December 2020 were retrospectively analyzed. Overall survival (OS) and prognostic factors for OS were analyzed statistically. Results: There were 40 (58.0%) males and 29 (42.0%) females, and their mean (range) age was 69.8 ± 14.6 (22–96) years old. The most common primary site was the palate (30 patients, 43.5%). Stage IVA was the most common disease stage (36 patients, 52.2%). Radical therapy was performed in 55 patients (79.7%). The 2-year and 5-year OS rates of the 69 patients were 64.6% and 42.5%, respectively. The 2-year and 5-year OS rates of the stage III patients were 85.9% and 72.5%, respectively, and those of the stage IVA patients were 56.3% and 26.0%, respectively. The 1-year OS rate of the stage IVB/IVC patients was 26.7%. The 2-year and 5-year OS rates of the radical therapy group were 74.1% and 50.5%, respectively, whereas the 2-year OS rate of the non-radical therapy group was 26.0%. An advanced T classification was the only identified prognostic factor for OS (hazard ratio: 6.312, 95% confidence interval: 1.133–38.522, p < 0.05). Conclusions: Early detection and radical treatment are essential for improving the prognosis of oral MM patients. Clinical relevance: Early detection and adequate radical therapy leads to the better prognosis of oral MM patients. [ABSTRACT FROM AUTHOR]

Background: Bullous pemphigoid is a common autoimmune bullous disease that mainly affects the elderly. Mucosal involvement in bullous pemphigoid remains rare and is in the order of 10% to 30%. Our objective was to evaluate the prevalence of mucosal involvement in our patients with bullous pemphigoid and to study its epidemiological, clinical, and therapeutic particularities. Material and Methods: We conducted a prospective epidemiological study, collecting patients with bullous pemphigoid, over a period of eleven years. We divided our study population into two groups, with and without mucosal damage, and compared different parameters between these two groups. Results: We collected 85 patients diagnosed with bullous pemphigoid. The mean age at diagnosis was 70.54 years. A neurological history was reported in nine (10.7%) of our patients, Drug intake was noted in 14.3%. Associations with autoimmune diseases were found in 25 patients. The typical form of PB was found in 74% of our patients with extensive skin involvement of more than 30% of the body surface in 44.7% of the patients. Twenty-nine patients (34.1%) presented mucosal lesions. The oral mucosa was the most frequently affected surface. Among the patients with mucosal involvement, twentyfive (86.2%) had isolated mucosal surface involvement. In patients with oral involvement, the most frequent mucosal lesions were erosions of the soft palate and the inner face of the cheeks. The comparative analysis between the two groups revealed that patients with mucosal involvement were younger, with an average age of 69.5 years vs. 71.12 years, p = 0.54. We also noted that patients with mucosal involvement more frequently presented with heard skin disease (p = 0.01). Regarding therapeutic management, we noted a more frequent need for the addition of systemic treatment to topical corticosteroids as compared to other patients (p = 0.01). Conclusion: The involvement of the oral mucosa remains rare and is correlated with more severe and extensive involvement of the disease with the ineffectiveness of first-line treatment. Further studies are needed at the national level to better assess these characteristics in the Moroccan population. [ABSTRACT FROM AUTHOR]

Background: Offset analgesia (OA) is commonly used to quantify endogenous pain inhibition. However, the potential role of afferent inputs and the subsequent peripheral factors from different body areas on the underlying mechanisms are still unclear. Objectives: The aim of this cross‐sectional study was to compare the magnitude of OA in four different body areas representing (a) glabrous and non‐glabrous skin, (b) trigeminal and extra‐trigeminal areas, and (c) intra‐ and extra‐oral tissue. Methods: OA was assessed at the oral mucosa of the lower lip, the skin of the cheek, the forearm and the palm of the hand in 32 healthy and pain‐free participants. OA testing included two trials: (1) a constant trial (30 s of constant heat stimulation at an individualised temperature of Pain50 [pain intensity of 50 out of 100]) and (2) an offset trial (10 s of individualised Pain50, followed by 5 s at Pain50 + 1°C and 15 s at Pain50). Participants continuously rated their pain during each trial with a computerised visual analogue scale. Results: A significant OA response was recorded at the oral mucosa (p <.001, d = 1.24), the cheek (p <.001, d = 0.84) and the forearm (p <.001, d = 1.04), but not at the palm (p =.19, d = 0.24). Significant differences were shown for OA recorded at the cheek versus the mucosa (p =.02), and between palm and mucosa (p =.007), but not between the remaining areas (p >.05). Conclusion: This study suggests that intra‐oral endogenous pain inhibition assessed with OA is enhanced and supports the role of peripheral mechanisms contributing to the OA response. [ABSTRACT FROM AUTHOR]

Background and aims: The conditions for jejunal glucose absorption in healthy subjects have not been thoroughly studied. In this study we investigated differences in the jejunal villi enlargement factor, as well as ultrastructural aspects of the surface enterocytes and mitochondria, comparing 2 weeks of high-carbohydrate (HCD) versus high-fat diets (HFD). We also measured the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) in relation to jejunal mitochondria. Methods: A single-centre, randomized, unblinded crossover study in 15 healthy volunteers ingesting strictly controlled equicaloric diets (either HCD or HFD), with 60% energy from the respective source. An enteroscopy was carried out after 2 weeks of each diet and jejunal mucosal biopsies were acquired. Conventional histology, immunofluorescent staining, transmission electron microscopy and confocal microscopy were used. Results: The villi did not demonstrate any change in the epithelial enlargement factor. Despite an increased mitosis, there were no changes in apoptotic indices. However, the ultrastructural analysis demonstrated a significant increase in the enlargement factor at the bases of the villi. The mitochondria demonstrated increased amounts of cristae after the HFD. The confocal microscopy revealed increased HMGCS2 per mitochondrial marker at the top of the villi after the HFD compared to the HCD. Conclusion: There is a morphometric adaption in the jejunal mucosa following the 2-week diets, not only on a histological level, but rather on the ultrastructural level. This study supports the notion that mitochondrial HMGCS2 is regulated by the fat content of the diet and is involved in the expression of monosaccharide transporters. [ABSTRACT FROM AUTHOR]

Psoriasis, with its wide variety of clinical forms and locations, some of which being rare, is a dermatological condition that often requires a differential diagnosis with numerous other skin disorders. With this paper we aim to present the main clinical characteristics that psoriasis can show on the mucous membranes, respectively genital psoriasis and the manifestations on the oral mucosa. [ABSTRACT FROM AUTHOR]

Surgical repair of esophageal perforation is a challenging procedure with a high risk of secondary complications, such as early esophageal leakage and late esophageal stricture, which can significantly reduce the patient's quality of life. A 34-year-old man underwent anterior cervical corpectomy decompression and fusion. On the ninth day post-operation, the patient developed fever and neck swelling. A computed tomography scan of the neck showed multiple subcutaneous pneumatosis. An esophageal perforation of approximately 1.5 cm in diameter was identified by esophagoscopy. During the operation, the fistula was first located using an esophagoscope. The distal end of the esophagoscope was then placed into the stomach to support the damaged segment of the esophagus. The esophageal mucosa was sutured under the microscope, and the perforation was successfully repaired. Postoperatively, the patient's body temperature decreased, and the infection indexes gradually returned to normal. Three months after the operation, the esophagoscopic review showed complete healing of the perforation. Esophagoscopy plays an important role in diagnosing and repairing esophageal perforations. The esophagoscope provides direct visualization of the perforation during diagnosis and detects smaller and not yet fully penetrated esophageal injuries. During the repair process, the esophagoscope immobilizes the esophagus, prevents its movement and facilitates suturing, maintains proper dilatation of the esophagus, provides space for suturing, and prevents esophageal stricture. [ABSTRACT FROM AUTHOR]

Background: The toxicological risk of Co-Cr dental alloys is actually a sensitive subject with the European regulatory changes, namely regulation (EU) 2017/745 and annex VI to the CLP regulation (EC) 1972/2008. Objectives: The objective of this review is to conduct a rigorous analysis of the cytocompatibility of cobalt–chromium (Co-Cr) dental alloys. Considering various parameters such as cytotoxicity, type IV hypersensitivity reaction, sensitization, and irritation, we investigated evidence of toxicity of Co-Cr in human dental applications. Data sources: Specific search strategies were performed in three electronic databases, namely Medline, Embase, and Web of Science, using a main restriction in the search regarding the publication date (1995–2022). Study selection: Out of a total of 836 articles, only 21 studies were selected and analyzed according to PRISMA methodology. Results: Among them, 10 in vitro studies using human samples and 11 in vivo studies on human patients were distinguished. Most of the in vitro studies confirmed that Co-Cr alloys have a good cytocompatibility compared to Ni alloys. Regarding the in vivo studies, it appeared that Co-Cr could rarely cause sensitization, irritation, and allergic reactions. Reactions were mainly observed for people allergic to Co or Cr. Nevertheless, titanium-based materials showed better results. Conclusions: This study proposes a new state of the art on Co-Cr dental alloys and will thus be very useful for carrying out additional studies. Relevance: This review will help practitioners in their daily clinical choice. [ABSTRACT FROM AUTHOR]

Cytological analyses of the oral cavity are necessary for the identification and correct evaluation of lesions in this anatomical region. Literature on this subject in reptiles is scarce, in contrast to other species kept as pets. The main objective of this descriptive study was to evaluate the normal cytological characteristics of the oral cavity of inland bearded dragons (Pogona vitticeps). Twenty-eight clinically healthy inland bearded dragons, including juveniles and adult males and females, from private collections were evaluated. Oral samples from the tongue and palate were obtained from each animal. Slides were stained with modified Wright–Giemsa stain and analyzed under an optical microscope. The contents of the slides were mostly hypocellular, with no evidence of microbiological overgrowth or inflammation, and showed mostly keratinized squamous cells; basal epithelial cells were seldom observed. Occasionally, goblet cells were observed in tongue samples, but were rare in palate samples. The results of this study contribute to a better characterization of the normal oral mucosa of inland bearded dragon and are in accordance with the few previously published studies. [ABSTRACT FROM AUTHOR]

Respiratory and digestive mucosal surfaces are continually exposed to common environmental antigens, which include potential allergens. Although innocuous in healthy individuals, allergens cause allergy in predisposed subjects and do so by triggering a pathologic T H 2 cell response that induces IgE class switching and somatic hypermutation in allergen-specific B cells. The ensuing affinity maturation and plasma cell differentiation lead to the abnormal release of high-affinity IgE that binds to powerful FcεRI receptors on basophils and mast cells. When cross-linked by allergen, FcεRI-bound IgE instigates the release of prestored and de novo –induced proinflammatory mediators. Aside from causing type I hypersensitivity reactions underlying allergy, IgE affords protection against nematodes or venoms from insects and snakes, which raises questions as to the fundamental differences between protective and pathogenic IgE responses. In this review, we discuss the impact of the mucosal environment, including the epithelial and mucus barriers, on the induction of protective IgE responses against environmental antigens. We further discuss how perturbations of these barriers may contribute to the induction of pathogenic IgE production. [ABSTRACT FROM AUTHOR]

This study aimed to prepare and assess active microneedle (MN) patches based on a novel biomaterial and their effective coupled (physical and electrical) transdermal delivery of a model drug (Linezoid). Modified MN patches (e.g. fabricated from Linezoid, boronated chitosan, polyvinyl alcohol and D-sorbitol) were engineered using a vacuum micromoulding method. Physicochemical, FTIR (Fourier transform infrared), in-silico, structural and thermal analysis of prepared formulations were conducted to ascertain MN quality, composition and integrity. In-vitro mechanical tests, membrane toxicity, drug release, antibiofilm, ex-vivo mucoadhesion, insertion and in-vivo antibiofilm studies were performed to further validate viability of the coupled system. Optimized MN patch formulation (CSHP3 - comprising of 3 % w/v boronated chitosan, 3.5 % w/v PVA and 10 % w/w D-sorbitol) exhibited sharp-tipped, equi-distant and uniform-surfaced micron-scaled projections with conforming physicochemical features. FTIR analysis confirmed modification (i.e., boronation) of chitosan and compatibility as well as interaction between CSHP3 constituents. In-silico analysis indicated non-covalent interactions between all formulation constituents. Moreover, boronated chitosan-mucin glycoprotein complex showed a stronger bonding (∼1.86 times higher CScore) as compared to linezolid-mucin counterpart. Thermal analysis indicated amorphous nature of CSHP3. A ∼ 1.42 times higher tensile strength was displayed by CSHP3 as compared to control (i.e., pure chitosan, polyvinyl alcohol and D-sorbitol-based MN patch). Membrane toxicity study indicated non-toxic and physiological compatible nature of CSHP3. Within 90 min, 91.99 ± 2.3 % linezolid was released from CSHP3. During release study on agarose gel, CSHP3-iontophoresis treatment resulted in a ∼ 1.78 and ∼ 1.20 times higher methylene blue-covered area and optical density, respectively, within 60 min as compared to CSHP3 treatment alone. Staphylococcus aureus biofilms treated with CSHP3 exhibited 65 ± 4.2 % reduction in their mass. CSHP3 MN patches remained adhered to the rabbit oral mucosa for 6 ± 0.15 h. Mucosa treated with CSHP3 and CSHP3-iontophoresis combination showed a generation of pathways in the epithelium layers without any damage to the underlying lamina propria. Eradication of Staphylococcus aureus from oral mucosal wounds and complete tissue regeneration was recorded following 7-day treatment using CSHP3-iontophoresis coupled approach., Competing Interests: Declaration of competing interest The authors have no conflict of interests., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To review the various basic research and treatments available to regenerate the vocal folds and to discuss the direction for future treatments., Methods: A comprehensive review was performed in PubMed database and Google Scholar utilizing search terms including combinations and variations of the following concepts: vocal fold anatomy, vocal fold disorders, and regenerative therapies. No particular inclusion or exclusion criteria were set due to the nature of this narrative review article., Results/discussion: The regenerative treatments available for each vocal fold layer are the following: 1) epidermal growth factor and transforming growth factor-β1 for the epithelial layer, 2) autologous fibroblasts, autologous bone-marrow derived mesenchymal stem cells (MSCs), autologous adipose tissue-derived stromal vascular fraction (ADSVF), basic fibroblast growth factor (bFGF), collagen-hyaluronic acid nanofiber, pirfenidone, hepatocyte growth factor (HGF), pulsed dye laser (PDL), diode laser, and platelet-rich plasma (PRP) for the lamina propria, 3) bFGF and controlled-release bFGF with autologous fascia, HGF, c-Met agonistic antibody, and PRP for the muscular layer, 4) and bFGF and PRP-loaded nerve guidance conduit for the nerve. Treatments deemed clinically safe with sustained efficacy assessed up to 6 months are HGF and PDL, while bFGF, autologous fibroblasts, autologous bone marrow-derived MSCs, ADSVF, and PRP have been studied up to 12 months., Conclusion: An ideal regenerative treatment is one that restores the injured or lost components of the vocal fold. The layered structure of the vocal fold allows for several mechanisms of action for these regenerative therapies. Further experimental and clinical studies are warranted, and these would dictate the impact of vocal fold regenerative therapies. Regenerative medicine may soon be at the forefront for treating vocal fold disorders. Clinicians should be open to advancements in treatment and consider the potential of novel therapies to treat specific pathologies., Competing Interests: Declaration of competing interest The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

There are often outbreaks of infectious diseases on farms, which not only disrupt production but also cause significant economic losses. Vaccines are given to prevent the spread of these infectious diseases, but they produce only systemic antibodies or antibodies in the mucosa of a particular system. So, a new mucosal vaccination route is needed where the vaccine will produce antibodies in the systemic circulation as well as in the mucosa of many systems. In our study, the cloaca was targeted because it is associated with the mucosa of many systems. Whole-mount and routine histological staining show both lymphatic nodules and diffuse lymphatic tissues in the lamina propria of cloaca. These lymphatic tissues are made up of Bu-1+ B-cells, CD3 + T-cells, and KUL01+ macrophages and monocytes. So, this is a new mucosa-associated lymphoid tissue, named cloaca-associated lymphoid tissue (CALT). The CALT contains antigen-presenting cells (dendritic cells, macrophages, B cells, MHC II molecules, and T cells) and is equipped with blood vessels and high endothelial venules, which indicate its functional status. More antibodies were produced in the treatment group compared to the vehicle control group after administration of the infectious bursal disease (IBD ) and the Newcastle disease (ND) vaccine through cloaca. In addition, the cloaca-associated route produces a higher number of antibodies than the other traditional routes, which reveals the uniqueness of this route. Cloacal-vaccinated chickens showed less damage to the follicle and epithelium of the bursa of Fabricius compared to other groups, indicating its lower cytotoxic effect. Therefore, the cloaca-associated mucosal vaccination route produces more antibodies than other mucosal vaccination routes, which will protect the chickens on the farm to a greater extent., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Md. Abdul Masum reports financial support was provided by University Grants Commission of Bangladesh. Md. Abdul Masum reports financial support was provided by Government of the People's Republic of Bangladesh Ministry of Science and Technology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Importance: Porcine epidemic diarrhea virus (PEDV) binds to particular cell surface receptors to penetrate cells. The virus specifically identifies certain carbohydrate structures present on the surface of the cell to facilitate the binding process. Nevertheless, the influence of viral infections on specific alterations of glycoconjugates in the small intestines remains unexplored., Objective: This work aimed to examine the alterations in glycoconjugates in the small intestines of piglets naturally infected with PEDV using lectin histochemistry., Methods: Six piglets including three PEDV-infected and three non-infected piglets were evaluated. Small intestinal samples were histopathologically examined, and lectin histochemistry was performed., Results: Piglets infected with PEDV had significant histological abnormalities in their small intestines, such as pronounced villous atrophy, varying degrees of villous fusion, and diverse mucosal alterations. Specific regions of the duodenum, jejunum, and ileum showed discernible variations in glycoconjugate distribution, as determined by lectin histochemistry. Compared with the controls, the PEDV-infected piglets showed significant changes in N-acetylglucosamine- and galactose-binding lectins (particularly wheat germ agglutinin and Arachis hypogaea (peanut) agglutinin) in multiple intestinal regions., Conclusions and Relevance: These findings can enhance understanding of how viruses such as PEDV impact the glycoconjugate composition of the small intestines and emphasize the potential connection between the pathogenesis of PEDV and glycoconjugate., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Korean Society of Veterinary Science.)

The Prevotella genus consists of obligate anaerobic Gram-negative bacteria that are symbiotic with the oral, intestinal, and vaginal mucosa. While several species of Prevotella have been implicated in pulmonary infections, identification of Prevotella as the causative agent of lung abscess is uncommon because of the requirement for stringent anaerobic culture conditions. In this report, we highlight a case of lung abscess caused by Prevotella salivae and Prevotella veroralis , underscoring the importance of third-generation metagenomic sequencing using devices from Oxford Nanopore Technologies for the precise diagnosis of specific pathogens., Competing Interests: Declaration of conflicting interestsThe 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.

Knowledge about the morphological features of the structure and functions of the digestive organs provides the basis for rational and effective use of feed, prevention and treatment of gastrointestinal diseases in poultry. In this regard, the study of the morphogenesis of the digestive system in birds and the mechanisms of their regulation is of great importance. The object of the study was the glandular part of the stomach (proventriculus) in chickens of Shaver 579 strain. The material for macro- and microscopic examinations was selected from birds at age of 1, 30, 60, 90, 120, 150, 180, 210, 240, 270, and 300 days and 1, 2, and 3 years; it was fixed in a 10% neutral formalin solution and embedded into paraffin according to conventional methods. For submicroscopic examinations, the material was selected from hens of this strain at age of 180 days. The structure of epitheliocytes in the superficial epithelium and secretory cells of the deep glands was studied in ultrathin sections. Digital indicators of research results were statistically processed by a personal computer using the Microsoft Excel program. The glandular stomach in chickens is a direct extension of the esophagus and has the form of a thick-walled tube, the wall of which is formed by mucous, muscular, and serous membranes. The superficial epithelium of the mucosa is represented by cylindrical epithelial cells that are located within the basal membrane. They are linked to each other by different types of contacts and have a well-defined polar differentiation. The lobules of the deep glands are formed by cells with well-developed synthesizing organelles and secretory granules. The morphogenesis of the glandular part of the stomach in chickens according to age aspect is manifested by changes in morphometric parameters of the thickness and the area of the membranes of its wall. The wall thickness increases (between the folds 4223.23 ± 189.25 and in the area of the folds 5561.32 ± 45.01 μm) unevenly in chickens up to the age of 240 days. The most developed membrane of the wall of the glandular stomach is the mucosa. Its area increases (by 82.14 ± 0.56%) in chickens up to the age of 180 days, and the area of muscular and serous membranes decreases (by 15.54 ± 0.65 and 2.32 ± 0.33%, respectively). In older birds, the thickness of the wall and the area of the membranes of the glandular stomach do not change significantly

This Perspective presents the potential of the Small Intestinal Axis, a sub-division of the Gut-immune Axis, to modulate systemic inflammation based on sensing contents of the gut lumen. Gut mucosal immunity regulates tolerance to food and gut contents and is a significant factor in maintaining systemic homeostasis without compromising immunity to pathogens. This is achieved through anatomical structures and signaling pathways that link the tolerogenic potential of the proximal small intestine to systemic immunity. Non-live preparations of microbes isolated from human small intestinal mucosa, and the extracellular vesicles (EVs) which they shed, can resolve systemic inflammation without systemic exposure after oral delivery. The mechanism involves primary interactions with pattern recognition receptors followed by trafficking of immune cells through mesenteric lymph nodes. This generates in the periphery a population of circulating CD4+ T cells which have regulatory function but an atypical FoxP3- phenotype. There is no modification of the resident gut microbiome. Discoveries using this novel approach of targeting mucosal microbial elements to the tolerogenic proximal regions of the small intestine are revealing some of the mysteries of the relationship between the gut and immune system.

Backgrounds: Janus kinase inhibitors (JAKi) are anti-inflammatory medications suppressing Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway by inhibiting various cytokines receptors on the membrane of cells. Mutations and polymorphisms on JAK and STAT proteins can cause dysregulation in the balance of immune system, and ultimately result in autoimmune disorders. Objectives: to record and summarize the overall efficacy and safety of JAKi in various autoimmune conditions such as alopecia areata (AA), psoriasis vulgaris (PV), psoriatic arthritis (PsA), atopic dermatitis (AD), vitiligo, hidradenitis suppurative (HS), lichen planus (LP), and pyoderma gangrenosum (PG). Methods: A thorough review of articles was performed across PubMed and Google Scholar on meta-analyses, systematic reviews, clinical trials and case studies evaluating the treatment of autoimmune disorders such as AA, PV, PsA, AD, vitiligo, LP, HS, and PG with JAKi. Duplicated data and animal experiments or in vitro/ex vivo studies were excluded. Results: all the reviewed articles reported beneficial effects of tofacitinib and ruxolitinib application in the treatment of disorders mentioned above with the autoimmune predisposition. Conclusion: tofacitinib and ruxolitinib showed potential efficacy in treating several autoimmune disorders. Based on records in the reviewed studies, both medications had acceptable safety profiles; however, physicians are recommended to outweigh the risks and benefits of such treatments for each specific condition.

The idea of a common mucosal immune system (CMS) is 50 years old. Its relevance to immune protection at mucosal sites and its potential to modulate the impact of vaccination-induced protection against infection of the airway has been poorly understood. The consequent failure of the current SARS-CoV-2 vaccination to satisfy expectations with respect to prevention of infection, viral transmission, duration of protection, and pattern of clinical protection, led to public health and medical decisions now under review. This review summarises knowledge of the CMS in man, including the powerful role it plays in immune protection and lessons with respect to what can and cannot be achieved by systemic and mucosal vaccination for the prevention of airway infection. The powerful impact in both health and disease of optimising delivery of immune protection using selected isolates from the respiratory microbiome is demonstrated through a review of randomised controlled trials (RCTs) in subjects with chronic airway disease, and in otherwise healthy individuals with risk factors, in whom the idea of mucosal immune resilience is introduced. This review is dedicated to two giants of mucosal immunology: Professors John Bienenstock and Allan Cripps. Their recent deaths are keenly felt by their colleagues and students.

The prevalence and severity of mucocutaneous manifestations in Covid‐19 infection are generally higher than those reported in Covid vaccines. Therefore, comparing the mucocutaneous reactions of the Covid‐19 infection and vaccination is necessary to enhance our knowledge about such reactions and guide us to evaluate the risk of infection or vaccination. A thorough literature search was conducted on PubMed, Google Scholar, and EBSCO (LISTA), and 2069 articles were downloaded. After screening, 11 studies remained for the final review. The literature review revealed that the prevalence and severity of postvaccine mucocutaneous adverse reactions have been less common compared to Covid‐19 infection. Postvaccine adverse reactions primarily occurred after the first dose administration and such reactions were manageable with antihistamines and corticosteroids administration. This comparative analysis highlights the frequency and potential severity of mucocutaneous reactions due to Covid‐19 infection and Covid‐19 vaccination. It also affirmed that potentially critical (serious) mucocutaneous reactions are more likely to occur in Covid‐19 infection compared to Covid vaccination. Moreover, postvaccine reactions predominantly happened after the first dose and were reported to be non‐life‐threatening, self‐manageable and with a lower incidence of potentially critical events. It was also concluded that the incidence of mucocutaneous reactions decreased in the following doses. Hence, given the low rate of such reactions following Covid‐19 vaccination, vaccines have a lower risk of mucocutaneous reactions occurrence than Covid‐19 infection. Further, due to the limited number of studies, we recommend that large‐scale trials evaluate such reactions comparing various types of Covid‐19 vaccines in healthy individuals and those with autoimmune skin disorders. [ABSTRACT FROM AUTHOR]

Background: Lingual microcystic lymphatic malformations (LMLMs) are rare congenital vascular malformations presenting as clusters of cysts filled with lymph fluid or blood. Even small well-limited lesions can be responsible for a heavy burden, inducing pain, aesthetic prejudice, or oozing, bleeding, infections. The natural history of LMLMs is progressive worsening punctuated by acute flares. Therapeutic options include surgery, laser excision, and radiofrequency ablation but all are potentially detrimental and expose to local relapse. Therefore, the management frequently relies on a "watchful waiting" approach. In complicated LMLMs, treatment with oral sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, is often used. Topical applications of sirolimus on the buccal mucosae have been reported in other oral diseases with good tolerance and none to slight detectable blood sirolimus concentrations. We aim to evaluate the efficacy and safety of a 1 mg/mL sirolimus solution applied once daily on LMLM of any stage in children and adults after 4, 8, 12, 16, 20, and 24 weeks of treatment compared to usual care (no treatment).Methods: This is a randomized, multicentric study using an individually randomized stepped-wedge design over 24 weeks to evaluate topical application of a 1 mg/mL sirolimus solution once daily, on LMLM, versus usual care (no treatment), the control condition. Participants begin with an observational period and later switch to the intervention at a randomized time (week 0, 4, 8, or 12). Visits occur every 4 weeks, either in the study center or by teleconsulting. The primary outcome will be the evaluation of global severity of the LMLM on monthly standardized photographs by 3 independent blinded experts using the physical global assessment (PGA) 0 to 5 scale. Secondary outcomes will include lesion size measurement and quality of life assessment, investigator, and patient-assessed global disease and specific symptoms (oozing, bleeding, sialorrhea, eating impairment, taste modification, aesthetic impairment, pain, and global discomfort) assessment. A biological monitoring will be performed including residual blood sirolimus concentration and usual laboratory parameters.Discussion: Given the disappointing state of current treatment options in LMLMs, topical sirolimus could become firstline therapy in treating LMLMs if its efficacy and safety were to be demonstrated.Trial Registration: ClinicalTrials.gov NCT04128722 . Registered on 24 September 2019. EudraCT: EUCTR2019-001530-33-FR Sponsor (University Hospital Center of Tours - CHRU Tours): DR190041-TOPGUN French regulatory authorities: ID RCB: 2019-001530-33. [ABSTRACT FROM AUTHOR]

Infectious diseases of the conjunctiva and cornea usually leave behind both broad local and systemic immunity. Case reports of SARS-CoV-2-positive conjunctivitis with subsequent systemic immunity suggest a new route of immunization preventing the primary infection of the airways. Material and Methods: A total of 24 Syrian field hamsters were treated. In systematic animal experiments, we infected the eyes of n = 8 animals (group 1) and the airways of another n = 8 animals (group 2) with SARS-CoV-2 (Wuhan type); n = 8 hamsters served as controls (group 3). The weight development of the animals was recorded. After two weeks of observation of disease symptoms, all animals were re-exposed to SARS-CoV-2 in the respiratory tract (challenge) to determine whether immunity to the virus had been achieved. Results: The epi-ocularly infected animals (group 1) showed no clinically visible disease during the ocular infection phase. At most, there was a slightly reduced weight gain compared to the control group (group 3), while the respiratory infected animals (group 2) all lost weight, became lethargic, and slowly recovered after two weeks. After the challenge, none of the animals in groups 1 and 2 became ill again. The animals in the negative control (group 3) all became ill. Cytotoxic antibodies were detectable in the blood of the infected groups before and after challenge, with higher titers in the epi-ocularly infected animals. Conclusion: By epi-ocular infection with SARS-CoV-2, the development of systemic immunity with formation of cytotoxic antibodies without severe general disease could be observed in the experimental animals, which did not induce any more disease upon a second infection in the respiratory tract. Therefore, it can be concluded that a purely epi-ocular infection with SARS-CoV2 only induces a weak disease pattern followed by systemic immunity. [ABSTRACT FROM AUTHOR]

Simple Summary: A well-balanced diet seems to play a key role in disease prevention and health promotion in young animals. Therefore, many attempts have been made to supplement feeds with novel nutritional components, with potential prebiotic capacity. It seems that chicory root fulfils those criteria as it contains high amounts of inulin-type fructans. Hence, the aim of the study was to determine the effect of dietary supplementation with 4% dried chicory root on the cecal mucosa proteome of piglets. It is shown that this feed additive may affect cellular metabolism in the cecal epithelium and may be beneficial for gut health. Prebiotics are known to have many beneficial effects on intestinal health by modulating the gut microbiota composition, thereby affecting epithelial cell proliferation and metabolism. This study had two aims: (1) to identify the protein constituents in the cecal mucosa of 50-day-old healthy (PIC × Penarlan P76) barrows, and (2) to assess the effects of 4% inclusion of dried chicory root in a cereal-based diet on the cecal mucosa proteome changes. Pigs (eight per group) were randomly allotted to the groups and were fed a control diet from the tenth day of life (C) or a diet supplemented with 4% of died chicory root (CR), for 40 days. At the age of 50 days, animals were sacrificed and cecal tissue samples were collected. It was found that feeding a CR diet significantly decreased the expression of 16 cecal mucosa proteins. Among them, fifteen proteins were down-regulated, while only one (KRT20) was shown to be up-regulated when compared to the C group. Dietary supplementation with CR caused down-expression of metabolism-associated proteins including enzymes involved in the process of glycolysis (G6PD, TPI1, ALDH9A1, CKMT1 and AKR1A1) as well as those engaged in transcriptional and translational activity (PRPF19, EEF1G) and several structural proteins (ACTR3, KRT77, CAP1 and actin). From our findings, it is possible to conclude that dietary chicory root at 4% had beneficial effects on the gut health of pigs as indicated by a changed abundance of certain cecal proteins such as KRT20, SERPINB1, HSP27, ANAXA2 and ANAXA4. [ABSTRACT FROM AUTHOR]