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Simple Summary: This paper characterizes the immunotherapy-related adverse effects in the oral tissues, in a large series of patients. This includes a description of the severity of oral symptoms, immediate clinical presentation, treatment, chronicity despite holding the immunotherapy, and the development of oral cancer. The management of these patients exemplified new diagnostic tools, detailed clinical presentation that may assist to differentiate between various oral irAEs and outlines unique adjustments in the topical treatment and inclusion of a new treatment modality for these irAEs. Lastly, this paper raises the awareness for second primary oral cancer and possible risk for oral malignant transformation. (1) Background: Immunotherapy-related adverse effects (irAEs) have been reported to manifest in oral tissues, mainly as lichenoid and non-lichenoid lesions and salivary gland dysfunction; however, the characterization of oral irAEs and their clinical impact is limited. (2) Methods: This is a retrospective clinical chart review of 14 patients with oral irAEs, describing the impact of the oral irAEs in terms of the immediate effect, treatment, chronicity of the irAEs and the development of oral cancer. (3) Results: Common symptoms were pain and dry mouth, causing no-to-severe pain and/or dry mouth sensation. The immediate sequala ranged from sensitivity to certain foods up to elimination of oral intake. Treatment included conventional palliation techniques with or without systemic steroids. Discontinuation of the immunotherapy agents was required in 6 patients. Innovative treatment modalities included photobiomodulation for oral mucosal pain relief, and salivary gland intraductal irrigations for relief of salivary gland hypofunction. Late sequala included the development of proliferative leukoplakia and oral cancer. (4) Conclusions: Patients treated with immunotherapy may develop debilitating oral irAEs. They should be followed for oral involvement so treatment may be initiated when the symptoms are mild to avoid discontinuation of the immunotherapy. Patients that develop oral lichenoid lesions should receive long-term follow-up, as they may have higher risk for oral cancer. [ABSTRACT FROM AUTHOR]

In the present study, we propose the use of swabs in non-lethal sampling procedures to collect the mucosa-adhered gut microbiota from the posterior intestine of fish, and therefore, we compare the bacterial communities collected by conventional scraping and by swabbing methods. For this purpose, samples of the posterior intestine of rainbow trout (Oncorhynchus mykiss) were collected first using the swabbing approach, and after fish euthanasia, by mucosa scraping. Finally, bacterial communities were compared by 16S rRNA gene Illumina sequencing. Results from the current study revealed that similar values of bacterial richness and diversity were found for both sampling procedures. Similarly, there were no differences between procedures when using qualitative metrics (Jaccard and unweighted UniFrac) for estimating inter-individual diversity, but the quantitative metrics (Bray-Curtis and weighted UniFrac) showed a higher dispersion when samples were obtained by swabbing compared to scraping. In terms of bacterial composition, there were differences in abundance for the phyla Firmicutes and Proteobacteria. The cause of these differential abundances may be the inability of the swab to access to certain areas, such as the basal region of the intestinal villi. Moreover, swabbing allowed a higher representation of low abundant taxa, which may also have an important role in host microbiome regardless of their low abundance. Overall, our results demonstrate that the sampling method is a factor to be considered in experimental design when studying gut bacterial communities to avoid potential biases in the interpretation or comparison of results from different studies. In addition, the advantages and disadvantages of each procedure (swabbing vs scraping) are discussed in detail, concluding that swabbing can be implemented as a reliable and non-lethal procedure for posterior gut microbiota studies, which is of particular interest for animal welfare and the 3Rs principle, and may offer a wide range of novel applications.

Abstract Interleukin‐22 (IL‐22) is an important cytokine in the intestinal environment. IL‐22 is mainly produced by immune cells and targeted at nonimmune cells such as epithelial and stromal cells in a broad array of tissues such as ‐but not restricted to‐ the liver and adipose tissue. IL‐22 therefore connects immune functions with metabolic functions of the host, and since it is induced by the microbiota, connects host functioning to the outside environment. IL‐22 induces epithelial cell proliferation aiding in rapid epithelium regeneration and wound healing. Additionally, IL‐22 activates antiapoptotic genes and DNA damage response pathways, enhancing epithelial cell survival. Recently, it has also been shown that IL‐22 induces Paneth cell differentiation in humans. However, IL‐22 can also contribute to intestinal epithelium damage and reduces microbial diversity in the intestine directly or indirectly by inducing excessive antimicrobial peptide production by epithelial cells. Moreover, IL‐22 enhances angiogenesis and may therefore support tumorigenesis in the intestine. In conclusion, it appears that whether IL‐22 has a beneficial or harmful effect in the mammalian intestine largely depends on its regulation. This review aims to provide a comprehensive overview of the current literature and emphasizes that IL‐22 signaling outcome depends on the timing and duration of IL‐22 production, the presence of it regulators such as IL‐22BP, and the specific location of the cytokine production in the gastrointestinal tract.

IntroductionAlterations in the gut immune system have been implicated in various diseases.The challenge of obtaining gut tissues from healthy individuals, commonly performed via surgical explants, has limited the number of studies describing the phenotype and function of gut-derived immune cells in health. MethodsHere, by means of recto-sigmoid colon biopsies obtained during routine care (colon cancer screening in healthy adults), the phenotype and function of immune cells present in the gut were described and compared to those found in blood.ResultsThe proportion of CD4+, CD8+, MAIT, γδ+ T, and NK cells phenotype, expression of integrins, and ability to produce cytokine in response to stimulation with PMA and ionomycin. T cells in the gut were found to predominantly have a memory phenotype as compared to T cells in blood where a naïve phenotype predominates. Recto-sigmoid mononuclear cells also had higher PD-1 and Ki67 expression. Furthermore, integrin expression and cytokine production varied by cell type and location in blood vs. gut.DiscussionThese findings demonstrate the differences in functionality of these cells when compared to their blood counterparts and validate previous studies on phenotype within gut-derived immune cells in humans (where cells have been obtained through surgical means). This study suggests that recto-sigmoid biopsies collected during colonoscopy can be a reliable yet more accessible sampling method for follow up of alterations of gut derived immune cells in clinical settings.

Crohn’s disease (CD) is associated with changes in the microbiome. The role of these changes and their precise association with disease course and activity remain ambiguous. In this prospective single-center study, the mucosal microbiome of surgical CD and non-CD patients was compared at the time of surgery. Microbial analyses were individually performed for ileal and colonic tissue samples obtained during surgery using 16S-rRNA-gene amplicon sequencing. Three groups out of the 46 included patients were formed: 1) a study group of CD of patients who received ileocecal resection due to CD involvement (CD study, n=10); 2) a control group of non-CD of patients who received intestinal resection due to indications other than CD (non-CD control, n=27); and 3) a second control group of CD who underwent resection of the intestine not affected by CD (CD non-affected control, n=9). Species richness and Shannon diversity were not different between all formed groups and regions analyzed (p>0.05). Several significant taxonomic differences were seen at the phylum-, order-, and genus-levels between the formed groups, such as a decrease of Firmicutes (phylum-level) and an increase of Bacteroides and Escherichia/Shigella/Pseudescherichia (genus-level) in CD study – colon vs. the non-CD control – colon (p ≤ 0.05). The CD non-affected control presented the largest amount of differentially abundant taxa in comparison to the other groups. These results underline that CD is accompanied by changes in affected and non-affected intestinal regions compared to non-CD controls. This study contributes the mucosal microbiome of a well-defined subset of surgical CD patients without confounding aspects of the fecal microbiome or regional microbial differences to the existing literature.

This article discusses a case of infantile bullous pemphigoid (IBP), a rare autoimmune bullous disease that typically affects individuals over 60 years old. The case involves a 6-month-old male who presented with erythema and blisters on the skin. The diagnosis was confirmed through histopathologic examination and direct immunofluorescence. The patient was treated with methyprednisolone and topical mupirocin ointment, and showed no recurrence or scarring after 12 years of follow-up. The article also explores the etiology, treatment options, and prognosis of IBP, as well as genetic and cultural factors that may contribute to its development. [Extracted from the article]

Objective: This research assessed the efficiencies of aloe vera, 0.1% triamcinolone acetonide, and 5% amlexanox in the management of OLP. Materials and Methods: A total of 120 participants diagnosed with oral lichen planus (OLP) were equally divided into three groups and treated with: aloe vera, (Group A), 0.1% triamcinolone acetonide (Group B), and 5% amlexanox (Group C) topical medicaments. The patients were evaluated for pain, using the visual analogue scale (VAS). They were also evaluated for ulcerative lesion type and erosive area on days 1, 7, and 15 of the study. Results: There was a statistically considerable decrease in the VAS pain scale score, reduction in the erosive area on buccal mucosa, and healing of ulcer from day 1st to 15th day with all three tested drugs. Conclusion: All drugs used in this study; aloe vera, triamcinolone acetonide, and amlexanox were effective in treating OLP patients. [ABSTRACT FROM AUTHOR]

Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by transmural disease. The concept of transmural healing (TH) has been proposed as an indicator of deep clinical remission of CD and as a predictor of favorable treatment endpoints. Understanding the pathophysiology involved in transmural disease is critical to achieving these endpoints. However, most studies have focused on the intestinal mucosa, overlooking the contribution of the intestinal wall in Crohn’s disease. Multi-omics approaches have provided new avenues for exploring the pathogenesis of Crohn’s disease and identifying potential biomarkers. We aimed to use transcriptomic and proteomic technologies to compare immune and mesenchymal cell profiles and pathways in the mucosal and submucosa/wall compartments to better understand chronic refractory disease elements to achieve transmural healing. The results revealed similarities and differences in gene and protein expression profiles, metabolic mechanisms, and immune and non-immune pathways between these two compartments. Additionally, the identification of protein isoforms highlights the complex molecular mechanisms underlying this disease, such as decreased RTN4 isoforms (RTN4B2 and RTN4C) in the submucosa/wall, which may be related to the dysregulation of enteric neural processes. These findings have the potential to inform the development of novel therapeutic strategies to achieve TH.

Objectives: This study aimed to compare the efficiencies of 0.05% clobetasol propionate, 0.1% triamcinolone acetonide, and 5% amlexanox in the management of oral lichen planus (OLP). Material and Method: A total of 120 patients diagnosed with oral lichen planus were equally divided into three groups and treated with 0.05% clobetasol propionate (group A), 0.1% triamcinolone acetonide (group B), and 5% amlexanox (group C) topical medicaments. The patients were evaluated for pain using the visual analog scale (VAS) and erosive lesion. Results: There was a statistically significant decrease in the VAS pain scale score from day 1 to day 15 in all of the tested groups. There was also a reduction in the erosive area on the right and left buccal mucosa on the 15th day with all three tested drugs. Triamcinolone acetonide (0.1%) was effective in reducing the erosive lesions on buccal mucosa when compared with 0.05% clobetasol propionate and 5% amlexanox. Conclusion: Clobetasol propionate, triamcinolone acetonide, and amlexanox were effective in treating OLP patients.

Background: Expansion of OKF6/TERT-2 oral epithelial cells in vitro is important for studying the molecular biology of disease and pathology affecting the oral cavity. Keratinocyte serum-free medium (KSFM) is the medium of choice for this cell line. This study compares three media for OKF6/TERT-2 cultures: KSFM, Dulbecco’s Modified Eagle Medium/Nutrient Mixture of Hams F-12 (DMEM/F12), and a composite medium comprised of DMEM/F-12 and KSFM (1:1 v/v), referred to as DFK. The toxicological effects of electronic cigarette liquids (e-liquids) on OKF6/TERT-2 cells cultured in these media were also compared. Methods: Cells were cultured in KSFM, DMEM/F12, or DFK, and cellular morphology, growth, wound healing and the gene expression of mucins and tight junctions were evaluated. Additionally, cytotoxicity was determined after e-liquid exposures. Results: Switching from KSFM to DMEM/F12 or DFK 24 h post-seeding leads to typical cellular morphologies, and these cultures reach confluency faster than those in KSFM. Wound-healing recovery occurred fastest in DFK. Except for claudin-1, there is no difference in expression of the other genes tested. Additionally, e-liquid cytotoxicity appears to be amplified in DFK cultures. Conclusions: DMEM/F12 and DFK are alternative media for OKF6/TERT-2 cell culture to study the molecular biology of disease and pathology, provided cells are initially seeded in KSFM.

Many metabolic diseases have been demonstrated to be associated with changes in the microbiome. However, no studies have yet been conducted to examine the characteristics of the mucosal microbiota of patients with hypercholesterolemia. We aimed to examine mucosa-associated microbiota in subjects with hypercholesterolemia. We conducted a case-control study, in which ileal mucosal samples were collected from 13 hypercholesterolemia patients and 13 controls for 16S rRNA gene sequencing. There were differences in the composition of ileal mucosal microbiota based on beta diversity between the hypercholesterolemia and control groups (P

ABSTRACTMicrobiota-derived short-chain fatty acids, including butyrate (BA), have multiple beneficial health effects. In the colon, BA concentrations range from 10 to 20 mM and up to 95% is utilized as energy by the mucosa. BA plays a key role in epithelial-barrier regulation and anti-inflammation, and regulates cell growth and differentiation, at least in part, due to its direct influence on stabilization of the transcription factor hypoxia-inducible factor (HIF). It remains unclear whether BA is the optimal metabolite for such a response. In this study, we explored metabolite mimicry as an attractive strategy for the biological response to HIF. We discovered that 4-mercapto butyrate (MBA) stabilizes HIF more potently and has a longer biological half-life than BA in intestinal epithelial cells (IECs). We validated the MBA-mediated HIF transcriptional activity through the induction of classic HIF gene targets in IECs and enhanced epithelial barrier formation in vitro. In-vivo studies with MBA revealed systemic HIF stabilization in mice, which was more potent than its parent BA metabolite. Mechanistically, we found that MBA enhances oxygen consumption and that the sulfhydryl group is essential for HIF stabilization, but exclusively as a four-carbon SCFA. These findings reveal a combined biochemical mechanism for HIF stabilization and provide a foundation for the discovery of potent metabolite-like scaffolds.

Summary: Immune checkpoint inhibitor (ICI) therapy has revolutionized the field of oncology over the past decade, leading to durable remissions in some patients but also producing a wide spectrum of treatment‐limiting inflammatory toxicities that are referred to as immune‐related adverse events (irAEs). Although irAEs can involve any organ system in the body, they most commonly affect the barrier tissues, including the gastrointestinal tract with colitis and enterocolitis affecting a significant fraction of patients on ICIs. We are beginning to understand the mechanisms that drive ICI colitis, with early experiments indicating a role for CD8+ resident memory T cells (TRMs) in the gut, which become activated and differentiate into cytotoxic cells in response to ICI therapy. The risk factors that define who will develop ICI colitis are not understood and substantial efforts are underway to identify potential biomarkers for risk of this and other toxicities. Optimal management of ICI colitis is also an area of active investigation. Current standard treatments are based largely on small, retrospective analyses, and while drugs like systemic glucocorticoids or the TNFα inhibitor infliximab do appear to be highly active in ICI colitis, the impact of these therapies on antitumor responses is poorly understood. As discussed in this review, future work will have to define the immune mechanisms driving ICI colitis in more detail and in comparison to antitumor responses in order to identify candidate pathways that can be targeted to improve ICI colitis without interfering in antitumor immunity. Studying these interventions will require randomized, controlled trials with both tumor and colitis endpoints, a goal that will necessitate collaboration across institutions and funding agencies. We are at a point where such collaborative trials are feasible, and have the potential to greatly improve the care of patients with ICI colitis as well as other irAEs. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Objective: To compare the success rate of external dacryocystorhinostomy with intramucosal injection and sponge application of Mitomycin C to circumosteal mucosa. Study Design: Quasi-experimental study Place and Duration of Study: Eye Department, Combined Military Hospital, Jhelum Cantt Pakistan, from Feb 2019 to Dec 2021. Methodology: One hundred ten patients were selected and randomly allocated into two equal Groups labelled Group-A and Group-B. Group-A patients received 0.1ml of intramucosal injection of 0.02% Mitomycin C, and Group-B patients had 0.02% Mitomycin C applied with a sponge to the circumboreal mucosa. The result of DCR was evaluated at six months and declared successful if the patients were asymptomatic of epiphora and a patent lacrimal passage was found on probing and irrigation. Failure was defined as symptomatic epiphora along with regurgitation on probing and syringing. In failed cases, nasal endoscopy was performed along with probing. Results: Success rates of external dacryocystorhinostomy in the Intramucosal Injection Group was 96%, and in the Sponge Application Group, it was 92%. A comparison of both techniques depicted a statistically insignificant difference in success rate (p=0.60). Conclusion: Mitomycin C use as an adjunctive agent during external dacryocystorhinostomy is a safe and effective technique in achieving a high rate of success, and the route of application, whether applied topically or injected intramucosal does not significantly affect the outcome of this procedure. [ABSTRACT FROM AUTHOR]

This study aims to compare the mucus permeating and mucoadhesive properties of three generations of thiolated cyclodextrins (CDs). Free thiol groups of thiolated γ-CDs (CD-SH) were S-protected with 2-mercaptonicotinic acid (MNA), leading to a second generation of thiolated CDs (CD-SS-MNA) and with 2 kDa polyethylene glycol (PEG) bearing a terminal thiol group leading to a third generation of thiolated CDs (CD-SS-PEG). The structure of these thiolated CDs was confirmed and characterized by FT-IR, 1H NMR and colorimetric assays. Thiolated CDs were evaluated regarding viscosity, mucus diffusion, and mucoadhesion. The viscosity of the mixture of CD-SH, CD-SS-MNA, or CD-SS-PEG with mucus increased up to 11-, 16-, and 14.1-fold compared to unmodified CD within 3 hours, respectively. Mucus diffusion increased in the following rank order: unprotected CD-SH < CD-SS-MNA < CD-SS-PEG. The residence time of CD-SH, CD-SS-MNA, and CD-SS-PEG on porcine intestine was up to 9.6-, 12.55-, and 11.2-fold prolonged compared to native CD, respectively. According to these results, S-protection of thiolated CDs can be a promising approach to improve their mucus permeating and mucoadhesive properties. Three generations of thiolated cyclodextrins (CDs) with different types of thiol ligands have been synthesized to improve mucus interaction. 1st generation of thiolated CDs was synthesized by converting hydroxyl groups into thiols by reaction with Thiourea. For 2nd generation, free thiol groups were S-protected by reaction with 2-mercaptonicotinic acid (MNA), resulting in high reactive disulfide bonds. For 3rd generation, terminally thiolated short PEG chains (2 kDa) were used for S-protection of thiolated CDs. Mucus penetrating properties were found to be increased as follows: 1st generation < 2nd generation < 3rd generation. Furthermore, mucoadhesive properties were improved in the following rank order: 1st generation < 3rd generation < 2nd generation. This study suggests that the S-protection of thiolated CDs can enhance mucus penetrating and mucoadhesive properties. [Display omitted] [ABSTRACT FROM AUTHOR]

Vitiligo is a common autoimmune pigmentary disorder characterized by destruction of functional melanocytes resulting in the appearance of depigmented patches on the skin and mucosa. These lesions pose a cosmetic challenge. The involvement of the mucosa is less, but may be the first symptom of this pathology. Depigmentation in the lips can be more easily observed and patients can be counseled regarding the condition and guided for treatment. Aims: The study describes the various clinic-epidemiological factors associated with lip vitiligo. Materials and Methods: The study sample included 100 patients of lip vitiligo of all age groups and gender. Patients with a history of herpes labialis, and history suggestive of post inflammatory depigmentation of lips secondary to various causes were excluded from this study. Also, patient vitiligo patients without lip involvement were excluded. The frequency, site, extension, association with vitiligo elsewhere, and systemic association were noted and tabulated. Results: Among 100 patients, 57 were males and 43 were females. Majority of our study subjects (63%) had onset of vitiligo between 11 and 30 years and 24% between 31 and 50 years. In the present study, 41 patients had only lip vitiligo, 55 patients had lip and vitiligo in other parts, four had involvement of lip and genital mucosa. Out of 100 patients, 71 complained that the lips were the initial lesion. The most type of vitiligo seen in our study subjects was the isolated lip vitiligo (41) and the least common was universal vitiligo (2). Leukotrichia was seen in three patients. In our study six patients had exclusive upper lip vitiligo and 40 patients had lower lip vitiligo. The remaining patients had both lower lip and upper lip involvement. Angle of the mouth was involved in 31 patients and five had marginal extension onto the skin. Of 100 patients with vitiligo nearly 19% had atleast one co-morbid condition. The most common autoimmune disease was thyroid dysfunction seen in 17% of patients. Conclusion: Though rare, lip vitiligo could be one of the earliest presentations of vitiligo and will aid in counseling the patients regarding the chronicity and thereby reduce the psychological morbidity. The data on lip vitiligo is sparse and to the best of our knowledge, there is no study on the demographic characteristics and clinical patterns of lip vitiligo. [ABSTRACT FROM AUTHOR]

In the past years, it has become clear that the family of Mas-related G protein-coupled receptors plays a central role in neuro-immune communication at mucosal barrier surfaces, in particular in the skin. Remarkably, MRGPR expression at other mucosal surfaces remains poorly characterized. To fill this gap in our understanding, the present study was undertaken to screen and verify the expression of the human MRGPR family members in the mucosal biopsies of the human gastrointestinal (GI) tract. Our findings revealed that, of all human MRGPRs family members, only MRGPRF mRNA is expressed at detectable levels in human mucosal biopsies of both terminal ileum and sigmoid colon. Furthermore, immunohistochemical stainings revealed that MRGPRF is specifically expressed by mucosal entero-endocrine cells (EECs). Overall, this study showed for the first time that the human ileum and colonic mucosa represent a novel expression site for the orphan MRGPRF, more specifically in EECs. [ABSTRACT FROM AUTHOR]

The current study observed the histological differences of the swim bladder of the tropical eel, Anguilla bicolor bicolor, as an adaptation resulting from hydrostatic change. A total of 15 eels were collected from Pasir Puncu, Keburuhan, Purworejo and Segara Anakan, Cilacap, Indonesia in June 2017, September 2020, and April 2021. The eels were grouped into 4 stages based on the silvering stage and sex, namely: yellow undifferentiated, yellow female, silver male, and silver female. The average length and body weight of yellow undifferentiated eels were 255.07 ± 45.91 mm and 13.66 ± 8.5 g, respectively; for yellow female, the values were 374.35 ± 41.51 mm and 56.5 ± 12.02 g; for silver male, the values were 432.43 ± 15.15 mm and 140.29 ± 13.85 g; and for silver female were 702 ± 0.00 mm and 545 ± 11.31 g. The present study successfully recorded the histological structure of the swim bladder of A. bicolor bicolor in silver male and silver female stages. Silver males and females displayed a greater significant development of the swim bladder than yellow stages in the gas gland, mucosa, and submucosa layers. These results suggest that an increase in the gas gland thickness allows a greater contribution from gas to gas secretion, the mucosa exerts a mechanical effect on the newly formed gas bubbles, and the submucosa thickness reduces gas conductivity from the swim bladder wall. [ABSTRACT FROM AUTHOR]

Background: Intensity modulated radiotherapy (IMRT) for head and neck cancer has led to a reduction in radiotherapy doses to normal tissues, like the salivary glands, while maintaining high rates of local control. Oral mucosal and skin toxicity is still a major source of treatment—related morbidity, occurring in most patients. Purpose: We conducted a dosimetric feasibility study with the goal of creating a methodology that could theoretically reduce the dose of radiation to skin and oral mucosa, while maintaining comparable avoidance of other organs at risk, and planning target volume (PTV) coverage. Methods: The clinical plans of patients treated previously were replanned using coplanar VMAT arcs on a TrueBeam STx using the photon optimizer (PO) version 15.6 and the Acuros XB dose calculation algorithm. Comparisons were made between three methodologies: "Conventional," "Skin Sparing" and a skin/mucosa avoiding ("SMART") technique, with dose metrics being compared using analysis of variance, with a Bonferroni correction to account for multiple pairwise comparisons. The maximum grade of mucositis and radiation dermatitis during treatment was correlated to different dose‐volume metrics to predict what could be clinically meaningful. Results: Sixteen patients met the study criteria and were replanned using the skin sparing and SMART techniques. Maximum doses to the skin sparing structure were reduced from 64.2 Gy to 56.6 and 55.9 Gy, in the skin sparing and SMART plans (p < 0.0001), and mean doses reduced from 26.7 Gy to 20.0 and 20.2 Gy, respectively (p < 0.0001). Maximum doses to the oral cavity structure were not reduced by either technique, however mean dose to the oral cavity structure was reduced from 39.03 Gy to 33.5 Gy by the SMART technique (p < 0.0001). There was a slight reduction in PTV_High coverage by the V95% in the SMART plans (99.52% vs. 98.79%, p = 0.0073), and a similar slight reduction in PTV_Low coverage by the V95% by both the skin sparing and SMART plans (99.74% vs. 97.89% vs. 97.42%, p < 0.0001). Maximum doses to organs at risk were not statistically different between techniques. Dose to oral cavity and maximum grade experienced during radiotherapy correlated. The Spearman correlation coefficient for dose to 20%, 50%, and 80% of the volume of oral cavity was 0.5 (p = 0.048), 0.64 (p = 0.007), and 0.62 (p = 0.010), respectively. Skin toxicity grade was only found to be correlated with the D20% of the skin sparing structure (Spearman correlation coefficient of 0.58, p = 0.0177). Conclusion: The SMART technique appears to be able to reduce maximum and mean skin dose, as well as mean oral cavity doses, while only slightly reducing PTV coverage, with acceptable OAR doses. We feel the improvements warrant investigation in a clinical trial. [ABSTRACT FROM AUTHOR]

The development of tuberculosis (TB) vaccines has been hindered by the complex nature of Mycobacterium tuberculosis (M.tb) and the absence of clearly defined immune markers of protection. While Bacillus Calmette-Guerin (BCG) is currently the only licensed TB vaccine, its effectiveness diminishes in adulthood. In our previous research, we identified that boosting BCG with an intranasally administered chimpanzee adenovirus expressing the PPE15 antigen of M.tb (ChAdOx1.PPE15) improved its protection. To enhance the vaccine’s efficacy, we combined PPE15 with the other three members of the Esx-5a secretion system and Ag85A into a multi-antigen construct (5Ag). Leveraging the mucosal administration safety of ChAdOx1, we targeted the site of M.tb infection to induce localized mucosal responses, while employing modified vaccinia virus (MVA) to boost systemic immune responses. The combination of these antigens resulted in enhanced BCG protection in both the lungs and spleens of vaccinated mice. These findings provide support for advancing ChAdOx1.5Ag and MVA.5Ag to the next stages of vaccine development.

Fibrosis is the result of extracellular matrix protein deposition and remains a leading cause of death in USA. Despite major advances in recent years, there remains an unmet need to develop therapeutic options that can effectively degrade or reverse fibrosis. The tumor necrosis super family (TNFSF) members, previously studied for their roles in inflammation and cell death, now represent attractive therapeutic targets for fibrotic diseases. In this review, we will summarize select TNFSF and their involvement in fibrosis of the lungs, the heart, the skin, the gastrointestinal tract, the kidney, and the liver. We will emphasize their direct activity on epithelial cells, fibroblasts, and smooth muscle cells. We will further report on major clinical trials targeting these ligands. Whether in isolation or in combination with other anti-TNFSF member or treatment, targeting this superfamily remains key to improve efficacy and selectivity of currently available therapies for fibrosis. [ABSTRACT FROM AUTHOR]

Objectives: The aim was to evaluate peri‐implant tissue levels over a 3‐year period for implants connected to either convex or concave final abutments at the time of implant placement. Materials and Methods: In this randomized, double‐masked, controlled clinical study, 28 patients with one missing maxillary premolar were assigned to receive one single implant with a permanent abutment of either convex (CONVEX Group) or concave (CONCAVE Group) emergence shape at the time of implant placement. Clinical and radiographic data were collected at the time of implant placement (IP), final prosthesis delivery (PR), 12 months (FU‐1), and 36 months (FU‐3) following implant placement. Results: At the FU‐3 13 patients were available from the CONCAVE Group (n = 13) and eleven from the CONVEX Group (n = 11). The mean change in buccal peri‐implant mucosa position (MP) from IP to FU‐3 was −0.54 ± 0.93 mm for the CONVEX Group and − 0.53 ± 0.87 mm for CONCAVE Group (p =.98). The amount of bone remodeling above the implant platform from IP to FU‐3 was −0.69 ± 0.48 mm for the CONVEX Group and −0.16 ± 0.22 mm for the CONCAVE Group (p =.005). Conclusion: The study failed to support the hypothesis that abutment macro‐design has an effect on buccal peri‐implant mucosa margin position over time. [ABSTRACT FROM AUTHOR]

Drug delivery via the oral mucous membrane is a promising alternative to the oral route. Sublingual route is a useful when rapid onset of action is desired with better patient compliance than orally ingested tablets. In terms of permeability, the sublingual area of the oral cavity (i.e., the floor of the mouth) is more permeable than the buccal (cheek) area, which in turn is more permeable than the palatal (roof of the mouth) area. The portion of drug absorbed through the sublingual blood vessels bypasses the hepatic first-pass metabolic processes giving acceptable bioavailability. Various techniques can be used to formulate sublingual tablets. New sublingual technologies address many pharmaceutical and patient needs, ranging from enhanced life-cycle management to convenient dosing for paediatric, geriatric, and psychiatric patients with dysphagia. This review highlights the different sublingual dosage forms, factors affecting the sublingual absorption, advantages, various in vitro and in vivo evaluation parameters, and commercially available sublingual dosage forms. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim to determine the age-related morphological features of the isthmus of fallopian tubes of parous elderly and senile women in comparison with women in early adulthood. Material and methods. For the morphological study, 79 parous women were divided into 3 groups: Group I included 26 women of early adulthood (aged from 22 to 35), Group II included 28 elderly women (aged from 57 to 74), Group III included 25 senile women (aged from 75 to 88). The histological, micrometric and statistical methods were used in the study. The preparations were stained with hematoxylin and eosin. The thickness of the mucous membrane of the isthmus of fallopian tubes was measured. Results. The mucous membrane of the isthmus in the old and senile age is characterized by thickened folds located close to each other, forming a narrowing of the uterine tube lumen. From the early adulthood to old age, the thickness of the uterine tube mucosa in the isthmus area was decreasing by 9.1% in the right tube and by 9.2% in the left tube. In the interval from the old age to senile age, the thickness of the right fallopian tube mucosa was decreasing by 4.7% and that of the left fallopian tube by 4.5% (p0.01). There was a tendency for asymmetry in the thickness of the mucous membrane in the isthmus area with predominant parameters in the right fallopian tube in all age groups under the study (p0.05). Conclusion. The results obtained during the study allow us to expand the previously available information on the age-related restructuring of the female reproductive system organs. This information may provide the basis for various kinds of "anti-age" and clinical research.

Background. Among the damaging factors affecting the mucociliary system of the nasal cavity, surgical wound is of particular relevance in the practice of an otorhinolaryngologist. The clinical assessment of regeneration of the mucociliary system is associated with certain diffi culties, since the intravital morphological examination of the nasal mucosa in patients is traumatic. Therefore, the development of animal models of experimental rhinitis is considered to be highly relevant in order to study the dynamics of mucociliary pathomorphological changes and assess the epithelium regeneration.Objectives. To evaluate the developed model of experimental rhinitis in laboratory rats by studying clinical, morphological and biochemical changes in the infl ammatory process.Methods. The experimental rhinitis model was developed and tested on 60 mature male Wistar rats. All animals were randomized into two groups: experimental group #1 (n = 30) — rats in which experimental rhinitis modeling was performed and group #2 (n = 30) — control, intact animals. In the course of the experiment, the authors examined the content of CRP in blood, evaluated the differential blood cell count, and studied a morphology of the nasal septum mucosa in 2, 5, 10 days after the injury to assess the dynamics of the infl ammatory process in rats of both groups. Statistical analysis of the study results was carried out by means of Statistica 8.0 (StatSoft Inc., USA).Results. After injury, the rats from group #1 developed acute rhinitis, which was clinically manifested by the release of mucous or mucopurulent secretion from the nostrils, sneezing and scratching the nose. An increase in CRP, band and segmented neutrophils, and a decrease in lymphocytes were observed in blood of the rats from group #1 in comparison with the control group. Microscopic analysis of changes in the nasal septum mucosa showed that the acute phase of exudative infl ammation developed on the second day: vascular congestion, edema, neutrophilic infl ammatory infi ltration of the submucosal membrane were observed against the background of foci of epithelial necrosis. The proportion of lymphocytes and macrophages in the infl ammatory infi ltrate increased by the fi fth day, initial signs of restoration of epithelial tissue — the formation of an undifferentiated regenerating epithelium — appeared by the tenth day.Conclusion. The results of the study show that an adequate experimental model of acute rhinitis in laboratory animals have been obtained. An acute infl ammatory process is characterized by clinical manifestations and changes in blood parameters. Particular destructive and reparative-proliferative changes develop in the mucous membrane of the nasal septum of experimental animals as a result of a surgical wound.

Vitiligo is a common autoimmune pigmentary disorder characterized by destruction of functional melanocytes resulting in the appearance of depigmented patches on the skin and mucosa. These lesions pose a cosmetic challenge. The involvement of the mucosa is less, but may be the first symptom of this pathology. Depigmentation in the lips can be more easily observed and patients can be counseled regarding the condition and guided for treatment. Aims: The study describes the various clinic-epidemiological factors associated with lip vitiligo. Materials and Methods: The study sample included 100 patients of lip vitiligo of all age groups and gender. Patients with a history of herpes labialis, and history suggestive of post inflammatory depigmentation of lips secondary to various causes were excluded from this study. Also, patient vitiligo patients without lip involvement were excluded. The frequency, site, extension, association with vitiligo elsewhere, and systemic association were noted and tabulated. Results: Among 100 patients, 57 were males and 43 were females. Majority of our study subjects (63%) had onset of vitiligo between 11 and 30 years and 24% between 31 and 50 years. In the present study, 41 patients had only lip vitiligo, 55 patients had lip and vitiligo in other parts, four had involvement of lip and genital mucosa. Out of 100 patients, 71 complained that the lips were the initial lesion. The most type of vitiligo seen in our study subjects was the isolated lip vitiligo (41) and the least common was universal vitiligo (2). Leukotrichia was seen in three patients. In our study six patients had exclusive upper lip vitiligo and 40 patients had lower lip vitiligo. The remaining patients had both lower lip and upper lip involvement. Angle of the mouth was involved in 31 patients and five had marginal extension onto the skin. Of 100 patients with vitiligo nearly 19% had atleast one co-morbid condition. The most common autoimmune disease was thyroid dysfunction seen in 17% of patients. Conclusion: Though rare, lip vitiligo could be one of the earliest presentations of vitiligo and will aid in counseling the patients regarding the chronicity and thereby reduce the psychological morbidity. The data on lip vitiligo is sparse and to the best of our knowledge, there is no study on the demographic characteristics and clinical patterns of lip vitiligo.

Introduction Vascular endothelial growth factor (VEGF) is signal molecule enrolled in diabetes mellitus type 2 (DM type 2) oral complications, but there are no studies showing the relation between VEGF and pressure caused by denture wearing in diabetic conditions. The aim of this study is to compare tissue VEGF levels in patients and animals with/without DM in conditions of chronic and acute pressure. Methods Research was conducted on DM type 2 and healthy partial denture wearers for more than 5 years (78), candidates for teeth extractions and experimental animals of the Wistar rats (40). For chronic conditions, VEGF was measured in 2 mucosal samples covered and not covered by denture in all denture wearers. Demonstrating acute conditions, after 3 days of wearing experimental plate VEGF was measured in 2 gingival samples of palatal mucosa of DM (20) and control rats (20). The concentrations of VEGF (pg/ml) in human and animal tissues were measured by commercially available ELISA kit. Results Tissue VEGF levels in control and diabetic partial denture wearers not covered by denture were without statistical difference. In comparison to noncovered tissue, VEGF decreased in samples covered by denture, being significantly lower in DM type 2, comparing to healthiest. VEGF levels in palatal mucosa without palatal base did not significantly differ in control and DM rats. VEGF levels under palatal base increased being significantly lower in DM rats comparing to controls. Conclusion Both, chronic and acute mechanical stress caused by wearing palatal denture (plate) decreased the VEGF levels in diabetic conditions comparing the health's suggesting the altered homeostasis.

Gastrointestinal simulations in vitro have only limited approaches to analyze the microbial communities inhabiting the mucosal compartment. Understanding and differentiating gut microbial ecosystems is crucial for a more comprehensive and accurate representation of the gut microbiome and its interactions with the host. Herein is suggested, in a short-term and static set-up (named “M-batches”), the analysis of mucosal and luminal populations of inhabitants of the human colon. After varying several parameters, such as the fermentation volume and the fecal inoculum (single or pool), only minor differences in microbial composition and metabolic production were identified. However, the pool created with feces from five donors and cultivated in a smaller volume (300 mL) seemed to provide a more stable luminal ecosystem. The study of commercially available coffee and green tea in the M-batches suggested some positive effects of these worldwide known beverages, including the increase in butyrate-producing bacteria and lactobacilli populations. We hope that this novel strategy can contribute to future advances in the study of intestinal ecosystems and host-microbe relationships and help elucidate roles of the microbiome in health and disease.

Fibrosis is the result of extracellular matrix protein deposition and remains a leading cause of death in USA. Despite major advances in recent years, there remains an unmet need to develop therapeutic options that can effectively degrade or reverse fibrosis. The tumor necrosis super family (TNFSF) members, previously studied for their roles in inflammation and cell death, now represent attractive therapeutic targets for fibrotic diseases. In this review, we will summarize select TNFSF and their involvement in fibrosis of the lungs, the heart, the skin, the gastrointestinal tract, the kidney, and the liver. We will emphasize their direct activity on epithelial cells, fibroblasts, and smooth muscle cells. We will further report on major clinical trials targeting these ligands. Whether in isolation or in combination with other anti-TNFSF member or treatment, targeting this superfamily remains key to improve efficacy and selectivity of currently available therapies for fibrosis.

Recently, the relationship between the goat host and its gastrointestinal microbiome has emerged as a hallmark of host-microbiota symbiosis, which was indispensable for the proper physiological function that convert the plant biomass to livestock products. However, little integrative information about the establishment of gastrointestinal microflora in goats exists. Herein, we characterized the colonizing process of the bacterial community in the digesta and mucosa of the rumen, cecum, and colon of the cashmere goat from birth to adulthood to compare its spatiotemporal difference via 16S rRNA gene sequencing. A total of 1,003 genera belonging to 43 phyla were identified. Principal coordinate analysis unveiled the similarity of microbial community between or within each age group increased and gradually developed toward mature whatever in digesta or mucosa. In the rumen, the composition of the bacterial community in digesta differed significantly from in mucosa across age groups; whereas in the hindgut, there was a high similarity of bacterial composition between the in digesta and mucosa in each age group before weaning, while the bacterial community structure differed markedly between these two types of samples after weaning. Taxonomic analysis indicated that 25 and 21 core genera coexisted in digesta and mucosa of the rumen and hindgut, respectively; but their abundances differed considerably by GIT region and/or age. In digesta, as goats aged, a lower abundance of Bacillus was observed with higher abundances of Prevotella 1 and Rikenellaceae RC9 in the rumen; while in the hindgut, the genera Escherichia-Shigella, Variovorax, and Stenotrophomonas decreased and Ruminococcaceae UCG-005, Ruminococcaceae UCG-010, and Alistipes increased with age increased. In mucosa, the rumen showed microbial dynamics with increases of Butyrivibrio 2 and Prevotellaceae UCG-001 and decreases of unclassified_f_Pasteurellaceae; while the genera Treponema 2 and Ruminococcaceae UCG-010 increased and Escherichia-Shigella decreased in the hindgut as goats aged. These results shed light on the colonization process of microbiota in the rumen and hindgut, which mainly include the initial, transit, and mature phases. Furthermore, there is a significant difference in the microbial composition between in digesta and mucosa, and both these exhibit a considerable spatiotemporal specificity. [ABSTRACT FROM AUTHOR]

Grasscutters (GRCs) are hystricognath rodents that predominate West African countries where they are captured and bred in captivity as "microlivestock" and for research. Consequently, research priority has, of late, shifted to aspects of GRC biology particularly with regard to morphofunctional aspects of its body systems. The olfactory system plays critical roles in regulating social, sexual, maternal and feeding behaviors. This study examines, histologically and ultrastructurally, the pattern and magnitude of remodeling of the GRC olfactory mucosa (OM) and nasal respiratory mucosa (NRM) between suckling and adult ages and compares these with what is documented for other mammals. In adults, tubular-type Bowman's glands, olfactory receptor neuron (ORN) axon bundles and blood vessels were uniformly distributed in the OM lamina propria contrary to sucklings where acinar-type Bowman's glands lay superficially and the bundles relatively deeper. Apically in the adult NRM epithelium, ciliated and non-ciliated cells were uniformly distributed as opposed to the sucklings where linearly arranged ciliated cells separated large numbers of non-ciliated cells. Quantitatively between the suckling and adult ages, respective increment values (%) were 28.2, 23.0, 28.1 and 52.9 for OM epithelial thickness, axon bundle diameter, ORN packing density and cilia number/ORN dendritic knob. Age-related increment in volume density (%) was 53.9, 31.6, 19.4 and 46.3 for Bowman's glands, axon bundles, OM vessels and NRM glands, respectively. We conclude that microstructural refinement of the OM and NRM varies in qualitative and quantitative detail depending on age and species and that phenotypic plasticity in these structures suggests environmentally driven morphology. [ABSTRACT FROM AUTHOR]

Objectives: To report a summary of published patient‐reported esthetic outcome measures (PROMs) of implant‐supported single crowns (SCs) compared with those of tooth‐supported SCs. Materials and Methods: Cochrane, Medline (PubMed), and EMBASE database search was performed by three reviewers on reports with patient‐reported esthetic outcomes of tooth‐ and implant‐supported SCs. Clinical studies with at least 12 months of mean follow‐up period and a minimum of 10 patients, and English, French, or German reports were included. To compare the subgroups, for aggregate‐level data, random‐effects meta‐regression was used. Results: Two thousand fifteen titles were identified (initial search) and screened independently concluding 53 full‐text articles to include in data extraction. Twenty‐two studies with 29 study cohorts were included. Patients were satisfied with the esthetics of implant‐ and tooth‐ supported crowns Mean visual analogue scale (VAS) value from the PROMs data of 1270 implant‐supported SCs evaluated by 1051 patients was 89.6% (80.0%–94.1%). The mean VAS value of patients (n = 201), who evaluated the esthetic outcome of 486 tooth‐supported SCs was 94.4% (92.3%–96.0%). VAS scores of patients regarding their perception of esthetics did not show any difference among different crown materials or type of implant used. The patients' perception of esthetics focusing on SC had a tendency to be higher when the crowns were supported by teeth, however, no statistical difference was found when compared with implant‐supported crowns (p = 0.067). Conclusions: Patient perception of esthetics in SCs was not affected by the type of support, crown material, implant, and presence of provisional crown for both implant‐ and tooth‐supported SCs. Clinical Significance: Despite that patient's expectations are increasing overall Patients are satisfied with with esthetic outcome of implant‐ and tooth‐supported crowns. [ABSTRACT FROM AUTHOR]

Background: Expansion of OKF6/TERT-2 oral epithelial cells in vitro is important for studying the molecular biology of disease and pathology affecting the oral cavity. Keratinocyte serum-free medium (KSFM) is the medium of choice for this cell line. This study compares three media for OKF6/TERT-2 cultures: KSFM, Dulbecco's Modified Eagle Medium/Nutrient Mixture of Hams F-12 (DMEM/F12), and a composite medium comprised of DMEM/F-12 and KSFM (1:1 v/v), referred to as DFK. The toxicological effects of electronic cigarette liquids (e-liquids) on OKF6/TERT-2 cells cultured in these media were also compared. Methods: Cells were cultured in KSFM, DMEM/F12, or DFK, and cellular morphology, growth, wound healing and the gene expression of mucins and tight junctions were evaluated. Additionally, cytotoxicity was determined after e-liquid exposures. Results: Switching from KSFM to DMEM/F12 or DFK 24 h post-seeding leads to typical cellular morphologies, and these cultures reach confluency faster than those in KSFM. Wound-healing recovery occurred fastest in DFK. Except for claudin-1, there is no difference in expression of the other genes tested. Additionally, e-liquid cytotoxicity appears to be amplified in DFK cultures. Conclusions: DMEM/F12 and DFK are alternative media for OKF6/TERT-2 cell culture to study the molecular biology of disease and pathology, provided cells are initially seeded in KSFM. [ABSTRACT FROM AUTHOR]

Nevus of Ota is a macular discoloration of the face which is most commonly found in the Japanese and females are more commonly affected than males. It is first described by Ota and Tanino in 1939, involves the skin along the distribution of first and second division of trigeminal nerve. Involvement of the palatal mucosa occurs rarely in nevus of Ota, it usually blends with the oral mucosa and is typically irregular, undefined and often present as a mottled patch. We describe here the case of nevus of Ota with palatal involvement in a 13-year-old Asiatic boy. His past medical history revealed the presence of the lesion since birth. There were no other pigmented lesion locations. The exact etiology of nevus of Ota is still unknown but they have the potential to undergo melanomatous change. [ABSTRACT FROM AUTHOR]

Rapid and proper diagnosis of mucocutaneous presentations of COVID-19 which in many cases are representing internal organ damage is a key way to better approach these patients, and it could be even lifesaving. In this original study, we reported consultant critical and non-critical cases of admitted COVID-19 patients and some interesting outpatient cases for 14 months, and some newly encountered vaccine-associated dermatoses. We presented 121 cases divided into 12 categories; all had full multi-aspects photographs attached as an atlas to a Supplementary File. These categories were:1- Generalized papulopustular eruptions (3 patients), 2- Erythroderma (4 patients), 3- Maculopapular lesions(16 patients), 4- Mucosal lesions (8 patients), 5- Urticarial lesions and angioedema (16 patients), 6- Vascular injuries (22 patients), 7- Vesiculobullous lesions (12 patients), 8- The specific new onset of mucocutaneous presentations or aggravation of any especial previous dermatoses (9 patients), 9- Nail changes (3 patients), 10- Hair loss (2 patients), 11- Non-specific mucocutaneous problems (16 patients) and 12-Vaccine-associated dermatoses (10 patients). In the pandemic, if we countered with extensive mucocutaneous lesions with vascular components or vesiculobullous erosive lesions in association with any cutaneous rash that could be an alarming sign of a probable life-threatening systemic event, we would need to approach them as soon as possible. [ABSTRACT FROM AUTHOR]

Sialolithiasis mainly affects the oral salivary glands due to the presence of small stones that obstruct the secretion of saliva. The treatment and control of pain and inflammation during the course of this pathology is essential to guarantee the patient's comfort. For this reason, a ketorolac calcium cross-linked alginate hydrogel was developed, and it was then applied in the area of the buccal cavity. The formulation was characterized (swelling and degradation profile, extrusion, extensibility, surface morphology, viscosity, and drug release). The drug release was studied ex vivo in static Franz cells and with a dynamic ex vivo method under artificial saliva continuous flow. The product exhibits adequate physicochemical properties considering the intended purpose, and the drug concentrations retained in the mucosa were high enough to deliver a therapeutic local concentration able to reduce the pain associated with the patient's conditions. The results confirmed the suitability of the formulation for application in the mouth. [ABSTRACT FROM AUTHOR]

Background: Peri-implant tissue score (PITS) has been used to assess and measure the success of osseointegrated endosseous dental implants by studying the peri-implant morphology in previously placed dental implants. Materials and Methods: A total of 300 patients who got implants placed previously were evaluated for bone levels, inflammatory status, recession, mucosa, and the patient profile in the time period of <1.5 years, 1.5–3 years, 3–4.5 years, and 4.5–6 years using a graduated periodontal plastic probe. Results: The results were statistically nonsignificant as the parameters did not differ significantly among different year groups. Conclusion: PITS is established as a noninvasive chairside diagnostic tool for clinicians to evaluate the overall implant health and the need for any intervention for the health of implant, but it does not prove to be that efficacious in the frame of time gap of implant placement. [ABSTRACT FROM AUTHOR]

As a catadromous fish, Asian sea bass (Lates calcarifer) juveniles migrate from seawater (SW) to freshwater (FW) for growth and development. During migration, they undergo physiological changes to acclimate to environmental salinity. Thus, it is crucial to understand how SW-to-FW migration affects the gut microbiota of catadromous fish. To the best of our knowledge, no study has revealed the effects of transfer to hypotonic environments on a catadromous fish microbiota. In this study, we aimed to determine the effects of FW transfer on the microbiota and cytokine gene expression in the intestines of juvenile catadromous Asian sea bass. The relationship between the water and the gut microbiota of this euryhaline species was also examined. We found that FW transfer affected both mucosa- and digesta-associated microbiota of Asian sea bass. Plesiomonas and Cetobacterium were dominant in both the mucosa- and digesta-associated microbiota of FW-acclimated sea bass. The pathogenic genera Vibrio, Staphylococcus, and Acinetobacter were dominant in the SW group. Although dominant fish microbes were present in the water, fish had their own unique microbes. Vitamin B6 metabolism was highly expressed in the FW fish microbiota, whereas arginine, proline, and lipid metabolism were highly expressed in the SW fish microbiota. Additionally, the correlation between cytokine gene expression and microbiota was found to be affected by FW transfer. Taken together, our results demonstrated that FW transfer altered the composition and functions of mucosa- and digestaassociated microbiota of catadromous Asian sea bass intestines, which correlated with cytokine gene expression. [ABSTRACT FROM AUTHOR]

Background Oral lesions can affect people’s quality of life by interfering with chewing, swallowing, and speech. These lesions may originate from epithelial or mesenchymal tissues. Malignant oral lesions can be life-threatening. Epidemiological data of oral lesions in Iran is limited. Objective This study aims to investigate the frequency of oral lesions in Rasht, Iran. Methods In this cross-sectional study, histopathologic data of oral lesions reported by Razi laboratory in Rasht from 2015 to 2019 were evaluated. The data collected: Patients’ age and sex, histopathologic findings, and location, type and origin of lesions. Non-specific diagnoses and dental and bone lesions were excluded. Results A total of 259 pathologic reports were included. The mean age patients was 52.09±19 years, and 40.2% were male. Oral lesions in patients aged <40 years were mainly benign (64.2%), whereas half of lesions in patients ≥70 years were mostly malignant. Tongue was the most common location of the lesions (34.7%) and the main location for malignant lesions (46.7%). Benign lesions were significantly higher in females whereas malignant lesions were significantly higher in males (P=0.011). Epithelial tissues were the most common site of origin (49%) and salivary glands were the least common site of origin (11.6%) for oral lesions. Conclusion Malignant oral lesions are more common in Iranian men aged >70 years, where the tongue is the most common site of involvement and epithelial tissue is the main site of origin. [ABSTRACT FROM AUTHOR]

First-pass metabolism alters arsenic biotransformation and its immunomodulatory activities. This study aims to determine the mRNA expression of intestinal-immunity- and permeability-associated genes, levels of cytokine/chemokines and levels of immunoglobulin isotypes when CD-1 mice were exposed to a single dose of intravenous (IV) sodium arsenite (50 µg/kg body weight (BW)) and to compare these responses to exposure via oral gavage (OG) (50 µg/kg BW). Samples were collected at 1, 4, 24 and 48 h post IV exposure and 24 and 48 h post OG. Sodium arsenite IV exposure led to a transient modulation of mRNA expression and protein levels of immunity-related genes involved in inflammation/apoptotic pathways and production of cytokines/chemokines, whereas it also led to downregulated expression of genes encoding tight junction, focal adhesion, and gap junction proteins, which are responsible for maintaining cell permeability. Oral exposure perturbed fewer cell-permeability-related genes at 24 and 48 h post exposure. At 24 h post exposure, OG decreased IgA and IgG2b levels; however, IV exposure significantly increased IgG2b, IgG3 and IgA in ileal tissue. Earlier, we showed significant downregulation of mRNA expression of genes involved in the immune-related pathways during OG in the intestinal mucosa of the same animals. Cumulatively, these results provide evidence that the exposure route of a xenobiotic can differentially impact the intestinal responses due to the impact of first-pass metabolism. [ABSTRACT FROM AUTHOR]