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Objective: To assess the clinical, microbiological, and patient-based effects of using a cetylpyridinium chloride (CPC) toothpaste and mouth rinse in orthodontic patients. Design: Parallel randomized controlled, triple-blinded trial (participants, examiners, outcomes' assessors). A computer-generated list was used to allocate treatments. Central allocation was used for concealment. Participants: Thirty-one placebo (10 males, 21 females; mean age 15.2 ± 2.1) and 32 test patients (15 males, 17 females; mean age 15.0 ± 1.8) with fixed orthodontic appliance were included in the study. Interventions: Patients were randomly assigned to both brush and rinse with placebo or with CPC-based products. Products were purposely prepared in white opaque bottles. After screening and professional prophylaxis, patients received a baseline examination, and started to use the assigned products. Patients were monthly assessed during a 3-month period. Main outcome measures: Plaque (PlI) and gingival (GI) indexes. Secondary outcome variables: Calculus index, tooth staining, subgingival microbiological samples, patient-based variables (questionnaire, compliance, and remaining mouth rinse), side-effects (debonded braces or mucosal injuries). Results: Sixty-three patients were randomized, 13 patients were excluded from analysis because of early dropout, leaving 50 patients for intention to treat analysis. PlI in the upper jaw diminished (0.18; SD = 0.82) after 1 month in the test group, while it increased (0.26; SD = 0.62) in the placebo group (P = 0.024). Statistically significant higher GI values were observed in the placebo group at 1 month (mean increase = 0.05; SD = 0.33 versus mean decrease = 0.03; SD = 0.38) and 3 months (mean = 0.05; SD = 0.43 versus mean = 0.02; SD = 0.34). The taste of the test product was rated higher than the placebo at 2- and 3-month visits (P < 0.05). Non-significant changes were observed in microbiological parameters, overgrowth of opportunistic species or rem, Depto. de Especialidades Clínicas Odontológicas, Fac. de Odontología, TRUE, pub

Objective: To assess the clinical, microbiological, and patient-based effects of using a cetylpyridinium chloride (CPC) toothpaste and mouth rinse in orthodontic patients. Design: Parallel randomized controlled, triple-blinded trial (participants, examiners, outcomes' assessors). A computer-generated list was used to allocate treatments. Central allocation was used for concealment. Participants: Thirty-one placebo (10 males, 21 females; mean age 15.2 ± 2.1) and 32 test patients (15 males, 17 females; mean age 15.0 ± 1.8) with fixed orthodontic appliance were included in the study. Interventions: Patients were randomly assigned to both brush and rinse with placebo or with CPC-based products. Products were purposely prepared in white opaque bottles. After screening and professional prophylaxis, patients received a baseline examination, and started to use the assigned products. Patients were monthly assessed during a 3-month period. Main outcome measures: Plaque (PlI) and gingival (GI) indexes. Secondary outcome variables: Calculus index, tooth staining, subgingival microbiological samples, patient-based variables (questionnaire, compliance, and remaining mouth rinse), side-effects (debonded braces or mucosal injuries). Results: Sixty-three patients were randomized, 13 patients were excluded from analysis because of early dropout, leaving 50 patients for intention to treat analysis. PlI in the upper jaw diminished (0.18; SD = 0.82) after 1 month in the test group, while it increased (0.26; SD = 0.62) in the placebo group (P = 0.024). Statistically significant higher GI values were observed in the placebo group at 1 month (mean increase = 0.05; SD = 0.33 versus mean decrease = 0.03; SD = 0.38) and 3 months (mean = 0.05; SD = 0.43 versus mean = 0.02; SD = 0.34). The taste of the test product was rated higher than the placebo at 2- and 3-month visits (P < 0.05). Non-significant changes were observed in microbiological parameters, overgrowth of opportunistic species or rem, This work was partially supported by a research contract between Dentaid (Cerdanyola, Barcelona, Spain) and the University Complutense of Madrid, Depto. de Especialidades Clínicas Odontológicas, Fac. de Odontología, TRUE, pub

This article provides detailed information on perinatal death in hyaline membrane disease.

We have developed a cell-based outer vocal fold replacement (COVR) as a potential therapy to improve voice quality after vocal fold (VF) injury, radiation, or tumor resection. The COVR consists of multipotent human adipose-derived stem cells (hASC) embedded within a three-dimensional fibrin scaffold that resembles vocal fold epithelium and lamina propria layers. Previous work has shown improved wound healing in rabbit studies. In this pilot study in pigs, we sought to develop methods for large animal implantation and phonatory assessment. Feasibility, safety, and structural and functional outcomes of the COVR implant are described. Of eight pigs studied, six animals underwent COVR implantation with harvest between 2 weeks and 6 months. Recovery of laryngeal tissue structure was assessed by vibratory and histologic analyses. Recovery of voice function was assessed by investigating acoustic parameters that were derived specifically for pigs. Results showed improved lamina propria qualities relative to an injured control animal at 6 months. Acoustic parameters reflected voice worsening immediately after surgery as expected; acoustics displayed clear voice recovery in the animal followed for 6 months after COVR. These methods form the basis for a larger-scale long-term pre-clinical safety and efficacy study.

Introduction: The SARS CoV 2 infection has resulted in several health, economic, and social crises in all areas. The disease shows a substantial biological diversity in humans causing a series of sequels in the trans- or post-infection period in the entire organism. Case Report: The manifestations that occur in the oral cavity and pharynx have not been evaluated. In this study, two clinical cases are reported. The first patient, a 67-year-old male, presents erosive lesions on the dorsal surface of his tongue after SARS CoV 2 infection. Results: Therapy consisting of reinforcing oral cleaning, use of antifungal solutions, mouthwashes containing superoxidation solution and B complex was given to the patient. The reported lesions improved satisfactorily. The second case, a 47-year-old male patient, presented vesiculobullous lesions on the lingual and labial mucosa accompanied by severe painful symptoms after SARS CoV 2 infection. An incisional biopsy was performed. The histopathological result was compatible with pemphigus vulgaris, and the treatment protocol was started with 0.1% topical mometasone and 2g miconazole gel, observing adequate involution of the lesions after 20 days. Conclusions: The aim of this study is to report on the lesions affecting the oral cavity and pharynx in post-COVID patients with the aim of carrying out a thorough intraoral examination, establishing a clinical or histopathological diagnosis to implement a specific treatment plan in each case to improve the health and quality of life of the patients., Introducción: La infección por virus de SARS CoV 2 ha dejado a su paso una estela de crisis en materia de salud, económica, social y en todos los ámbitos a la fecha seguimos realizando la observación del comportamiento de la enfermedad en los seres humanos con una diversidad biológica importante y que ha traído como consecuencia una serie de secuelas que se presentan en el periodo trans o posterior a la infección en toda la economía corporal. Reporte de Caso: Se ha evaluado poco las manifestaciones que se presentan en la cavidad bucal y faringe; se presentan dos casos clínicos el primero paciente masculino de 67 años de edad posterior a la infección por SARS CoV 2 presenta diluciones de continuidad en bordes laterales de la lengua se indica terapia y refuerza limpieza bucal, antimicótico, colutorios con solución de super oxidación y complejo B, las úlceras involucionan de manera satisfactoria. Resultados: El segundo caso masculino de 47 años posterior a la infección por SARS CoV 2 debuta con lesiones vesículo-ampollosas en mucosa lingual, labial con sintomatología dolorosa severa, se realiza biopsia incisional donde el resultado histopatológico es compatible con pénfigo vulgar, se inicia protocolo de tratamiento con mometasona tópica al 0.1% y miconazol gel 2g observándose una adecuada involución de las lesiones a los 20 días. Conclusiones: El objetivo de este trabajo es poner en contexto de la comunidad médica y científica las lesiones concernientes a la cavidad bucal y faringe que están presentando los pacientes post covid con el objetivo de realizar una exhaustiva exploración intraoral, establecer un diagnóstico clínico o histopatológico y con base en esto instaurar un plan de tratamiento específico en cada caso en particular con el fin fundamental de mejorar la salud y calidad de vida del paciente.

The main objective of this study is the evaluation of the use of a synthetic membrane, Nuclepore, as a model for permeation studies through sublingual mucosa. The permeability of two types of membranes, porcine sublingual oral mucosa and a synthetic Nuclepore membrane, to water was compared. Moreover, the water permeability of membranes modified with waterproofing formulations was measured to study their ability to protect against the penetration of viruses, toxins, etc. A relatively high correlation (R2 0.88) was obtained between the transmucosal water loss (TMWL) values of the artificial membrane and the mucosa. These results support the possible use of this synthetic membrane in the screening of the water permeability of formulations. In addition, studies of the permeation of different actives, drugs, and biocides through the two membranes were carried out, and these results were compared with their skin permeation data. The synthetic membrane does not seem to discern between compounds in terms of permeability. However, the permeation of caffeine through intact or modified membranes incorporating waterproofing formulations presents similar permeation profiles through the synthetic membrane and mucosa. The results from these assays should lend support to the use of this synthetic membrane when screening formulations to be applied in oral penetration studies, This work was supported by the Consejo Superior de Investigaciones Científicas “Modificación de la mucosa como protección frente al SARS-CoV-2” (CSIC-COV19-130), Postprint (published version)

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 work was supported by the Consejo Superior de Investigaciones Científicas “Modificación de la mucosa como protección frente al SARS-CoV-2” (CSIC-COV19-130), Postprint (published version)

Mucous membrane pemphigoid (MMP) is the subgroup of pemphigoid which predominantly affects mucous membranes. Scarring and limited skin involvement are possible. Several subtypes are classified based on clinical symptoms and target antigens, such as ocular mucous membrane pemphigoid, localized vulvar pemphigoid (LVP) and anti-laminin 332 MMP (anti-LN-332 MMP). Autoantibodies are directed against various structural proteins in the epidermal basement membrane zone (EBMZ), with the 180-kD antigen (BP180) as the main target antigen. Other antigens, such as BP230, the heterotrimeric glycoprotein laminin 332 and A6B4 integrin can also be targeted by autoantibodies. Various mucosa can be affected and are histologically characterized as nonkeratinized stratified squamous epithelium. The clinically heterogeneous disease is characterized by erosions and blistering of the oral mucosa (85%), conjunctiva (30-60%), and less frequently, the nasal mucosa (20-40%), esophagus (5-15%), pharyneal (20%) or laryngeal mucosa (5-10%) and anogenital mucosa (25%). Clinical severity is highly variable in the different subtypes of MMP. Previously, the term cicatricial pemphigoid was used for MMP. Progressive scar formation is a severe complication in ocular MMP and anti-LN-332 MMP, but scarring does not occur in all patients with MMP. Patient and doctors delay is frequently seen in MMP because of the heterogeneous clinical presentation and unfamiliarity among clinicians. For an accurate diagnosis, direct immunofluorescence microscopy (DIF) and detection of circulating autoantibodies in serum is essential. The multidisciplinary management and prognosis of MMP depends on the severity and extent of the disease and involves topical corticosteroids and immunomodulatory and immunosuppressive drugs.

Age Features of the Structure and Distribution of Lymphoid Formations in the Rectum Wall of Rats. It is established that lymphoid formations of the anal walls have various localizations and thickness of localization depending on the age and sections of therectum. Lymphoid formations in the presphincteric section transitional zone are located as accumulations of lymphocytes. By the age of 3 months lymphoid nodules are formed of them in the presphincteric section and in the transitional zone this process is completed by the age of 6 months. Lymphoid structures are presented by diffuse lymphoid tissue in the inner sphincter. In various zones of the lymphatic canal lymphoid accumulations have various forms.

Age Features of the Structure and Distribution of Lymphoid Formations in the Rectum Wall of Rats. It is established that lymphoid formations of the anal walls have various localizations and thickness of localization depending on the age and sections of therectum. Lymphoid formations in the presphincteric section transitional zone are located as accumulations of lymphocytes. By the age of 3 months lymphoid nodules are formed of them in the presphincteric section and in the transitional zone this process is completed by the age of 6 months. Lymphoid structures are presented by diffuse lymphoid tissue in the inner sphincter. In various zones of the lymphatic canal lymphoid accumulations have various forms.

Pneumonia is a serious infectious disease that affects people of all ages. And children are no exception. Recently, there has been an increase in the number of acute infectious diseases of the respiratory system, and lung inflammation is the most dangerous of them. Therefore, parents should understand what it is – pneumonia, how to recognize this disease, and what to do in case of its occurrence in the child.

Afferent and efferent units of immune system of mucous membrane of the small intestine in white outbred rats have been studied light-and electron microscopically. On the basis of the received findings it was established that afferent unit stimulates and regulates T-, B - blast’s coo relation. Action of epithelium, stimulated T- and B - lymphocytes and cells of connective tissue has been integrated in efferent unit.

Age Features of the Structure and Distribution of Lymphoid Formations in the Rectum Wall of Rats. It is established that lymphoid formations of the anal walls have various localizations and thickness of localization depending on the age and sections of therectum. Lymphoid formations in the presphincteric section transitional zone are located as accumulations of lymphocytes. By the age of 3 months lymphoid nodules are formed of them in the presphincteric section and in the transitional zone this process is completed by the age of 6 months. Lymphoid structures are presented by diffuse lymphoid tissue in the inner sphincter. In various zones of the lymphatic canal lymphoid accumulations have various forms.

Age Features of the Structure and Distribution of Lymphoid Formations in the Rectum Wall of Rats. It is established that lymphoid formations of the anal walls have various localizations and thickness of localization depending on the age and sections of therectum. Lymphoid formations in the presphincteric section transitional zone are located as accumulations of lymphocytes. By the age of 3 months lymphoid nodules are formed of them in the presphincteric section and in the transitional zone this process is completed by the age of 6 months. Lymphoid structures are presented by diffuse lymphoid tissue in the inner sphincter. In various zones of the lymphatic canal lymphoid accumulations have various forms.

Pneumonia is a serious infectious disease that affects people of all ages. And children are no exception. Recently, there has been an increase in the number of acute infectious diseases of the respiratory system, and lung inflammation is the most dangerous of them. Therefore, parents should understand what it is – pneumonia, how to recognize this disease, and what to do in case of its occurrence in the child.

Afferent and efferent units of immune system of mucous membrane of the small intestine in white outbred rats have been studied light-and electron microscopically. On the basis of the received findings it was established that afferent unit stimulates and regulates T-, B - blast’s coo relation. Action of epithelium, stimulated T- and B - lymphocytes and cells of connective tissue has been integrated in efferent unit.

Afferent and efferent units of immune system of mucous membrane of the small intestine in white outbred rats have been studied light-and electron microscopically. On the basis of the received findings it was established that afferent unit stimulates and regulates T-, B - blast’s coo relation. Action of epithelium, stimulated T- and B - lymphocytes and cells of connective tissue has been integrated in efferent unit.

Pneumonia is a serious infectious disease that affects people of all ages. And children are no exception. Recently, there has been an increase in the number of acute infectious diseases of the respiratory system, and lung inflammation is the most dangerous of them. Therefore, parents should understand what it is – pneumonia, how to recognize this disease, and what to do in case of its occurrence in the child.

Age Features of the Structure and Distribution of Lymphoid Formations in the Rectum Wall of Rats. It is established that lymphoid formations of the anal walls have various localizations and thickness of localization depending on the age and sections of therectum. Lymphoid formations in the presphincteric section transitional zone are located as accumulations of lymphocytes. By the age of 3 months lymphoid nodules are formed of them in the presphincteric section and in the transitional zone this process is completed by the age of 6 months. Lymphoid structures are presented by diffuse lymphoid tissue in the inner sphincter. In various zones of the lymphatic canal lymphoid accumulations have various forms.

Pneumonia is a serious infectious disease that affects people of all ages. And children are no exception. Recently, there has been an increase in the number of acute infectious diseases of the respiratory system, and lung inflammation is the most dangerous of them. Therefore, parents should understand what it is – pneumonia, how to recognize this disease, and what to do in case of its occurrence in the child.

Afferent and efferent units of immune system of mucous membrane of the small intestine in white outbred rats have been studied light-and electron microscopically. On the basis of the received findings it was established that afferent unit stimulates and regulates T-, B - blast’s coo relation. Action of epithelium, stimulated T- and B - lymphocytes and cells of connective tissue has been integrated in efferent unit.

Age Features of the Structure and Distribution of Lymphoid Formations in the Rectum Wall of Rats. It is established that lymphoid formations of the anal walls have various localizations and thickness of localization depending on the age and sections of therectum. Lymphoid formations in the presphincteric section transitional zone are located as accumulations of lymphocytes. By the age of 3 months lymphoid nodules are formed of them in the presphincteric section and in the transitional zone this process is completed by the age of 6 months. Lymphoid structures are presented by diffuse lymphoid tissue in the inner sphincter. In various zones of the lymphatic canal lymphoid accumulations have various forms.

Pneumonia is a serious infectious disease that affects people of all ages. And children are no exception. Recently, there has been an increase in the number of acute infectious diseases of the respiratory system, and lung inflammation is the most dangerous of them. Therefore, parents should understand what it is – pneumonia, how to recognize this disease, and what to do in case of its occurrence in the child.

Afferent and efferent units of immune system of mucous membrane of the small intestine in white outbred rats have been studied light-and electron microscopically. On the basis of the received findings it was established that afferent unit stimulates and regulates T-, B - blast’s coo relation. Action of epithelium, stimulated T- and B - lymphocytes and cells of connective tissue has been integrated in efferent unit.

Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids. Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins. Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells. Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.

Puel and Casanova and Kisand et al. challenge our conclusions that interferonopathy and not IL-17/IL-22 autoantibodies promote candidiasis in autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy. We acknowledge that conclusive evidence for causation is difficult to obtain in complex human diseases. However, our studies clearly document interferonopathy driving mucosal candidiasis with intact IL-17/IL-22 responses in Aire-deficient mice, with strong corroborative evidence in patients.

Mother-to-child transmission (MTCT) of HIV-1 may occur during pregnancy, labor, and breastfeeding; however, the molecular mechanism of MTCT of virus remains poorly understood. Infant tonsil mucosal epithelium may sequester HIV-1, serving as a transient reservoir, and may play a critical role in MTCT. Innate immune proteins human beta-defensins 2 (hBD-2) and -3 may inactivate intravesicular virions. To establish delivery of hBD-2 and -3 into vesicles containing HIV-1, we tagged hBDs with the protein transduction domain (PTD) of HIV-1 Tat, which facilitates an efficient translocation of proteins across cell membranes. Our new findings showed that hBD-2 and -3 proteins tagged with PTD efficiently penetrated polarized tonsil epithelial cells by endocytosis and direct penetration. PTD-initiated internalization of hBD-2 and -3 proteins into epithelial cells led to their subsequent penetration of multivesicular bodies (MVB) and vacuoles containing HIV-1. Furthermore, PTD played a role in the fusion of vesicles containing HIV-1 with lysosomes, where virus was inactivated. PTD-initiated internalization of hBD-2 and -3 proteins into ex vivo tonsil tissue explants reduced the spread of virus from epithelial cells to CD4+ T lymphocytes, CD68+ macrophages, and CD1c+ dendritic cells, suggesting that this approach may serve as an antiviral strategy for inactivating intraepithelial HIV-1 and reducing viral MTCT.

Puel and Casanova and Kisand et al. challenge our conclusions that interferonopathy and not IL-17/IL-22 autoantibodies promote candidiasis in autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy. We acknowledge that conclusive evidence for causation is difficult to obtain in complex human diseases. However, our studies clearly document interferonopathy driving mucosal candidiasis with intact IL-17/IL-22 responses in Aire-deficient mice, with strong corroborative evidence in patients.

The majority of HIV infections are established through the genital or rectal mucosa. Fibroblasts are abundant in these tissues, and although not susceptible to infection, can potently enhance HIV infection of CD4+ T cells. Hyaluronic acid (HA) is a major component of the extracellular matrix of fibroblasts, and its levels are influenced by the inflammatory state of the tissue. Since inflammation is known to facilitate HIV sexual transmission, we investigated the role of HA in genital mucosal fibroblast-mediated enhancement of HIV infection. Depletion of HA by CRISPR-Cas9 in primary foreskin fibroblasts augmented the ability of the fibroblasts to increase HIV infection of CD4+ T cells. This amplified enhancement required direct contact between the fibroblasts and CD4+ T cells, and could be attributed to both increased rates of trans-infection and the increased ability of HA-deficient fibroblasts to push CD4+ T cells into a state of higher permissivity to infection. This HIV-permissive state was characterized by differential expression of genes associated with regulation of cell metabolism and death. Our results suggest that conditions resulting in diminished cell-surface HA on fibroblasts, such as genital inflammation, can promote HIV transmission by conditioning CD4+ T cells toward a state more vulnerable to infection by HIV.

Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids. Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins. Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells. Availability of defined mucin TR O-glycodomains advances experimental studies into the versatile role of mucins at the interface with pathogenic microorganisms and the microbiome, and sparks new strategies for molecular dissection of specific roles of adhesins, glycoside hydrolases, glycopeptidases, viruses and other interactions with mucin TRs as highlighted by examples.

Afferent and efferent units of immune system of mucous membrane of the small intestine in white outbred rats have been studied light-and electron microscopically. On the basis of the received findings it was established that afferent unit stimulates and regulates T-, B - blast’s coo relation. Action of epithelium, stimulated T- and B - lymphocytes and cells of connective tissue has been integrated in efferent unit.

Pneumonia is a serious infectious disease that affects people of all ages. And children are no exception. Recently, there has been an increase in the number of acute infectious diseases of the respiratory system, and lung inflammation is the most dangerous of them. Therefore, parents should understand what it is – pneumonia, how to recognize this disease, and what to do in case of its occurrence in the child.

Age Features of the Structure and Distribution of Lymphoid Formations in the Rectum Wall of Rats. It is established that lymphoid formations of the anal walls have various localizations and thickness of localization depending on the age and sections of therectum. Lymphoid formations in the presphincteric section transitional zone are located as accumulations of lymphocytes. By the age of 3 months lymphoid nodules are formed of them in the presphincteric section and in the transitional zone this process is completed by the age of 6 months. Lymphoid structures are presented by diffuse lymphoid tissue in the inner sphincter. In various zones of the lymphatic canal lymphoid accumulations have various forms.

Membrane-associated mucins protect epithelial cell surfaces against pathogenic threats by serving as nonproductive decoys that capture infectious agents and clear them from the cell surface and by erecting a physical barrier that restricts their access to target receptors on host cells. However, the mechanisms through which mucins function are still poorly defined because of a limited repertoire of tools available for tailoring their structure and composition in living cells with molecular precision. Using synthetic glycopolymer mimetics of mucins, we modeled the mucosal glycocalyx on red blood cells (RBCs) and evaluated its influence on lectin (SNA) and virus (H1N1) adhesion to endogenous sialic acid receptors. The glycocalyx inhibited the rate of SNA and H1N1 adhesion in a size- and density-dependent manner, consistent with the current view of mucins as providing a protective shield against pathogens. Counterintuitively, increasing the density of the mucin mimetics enhanced the retention of bound lectins and viruses. Careful characterization of SNA behavior at the RBC surface using a range of biophysical and imaging techniques revealed lectin-induced crowding and reorganization of the glycocalyx with concomitant enhancement in lectin clustering, presumably through the formation of a more extensive glycan receptor patch at the cell membrane. Our findings indicate that glycan-targeting pathogens may exploit the biophysical and biomechanical properties of mucins to overcome the mucosal glycocalyx barrier.

Colic diverticulum is defined by an acquired anatomical abnormality of the colon, characterized by the presence of pseudodiverticula formed by herniations of the mucosa and submucosa through the muscular layer of the colon. It is one of the most common pathologies of the large intestine in the Western world and its prevalence during the last century has probably increased due to changes in lifestyle. Diverticular disease of the colon is a common condition with variable clinical presentation and its clinical presentation ranges from being asymptomatic to the presence of symptoms and the development of various complications. Usually the diagnosis is made accidentally, by performing a colonoscopy or enema with contrast medium. Asymptomatic cases do not require treatment and symptomatic patients undergo dietary modifications and oral treatment. Complications require specific management, either with antibiotic or surgical treatment., La diverticulosis cólica se define por una anomalía anatómica adquirida del colon, que se caracteriza por la presencia de seudodivertículos formados por herniaciones de la mucosa y submucosa a través de la capa muscular del colon. Es una de las patologías más comunes a nivel del intestino grueso en el mundo occidental y su prevalencia durante el último siglo se ha incrementado probablemente debido a cambios en los estilos de vida. La enfermedad diverticular del colon es una condición común con presentación clínica variable y su presentación clínica abarca desde ser asintomática hasta la presencia de síntomas y el desarrollo de diversas complicaciones. Generalmente el diagnóstico se realiza de forma incidental, al realizar una colonoscopia o enema con medio de contraste. Los casos asintomáticos no requieren tratamiento y los pacientes sintomáticos se realiza modificaciones en la dieta y tratamiento oral. Las complicaciones requieren un manejo específico, ya sea con tratamiento antibiótico o quirúrgico.

ProblemPregnant women are at increased risk of HIV acquisition, but the biological mechanisms contributing to this observation are not well understood.Method of studyHere, we assessed host immune and microbiome differences in the vaginal mucosa of healthy pregnant and non-pregnant women using a metaproteomics approach. Cervicovaginal lavage (CVL) samples were collected from 23 pregnant and 25 non-pregnant women.ResultsMass spectrometry analysis of CVL identified 550 human proteins and 376 bacterial proteins from 11 genera. Host proteome analysis indicated 56 human proteins (10%) were differentially abundant (P < .05) between pregnant and non-pregnant women, including proteins involved in angiogenesis (P = 3.36E-3), cell movement of phagocytes (P = 1.34E-6), and permeability of blood vessels (P = 1.27E-4). The major bacterial genera identified were Lactobacillus, Gardnerella, Prevotella, Megasphaera, and Atopobium. Pregnant women had higher levels of Lactobacillus species (P = .017) compared with non-pregnant women. Functional pathway analysis indicated that pregnancy associated with changes to bacterial metabolic pathway involved in energy metabolism, which were increased in pregnant women (P = .035).ConclusionOverall, pregnant women showed differences in the cervicovaginal proteome and microbiome that may be important for HIV infection risk.

IntroductionThe majority of new HIV infections occur through mucosal transmission. The availability of readily applicable and accessible platforms for anti-retroviral (ARV) delivery is critical for the prevention of HIV acquisition through sexual transmission in both women and men. There is a compelling need for developing new topical delivery systems that have advantages over the pills, gels and rings, which currently fail to guarantee protection against mucosal viral transmission in vulnerable populations due to lack of user compliance. The silk fibroin (SF) platform offers another option that may be better suited to individual circumstances and preferences to increase efficacy through user compliance. The objective of this study was to test safety and efficacy of SF for anti-HIV drug delivery to mucosal sites and for viral prevention.MethodsWe formulated a potent HIV inhibitor Griffithsin (Grft) in a mucoadhesive silk fibroin (SF) drug delivery platform and tested the application in a non-human primate model in vivo and a pre-clinical human cervical and colorectal tissue explant model. Both vaginal and rectal compartments were assessed in rhesus macaques (Mucaca mulatta) that received SF (n = 4), no SF (n = 7) and SF-Grft (n = 11). In this study, we evaluated the composition of local microbiota, inflammatory cytokine production, histopathological changes in the vaginal and rectal compartments and mucosal protection after ex vivo SHIV challenge.ResultsEffective Grft release and retention in mucosal tissues from the SF-Grft platform resulted in protection against HIV in human cervical and colorectal tissue as well as against SHIV challenge in both rhesus macaque vaginal and rectal tissues. Mucoadhesion of SF-Grft inserts did not cause any inflammatory responses or changes in local microbiota.ConclusionsWe demonstrated that in vivo delivery of SF-Grft in rhesus macaques fully protects against SHIV challenge ex vivo after two hours of ap

Changing ocean conditions driven by anthropogenic activities may have a negative impact on fisheries by increasing stress and disease. To understand how environment and host biology drives mucosal microbiomes in a marine fish, we surveyed five body sites (gill, skin, digesta, gastrointestinal tract [GI], and pyloric ceca) from 229 Pacific chub mackerel, Scomber japonicus, collected across 38 time points spanning 1 year from the Scripps Institution of Oceanography Pier (La Jolla, CA). Mucosal sites had unique microbial communities significantly different from the surrounding seawater and sediment communities with over 10 times more total diversity than seawater. The external surfaces of skin and gill were more similar to seawater, while digesta was more similar to sediment. Alpha and beta diversity of the skin and gill was explained by environmental and biological factors, specifically, sea surface temperature, chlorophyll a, and fish age, consistent with an exposure gradient relationship. We verified that seasonal microbial changes were not confounded by regional migration of chub mackerel subpopulations by nanopore sequencing a 14,769-bp region of the 16,568-bp mitochondria across all temporal fish specimens. A cosmopolitan pathogen, Photobacterium damselae, was prevalent across multiple body sites all year but highest in the skin, GI, and digesta between June and September, when the ocean is warmest. The longitudinal fish microbiome study evaluates the extent to which the environment and host biology drives mucosal microbial ecology and establishes a baseline for long-term surveys linking environment stressors to mucosal health of wild marine fish.IMPORTANCE Pacific chub mackerel, Scomber japonicus, are one of the largest and most economically important fisheries in the world. The fish is harvested for both human consumption and fish meal. Changing ocean conditions driven by anthropogenic stressors like climate change may negatively impact fisheries. One mechanism

Purpose of review:This review summarizes recent literature defining tissue-resident memory T cells (TRM) and discusses implications for HIV pathogenesis, vaccines, and eradication efforts.Recent findings:Investigations using animal models and human tissues have identified a TRM transcriptional profile and elucidated signals within the tissue microenvironment leading to TRM development and maintenance. TRM are major contributors to host response in infectious diseases and cancer; in addition, TRM contribute to pathogenic inflammation in a variety of settings. Although TRM are daunting to study in HIV infection, recent work has helped define their molecular signatures and effector functions and tested strategies for their mobilization. Exclusive reliance on blood sampling to gain an understanding of host immunity overlooks the contribution of TRM, which differ in significant ways from their counterparts in circulation. It is hoped that greater understanding of these cells will lead to novel approaches to prevent and/or eradicate HIV infection.

Purpose of review:This review summarizes recent literature defining tissue-resident memory T cells (TRM) and discusses implications for HIV pathogenesis, vaccines, and eradication efforts.Recent findings:Investigations using animal models and human tissues have identified a TRM transcriptional profile and elucidated signals within the tissue microenvironment leading to TRM development and maintenance. TRM are major contributors to host response in infectious diseases and cancer; in addition, TRM contribute to pathogenic inflammation in a variety of settings. Although TRM are daunting to study in HIV infection, recent work has helped define their molecular signatures and effector functions and tested strategies for their mobilization. Exclusive reliance on blood sampling to gain an understanding of host immunity overlooks the contribution of TRM, which differ in significant ways from their counterparts in circulation. It is hoped that greater understanding of these cells will lead to novel approaches to prevent and/or eradicate HIV infection.

Changing ocean conditions driven by anthropogenic activities may have a negative impact on fisheries by increasing stress and disease. To understand how environment and host biology drives mucosal microbiomes in a marine fish, we surveyed five body sites (gill, skin, digesta, gastrointestinal tract [GI], and pyloric ceca) from 229 Pacific chub mackerel, Scomber japonicus, collected across 38 time points spanning 1 year from the Scripps Institution of Oceanography Pier (La Jolla, CA). Mucosal sites had unique microbial communities significantly different from the surrounding seawater and sediment communities with over 10 times more total diversity than seawater. The external surfaces of skin and gill were more similar to seawater, while digesta was more similar to sediment. Alpha and beta diversity of the skin and gill was explained by environmental and biological factors, specifically, sea surface temperature, chlorophyll a, and fish age, consistent with an exposure gradient relationship. We verified that seasonal microbial changes were not confounded by regional migration of chub mackerel subpopulations by nanopore sequencing a 14,769-bp region of the 16,568-bp mitochondria across all temporal fish specimens. A cosmopolitan pathogen, Photobacterium damselae, was prevalent across multiple body sites all year but highest in the skin, GI, and digesta between June and September, when the ocean is warmest. The longitudinal fish microbiome study evaluates the extent to which the environment and host biology drives mucosal microbial ecology and establishes a baseline for long-term surveys linking environment stressors to mucosal health of wild marine fish.IMPORTANCE Pacific chub mackerel, Scomber japonicus, are one of the largest and most economically important fisheries in the world. The fish is harvested for both human consumption and fish meal. Changing ocean conditions driven by anthropogenic stressors like climate change may negatively impact fisheries. One mechanism

ProblemPregnant women are at increased risk of HIV acquisition, but the biological mechanisms contributing to this observation are not well understood.Method of studyHere, we assessed host immune and microbiome differences in the vaginal mucosa of healthy pregnant and non-pregnant women using a metaproteomics approach. Cervicovaginal lavage (CVL) samples were collected from 23 pregnant and 25 non-pregnant women.ResultsMass spectrometry analysis of CVL identified 550 human proteins and 376 bacterial proteins from 11 genera. Host proteome analysis indicated 56 human proteins (10%) were differentially abundant (P < .05) between pregnant and non-pregnant women, including proteins involved in angiogenesis (P = 3.36E-3), cell movement of phagocytes (P = 1.34E-6), and permeability of blood vessels (P = 1.27E-4). The major bacterial genera identified were Lactobacillus, Gardnerella, Prevotella, Megasphaera, and Atopobium. Pregnant women had higher levels of Lactobacillus species (P = .017) compared with non-pregnant women. Functional pathway analysis indicated that pregnancy associated with changes to bacterial metabolic pathway involved in energy metabolism, which were increased in pregnant women (P = .035).ConclusionOverall, pregnant women showed differences in the cervicovaginal proteome and microbiome that may be important for HIV infection risk.

IntroductionThe majority of new HIV infections occur through mucosal transmission. The availability of readily applicable and accessible platforms for anti-retroviral (ARV) delivery is critical for the prevention of HIV acquisition through sexual transmission in both women and men. There is a compelling need for developing new topical delivery systems that have advantages over the pills, gels and rings, which currently fail to guarantee protection against mucosal viral transmission in vulnerable populations due to lack of user compliance. The silk fibroin (SF) platform offers another option that may be better suited to individual circumstances and preferences to increase efficacy through user compliance. The objective of this study was to test safety and efficacy of SF for anti-HIV drug delivery to mucosal sites and for viral prevention.MethodsWe formulated a potent HIV inhibitor Griffithsin (Grft) in a mucoadhesive silk fibroin (SF) drug delivery platform and tested the application in a non-human primate model in vivo and a pre-clinical human cervical and colorectal tissue explant model. Both vaginal and rectal compartments were assessed in rhesus macaques (Mucaca mulatta) that received SF (n = 4), no SF (n = 7) and SF-Grft (n = 11). In this study, we evaluated the composition of local microbiota, inflammatory cytokine production, histopathological changes in the vaginal and rectal compartments and mucosal protection after ex vivo SHIV challenge.ResultsEffective Grft release and retention in mucosal tissues from the SF-Grft platform resulted in protection against HIV in human cervical and colorectal tissue as well as against SHIV challenge in both rhesus macaque vaginal and rectal tissues. Mucoadhesion of SF-Grft inserts did not cause any inflammatory responses or changes in local microbiota.ConclusionsWe demonstrated that in vivo delivery of SF-Grft in rhesus macaques fully protects against SHIV challenge ex vivo after two hours of ap

Successful rearing of fish in hatcheries is critical for conservation, recreational fishing, commercial fishing through wild stock enhancements, and aquaculture production. Flowthrough (FT) hatcheries require more water than recirculating aquaculture systems (RAS), which enable up to 99% of their water to be recycled, thus significantly reducing environmental impacts. Here, we evaluated the biological and physical microbiome interactions of three Atlantic salmon hatcheries (RAS n = 2, FT n = 1). Gill, skin, and digesta from six juvenile fish along with tank biofilms and water were sampled from tanks in each of the hatcheries (60 fish across 10 tanks) to assess the built environment and mucosal microbiota using 16S rRNA gene sequencing. The water and tank biofilm had more microbial richness than fish mucus, while skin and digesta from RAS fish had 2 times the richness of FT fish. Body sites each had unique microbiomes (P < 0.001) and were influenced by hatchery system type (P < 0.001), with RAS being more similar. A strong association between the tank and fish microbiome was observed. Water and tank biofilm richness was positively correlated with skin and digesta richness. Strikingly, the gill, skin, and digesta communities were more similar to that in the origin tank biofilm than those in all other experimental tanks, suggesting that the tank biofilm has a direct influence on fish-associated microbial communities. Lastly, microbial diversity and mucous cell density were positively associated with fish growth and length. The results from this study provide evidence for a link between the tank microbiome and the fish microbiome, with the skin microbiome as an important intermediate.IMPORTANCE Atlantic salmon, Salmo salar, is the most farmed marine fish worldwide, with an annual production of 2,248 million metric tons in 2016. Salmon hatcheries are increasingly changing from flowthrough toward recirculating aquaculture system (RAS) design to accommodate more cont

This paper addresses a confusing issue of preputial anatomy of the mouse. The term "internal prepuce" was used in 2013 to describe a preputial structure integral to the mouse glans penis. Subsequently in 2015 the same term was applied by another group to describe entirely different morphology, generating confusion in the literature. Because it is inappropriate to use the same term to describe entirely different structures, we take this opportunity to provide further descriptive information on the internal prepuce of the mouse employing gross dissection, analysis of serial histologic section sets, three-dimensional reconstruction, scanning electron microscopy and immunohistochemistry. For this purpose, we review and illustrate the relevant literature and provide some additional new data using standard morphological techniques including immunohistochemistry. The mouse internal prepuce is integral to the glans penis and clearly is involved in sexual function in so far as it contains a major erectile body innervated by penile nerves. The development of the mouse internal prepuce is described for the first time and related to the development of the corpus cavernosum glandis.

Innate lymphoid cells (ILCs) are important regulators of the early responses to infection at mucosal barriers, including the intestine. Recently, we have shown that specific ILC3 subsets protect against enteric bacterial pathogens. Here, we describe a mouse model of oral infection by Yersinia enterocolitica (Y. enterocolitica) and several different methodologies to assess the severity of the infection. We also detail how ILC3 subsets can be isolated from the mouse small intestine and transferred into recipient immune deficient mice to study the function of these ILCs in the small intestine.

Innate lymphoid cells (ILCs) are a lymphocyte population that is mostly resident at mucosal surfaces. They help to induce an appropriate immune response to the microbiome at homeostasis. In healthy people, the mucosal immune system works symbiotically with organisms that make up the microbiota. ILCs play a critical role in orchestrating this balance, as they can both influence and in turn be influenced by the microbiome. ILCs also are important regulators of the early response to infections by diverse types of pathogenic microbes at mucosal barriers. Their rapid responses initiate inflammatory programs, production of antimicrobial products and repair processes. This review will focus on the role of ILCs in response to the microbiota and to microbial infections of the lung and intestine.

Вивчали морфометричні показники залоз слизової оболонки яйцепроводу курей, перепілок, цесарок, качок і гусок у період яйцевідкладання. Роботу проводили на базі морфологічної лабораторії кафедри анатомії і гістології Житомирського національного агроекологічного університету (м. Житомир, Україна). Використовували мікроскопічні, морфометричні і статистичні методи досліджень. Встановлено, що власна пластинка слизової оболонки відділів, крім піхви, яйцепроводу дослідних птахів представлена пухкою волокнистою сполучною тканиною. Вона містить прості трубчасті розгалужені залози. Діаметр секреторних відділів залоз, об’єм цитоплазми і ядерно-цитоплазматичне відношення гландулоцитів – лабільні показники і тісно пов’язані з функціональною активністю цих клітин, яка визначається фазою секреторного циклу. За наявності яйця у матці яйцепроводу перепілок, цесарок, курей, качок, гусок високі показники об’єму гландулоцитів білкового відділу і перешийка на фоні низького значення ядерно-цитоплазматичного відношення (0,124±0,01–0,161±0,011 і 0,204±0,021–0,225±0,035 відповідно) свідчать про фазу синтезу секрету гландулоцитами. Вперше вивчено субмікроскопічну будову клітин залозистого епітелію слизової оболонки яйцепроводу перепілок. Встановлено, що у цитоплазмі гландулоцитів серед органел загального призначення найкраще розвинута гранулярна ендоплазматична сітка. Між її довгими і розширеними канальцями реєструються секреторні гранули, які містять гомогенний, великої електронної щільності матеріал. За наявності яйця у матці яйцепроводу діаметр секреторних гранул у цитоплазмі гландулоцитів секреторних відділів білкового відділу максимальний (3,45±0,21 мкм), матки – мінімальний (0,85±0,04 мкм). Параметри морфометрії залоз слизової оболонки яйцепроводу клінічно здорових птахів слід використовувати в якості показників норми при діагностиці захворювань яйцепроводу різного генезису і при проведенні експериментальних досліджень., The peculiarities of morphometric indexes of glands of the mucous membrane of the oviduct in hens, quails, guinea fowls, ducks, gooses have been studied during oviposition. The research has been conducted on the basis of morphological laboratory of anatomy and histology departments of the Zhytomyr National Agroecological University (Zhytomyr, Ukraine). Microscopic, morphometric and statistic methods of research have been applied. The lamina propria of the mucosa of the oviduct of birds represented by loose fibrous connective tissue. In all parts of the body, except the vagina, it contains simple tubular branched glands. Diameter of secretory parts of the glands, the volume of cytoplasm and nuclear-cytoplasmatic attitude of glandulocytes is labile indicators and are closely associated with the functional activity of these cells, which are determined by the phase of the secretory cycle. In the presence of eggs in the uterus of the oviduct of quails, Guinea fowl, chickens, ducks, geese high indexes of glandulocytes volume of the magnum and the isthmus on the background of low values of nuclear-cytoplasmic ratio (0.124±0.01–0.161±0.011 and 0.211±0.021–0.225±0.035, respectively) indicate phase of secret synthesis by glandulocytes. The submicroscopic structure of the cell of glandular epithelium of the mucous membrane of the oviduct of the quails is studied for the first time. It is established that in the glandulocyted cytoplasm among the organelles of general purpose granular endoplasmic net is best-developed. The secretory granules containing a homogeneous, large electron density material are logged between its long and dilated tubules. In the presence of eggs in the uterus of the oviduct diameter of the secretory granules in the glandulocytes cytoplasm of secretory part of magnum is maximal (3.45±0.21 μm), of uterus – minimal (0.85±0.04 μm). The parameters of morfometer of glands of the mucous membrane of the oviduct of clinically healthy fowls are suggested to use as, Изучали морфометрические показатели желез слизистой оболочки яйцевода кур, перепелок, цесарок, уток, гусынь в период яйцекладки. Работу проводили на базе морфологической лаборатории кафедры анатомии и гистологии Житомирского национального агроэкологического университета (г. Житомир, Украина). Использовали микроскопические, морфометрические и статистические методы исследований. Установлено, что собственная пластинка слизистой оболочки отделов, кроме влагалища, яйцевода исследуемых птиц представлена рыхлой волокнистой соединительной тканью. Она содержит простые трубчастые разветвленные железы. Диаметр секреторных отделов, объем цитоплазмы и ядерно-цитоплазматическое отношение гландулоцитов – лабильные показатели и тесно связаны с функциональной активностью этих клеток, которая определяется фазой секреторного цикла. При наличии яйца в матке яйцевода перепелок, цесарок, кур, уток, гусынь высокие показатели объема гландулоцитов белкового отдела и перешийка на фоне низкого значения ядерно-цитоплазматического отношения (0,124±0,01–0,161±0,011 і 0,204±0,021–0,225±0,035 соответственно) свидетельствует о фазе синтеза секрета гландулоцитами. Впервые изучено субмикроскопическое строение клеток железистого эпителия слизистой оболочки яйцевода перепелок. Установлено, что в цитоплазме гландулоцитов среди органел общего назначения наиболее развита гранулярная эндоплазматическая сетка. Между ее длинными и разветвленными канальцами регистрируются секреторные гранулы, которые содержат гомогенный, большой электронной плотности материал. При наличии яйца в матке яйцевода диаметр секреторных гранул в цитоплазме гландулоцитов секреторных отделов белкового отдела максимальный (3,45±0,21 мкм), матки – минимальный (0,85±0,04 мкм). Параметры морфометрии желез слизистой оболочки яйцевода клинически здоровых птиц следует использовать в качестве показателей нормы при диагностике заболеваний яйцевода различного генезиса и при проведении экспериментальных исследований.

Trichomonas vaginalis, a prevalent sexually transmitted parasite, adheres to and induces cytolysis of human mucosal epithelial cells. We have characterized a hypothetical protein, TVAG_393390, with predicted tertiary structure similar to that of mammalian cadherin proteins involved in cell-cell adherence. TVAG_393390, renamed cadherin-like protein (CLP), contains a calcium-binding site at a position conserved in cadherins. CLP is surface localized, and its mRNA and protein levels are significantly upregulated upon parasite adherence to host cells. To test the roles of CLP and its calcium-binding dependency during host cell adherence, we first demonstrated that wild-type CLP (CLP) binds calcium with a high affinity, whereas the calcium-binding site mutant protein (CLP-mut) does not. CLP and CLP-mut constructs were then used to overexpress these proteins in T. vaginalis Parasites overexpressing CLP have ∼3.5-fold greater adherence to host cells than wild-type parasites, and this increased adherence is ablated by mutating the calcium-binding site. Additionally, competition with recombinant CLP decreased parasite binding to host cells. We also found that overexpression of CLP induced parasite aggregation which was further enhanced in the presence of calcium, whereas CLP-mut overexpression did not affect aggregation. Lastly, parasites overexpressing wild-type CLP induced killing of host cells ∼2.35-fold, whereas parasites overexpressing CLP-mut did not have this effect. These analyses describe the first parasitic CLP and demonstrate a role for this protein in mediating parasite-parasite and host-parasite interactions. T. vaginalis CLP may represent convergent evolution of a parasite protein that is functionally similar to the mammalian cell adhesion protein cadherin, which contributes to parasite pathogenesis.IMPORTANCE The adherence of pathogens to host cells is critical for colonization of the host and establishing infection. Here we identify a protein with no known fu

Mucosal melanoma is a rare and poorly characterized subtype of human melanoma. Here we perform a cross-species analysis by sequencing tumor-germline pairs from 46 primary human muscosal, 65 primary canine oral and 28 primary equine melanoma cases from mucosal sites. Analysis of these data reveals recurrently mutated driver genes shared between species such as NRAS, FAT4, PTPRJ, TP53 and PTEN, and pathogenic germline alleles of BRCA1, BRCA2 and TP53. We identify a UV mutation signature in a small number of samples, including human cases from the lip and nasal mucosa. A cross-species comparative analysis of recurrent copy number alterations identifies several candidate drivers including MDM2, B2M, KNSTRN and BUB1B. Comparison of somatic mutations in recurrences and metastases to those in the primary tumor suggests pervasive intra-tumor heterogeneity. Collectively, these studies suggest a convergence of some genetic changes in mucosal melanomas between species but also distinctly different paths to tumorigenesis.