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Epiphrenic or Grenet esophageal diverticula are pulsatile diverticula in which the mucosa and submucosa pass through the muscular layer and, by definition, are within 10 cm of the junction between the food and the stomach. Most patients are asymptomatic, but their significance is the possibility of serious complications, such as tracheal fistulas, hemorrhages, vocal cord paralysis, retained foreign bodies, and an increased risk of cancer. It is an avoidance of the mucosa and submucosa layers of the esophagus that usually affects the third distal segment of the esophagus. These lesions are considered characteristic because between 70% and 90% of cases are accompanied by esophageal dysmotility disorders. A 58-year-old male patient is reported to have epigastric pain and heartburn, which is why he went to this health center and an endoscopy was performed, which revealed Grenet diverticulum., Los divertículos esofágicos epifrénicos o Grenet son divertículos pulsátiles en los que la mucosa y la submucosa pasan a través de la capa muscular y, por definición, se encuentran dentro de los 10 cm de la unión entre el alimento y el estómago. La mayoría de los pacientes son asintomáticos, pero su importancia es la posibilidad de complicaciones graves, como fístulas traqueales, hemorragias, parálisis de las cuerdas vocales, retención de cuerpos extraños y un mayor riesgo de cáncer. Es una evitación de las capas mucosa y submucosa del esófago que suele afectar al tercer segmento distal del esófago. Estas lesiones se consideran características porque entre el 70 % y el 90 % de los casos se acompañan de trastornos de la dismotilidad esofágica. Se reporta un paciente masculino de 58 años quien refiere epigastralgias y acidez, motivo por el cual acude a esta casa de salud y se realiza endoscopia que evidencia divertículo Grenet.

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.

Epiphrenic or Grenet esophageal diverticula are pulsatile diverticula in which the mucosa and submucosa pass through the muscular layer and, by definition, are within 10 cm of the junction between the food and the stomach. Most patients are asymptomatic, but their significance is the possibility of serious complications, such as tracheal fistulas, hemorrhages, vocal cord paralysis, retained foreign bodies, and an increased risk of cancer. It is an avoidance of the mucosa and submucosa layers of the esophagus that usually affects the third distal segment of the esophagus. These lesions are considered characteristic because between 70% and 90% of cases are accompanied by esophageal dysmotility disorders. A 58-year-old male patient is reported to have epigastric pain and heartburn, which is why he went to this health center and an endoscopy was performed, which revealed Grenet diverticulum., Los divertículos esofágicos epifrénicos o Grenet son divertículos pulsátiles en los que la mucosa y la submucosa pasan a través de la capa muscular y, por definición, se encuentran dentro de los 10 cm de la unión entre el alimento y el estómago. La mayoría de los pacientes son asintomáticos, pero su importancia es la posibilidad de complicaciones graves, como fístulas traqueales, hemorragias, parálisis de las cuerdas vocales, retención de cuerpos extraños y un mayor riesgo de cáncer. Es una evitación de las capas mucosa y submucosa del esófago que suele afectar al tercer segmento distal del esófago. Estas lesiones se consideran características porque entre el 70 % y el 90 % de los casos se acompañan de trastornos de la dismotilidad esofágica. Se reporta un paciente masculino de 58 años quien refiere epigastralgias y acidez, motivo por el cual acude a esta casa de salud y se realiza endoscopia que evidencia divertículo Grenet.

Type 3 Innate lymphoid cells (ILC3s) have been described as tissue-resident cells and characterized throughout the body, especially in mucosal sites and classical first barrier organs such as skin, gut and lungs, among others. A significant part of the research has focused on their role in combating pathogens, mainly extracellular pathogens, with the gut as the principal organ. However, some recent discoveries in the field have unveiled their activity in other organs, combating intracellular pathogens and as part of the response to viruses. In this review we have compiled the latest studies on the role of ILC3s and the molecular mechanisms involved in defending against different microbes at the mucosal surface, most of these studies have made use of conditional transgenic mice. The present review therefore attempts to provide an overview of the function of ILC3s in infections throughout the body, focusing on their specific activity in different organs., Programa Ramón y Cajal, Ministerio de Ciencia, Innovación e Universidades, Fondo Europeo de Desarrollo Regional, Depto. de Inmunología, Oftalmología y ORL, Fac. de Medicina, TRUE, pub

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)

Conventional therapy for inflammatory bowel disease using long-term anti-inflammatory drugs does not seem to provide optimal results. Adjuvant therapy using vitamin D3 is believed to have an essential role in repairing the colonic mucosa through the activation of colonic stem cells. The aim of this study was to demonstrate the effect of vitamin D3 in mucosal repair through stem cell activation, marked by leucin-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and B lymphoma Mo-MLV insertion region 1 (Bmi1) expression and decrease the mouse colitis histology index (MCHI) score. In this study, 50 Mus musculus strain BALB/c were divided into five groups: negative control group, colitis group, and colitis groups with vitamin D3 administration of 0.2 mcg, 0.4 mcg, and 0.6 mcg per 25 g body weight for seven days. Dextran sulfate sodium (DSS) 5% was used to induce colitis. Lgr5-Bmi1 expression was measured using immunodoublestain fluorescent labeling method. Our data suggested that administration of vitamin D3 significantly increased expression of Lgr5-Bmi1 in the colonic mucosa. The colitis group treated with the highest dose of vitamin D3 (0.6 mcg/25 gram) showed the lowest MCHI score (3.60±0.64) while the lowest dose of vitamin D3 had the highest MCHI score (12.60±1.47). In conclusion, stimulating stem cells, vitamin D3 administration stimulates mucosal regeneration, as demonstrated by upregulated expression of Lgr5-Bmi-1.

The different types of oral pathologies that we find in the oral cavity in pediatric patients that can be located in the oral mucosa, tongue, lips and palate. In the newborn, it is important as oral health professionals to know the various oral pathologies with their respective diagnosis, treatment and appropriate follow-up to be able to identify the lesions, checking that they do not make it difficult for the neonate to not be able to feed or breathe properly and provide them with an excellent quality of life. life. Much of the oral cavity is lined by oral mucosa. Made up of a lining epithelium and loose connective tissue that provides support and nutrition, called the lamina propria or corium. Functionally we find the tongue, which is covered by a specialized mucosa. Among some oral pathologies, these include Bohn's nodules, cystic growths from the dental lamina, present on the edges of the gingival pads of infants, which can cause concern in parents and be confused with other pathologies. An 8-day-old male patient is reported who was diagnosed with Bohn's nodules, without receiving treatment and only being followed up after 1 month, it resolved spontaneously., Los distintos tipos de patologías bucales que encontramos en la cavidad oral en los pacientes pediátricos que se pueden localizar en la mucosa bucal, la lengua, los labios y del paladar. En el Recién nacido es importante como profesionales de la salud oral conocer las diversas patologías bucales con su respectivo diagnóstico, tratamiento y seguimiento apropiado para poder identificar las lesiones comprobando que no dificulte al neonato a no poder alimentarse o respirar adecuadamente y brindarle una excelente calidad de vida. Gran parte de la cavidad oral esta tapizada por mucosa bucal. Conformada por un epitelio de revestimiento y por tejido conectivo laxo que da soporte y nutrición, denominado lámina propia o corium. En lo funcional encontramos a la lengua, que está cubierto por una mucosa especializada. Dentro de algunas patologías orales estas se encuentran los nódulos de Bohn, abultamientos quísticos procedentes de la lámina dental, presente en los bordes de las almohadillas gingivales de los lactantes, el cual puede causar preocupación en los padres y confundirse con otras patologías. Se reporta un paciente masculino de 8 días de nacimiento que es diagnosticado de nódulos de Bohn, sin recibir tratamiento y solo estar en seguimiento después de 1 mes se resolvió espontáneamente.

Background Microbial communities have long been suspected to influence inflammatory processes in the gastrointestinal tract of patients with inflammatory bowel disease. However, these effects are often influenced by treatments and can rarely be analyzed in treatment-naïve onset cases. Specifically, microbial differences between IBD pathologies in new onset cases have rarely been investigated and can provide novel insight into the dynamics of the microbiota in Crohn’s disease (CD) and ulcerative colitis (UC). Methods Fifty-six treatment-naïve IBD onset patients (67.3% CD, 32.7% UC) and 97 healthy controls were recruited from the Maltese population. Stool samples were collected after diagnosis but before administration of anti-inflammatory treatments. Fecal microbial communities were assessed via 16S rRNA gene sequencing and subjected to ecological analyses to determine disease-specific differences between pathologies and disease subtypes or to predict future treatment options. Results We identified significant differences in community composition, variability, and diversity between healthy and diseased individuals—but only small to no differences between the newly diagnosed, treatment-naïve UC and CD cohorts. Network analyses revealed massive turnover of bacterial interactions between healthy and diseased communities, as well as between CD and UC communities, as signs of disease-specific changes of community dynamics. Furthermore, we identified taxa and community characteristics serving as predictors for prospective treatments. Conclusion Untreated and newly diagnosed IBD shows clear differences from healthy microbial communities and an elevated level of disturbance, but only the network perspective revealed differences between pathologies. Furthermore, future IBD treatment is to some extent predictable by microbial community characteristics., Background Microbial communities have long been suspected to influence inflammatory processes in the gastrointestinal tract of patients with inflammatory bowel disease. However, these effects are often influenced by treatments and can rarely be analyzed in treatment-naive onset cases. Specifically, microbial differences between IBD pathologies in new onset cases have rarely been investigated and can provide novel insight into the dynamics of the microbiota in Crohn's disease (CD) and ulcerative colitis (UC). Methods Fifty-six treatment-naive IBD onset patients (67.3% CD, 32.7% UC) and 97 healthy controls were recruited from the Maltese population. Stool samples were collected after diagnosis but before administration of anti-inflammatory treatments. Fecal microbial communities were assessed via 16S rRNA gene sequencing and subjected to ecological analyses to determine disease-specific differences between pathologies and disease subtypes or to predict future treatment options. Results We identified significant differences in community composition, variability, and diversity between healthy and diseased individuals-but only small to no differences between the newly diagnosed, treatment-naive UC and CD cohorts. Network analyses revealed massive turnover of bacterial interactions between healthy and diseased communities, as well as between CD and UC communities, as signs of disease-specific changes of community dynamics. Furthermore, we identified taxa and community characteristics serving as predictors for prospective treatments. Conclusion Untreated and newly diagnosed IBD shows clear differences from healthy microbial communities and an elevated level of disturbance, but only the network perspective revealed differences between pathologies. Furthermore, future IBD treatment is to some extent predictable by microbial community characteristics.Lay Summary Treatment-naive IBD onset patients from Malta show clear differences from healthy microbial communities a

The different types of oral pathologies that we find in the oral cavity in pediatric patients that can be located in the oral mucosa, tongue, lips and palate. In the newborn, it is important as oral health professionals to know the various oral pathologies with their respective diagnosis, treatment and appropriate follow-up to be able to identify the lesions, checking that they do not make it difficult for the neonate to not be able to feed or breathe properly and provide them with an excellent quality of life. life. Much of the oral cavity is lined by oral mucosa. Made up of a lining epithelium and loose connective tissue that provides support and nutrition, called the lamina propria or corium. Functionally we find the tongue, which is covered by a specialized mucosa. Among some oral pathologies, these include Bohn's nodules, cystic growths from the dental lamina, present on the edges of the gingival pads of infants, which can cause concern in parents and be confused with other pathologies. An 8-day-old male patient is reported who was diagnosed with Bohn's nodules, without receiving treatment and only being followed up after 1 month, it resolved spontaneously., Los distintos tipos de patologías bucales que encontramos en la cavidad oral en los pacientes pediátricos que se pueden localizar en la mucosa bucal, la lengua, los labios y del paladar. En el Recién nacido es importante como profesionales de la salud oral conocer las diversas patologías bucales con su respectivo diagnóstico, tratamiento y seguimiento apropiado para poder identificar las lesiones comprobando que no dificulte al neonato a no poder alimentarse o respirar adecuadamente y brindarle una excelente calidad de vida. Gran parte de la cavidad oral esta tapizada por mucosa bucal. Conformada por un epitelio de revestimiento y por tejido conectivo laxo que da soporte y nutrición, denominado lámina propia o corium. En lo funcional encontramos a la lengua, que está cubierto por una mucosa especializada. Dentro de algunas patologías orales estas se encuentran los nódulos de Bohn, abultamientos quísticos procedentes de la lámina dental, presente en los bordes de las almohadillas gingivales de los lactantes, el cual puede causar preocupación en los padres y confundirse con otras patologías. Se reporta un paciente masculino de 8 días de nacimiento que es diagnosticado de nódulos de Bohn, sin recibir tratamiento y solo estar en seguimiento después de 1 mes se resolvió espontáneamente.

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.

Background: Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry. Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut. To secure better postnatal gut colonization, we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period. Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli (ETEC). Methods: Seventy-two 1-day-old piglets were randomized to four groups: colonic microbiota transplantation (CMT, n = 18), colonic content filtrate transplantation (CcFT, n = 18), gastric microbiota transplantation (GMT, n = 18), or saline (CON, n = 18). Inoculations were given on d 2 and 3 of life, and all piglets were milk-fed until weaning (d 20) and shortly after challenged with ETEC (d 24). We assessed growth, diarrhea prevalence, ETEC concentration, organ weight, blood parameters, small intestinal morphology and histology, gut mucosal function, and microbiota composition and diversity. Results: Episodes of diarrhea were seen in all groups during both the milk- and the solid-feeding phase, possibly due to stress associated with single housing. However, CcFT showed lower diarrhea prevalence on d 27, 28, and 29 compared to CON (all P < 0.05). CcFT also showed a lower ETEC prevalence on d 27 (P < 0.05). CMT showed a higher alpha diversity and a difference in beta diversity compared to CON (P < 0.05). Growth and other paraclinical endpoints were similar across groups. Conclusion: In conclusion, only CcFT reduced ETEC-related post-weaning diarrhea. However, the protective effect was marginal, sugge

Background: Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry. Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut. To secure better postnatal gut colonization, we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period. Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli (ETEC). Methods: Seventy-two 1-day-old piglets were randomized to four groups: colonic microbiota transplantation (CMT, n = 18), colonic content filtrate transplantation (CcFT, n = 18), gastric microbiota transplantation (GMT, n = 18), or saline (CON, n = 18). Inoculations were given on d 2 and 3 of life, and all piglets were milk-fed until weaning (d 20) and shortly after challenged with ETEC (d 24). We assessed growth, diarrhea prevalence, ETEC concentration, organ weight, blood parameters, small intestinal morphology and histology, gut mucosal function, and microbiota composition and diversity. Results: Episodes of diarrhea were seen in all groups during both the milk- and the solid-feeding phase, possibly due to stress associated with single housing. However, CcFT showed lower diarrhea prevalence on d 27, 28, and 29 compared to CON (all P < 0.05). CcFT also showed a lower ETEC prevalence on d 27 (P < 0.05). CMT showed a higher alpha diversity and a difference in beta diversity compared to CON (P < 0.05). Growth and other paraclinical endpoints were similar across groups. Conclusion: In conclusion, only CcFT reduced ETEC-related post-weaning diarrhea. However, the protective effect was mar

Post-weaning diarrhea (PWD) remains a major source of mortality and morbidity in swine production. Transplantation of bacteria-free filtrate of feces (fecal filtrate transplant, FFT) has shown gut protective effects in neonatal pigs, and early postnatal establishment of the gut microbiome is suggested to determine later stability and robustness of the gut. We, therefore, hypothesized that early postnatal transplantation of bacteria-free feces would have a protective effect against PWD. Using fecal filtrates derived from healthy lactating sows, we compared oral administration of fecal filtrate transplantation (FFT, n = 20) and saline (CON, n = 18) in newborn piglets. We assessed growth, diarrhea prevalence, blood parameters, organ measurements, morphology, and gut brush border enzymes and analyzed luminal bacterial composition using 16S rRNA gene amplicon sequencing. The two groups showed similar average daily gain (ADG) during the suckling period, whereas in the post-weaning period, a negative ADG was observed in both groups. While diarrhea was largely absent in both groups before weaning, there was a lower diarrhea prevalence on days 27 (p = 2.07*10−9), 28 (p = 0.04), and 35 (p = 0.04) in the FFT group relative to CON. At weaning on day 27, the FFT group had higher numbers of red blood cells, monocytes, and lymphocytes, while on day 35, i.e., 1 week after weaning, the two groups were similar regarding hematology. The biochemical profile was largely similar between FFT and CON on days 27 and 35, except for a higher level of alanine aminotransferase and a lower level of Mg in the FFT group. Likewise, organ weights relative to body weight were largely similar on day 35, albeit with a lower stomach weight and more colon content in FFT relative to CON. Gut mucosal percentage and mucosal enzyme activity were similar between the two groups on days 27 and 35. Gut bacterial composition was slightly different on day 35 but not on day 27. In conclusio

Background: Diarrhea is a major cause of reduced growth and mortality in piglets during the suckling and weaning periods and poses a major threat to the global pig industry. Diarrhea and gut dysbiosis may in part be prevented via improved early postnatal microbial colonization of the gut. To secure better postnatal gut colonization, we hypothesized that transplantation of colonic or gastric content from healthy donors to newborn recipients would prevent diarrhea in the recipients in the post-weaning period. Our objective was to examine the impact of transplanting colonic or gastric content on health and growth parameters and paraclinical parameters in recipient single-housed piglets exposed to a weaning transition and challenged with enterotoxigenic Escherichia coli (ETEC). Methods: Seventy-two 1-day-old piglets were randomized to four groups: colonic microbiota transplantation (CMT, n = 18), colonic content filtrate transplantation (CcFT, n = 18), gastric microbiota transplantation (GMT, n = 18), or saline (CON, n = 18). Inoculations were given on d 2 and 3 of life, and all piglets were milk-fed until weaning (d 20) and shortly after challenged with ETEC (d 24). We assessed growth, diarrhea prevalence, ETEC concentration, organ weight, blood parameters, small intestinal morphology and histology, gut mucosal function, and microbiota composition and diversity. Results: Episodes of diarrhea were seen in all groups during both the milk- and the solid-feeding phase, possibly due to stress associated with single housing. However, CcFT showed lower diarrhea prevalence on d 27, 28, and 29 compared to CON (all P < 0.05). CcFT also showed a lower ETEC prevalence on d 27 (P < 0.05). CMT showed a higher alpha diversity and a difference in beta diversity compared to CON (P < 0.05). Growth and other paraclinical endpoints were similar across groups. Conclusion: In conclusion, only CcFT reduced ETEC-related post-weaning diarrhea. However, the protective effect was mar

Post-weaning diarrhea (PWD) remains a major source of mortality and morbidity in swine production. Transplantation of bacteria-free filtrate of feces (fecal filtrate transplant, FFT) has shown gut protective effects in neonatal pigs, and early postnatal establishment of the gut microbiome is suggested to determine later stability and robustness of the gut. We, therefore, hypothesized that early postnatal transplantation of bacteria-free feces would have a protective effect against PWD. Using fecal filtrates derived from healthy lactating sows, we compared oral administration of fecal filtrate transplantation (FFT, n = 20) and saline (CON, n = 18) in newborn piglets. We assessed growth, diarrhea prevalence, blood parameters, organ measurements, morphology, and gut brush border enzymes and analyzed luminal bacterial composition using 16S rRNA gene amplicon sequencing. The two groups showed similar average daily gain (ADG) during the suckling period, whereas in the post-weaning period, a negative ADG was observed in both groups. While diarrhea was largely absent in both groups before weaning, there was a lower diarrhea prevalence on days 27 (p = 2.07*10−9), 28 (p = 0.04), and 35 (p = 0.04) in the FFT group relative to CON. At weaning on day 27, the FFT group had higher numbers of red blood cells, monocytes, and lymphocytes, while on day 35, i.e., 1 week after weaning, the two groups were similar regarding hematology. The biochemical profile was largely similar between FFT and CON on days 27 and 35, except for a higher level of alanine aminotransferase and a lower level of Mg in the FFT group. Likewise, organ weights relative to body weight were largely similar on day 35, albeit with a lower stomach weight and more colon content in FFT relative to CON. Gut mucosal percentage and mucosal enzyme activity were similar between the two groups on days 27 and 35. Gut bacterial composition was slightly different on day 35 but not on day 27. In conclusio

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.

Background: Despite the fact that Helicobacter spp. has been detected in equine gastric mucosa, no evidence exists about this infection in Colombian horses affected by equine ulcerative gastric syndrome (EGUS), nor in dental tartar. Objective: To detect Helicobacter spp. DNA in equine gastric mucosa and dental tartar and determine the relationship between the presence of Helicobacter spp. and gastric lesions. Methods: Samples of glandular gastric mucosa and dental tartar were collected from 30 equine slaughterhouses. Macroscopic lesions of the stomachs were classified and the total DNA in all samples was extracted using a commercial extraction kit. A final-point PCR was performed using primers for amplification of a segment of 251 bp of the gene encoding the 16s rRNA region; the amplified fragments were subjected to a second PCR to determine the presence of H. pylori, the VacA gene was typified. The resulting amplicons were sequenced. Results: It was possible to amplify 16s rRNA in several samples but there was no amplification of VacA. Fragments of the sequences were compatible with H. heilmannii. The 23.3 and 10% of gastric and tartar samples were positive for 16s rRNA of Helicobacter spp., respectively. Conclusion: Although genetic material of Helicobacter spp. was found in some animals, there was no relationship with gastric lesions. It is possible that helicobacteriosis has no bearing in EGUS etiology., Antecedentes: Apesar do Helicobacter spp. ter sido detectado na mucosa gástrica de equinos, não há evidências dessa infecção em cavalos crioulos colombianos afetados pela síndrome ulcerativa gástrica (SUGE), ou no sarro. Objetivo: Detectar ADN de Helicobacter spp. na mucosa gástrica e do sarro dental de equinos, e determinar a relação entre a presença de Helicobacter spp. e lesões gástricas. Métodos: Amostras de mucosa gástrica glandular e sarro dental foram coletadas de 30 equinos de abatedouro, as lesões macroscópicas dos estômagos foram classificadas. Se realizou extração de ADN total em todas as amostras através de kit comercial. Realizou-se PCR ponto final, amplificando o segmento de 251 pb do gene que codifica para a região 16s ARNr; os fragmentos amplificados foram sometidos novamente a PCR para determinar a presença de H. pylori, ao tipificar o gene VacA, e seguidamente foram sequenciados. Resultados: O houve amplificação do 16s ARNr em várias amostras, mas não amplificação de VacA. Fragmentos das sequencias foram compatíveis com H. heilmannii. O 23,3 e 10% das amostras gástricas e do sarro foram positivas para 16s ARNr de Helicobacter, respectivamente. Conclusão: Embora material genético de Helicobacter spp. encontrou-se em algumos animais não houve relação com lesões gástricas. Possivelmente a helicobacterioses não tem papel relevante na etiologia da SUGE., Antecedentes: A pesar de que se ha detectado Helicobacter spp. en mucosa gástrica equina, no existe evidencia de esta infección en caballos criollos colombianos afectados por síndrome ulcerativo gástrico (SUGE), ni tampoco reportes en sarro dental. Objetivo: Detectar ADN de Helicobacter spp. en sarro dental y mucosa gástrica de equinos, y determinar la relación entre la presencia de la bacteria y lesiones gástricas. Métodos: Las muestras de mucosa glandular gástrica y sarro dental fueron colectadas de 30 equinos que se encontraban en planta de beneficio. Las lesiones macroscópicas fueron clasificadas y el ADN total de las muestras fue extraído utilizando un kit comercial. Se desarrolló PCR convencional usando cebadores específicos para la amplificación de un segmento de 251 pb de un gen que codifica la región 16S del ARNr; los fragmentos amplificados fueron sometidos a una segunda PCR para determinar la presencia de H. pylori mediante la amplificación del gen VacA. Los amplificados resultantes fueron secuenciados. Resultados: Fue posible amplificar 16s ARNr en varias muestras, pero no hubo amplificación de VacA. Los fragmentos de las secuencias fueron compatibles con H. heilmannii. El 23,3 y 10% de las muestras gástricas y sarro fueron positivas para 16s ARNr de Helicobacter spp., respectivamente. Conclusión: Aunque el material genético de Helicobacter spp. se encontró en algunos animales, no hubo relación con las lesiones gástricas. Es posible que la helicobacteriosis no tenga incidencia en la etiología del EGUS.

Medical treatment of autoimmune bullous diseases (AIBD) is focused on immunosuppression. In addition, proper wound care is equally important and can improve wound healing and recovery. Goals of wound care management include relieving pain, preventing infection, enhancing regeneration, and encouraging patient mobility and quality of life. Wound care in AIBD patients can be challenging as immunosuppressants may slow wound healing, large areas may be affected, skin fragility and wounds may occur on difficult to dress body sites, non-blistered skin may be fragile as well, and affected patients are often of higher age and less mobile. A personalized wound care plan is warranted, preferably established by experienced nurses.

Background: Despite the fact that Helicobacter spp. has been detected in equine gastric mucosa, no evidence exists about this infection in Colombian horses affected by equine ulcerative gastric syndrome (EGUS), nor in dental tartar. Objective: To detect Helicobacter spp. DNA in equine gastric mucosa and dental tartar and determine the relationship between the presence of Helicobacter spp. and gastric lesions. Methods: Samples of glandular gastric mucosa and dental tartar were collected from 30 equine slaughterhouses. Macroscopic lesions of the stomachs were classified and the total DNA in all samples was extracted using a commercial extraction kit. A final-point PCR was performed using primers for amplification of a segment of 251 bp of the gene encoding the 16s rRNA region; the amplified fragments were subjected to a second PCR to determine the presence of H. pylori, the VacA gene was typified. The resulting amplicons were sequenced. Results: It was possible to amplify 16s rRNA in several samples but there was no amplification of VacA. Fragments of the sequences were compatible with H. heilmannii. The 23.3 and 10% of gastric and tartar samples were positive for 16s rRNA of Helicobacter spp., respectively. Conclusion: Although genetic material of Helicobacter spp. was found in some animals, there was no relationship with gastric lesions. It is possible that helicobacteriosis has no bearing in EGUS etiology., Antecedentes: Apesar do Helicobacter spp. ter sido detectado na mucosa gástrica de equinos, não há evidências dessa infecção em cavalos crioulos colombianos afetados pela síndrome ulcerativa gástrica (SUGE), ou no sarro. Objetivo: Detectar ADN de Helicobacter spp. na mucosa gástrica e do sarro dental de equinos, e determinar a relação entre a presença de Helicobacter spp. e lesões gástricas. Métodos: Amostras de mucosa gástrica glandular e sarro dental foram coletadas de 30 equinos de abatedouro, as lesões macroscópicas dos estômagos foram classificadas. Se realizou extração de ADN total em todas as amostras através de kit comercial. Realizou-se PCR ponto final, amplificando o segmento de 251 pb do gene que codifica para a região 16s ARNr; os fragmentos amplificados foram sometidos novamente a PCR para determinar a presença de H. pylori, ao tipificar o gene VacA, e seguidamente foram sequenciados. Resultados: O houve amplificação do 16s ARNr em várias amostras, mas não amplificação de VacA. Fragmentos das sequencias foram compatíveis com H. heilmannii. O 23,3 e 10% das amostras gástricas e do sarro foram positivas para 16s ARNr de Helicobacter, respectivamente. Conclusão: Embora material genético de Helicobacter spp. encontrou-se em algumos animais não houve relação com lesões gástricas. Possivelmente a helicobacterioses não tem papel relevante na etiologia da SUGE., Antecedentes: A pesar de que se ha detectado Helicobacter spp. en mucosa gástrica equina, no existe evidencia de esta infección en caballos criollos colombianos afectados por síndrome ulcerativo gástrico (SUGE), ni tampoco reportes en sarro dental. Objetivo: Detectar ADN de Helicobacter spp. en sarro dental y mucosa gástrica de equinos, y determinar la relación entre la presencia de la bacteria y lesiones gástricas. Métodos: Las muestras de mucosa glandular gástrica y sarro dental fueron colectadas de 30 equinos que se encontraban en planta de beneficio. Las lesiones macroscópicas fueron clasificadas y el ADN total de las muestras fue extraído utilizando un kit comercial. Se desarrolló PCR convencional usando cebadores específicos para la amplificación de un segmento de 251 pb de un gen que codifica la región 16S del ARNr; los fragmentos amplificados fueron sometidos a una segunda PCR para determinar la presencia de H. pylori mediante la amplificación del gen VacA. Los amplificados resultantes fueron secuenciados. Resultados: Fue posible amplificar 16s ARNr en varias muestras, pero no hubo amplificación de VacA. Los fragmentos de las secuencias fueron compatibles con H. heilmannii. El 23,3 y 10% de las muestras gástricas y sarro fueron positivas para 16s ARNr de Helicobacter spp., respectivamente. Conclusión: Aunque el material genético de Helicobacter spp. se encontró en algunos animales, no hubo relación con las lesiones gástricas. Es posible que la helicobacteriosis no tenga incidencia en la etiología del EGUS.

[Resumen] Philasterides dicentrarchi es el principal agente etiológico de la escuticociliatosis, una enfermedad que causa importantes mortalidades en la acuicultura del rodaballo. Con relación a esto, ha aumentado el interés en conocer los mecanismos de defensa frente a este parásito y desarrollar vacunas eficaces para la prevención de esta enfermedad. Los peces teleósteos, como es el caso del rodaballo, tienen un sistema inmunitario que participa en la inmunidad innata y adquirida. En esta última participan 3 tipos de inmunoglobulinas IgM, IgD e IgT; la primera con una función importante en la inmunidad sistémica, mientras que a la IgT se le atribuye una función especial en la inmunidad de las mucosas. Estudios previos han demostrado que una vacuna administrada por inyección genera protección en rodaballo contra P. dicentrarchi, aunque esta vacuna provoca efectos secundarios en el pez, por lo que resulta interesante buscar una alternativa a este método de vacunación. En este trabajo se evaluó la actividad parasiticida del suero y del moco intestinal de rodaballos inmunizados con una vacuna administrada por inmersión que se compone de un adyuvante comercial y de antígeno entero inactivado de P. dicentrarchi. Además, se determinó el nivel de anticuerpos IgM e IgT específicos presentes en el suero y en el moco de rodaballos inmunizados mediante un ELISA doble indirecto, y se analizó la expresión génica mediante qPCR en riñón, branquias, piel e intestino de inmunoglobulinas y otros genes relacionados con la respuesta inmunitaria tanto innata como adquirida. Nuestros resultados evidencian una estimulación importante a nivel de las branquias y del intestino, lo que sugiere una respuesta protectora sobre a todo a nivel de las mucosas. En futuros trabajos sería interesante realizar infecciones experimentales con Philasterides dicentrarchi para evaluar la protección generada en rodaballo por este método de vacunación.

The oral mucosa is a site of intense immune activity, where a large variety of immune cells meet to provide a first line of defense against pathogenic organisms. Interestingly, the oral mucosa is exposed to a plethora of antigens from food and commensal bacteria that must be tolerated. The mechanisms that enable this tolerance are not yet fully defined. Many works have focused on active immune mechanisms involving dendritic and regulatory T cells. However, epithelial cells also make a major contribution to tolerance by influencing both innate and adaptive immunity. Therefore, the tolerogenic mechanisms concurring in the oral mucosa are intertwined. Here, we review them systematically, paying special attention to the role of oral epithelial cells., Comunidad de Madrid, Universidad Complutense de Madrid, Depto. de Inmunología, Oftalmología y ORL, Fac. de Medicina, TRUE, pub

Introduction: Recurrent urethral diverticulum has been reported in 23% of cases after primary repair and can be difficult to manage. The aim of this video is to demonstrate a surgical technique of repairing a recurrent diverticulum in a woman who had two previous procedures, one with a Martius labial fat pad graft. Method(s): A 40-year-old woman presented with a symptomatic recurrent urethral diverticulum after two previous repairs. She underwent surgery with excision of the diverticular mucosa and multilayer urethral closure using the diverticulum wall after mobilization and then repositioning of the Martius labial fat pad interposition. Result(s): There were no surgical complications intra- or postoperatively, and the patient had improvement of her symptoms postoperatively with resolution of the diverticulum on ultrasound. Conclusion(s): Mobilizing and repositioning a Martius labial fat pad is a feasible technique for complex recurrent urethral diverticulum repairs. The graft alone without meticulous urethral repair will not prevent diverticulum recurrence, fistula formation or stress urinary incontinence. This procedure requires experienced surgeons to minimize surgical complications and optimize outcome.Copyright © 2020, The International Urogynecological Association.

In the conditions of intensive development of industry, the relevance ofstudying the role of harmful production factors in the formation of variouspathological processes in employees of enterprises increases. The long-terminfluence of a complex of factors, simultaneously with the deterioration ofthe health of workers, can lead to pathological changes in the oral mucosa,periodontal diseases, and hard tissues of the teeth. Of particular relevance isthe problem of the prevalence and intensity of diseases of the hard tissues ofthe teeth and periodontal pathology

In the conditions of intensive development of industry, the relevance ofstudying the role of harmful production factors in the formation of variouspathological processes in employees of enterprises increases. The long-terminfluence of a complex of factors, simultaneously with the deterioration ofthe health of workers, can lead to pathological changes in the oral mucosa,periodontal diseases, and hard tissues of the teeth. Of particular relevance isthe problem of the prevalence and intensity of diseases of the hard tissues ofthe teeth and periodontal pathology

Introduction: Recurrent urethral diverticulum has been reported in 23% of cases after primary repair and can be difficult to manage. The aim of this video is to demonstrate a surgical technique of repairing a recurrent diverticulum in a woman who had two previous procedures, one with a Martius labial fat pad graft. Method(s): A 40-year-old woman presented with a symptomatic recurrent urethral diverticulum after two previous repairs. She underwent surgery with excision of the diverticular mucosa and multilayer urethral closure using the diverticulum wall after mobilization and then repositioning of the Martius labial fat pad interposition. Result(s): There were no surgical complications intra- or postoperatively, and the patient had improvement of her symptoms postoperatively with resolution of the diverticulum on ultrasound. Conclusion(s): Mobilizing and repositioning a Martius labial fat pad is a feasible technique for complex recurrent urethral diverticulum repairs. The graft alone without meticulous urethral repair will not prevent diverticulum recurrence, fistula formation or stress urinary incontinence. This procedure requires experienced surgeons to minimize surgical complications and optimize outcome.Copyright © 2020, The International Urogynecological Association.

Otitis media (OM) encompasses a spectrum of clinical presentations ranging from the readily identifiable Acute OM (AOM), which is characterised by otalgia and fever, to chronic otitis media with effusion (COME) where impaired hearing due to middle ear effusion may be the only clinical symptom. Chronic suppurative OM (CSOM) presents as a more severe form of OM, involving perforation of the tympanic membrane. The pathogenesis of OM in these varied clinical presentations is unclear but activation of the innate inflammatory responses to viral and/or bacterial infection of the upper respiratory tract performs an integral role. This localised inflammatory response can persist even after pathogens are cleared from the middle ear, eustachian tubes and, in the case of respiratory viruses, even the nasal compartment. Children prone to OM may experience an over exuberant inflammatory response that underlies the development of chronic forms of OM and their sequelae, including hearing impairment. Treatments for chronic effusive forms of OM are limited, with current therapeutic guidelines recommending a “watch and wait” strategy rather than active treatment with antibiotics, corticosteroids or other anti-inflammatory drugs. Overall, there is a clear need for more targeted and effective treatments that either prevent or reduce the hyper-inflammatory response associated with chronic forms of OM. Improved treatment options rely upon an in-depth understanding of OM pathogenesis, particularly the role of the host innate immune response during acute OM. In this paper, we review the current literature regarding the innate immune response within the middle ear to bacterial and viral otopathogens alone, and as co-infections. This is an important consideration, as the role of respiratory viruses as primary pathogens in OM is not yet fully understood. Furthermore, increased reporting from PCR-based diagnostics, indicates that viral/bacterial co-infections in the middle ear are more commo

Water is a vital component regulating the properties of topical formulations and their interaction with biological barriers, such as skin and mucosa. Changing the watercontent within the frame of the pharmaceutical triangle will have a huge impact on which type of formulation, such as a cream, ointment, gel, or lotion, is formed, as well as the physical properties of the formulation. The composition of a formulation, and the subsequent reformulation after application, will govern the features of the residual film. This will in turn affect the barrier properties of the underlying tissue and consequently the penetration of various substances across skin or mucosa.The primary aim of this thesis has been to provide further understanding on differences between traditional surfactant-based formulations and particle-stabilized, Pickering, formulations and how specific excipients, like alcohols, emollients, and thickeners can affect their physical and/or sensorial properties. The secondary aim has been to gain more knowledge on the role of water in topical formulations and how it affects the properties of the underlaying tissue on application. By combining a portfolio of physicochemical techniques combined with sensory science, we have been able to identify differences between Pickering and surfactantstabilized formulations. Starch-based Pickering emulsions were perceived as less greasy and sticky than traditional creams, even at high oil content. Moreover, we were able develop a novel type of alcohol-based Pickering emulsion with combined moisturizing and antiseptic properties. We have also been able to link sensory attributes, evaluated by human volunteers, with physicochemical characterizations. Furthermore, the in vitro ForceBoard™ method was developed further and we evaluated its potential to be used as an ex vivo method using excised skin. In addition, we have shown that that the water gradient over a biological barrier has a general relevance with respect to drug abs

In the conditions of intensive development of industry, the relevance ofstudying the role of harmful production factors in the formation of variouspathological processes in employees of enterprises increases. The long-terminfluence of a complex of factors, simultaneously with the deterioration ofthe health of workers, can lead to pathological changes in the oral mucosa,periodontal diseases, and hard tissues of the teeth. Of particular relevance isthe problem of the prevalence and intensity of diseases of the hard tissues ofthe teeth and periodontal pathology

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development.

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development.

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development.

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development., Funding Agencies|Center for Clinical Research Dalarna; Swedish Society of Medicine; Swedish Research CouncilSwedish Research CouncilEuropean Commission; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC); King Gustaf Vs 80-year foundation; Swedish Rheumatism association; Ostergotland County Council; Reinhold Sund foundation

Immunological correlates of natural resistance to HIV have been identified in HIV-exposed seronegative (HESN) individuals and include a low-inflammatory genital mucosal status. The cervicovaginal epithelium has not been studied for such correlates despite constituting an important barrier against sexual HIV transmission. To fill this gap in knowledge, we collected samples of blood, cervical mononuclear cells, cervicovaginal lavage, and ectocervical tissue from Kenyan HESN sex workers (n = 29) and controls (n = 33). The samples were analyzed by flow cytometry, protein profiling, 16S rRNA gene sequencing, in situ image analysis, and tissue-based RNA sequencing. A significantly higher relative proportion of regulatory T cells in blood (B7(+)CD25(hi)FoxP3(+)CD127(lo)CD4(+) and B7(+)Helios(+)FoxP3(+)CD4(+)), and a significantly lower proportion of activated cervical T cells (CCR5(+)CD69(+)CD4(+) and CCR5(+)CD69(+)CD8(+)), were found in the HESN group compared with the controls. In contrast, there were no statistically significant differences between the study groups in cervicovaginal protein and microbiome compositions, ectocervical epithelial thickness, E-cadherin expression, HIV receptor expression, and tissue RNA transcriptional profiles. The identification of an intact ectocervical microenvironment in HESN individuals add new data to current knowledge about natural resistance to sexual transmission of HIV., QC 20210420

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development., Funding Agencies|Center for Clinical Research Dalarna; Swedish Society of Medicine; Swedish Research CouncilSwedish Research CouncilEuropean Commission; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC); King Gustaf Vs 80-year foundation; Swedish Rheumatism association; Ostergotland County Council; Reinhold Sund foundation

White Leghorn chickens were divided into the control, low-carbohydrate (CHO), and CHO-free groups to investigate dietary CHO’s significance on histological features of chicken ileal mucosa. Paraffin sections of distal ileum from each chicken were stained by periodic acid-Schiff reaction and subjected to morphometrical analysis. Most villi in the control group had a fingerlike shape but those of the experimental groups showed irregular shapes. Villus height, crypt depth and the number of mitotic cells per crypt were significantly lower in the CHO-free group than in the control group. The density of goblet cells also showed a significant decreasing trend with a reduction in dietary CHO level. In conclusion, dietary CHO positively affects the proliferation of epithelial cells in the chicken ileum.

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.

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development.

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development., Funding Agencies|Center for Clinical Research Dalarna; Swedish Society of Medicine; Swedish Research CouncilSwedish Research CouncilEuropean Commission; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC); King Gustaf Vs 80-year foundation; Swedish Rheumatism association; Ostergotland County Council; Reinhold Sund foundation

White Leghorn chickens were divided into the control, low-carbohydrate (CHO), and CHO-free groups to investigate dietary CHO’s significance on histological features of chicken ileal mucosa. Paraffin sections of distal ileum from each chicken were stained by periodic acid-Schiff reaction and subjected to morphometrical analysis. Most villi in the control group had a fingerlike shape but those of the experimental groups showed irregular shapes. Villus height, crypt depth and the number of mitotic cells per crypt were significantly lower in the CHO-free group than in the control group. The density of goblet cells also showed a significant decreasing trend with a reduction in dietary CHO level. In conclusion, dietary CHO positively affects the proliferation of epithelial cells in the chicken ileum.

Coffee is one of the most popular beverages consumed worldwide. Roasted coffee is a complex mixture of thousands of bioactive compounds, and some of them have numerous potential health-promoting properties that have been extensively studied in the cardiovascular and central nervous systems, with relatively much less attention given to other body systems, such as the gastrointestinal tract and its particular connection with the brain, known as the brain–gut axis. This narrative review provides an overview of the effect of coffee brew; its by-products; and its components on the gastrointestinal mucosa (mainly involved in permeability, secretion, and proliferation), the neural and non-neural components of the gut wall responsible for its motor function, and the brain–gut axis. Despite in vitro, in vivo, and epidemiological studies having shown that coffee may exert multiple effects on the digestive tract, including antioxidant, anti-inflammatory, and antiproliferative effects on the mucosa, and pro-motility effects on the external muscle layers, much is still surprisingly unknown. Further studies are needed to understand the mechanisms of action of certain health-promoting properties of coffee on the gastrointestinal tract and to transfer this knowledge to the industry to develop functional foods to improve the gastrointestinal and brain–gut axis health.

The aim of this pilot study was to determine viral loads and distribution over the total length, at short distances, and in the separate layers of the intestine of virus-infected animals for future inactivation studies. Two calves, two pigs, and two goats were infected with bovine viral diarrhoea virus (BVDV), classical swine fever virus (CSFV), and peste des petits ruminants virus (PPRV), respectively. Homogenously distributed maximum BVDV viral loads were detected in the ileum of both calves, with a mean titer of 6.0 log10 TCID50-eq/g. The viral loads in colon and caecum were not distributed homogenously. In one pig, evenly distributed CSFV mean viral loads of 4.5 and 4.2 log10 TCID50-eq/g were found in the small and large intestines, respectively. Mucosa, submucosa, and muscular layer/serosa showed mean viral loads of 5.3, 3.4, and 4.0 log10 TCID50-eq/g, respectively. Homogenous distribution of PPRV was shown in the ileum of both goats, with a mean viral load of 4.6 log10 TCID50-eq/g. Mean mucosa, submucosa, and muscular layer/serosa viral loads were 3.5, 2.8, and 1.7 log10 TCID50-eq/g, respectively. This pilot study provides essential data for setting up inactivation experiments with intestines derived from experimentally infected animals, in which the level and the homogeneous distribution of intestinal viral loads are required. View Full-Text

Water is a vital component regulating the properties of topical formulations and their interaction with biological barriers, such as skin and mucosa. Changing the watercontent within the frame of the pharmaceutical triangle will have a huge impact on which type of formulation, such as a cream, ointment, gel, or lotion, is formed, as well as the physical properties of the formulation. The composition of a formulation, and the subsequent reformulation after application, will govern the features of the residual film. This will in turn affect the barrier properties of the underlying tissue and consequently the penetration of various substances across skin or mucosa.The primary aim of this thesis has been to provide further understanding on differences between traditional surfactant-based formulations and particle-stabilized, Pickering, formulations and how specific excipients, like alcohols, emollients, and thickeners can affect their physical and/or sensorial properties. The secondary aim has been to gain more knowledge on the role of water in topical formulations and how it affects the properties of the underlaying tissue on application. By combining a portfolio of physicochemical techniques combined with sensory science, we have been able to identify differences between Pickering and surfactantstabilized formulations. Starch-based Pickering emulsions were perceived as less greasy and sticky than traditional creams, even at high oil content. Moreover, we were able develop a novel type of alcohol-based Pickering emulsion with combined moisturizing and antiseptic properties. We have also been able to link sensory attributes, evaluated by human volunteers, with physicochemical characterizations. Furthermore, the in vitro ForceBoard™ method was developed further and we evaluated its potential to be used as an ex vivo method using excised skin. In addition, we have shown that that the water gradient over a biological barrier has a general relevance with respect to drug abs

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development.

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development., Funding Agencies|Center for Clinical Research Dalarna; Swedish Society of Medicine; Swedish Research CouncilSwedish Research CouncilEuropean Commission; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC); King Gustaf Vs 80-year foundation; Swedish Rheumatism association; Ostergotland County Council; Reinhold Sund foundation

Autoantibodies related to rheumatoid arthritis (RA), such as anti-citrullinated protein antibodies (ACPA), are often detectable in the preclinical period years before arthritis onset. However, events triggering arthritis development remain incompletely known. We aimed to determine whether ACPA isotype levels are prognostic for arthritis development in patients presenting with immunoglobulin (Ig)G ACPA and musculoskeletal pain. Study participants (n = 82) had musculoskeletal pain of any sort and duration and a positive IgG ACPA test. None of the patients had arthritis upon clinical examination at baseline, but during follow-up (mean = 6 years), 48% developed at least one arthritic joint. IgG, IgA, IgM and secretory component (SC)-containing ACPA was measured in longitudinally collected serum samples. Cox regression analysis was performed to test the prognostic value of baseline antibody levels and changes over time. All analysed ACPA isotype levels were associated with arthritis development in univariable Cox regression analysis. In multivariable analysis, baseline SC ACPA levels were independently prognostic for arthritis development in multivariable analysis [hazard ratio (HR) = 1 center dot 006, 95% confidence interval (CI) = 1 center dot 001-1 center dot 010, P = 0 center dot 012]. There were no significant changes in ACPA isotype levels over time, and no significant association between changes over time and arthritis development. In this prospective longitudinal study, baseline serum SC ACPA levels, but neither IgG, IgA nor IgM ACPA are prognostic for future arthritis development. Repeated measurement of ACPA isotypes do not bring additional prognostic value. The results reinforce a mucosal connection in RA development and encourage further exploration of the mechanisms underlying secretory ACPA formation as a trigger for arthritis development., Funding Agencies|Center for Clinical Research Dalarna; Swedish Society of Medicine; Swedish Research CouncilSwedish Research CouncilEuropean Commission; Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC); King Gustaf Vs 80-year foundation; Swedish Rheumatism association; Ostergotland County Council; Reinhold Sund foundation

Objectives: To determine whether treatment with tacrolimus plus sirolimus (Tac/Sir) as a prophylaxis for graft-versus-host disease worsens severe oral mucositis and delays healing compared to cyclosporine plus methotrexate (CsA/Mtx) following haematopoietic stem cell transplantation. Subjects and methods: The study comprised 141 patients: 73 randomized to receive Tac/Sir and 68 to receive CsA/Mtx. The oral mucositis assessment scale and toxicity grading according to WHO were used to assess the severity, peak and duration of oral mucositis from the day -3 to day 24 post-transplant. Results: Eighty-seven patients developed oral mucositis in the first 24 days post-transplant. No significant difference in oral mucositis severity between the Tac/Sir and CsA/Mtx groups was observed. The peak oral mucositis score occurred on day 10 in both groups. Although oral mucositis scores had returned to baseline in the CsA/Mtx group on day 24 post-transplant, no significant difference compared with the Tac/Sir group was found. Conclusions: The introduction of tacrolimus/sirolimus as a graft-versus-host disease prophylaxis in haematopoietic stem cell transplantation increased neither the incidence nor severity of oral mucositis compared with cyclosporine/methotrexate. Furthermore, oral mucositis healing was not prolonged and followed the same time pattern as cyclosporine/methotrexate.

The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.

The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.

The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.

The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.