Mucosal Fluid Research Articles

SARS-CoV-2 Specific IgG Antibodies Persist Over a 12-Month Period in Oral Mucosal Fluid Collected From Previously Infected Individuals.

BackgroundDeveloping an understanding of the antibody response, seroprevalence, and seroconversion from natural infection and vaccination against SARS-CoV-2 will give way to a critical epidemiological tool to predict reinfection rates, identify vulnerable communities, and manage future viral outbreaks. To monitor the antibody response on a larger scale, we need an inexpensive, less invasive, and high throughput method.MethodsHere we investigate the use of oral mucosal fluids from individuals recovered from SARS-CoV-2 infection to monitor antibody response and persistence over a 12-month period. For this cohort study, enzyme-linked immunosorbent assays (ELISAs) were used to quantify anti-Spike(S) protein IgG antibodies in participants who had prior SARS-CoV-2 infection and regularly (every 2-4 weeks) provided both serum and oral fluid mucosal fluid samples for longitudinal antibody titer analysis.ResultsIn our study cohort (n=42) with 17 males and 25 females with an average age of 45.6 +/- 19.3 years, we observed no significant change in oral mucosal fluid IgG levels across the time course of antibody monitoring. In oral mucosal fluids, all the participants who initially had detectable antibodies continued to have detectable antibodies throughout the study.ConclusionsBased on the results presented here, we have shown that oral mucosal fluid-based assays are an effective, less invasive tool for monitoring seroprevalence and seroconversion, which offers an alternative to serum-based assays for understanding the protective ability conferred by the adaptive immune response from viral infection and vaccination against future reinfections.

Detection of persistent SARS-CoV-2 IgG antibodies in oral mucosal fluid and upper respiratory tract specimens following COVID-19 mRNA vaccination

COVID-19 mRNA vaccines are highly effective at preventing COVID-19. Prior studies have found detectable SARS-CoV-2 IgG antibodies in oral mucosal specimens of participants with history of COVID-19. To assess the development of oral SARS-CoV-2 IgG antibodies among people who received either the Moderna or Pfizer/BioNTech COVID-19 vaccination series, we developed a novel SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) to quantify the concentrations of oral and nasal mucosal SARS-CoV-2 IgG levels. We enrolled 52 participants who received the Moderna vaccine and 80 participants who received the Pfizer/BioNTech vaccine. Oral mucosal specimens were self-collected by participants prior to or on the day of vaccination, and on days 5, 10, 15, and 20 following each vaccination dose and 30, 60, and 90 days following the second vaccination dose. A subset of the cohort provided additional nasal mucosal specimens at every time point. All participants developed detectable oral mucosal SARS-CoV-2 IgG antibodies by 15 days after the first vaccination dose. There were no significant differences in oral mucosal antibody concentrations once participants were fully vaccinated in the Moderna and Pfizer/BioNTech vaccines. Oral or nasal mucosal antibody testing could be an inexpensive and less invasive alternative to serum antibody testing. Further research is needed to understand the duration of detectable oral or nasal mucosal antibodies and how antibody concentrations change with time.

618 STUDY ON THE RELATIONSHIP BETWEEN GASTROESOPHAGEAL REFLUX SYMPTOMS AND ESOPHAGEAL MICROBIOTA

Abstract The occurrence of gastroesophageal reflux symptoms is related to the changes of esophageal mucosal sensitivity and esophageal motility. Studies have found that changes in gut microbiota can cause lower digestive tract symptoms by changing intestinal sensitivity and intestinal motility. The current study aimed to explore whether changes of esophageal microbiota can cause gastroesophageal reflux symptoms by altering esophageal sensitivity and esophageal motility. Methods Patients who were admitted to our hospital due to heartburn and reflux symptoms were prospectively included. Ten healthy volunteers and 10 patients with duodenal ulcer were included as controls. Both patients’ and healthy volunteers’ distal esophagus mucosal tissues and gastric fluid were collected under endoscopy for extraction of bacterial DNA. Patients and volunteers were divided into different groups according to disease situations, esophageal motility status, proton pump inhibitor (PPI) treatment efficacy. The α-diversity, β-diversity and specific composition of the microbiota among different groups were compared. Results A total of 12 patients with gastroesophageal reflux disease (G), 16 patients with functional esophageal disorder (F), 10 healthy volunteers (H), and 10 duodenal ulcer patients (D) were included. Esophageal mucosal microbiota analysis revealed that the microbiota composition was similar in patients with gastroesophageal reflux disease and functional esophageal disorders, which significantly different from that in healthy volunteers and patients with duodenal ulcers. Both gastroesophageal reflux disease patients and functional esophageal disorder patients had higher proportion of Pseudomonas than healthy controls and duodenal ulcer patients (G vs. F vs. H vs. D = 25.5% vs. 41.9% vs. 0.2% vs. 1.2%；P = 0.041). Conclusion The microbiota composition of patients with gastroesophageal reflux disease and patients with functional esophageal disorder were similar and were both significantly different from that of healthy volunteers and patients with duodenal ulcer. The increased proportion of Gram-negative bacteria such as Pseudomonas may play an important role in the occurrence of gastroesophageal reflux symptoms.

Pharmacokinetics of vaginally applied integrase inhibitors in macaques.

We conducted a detailed pharmacokinetic assessment in macaques treated with vaginal gels formulated with HIV integrase strand transfer inhibitors (INSTIs) to better understand drug distribution and identify INSTI concentrations associated with previously demonstrated in vivo protection against vaginal simian HIV challenge. Six macaques received vaginal gel containing 1% raltegravir (30 mg) once-weekly over 6 weeks. Following a washout period, five macaques received once-weekly gel containing 0.23% L-870,812 (7 mg). Drug concentrations were measured in plasma, mucosal fluids and vaginal tissues at baseline and 2, 5 and 24 h post-dosing. The median maximum concentration (Cmax) for raltegravir and L-870,812 in plasma was below the limit of quantification and 41.1 ng/mL, respectively. The Cmax in vaginal fluids (1441 and 1250 μg/mL) and tissues (266.7 and 368.4 μg/g) was achieved 2-5 h after dosing, respectively. A similar half-life was observed for raltegravir and L-870,812 in vaginal fluids (8-10 h) and remained 3-4 orders of magnitude above the protein-adjusted IC95 (0.016 and 0.106 μg/mL, respectively) at 24 h. Drug concentrations in vaginal fluids correlated well with those in vaginal tissues (Pearson r ≥ 0.788). Both drugs were consistently detected in rectal fluids 2 h after vaginal dosing, albeit at much lower levels (31-92-fold) than those in vaginal fluids. To the best of our knowledge, this study provides the first data on INSTI levels in vaginal tissues associated with in vivo protection and demonstrates rectal drug distribution of INSTIs after vaginal dosing. These findings may inform dose selection for topical products with INSTIs for HIV prevention.

Gastric microbiome in horses with and without equine glandular gastric disease.

BackgroundThe role of the gastric microbiome in development or persistence of equine glandular gastric disease (EGGD) remains to be investigated.Hypothesis/ObjectivesThe objective was to characterize the glandular mucosal and gastric fluid microbiomes of horses with and without EGGD. It was hypothesized that differences in the mucosal microbiome are associated with EGGD.AnimalsTwenty‐four horses were enrolled.MethodsGastroscopy was performed and EGGD scores recorded (score 0, n = 6; score 1, n = 8; score ≥2, n = 10). Gastric fluid and pinch biopsies of healthy glandular mucosa and EGGD lesions were collected via gastroscope. 16S rRNA amplicon sequencing of the gastric fluid and glandular mucosal biopsies was performed. Relationships between gastric fluid and mucosal microbial community composition were evaluated among EGGD score groups (EGGD 0‐BX, EGGD 1‐BX, EGGD ≥2‐BX) and among endoscopic appearances: controls from horses without EGGD and normal areas, hyperemic areas, and lesions from horses with EGGD.ResultsMicrobial community structure of mucosal biopsies differed among EGGD score groups (Jaccard similarity index; P = .009). Principal coordinate analysis showed separate clusters for EGGD 0‐BX and EGGD ≥2‐BX.Conclusions and Clinical ImportanceA modest difference was detected in the community structure of the gastric glandular mucosal microbiome in association with EGGD score.

Influence of bacterial endotoxin on mucosal immune response to phosphorylcholine

Bacterial lipopolysaccharide (LPS), a component of the outer membrane of gram-negative bacteria that initiates inflammation by activation innate immune responses through Toll-like receptor 4 (TLR4). However, the influence of LPS on the mucosal immune reactions remains to be addressed. This study was examined the effect of LPS in nasal vaccination model. BALB/c and C57BL/6 mice were nasally immunized with keyhole limpet hemocyanin (KLH) conjugated with hapten phosphorylcholine (PC) or trinitrophenol (TNP) with LPS as a mucosal adjuvant, in the presence or absence of cholera toxin (CT). The antibody titers were measured in serum, saliva, and nasal wash fluids by an enzyme-linked immunosorbent assay (ELISA) in IgM, IgG, and IgA isotype-specific manner. The epitope-specific antibody production induced in blood and mucosal fluid was further enhanced by LPS for all isotypes examined. Besides, LPS, which has rarely been regarded as a mucosal adjuvant, was tested for its adjuvanticity by comparing the nasal immunization with PC-KLH plus LPS or with PC-KLH plus CT. LPS showed high adjuvanticity almost equal to CT. Possible differences of LPS from CT as a mucosal adjuvant remains to be elucidated.

Neonatal airway immune profiles and asthma and allergy endpoints in childhood.

The immune system plays a key role in the pathogenesis of asthma and allergy, but the role of the airway cytokine and chemokine composition in vivo in early life prior to symptom development has not been described previously. Here, we aimed to examine whether the neonatal airway immune composition associates with development of allergy and asthma in childhood. We measured unstimulated levels of 20 immune mediators related to the Type 1, Type 2, Type 17, or regulatory immune pathways in the airway mucosal lining fluid of 620 one-month-old healthy neonates from the COPSAC2010 birth cohort. Allergy and asthma were diagnosed at our research clinic by predefined algorithms and objective assessments at age 6years. Principal component analyses were used to describe the airway cytokine and chemokine composition. A neonatal airway immune profile particularly characterized by enhanced IL-1β and reduced CCL26 was significantly associated with later development of elevated specific IgE to inhaled allergens, a positive skin prick test, and allergic rhinitis, but not with food sensitization. Conversely, reduced Type 17 immune-associated markers, including IL-1β and CXCL8, showed trend of association with development of early asthma endpoints. Development of early asthma endpoints and inhalant allergy during the first 6years of life seems associated with distinctly perturbed airway immune profiles in neonatal life, which is suggestive of an early origin and different pathogenesis of childhood asthma and allergy. These exploratory findings suggest pre- and perinatal life as an important window of opportunity for prevention of asthma and inhalant allergy.

A novel anatomical classification of the frontal sinus: can it be useful in clinical approach to frontal sinusitis?

BackgroundWe aimed to test the clinical relevance of a newly introduced anatomical classification system of the frontal sinus and to investigate the relation between the frontal sinus type according to this system and the development of frontal sinusitis. We retrospectively evaluated the computed tomography images of 808 frontal sinuses of 404 patients and classified the sinuses as small, medium-sized, and large, based on their size and relation to the orbital roof. We related this classification to the presence or absence of the findings of frontal sinusitis including mucosal thickening, retention cyst/polyp, and/or fluid collection.ResultsWe found that the most common frontal sinus type is medium-sized (65.84%), followed by the small (22.89%) and large (11.26%) types, respectively. There was no significant difference between the right and left sides in terms of frontal sinus type (P<0.05). We recorded sinusitis in 28 (15.1%) small, 180 (33.8%) medium-sized, and 40 (43.9%) large sinuses. And we showed that the prevalence of sinusitis in medium-sized and large sinuses is significantly higher than that in small sinuses for both sides (P values were 0.001 and 0.015, respectively for the right, and 0.005 and 0.001, respectively for the left side).ConclusionThe result obtained in this study may be considered the first step in demonstrating the clinical benefit of this classification. However, there is no doubt that further comprehensive studies with large series are needed to fully determine the clinical relevance of this newly introduced classification system.

Radiological changes in maxillary sinus morphology after lateral sinus floor augmentation

&lt;b&gt;Background:&lt;/b&gt; Restoration of the masticatory function in patients with edentulous posterior maxilla is often challenging due to the severe atrophy of the alveolar ridges and proximity of the maxillary sinus, resulting in insufficient bone quantity for implant-supported dentures. &lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; The purpose of this study was to analyze the changes in Schneiderian membrane thickness after lateral sinus floor augmentation (LSFA) using cone beam computed tomography (CBCT). &lt;br&gt;&lt;b&gt;Material and methods:&lt;/b&gt; W LSFA procedures using different bone grafting materials were performed in 87 patients, operated on in two clinical institutions from 2016 to 2018. CBCT examination was performed in all patients before the LSFA procedure, at 1 month after surgery, and after 6 months, before implant placement or loading. &lt;br&gt;&lt;b&gt;Results:&lt;/b&gt; Minor r adiological changes in mucous membrane morphology were observed preoperatively in 17.1% of patients. Postoperative CBCT in the early postsurgical period demonstrated that the number of intact non-specific sinuses decreased significantly, i.e. from 86.7% to 26.7%. The number of cases with local hypertrophia of the mucous membrane increased from 20.3% to 26.7%. Mucosal thickening was observed in 41.7% vs 7.5%. The number of intact sinuses increased to 57.8%. The number of cases with local membrane hypertrophia also increased – to 37.4%. The number of cases with mucosal thickening or fluid accumulation decreased significantly to 11.8 and 5.3% respectively. In 2 cases the development of chronic sinusitis required secondary surgeries. &lt;br&gt;&lt;b&gt;Conclusion:&lt;/b&gt; The present retrospective study revealed that minor radiological changes in the morphology of the maxillary sinus mucosa were observed preoperatively in 17.1% of patients who underwent LSFA procedures. In the early and late postoperative period their frequency increased to 68.5% and 47.1%, r espectively. However, the clinical signs o f sinusitis developed only in 19.26% of patients. No significant correlations were found between the frequency and severity of postoperative radiological changes and residual bone height, sinus anatomy, initial state of the mucous membrane and type of the grafting material.

Role of Polymeric Immunoglobulin Receptor in IgA and IgM Transcytosis.

Transcytosis of polymeric IgA and IgM from the basolateral surface to the apical side of the epithelium and subsequent secretion into mucosal fluids are mediated by the polymeric immunoglobulin receptor (pIgR). Secreted IgA and IgM have vital roles in mucosal immunity in response to pathogenic infections. Binding and recognition of polymeric IgA and IgM by pIgR require the joining chain (J chain), a small protein essential in the formation and stabilization of polymeric Ig structures. Recent studies have identified marginal zone B and B1 cell-specific protein (MZB1) as a novel regulator of polymeric IgA and IgM formation. MZB1 might facilitate IgA and IgM transcytosis by promoting the binding of J chain to Ig. In this review, we discuss the roles of pIgR in transcytosis of IgA and IgM, the roles of J chain in the formation of polymeric IgA and IgM and recognition by pIgR, and focus particularly on recent progress in understanding the roles of MZB1, a molecular chaperone protein.

Vaginal microbiome-hormonal contraceptive interactions associate with the mucosal proteome and HIV acquisition.

Alterations to the mucosal environment of the female genital tract, such as genital inflammation, have been associated with increased HIV acquisition in women. As the microbiome and hormonal contraceptives can affect vaginal mucosal immunity, we hypothesized these components may interact in the context of HIV susceptibility. Using previously published microbiome data from 685 women in the CAPRISA-004 trial, we compared relative risk of HIV acquisition in this cohort who were using injectable depot medroxyprogesterone acetate (DMPA), norethisterone enanthate (NET-EN), and combined oral contraceptives (COC). In women who were Lactobacillus-dominant, HIV acquisition was 3-fold higher in women using DMPA relative to women using NET-EN or COC (OR: 3.27; 95% CI: 1.24–11.24, P = 0.0305). This was not observed in non-Lactobacillus-dominant women (OR: 0.95, 95% CI: 0.44–2.15, P = 0.895) (interaction P = 0.0686). Higher serum MPA levels associated with increased molecular pathways of inflammation in the vaginal mucosal fluid of Lactobacillus-dominant women, but no differences were seen in non-Lactobacillus dominant women. This study provides data suggesting an interaction between the microbiome, hormonal contraceptives, and HIV susceptibility.

Systemic and mucosal antibody responses specific to SARS-CoV-2 during mild versus severe COVID-19

BackgroundWhereas severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody tests are increasingly being used to estimate the prevalence of SARS-CoV-2 infection, the determinants of these antibody responses remain unclear.ObjectivesOur aim was to evaluate systemic and mucosal antibody responses toward SARS-CoV-2 in mild versus severe coronavirus disease 2019 (COVID-19) cases.MethodsUsing immunoassays specific for SARS-CoV-2 spike proteins, we determined SARS-CoV-2–specific IgA and IgG in sera and mucosal fluids of 2 cohorts, including SARS-CoV-2 PCR-positive patients (n = 64) and PCR-positive and PCR-negtive health care workers (n = 109).ResultsSARS-CoV-2–specific serum IgA titers in patients with mild COVID-19 were often transiently positive, whereas serum IgG titers remained negative or became positive 12 to 14 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2–specific serum IgA and IgG titers after symptom onset. Very high titers of SARS-CoV-2–specific serum IgA were correlated with severe acute respiratory distress syndrome. Interestingly, some health care workers with negative SARS-CoV-2–specific serum antibody titers showed SARS-CoV-2–specific IgA in mucosal fluids with virus-neutralizing capacity in some cases. SARS-CoV-2–specific IgA titers in nasal fluids were inversely correlated with age.ConclusionsSystemic antibody production against SARS-CoV-2 develops mainly in patients with severe COVID-19, with very high IgA titers seen in patients with severe acute respiratory distress syndrome, whereas mild disease may be associated with transient production of SARS-CoV-2–specific antibodies but may stimulate mucosal SARS-CoV-2–specific IgA secretion.

Teknik modifikasi ekstraoral radiografi Newman dan Friedman sebagai alternatif radiografi intraoral periapikal pada masa pandemi COVID-19

Objectives: This review is aimed to propose a method that could be an alternative in taking intra-oral radiographs during the COVID-19 pandemic. &#x0D; Literature Review: The COVID-19 pandemic is the most concerning health problem in the world today. The transmission of COVID-19 is through direct or close contact with infected secretions or aerosol droplets. Individuals with COVID-19 may be asymptomatic or presymptomatic (20%-86% of all infections). Thus, patients with undiagnosed COVID-19 can come to dental clinics and Oral and Maxillofacial Radiology centers anytime. The Oral and Maxillofacial Radiology centers from dental clinics can be a source of transmission of COVID-19 to operator and dental patients. In extraoral radiography modification technique of Newman and Friedman, the sensor is placed on the cheek outside of the oral mucosa, so that the sensor does not contact the mucosal fluid from the patient. &#x0D; Conclusion: Newman and Friedman's extraoral radiography modification techniques can be use as an alternatives to periapical intraoral radiographs to minimize the transmission of COVID-19.

How Does HIV Env Structure Informs Vaccine Design?

BackgroundThe DHVI Division of Structural Biology seeks to use atomic level structural information for design of an effective HIV-1 vaccine. Through visualization of the HIV-1 envelope (Env) and its interactions with the human immune system, we obtain structural information that we translate into the rational development vaccine immunogensMethodsWe use negative stain electron microscopy (NSEM), cryo-electron microscopy (cryo-EM), and x-ray crystallography as the major structural techniques for visualization of HIV-1 Env, and combine these with biochemical and biophysical studies, as well as computational methods to obtain a basic understanding of the functions and interactions of the HIV-1 Env.Results:1.The DHVI NSEM pipeline runs on a daily basis to quality control vaccine immunogens for animal studies and other applications. Offering rapid sample turnover and economical operations, the NSEM pipeline is the most widely utilized resource of the DHVI Division of Structural Biology. Over the last year, the NSEM team has focused efforts on improving operational speed and data processing allowing high-quality visualization of a large variety of samples including HIV-1 Env immunogens, antibodies, nanoparticles, and VLPs. In the last year we have also expanded our NSEM studies to the analyses of serum samples and mucosal fluids.2.To understand the mechanism of HIV-1 entry we have determined structures of HIV-1 entry intermediates. We have determined a 3.8 Å resolution structure of a single CD4 bound to a closed HIV-1 Env trimer revealing new contacts of CD4 with Env. We have also structurally characterized an Env designed to prevent CD4-induced rearrangements by targeted disruption of an allosteric network modulating Env conformational changes.3.We have structurally characterized the HIV-1 glycan-V3 targeting DH270 Broadly Neutralizing Antibody Lineage. The structures revealed movements in the V1 loop and interactive glycans, shifts in antibody orientations, antibody VH-VL orientations, and antibody elbow angles, as the lineage progressed to maturation.4.We have solved a structure in complex with the HIV-1 Env immunogen Man5-enriched CH505.N279K.G458Y.SOSIP.664 of the unmutated common ancestor (UCA) of the HIV-1 CD4-binding site targeting CH235 Broadly Neutralizing Antibody Lineage. The structure revealed interactions of the N279K and G458Y mutations with the CDR L3 loop of CH235 UCA thus providing a structural understanding of the role of these mutations in facilitating binding to the CH235 UCA. (see also Henderson et al abstract)5.Using NSEM and cryo-EM we have characterized the structural properties of a novel class of 2G12-mimetic, yet non domain-swapped Fab dimer glycan-reactive (FDG) antibodies. These studies showed that the Fab-dimerized 2G12-like motif is more common than previously thought, and that creation of a Fab-dimerized paratope for an HIV-1 neutralizing antibody does not require VH domain-swapping.6.Finally, the structural team is an integral part of the CHAVD Kalma Immunogen Design Team, wherein we are defining the structural basis of bnAb affinity maturation to guide sequential immunogen design.Conclusions:These results highlight the power of structural information on HIV-1 vaccine design, from leveraging a basic understanding of HIV-1 entry mechanism for immunogen design, to rapid visualization of Env immunogens by NSEM for quality control, discovery of novel antibody interactions, and atomic level visualization of antibody/Env interactions.

Increased nasal mucosal interferon and CCL13 response to a TLR7/8 agonist in asthma and allergic rhinitis

Acute respiratory viral infections are a major cause of respiratory morbidity and mortality, especially in patients with preexisting lung diseases such as asthma. Toll-like receptors are critical in the early detection of viruses and in activating innate immunity in the respiratory mucosa, but there is no reliable and convenient method by which respiratory mucosal innate immune responses can be measured. We sought to assess invivo immune responses to an innate stimulus and compare responsiveness between healthy volunteers and volunteers with allergy. We administered the Toll-like receptor 7/8 agonist resiquimod (R848; a synthetic analogue of single-stranded RNA) or saline by nasal spray to healthy participants without allergy (n= 12), those with allergic rhinitis (n= 12), or those with allergic rhinitis with asthma (n= 11). Immune mediators in blood and nasal fluid and mucosal gene expression were monitored over time. R848 was well tolerated and significantly induced IFN-α2a, IFN-γ, proinflammatory cytokines (TNF-α, IL-2, IL-12p70), and chemokines (CXCL10, C-C motif chemokine ligand [CCL]2, CCL3, CCL4, and CCL13) in nasal mucosal fluid, without causing systemic immune activation. Participants with allergic rhinitis or allergic rhinitis with asthma had increased IFN-α2a, CCL3, and CCL13 responses relative to healthy participants; those with asthma had increased induction of IFN-stimulated genes DExD/H-box helicase 58, MX dynamin-like GTPase 1, and IFN-induced protein with tetratricopeptide repeats 3. Responses to nasal delivery of R848 enables simple assessment of mucosal innate responsiveness, revealing that patients with allergic disorders have an increased nasal mucosal IFN and chemokine response to the viral RNA analogue R848. This highlights that dysregulated innate immune responses of the nasal mucosa in allergic individuals may be important in determining the outcome of viral exposure.

Early life bacterial airway colonization, local immune mediator response and risk of otitis media

Introduction. Acute otitis media (AOM) is the most common bacterial infection in early childhood, but the underlying mechanisms making some children more susceptible are poorly understood.Aim. To examine the associations between bacterial airway colonization in early life and the risk of AOM and tympanostomy tube insertion (TTI), and whether such associations are modulated by an insufficient local immune mediator response to bacterial colonization.Methodology. Bacterial cultures from hypopharyngeal samples were obtained at 1 week, 1 month and 3 months of age in the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort comprising 700 children. Twenty immune mediators were quantified from airway mucosal lining fluid sampled at 1 month. AOM symptoms were registered in a daily diary until 3 years. Information on TTI in the first 3 years was obtained from national registers.Results. Children colonized with Streptococcus pneumoniae at 1 month of age had increased incidence of AOM [aIRR 2.43 (1.14-5.21)] and children colonized with Moraxella catarrhalis at 1 month or Haemophilus influenzae at 3 months had an increased risk of TTI [aHR 1.45 (1.00-2.10) and 1.73 (1.10-2.71)]. There were no associations between the local immune mediator response to colonization and risk of AOM or TTI.Conclusion. Pathogenic bacterial airway colonization in early life was found to be associated with an increased risk of otitis media, albeit not consistently. These associations were independent of the local immune response to colonization.

Radiological changes in maxillary sinus morphology after lateral sinus floor augmentation.

&lt;b&gt;Background:&lt;/b&gt; Restoration of the masticatory function in patients with edentulous posterior maxilla is often challenging due to the severe atrophy of the alveolar ridges and proximity of the maxillary sinus, resulting in insufficient bone quantity for implant-supported dentures. &lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; The purpose of this study was to analyze the changes in Schneiderian membrane thickness after lateral sinus floor augmentation (LSFA) using cone beam computed tomography (CBCT). &lt;br&gt;&lt;b&gt;Material and methods:&lt;/b&gt; WLSFA procedures using different bone grafting materials were performed in 87 patients, operated on in two clinical institutions from 2016 to 2018. CBCT examination was performed in all patients before the LSFA procedure, at 1 month after surgery, and after 6 months, before implant placement or loading. &lt;br&gt;&lt;b&gt;Results: &lt;/b&gt;Minor r adiological changes in mucous membrane morphology were observed preoperatively in 17.1% of patients. Postoperative CBCT in the early postsurgical period demonstrated that the number of intact non-specific sinuses decreased significantly, i.e. from 86.7% to 26.7%. The number of cases with local hypertrophia of the mucous membrane increased from 20.3% to 26.7%. Mucosal thickening was observed in 41.7% vs 7.5%. The number of intact sinuses increased to 57.8%. The number of cases with local membrane hypertrophia also increased - to 37.4%. The number of cases with mucosal thickening or fluid accumulation decreased significantly to 11.8 and 5.3% respectively. In 2 cases the development of chronic sinusitis required secondary surgeries. &lt;br&gt;&lt;b&gt;Conclusion:&lt;/b&gt; The present retrospective study revealed that minor radiological changes in the morphology of the maxillary sinus mucosa were observed preoperatively in 17.1% of patients who underwent LSFA procedures. In the early and late postoperative period their frequency increased to 68.5% and 47.1%, respectively. However, the clinical signs of sinusitis developed only in 19.26% of patients. No significant correlations were found between the frequency and severity of postoperative radiological changes and residual bone height, sinus anatomy, initial state of the mucous membrane and type of the grafting material.

Use of PELC/CpG Adjuvant for Intranasal Immunization with Recombinant Hemagglutinin to Develop H7N9 Mucosal Vaccine.

Human infections with H7N9 avian influenza A virus can result in severe diseases with high mortality. Developing an effective vaccine is urgently needed to prevent its pandemic potential. Vaccine delivery routes via mucosal surfaces are known to elicit mucosal immune responses such as secretory IgA antibodies in mucosal fluids, thus providing first-line protection at infection sites. PEG-b-PLACL (PELC) is a squalene-based oil-in-water emulsion adjuvant system that can enhance antigen penetration and uptake in nasal mucosal layers with enhanced mucin interactions. In this study, intranasal immunizations with recombinant H7 (rH7) proteins with a PELC/CpG adjuvant, as compared to the use of poly (I:C) or bacterial flagellin adjuvant, elicited higher titers of H7-specific IgG, IgA, hemagglutination inhibition, and neutralizing antibodies in sera, and increased numbers of H7-specific IgG- and IgA-antibody secreting cells in the spleen. Both PELC/CpG and poly (I:C) adjuvants at a dose as low as 5 μg HA provided an 80% survival rate against live virus challenges, but a lower degree of PELC/CpG-induced Th17 responses was observed. Therefore, the mucosal delivery of rH7 proteins formulated in a PELC/CpG adjuvant can be used for H7N9 mucosal vaccine development.

Plasma concentration of injectable contraceptive correlates with reduced cervicovaginal growth factor expression in South African women.

Long-acting injectable contraceptives have been associated with mucosal immune changes and increased HIV acquisition, but studies have often been hampered by the inaccuracy of self-reported data, unknown timing of injection, and interactions with mucosal transmission co-factors. We used mass spectrometry to quantify the plasma concentrations of injectable contraceptives in women from the CAPRISA004 study (n = 664), with parallel quantification of 48 cytokines and >500 host proteins in cervicovaginal lavage. Higher DMPA levels were associated with reduced CVL concentrations of GCSF, MCSF, IL-16, CTACK, LIF, IL-1α, and SCGF-β in adjusted linear mixed models. Dose-dependent relationships between DMPA concentration and genital cytokines were frequently observed. Unsupervised clustering of host proteins by DMPA concentration suggest that women with low DMPA had increases in proteins associated with mucosal fluid function, growth factors, and keratinization. Although DMPA was not broadly pro-inflammatory, DMPA was associated with increased IP-10 in HSV-2 seropositive and older women. DMPA-cytokine associations frequently differed by vaginal microbiome; in non-Lactobacillus-dominant women, DMPA was associated with elevated IL-8, MCP-1, and IP-10 concentrations. These data confirm a direct, concentration-dependant effect of DMPA on functionally important immune factors within the vaginal compartment. The biological effects of DMPA may vary depending on age, HSV-2 status, and vaginal microbiome composition.

Permeability of Piroxicam with Sodium Lauryl Sulfate as Surfactant

Piroxicam is a nonsteroidal anti-inflammatory drug (NSAID) which have characteristic insoluble in water and poorly fluidity. The profile absorption from piroxicam was depend on its dissolution rate in the gastrointestinal tract (GI). To improve the solubility in the water, it can used Sodium Lauryl Sulfate (SLS) as a surfactant which have mechanism by forming a micelle. The aim of this study was to measure the influence gradiet concentration of SLS with Piroxicam absorption that can observe by inverted intestinal sac method. The concentration of piroxicam solution that added by SLS are 1, 2, and 3% respectively. The preparation method using Crane and Wilson tube containing mucosal fluid. After preparation, it was taken at 37°C in waterbath and added with serosal solution to intestinal sac by turned upside down and tied to a cannula. The sample was placed in the tube containing mucosal fluid and constantly flowing by oxygen gas. To measure the absorsion of piroxicam that used serosal solution which every 15 minutes was taken on tube. After this, it was diluted using Ba(OH)2 and ZnSO4 then continuous with separating process. The absorbant of supernatant was measured using Spectrophotometer UV-Vis. Data analyse was calculated by one-way ANOVA. According to Pm, the values 0.25x10-3 cm/minute (0% SLS), 0.39x10-3 cm/minute (1% SLS), 1.45x10-3 cm/minute (2% SLS) and 1.26x10-3 cm/minute (3% SLS) respectively. In conclusion, 2 % SLS significantly give the highest absorption of piroxicam by altering the membrane permeability.