Modified Killian Method for Flexible Nasopharyngoscopic Observation of the Hypopharynx: A Systematic Review and Meta-Analysis.

OBJECTIVE: Flexible nasopharyngoscopy is a common procedure for evaluating the hypopharynx. The modified Killian method has been reported to enhance visualization during this examination. The aim of this study was to compare the visibility of the hypopharynx using conventional and modified Killian methods. METHODS: A systematic literature search was conducted in PubMed, EMBASE, and the Cochrane Library to identify studies that compared the visibility of the hypopharynx using the 2 methods. Comprehensive meta-analysis software was used to analyze the data. Studies that evaluated the overall hypopharyngeal visibility score and the visibility of the pyriform sinus, postcricoid region, and upper esophageal sphincter were included. RESULTS: Five studies were included in the analysis. The pooled results showed that the modified Killian method significantly improved overall visibility score (SMD=1.09; 95% CI, 0.39-1.80) and complete visibility of the pyriform sinus, postcricoid region, and upper esophageal sphincter (log OR=3.83; 95% CI, 2.30-5.35; log OR=4.20; 95% CI, 3.21-5.19; log OR=3.38; 95% CI, 1.68-5.08). CONCLUSION: The modified Killian method is a valuable technique for improving hypopharyngeal visibility during flexible nasopharyngoscopy. This technique can enhance the detection of potential abnormalities or lesions, leading to better diagnostic accuracy and improved patient outcomes.

A Classification and Prediction Hybrid Model Construction with the IQPSO-SVM Algorithm for Atrial Fibrillation Arrhythmia.

Atrial fibrillation (AF) is the most common cardiovascular disease (CVD), and most existing algorithms are usually designed for the diagnosis (i.e., feature classification) or prediction of AF. Artificial intelligence (AI) algorithms integrate the diagnosis of AF electrocardiogram (ECG) and predict the possibility that AF will occur in the future. In this paper, we utilized the MIT-BIH AF Database (AFDB), which is composed of data from normal people and patients with AF and onset characteristics, and the AFPDB database (i.e., PAF Prediction Challenge Database), which consists of data from patients with Paroxysmal AF (PAF; the records contain the ECG preceding an episode of PAF), and subjects who do not have documented AF. We extracted the respective characteristics of the databases and used them in modeling diagnosis and prediction. In the aspect of model construction, we regarded diagnosis and prediction as two classification problems, adopted the traditional support vector machine (SVM) algorithm, and combined them. The improved quantum particle swarm optimization support vector machine (IQPSO-SVM) algorithm was used to speed the training time. During the verification process, the clinical FZU-FPH database created by Fuzhou University and Fujian Provincial Hospital was used for hybrid model testing. The data were obtained from the Holter monitor of the hospital and encrypted. We proposed an algorithm for transforming the PDF ECG waveform images of hospital examination reports into digital data. For the diagnosis model and prediction model trained using the training set of the AFDB and AFPDB databases, the sensitivity, specificity, and accuracy measures were 99.2% and 99.2%, 99.2% and 93.3%, and 91.7% and 92.5% for the test set of the AFDB and AFPDB databases, respectively. Moreover, the sensitivity, specificity, and accuracy were 94.2%, 79.7%, and 87.0%, respectively, when tested using the FZU-FPH database with 138 samples of the ECG composed of two labels. The composite classification and prediction model using a new water-fall ensemble method had a total accuracy of approximately 91% for the test set of the FZU-FPH database with 80 samples with 120 segments of ECG with three labels.

Stapler closure versus manual closure in total laryngectomy for laryngeal cancer: A systematic review and meta-analysis.

OBJECTIVE: Total laryngectomy (TL) is a life-saving procedure for individuals with advanced laryngeal cancer and those suffering from recurrence after initial treatment. The present study aimed to evaluate the differences between stapler closure (SC) and manual closure (MC) of the pharynx during TL for patients with laryngeal cancer. DESIGN/SETTING: A systematic literature search was performed using the PubMed, EMBASE and Cochrane Library databases. The data were analysed using Comprehensive Meta-Analysis software (Version 3; Biostat). Dichotomous data were calculated as odds ratios (ORs), and continuous data were calculated as mean differences (MD) with 95% confidence intervals (CI). MAIN OUTCOME/RESULTS: A total of seven studies (535 patients) were included in this meta-analysis. Pooled analysis showed that the operative time of TL was significantly reduced in the SC group (MD, -63.2; 95% CI, -106.0 to -20.4). Moreover, the SC group had a lower incidence of pharyngocutaneous fistula (OR = 0.38; 95% CI, 0.18 to 0.83; P = .016) and hospital stay (MD, -2.9; 95% CI, -5.6 to -0.1). The incidence of postoperative surgical site infection (OR = 0.41; 95% CI, 0.02 to 8.73; P = .565) was comparable between the two groups. CONCLUSION: Based on these results, SC may be a useful option for patients who need TL.

Blomia tropicalis-Specific TCR Transgenic Th2 Cells Induce Inducible BALT and Severe Asthma in Mice by an IL-4/IL-13-Dependent Mechanism.

Previous studies have highlighted the importance of lung-draining lymph nodes in the respiratory allergic immune response, whereas the lung parenchymal immune system has been largely neglected. We describe a new in vivo model of respiratory sensitization to Blomia tropicalis, the principal asthma allergen in the tropics, in which the immune response is focused on the lung parenchyma by transfer of Th2 cells from a novel TCR transgenic mouse, specific for the major B. tropicalis allergen Blo t 5, that targets the lung rather than the draining lymph nodes. Transfer of highly polarized transgenic CD4 effector Th2 cells, termed BT-II, followed by repeated inhalation of Blo t 5 expands these cells in the lung >100-fold, and subsequent Blo t 5 challenge induced decreased body temperature, reduction in movement, and a fall in specific lung compliance unseen in conventional mouse asthma models following a physiological allergen challenge. These mice exhibit lung eosinophilia; smooth muscle cell, collagen, and goblet cell hyperplasia; hyper IgE syndrome; mucus plugging; and extensive inducible BALT. In addition, there is a fall in total lung volume and forced expiratory volume at 100 ms. These pathophysiological changes were substantially reduced and, in some cases, completely abolished by administration of neutralizing mAbs specific for IL-4 and IL-13 on weeks 1, 2, and 3. This IL-4/IL-13-dependent inducible BALT model will be useful for investigating the pathophysiological mechanisms that underlie asthma and the development of more effective drugs for treating severe asthma.

Hyper-responsive T-cell cytokine profile in association with development of early childhood wheeze but not eczema at 2 years.

BACKGROUND: Eczema is a known risk factor for the development of wheeze in childhood. Cord blood T-cell cytokine responses have been shown to be associated with the development of both early childhood eczema and wheeze. Our objective is to study and compare the influence of intrinsic T-cell cytokine responses on the development of wheezing and eczema in the first 2 years of life in a birth cohort of at risk (first degree family with atopic disease) infants. METHODS: Cord blood samples were collected from 195 eligible subjects of a birth cohort of 253 subjects. The subjects studied were those who developed either wheezing (n = 34) or eczema (n = 29) in the first 2 years of life, and 65 healthy infants served as control. Cytokines from phytohaemagglutinin stimulated mononuclear cells were analyzed using multiplex cytokine assays and the cytokine profiles in the 3 groups were compared. RESULTS: Most of the subjects were non-atopic with only 3/34 (9%) wheeze and 9/29 (31%) eczema subjects sensitized to the common dietary or inhalant allergens. After adjustment for potential risk factors, wheeze, but not eczema subjects, presented with hyper-responsive cytokine profiles with increased production of T-cell cytokines IL-2 and IL-5. IL-5 was the strongest risk factor associated to the development of wheeze at 2 years of age (OR, 35; 95% CI, 5.0 -246.7). CONCLUSION: Cord blood cytokine responses in early onset wheeze and eczema are distinctly different. This suggests that the tendency to develop early onset wheeze may be influenced by preexisting immune factors independent to those for eczema.

Airway inflammation and IgE production induced by dust mite allergen-specific memory/effector Th2 cell line can be effectively attenuated by IL-35.

CD4(+) memory/effector T cells play a central role in orchestrating the rapid and robust immune responses upon re-encounter with specific Ags. However, the immunologic mechanism(s) underlying these responses are still not fully understood. To investigate this, we generated an allergen (major house dust mite allergen, Blo t 5)-specific murine Th2 cell line that secreted IL-4, IL-5, IL-10, and IL-13, but not IL-9 or TNF-α, upon activation by the cognate Ag. These cells also exhibited CD44(high)CD62L(-) and CD127(+) (IL-7Rα(+)) phenotypes, which are characteristics of memory/effector T cells. Experiments involving adoptive transfer of this Th2 cell line in mice, followed by three intranasal challenges with Blo t 5, induced a dexamethasone-sensitive eosinophilic airway inflammation. This was accompanied by elevation of Th2 cytokines and CC- and CXC-motif chemokines, as well as recruitment of lymphocytes and polymorphic mononuclear cells into the lungs. Moreover, Blo t 5-specific IgE was detected 4 d after the last intranasal challenge, whereas elevation of Blo t 5-specific IgG1 was found at week two. Finally, pulmonary delivery of the pVAX-IL-35 DNA construct effectively downregulated Blo t 5-specific allergic airway inflammation, and i.m. injection of pVAX-IL-35 led to long-lasting suppression of circulating Blo t 5-specific and total IgE. This model provides a robust research tool to elucidate the immunopathogenic role of memory/effector Th2 cells in allergic airway inflammation. Our results suggested that IL-35 could be a potential therapeutic target for allergic asthma through its attenuating effects on allergen-specific CD4(+) memory/effector Th2 cell-mediated airway inflammation.

Characterization of an immunomodulatory Der p 2-FIP-fve fusion protein produced in transformed rice suspension cell culture.

Der p 2, a major allergen of Dermatophagoides pteronyssinus mites, is one of the most clinically relevant allergens to allergic patients worldwide. FIP-fve protein (Fve) from the golden needle mushroom (Flammulina velutipes) is an immunomodulatory protein with potential Th1-skewed adjuvant properties. Here, we produced and immunologically evaluated a Der p 2-Fve fusion protein as a potential immunotherapeutic for allergic diseases. Using an inducible expression system in cultured rice suspension cells, the recombinant Der p 2-Fve fusion protein (designated as OsDp2Fve) was expressed in rice cells under the control of an α-amylase gene (αAmy8) promoter and secreted under sucrose starvation. OsDp2Fve was partially purified from the cultured medium. The conformation of Der p 2 in OsDp2Fve remains intact as reflected by its unaltered allergenicity, as assessed by human IgE ELISA and histamine release assays, compared to non-fusion Der p 2 protein. Furthermore, the Fve protein expressed in OsDp2Fve retains its in vitro lymphoproliferative activity but loses its hemagglutination and lymphoagglutination effects compared to the native protein. Notably, in vivo evaluation showed that mice administered with OsDp2Fve possessed an enhanced production of Der p 2-specific IgG antibodies without potentiating the production of Der p 2-specific IgE and Th2 effector cytokines in comparison with mice co-administered with native Fve and Der p 2 proteins. These results suggest that the recombinant Der p 2-Fve fusion protein produced in rice suspension cell cultures has a great potential for allergy immunotherapy.

The effects of emotional films and subtitle types on eye movement patterns.

BACKGROUND: In Taiwan, the use of subtitle is common in TV programs and movies. However, studies on subtitles mostly focus on foreign language learning and film subtitle translation. Few studies address how subtitle types and emotion-laden films affect the viewers' eye movement patterns. PURPOSE: We aim to examine how the emotion type of film (happy, sad, angry, fear, or neutral) and subtitle type (meaningful subtitle, no subtitle, or meaningless subtitle) affect the dwell times and fixation counts in the subtitle area. METHODS: This study is a 5 (emotion type of film) × 3 (subtitle type) between-participants design. There were 15 participants per condition, resulting in a total of 225 participants. After watching a film, participants filled out a self-reported questionnaire regarding this film. RESULTS: The subtitled films have more fixation counts and dwell time for the meaningful subtitle compared to meaningless subtitle and no subtitle. The dwell time was longer on the subtitle area for the sad film than the neutral and happy films. Also, the dwell time was longer on the subtitle area for the fear film than the happy film. There were more fixation counts on the subtitle area for the sad film than the angry and happy films. CONCLUSIONS: The subtitle meaning is critical in directing overt attention. Also, overt attention directed to the subtitle area is affected by the different emotion types of films.

Prediction of Epiglottic Collapse in Obstructive Sleep Apnea Patients: Epiglottic Length.

OBJECTIVE: This study aims to explore the factors that contribute to epiglottic collapse (EC) in patients with obstructive sleep apnea (OSA). METHODS: This study enrolled 35 patients (34 males; median age, 39 years; median apnea-hypopnea index (AHI), 55.4 events/h; median body mass index (BMI), 26.9 kg/m2). EC (epiglottis attaching onto the posterior pharyngeal wall) was diagnosed by drug-induced sleep computed tomography (DI-SCT). Three dimensions were assessed for comparison between the EC and non-EC (NEC) groups that included anatomical measurement: epiglottic length and angle, endoscopic classification of epiglottis obstructing the glottis (Type I, none; Type II, partial; and Type III, total), and dynamic hyoid movement during DI-SCT (Δ hyoid = √(x2 + y2), maximal displacement of hyoid in x and y axes during sleep breathing cycle). RESULTS: EC was found in 12 patients (34%). No difference in age, gender, AHI, and BMI between the two groups was noted. The anatomical measurement revealed that epiglottis length was significantly different between the EC and NEC groups (21.2 vs 15.8 mm; p < 0.001), with a cutoff value of 16.6 mm (sensitivity, 100%; specificity, 65.2%). The EC group patients showed larger hyoid movement than the NEC group patients (Δ hyoid, 4.8 vs 3.0 mm; p = 0.027). By contrast, epiglottic angle and endoscopic classification revealed an insignificant difference between the two groups. CONCLUSION: Epiglottis is a potential collapse site among multilevel obstruction in moderate to severe OSA patients. Epiglottic length is highly sensitive in predicting EC, with the cutoff value of 16.6 mm. Hyoid movement plays a role in contributing to EC in OSA patients.

Quantitative Evaluation of Subglottic Stenosis Using Ultrashort Echo Time MRI in a Rabbit Model.

OBJECTIVE/HYPOTHESIS: To assess the ability of ultra-short echo time (UTE)-MRI to detect subglottic stenosis (SGS) and evaluate response to balloon dilation. To correlate measurements from UTE-MRI with endotracheal-tube (ETT)-sizing and to investigate whether SGS causes change in airway dynamics. STUDY DESIGN: Animal research study. METHODS: Eight adult New-Zealand white rabbits were used as they approximate neonatal airway-size. The airways were measured using ETT-sizing and 3D UTE-MRI at baseline, 2 weeks post-cauterization induced SGS injury, and post-balloon dilation treatment. UTE-MR images were acquired to determine airway anatomy and motion. Airways were segmented from MR images. Cross-sectional area (CSA), major and minor diameters (Dmajor and Dminor ), and eccentricity were measured. RESULTS: Post-injury CSA at SGS was significantly reduced (mean 38%) compared to baseline (P = .003) using UTE-MRI. ETT-sizing correlated significantly with MRI-measured CSA at the SGS location (r = 0.6; P < .01), particularly at the post-injury timepoint (r = 0.93; P < .01). Outer diameter from ETT-sizing (OD) correlated significantly with Dmajor (r = 0.63; P < .01) from UTE-MRI at the SGS location, especially for the post-injury timepoint (r = 0.91; P < .01). Mean CSA of upper trachea did not change significantly between end-expiration and end-inspiration at any timepoint (all P > .05). Eccentricity of the upper trachea increased significantly post-balloon dilation (P < .05). CONCLUSIONS: UTE-MRI successfully detected SGS and treatment response in the rabbit model, with good correlation to ETT-sizing. Balloon dilation increased CSA at SGS, but not to baseline values. SGS did not alter dynamic motion for the trachea in this rabbit model; however, tracheas were significantly eccentric post-balloon dilation. UTE-MRI can detect SGS without sedation or ionizing radiation and may be a non-invasive alternative to ETT-sizing. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E1971-E1979, 2021.

Effects of personal exposure to particulate matter and ozone on arterial stiffness and heart rate variability in healthy adults.

The effects on heart rate variability (HRV) and arterial stiffness from exposure to ambient particulate matter and ozone have not been studied simultaneously. The aim of this study was to analyze these effects with refined exposure estimates from personal measurements of ozone and size-resolved particulate matter mass concentrations. The authors recruited 17 mail carriers in a panel study in Taipei County, Taiwan, during February-March, 2007, and each subject was followed for 5-6 days. Personal ozone and size-fractionated particulate matter exposures were monitored during working hours while carriers delivered mail outdoors. Cardiovascular effects were evaluated with heart rate variability (HRV) indices and an arterial stiffness index, the cardio-ankle vascular index (CAVI). The authors used linear mixed models to examine the association between personal exposure data and the HRV index and CAVI. They found that an interquartile range increase in personal exposure to ozone and particulate matter of between 1.0 and 2.5 microm was associated with a 4.8% and 2.5% increase in CAVI, respectively, in the single-pollutant models. In contrast, the personal exposure data showed no significant effects on HRV. In 2-pollutant models, personal ozone exposure remained significantly associated with the CAVI measurements. The study results indicate that vascular function may be more sensitive to air pollutants than the autonomic balance.

Roles of structure and structural dynamics in the antibody recognition of the allergen proteins: an NMR study on Blomia tropicalis major allergen.

Blo t 5 is the major allergen from Blomia tropicalis mites and shows strong IgE reactivity with up to 90% of asthmatic and rhinitis patients' sera. The NMR solution structure of Blo t 5 comprises three long alpha helices, forming a coiled-coil, triple-helical bundle with a left-handed twist. TROSY-NMR experiments were used to study Blo t 5 interaction with the Fab' of a specific monoclonal antibody, mAb 4A7. The mAb epitope comprises two closely spaced surfaces, I and II, connected by a sharp turn and bearing critical residues Asn46 and Lys47 on one surface, and Lys54 and Arg57 on the other. This discontinuous epitope overlaps with the human IgE epitope(s) of Blo t 5. Epitope surface II is further predicted to undergo conformational exchange in the millisecond to microsecond range. The results presented are critical for the design of a hypoallergenic Blo t 5 for efficacious immunotherapy of allergic diseases.

Surgical Management of Anterior Glottic Webs.

Congenital webs are rare and represent <5% of all congenital laryngeal anomalies. They are usually a partial laryngeal atresia rather than a true web, and present as a thick and fibrotic web with subglottic extension and associated subglottic stenosis. All patients with a congenital anterior glottic web should be evaluated for chromosome 22q11.2 deletion syndrome. Management strategies are mainly based on the severity of airway obstruction and the anatomical extension of the webs. Simple division of the web endoscopically may be adequate for rare thin webs, however, an open approach is usually warranted for thick glottic webs regardless of Cohen grades. Open repair can be either with keel placement or reconstruction of the anterior commissure.

Coadministration of the fungal immunomodulatory protein FIP-Fve and a tumour-associated antigen enhanced antitumour immunity.

Fve is a fungal protein isolated from the golden needle mushroom Flammulina velutipes and has previously been reported to trigger immunological responses in both mouse and human lymphocytes. In this study, we evaluated the potential application of Fve as an adjuvant for tumour immunotherapy and examined the underlying mechanism(s). When the human papillomavirus (HPV)-16 E7 oncoprotein was used as a model antigen, mice coimmunized with HPV-16 E7 and Fve showed enhanced production of HPV-16 E7-specific antibodies as well as expansion of HPV-16 E7-specific interferon (IFN)-gamma-producing CD4(+) and CD8(+) T cells as compared with mice immunized with HPV-16 E7 alone. Tumour protection assays showed that 60% of mice coimmunized with HPV-16 E7 plus Fve, as compared with 20% of those immunized only with HPV-16 E7, remained tumour-free for up to 167 days after challenge with the tumour cells. Tumour therapeutic assays showed that HPV-16 E7 plus Fve treatment significantly prolonged the survival of tumour-bearing mice as compared with those treated only with HPV-16 E7. In vivo cell depletion and adoptive T-cell transfer assays showed that CD4(+) and CD8(+) T cells and IFN-gamma played critical roles in conferring the antitumour effects. Interestingly, Fve could stimulate the maturation of splenic dendritic cells in vivo and induce antigen-specific CD8(+) T-cell immune responses. In summary, Fve has potent adjuvant properties that enhance T helper type 1 antigen-specific humoral and cellular immune responses which confer strong antitumour effects. The use of Fve as an adjuvant could be an attractive alternative to the current vaccination strategy for cancer immunotherapy.

G-quadruplex stabilizer 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide induces accelerated senescence and inhibits tumorigenic properties in cancer cells.

Carbazole derivatives that stabilized G-quadruplex DNA structure formed by human telomeric sequence have been designed and synthesized. Among them, 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC) showed an increase in G-quadruplex melting temperature by 13 degrees C and has a potent inhibitory effect on telomerase activity. Treatment of H1299 cancer cells with 0.5 mumol/L BMVC did not cause acute toxicity and affect DNA replication; however, the BMVC-treated cells ceased to divide after a lag period. Hallmarks of senescence, including morphologic changes, detection of senescence-associated beta-galactosidase activity, and decreased bromodeoxyuridine incorporation, were detected in BMVC-treated cancer cells. The BMVC-induced senescence phenotype is accompanied by progressive telomere shortening and detection of the DNA damage foci, indicating that BMVC caused telomere uncapping after long-term treatments. Unlike other telomerase inhibitors, the BMVC-treated cancer cells showed a fast telomere shortening rate and a lag period of growth before entering senescence. Interestingly, BMVC also suppressed the tumor-related properties of cancer cells, including cell migration, colony-forming ability, and anchorage-independent growth, indicating that the cellular effects of BMVC were not limited to telomeres. Consistent with the observations from cellular experiments, the tumorigenic potential of cancer cells was also reduced in mouse xenografts after BMVC treatments. Thus, BMVC repressed tumor progression through both telomere-dependent and telomere-independent pathways.

Drug-Induced Sleep Computed Tomography-Directed Upper Airway Surgery for Obstructive Sleep Apnea: A Pilot Study.

OBJECTIVE: A surgical response to upper airway (UA) surgery for obstructive sleep apnea (OSA) depends on adequate correction of collapsible sites in the UA. This pilot study aimed to examine the surgical response to UA surgery directed by drug-induced sleep computed tomography (DI-SCT) for OSA. STUDY DESIGN: Prospective case series. SETTING: Tertiary referral center. SUBJECTS AND METHODS: This study recruited 29 OSA patients (median age, 41 years; median body mass index, 26.9 kg/m2) who underwent single-stage DI-SCT-directed UA surgery between October 2012 and September 2014. DI-SCT was performed with propofol for light sedation with a bispectral monitor before and after UA surgery. Nonresponders were defined as those with a reduction in apnea-hypopnea index <50% after 6 months following UA surgery. RESULTS: DI-SCT showed that 28 (97%) patients had collapses at multiple sites, all of whom underwent multilevel UA surgery accordingly. The apnea-hypopnea index decreased from 53.6 to 26.8 ( P < .001). There were 18 (62%) nonresponders and 11 (38%) responders. Multiple-site collapses could not predict surgical response ( P > .99). The nonresponders had significant improvements in velopharyngeal, oropharyngeal lateral wall, and tongue collapses (all P < .05), whereas the responders had significant improvements in velopharyngeal and oropharyngeal lateral wall collapses (both P ≤ .05). CONCLUSION: Despite multilevel OSA surgery, residual UA obstruction in nonresponders likely occurs due to multiple mechanisms. DI-SCT may help to elucidate the reasons for a nonresponse.

Parapharyngeal fat pad area at the subglosso-supraglottic level is associated with corresponding lateral wall collapse and apnea-hypopnea index in patients with obstructive sleep apnea: a pilot study.

The aim of this study was to assess associations between fat pad areas at various anatomic levels and the sites of lateral wall collapse and disease severity in adult patients with obstructive sleep apnea (OSA). Forty-one patients with OSA who prospectively underwent drug-induced sleep computed tomography were included. Areas of parapharyngeal fat pads and degrees of lateral wall collapse at three representative anatomic levels (nasopharynx, oropharynx, and subglosso-supraglottis), and apnea-hypopnea index (AHI) were measured. In the subglosso-supraglottic region, the parapharyngeal fat pad area in 17 (41%) patients with complete lateral wall collapse was significantly larger than that in 24 (59%) patients without complete collapse (median, 236.0 mm2 vs 153.0 mm2; P = 0.02). In multivariate regression analysis, the parapharyngeal fat pad area at the subglosso-supraglottic level (ß = 0.02; P = 0.01) and body mass index (ß = 3.24; P = 0.01) were independently associated with AHI. Our preliminary results supported that parapharyngeal fat pads at the subglosso-supraglottic level may be involved in the development of lateral wall collapse and then determine the severity of OSA. Further studies are warranted to investigate the effect of reducing parapharyngeal fat pads in the treatment of OSA.

The modulatory effects of lipopolysaccharide-stimulated B cells on differential T-cell polarization.

Lipopolysaccharide (LPS) is a major component of environmental microbial products. Studies have defined the LPS dose as a critical determining factor in driving differential T-cell polarization but the direct effects of LPS on individual antigen-presenting cells is unknown. Here, we investigated the effects of LPS doses on naive B cells and the subsequent modulatory effects of these LPS-activated B cells on T-cell polarization. The LPS was able to induce a proliferative response starting at a dose of 100 ng/ml and was capable of enhancing antigen internalization at a dose of 1 microg/ml in naive B cells. Following LPS stimulation, up-regulation of the surface markers CD40, CD86, I-Ad, immunoglobulin M, CD54 and interleukin-10 production, accompanied by down-regulation of CD5 and CD184 (CXCR4) were observed in a LPS dose-dependent manner. Low doses (<10 ng/ml) of LPS-activated B cells drove T helper type 2 polarization whereas high doses (>0.1 microg/ml) of LPS-activated B cells resulted in T regulatory type 1 cell polarization. In conclusion, LPS-activated B cells acquire differential modulatory effects on T-cell polarization. Such modulatory effects of B cells are dependent on the stimulation with LPS in a dose-dependent manner. These observations may provide one of the mechanistic explanations for the influence of environmental microbes on the development of allergic diseases.

Comparison of microbiota and allergen profile in house dust from homes of allergic and non-allergic subjects- results from the GUSTO study.

BACKGROUND: The prevalence of allergic diseases, such as asthma, allergic rhinitis, eczema and food allergy, has been increasing worldwide, as shown in a large number of studies, including the International Study of Asthma and Allergies in Childhood (ISAAC). However, there is significant variation in the prevalence of these diseases in different regions, suggesting that there may be location-specific factors such as environment and microbial exposure affecting allergic disease prevalence. Hence, in this study we determine if there is a difference in microbiota composition and allergen concentration of household dust collected from the homes of non-allergic and allergic subjects from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort. METHODS: From the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort, 25 allergic subjects and 25 non-allergic subjects were selected at the year 5.5 follow up. Definitions of allergic outcomes were standardized in the questionnaires administered at 3, 6, 9, 12, 15, 18, 24, 36, 48 and 60 months to ensure consistency during interviews and home visits. Allergen sensitization was determined by skin prick testing (SPT) at 18, 36 and 60 months. Dust samples were collected from the subject's bed, sofa, and play area. DNA extraction was carried out and V3-V4 hypervariable regions of bacterial 16S rRNA gene were sequenced. Protein extraction was performed and allergens assayed by using multiplex assay and ELISA. RESULTS: The most abundant phyla in house dust were Actinobacteria (29.8%), Firmicutes (27.7%), and Proteobacteria (22.4%). Although there were no differences in bacteria abundance and diversity between house dust samples of allergic and non-allergic subjects, the relative abundance of Anaplasmataceae, Bacteroidaceae, and Leptospiraceae were significantly higher in dust samples of allergic subjects as compared to non-allergic subjects in 2 or more locations. The concentration of Der p 1 was significantly lower in bed dust samples of allergic subjects (Median [Interquartile range], 174 ng/g [115-299 ng/g]) as compared to non-allergic subjects (309 ng/g [201-400 ng/g]; P < 0.05). The concentration of tropomyosin was significantly higher in sofa dust samples of allergic subjects (175 ng/g [145-284 ng/g] as compared to non-allergic subjects (116 ng/g [52.8-170 ng/g]; P < 0.05). CONCLUSION: In conclusion, we found a differential microbiota and allergen profile between homes of allergic and non-allergic subjects. TRIAL REGISTRATION: NCT01174875 Registered 1 July 2010, retrospectively registered.

The Blomia tropicalis allergens.

Blomia tropicalis allergens are the most important mite allergens in tropical regions. Most of them only have 30-40% sequence identity with their Dermatophagoides counterparts and they share low IgE cross reactivity and exhibit different immunobiology. Unlike the pyroglyphid counterparts, Blo t 5 is the major allergen whereas Blo t 1 only has modest allergenicity.