Lactobacillus acidophilus and propionate attenuate Sjögren's syndrome by modulating the STIM1-STING signaling pathway.

BACKGROUND: Sjögren's syndrome (SS) is an autoimmune disease characterized by inflammation of the exocrine gland. An imbalance of gut microbiota has been linked to SS. However, the molecular mechanism is unclear. We investigated the effects of Lactobacillus acidophilus (L. acidophilus) and propionate on the development and progression of SS in mouse model. METHODS: We compared the gut microbiomes of young and old mice. We administered L. acidophilus and propionate up to 24 weeks. The saliva flow rate and the histopathology of the salivary glands were investigated, and the effects of propionate on the STIM1-STING signaling pathway were evaluated in vitro. RESULTS: Lactobacillaceae and Lactobacillus were decreased in aged mice. SS symptoms were ameliorated by L. acidophilus. The abundance of propionate-producing bacterial was increased by L. acidophilus. Propionate ameliorated the development and progression of SS by inhibiting the STIM1-STING signaling pathway. CONCLUSIONS: The findings suggest that Lactobacillus acidophilus and propionate have therapeutic potential for SS. Video Abstract.

Effect of IL-10-producing B cells in peripheral blood and tumor tissue on gastric cancer.

BACKGROUND: Interleukin (IL)-10-producing B (B10) cells are generated in response to signals from the tumor microenvironment and promote tumor growth by interacting with B10 cells. We investigated the distributions of immune cells in peripheral blood and tumor tissue samples from patients with gastric cancer (GC). METHODS: Patients with GC who underwent radical gastrectomy in Seoul St. Mary's Hospital between August 2020 and May 2021 were enrolled in this study. Forty-two samples of peripheral blood were collected, and a pair of gastric mucosal samples (normal and cancerous mucosa; did not influence tumor diagnosis or staging) was collected from each patient after surgery. B10 cells in peripheral blood and cancer mucosa samples were investigated by flow cytometry and immunofluorescence. AGS cells, gastric cancer cell line, were cultured with IL-10 and measured cell death and cytokine secretion. Also, AGS cells were co-cultured with CD19 + B cells and measured cytokine secretion. RESULTS: The population of B10 cells was significantly larger in the blood of patients with GC compared with controls. In confocal images of gastric mucosal tissues, cancerous mucosa contained more B10 cells than normal mucosa. The population of B10 cells in cancerous mucosa increased with cancer stage. When AGS cells were cultured under cell-death conditions, cellular necrosis was significantly decreased, and proliferation was increased, for 1 day after IL-10 stimulation. Tumor necrosis factor (TNF)-α, IL-8, IL-1ß, and vascular endothelial growth factor secretion by cancer cells was significantly increased by coculture of AGS cells with GC-derived CD19+ B cells. CONCLUSIONS: B cells may be one of the populations that promote carcinogenesis by inducing the production of inflammatory mediators, such as IL-10, in GC. Targeting B10 cells activity could improve the outcomes of antitumor immunotherapy. Video Abstract.

Risk of uveitis in patients with psoriasis in Korea: A nationwide population-based cohort study.

BACKGROUND: Evidence for the association between psoriasis and uveitis according to the severity of psoriasis including psoriatic arthritis (PsA) and type of uveitis is lacking, and there are no data on the frequency or timing of recurrence of uveitis in patients with psoriasis. OBJECTIVES: We aimed to evaluate the risk of first occurrence and recurrence of uveitis in patients with psoriasis in the Korean population. We further evaluated the risk of uveitis according to the severity of psoriasis, comorbidity of PsA and location of uveitis. METHODS: In a nationwide retrospective cohort study, we compared 317,940 adult patients who had psoriasis with 635,880 matched controls. Incidence rates (IRs) and estimated IR ratios of the first occurrence and recurrence of uveitis were calculated using survival analysis and Poisson regression, respectively. RESULTS: The rate of uveitis incidence and uveitis recurrence in patients with psoriasis was 1.18 and 2.31 per 1000 person-years, respectively. Compared to the controls, the IR ratios of development and recurrence of uveitis in patients with psoriasis were 1.14 (95% CI 1.08, 1.2) and 1.16 (95% CI 1.12, 1.21), respectively. The recurrence rate of uveitis was highest within 3 years after the onset of psoriasis. The corresponding IR ratios for uveitis recurrence in patients with mild psoriasis, severe psoriasis and PsA were 1.11 (1.06, 1.16), 1.24 (1.16, 1.33) and 1.49 (1.31, 1.7), respectively. Patients with psoriasis had an increased risk of recurrence of anterior uveitis, and patients with both psoriasis and PsA had an increased risk of recurrence of both anterior-uveitis and panuveitis. CONCLUSIONS: Patients with psoriasis had a higher risk of both development and recurrence of uveitis, especially with severe psoriasis and PsA. The timing of uveitis recurrence was related to the onset of psoriasis, and patients who had psoriasis with PsA had an increased risk of vision-threatening panuveitis.

An Anatomic Analysis of the Bony Vault: From the Perspective of Osteotomy in Rhinoplasty.

BACKGROUND: Osteotomy is one of the most traumatic but critical procedures in rhinoplasty. A detailed preoperative analysis of the bony vault is essential to performing a successful osteotomy. OBJECTIVES: This study aimed to analyze bone thickness along the osteotomy path in primary rhinoplasty patients. METHODS: Preoperative 3-dimensional facial bone computed tomography images of 250 patients who underwent primary rhinoplasty were analyzed, and their bony vaults categorized based on symmetry. The bone thickness was measured at 3 points along the lateral and at 2 points along the medial and intermediate osteotomy paths. RESULTS: Of the 250 patients analyzed, 88 (35.2%) had asymmetric and 162 (64.8%) had symmetric bony vaults. The mean thickness of the bony vault was thickest at the middle level of the lateral osteotomy path, and the bony vault was thicker in male patients at all points of medial and lateral osteotomies. Furthermore, in the asymmetric bony vault, the deviated side was thicker than the contralateral side along all osteotomy paths. In particular, the deviated side was thicker, and the contralateral side was thinner, in the asymmetric bony vault than in the symmetric bony vault at the middle level of the lateral osteotomy path. CONCLUSIONS: The thickness of the bony vault differs according to osteotomy path and gender. The lateral osteotomy, especially at the midpoint of the deviated side in male patients, is crucial in achieving a more controlled fracture.

Ideal Reference Lines for Assessment of Facial Asymmetry in Rhinoplasty Patients.

BACKGROUND: Assessing facial asymmetry is important to prevent unsatisfactory results in rhinoplasty. There has yet to be a consensus on reference lines for determining asymmetry. This study aimed to determine ideal reference lines to assess facial asymmetry and identify predictors of subjective perceptions of facial asymmetry. METHODS: Preoperative photographs of 47 patients who underwent rhinoplasty were adjusted according to two reference lines (vertical line from the mid-glabella to Cupid's bow and horizontal interpupillary line). In total, 94 photographs were generated, randomly ordered, and evaluated by two independent observers for anthropometric measurements including six distances (distances from the midline to the medial and lateral canthi, ala, oral commissure, width of midface at maximum distance, and mandible width) and three angles (lateral canthal, lateral alar, and lip margin angles). Photographs were rated by 18 independent observers for subjective perceptions of facial asymmetry. RESULTS: Observers perceived faces as asymmetric if accompanied by nasal deviation, irrespective of the reference line (p < 0.001). Based on the horizontal reference line, subjective perceptions of asymmetry were correlated with the midline to lateral alar margin distance (r = 0.489, p = 0.003) and sum of the distance ratios (r = 0.354, p = 0.037). None of the objective parameters correlated with subjective perceptions when adopting the vertical reference line. A deviated nose and lateral alar angle were significant predictors of subjective perceptions of facial asymmetry. CONCLUSION: To assess facial asymmetry, the horizontal reference line should be determined first followed by the perpendicular vertical line. The nose is the most important feature determining overall facial asymmetry. LEVEL OF EVIDENCE V: "This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ."

Impact of allergic rhinitis on quality of life after powered intracapsular tonsillectomy and adenoidectomy.

BACKGROUND: Allergic rhinitis (AR) has been reported to worsen quality of life (QoL) after adenotonsillectomy. Although powered intracapsular tonsillectomy and adenoidectomy (PITA) has been widely performed, it is not clear whether comorbid AR may worsen QoL in patients who undergo PITA. PURPOSE: To evaluate QoL after PITA in relation to AR. METHODS: Children undergoing PITA for sleep-disordered breathing were enrolled and divided into AR and non-AR groups. QoL was evaluated using serial applications of the Obstructive Sleep Apnea-18 (OSA-18) questionnaire and compared between the two groups. RESULTS: Of 151 enrolled patients, 73 were categorized into the AR and 78 into non-AR groups. After surgery, patients exhibited marked improvement in OSA-18 scores in both groups, with similar results at each follow-up. The degree of improvement in OSA-18 scores was less in the AR group 3 months after surgery; however, this difference was not significant 6 months after surgery. CONCLUSIONS: Although comorbid AR may initially appear to impede improvement in QoL after PITA, QoL was improved similarly 6 months after PITA, irrespective of AR status. In children with comorbid AR, PITA could be safely performed to treat sleep-disordered breathing without concerns regarding worsening of QoL.

Does the Supine Position Affect the Nasal Profile in Rhinoplasty Patients? A Comparison of Nasal Anthropometric Measurements in Different Body Positions.

BACKGROUND: Rhinoplasty surgeons are aware that the nasal profile differs according to body position, namely, the erect position in the consultation room vs the supine position on the operating table. It is not clear whether this difference is caused by an optical illusion or skin laxity due to positional change. OBJECTIVES: To evaluate anthropometric measurements of the nose with different body positions and determine whether the supine position affects the nasal profile. METHODS: In this retrospective study, 103 patients who underwent primary rhinoplasty were enrolled. Preoperatively, all patients underwent lateral cephalography in the erect position, and facial computed tomography (CT), in the supine position. We measured four nasal anthropometric parameters (the nasofrontal, nasolabial, and nasomental angles, and Simon's ratio) on lateral cephalograms and facial CT images, and compared these parameters between the two body positions. RESULTS: The nasofrontal angle was greater on facial CT than on cephalograms (P < 0.01). This difference was not related to age, sex, or body mass index (P > 0.05 each). We found no significant difference (P > 0.05) between the two positions in the nasolabial angle, nasomental angle, or Simon's ratio. CONCLUSIONS: The supine position does affect the nasal profile, especially in the radix area. Surgeons need to consider this difference in patients undergoing rhinoplasty. LEVEL OF EVIDENCE: 2.

Stereoselective Chirality Extension of syn,anti- and syn,syn-Oxazine and Stereochemical Analysis of Chiral 1,3-Oxazines: Stereoselective Total Syntheses of (+)-1-Deoxygalactonojirimycin and (-)-1-Deoxygulonojirimycin.

This paper describes the stereoselective total syntheses of (+)-1-deoxygalactonojirimycin and (-)-1-deoxygulonojirimycin via new chiral building blocks syn,anti,syn-oxazine 11a and syn,syn,anti-oxazine 13a. These were accomplished in four steps in 44.1 and 33.7% overall yields, respectively. These chirons were derived from the stereoselective addition of a nucleophile to the corresponding aldehydes of syn,anti-oxazine 10 and syn,syn-oxazine 12. Furthermore, this paper describes the stereochemical analysis of three types of chiral 1,3-oxazines; anti,syn-, syn,anti-, and syn,syn-oxazines using the NOESY technique.

Objective Parameters for Evaluating Internal Nasal Valve Compromise: Beyond the Angle Perspective.

Objectives: Since nasal valve surgery for internal nasal valve (INV) compromise has gained popularity, controversies over its indications and insurance coverage disputes have emerged due to the absence of a gold-standard evaluation. Therefore, we aimed to identify the objective parameters for the INV compromise. Methods: We analyzed 186 INVs in 93 patients who underwent nasal valve surgery. The data included facial computed tomography images, acoustic rhinometry, modified Cottle test, and symptom scores. The patients were categorized based on their symptoms and modified Cottle's test results. We measured the INV angle, area, volume, lateral wall thickness, septal angle, and nasal bone area using computed tomography (CT). Results: The compromised INV group (nasal obstruction with a positive modified Cottle test) was characterized by smaller INV areas on both the coronal and axial views, smaller INV volume on the axial view, and thinner lateral wall on the coronal view (all P < 0.05). Acoustic rhinometry revealed a smaller minimal cross-sectional area and volume in the compromised INV group (both P < .001). Regression analysis revealed significant associations between a compromised INV and the INV area on the axial view and the minimal cross-sectional area on acoustic rhinometry. Conclusion: Relying solely on the INV angle in CT scans has limitations in assessing compromised INV. Instead, the INV area on axial CT scans and the minimal crosssectional area on acoustic rhinometry hold potential as objective parameters for evaluating INV compromise.

Automated mass screening and association rules analysis for comorbidities of psoriasis: A population-based case-control study.

Patients with psoriasis frequently have comorbidities, which are linked to higher mortality rates. An in-depth investigation of comorbidities and their effects on health can help improve the management of patients with psoriasis. We conducted a comprehensive and unbiased investigation of comorbidities in patients with psoriasis and explored the pattern of association between comorbidities. A nationwide population-based study included 384 914 patients with psoriasis and 384 914 matched controls between 2011 and 2021. We used automated mass screening of all diagnostic codes to identify psoriasis-associated comorbidities and applied association rule analysis to explore the patterns of comorbidity associations in patients with psoriasis. Patients with psoriasis had an increased risk of autoimmunity-related diseases such as inflammatory arthritis, Crohn's disease, type 1 diabetes, and acute myocardial infarction. The comorbidities of patients with psoriasis with a history of cardiovascular events demonstrated strong interrelationships with other cardiovascular risk factors including type 2 diabetes mellitus, essential hypertension, and dyslipidemia. We also found comorbidities, such as malignant skin tumors and kidney and liver diseases, which could have adverse effects of anti-psoriasis therapy. In contrast, patients with psoriasis showed a decreased association with upper respiratory tract infection. Our results imply that comorbidities in patients with psoriasis are associated with the systemic inflammation of psoriasis and the detrimental effects of its treatment. Furthermore, we found patterns of associations between the cardiovascular risk factors and psoriasis. Mass screening and association analyses using large-scale databases can be used to investigate impartially the comorbidities of psoriasis and other diseases.

Gut microbiome-derived butyrate inhibits the immunosuppressive factors PD-L1 and IL-10 in tumor-associated macrophages in gastric cancer.

Early detection and surgical treatment are essential to achieve a good outcome in gastric cancer (GC). Stage IV and recurrent GC have a poor prognosis. Therefore, new treatments for GC are needed. We investigated the intestinal microbiome of GC patients and attempted to reverse the immunosuppression of the immune and cancer cells of GC patients through the modulation of microbiome metabolites. We evaluated the levels of programmed death-ligand 1 (PD-L1) and interleukin (IL)-10 in the peripheral blood immunocytes of GC patients. Cancer tissues were obtained from patients who underwent surgical resection of GC, and stained sections of cancer tissues were visualized via confocal microscopy. The intestinal microbiome was analyzed using stool samples of healthy individuals and GC patients. Patient-derived avatar model was developed by injecting peripheral blood mononuclear cells (PBMCs) from advanced GC (AGC) patients into NSG mice, followed by injection of AGS cells. PD-L1 and IL-10 had higher expression levels in immune cells of GC patients than in those of healthy controls. The levels of immunosuppressive factors were increased in the immune and tumor cells of tumor tissues of GC patients. The abundances of Faecalibacterium and Bifidobacterium in the intestinal flora were lower in GC patients than in healthy individuals. Butyrate, a representative microbiome metabolite, suppressed the expression levels of PD-L1 and IL-10 in immune cells. In addition, the PBMCs of AGC patients showed increased levels of immunosuppressive factors in the avatar mouse model. Butyrate inhibited tumor growth in mice. Restoration of the intestinal microbiome and its metabolic functions inhibit tumor growth and reverse the immunosuppression due to increased PD-L1 and IL-10 levels in PBMCs and tumor cells of GC patients.

Change of prevalence and clinical aspects of fungal ball according to temporal difference.

Fungal ball in paranasal sinus was reported to be rare, but these days we have encountered numerous cases. We retrospectively analyzed the data of 4,485 patients with chronic rhinosinusitis (CRS) who underwent sinus surgery from 1999 to 2010. Patients were categorized into group A (patients from 1999 to 2004) and group B (patients from 2005 to 2010). We compared the prevalence and clinical aspects of fungal ball between the two groups by analyzing the medical records, PNS CT findings, surgical findings, and pathologic reports. One hundred and twelve patients were diagnosed with fungal ball during the study periods. The prevalence of fungal ball was 0.9 % (23/2,333) in group A and 4.1 % (89/2,152) in group B, showing that it increased 4.6 times over 6 years. The prevalence of underlying diseases was 21.7 % (5/23) for hypertension and 8.7 % (2/23) for diabetes in group A, and 23.6 % (21/89) for hypertension and 14.6 % (13/89) for diabetes in group B. On PNS CT examination, calcification was identified in 78.2 % (18/23) of cases in group A and 44.9 % (40/89) in group B. The most involved paranasal sinus in group A was the co-involved maxillary and ethmoid sinuses at 26.1 % (6/23), whereas, the most prevalent involved sinus in group B was the maxillary sinus at 33.7 % (30/89). We found that the prevalence of fungal ball has increased steadily each year since 2005, accompanied by changes in the clinical aspects. These facts should be kept in mind when diagnosing and treating patients with medically intractable CRS.

Association between cardio-cerebrovascular disease and systemic antipsoriatic therapy in psoriasis patients using population-based data: A nested case-control study.

The effect of antipsoriatic therapy on cardio-cerebrovascular disease (CCVD) is not well described. Thus, we performed a population-based nested case-control study to investigate the effect of systemic antipsoriatic therapy on CCVD in psoriasis patients. Using nationwide cohort data from the Korean National Health Insurance Claims database, newly diagnosed psoriasis patients were identified. Among the enrolled participants, postenrollment development of CCVD events (ischemic heart disease, myocardial infarction, cerebral infarction, and cerebral hemorrhage) was investigated. To evaluate the effect of systemic antipsoriatic therapy on CCVD risk, we calculated the proportion of the treatment period with systemic antipsoriatic therapy during the study period (PTP [%]: the sum of all systemic antipsoriatic therapy durations divided by total observation period). Among 251 813 participants, 6262 experienced CCVD events during the study period (CCVD group). Controls included 245 551 patients without CCVD history during the study period (non-CCVD group). The non-CCVD group had greater PTP than the CCVD group (CCVD 2.12 ± 7.92, non-CCVD 2.64 ± 9.64; P < 0.001). In multiple logistic regression analysis, PTP was inversely associated with the CCVD risk after adjusting for age, sex, diabetes, hypertension, and dyslipidemia. A 10% increase in PTP reduced CCVD risk by 0.96 (95% confidence interval 0.93 to 0.99). Reduced CCVD risk was robust for both conventional antipsoriatic therapy and biologics. Our study found that systemic antipsoriatic therapy use was inversely associated with CCVD risk in psoriasis patients. These findings suggested that systemic antipsoriatic therapy could reduce CCVD development in patients with psoriasis.

Altered intrinsic brain functional network dynamics in moderate-to-severe obstructive sleep apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) can affect temporal fluctuations in brain activity during rest. Dynamic functional connectivity (dFC) captures the fluctuations in FC during the resting state. This study aimed to investigate differences in dFC between moderate-to-severe OSA patients and healthy controls using resting-state functional magnetic resonance imaging (fMRI) and sliding-window analysis. METHODS: Thirty-seven consecutive patients with moderate-to-severe OSA and 16 age- and sex-matched controls underwent resting-state fMRI in the morning following overnight polysomnography. The dynamics of aberrant FC between the groups and the correlation between the dynamics and clinical variables were evaluated. RESULTS: dFC analysis revealed two distinct connectivity states: hypoconnected (State I) and hyperconnected (State II). In OSA patients, State I occurred 34% more often than in the controls and the occurrence of State II was proportionally reduced. The time in State I positively correlated with the Pittsburg Sleep Quality Index score in the OSA patients. CONCLUSIONS: This study showed dFC alterations in moderate-to-severe OSA patients, which may serve as a novel physiological biomarker for OSA.

Altered functional connectivity of the ascending reticular activating system in obstructive sleep apnea.

Repeated arousals during sleep in obstructive sleep apnea (OSA) may lead to altered functional connectivity (FC) of the ascending reticular activating system (ARAS). We evaluated resting-state FC between eight ARAS nuclei and 105 cortical/subcortical regions in OSA patients and healthy controls. Fifty patients with moderate to severe OSA and 20 controls underwent overnight polysomnography and resting-state functional magnetic resonance imaging. Seed-to-voxel analysis of ARAS-cortex FC was compared between OSA patients and controls. The ARAS nuclei included the locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), and ventral tegmental area (VTA). FC values of three ARAS nuclei (the LC, LDTg, and VTA) significantly differed between the groups. FC of the LC with the precuneus, posterior cingulate gyrus, and right lateral occipital cortex (LOC) was stronger in OSA patients than controls. FC between the LDTg and right LOC was stronger in OSA patients than controls, but FC between the VTA and right LOC was weaker. Average LC-cortex FC values positively correlated with the arousal, apnea, and apnea-hypopnea index in OSA patients. Alterations in ARAS-cortex FC were observed in OSA patients. The strength of LC-cortex noradrenergic FC was related to arousal or OSA severity in patients.

Prognostic significances of PD-L1- and CTLA-4-positive T cells and positive correlations of immunosuppressive marker expression between cancer tissue and peripheral blood in patients with gastric cancer.

Introduction: Although tumor, node, metastasis (TNM) staging has been used for prognostic assessment of gastric cancer (GC), the prognosis may vary among patients with the same TNM stage. Recently, the TNM-Immune (TNM-I) classification staging system has been used for prognostic assessment of colorectal cancer based on intra-tumor T-cell status, which is a superior prognostic factor compared with the American Joint Committee on Cancer staging manual. However, an immunoscoring system with prognostic significance for GC has not been established. Method: Here, we evaluated immune phenotypes in cancer and normal tissues, then examined correlations between tissues and peripheral blood. GC patients who underwent gastrectomy at Seoul St. Mary's Hospital between February 2000 and May 2021 were included. We collected 43 peripheral blood samples preoperatively and a pair of gastric mucosal samples postoperatively, including normal and cancer mucosa, which did not influence tumor diagnosis and staging. Tissue microarray samples of GC were collected from 136 patients during surgery. We investigated correlations of immune phenotypes between tissues and peripheral blood using immunofluorescence imaging and flow cytometry, respectively. GC mucosa exhibited an increased number of CD4+ T cells, as well as increased expression levels of immunosuppressive markers (e.g., programmed death-ligand-1 [PD-L1], cytotoxic T lymphocyte antigen-4 [CTLA-4], and interleukin-10), in CD4+ T cells and non-T cells. Result: The expression levels of immunosuppressive markers were significantly increased in cancer tissues and peripheral blood mononuclear cells. In gastric mucosal tissues and peripheral blood of GC patients, similar immunosuppression phenotypes were observed, including increased numbers of PD-L1- and CTLA-4-positive T cells. Discussion: Therefore, peripheral blood analysis may be an important tool for prognostic assessment of GC patients.

SARS-CoV-2 spike protein accelerates systemic sclerosis by increasing inflammatory cytokines, Th17 cells, and fibrosis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) induces a dysfunctional immune response, inflammation, autoantibody production, and coagulopathy, which are symptoms that bear resemblance to those of autoimmune diseases, including systemic sclerosis (SSc). METHODS: While there is a single case report suggesting an association between COVID-19 and SSc, the effects of COVID-19 on SSc are not yet fully understood. Human embryonic kidney 293 (HEK293) cells were transfected with the SARS-CoV-2 spike protein gene, in the presence of TGF-ß. The expression levels of fibrosis-related proteins were measured via Western blotting. A bleomycin (BLM)-induced SSc mouse model was employed, wherein mice were injected with the gene encoding the SARS-CoV-2 spike protein and the ACE2 receptor. The levels of fibrosis, autoantibodies, thrombotic factors, and inflammatory cytokines in tissues and serum were analyzed. RESULTS: In vitro, the expression levels of fibrosis marker proteins were elevated in the spike protein group compared to the control group. In vivo, the skin thickness of SSc mice increased following exposure to the SARS-CoV-2 spike protein. Furthermore, the levels of autoantibodies and thrombotic factors, such as anti-phospholipid antibodies (APLA), were significantly increased in the presence of the protein. Flow cytometry analysis revealed increased expression of the proinflammatory cytokine IL-17 in the skin, lungs, and blood. Moreover, tissue fibrosis and levels of inflammatory cytokines in skin and lung tissues were markedly escalated in SSc mice subjected to the protein. CONCLUSION: COVID-19 may accelerate the development and progression of SSc by intensifying fibrosis through the upregulation of inflammation, autoantibody production, and thrombosis.

The effect of allergic rhinitis on the degree of stress, fatigue and quality of life in OSA patients.

Both allergic rhinitis (AR) and obstructive sleep apnea (OSA) are known to increase stress and fatigue, but the result of their coexistence has not been studied. The objective of this study was to evaluate the amount of stress and fatigue when AR is combined with OSA. One hundred and twelve patients diagnosed with OSA by polysomnography were enrolled. Among them, 37 patients were diagnosed with AR by a skin prick test and symptoms (OSA-AR group) and 75 patients were classified into the OSA group since they tested negative for allergies. We evaluated the Epworth sleepiness scale (ESS), stress score, fatigue score, ability to cope with stress, and rhinosinusitis quality of life questionnaire (RQLQ) with questionnaires and statistically compared the scores of both groups. There were no significant differences in BMI and sleep parameters such as LSAT, AHI, and RERA between the two groups. However, the OSA-AR group showed a significantly higher ESS score compared to the OSA group (13.7 ± 4.7 vs. 9.3 ± 4.8). Fatigue scores were also significantly higher in the OSA-AR group than in the OSA group (39.8 ± 11.0 vs. 30.6 ± 5.4). The OSA-AR group had a significantly higher stress score (60.4 ± 18.6 vs. 51.2 ± 10.4). The ability to cope with stress was higher in the OSA group, although this difference was not statistically significant. RQLQ scores were higher in the OSA-AR group (60.2 ± 16.7 compared to 25.1 ± 13.9). In conclusion, management of allergic rhinitis is very important in treating OSA patients in order to eliminate stress and fatigue and to minimize daytime sleepiness and quality of life.

Comparison of pre- and post-operative stress levels in patients with allergic rhinitis and non-allergic rhinitis.

The effects of stressful events, such as surgery, on patients with allergic diseases are unclear. The aim of this study was to evaluate whether patients with allergic rhinitis (AR) are more susceptible to stress and oxidative stress than non-allergic individuals. 20 AR patients and 20 non-allergic rhinitis (NAR) patients were recruited to this study and underwent nasal septoplasty. To evaluate the degrees of stress and oxidative stress, we collected urine and blood samples 1 day before and 1 day after surgery. Stress was assessed by measuring urine cortisol levels. Oxidative stress was assessed by calculating the balance of reactive oxygen metabolites (ROM) measured by the diacron reactive oxygen metabolites test, and antioxidant capacity (AC) was measured by the biological antioxidant potential test. In both groups, the level of post-operative urine cortisol was significantly higher than the pre-operative level, with no significant difference between the two groups. ROM levels were significantly higher in both groups after surgery than before surgery. The antioxidant capacity of the AR group was lower after surgery than before surgery, while it was greater in the NAR group after surgery. There were no significant differences in pre- or post-operative ROM or AC levels between the two groups. The ROM/AC ratio was significantly higher after surgery in the AR group than it was in the NAR group. The post-operative ROM/AC imbalance of AR patients suggests that these patients might be vulnerable to stress, especially oxidative stress.

Sphingosylphosphorylcholine ameliorates experimental sjögren's syndrome by regulating salivary gland inflammation and hypofunction, and regulatory B cells.

Sjögren syndrome (SS) is an autoimmune disease in which immune cells infiltrate the exocrine gland. Since SS is caused by a disorder of the immune system, treatments should regulate the immune response. Sphingosylphosphorylcholine (SPC) is a sphingolipid that mediates cellular signaling. In immune cells, SPC has several immunomodulatory functions. Accordingly, this study verifies the immunomodulatory ability and therapeutic effect of SPC in SS. To understand the function of SPC in SS, we treated SPC in female NOD/ShiJcl (NOD) mice. The mice were monitored for 10 weeks, and inflammation in the salivary glands was checked. After SPC treatment, we detected the expression of regulatory B (Breg) cells in mouse splenocytes and the level of salivary secretion-related genes in human submandibular gland (HSG) cells. Salivary flow rate was maintained in the SPC-treated group compared to the vehicle-treated group, and inflammation in the salivary gland tissues was relieved by SPC. SPC treatment in mouse cells and HSG cells enhanced Breg cells and salivary secretion markers, respectively. This study revealed that SPC can be considered as a new therapeutic agent against SS.