Analysis of the Effectiveness of Anterior Septal Reconstruction in Asians.

Background: Although anterior septal reconstruction (ASR) is effective, it is less commonly employed in Asian patients compared with the septal extension graft technique, even in cases of severe antero-caudal septal deviation. Objective: To compare airflow and patient perceptions after ASR in patients of Korean descent with caudal septal deviations and external nasal deformities, we considered the potential tendency of their septal cartilage to be smaller and less robust compared with that of Caucasians. The measurements were conducted using acoustic rhinometry and patient-reported outcomes. Methods: We analyzed 103 patients using preoperative and 3-month postoperative assessments: Korean version of the Standardized Cosmesis and Health Nasal Outcomes Survey (K-SCHNOS), obstructive (SCHNOS-O), and cosmetic (SCHNOS-C) scores, and minimal cross-sectional area (MCA) measured by acoustic rhinometry. Results: Among 103 patients (mean age 33.36 years, median age 32 years, age range 17-70 years, 77 men [75%], and 26 women [25%]), the average follow-up period for the patients was 264.6 days (median 202 days and range 13-1540 days), SCHNOS-O scores improved significantly from 64.02 ± 4.89 to 19.31 ± 4.45 after ASR (p < 0.001), as did SCHNOS-C scores, improving from 60.61 ± 7.71 to 14.25 ± 4.66 (p < 0.001). MCA increased from 0.30 ± 0.16 cm2 to 0.56 ± 0.38 cm2 (p < 0.001). Conclusions: As measured by MCA and SCHNOS scores at 3 months postoperatively, ASR proves valuable for correcting antero-caudal septal deviations and nasal deformities in Asians, despite the tendency of their septal cartilage to be smaller and less strong compared with that of Caucasians.

Discovery of a novel homoisoflavonoid derivative 5g for anti-osteoclastic bone loss via targeting FGFR1.

Several flavonoids have been shown to exert anti-osteoporosis activity. However, the structure-activity relationship and the mechanism of anti-osteoporosis activity of flavonoids remain unknown. In this study, we prepared a series of novel homoisoflavonoid (HIF) derivatives to evaluate their inhibitory effects on osteoclastogenesis using TRAP-activity in vitro assay. Then, the preliminary structure-activity relationship was studied. Among the evaluated novel flavonoids, derivative 5g exerted the most inhibitory bioactivity on primary osteoclast differentiation without interfering with osteogenesis. It was hence selected for further in vitro, in vivo and mechanism of action investigation. Results show that 5g likely directly binds to the fibroblast growth factor receptor 1 (FGFR1), decreasing the activation of ERK1/2 and IκBα/NF-κB signaling pathways, which in turn blocks osteoclastogenesis in vitro and osteoclastic bone loss in vivo. Our study shows that homoisoflavonoid (HIF) derivatives 5g can serve as a potential novel candidate for treating osteoporosis via inhibition of FGFR1.

PNPLA1 knockdown inhibits esterification of γ-linolenic acid to ceramide 1 in differentiated keratinocytes.

Patatin-like phospholipase domain-containing 1 (PNPLA1) is crucial in the esterification of linoleic acid (LA; 18:2n-6) to ω-hydroxy fatty acids (FA) of ceramide 1 (Cer1), the major barrier lipid of the differentiated epidermis. We previously reported that γ-linolenic acid (GLA; 18:3n-6) as well as LA is esterified to Cer1 subspecies with sphingosine (d18:1) or eicosasphingosine (d20:1) amide-linked to two different ω-hydroxy FA (30wh:0; 32wh:1). Here, we further investigated whether PNPLA1 is also responsible for esterification of GLA to these Cer1 subspecies in normal human keratinocytes (NHK). As late/terminal differentiation was induced in NHK, PNPLA1 and differentiation markers were expressed, and LA-esterified Cer1 subspecies (18:2n-6/C30wh:0 or C32wh:0/d18:1; 18:2n-6/C32wh:0/d20:1) were detected, which were further increased with LA treatment. GLA-esterified Cer1 subspecies (18:3n-6/C30wh:0 or C32wh:0/d18:1; 18:3n-6/C32wh:0/d20:1) were detected only with GLA treatment. Specific small interfering RNA-mediated knockdown of PNPLA1 (KDP) in differentiated NHK decreased levels of these LA-esterified Cer1 subspecies overall and of involucrin (IVL), a terminal differentiation marker. Moreover, KDP resulted in lesser LA/GLA responses as characterized by more significant decreases in IVL and LA/GLA-esterified Cer1 subspecies overall and an accumulation of non-esterified ω-hydroxy ceramides, their putative precursors; the decrease of 18:3n-6/C32wh:0/d18:1, the predominant GLA-esterified Cer1 subspecies, specifically paralleled the increase of C32wh:0/d18:1, its corresponding precursor. PNPLA1 is responsible for NHK terminal differentiation and also for esterification of GLA to the ω-hydroxy FA of Cer1.

Predictors of Early and Late Lung Function Improvement in Severe Eosinophilic Asthma on Type2-Biologics in the PRISM Study.

BACKGROUND: The determinants linked to the short- and long-term improvement in lung function in patients with severe eosinophilic asthma (SEA) on biological treatment (BioT) remain elusive. OBJECTIVE: We sought to identify the predictors of early and late lung function improvement in patients with SEA after BioT. METHODS: 140 adult patients with SEA who received mepolizumab, dupilumab, or reslizumab were followed up for 6 months to evaluate improvement in forced expiratory volume in one second (FEV1). Logistic regression was used to determine the association between potential prognostic factors and improved lung function at 1 and 6 months of treatment. RESULTS: More than a third of patients with SEA using BioT showed early and sustained improvements in FEV1 after 1 month. A significant association was found between low baseline FEV1 and high blood eosinophil count and sustained FEV1 improvement after 1 month (0.54 [0.37-0.79] and 1.88 [1.28-2.97] odds ratios and 95% confidence interval, respectively). Meanwhile, among patients who did not experience FEV1 improvement after 1 month, 39% exhibited improvement at 6 months follow-up. A high ACT score measured at this visit was the most reliable predictor of late response after 6 months of treatment (OR and 95% CI 1.75 [1.09-2.98]). CONCLUSION: Factors predicting the efficacy of biological agents that improve lung function in SEA vary according to the stage of response.

A comparison of treatment response to biologics in asthma-COPD overlap and pure asthma: Findings from the PRISM study.

Background: Despite the increasing use of biologics in severe asthma, there is limited research on their use in asthma-chronic obstructive pulmonary disease overlap (ACO). We compared real-world treatment responses to biologics in ACO and asthma. Methods: We conducted a multicenter, retrospective, cohort study using data from the Precision Medicine Intervention in Severe Asthma (PRISM). ACO was defined as post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7 and a smoking history of >10 pack-years. Physicians selected biologics (omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab) based on each United States Food & Drug Administration (FDA) approval criteria. Results: After six-month treatment with biologics, both patients with ACO (N = 13) and asthma (N = 81) showed positive responses in FEV1 (10.69 ± 17.17 vs. 11.25 ± 12.87 %, P = 0.652), Asthma Control Test score (3.33 ± 5.47 vs. 5.39 ± 5.42, P = 0.290), oral corticosteroid use (-117.50 ± 94.38 vs. -115.06 ± 456.85 mg, P = 0.688), fractional exhaled nitric oxide levels (-18.62 ± 24.68 vs. -14.66 ± 45.35 ppb, P = 0.415), sputum eosinophils (-3.40 ± 10.60 vs. -14.48 ± 24.01 %, P = 0.065), blood eosinophils (-36.47 ± 517.02 vs. -363.22 ± 1294.59, P = 0.013), and exacerbation frequency (-3.07 ± 4.42 vs. -3.19 ± 5.11, P = 0.943). The odds ratio for exacerbation and time-to-first exacerbation showed no significant difference after full adjustments, and subgroup analysis according to biologic type was also showed similar results. Conclusions: Biologics treatment response patterns in patients with ACO and asthma were comparable, suggesting that biologics should be actively considered for ACO patients as well.

Prospective direct comparison of biologic treatments for severe eosinophilic asthma: Findings from the PRISM study.

BACKGROUND: Although various monoclonal antibodies have been used as add-on therapy for severe eosinophilic asthma (SEA), to the best of our knowledge, no direct head-to-head comparative study has evaluated their efficacy. OBJECTIVE: To compare the efficacy of reslizumab, mepolizumab, and dupilumab in patients with SEA. METHODS: This was a multicenter, prospective observational study in patients with SEA who had received 1 of these biologic agents for at least 6 months. Cox proportional hazard models were used to compare the risk of the first exacerbation event, adjusting for sputum or blood eosinophils and common asthma-related covariates. The annual exacerbation rate was analyzed using a negative binomial model, and a mixed-effect model was used to analyze changes in forced expiratory volume in 1 second and asthma control test score over time. RESULTS: A total of 141 patients with SEA were included in the analysis; 71 (50%) received dupilumab; 40 (28%) received reslizumab, and 30 (21%) received mepolizumab. During the 12-month follow-up, 27.5%, 43.3%, and 38.0% of patients in the reslizumab, mepolizumab, and dupilumab groups, respectively, experienced at least 1 exacerbation. However, after adjusting for confounding factors, the dupilumab and mepolizumab groups showed similar outcomes in time-to-first exacerbation, exacerbation rate, forced expiratory volume in 1 second, and asthma control test score to those of the reslizumab group. CONCLUSION: In patients with SEA, treatment with reslizumab, mepolizumab, and dupilumab resulted in comparable clinical outcomes within a 12-month period. The cohort protocol was sanctioned by the Institutional Review Board of each study center (clinicaltrial.gov identifier NCT05164939).

Synthesis and evaluation of 2-NMPA derivatives as potential agents for prevention of osteoporosis in vitro and in vivo.

Abnormal osteoclast differentiation causes various bone disorders such as osteoporosis. Targeting the formation and activation of osteoclasts has been recognized as an effective approach for preventing osteoporosis. Herein, we synthesized eleven 2-NMPA derivatives which are (2-(2-chlorophenoxy)-N-(4-alkoxy-2-morpholinophenyl) acetamides, and evaluated their suppression effects on osteoclastogenesis in vitro by using TRAP-staining assay. Among the synthesized eleven novel 2-NMPAs, 4-(2-(2-chlorophenoxy)acetamido)-3-morpholinophenyl trifluoromethanesulfonate (11b), 4-(2-(2-chlorophenoxy) acetamido)-3-morpholinophenyl-3-(N-(2-oxo-2-((2-(phenylthio) phenyl) amino) ethyl)methylsulfonamido)benzoate (11d), and 4-(2-(2-chlorophenoxy) acetamido)-3-morpholinophenyl 4-acetamidobenzenesulfonate (11h) displayed highly inhibitory bioactivity on the differentiation of primary osteoclasts. 11h was selected for further investigation of the inhibitory effects and potential mechanism involved in the suppression of osteoclastogenesis. In vitro analysis suggested that 11h inhibited osteoclastogenesis with an IC50 of 358.29 nM, decreased the formation of F-action belts and bone resorption, without interfering cell viability and osteoblast differentiation. Furthermore, the mRNA expressions of osteoclast-specific genes such as Acp5, Nfatc1, Dc-stamp, Atp6v0d2, Mmp9, and Ctsk significantly decreased following 11h treatment. RANKL-induced osteoclast-specific proteins analysis demonstrated that 11h suppressed osteoclast differentiation by downregulating of RANKL-mediated TRAF6 expression, followed by inactivation of PI3K/AKT and IκBα/NF-κB signaling pathways. Finally, 11h inhibited ovariectomy-induced bone loss in vivo. Therefore, the current work highlighted the therapeutic potential of 11h as an anti-osteoporosis lead compound.

Venous congestion affects neuromuscular changes in pigs in terms of muscle electrical activity and muscle stiffness.

Early detection of venous congestion (VC)-related diseases such as deep vein thrombosis (DVT) is important to prevent irreversible or serious pathological conditions. However, the current way of diagnosing DVT is only possible after recognizing advanced DVT symptoms such as swelling, pain, and tightness in affected extremities, which may be due to the lack of information on neuromechanical changes following VC. Thus, the goal of this study was to investigate acute neuromechanical changes in muscle electrical activity and muscle stiffness when VC was induced. The eight pigs were selected and the change of muscle stiffness from the acceleration and muscle activity in terms of integral electromyography (IEMG) was investigated in three VC stages. Consequently, we discovered a significant increase in the change in muscle stiffness and IEMG from the baseline to the VC stages (p < 0.05). Our results and approach can enable early detection of pathological conditions associated with VC, which can be a basis for further developing early diagnostic tools for detecting VC-related diseases.

Diagnostic Accuracy of Carcinoembryonic Antigen (CEA) in Detecting Colorectal Cancer Recurrence Depending on Its Preoperative Level.

BACKGROUND: Serum carcinoembryonic antigen (CEA) increase in patients with colorectal cancer (CRC) recurrence was observed to vary depending on their initial values. This study aimed to evaluate the diagnostic accuracy of CEA for detecting CRC recurrence in patients with normal and elevated initial CEA levels. METHODS: A total of 261 CRC recurrence patients who underwent curative resection were included and divided into two groups, normal and elevated initial CEA. Analysis was performed comparing patient, tumor, and recurrence characteristics retrospectively. RESULTS: There were 192 patients with normal and 69 with high initial CEA levels. Patient and tumor characteristics were similar. Eighty-six patients had elevated CEA at the time of recurrence, and the overall sensitivity of CEA for recurrence was 33.0%. In the high initial CEA group, 59.4% exhibited increased CEA level at recurrence, whereas in patients with normal initial CEA levels, only 23.4% showed elevated levels (p < 0.001). Patients with both high CEA preoperatively and at recurrence had more local recurrence, but there was no statistical significance (p = 0.053), and the rate of lung metastasis was higher in patients whose CEA remained normal at recurrence (38.3% vs. 24.4%, p = 0.026). The overall survival of patients with elevated CEA at recurrence was worse than those with normal CEA levels (56.9% vs. 42.4%, p = 0.003). CONCLUSION: The diagnostic accuracy of CEA for detecting recurrence depends on initial CEA level. Regardless of the initial CEA level, elevation at recurrence was significantly associated with overall survival in patients with recurrent CRC.

Establishment of a TNFRSF11B knock-out human induced pluripotent stem cell line (KSCBi002-B-2) via CRISPR/Cas9 system.

A TNFRSF11B (TNF Receptor Superfamily Member 11b) gene encodes a soluble decoy receptor, osteoprotegerin (OPG), which has a key role in repressing osteoclast differentiation. In this report, we generated a biallelic knock-out hiPSC line for the TNFRSF11B gene via CRISPR/Cas9. When TNFRSF11B Knock-out hiPSCs were differentiated into mesenchymal progenitor cells (MPCs), the expression level of OPG was significantly decreased compared to normal hiPSC-derived MPCs. This knock-out hiPSCs will provide a chance to study Paget disease of bone 5 (juvenile Paget disease).

WITHDRAWN: Prospective direct comparison of biological treatments on severe eosinophilic asthma: Findings from the PRISM study.

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Discovery of PMSA Derivative 11 as a Novel Lead Compound for Therapeutic Treatment of Osteoporosis In Vitro and In Vivo.

To discover a potent candidate for suppressing mature osteoclasts formation in vitro using a TRAP staining assay. A series of PMSA derivatives were synthesized and evaluated for their bioactivity in our current study. Our results showed that PMSA derivative 11 exhibited the most promising bioactivity, with an IC50 value of 322.9 nM, which was ∼15-fold better than PMSA-3-Ac in suppressing osteoclastogenesis in vitro. Additionally, 11 blocked the formation of F-action belts and bone resorption in a concentration-dependent manner. Mechanistically, 11 decreased the expression of genes required for osteoclastogenesis by blocking NFATc1 translocation from the cytoplasm to nucleus. Furthermore, 11 demonstrated a therapeutic inhibitory effect on the differentiation of human iPSC-derived primary osteoclasts. In vivo investigation showed that 11 prevented excessive osteoclastogenesis-mediated bone loss in ovariectomized osteoporosis mimic mice. These findings highlighted the therapeutic potential of 11 as a lead compound for anti-osteoporosis by targeting NFATc1 translocation.

Serum Zonulin Is a Biomarker for Severe Asthma.

Zonulin is a regulator of epithelial and endothelial barrier function. It regulates intestinal permeability through disrupting tight junctions. Defective epithelial barrier function is a hallmark of airway inflammation in asthma. This study aimed to investigate the role of zonulin in the pathogenesis of severe asthma. We enrolled 56 adult patients with asthma (29 severe asthma and 27 mild-to-moderate asthma) and 33 normal controls. The clinical data, sera, and lung tissues of the patients were provided by the Cohort for Reality and Evolution of adult Asthma in Korea (COREA) and the Biobank of Soonchunhyang University Bucheon Hospital, South Korea. Serum zonulin levels were estimated using an enzyme-linked immunosorbent assay, and zonulin expression in the bronchial tissue was evaluated by immunohistochemical staining. The serum zonulin levels were significantly higher in patients with severe asthma (51.98 ± 19.66 ng/mL) than in those with mild-to-moderate asthma and normal controls (26.35 ± 13.70 vs. 17.26 ± 10.29 ng/mL, P < 0.001). They significantly correlated with percent predicted forced expiratory volume in one second (%FEV1) (r = -0.35, P = 0.009). The zonulin expression in the bronchial epithelium was greater in patients with severe asthma. A serum zonulin cutoff value to distinguish between severe and mild-to-moderate asthmatics was 38.83 ng/mL. Zonulin may play an important role in the pathogenesis of severe asthma, and serum zonulin could be a potential biomarker for severe asthma.

Parnassin, a Novel Therapeutic Peptide, Alleviates Skin Lesions in a DNCB-Induced Atopic Dermatitis Mouse Model.

Atopic dermatitis (AD) is a chronic inflammatory skin disease which requires continuous treatment due to its relapsing nature. The current treatment includes steroids and nonsteroidal agents targeting inflammation but long-term administration causes various side effects such as skin atrophy, hirsutism, hypertension and diarrhea. Thus, there is an unmet need for safer and effective therapeutic agents in the treatment of AD. Peptides are small biomolecule drugs which are highly potent and remarkably have less side effects. Parnassin is a tetrapeptide with predicted anti-microbial activity curated from Parnassius bremeri transcriptome data. In this study, we confirmed the effect of parnassin on AD using a DNCB-induced AD mouse model and TNF-α/IFN-γ-stimulated HaCaT cells. In the AD mouse model, topical administration of parnassin improved skin lesions and symptoms in AD mice, such as epidermal thickening and mast cell infiltration, similar to the existing treatment, dexamethasone, and did not affect body weight, or the size and weight of spleen. In TNF-α/IFN-γ-stimulated HaCaT cells, parnassin inhibited the expression of Th2-type chemokine CCL17 and CCL22 genes by suppressing JAK2 and p38 MAPK signaling kinases and their downstream transcription factor STAT1. Parnassin also significantly reduced the gene expression of TSLP and IL-31, which are pruritus-inducing cytokines. These findings suggested that parnassin alleviates AD-like lesions via its immunomodulatory effects and can be used as a candidate drug for the prevention and treatment of AD because it is safer than existing treatments.

Canadian public perceptions and experiences with information during the COVID-19 pandemic: strategies to optimize future risk communications.

BACKGROUND: The COVID-19 pandemic accelerated the spread of misinformation worldwide. The purpose of this study was to explore perceptions of misinformation and preferred sources of obtaining COVID-19 information from those living in Canada. In particular, we sought to explore the perceptions of East Asian individuals in Canada, who experienced stigma related to COVID-19 messaging. METHODS: We conducted a qualitative thematic analysis study. Interviews were offered in English, Mandarin and Cantonese. Interviewers probed for domains related to knowledge about COVID-19, preferred sources of information, perceived barriers and facilitators of misinformation, and preferences for communication during a health emergency. Interviews were recorded, translated, transcribed verbatim and analyzed using a framework approach. Transcripts were independently double-coded until > 60% agreement was reached. This study received research ethics approval. RESULTS: Fifty-five interviews were conducted. The majority of participants were women (67%); median age was 52 years. 55% of participants were of East-Asian descent. Participants obtained information about COVID-19 from diverse English and non-English sources including news media, government agencies or representatives, social media, and personal networks. Challenges to seeking and understanding information included: encountering misinformation, making sense of evolving or conflicting public health guidance, and limited information on topics of interest. 65% of participants reported encountering COVID-19  misinformation. East Asian participants called on government officials to champion messaging to reduce stigmatizing and racist rhetoric and highlighted the importance of having accessible, non-English language information sources. Participants provided recommendations for future public health communications guidance during health emergencies, including preferences for message content, information messengers, dissemination platforms and format of messages. Almost all participants preferred receiving information from the Canadian government and found it helpful to utilize various mediums and platforms such as social media and news media for future risk communication, urging for consistency across all platforms. CONCLUSIONS: We provide insights on Canadian experiences navigating COVID-19 information, where more than half perceived encountering misinformation on platforms when seeking COVID-19 information . We provide recommendations to inform public health communications during future health emergencies.

(S)-2-(Cyclobutylamino)-N-(3-(3,4-dihydroisoquinolin-2(1H)-yl)-2-hydroxypropyl)isonicotinamide Attenuates RANKL-Induced Osteoclast Differentiation by Inhibiting NF-κB Nuclear Translocation.

Osteoporosis is a common skeletal disease; however, effective pharmacological treatments still need to be discovered. This study aimed to identify new drug candidates for the treatment of osteoporosis. Here, we investigated the effect of EPZ compounds, protein arginine methyltransferase 5 (PRMT5) inhibitors, on RANKL-induced osteoclast differentiation via molecular mechanisms by in vitro experiments. EPZ015866 attenuated RANKL-induced osteoclast differentiation, and its inhibitory effect was more significant than EPZ015666. EPZ015866 suppressed the F-actin ring formation and bone resorption during osteoclastogenesis. In addition, EPZ015866 significantly decreased the protein expression of Cathepsin K, NFATc1, and PU.1 compared with the EPZ015666 group. Both EPZ compounds inhibited the nuclear translocation of NF-κB by inhibiting the dimethylation of the p65 subunit, which eventually prevented osteoclast differentiation and bone resorption. Hence, EPZ015866 may be a potential drug candidate for the treatment of osteoporosis.

Peroxiredoxin 5 regulates osteogenic differentiation through interaction with hnRNPK during bone regeneration.

Peroxiredoxin 5 (Prdx5) is involved in pathophysiological regulation via the stress-induced cellular response. However, its function in the bone remains largely unknown. Here, we show that Prdx5 is involved in osteoclast and osteoblast differentiation, resulting in osteoporotic phenotypes in Prdx5 knockout (Prdx5Ko) male mice. To investigate the function of Prdx5 in the bone, osteoblasts were analyzed through immunoprecipitation (IP) and liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) methods, while osteoclasts were analyzed through RNA-sequencing. Heterogeneous nuclear ribonucleoprotein K (hnRNPK) was identified as a potential binding partner of Prdx5 during osteoblast differentiation in vitro. Prdx5 acts as a negative regulator of hnRNPK-mediated osteocalcin (Bglap) expression. In addition, transcriptomic analysis revealed that in vitro differentiated osteoclasts from the bone marrow-derived macrophages of Prdx5Ko mice showed enhanced expression of several osteoclast-related genes. These findings indicate that Prdx5 might contribute to the maintenance of bone homeostasis by regulating osteoblast differentiation. This study proposes a new function of Prdx5 in bone remodeling that may be used in developing therapeutic strategies for bone diseases.

Crucial Role of Lysine-Specific Histone Demethylase 1 in RANKL-Mediated Osteoclast Differentiation.

Epigenetic regulators are involved in osteoclast differentiation. This study proposes that the inhibitors of epigenetic regulators could be effective in the treatment of osteoporosis. This study identified GSK2879552, a lysine-specific histone demethylase 1 (LSD1) inhibitor, as a candidate for the treatment of osteoporosis from epigenetic modulator inhibitors. We investigate the function of LSD1 during RANKL-induced osteoclast formation. LSD1 small-molecule inhibitors effectively inhibit the RANKL-induced osteoclast differentiation in a dose-dependent manner. LSD1 gene knockout in macrophage cell line Raw 264.7 also inhibits RANKL-mediated osteoclastogenesis. LSD1-inhibitor-treated primary macrophage cells and LSD1 gene knockout Raw 264.7 cells failed to show actin ring formation. LSD1 inhibitors prevent the expression of RANKL-induced osteoclast-specific genes. They also downregulated the protein expression of osteoclast-related markers in osteoclastogeneses, such as Cathepsin K, c-Src, and NFATc1. Although LSD1 inhibitors were shown to reduce the in vitro demethylation activity of LSD1, they did not modulate the methylation of Histone 3 K4 and K9 during osteoclastogenesis. The ovariectomy (OVX)-induced osteoporosis model revealed that GSK2879552 slightly restores OVX-induced cortical bone loss. LSD1 can be employed as a positive regulator to promote osteoclast formation. Hence, inhibition of LSD1 activities is a potential target for preventing bone diseases characterized by excessive osteoclast activities.

Trends and an Online Survey on the Use of Rigid Bronchoscopy in Korea.

BACKGROUND: Although almost all interventional pulmonologists agree that rigid bronchoscopy is irreplaceable in the field of interventional pulmonology, less is known about the types of diseases that the procedure is used for and what difficulties the operators face during the procedure. The purpose of this study is to evaluate what diseases rigid bronchoscopy is used for, whether it is widely used, and what challenges the operators face in Korea. METHODS: We enrolled 14 hospitals in this retrospective cohort of patients who underwent rigid bronchoscopy between 2003 and 2020. An online survey was conducted with 14 operators to investigate the difficulties associated with the procedure. RESULTS: While the number of new patients at Samsung Medical Center (SMC) increased from 189 in 2003-2005 to 468 in 2018-2020, that of other institutions increased from 0 to 238. The proportion of SMC patients in the total started at 100% and steadily decreased to 59.2%. The proportion of malignancy as the indication for the procedure steadily increased from 29.1% to 43.0%, whereas post-tuberculous stenosis (25.4% to 12.9%) and post-intubation stenosis (19.0% to 10.9%) steadily decreased (all P for trends < 0.001). In the online survey, half of the respondents stated that over the past year they performed less than one procedure per month. The fewer the procedures performed within the last year, the more likely collaboration with other departments was viewed as a recent obstacle (Spearman correlation coefficient, rs = -0.740, P = 0.003) and recent administrative difficulties were encountered (rs = -0.616, P = 0.019). CONCLUSION: This study demonstrated that the number of patients undergoing rigid bronchoscopy has been increasing, especially among cancer patients. For this procedure to be used more widely, it will be important for beginners to systematically learn about the procedure itself as well as to achieve multidisciplinary consultation.

A fatal case report of invasive pulmonary aspergillosis and mucormycosis coinfection in an immunocompetent patient with coronavirus disease 2019 in Korea.

Systemic glucocorticoid treatment is highly recommended in critically ill coronavirus disease 2019 (COVID-19) patients. However, secondary fungal infections are of concern in such patients. Here, we describe the first case of COVID-19-associated invasive pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) coinfection in a COVID-19 positive immunocompetent patient in Korea. A 69-year-old man was admitted to our hospital with COVID-19 pneumonia. He had no underlying comorbidities and was not taking medications. He received remdesivir, dexamethasone, and antibiotic therapy under mechanical ventilation. Although his condition improved temporarily, multiple cavities were observed on chest computed tomography, and Aspergillus fumigatus was cultured from tracheal aspiration culture. He was diagnosed with probable CAPA and received voriconazole therapy. However, his condition was not significantly improved despite having received voriconazole therapy for 4 weeks. After release from COVID-19 quarantine, he underwent bronchoscopy examination and was then finally diagnosed with CAPA and CAM coinfection on bronchoscopic biopsy. Antifungal treatment was changed to liposomal amphotericin B. However, his progress deteriorated, and he died 4 months after admission. This case highlights that clinical suspicion and active checkups are required to diagnose secondary fungal infections in immunocompetent COVID-19 patients who receive concurrent glucocorticoid therapy.