Empirical Therapy Versus Tailored Therapy of Helicobacter pylori in Korea: Results of the K-CREATE Study.

BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.

Comparison of Surgical Burden, Radiographic and Clinical Outcomes According to the Severity of Baseline Sagittal Imbalance in Adult Spinal Deformity Patients.

OBJECTIVE: To determine the clinical impact of the baseline sagittal imbalance severity in patients with adult spinal deformity (ASD). METHODS: We retrospectively reviewed patients who underwent ≥ 5-level fusion including the pelvis, for ASD with a ≥ 2-year follow-up. Using the Scoliosis Research Society-Schwab classification system, patients were classified into 3 groups according to the severity of the preoperative sagittal imbalance: mild, moderate, and severe. Postoperative clinical and radiographic results were compared among the 3 groups. RESULTS: A total of 259 patients were finally included. There were 42, 62, and 155 patients in the mild, moderate, and severe groups, respectively. The perioperative surgical burden was greatest in the severe group. Postoperatively, this group also showed the largest pelvic incidence minus lumbar lordosis mismatch, suggesting a tendency towards undercorrection. No statistically significant differences were observed in proximal junctional kyphosis, proximal junctional failure, or rod fractures among the groups. Visual analogue scale for back pain and Scoliosis Research Society-22 scores were similar across groups. However, severe group's last follow-up Oswestry Disability Index (ODI) scores significantly lower than those of the severe group. CONCLUSION: Patients with severe sagittal imbalance were treated with more invasive surgical methods along with increased the perioperative surgical burden. All patients exhibited significant radiological and clinical improvements after surgery. However, regarding ODI, the severe group demonstrated slightly worse clinical outcomes than the other groups, probably due to relatively higher proportion of undercorrection. Therefore, more rigorous correction is necessary to achieve optimal sagittal alignment specifically in patients with severe baseline sagittal imbalance.

MicroRNA-19b exacerbates systemic sclerosis through promoting Th9 cells.

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and multiple vital organs, but the immunological pathogenesis of SSc remains unclear. We show here that miR-19b promotes Th9 cells that exacerbate SSc. Specifically, miR-19b and interleukin (IL)-9 increase in CD4+ T cells in experimental SSc in mice induced with bleomycin. Inhibiting miR-19b reduces Th9 cells and ameliorates the disease. Mechanistically, transforming growth factor beta (TGF-ß) plus IL-4 activates pSmad3-Ser213 and TRAF6-K63 ubiquitination by suppressing NLRC3. Activated TRAF6 sequentially promotes TGF-ß-activated kinase 1 (TAK1) and nuclear factor κB (NF-κB) p65 phosphorylation, leading to the upregulation of miR-19b. Notably, miR-19b activated Il9 gene expression by directly suppressing atypical E2F family member E2f8. In patients with SSc, higher levels of IL9 and MIR-19B correlate with worse disease progression. Our findings reveal miR-19b as a key factor in Th9 cell-mediated SSc pathogenesis and should have clinical implications for patients with SSc.

The Safety of Aztreonam Versus Ceftazidime in Patients Labeled With Penicillin Allergy: A Cohort Study.

PURPOSE: Penicillin allergy is the most common drug allergy among hospitalized patients. Traditionally, aztreonam is recommended for patients labeled with penicillin allergy (PLWPA) in our institutional empirical antibiotic guidelines. Due to a global aztreonam shortage in December 2022, the antimicrobial stewardship unit recommended ceftazidime as a substitute. There is a paucity of real-world data on the safety profile of ceftazidime in PLWPA. Hence, we evaluated tolerability outcomes of ceftazidime use in PLWPA. METHODS: This retrospective cohort study compared PLWPA in Singapore General Hospital who received aztreonam (October 2022-December 2022) or ceftazidime (December 2022-February 2023). Patients were stratified according to their risk of allergic reaction (AR) based on history of penicillin allergy. The severity of AR was based on the Delphi study grading system. The primary outcome was development of AR after initiation of aztreonam or ceftazidime. The secondary tolerability outcomes include hepatotoxicity and neurotoxicity. FINDINGS: There were 168 patients in the study; 69 were men (41.1%) and the median age was 69 years (interquartile range: 59-76 years). Incidence of AR was statistically similar in both arms: 1 of 102 patients (0.98%) in the aztreonam arm vs 2 of 66 patients (3.03%) in the ceftazidime arm (P = 0.33). The patient in the aztreonam arm was deemed at medium risk of having an AR and developed localized rashes (grade 1). Both patients in the ceftazidime arm were deemed at high risk of AR and developed localized skin reaction (grade 1). Hepatotoxicity was observed in 1 patient prescribed aztreonam. No patients in the ceftazidime arm developed adverse events. IMPLICATIONS: Ceftazidime appears to be better tolerated and cheaper compared with aztreonam in PLWPA, and serves as an antimicrobial stewardship strategy to conserve broader-spectrum antibiotics use.

Parathyroid-on-a-chip simulating parathyroid hormone secretion in response to calcium concentration.

The parathyroid gland is an endocrine organ that plays a crucial role in regulating calcium levels in blood serum through the secretion of parathyroid hormone (PTH). Hypoparathyroidism is a chronic disease that can occur due to parathyroid defects, but due to the difficulty of creating animal models of this disease or obtaining human normal parathyroid cells, the evaluation of parathyroid functionality for drug development is limited. Although parathyroid-like cells that secrete PTH have recently been reported, their functionality may be overestimated using traditional culture methods that lack in vivo similarities, particularly vascularization. To overcome these limitations, we obtained parathyroid organoids from tonsil-derived mesenchymal stem cells (TMSCs) and fabricated a parathyroid-on-a-chip, capable of simulating PTH secretion based on calcium concentration. This chip exhibited differences in PTH secretion according to calcium concentration and secreted PTH within the range of normal serum levels. In addition, branches of organoids, which are difficult to observe in animal models, were observed in this chip. This could serve as a guideline for successful engraftment in implantation therapies in the future.

Efficacy and safety of three-dimensional magnetically assisted capsule endoscopy for upper gastrointestinal and small bowel examination.

BACKGROUND: Magnetically assisted capsule endoscopy (MACE) showed the feasibility for upper gastrointestinal examination. To further enhance the performance of conventional MACE, it is necessary to provide quality-improved and three-dimensional images. The aim of this clinical study was to determine the efficacy and safety of novel three-dimensional MACE (3D MACE) for upper gastrointestinal and small bowel examination at once. METHODS: This was a prospective, single-center, non-randomized, and sequential examination study (KCT0007114) at Dongguk University Ilsan Hospital. Adult patients who visited for upper endoscopy were included. The study protocol was conducted in two stages. First, upper gastrointestinal examination was performed using 3D MACE, and a continuous small bowel examination was performed by conventional method of capsule endoscopy. Two hours later, an upper endoscopy was performed for comparison with 3D MACE examination. The primary outcome was confirmation of major gastric structures (esophagogastric junction, cardia/fundus, body, angle, antrum, and pylorus). Secondary outcomes were confirmation of esophagus and duodenal bulb, accuracy for gastric lesions, completion of small bowel examination, 3D image reconstruction of gastric lesion, and safety. RESULTS: Fifty-five patients were finally enrolled. The examination time of 3D MACE was 14.84 ± 3.02 minutes and upper endoscopy was 5.22 ± 2.39 minutes. The confirmation rate of the six major gastric structures was 98.6% in 3D MACE and 100% in upper endoscopy. Gastric lesions were identified in 43 patients during 3D MACE, and 40 patients during upper endoscopy (Sensitivity 0.97). 3D reconstructed images were acquired for all lesions inspected by 3D MACE. The continuous small bowel examination by 3D MACE was completed in 94.5%. 3D MACE showed better overall satisfaction (3D MACE 9.55 ± 0.79 and upper endoscopy 7.75 ± 2.34, p<0.0001). There were no aspiration or significant adverse event or capsule retention in the 3D MACE examination. CONCLUSIONS: Novel 3D MACE system is more advanced diagnostic modality than the conventional MACE. And it is possible to perform serial upper gastrointestinal and small bowel examination as a non-invasive and one-step test. It would be also served as a bridge to pan-endoscopy.

Effect of perioperative intravenous ibuprofen versus acetaminophen on postoperative opioid consumption and pain after general anesthesia: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

BACKGROUND: Ibuprofen and acetaminophen are widely used as adjuvant analgesics for postoperative pain. This meta-analysis compared the effects of intravenous (IV) ibuprofen and acetaminophen on postoperative opioid consumption and pain intensity after general anesthesia. METHODS: PubMed/MEDLINE, EMBASE, and Cochrane Library databases were searched to identify relevant studies published up to May 2023. Randomized controlled trials comparing the effects of perioperative IV ibuprofen and acetaminophen on postoperative opioid consumption and pain after general anesthesia were included in the meta-analysis and trial sequential analysis (TSA). RESULTS: Eight studies with 494 participants were included. Compared to IV acetaminophen, IV ibuprofen significantly reduced 24 h opioid consumption, presented as morphine equivalents (mean difference [MD]: -6.01 mg, 95% CI [-8.60, -3.42], P < 0.00001, I2 = 55%), and pain scores (on a scale of 0-10) at 4-6 h (MD: -0.83, 95% CI [-1.29, -0.37], P = 0.0004, I2 = 65%) and 12 h (MD: -0.38, 95% CI [-0.68, -0.08], P = 0.01, I2 = 11%) postoperatively. These results were statistically significant in TSA. Pain scores at 24 h postoperatively and side effects were not significantly different between the two groups in the meta-analysis, and TSA revealed that the sample size was too small to adequately evaluate the effects, requiring further studies for conclusive results. CONCLUSIONS: Perioperative IV ibuprofen reduced 24 h opioid consumption and pain severity up to 12 h postoperatively compared to acetaminophen. Additional research is required to assess pain intensity beyond 12 h and side effects.

Hope for vascular cognitive impairment: Ac-YVAD-cmk as a novel treatment against white matter rarefaction.

Vascular cognitive impairment (VCI) is the second leading cause of dementia with limited treatment options, characterised by cerebral hypoperfusion-induced white matter rarefaction (WMR). Subcortical VCI is the most common form of VCI, but the underlying reasons for region susceptibility remain elusive. Recent studies employing the bilateral cortical artery stenosis (BCAS) method demonstrate that various inflammasomes regulate white matter injury and blood-brain barrier dysfunction but whether caspase-1 inhibition will be beneficial remains unclear. To address this, we performed BCAS on C57/BL6 mice to study the effects of Ac-YVAD-cmk, a caspase-1 inhibitor, on the subcortical and cortical regions. Cerebral blood flow (CBF), WMR, neuroinflammation and the expression of tight junction-related proteins associated with blood-brain barrier integrity were assessed 15 days post BCAS. We observed that Ac-YVAD-cmk restored CBF, attenuated BCAS-induced WMR and restored subcortical myelin expression. Within the subcortical region, BCAS activated the NLRP3/caspase-1/interleukin-1beta axis only within the subcortical region, which was attenuated by Ac-YVAD-cmk. Although we observed that BCAS induced significant increases in VCAM-1 expression in both brain regions that were attenuated with Ac-YVAD-cmk, only ZO-1 and occludin were observed to be significantly altered in the subcortical region. Here we show that caspase-1 may contribute to subcortical regional susceptibility in a mouse model of VCI. In addition, our results support further investigations into the potential of Ac-YVAD-cmk as a novel treatment strategy against subcortical VCI and other conditions exhibiting cerebral hypoperfusion-induced WMR.

Osteoporosis Is Associated with an Increased Risk of Colorectal Neoplasms Regardless of Sex: Nationwide Population-Based Cohort Study.

Vitamin D may have anticancer effects against colorectal cancer (CRC). Bone mineral density (BMD) reflects the long-term vitamin D status. This study investigated the association between osteoporosis and colorectal neoplasms (CRN). The data were obtained from the National Health Insurance Service sample cohort, which included 60,386 osteoporosis patients and 8224 controls who underwent BMD in 2002-2019. The logistic regression models included age, sex, income level, and comorbidity. Sensitivity tests were performed using the data from the National Health Screening Program. In total, 7706 (11.2%) patients were diagnosed with CRN, and the proportion was significantly higher in osteoporosis patients than in controls (11.7% vs. 8.1%). In the multivariate analysis, osteoporosis was associated with an increased risk of CRN (odds ratio (OR) = 1.91, 95% confidence interval = 1.75-2.09, p < 0.0001), which was significant for both colorectal adenomas and CRC (OR = 1.88 and 1.83, respectively). A subgroup analysis by sex revealed a significant association between osteoporosis and CRN in both women and men (OR = 2.06 and 1.66, respectively). The sensitivity tests revealed results similar to those of the original dataset. In conclusion, osteoporosis is significantly associated with CRN risk in both sexes. In high-risk patients with low BMD, appropriate screening for CRN and vitamin D supplementation are required, regardless of sex.

A distinct Fusobacterium nucleatum clade dominates the colorectal cancer niche.

Fusobacterium nucleatum (Fn), a bacterium present in the human oral cavity and rarely found in the lower gastrointestinal tract of healthy individuals1, is enriched in human colorectal cancer (CRC) tumours2-5. High intratumoural Fn loads are associated with recurrence, metastases and poorer patient prognosis5-8. Here, to delineate Fn genetic factors facilitating tumour colonization, we generated closed genomes for 135 Fn strains; 80 oral strains from individuals without cancer and 55 unique cancer strains cultured from tumours from 51 patients with CRC. Pangenomic analyses identified 483 CRC-enriched genetic factors. Tumour-isolated strains predominantly belong to Fn subspecies animalis (Fna). However, genomic analyses reveal that Fna, considered a single subspecies, is instead composed of two distinct clades (Fna C1 and Fna C2). Of these, only Fna C2 dominates the CRC tumour niche. Inter-Fna analyses identified 195 Fna C2-associated genetic factors consistent with increased metabolic potential and colonization of the gastrointestinal tract. In support of this, Fna C2-treated mice had an increased number of intestinal adenomas and altered metabolites. Microbiome analysis of human tumour tissue from 116 patients with CRC demonstrated Fna C2 enrichment. Comparison of 62 paired specimens showed that only Fna C2 is tumour enriched compared to normal adjacent tissue. This was further supported by metagenomic analysis of stool samples from 627 patients with CRC and 619 healthy individuals. Collectively, our results identify the Fna clade bifurcation, show that specifically Fna C2 drives the reported Fn enrichment in human CRC and reveal the genetic underpinnings of pathoadaptation of Fna C2 to the CRC niche.

The combined use of anti-peptic agents is associated with an increased risk of osteoporotic fracture: a nationwide case-control study.

BACKGROUND/AIMS: Long-term use of acid suppressants such as proton pump inhibitors (PPIs) and histamine 2 receptor antagonist (H2RA) has been associated with the risk of osteoporotic fracture. Acid suppressants and muco-protective agents (MPAs) are often used together as anti-ulcer agents. We evaluated the association between the risk of osteoporotic fracture and the combined use of these anti-peptic agents. METHODS: A population-based case-control study was conducted by analyzing the Korean National Health Insurance Data from 2014 to 2020. Patients who had been prescribed anti-peptic agents, such as PPI, H2RA, or MPA, were included. Considering the incidence of osteoporotic fractures, the case group (n = 14,704) and control group (n = 58,816) were classified by 1:4 matching based on age and sex. RESULTS: The use of all types of anti-peptic agents was associated with an increased risk of osteoporotic fractures (PPI: hazard osteoratio [HR], 1.31; H2RA: HR, 1.44; and MPA: HR, 1.33; all p < 0.001). Compared to PPI alone, the combined use of "PPI and H2RA" (HR, 1.58; p = 0.010) as well as "PPI, H2RA, and MPA" (HR, 1.71; p = 0.001) was associated with an increased risk of osteoporotic fracture. However, compared with PPI alone, "MPA and PPI or H2RA" was not associated with an increased risk of osteoporotic fracture. CONCLUSION: This study found that the combined use of "PPI and H2RA" was associated with a higher risk of osteoporotic fractures. In cases where deemed necessary, the physicians may initially consider prescribing the combination use of MPA.

Transcriptional corepressor activity of CtBP1 is regulated by ISG15 modification.

C-terminal binding protein 1 (CtBP1) is a critical transcriptional corepressor of many tumor suppressor genes and plays diverse roles in the progression of cancers. The transcriptional repression function of CtBP1 is mediated by recruiting histone-modifying enzymes, such as histone deacetylases and histone methyltransferases, to target genes by binding with DNA-interacting factors. Several post-translational modifications of CtBP1 have been identified, including ubiquitination, phosphorylation, and SUMOylation. This paper reports that CtBP1 is conjugated by ISG15. Endogenous CtBP1 was modified by ISG15 after interferon-α treatment in HeLa cells. The ISGylation process of CtBP1 was regulated by deISGylation enzyme USP18 and ISG15 E3 ligase EFP. Interestingly, CtBP1 ISGylation affected the binding affinity between CtBP1 and some components of CtBP1-associated transcriptional complexes. HDAC1 and LSD1 bound more efficiently to ISG15-conjugated CtBP1 than non-conjugated CtBP1. On the other hand, binding between CtBP1 and HDAC4 was unaffected by ISG15 modification. Furthermore, ISG15 modification enhanced the transcriptional repression activity of CtBP1 on several target genes related to EMT and apoptosis. These findings suggest that the ISG15 modification of CtBP1 modulates the function and activity of CtBP1 and that CtBP1 ISGylation may provide a new insight for CtBP1-mediated cancers.

Reading of small bowel capsule endoscopy after frame reduction using an artificial intelligence algorithm.

OBJECTIVES: Poorly visualized images that appear during small bowel capsule endoscopy (SBCE) can confuse the interpretation of small bowel lesions and increase the physician's workload. Using a validated artificial intelligence (AI) algorithm that can evaluate the mucosal visualization, we aimed to assess whether SBCE reading after the removal of poorly visualized images could affect the diagnosis of SBCE. METHODS: A study was conducted to analyze 90 SBCE cases in which a small bowel examination was completed. Two experienced endoscopists alternately performed two types of readings. They used the AI algorithm to remove poorly visualized images for the frame reduction reading (AI user group) and conducted whole frame reading without AI (AI non-user group) for the same patient. A poorly visualized image was defined as an image with < 50% mucosal visualization. The study outcomes were diagnostic concordance and reading time between the two groups. The SBCE diagnosis was classified as Crohn's disease, bleeding, polyp, angiodysplasia, and nonspecific finding. RESULTS: The final SBCE diagnoses between the two groups showed statistically significant diagnostic concordance (k = 0.954, p < 0.001). The mean number of lesion images was 3008.5 ± 9964.9 in the AI non-user group and 1401.7 ± 4811.3 in the AI user group. There were no cases in which lesions were completely removed. Compared with the AI non-user group (120.9 min), the reading time was reduced by 35.6% in the AI user group (77.9 min). CONCLUSIONS: SBCE reading after reducing poorly visualized frames using the AI algorithm did not have a negative effect on the final diagnosis. SBCE reading method integrated with frame reduction and mucosal visualization evaluation will help improve AI-assisted SBCE interpretation.

The Effect of Tegoprazan on the Treatment of Endoscopic Resection-Induced Artificial Ulcers: A Multicenter, Randomized, Active-Controlled Study.

Background/Aims: : Tegoprazan is a novel potassium-competitive acid blocker that has beneficial effects on acid-related disorders such as gastroesophageal reflux and peptic ulcer diseases. This study aimed to validate the effect of tegoprazan on endoscopic submucosal dissection (ESD)-induced artificial ulcers. Methods: : Patients from 16 centers in Korea who underwent ESD for gastric neoplasia were enrolled. After ESD, pantoprazole was administered intravenously for 48 hours. The patients were randomly allocated to either the tegoprazan or esomeprazole group. Tegoprazan 50 mg or esomeprazole 40 mg were administered for 4 weeks, after which gastroscopic evaluation was performed. If the artificial ulcer had not healed, the same dose of tegoprazan or esomeprazole was administered for an additional 4 weeks, and a gastroscopic evaluation was performed. Results: : One hundred sixty patients were enrolled in this study. The healing rates of artificial ulcers at 4 weeks were 30.3% (23/76) and 22.1% (15/68) in the tegoprazan and esomeprazole groups, respectively (p=0.006). At 8 weeks after ESD, the cumulative ulcer healing rates were 73.7% (56/76) and 77.9% (53/68) in the tegoprazan and esomeprazole groups, respectively (p=0.210). Delayed bleeding occurred in two patients in the tegoprazan group (2.6%) and in one patient in the esomeprazole group (1.5%). Other adverse events were negligible in both groups. Conclusions: : Tegoprazan showed similar effects on post-ESD artificial ulcer healing in comparison with esomeprazole.

A Systematic Scoping Review on Dignity Assessment Tools.

CONTEXT: The provision of person-centered dignity-conserving care is central to palliative care. It is important to reevaluate current methods of assessing dignity as the concept of dignity is multifaceted. OBJECTIVES: The aim of this study is to understand the tools which are used to assess a patient's dignity and the elements of dignity evaluated in these tools. METHODS: Two independent and concurrent Systematic Evidence-Based Approach guided systematic scoping reviews (SSR in SEBA) on existing dignity assessment tools and on accounts of assessments of dignity were carried out. The SSR in SEBA on dignity assessment tools involving PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Scopus, and CINAHL databases saw 22 full-text articles included from the 645 articles reviewed. The SSR in SEBA on accounts of assessments of dignity featured in the PubMed database identified 102 full-text articles which saw 46 articles included. RESULTS: The domains identified were factors affecting patients' definition of dignity; elements of dignity-conserving care; and components of effective tools. CONCLUSION: Current accounts to assess dignity and assessment tools fail to capture shifting self-concepts of dignity holistically. A portfolio-like appraisal of dignity is proposed to achieve assessments that are timely, longitudinal, and patient-specific. Portfolio-based assessments by members of the multidisciplinary team will better direct timely evaluations of relevant aspects of changing concepts of dignity, without losing the patient's holistic perception of dignity.

Reduced risk of gastrointestinal bleeding associated with eupatilin in aspirin plus acid suppressant users: nationwide population-based study.

BACKGROUND/AIMS: Mucoprotective agents, such as eupatilin, are often prescribed to prevent gastrointestinal (GI) bleeding in addition to an acid suppressant despite the absence of a large-scale study. We evaluated the additional effect of eupatilin on the prevention of GI bleeding in both the upper and lower GI tract in concomitant aspirin and acid suppressant users using the nationwide database of national claims data from the Korean National Health Insurance Service (NHIS). METHODS: An aspirin cohort was constructed using the NHIS claims data from 2013 to 2020. Patients who manifested with hematemesis, melena, or hematochezia were considered to have GI bleeding. A Cox proportional hazards regression model was used to determine the risk factors for GI bleeding associated with the concomitant use of GI drugs and other covariates among aspirin users. RESULTS: Overall, a total of 432,208 aspirin users were included. The concurrent use of an acid suppressant and eupatilin (hazard ratio [HR] = 0.85, p = 0.016, vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Moreover, a more than 3-month duration (HR = 0.88, p = 0.030) of acid suppressant and eupatilin prescription (vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. CONCLUSION: Eupatilin administration for ≥ 3 months showed additional preventive effect on GI bleeding in concomitant aspirin and acid suppressant users. Thus, cotreatment with eupatilin with a duration of 3 months or longer is recommended for reducing GI bleeding among aspirin plus acid suppressant users.

SARS-CoV-2 exploits cellular RAD51 to promote viral propagation: implication of RAD51 inhibitor as a potential drug candidate against COVID-19.

IMPORTANCE: Viruses are constantly evolving to promote propagation in the host. Here, we show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes host RAD51 for replication. Silencing of RAD51 impaired SARS-CoV-2 propagation. Viral RNA colocalized with RAD51 in the cytoplasm of SARS-CoV-2-infected cells, suggesting that both viral RNA and RAD51 may form a replication complex. We, therefore, evaluated RAD51 inhibitors as possible therapeutic agents against SARS-CoV-2. Indeed, RAD51 inhibitors exerted antiviral activities against not only Wuhan but also variants of SARS-CoV-2. Molecular docking model shows that RAD51 inhibitors impede SARS-CoV-2 propagation by interfering with dimerization of RAD51. These data suggest that RAD51 may represent a novel host-based drug target for coronavirus disease 2019 treatment.

A natural product YSK-A blocks SARS-CoV-2 propagation by targeting multiple host genes.

Natural products and herbal medicine have been widely used in drug discovery for treating infectious diseases. Recent outbreak of COVID-19 requires various therapeutic strategies. Here, we used YSK-A, a mixture of three herbal components Boswellia serrata, Commiphora myrrha, and propolis, to evaluate potential antiviral activity against SARS-CoV-2. We showed that YSK-A inhibited SARS-CoV-2 propagation with an IC50 values of 12.5 µg/ml and 15.42 µg/ml in Vero E6 and Calu-3 cells, respectively. Using transcriptome analysis, we further demonstrated that YSK-A modulated various host gene expressions in Calu-3 cells. Among these, we selected 9 antiviral- or immune-related host genes for further study. By siRNA-mediated knockdown experiment, we verified that MUC5AC, LIF, CEACAM1, and GDF15 host genes were involved in antiviral activity of YSK-A. Therefore, silencing of these genes nullified YSK-A-mediated inhibition of SARS-CoV-2 propagation. These data indicate that YSK-A displays an anti-SARS-CoV-2 activity by targeting multiple antiviral genes. Although the exact antiviral mechanism of each constituent has not been verified yet, our data indicate that YSK-A has an immunomodulatory effect on SARS-CoV-2 and thus it may represent a novel natural product-derived therapeutic agent for treating COVID-19.

Self-Healing Sulfonated Poly(ether ether ketone)-Based Polymer Electrolyte Membrane for Direct Methanol Fuel Cells: Effect of Solvent Content.

Proton exchange membranes (PEMs) with superior characteristics are needed to advance fuel cell technology. Nafion, the most used PEM in direct methanol fuel cells (DMFCs), has excellent proton conductivity but suffers from high methanol permeability and long-term performance degradation. Thus, this study aimed to create a healable PEM with improved durability and methanol barrier properties by combining sulfonated poly(ether ether ketone) (SPEEK) and poly-vinyl alcohol (PVA). The effect of changing the N,N-dimethylacetamide (DMAc) solvent concentration during membrane casting was investigated. Lower DMAc concentrations improved water absorption and, thus, membrane proton conductivity, but methanol permeability increased correspondingly. For the best trade-off between these two characteristics, the blend membrane with a 10 wt% DMAc solvent (SP10) exhibited the highest selectivity. SP10 also showed a remarkable self-healing capacity by regaining 88% of its pre-damage methanol-blocking efficiency. The ability to self-heal decreased with the increasing solvent concentration because of the increased crosslinking density and structure compactness, which reduced chain mobility. Optimizing the solvent concentration during membrane preparation is therefore an important factor in improving membrane performance in DMFCs. With its exceptional methanol barrier and self-healing characteristics, the pioneering SPEEK/PVA blend membrane may contribute to efficient and durable fuel cell systems.

Treatment of postural headache occurred 26 days after spinal pain procedure - A case report.

BACKGROUND: Cerebrospinal fluid (CSF) leakage may cause intracranial hypotension and postural headache. Secondary intracranial hypotension may result from an iatrogenic dural puncture or traumatic injury associated with pain procedures. CASE: A 45-year-old male developed a headache 26 days after spinal pain procedure. Headache was characterized as postural, worsening with standing or sitting and improving while lying down. The pain did not resolve despite the administration of oral and intravenous analgesics. A spinal magnetic resonance imaging revealed epidural venous congestion and a suspicious CSF leak around the left L4/5 level. The patient received an epidural blood patch (EBP), the headache improved dramatically, and the patient was discharged. CONCLUSIONS: Delayed postural headaches may not be directly related to pain management. Nevertheless, intracranial hypotension related to pain management should be suspected even in this case. If confirmed, quickly applying an EBP is an effective treatment option.