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1.
Cardiol J ; 2021 Sep 15.
Article in English | MEDLINE | ID: mdl-34523115

ABSTRACT

BACKGROUND: It remains unclear whether P2Y12 monotherapy, especially clopidogrel, following short-duration dual antiplatelet therapy (DAPT) is associated with favorable outcomes in patients undergoing complex percutaneous coronary intervention (PCI). Therefore, this study analyzed the efficacy and safety of P2Y12 inhibitor monotherapy, mostly clopidogrel (78%), in complex PCI following short-term DAPT. METHODS: The post-hoc analysis of the SMART-CHOICE trial involving 2,993 patients included 498 cases of complex PCIs, defined by at least one of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with ≥ 2 stents implanted, and a total stent length of ≥ 60 mm. The primary endpoint was major adverse cardiac and cerebrovascular event (MACCE), defined as the composite of all-cause death, myocardial infarction, and stroke. The primary safety endpoint included bleeding, defined as Bleeding Academic Research Consortium (BARC) types 2 to 5. RESULTS: Complex PCI group had a higher risk of MACCE (4.0% vs. 2.3%, hazard ratio [HR] = 1.74, 95% confidence interval [CI]: 1.05-2.89, p = 0.033) and a similar risk of BARC types 2-5 bleeding (2.6% vs. 2.6%, HR = 1.02, 95% CI: 0.56-1.86, p = 0.939) compared with those without complex PCIs. Patients undergoing complex PCIs, followed by P2Y12 inhibitor monotherapy and 12 months of DAPT exhibited similar rates of MACCE (3.8% vs. 4.2%, HR = 0.92, 95% CI: 0.38-2.21, p = 0.853). CONCLUSIONS: P2Y12 inhibitor monotherapy, mostly clopidogrel, following 3 months of DAPT did not increase ischemic events in patients with complex PCIs.

2.
Article in English | MEDLINE | ID: mdl-34562328

ABSTRACT

BACKGROUND AND AIM: The efficacy and safety of the recently introduced low-volume purgatives in elderly people are not well known. Therefore, in this trial, we aimed to evaluate and compare the efficacy of two low-volume agents, oral sulfate solution (OSS) and 2-L polyethylene glycol with ascorbic acid (PEG-Asc), in elderly people. METHODS: A prospective, randomized, single-blinded, multicenter, non-inferiority trial was performed at three university-affiliated hospitals in South Korea. Outpatients aged 65-80 years, who underwent elective colonoscopy, were enrolled. The primary outcome was the rate of adequate bowel preparation assessed using the Boston Bowel Preparation Scale. RESULTS: A total of 199 subjects were randomized into the OSS (n = 99) or the 2-L PEG-Asc (n = 100) group. Of them, 189 subjects were included in the analysis of the primary outcome (OSS group 95 vs PEG-Asc group 94). The proportion of adequate bowel preparation was 89.5% (85/95) in the OSS group and 93.6% (88/94) in the 2-L PEG-Asc group. OSS was not inferior to 2-L PEG-Asc according to the prespecified non-inferiority margin of -15% (95% confidence interval for the difference, -12.1 to 3.8). Vomiting (11.6% vs 2.1%) and thirst (24.2% vs 11.7%) were more common in the OSS group than in the 2-L PEG-Asc group. CONCLUSIONS: OSS is an effective low-volume purgative that is non-inferior to 2-L PEG-Asc in elderly people. Both the low-volume agents were identified to be well tolerated and safe in the healthy elderly population.

3.
Article in English | MEDLINE | ID: mdl-34542059

ABSTRACT

BACKGROUND: Many patients complain of chronic cervical radicular pain, and pulsed radiofrequency (PRF) is known to have a positive effect for alleviating neuropathic pain. OBJECTIVES: In the present study, we used ultrasound (US) guidance and compared the effects of monopolar PRF with those of bipolar PRF in patients with chronic cervical radicular pain refractory to repeated transforaminal epidural steroid injections. METHODS: Sixty-six patients with chronic cervical radicular pain were included in this study. Patients were randomly assigned to one of the two groups: monopolar or bipolar PRF group (n= 33 per group). Pain intensity was evaluated using a numeric rating scale (NRS) at pretreatment, and at 1 and 3 months after the treatment. Target stimulation site was the extraforaminal nerve root. RESULTS: Compared to the pretreatment NRS scores, patients in both groups showed a significant decrease in NRS scores at 1 and 3 months after the treatment. Reductions in the NRS scores over time were significantly larger in the bipolar PRF group. Three months after the treatment, 18 patients (54.5%) in the monopolar PRF group and 27 (81.8%) in the bipolar PRF group reported successful pain relief (pain relief of ⩾50%). CONCLUSIONS: US-guided PRF can be an effective interventional technique for the management of chronic refractory cervical radiculopathy. Moreover, bipolar PRF has better treatment outcome than monopolar PRF.

4.
Neuron ; 109(17): 2691-2706.e5, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34473953

ABSTRACT

Although sex dimorphism is increasingly recognized as an important factor in pain, female-specific pain signaling is not well studied. Here we report that administration of IL-23 produces mechanical pain (mechanical allodynia) in female but not male mice, and chemotherapy-induced mechanical pain is selectively impaired in female mice lacking Il23 or Il23r. IL-23-induced pain is promoted by estrogen but suppressed by androgen, suggesting an involvement of sex hormones. IL-23 requires C-fiber nociceptors and TRPV1 to produce pain but does not directly activate nociceptor neurons. Notably, IL-23 requires IL-17A release from macrophages to evoke mechanical pain in females. Low-dose IL-17A directly activates nociceptors and induces mechanical pain only in females. Finally, deletion of estrogen receptor subunit α (ERα) in TRPV1+ nociceptors abolishes IL-23- and IL-17-induced pain in females. These findings demonstrate that the IL-23/IL-17A/TRPV1 axis regulates female-specific mechanical pain via neuro-immune interactions. Our study also reveals sex dimorphism at both immune and neuronal levels.


Subject(s)
Estrogen Receptor alpha/metabolism , Interleukin-17/metabolism , Interleukin-23/metabolism , Macrophages/metabolism , Nociceptive Pain/metabolism , Nociceptors/metabolism , TRPV Cation Channels/metabolism , Animals , Cells, Cultured , Female , Humans , Interleukin-17/pharmacology , Interleukin-23/pharmacology , Male , Mice , Mice, Inbred C57BL , Nerve Fibers, Unmyelinated/metabolism , Nerve Fibers, Unmyelinated/physiology , Nociceptive Pain/physiopathology , Nociceptors/drug effects , Nociceptors/physiology , Sex Factors , Signal Transduction
5.
Sci Rep ; 11(1): 15757, 2021 08 03.
Article in English | MEDLINE | ID: mdl-34345008

ABSTRACT

This study investigated the impact of bronchiectasis on patients admitted to the intensive care unit (ICU) at a hospital in Korea. Patients with bronchiectasis were diagnosed using results of chest computed tomography performed before ICU admission. The severity of bronchiectasis was based on the number of affected lobes, and patients with ≥ 3 bronchiectatic lobes were classified into the severe bronchiectasis group. Overall, 823 patients were enrolled. The mean age was 66.0 ± 13.9 years, and 63.4% were men. Bronchiectasis and severe bronchiectasis were present in 148 (18.0%) and 108 (13.1%) patients, respectively. The increase in the number of bronchiectatic lobes was related to the rise in ICU mortality (P for trend = 0.012) and in-hospital mortality (P for trend = 0.004). Patients with severe bronchiectasis had higher odds for 28-day mortality [odds ratio (OR) 1.122, 95% confidence interval (CI) 1.024-1.230], ICU mortality (OR 1.119, 95% CI 1.023-1.223), and in-hospital mortality (OR 1.208, 95% CI 1.092-1.337). The severe bronchiectasis group showed lower overall survival (log-rank P < 0.001), and the adjusted hazard ratio was 1.535 (95% CI 1.178-2.001). Severe bronchiectasis had a negative impact on all-cause mortality during ICU and hospital stays, resulting in a lower survival rate.

6.
Sci Rep ; 11(1): 15637, 2021 08 02.
Article in English | MEDLINE | ID: mdl-34341385

ABSTRACT

Chronic pancreatitis (CP) related main pancreatic duct (MPD) stricture has been a challenge for endoscopists. Fully covered self-expandable metal stents (FC-SEMS) has been tried in CP patients, but the efficacy and safety are still controversial. Thus, we aim to compare the long-term clinical efficacy of FC-SEMS vs. plastic stent placement in persistent MPD strictures secondary to CP. Between 2007 and 2018, 80 chronic pancreatitis patients (58 males, median age 49 years), who underwent endoscopic placement of FC-SEMS (n = 26) and plastic stent (n = 54) for persistent MPD strictures after at least 3 months of initial single plastic stenting, were retrospectively analyzed during a median follow-up duration of 33.7 months. As a result, MPD stricture resolution rate was statistically higher in FC-SEMS group (87.0% vs. 42.0%, p < 0.001). Although immediate complications occurred similarly (38.5% vs. 37.0%, p = 0.902), spontaneous migration (26.9%) and de novo strictures (23.1%) were pronounced delayed complications in FC-SEMS group. Pain relief during follow-up was significantly higher in FC-SEMS group (76.9% vs. 53.7%, p = 0.046). The total procedure cost was similar in both groups ($1,455.6 vs. $1,596.9, p = 0.486). In comparison with plastic stent, FC-SEMS placement for persistent MPD strictures had favorable long-term clinical efficacy, with its typical complications like spontaneous migration and de novo strictures.

7.
Pharmaceutics ; 13(8)2021 Jul 27.
Article in English | MEDLINE | ID: mdl-34452103

ABSTRACT

AC1497 is an effective dual inhibitor of malate dehydrogenase 1 and 2 targeting cancer metabolism. However, its poor aqueous solubility results in low bioavailability, limiting its clinical development. This study was conducted to develop an effective self-nanoemulsifying drug delivery system (SNEDDS) of AC1497 to improve its oral absorption. Based on the solubility of AC1497 in various oils, surfactants, and cosurfactants, Capryol 90, Kolliphor RH40, and Transcutol HP were selected as the components of SNEDDS. After testing various weight ratios of Capryol 90 (20-30%), Kolliphor RH40 (35-70%), and Transcutol HP (10-35%), SNEDDS-F4 containing 20% Capryol 90, 45% Kolliphor RH40, and 35% Transcutol HP was identified as an optimal SNEDDS with a narrow size distribution (17.8 ± 0.36 nm) and high encapsulation efficiency (93.6 ± 2.28%). Drug release from SNEDDS-F4 was rapid, with approximately 80% of AC1497 release in 10 min while the dissolution of the drug powder was minimal (<2%). Furthermore, SNEDDS-F4 significantly improved the oral absorption of AC1497 in rats. The maximum plasma concentration and area under the plasma concentration-time curve of AC1497 were, respectively 6.82- and 3.14-fold higher for SNEDDS-F4 than for the drug powder. In conclusion, SNEDDS-F4 with Capryol 90, Kolliphor RH40, and Transcutol HP (20:45:35, w/w) effectively improves the solubility and oral absorption of AC1497.

8.
Vaccines (Basel) ; 9(7)2021 Jul 02.
Article in English | MEDLINE | ID: mdl-34358141

ABSTRACT

Following the clinical success of cancer immunotherapies such as immune checkpoint inhibitors blocking B7/CTLA-4 or PD-1/PD-L1 signaling and ongoing numerous combination therapies in the clinic,3 bispecific antibodies (BsAbs) are now emerging as a growing class of immunotherapies with the potential to improve clinical efficacy and safety further. Here, we describe four classes of BsAbs: (a) immune effector cell redirectors; (b) tumor-targeted immunomodulators; (c) dual immunomodulators; and (d) dual tumor-targeting BsAbs. This review describes each of these classes of BsAbs and presents examples of BsAbs in development. We reviewed the biological rationales and characteristics of BsAbs and summarized the current status and limitations of clinical development of BsAbs and strategies to overcome limitations. The field of BsAb-based cancer immunotherapy is growing, and more data from clinical trials are accumulating. Thus, BsAbs could be the next generation of new treatment options for cancer patients.

9.
Small ; : e2102602, 2021 Aug 02.
Article in English | MEDLINE | ID: mdl-34339104

ABSTRACT

In this study, high-purity and centimeter-scale bulk Ta2 Ni3 Se8 crystals are obtained by controlling the growth temperature and stoichiometric ratio between tantalum, nickel, and selenium. It is demonstrated that the bulk Ta2 Ni3 Se8 crystals could be effectively exfoliated into a few chain-scale nanowires through simple mechanical exfoliation and liquid-phase exfoliation. Also, the calculation of electronic band structures confirms that Ta2 Ni3 Se8 is a semiconducting material with a small bandgap. A field-effect transistor is successfully fabricated on the mechanically exfoliated Ta2 Ni3 Se8 nanowires. Transport measurements at room temperature reveal that Ta2 Ni3 Se8 nanowires exhibit ambipolar semiconducting behavior with maximum mobilities of 20.3 and 3.52 cm2 V-1 s-1 for electrons and holes, respectively. The temperature-dependent transport measurement (from 90 to 295 K) confirms the carrier transport mechanism of Ta2 Ni3 Se8 nanowires. Based on these characteristics, the obtained 1D vdW material is expected to be a potential candidate for additional 1D materials as channel materials.

10.
Plant Foods Hum Nutr ; 76(3): 326-333, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34279786

ABSTRACT

This study comprehensively presents the relationship between the bioactive substance of 70% (v/v) aqueous ethanol extract of 38 species of seaweeds (SWEs), and anti-glycation activities. The contents of bioactive substance of SWEs, such as total phenolic, total flavonoid and condensed tannins, were determined through a colorimetric analysis. Among the tested species, Ecklonia bicyclis, Ishige foliacea, and Cladophora urightiana var. minor had the highest amount of total phenolic (255.75 mg GAE/g DW), total condensed tannins (63.36 mg CE/g DW), and total flavonoid content (85.26 mg CE/g DW), respectively. Anti-glycation properties of SWEs were evaluated through advanced glycation end-products (AGEs) formation, AGEs-collagen cross-link formation, and AGEs-collagen cross-link breaking assay. Brown algae species exhibited a more prominent inhibitory activity on AGEs formation and AGEs-collagen cross-links, and the breaking of AGEs-collagen cross-links compared to that exhibited by aminoguanidine and ALT-711 (positive controls). Using principal component analysis, we confirmed that the AGEs formation inhibitory property and AGEs-collagen cross-links breaking activity were closely correlated with total phenolic and the condensed tannin contents contained in SWEs. Therefore, the bioactive substances such as phenolics and condensed tannins in seaweeds can be used as predictive indices in selecting compounds for the development of a therapeutic agent that prevents diabetic complications related to the AGEs. In addition, our results suggest that brown algae species, which contains more bioactive substances than green and red algae species, can be utilized as a promising natural resource for the prevention and alleviation of AGEs-related diabetic complications as AGE inhibitor and cross-links breaker.


Subject(s)
Glycation End Products, Advanced , Seaweed , Phenols , Plant Extracts/pharmacology , Principal Component Analysis
11.
Adv Ther ; 38(8): 4366-4387, 2021 08.
Article in English | MEDLINE | ID: mdl-34250583

ABSTRACT

INTRODUCTION: Long-term, real-world safety and effectiveness data are required to support biosimilar use. This analysis pooled 5-year findings from observational studies of infliximab biosimilar CT-P13 treatment in patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and ankylosing spondylitis (AS). METHODS: Patients enrolled in the CT-P13 4.2, 4.3, or 4.4 Korea/European Union registries were analysed if they had initiated infliximab treatment with CT-P13 (CT-P13 group) or had switched from reference infliximab to CT-P13 (switched to CT-P13 group). The primary objective was to investigate long-term safety by evaluating adverse events of special interest (AESIs) per the CT-P13 risk-management plan. Incidence rates per 100 patient-years (PYs) were calculated. Additional long-term safety endpoints, immunogenicity (assessments optional), and effectiveness were evaluated. RESULTS: Overall, 736 patients (642 CT-P13; 94 switched to CT-P13) were analysed. Median (range) exposure to CT-P13 was 19.433 (0.03-63.11) months overall. The incidence of treatment-emergent adverse events was 69.0% (CT-P13 group) and 60.6% (switched to CT-P13 group). Infusion-related reaction/hypersensitivity/anaphylactic reaction was the most frequent AESI overall, with an incidence of 4.3828 per 100 PY (95% confidence interval: 3.3603-5.6185). For most AESIs, incidence rates per 100 PY were broadly comparable between treatment groups, considering overlapping 95% confidence intervals. At baseline, 42/445 (9.4%) and 21/59 (35.6%) evaluable patients in the CT-P13 and switched to CT-P13 groups, respectively, were antidrug antibody (ADA)-positive. After CT-P13 treatment during the study, 188/425 (44.2%) evaluable patients had ≥ 1 ADA-positive result, including 147/425 (34.6%) patients with negative or no ADA results reported at baseline. Effectiveness tended to increase over time for all indications. CONCLUSION: The analysis did not identify any new safety findings for patients with RA, IBD, and AS treated with CT-P13 for up to 5 years in those who were infliximab-naïve at CT-P13 initiation, or those who had switched from reference infliximab to CT-P13. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02557295 (CT-P13 4.2; retrospectively registered on 23 September 2015); NCT02326155 (CT-P13 4.3; retrospectively registered on 25 December 2014); NCT02557308 (CT-P13 4.4; retrospectively registered on 23 September 2015).


Subject(s)
Arthritis, Rheumatoid , Biosimilar Pharmaceuticals , Inflammatory Bowel Diseases , Spondylitis, Ankylosing , Antibodies, Monoclonal , Arthritis, Rheumatoid/drug therapy , Biosimilar Pharmaceuticals/adverse effects , Humans , Inflammatory Bowel Diseases/drug therapy , Infliximab/therapeutic use , Spondylitis, Ankylosing/drug therapy , Treatment Outcome
12.
Int J Rheum Dis ; 24(9): 1137-1147, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34250745

ABSTRACT

AIM: To evaluate clinical characteristics and natural history of non-radiographic axial spondyloarthritis (nr-axSpA) using KOrean Nonradiographic Axial SPondyloArthritis (KONASPA) data. METHODS: Data were collected from 11 centers in South Korea. A total of 278 patients with nr-axSpA from January 2018 to July 2020 were included. Demographic data, clinical features, comorbidities, disease activity, medications, and laboratory results were collected. RESULTS: Mean age at symptom onset was 28.2 ± 14.2 years. Of 278 patients, 152 (54.7%) were male. Mean Bath Ankylosing Spondylitis Disease Activity Index at diagnosis was 3.5 ± 2.1. Dyslipidemia was the most common comorbidity (8.4%), followed by hypertension (6.1%). Mean age at diagnosis of nr-axSpA was older in female patients than in male patients (31.8 ± 15.8 years vs 24.9 ± 12.0 years, P < 0.001). Enthesitis and uveitis were more frequently found in female patients than in male patients. Thirty-one (11.1%) participants with nr-axSpA progressed to ankylosing spondylitis. The median follow-up duration was 48 months. In multivariable Cox regression analysis, age at symptom onset (hazard ratio [HR] 0.93, 95% confidence interval (CI) 0.88-0.97, P = 0.006), body mass index (BMI) (HR 1.24, 95% CI 1.06-1.44, P = 0.005) and sacroiliitis grade (HR 1.86, 95% CI 1.19-2.92, P = 0.006) were associated with progression to ankylosing spondylitis. CONCLUSIONS: Results of nationwide data revealed that women with nr-axSpA showed a late disease onset and more extra-articular manifestations than men. Young age at symptom onset, high BMI, and presence of radiographic sacroiliitis at diagnosis were risk factors for progression to AS.

13.
ACS Nano ; 2021 Jul 22.
Article in English | MEDLINE | ID: mdl-34291918

ABSTRACT

Controlling the microstructures in fibers, such as crystalline structures and microvoids, is a crucial challenge for the development of mechanically strong graphene fibers (GFs). To date, although GFs graphitized at high temperatures have exhibited high tensile strength, GFs still have limited the ultimate mechanical strength owing to the presence due to the structural defects, including the imperfect alignment of graphitic crystallites and the presence of microsized voids. In this study, we significantly enhanced the mechanical strength of GF by controlling microstructures of fibers. GF was hybridized by incorporating polyacrylonitrile (PAN) in the graphene oxide (GO) dope solution. In addition, we controlled the orientation of the inner structure by applying a tensile force at 800 °C. The results suggest that PAN can act as a binder for graphene sheets and can facilitate the rearrangement of the fiber's microstructure. PAN was directionally carbonized between graphene sheets due to the catalytic effect of graphene. The resulting hybrid GFs successfully displayed a high strength of 1.10 GPa without undergoing graphitization at extremely high temperatures. We believe that controlling the alignment of nanoassembled structure is an efficient strategy for achieving the inherent performance characteristics of graphene at the level of multidimensional structures including films and fibers.

14.
Yonsei Med J ; 62(8): 702-707, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34296547

ABSTRACT

PURPOSE: We aimed to determine the relationship between environmental exposure and nontuberculous mycobacterial pulmonary disease (NTM-PD) in Korea. MATERIALS AND METHODS: A group of 150 patients with NTM-PD and a control group of 217 patients with other respiratory diseases were prospectively enrolled between June 2018 and December 2020 in Seoul, Korea. They were surveyed with a standardized questionnaire, and their medical records were reviewed. Odds ratio (OR) and 95% confidence intervals (CI) were calculated with multivariate logistic regression analysis. RESULTS: The mean ages of the NTM-PD and control groups were similar (63.8±9.2 years vs. 63.5±10.0 years; p=0.737), and most patients were female (76.0% vs. 68.7%; p=0.157) and nonsmokers (82.0% vs. 72.8%; p=0.021). Mycobacterium avium (49.3%) was the most commonly identified strain among NTM-PD patients, followed by M. intracellulare (32.0%) and M. abscessus subspecies massiliense (12.7%). There were no differences in housing type or frequency of soil- or pet-related exposure between the case and the control groups. However, in subgroup analysis excluding patients with M. intracellulare infection, more case patients frequently visited public baths ≥1 time/week (35.3% vs. 19.4%, p=0.003); this remained significant after multivariate analysis (OR, 2.84; 95% CI, 1.58-5.17). CONCLUSION: Frequent exposure to water at public baths might affect the odds of contracting NTM-PD, excluding individuals infected with M. intracellulare strains.


Subject(s)
Lung Diseases , Nontuberculous Mycobacteria , Aged , Female , Humans , Lung Diseases/epidemiology , Middle Aged , Mycobacterium avium Complex , Republic of Korea/epidemiology , Risk Factors , Seoul
15.
Sci Total Environ ; 797: 148944, 2021 Nov 25.
Article in English | MEDLINE | ID: mdl-34298360

ABSTRACT

The land-use change from natural to managed farmland ecosystems can undergo perturbations and significantly impact soil environment and communities. To understand how anthropogenic land-use alteration determines in-depth relationships among soil environmental factors and soil bacterial communities, high-resolution characterization was performed using soil samples (27 spots × 3 depths; top 10-20 cm, middle 90-100 cm, bottom 180-190 cm) from a natural forest and a 50 year-old farmland. The soil bacterial community abundance (number of OTU's per sample) and diversity (Faith's phylogenetic diversity) was significantly higher in the top layer of farmland soil than in forest soil. However, the differences in bacterial community abundance between farmland and forest decreased with depth, suggesting that the effect of fertilization was limited to top and middle layers. The phyla Acidobacteria and Proteobacteria were distributed distinctively during the land-use change. The subgroups Gp1-3 of Acidobacteria were more abundant in the forest samples (pH 3.5-5), while Gp4-7 and Gp10 were predominant in the farmland (pH 4.5-9.5). Members belonging to α-Proteobacteria and Xanthomonadales in γ-Proteobacteria were dominant in the forest, whereas ß-, δ-, and γ-Proteobacteria were relatively abundant in the farmland. Both multivariate and correlation network analyses revealed that Acidobacteria and Proteobacteria communities were significantly affected by soil pH, as well as toxic metals from pesticides (Zn, Cr, Ni, Cu, Cd, As) and terminal electron acceptors (NO3, bioavailable Fe(III), SO4). In line with the long history of anthropogenic fertilization, the farmland site showed high abundance of membrane and ATP-binding cassette transporter genes, suggesting the key for uptake of nutrients and for protection against toxic metals and environmental stresses. This study provides new insights into the use of both Acidobacteria and Proteobacteria community structures as a bacterial indicator for land-use change.


Subject(s)
Acidobacteria , Soil , Acidobacteria/genetics , Ecosystem , Farms , Ferric Compounds , Forests , Phylogeny , Proteobacteria/genetics , RNA, Ribosomal, 16S , Soil Microbiology
16.
J Hazard Mater ; 418: 126365, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34329019

ABSTRACT

As the most widely used anionic surfactant, linear alkylbenzene sulfonate (LAS) requires biological alkane degradation when it is treated using an activated sludge (AS) process in a wastewater treatment plant because of its structural carboxylic unavailability. As consumption of LAS is gradually increasing, LAS loading into the WWTP is accordingly increasing. However, fewer studies have examined the involvement of the AS microbial community in the LAS degradation. In this study, metagenomic approaches were used to define microbiomes involved in LAS degradation in AS, with a particular focus on ω-hydroxylation. The abundance and diversity of alkane-degrading genes were investigated, and these genes were integrated with reconstructed metagenome-assembled genomes (MAGs). Additionally, the association of functional genes and MAGs with respect to LAS degradation was investigated. The results showed that alkB and cytochrome P450 genes were only shared within specific MAGs. Unique sets of genes with diverse abundances were detected in each sample. The MAGs with the alkB and cytochrome P450 genes were strongly associated with the other MAGs and involved in positive commensal interactions. The findings provided significant insights into how the AS microbiomes, which have continuously treated anionic surfactants for decades, potentially metabolize LAS and interact with commensal bacteria.


Subject(s)
Alkanesulfonic Acids , Microbiota , Metagenome , Microbiota/genetics , Sewage , Surface-Active Agents
17.
Cancer Med ; 10(17): 5809-5822, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34258882

ABSTRACT

OBJECTIVES: The optimal sequence for the administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for treating non-small cell lung cancer (NSCLC) is still unclear. This study aimed to evaluate the efficacy of sequential afatinib and osimertinib treatment in patients with NSCLC harboring EGFR mutations. MATERIALS AND METHODS: Electronic records of patients with EGFR-mutated NSCLC, who were administered afatinib and osimertinib (group A) or other chemotherapy (group B) between October 2014 and 2019, across 16 hospitals in South Korea were reviewed. The primary outcome, time on treatment (TOT), secondary outcome, and overall survival (OS) were estimated using the Kaplan-Meier method and log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. RESULTS: Of the 737 patients who received frontline afatinib treatment, 324 with complete records were selected (group A: 126, group B: 198). All patients in group A were T790M positive after afatinib, while patients in group B were all negative or unknown. The median TOT was 35.4 months (95% confidence interval [CI]: 27.7-45.6) in group A and 20.8 months (95% CI: 19.4-24.0) in group B. The median TOT with afatinib was 13.0 months (95% CI: 12.0-13.9) overall and 15.7 months (95% CI: 13.9-17.3) in group A. The 2- and 3-year survival rates were 86.0 and 69.3% in group A and 75.9 and 55.3% in group B, respectively. CONCLUSION: Sequential afatinib and osimertinib treatment resulted in better survival rates than treatment with afatinib followed by other chemotherapies.

18.
Sci Rep ; 11(1): 11489, 2021 06 01.
Article in English | MEDLINE | ID: mdl-34075086

ABSTRACT

We used 16S ribosomal RNA sequencing to evaluate changes in the gut microbiota of mice fed a diet supplemented with either raw or cooked beef loin powder for 9 weeks. Male BALB/c mice (n = 60) were randomly allocated to five groups: mice fed AIN-93G chow (CON), chow containing 5% (5RB) and 10% (10RB) raw beef loin powder, and chow containing 5% (5CB) and 10% (10CB) cooked beef loin powder. Dietary supplementation with both RB and CB increased the relative abundance of Clostridiales compared to the CON diet (p < 0.05). Mice fed 10RB showed a significantly higher relative abundance of Firmicutes (p = 0.018) and Lactobacillus (p = 0.001) than CON mice, and the ratio of Firmicutes/Bacteroidetes showed an increasing trend in the 10RB mice (p > 0.05). Mice fed 10CB showed a higher abundance of Peptostreptococcaceae and a lower abundance of Desulfovibrionaceae compared with the CON mice (p < 0.05). Genes for glycan biosynthesis, which result in short-chain fatty acid synthesis, were enriched in the CB mice compared to the RB mice, which was correlated to a high abundance of Bacteroides. Overall, dietary RB and CB changed the gut microbiota of mice (p < 0.05).

19.
Article in English | MEDLINE | ID: mdl-34151824

ABSTRACT

BACKGOUND: Lateral epicondylitis (LE) is one of the most common musculoskeletal disorders that causes pain. OBJECTIVES: We evaluated the effect of the inclusion of a minimal dose of corticosteroid in a solution comprising autologous whole blood (AWB), 20% dextrose, and 2% lidocaine for treating LE. METHODS: In this randomized prospective trial LE patients were allocated to the CS+ group (n= 70; solution comprising 1 mL AWB, 1 mL 20% dextrose, 0.4 mL 2% lidocaine, and 0.1 mL (0.4 mg) dexamethasone palmitate; injected into the common wrist extensor tendon) or the CS- group (n= 70; same solution as above but without dexamethasone palmitate). Five injections were administered at monthly intervals. At each visit, pain intensity was evaluated using the numeric rating scale (NRS), and grip strength was measured using a hand-grip dynamometer. RESULTS: In the CS+ and CS- groups, 1 and 10 patients dropped out, respectively. In both groups, the NRS scores at each evaluation were significantly lower than the pretreatment scores. The NRS scores from pretreatment to the second and third visits were significantly lower in the CS+ group than those in the CS- group. However, at the fourth and fifth visits, and 6 months after the last injection (the sixth visit), the degree of pain reduction between the groups was not significantly different. Grip strength increased significantly over time in both groups. At each evaluation, grip strength was significantly higher than that at the pretreatment stage. However, the degree of increase was not significantly different between groups. CONCLUSIONS: The inclusion of a minimal dose of corticosteroid in the AWB and 20% dextrose injection can reduce pain, especially during early treatment.

20.
PLoS One ; 16(5): e0252135, 2021.
Article in English | MEDLINE | ID: mdl-34038481

ABSTRACT

Skeletal muscle atrophy is a feature of aging (termed sarcopenia) and various diseases, such as cancer and kidney failure. Effective drug treatment options for muscle atrophy are lacking. The tapeworm medication, niclosamide is being assessed for repurposing to treat numerous diseases, including end-stage cancer metastasis and hepatic steatosis. In this study, we investigated the potential of niclosamide as a repurposing drug for muscle atrophy. In a myotube atrophy model using the glucocorticoid, dexamethasone, niclosamide did not prevent the reduction in myotube diameter or the decreased expression of phosphorylated FOXO3a, which upregulates the ubiquitin-proteasome pathway of muscle catabolism. Treatment of normal myotubes with niclosamide did not activate mTOR, a major regulator of muscle protein synthesis, and increased the expression of atrogin-1, which is induced in catabolic states. Niclosamide treatment also inhibited myogenesis in muscle precursor cells, enhanced the expression of myoblast markers Pax7 and Myf5, and downregulated the expression of differentiation markers MyoD, MyoG and Myh2. In an animal model of muscle atrophy, niclosamide did not improve muscle mass, grip strength or muscle fiber cross-sectional area. Muscle atrophy is also feature of cancer cachexia. IC50 analyses indicated that niclosamide was more cytotoxic for myoblasts than cancer cells. In addition, niclosamide did not suppress the induction of iNOS, a key mediator of atrophy, in an in vitro model of cancer cachexia and did not rescue myotube diameter. Overall, these results suggest that niclosamide may not be a suitable repurposing drug for glucocorticoid-induced skeletal muscle atrophy or cancer cachexia. Nevertheless, niclosamide may be employed as a compound to study mechanisms regulating myogenesis and catabolic pathways in skeletal muscle.

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