Alginate microribbons with longitudinally grooved microstructures are continuously fabricated by means of a microfluidic system. The number and dimensions of the microgroovesare successfully ...controlled by regulation of the slit‐shaped channel (yellow in figure). This method opens up the possibility of mass production of scaffolds for tissue engineering purposes, as it is proved that the grooved flat fibers can be used to align other types of cells in culture.
With an increase in the aging population, the number of older adults who require long-term care (LTC) is growing, enhancing drug-related issues. The reduced capacity of LTC users to precisely utilize ...medical services poses additional challenges owing to restrictions in daily activities. We compared older adults who required LTC with those who did not require LTC to confirm differences in the use of potentially inappropriate medications (PIMs), frequently used PIMs, and associating factors in Korea.
Using the Korean National Health Insurance Service cohort data, adults aged ≥ 65 years as of 2017 who were LTC beneficiaries (at home and LTC facilities) were selected and matched 1:1 with a control group (LTC non-beneficiaries). PIM was defined based on the 2019 American Society of Geriatrics Beers criteria. PIM use and medical resource utilization according to LTC requirements were compared for one year after the index date. After correcting for other confounding variables, differences in the risk of PIM use on person-based according to LTC eligibility were assessed using multivariate logistic regression.
Among the 13,251 older adults requiring LTC in 2017, 9682 were matched with counterparts and included. Among those who received an outpatient prescription including PIM at least once yearly, 83.6 and 87.6% were LTC beneficiaries and LTC non-beneficiaries, respectively (p < 0.001). Using the number of outpatient prescriptions as the baseline, 37.2 and 33.2% were LTC beneficiaries and LTC non-beneficiaries, respectively (p < 0.001). In both groups, elevated PIM use depended on increased medical resource utilization, as shown by increased outpatient visits and medical care institutions visited. Adjusting other influencing factors, the need for LTC did not significantly associated with PIM use (odds ratio OR 0.93, 95% confidence interval CI 0.84-1.04); the number of drugs consumed (3-4: OR 1.42, 95% CI 1.25-1.61; 5-9: OR 2.24, 95% CI 1.98-2.53; 10 and more: OR 3.72, 95% CI 3.03-4.55; reference group: 2 and less), frequency of visits (7-15: OR 1.95, 95% CI 1.71-2.23; 16-26: OR 3.51, 95% CI 3.02-4.07; 27-42: OR 5.84, 95% CI 4.84-7.05; 43 and more: OR 10.30, 95% CI 8.15-13.01; reference group: 6 and less), and visits to multiple medical care institutions (3-4: OR 1.96, 95% CI 1.76-2.19; 5 and more: OR 3.21, 95% CI 2.76-3.73; reference group: 2 and less) emerged as primary influencing factors. PIMs mainly prescribed included first-generation antihistamines, benzodiazepines, and Z-drugs in both groups; quetiapine ranked second-highest among LTC beneficiaries.
The LTC demand did not significantly associated with PIM utilization. However, the number of drugs consumed, and the pattern of medical resource use were important factors, regardless of LTC requirements. This highlights the need to implement comprehensive drug management focusing on patients receiving polypharmacy and visiting multiple care institutions, regardless of LTC needs.
Tuberculosis (TB) is one of the serious infectious diseases in South Korea, with 49 new cases per 100,000 people and 629 multi-drug resistant (MDR) cases reported in 2020. TB is increasing among ...immigrants in S. Korea, and various TB case finding strategies are being performed for screening. We compared active case finding (ACF) with passive case finding (semi-PCF) across epidemiological characteristics and investigated a cost-effective strategy for screening immigrants for TB.
ACF driven by non-governmental organizations and semi-PCF as part of the government's visa renewal process using CXR with additional acid-fast bacilli (AFB) smear and cultures were performed. Epidemiological parameters were compared between the two TB screening projects, and costs were collected. Cost-effectiveness was evaluated using a decision analysis model from the health system perspective. The primary outcome was incremental cost-effectiveness ratio (ICER) per averted TB case. Additional probabilistic sensitivity analysis was conducted.
ACF (2.02%) showed a higher TB prevalence rate than semi-PCF (0.67%) on CXR. For subjects older than 60 years, the suspected TB rate on CXR was significantly higher in ACF (36.6%) than in semi-PCF (12.2%) (P<0.01). TB incidence among the family visa type was significantly higher in ACF (1.96%) than in semi-PCF (0.88%) (P < 0.0012). Costs for ACF ($666.92) were $20.784 higher than for semi-PCF ($646.13), but TB progression decreased by 0.02, resulting in an ICER of $948.18 per averted TB case. In sensitivity analysis, the indirect costs of ACF and semi-PCF had the highest impact on ICER.
ACF found more TB cases than semi-PCF through CXR screening, and suspect cases with old age and family visa type were more common in ACF than in semi-PCF. ACF is cost-effective as a TB screening strategy for immigrants.
Despite its significant impact on mortality, tuberculosis (TB)-diabetes mellitus (DM) co-prevalence has not been well-elucidated for the cause of death. We investigated the impact of DM on TB-related ...and non-TB-related deaths in patients with TB. This retrospective nationwide cohort study included patients diagnosed with TB between 2011 and 2017 in South Korea. We performed Fine and Gray regression model analyses to assess the mortality risk of DM classified by cause of death. Of 239,848 patients, 62,435 (26.0%) had DM, and 20,203 died during anti-TB treatment. Of all deaths, 47.9% (9,668) were caused by TB, and the remaining 52.1% (10,535) was attributed to various non-TB-related causes. The mortality rate was higher in the DM than in the non-DM groups in both men and women. DM was associated with a higher risk of TB-related (adjusted hazard ratio aHR 1.07, 95% confidence interval CI 1.01-1.13) and non-TB-related (aHR 1.21, 95% CI 1.15-1.27) deaths in men; however, only a higher risk of non-TB-related deaths (aHR 1.29, 95% CI 1.20-1.38) in women. Our findings indicate that DM is independently associated with a greater risk of death during anti-TB treatment among patients with TB for both TB-related and non-TB-related deaths.
Gastric adenocarcinoma (GAC) is a lethal disease characterized by genomic and clinical heterogeneity. By integrating 8 previously established genomic signatures for GAC subtypes, we identified 6 ...clinically and molecularly distinct genomic consensus subtypes (CGSs). CGS1 have the poorest prognosis, very high stem cell characteristics, and high IGF1 expression, but low genomic alterations. CGS2 is enriched with canonical epithelial gene expression. CGS3 and CGS4 have high copy number alterations and low immune reactivity. However, CGS3 and CGS4 differ in that CGS3 has high HER2 activation, while CGS4 has high SALL4 and KRAS activation. CGS5 has the high mutation burden and moderately high immune reactivity that are characteristic of microsatellite instable tumors. Most CGS6 tumors are positive for Epstein Barr virus and show extremely high levels of methylation and high immune reactivity. In a systematic analysis of genomic and proteomic data, we estimated the potential response rate of each consensus subtype to standard and experimental treatments such as radiation therapy, targeted therapy, and immunotherapy. Interestingly, CGS3 was significantly associated with a benefit from chemoradiation therapy owing to its high basal level of ferroptosis. In addition, we also identified potential therapeutic targets for each consensus subtype. Thus, the consensus subtypes produced a robust classification and provide for additional characterizations for subtype-based customized interventions.
Obesity is a common metabolic disorder caused by a sedentary lifestyle, and a high-fat and a high-glucose diet in the form of fast foods. High-fat diet-induced obesity is a major cause of diabetes ...and cardiovascular diseases, whereas exercise and physical activity can ameliorate these disorders. Moreover, exercise and the gut microbiota are known to be interconnected, since exercise can increase the gut microbial diversity and contribute to the beneficial health effects. In this context, we analyzed the effect of diet and exercise on the gut microbiota of mice, by next-generation sequencing of the bacterial V4 region of 16S rRNA. Briefly, mice were divided into four groups: chow-diet (CD), high-fat diet (HFD), high-fat diet + exercise (HFX), and exercise-only (EX). The mice underwent treadmill exercise and diet intervention for 8 weeks, followed by the collection of their feces and DNA extraction for sequencing. The data were analyzed using the QIIME 2 bioinformatics platform and R software to assess their gut microbial composition, richness, and diversity. The Bacteroidetes to Firmicutes ratio was found to be decreased manifold in the HFD and HFX groups compared to the CD and EX groups. The gut microbial richness was comparatively lower in the HFD and HFX groups and higher in the CD and EX groups (ACE, Chao1, and observed OTUs). However, the Shannon alpha diversity index was higher in the HFD and HFX groups than in the CD and EX groups. The beta diversity based on Jaccard, Bray–Curtis, and weighted UniFrac distance metrics was significant among the groups, as measured by PERMANOVA. Paraprevotella, Desulfovibrio, and Lactococcus were the differentially abundant/present genera based on the intervention groups and in addition to these three bacteria, Butyricimonas and Desulfovibrio C21c20 were differentially abundant/present based on diet. Hence, diet significantly contributed to the majority of the changes in the gut microbiota.
Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested ...as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis. Moreover, a molecular docking study revealed that kaempferol inhibited FGFR3 activity by binding to the active pocket of the FGFR3 kinase domain. Kaempferol forms hydrogen bonds with the FGFR3 backbone oxygen of Glu555 and Ala558 and the side chain of Lys508. Notably, the inhibition of bFGF-FGFR3-RSK2 signaling by kaempferol suppresses the proliferation and migration of RA FLSs and the release of activated T-cell-mediated inflammatory cytokines, such as IL-17, IL-21, and TNF-α. We further found that activated phospho-FGFR3 and -RSK2 were more highly observed in RA than in OA synovium. The hyperplastic lining and sublining lymphoid aggregate layers of RA synovium showed p-RSK2-expressing CD68
macrophages with high frequency, while pRSK2-expressing CD4
T-cells was observed at a lower frequency. Notably, kaempferol administration in collagen-induced arthritis mice relieved the frequency and severity of arthritis. Kaempferol reduced osteoclast differentiation in vitro and in vivo relative to the controls and was associated with the inhibition of osteoclast markers, such as tartrate-resistant acid phosphatase, integrin β3, and MMP9. Conclusively, our data suggest that bFGF-induced FGFR3-RSK2 signaling may play a critical role during the initiation and progression of RA in terms of FLS proliferation and enhanced osteoclastogenesis, and that kaempferol may be effective as a new treatment for RA.
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•USC-CM affects skin immune response through the regulation of Th2 cells and B cells.•USC-CM was verified by In vivo that the corneometer of patients with AD increased and the TEWL ...decreased.•Our findings suggest that USC-CM may have potential therapeutic effect for AD as cosmetics and drug materials.
Atopic dermatitis (AD) is an inflammatory skin disease in which type 2 allergic inflammation plays a critical role. In this study, the anti-inflammatory effect of conditioned media from human umbilical cord blood-derived mesenchymal stem cells (USC-CM) was investigated in order to apply it as an effective treatment with a low risk of side effects that can overcome the limitations of AD treatment which is currently in use. We found that USC-CM has various growth factors and cytokines associated with anti-inflammatory effect. RT-PCR and ELISA analysis showed that USC-CM inhibited the levels of type 2 cytokine and chemokine Thymus and activation-regulated chemokine (TARC), TNF-α and IL-6 in TNF-α/IFN-γ-stimulated HaCaT cells. In addition, USC-CM inhibited IL-4 and IL-13 levels in Th2 cells. Therefore, the results of our study demonstrated that USC-CM has anti-inflammatory effect in TNF-α/IFN-γ-stimulated HaCaT cells which associated with the inhibition of the immunoglobulin (IgE) secretion by activating B cell line. Our In vivo results showed that when the USC-CM was applied to lesions of patients with the mild AD for 4 weeks, the skin barrier was strengthened by increasing the level of Corneometer and decreasing the value of transepidermal water loss (TEWL). In conclusion, the results suggest that USC-CM may have therapeutic effect for AD as cosmetics and drug materials.
Abstract
Transfer learning using a pre-trained model with the ImageNet database is frequently used when obtaining large datasets in the medical imaging field is challenging. We tried to estimate the ...value of deep learning for facial US images by assessing the classification performance for facial US images through transfer learning using current representative deep learning models and analyzing the classification criteria. For this clinical study, we recruited 86 individuals from whom we acquired ultrasound images of nine facial regions. To classify these facial regions, 15 deep learning models were trained using augmented or non-augmented datasets and their performance was evaluated. The F-measure scores average of all models was about 93% regardless of augmentation in the dataset, and the best performing model was the classic model VGGs. The models regarded the contours of skin and bones, rather than muscles and blood vessels, as distinct features for distinguishing regions in the facial US images. The results of this study can be used as reference data for future deep learning research on facial US images and content development.
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