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Background and Objectives: The majority of patients who undergo hip fracture surgery do not recover their former level of physical function; hence, it is essential to establish a specific rehabilitation strategy for maximal functional recovery of patients after a hip fracture. Knowing which indicators of physical function in hip fracture patients have a significant impact on the decision regarding the place or timing of discharge would make it possible to plan and prepare for discharge as soon as possible. Therefore, this study aimed to investigate the relationship between physical function and discharge destination for older adult patients with hip fracture. Materials and Methods: In this retrospective cohort study, 150 hip fracture patients (mean age 78.9 ± 10.6 years) between January 2019 and June 2021 were enrolled. Patients were categorized into two groups according to their discharge destination, either home or facility. Demographic and disease-related characteristic data were collected from the medical records. All the patients completed performance-based physical function tests including the 10 Meter Walk Test (10MWT), Timed Up and Go test (TUG), Koval's grade, and Berg Balance Scale (BBS) at the start of rehabilitation and at discharge. A backward stepwise binary logistic regression analysis was then performed to determine the independent factors of the discharge destination. Results: The home discharge group had a significantly lower Koval's grade, lower TUG, higher BBS both at baseline and discharge, and younger age. Backward stepwise logistic binary regression analysis showed that TUG, BBS, and 10MWT at baseline and discharge were significant variables affecting the discharge destination after hip fracture. Conclusions: These results demonstrate that balance and gait in older adult patients with hip fractures are highly influential factors in the determining the discharge destination. [ABSTRACT FROM AUTHOR]

The devastating effects of COVID-19 have highlighted the importance of prophylactic and therapeutic strategies to combat respiratory diseases. Stimulator of interferon gene (STING) is an essential component of the host defense mechanisms against respiratory viral infections. Although the role of the cGAS/STING signaling axis in the innate immune response to DNA viruses has been thoroughly characterized, mounting evidence shows that it also plays a key role in the prevention of RNA virus infections. In this study, we investigated the role of STING activation during Influenza virus (IFV) infection. In both mouse bone marrow-derived macrophages and monocytic cell line THP-1 differentiated with PMA, we found that dimeric amidobenzimidazole (diABZI), a STING agonist, had substantial anti-IFV activity against multiple strains of IFV, including A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. On the other hand, a pharmacological antagonist of STING (H-151) or the loss of STING in human macrophages leads to enhanced viral replication but suppressed IFN expression. Furthermore, diABZI was antiviral against IFV in primary air–liquid interface cultures of nasal epithelial cells. Our data suggest that STING agonists may serve as promising therapeutic antiviral agents to combat IFV. [ABSTRACT FROM AUTHOR]

The beach chair position (BCP) is widely used in shoulder surgery; however, it frequently leads to hypotension. Hypotension in BCP is prevalent among older patients who are at risk of secondary complications such as ischemic injuries. Therefore, this prospective study aimed to investigate the association and predictive value of frailty, as assessed by ultrasound-measured quadriceps depth and questionnaire, in patients aged ≥65 years undergoing elective shoulder surgery under general anesthesia. A multivariable logistic regression analysis was performed to identify independent risk factors for hypotension in BCP under general anesthesia. Receiver operating characteristic curves were constructed to assess the predictive values of various parameters. The results indicated that a quadriceps depth < 2.3 cm and BCP for an extended period significantly increased the risk of hypotension. The combined consideration of quadriceps depth < 2.3 cm and frailty demonstrated markedly superior predictive power compared with each factor individually. In conclusion, the study findings facilitate the screening and identification of risk factors for older patients undergoing surgery in BCP, thereby enhancing perioperative management. [ABSTRACT FROM AUTHOR]

Background/Objectives: The psoas: lumbar vertebral index (PLVI) is a simple and convenient measure to assess central sarcopenia. Recent studies have utilized the psoas area to indirectly assess sarcopenia and frailty, exploring their associations with various health outcomes. This study aims to investigate the relationship between the PLVI and postherpetic neuralgia (PHN) in patients aged 60 years and above following a herpes zoster (HZ) infection. Methods: We conducted a retrospective analysis of data from 351 patients (≥60 years) who developed HZ between January 2019 and December 2023; the patients were divided into two groups based on the presence or absence of PHN after HZ onset. Results: The analyses using receiver operating characteristic curves revealed a value for the area under the curve of 0.813 for PLVI and 0.769 for the modified frailty index (mFI). In a multivariate logistic regression analysis, numerical rating scale scoring, a low PLVI, and a greater number of categorical mFI variables (adjusted odds ratio: 1.30, 3.27, and 2.46, respectively) were found to be significant independent predictors of PHN. Conclusions: Our findings highlight the association between a low PLVI and PHN in an older population. The PLVI may have potential as a predictive tool for PHN in older patients with HZ, but further research is needed to confirm these results. [ABSTRACT FROM AUTHOR]

Introduction: Solid pseudopapillary neoplasms (SPNs) are rare and mainly originate from the pancreas. SPNs originating from the ovary (SPN-O) are extremely rare, and only 13 cases have been reported in the English literature since 2010. Case: We report a 31-year-old woman with SPN-O accompanied by multiple metastases in the abdominal cavity. The patient underwent staging surgery and cytoreduction. Furthermore, the multidisciplinary board decided on adjuvant chemotherapy with an FP regimen (fluorouracil plus cisplatin) because a microscopic metastasis was discovered in the peritoneum near the appendix. Next-generation sequencing showed some pathologic mutations of oncogenes/cancer-associated genes, including CTNNB1 and TP53. This is the fourteenth case of SPN-O and the first one to demonstrate the TP53 pathogenic mutant variant in SPN-O. The patient showed 8 months of disease-free survival until February 2024. Conclusion: The combination of R0 cytoreduction with FOLFIRI chemotherapy appears to be an effective and feasible treatment option. [ABSTRACT FROM AUTHOR]

Background and Objectives: This study aimed to explore biomarker change after NAC (neoadjuvant chemotherapy) and to investigate biomarker expression as a prognostic factor in patients with residual disease (RD) after NAC. Materials and Methods: We retrospectively evaluated 104 patients with invasive breast cancer, who underwent NAC and surgery at Pusan National University Hospital from 2015 to July 2022. The expression of the biomarker was assessed, and the overall survival (OS) and disease-free survival (DFS) were investigated. Results: After NAC, 24 patients (23.1%) out of 104 total patients had a pathological complete response (pCR). We found that changes in at least one biomarker were observed in 41 patients (51.2%), among 80 patients with RD. In patients with RD after NAC (n = 80), a subtype change was identified in 20 patients (25.0%). Any kind of change in the HER2 status was present 19 (23.7%) patients. The hormone receptor (HR)+/HER2+ subtype was significantly associated with better disease-free survival (DFS) (HR, 0.13; 95% CI, 0.02–0.99; p = 0.049). No change in p53 was associated with better DFS, and negative-to-positive change in p53 expression after NAC was correlated with worse DFS (p < 0.001). Negative-to-positive change in p53 was an independent, worse DFS factor in the multivariate analysis (HR,18.44; 95% CI, 1.86–182.97; p = 0.013). Conclusions: Biomarker change and subtype change after NAC were not infrequent, which can affect the further treatment strategy after surgery. The expression change of p53 might have a prognostic role. Overall, we suggest that the re-evaluation of biomarkers after NAC can provide a prognostic role and is needed for the best decision to be made on further treatment. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA), a potent nephrotoxin, is one of the most deleterious mycotoxins, with its prevalence in agricultural crops and their processed foods around the world. OTA is a major concern to food safety, as OTA exposure through dietary intake may lead to a significant level of accumulation in the body as a result of its long half-life (about 35 days). Its potent renal toxicity and high risk of exposure as well as the difficulty in controlling environmental factors OTA production has prompted the need for timely information on practical strategies for the food industry to effectively manage OTA contamination during food processing. The effects of various food processes, including both nonthermal and thermal methods, on the reduction in OTA were summarized in this review, with emphasis on the toxicity of residual OTA as well as its known and unknown degradation products. Since complete removal of OTA from foodstuffs is not feasible, additional strategies that may facilitate the reduction in OTA in food, such as adding baking soda and sugars, was also discussed, so that the industry may understand and apply practical measures to ensure the safety of its products destined for human consumption. [ABSTRACT FROM AUTHOR]

This study was conducted to identify the types of perceptions toward healthcare safety nets. This study applied a Q-methodology. From a Q-population of 91 samples that included a review of the related literature and interviews with five tertiary hospital nurses and five long-term care (LTC) hospital nurses, 33 Q-samples were selected. The data were analyzed with the PC-QUANL program. We recruited 32 nurses in a tertiary hospital and 33 nurses in an LTC hospital. The perceptions of the healthcare safety net of tertiary hospital nurses were categorized into four types: (1) systematic system request; (2) realistic work support; (3) government support; and (4) emotional support. The perceived subjectivity of the healthcare safety net of LTC hospital nurses were categorized into four types: (1) reward system and facility environmental support; (2) realistic work support; (3) social prevention infrastructure support; and (4) government support. This study provides basic data for these different hospital settings, as well as to inform future government policy and system improvements in an era characterized by infectious diseases. Specifically, this study presents the types of perceptions of healthcare safety nets of nurses in two hospital settings that deliver care for patients. [ABSTRACT FROM AUTHOR]

The high-risk human papillomavirus (HR-HPV) has been known as the most important carcinogen in uterine cervical carcinoma. However, there is limited evidence of the malignant potential of these concurrent multiple infections. This study included women who had undergone cervical conization. They underwent an HPV test by cervical swab within 12 months before the surgery. They were divided into two groups: one with a single infection with HR-HPV16 and the other with concurrent multiple infections with HR-HPVs, including genotype 16. Pathologic examination classified cases as CIS+ to assess and compare the malignant potential in both groups, including carcinoma in situ (CIS) and invasive carcinoma. Of the 220 patients infected with HR-HPV16, the single infection group consisted of 120 patients (54.5%), whereas the concurrent multiple infections consisted of 100 (45.5%) patients. The rates of HSIL were significantly higher in the concurrent multiple infection group. However, the odds ratio for CIS+ did not show a significant difference between both groups (1.417, 95% CI = 0.831–2.414, p = 0.200). The malignant potential was not significantly different between concurrent multiple infections with HR-HPVs, including 16, and a single infection with 16 in Korean women. [ABSTRACT FROM AUTHOR]

The incidences of herpes zoster (HZ) and postherpetic neuralgia (PHN) are significantly influenced by age. As individuals age, the occurrence of spinal disorders increases, thereby raising the likelihood of HZ and PHN coexistence. Considering this, our study aimed to explore the potential impact of pre-existing spinal disorders at the nerve level where HZ developed, on the severity of zoster-associated pain (ZAP) and the incidence of PHN. For our investigation, we retrospectively analyzed a total of 237 patients who presented with HZ and ZAP at various sensory levels (cervical, thoracic, lumbar, and sacral) with or without pre-existing spinal disorders. The presence or absence of spinal disorders at the sensory level affected by HZ was determined using computed tomography or magnetic resonance imaging. Our study results revealed that the group with spinal disorders at the sensory level where HZ developed did not exhibit an increased incidence of PHN. However, 3–6 months after HZ onset, this same group showed significantly higher ZAP scores compared to the group without spinal disorders. It implies a need for heightened pain management, as the coexistence of these conditions can increase pain severity. This study furnishes an initial standpoint to delve into intricate interactions between two diseases. [ABSTRACT FROM AUTHOR]

Transcutaneous carbon dioxide (PtcCO2) monitoring is known to be effective at estimating the arterial partial pressure of carbon dioxide (PaCO2) in patients with sedation-induced respiratory depression. We aimed to investigate the accuracy of PtcCO2 monitoring to measure PaCO2 and its sensitivity to detect hypercapnia (PaCO2 > 60 mmHg) compared to nasal end-tidal carbon dioxide (PetCO2) monitoring during non-intubated video-assisted thoracoscopic surgery (VATS). This retrospective study included patients undergoing non-intubated VATS from December 2019 to May 2021. Datasets of PetCO2, PtcCO2, and PaCO2 measured simultaneously were extracted from patient records. Overall, 111 datasets of CO2 monitoring during one-lung ventilation (OLV) were collected from 43 patients. PtcCO2 had higher sensitivity and predictive power for hypercapnia during OLV than PetCO2 (84.6% vs. 15.4%, p < 0.001; area under the receiver operating characteristic curve; 0.912 vs. 0.776, p = 0.002). Moreover, PtcCO2 was more in agreement with PaCO2 than PetCO2, indicated by a lower bias (bias ± standard deviation; −1.6 ± 6.5 mmHg vs. 14.3 ± 8.4 mmHg, p < 0.001) and narrower limit of agreement (−14.3–11.2 mmHg vs. −2.2–30.7 mmHg). These results suggest that concurrent PtcCO2 monitoring allows anesthesiologists to provide safer respiratory management for patients undergoing non-intubated VATS. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to determine the predictive value of radiologically measured psoas muscle area (PMA) for intraoperative hypotension (IOH) using receiver operating characteristic (ROC) curves in older adult patients with hip fractures. The cross-sectional axial area of the psoas muscle was measured by CT at the level of the 4th lumbar vertebrae and normalized by body surface area (BSA). The modified frailty index (mFI) was used to assess frailty. IOH was defined as an absolute threshold of mean arterial blood pressure (MAP) < 65 mmHg or a relative decrease in MAP > 30% from baseline MAP. Among the 403 patients, 286 (71.7%) had developed IOH. PMA normalized by BSA in male patients was 6.90 ± 0.73 in the no-IOH group and 4.95 ± 1.20 in the IOH group (p < 0.001). PMA normalized by BSA in female patients was 5.18 ± 0.81 in the no-IOH group and 3.78 ± 0.75 in the IOH group (p < 0.001). The ROC curves showed that the area under the curve for PMA normalized by BSA and modified frailty index (mFI) were 0.94 for male patients, 0.91 for female patients, and 0.81 for mFI (p < 0.001). In multivariate logistic regression, low PMA normalized by BSA, high baseline systolic blood pressure, and old age were significant independent predictors of IOH (adjusted odds ratio: 3.86, 1.03, and 1.06, respectively). PMA measured by computed tomography showed an excellent predictive value for IOH. Low PMA was associated with developing IOH in older adult patients with hip fractures. [ABSTRACT FROM AUTHOR]

Complex regional pain syndrome (CRPS) is a condition associated with neuropathic pain that causes significant impairment of daily activities and functioning. Nuclear factor kappa B (NFκB) is thought to play an important role in the mechanism of CRPS. Recently, exosomes loaded with super-repressor inhibitory kappa B (Exo-srIκB, IκB; inhibitor of NFκB) have been shown to have potential anti-inflammatory effects in various inflammatory disease models. We investigated the therapeutic effect of Exo-srIκB on a rodent model with chronic post-ischemia pain (CPIP), a representative animal model of Type I CRPS. After intraperitoneal injection of a vehicle, Exo-srIκB, and pregabalin, the paw withdrawal threshold (PWT) was evaluated up to 48 h. Administration of Exo-srIκB increased PWT compared to the vehicle and pregabalin, and the relative densities of p-IκB and IκB showed significant changes compared to the vehicle 24 h after Exo-srIκB injection. The levels of several cytokines and chemokines were reduced by the administration of Exo-srIκB in mice with CPIP. In conclusion, our results showed more specifically the role of NFκB in the pathogenesis of CRPS and provided a theoretical background for novel treatment options for CRPS. [ABSTRACT FROM AUTHOR]

Sjögren's syndrome (SS) is a systemic autoimmune disease delineated by chronic lymphocytic infiltrates into the lacrimal or salivary glands, leading to severe dry eye and dry mouth. Mesenchymal stem cells have been shown to be effective in treating numerous autoimmune diseases. This study aimed to illustrate the effects of mesenchymal stem cells on the attenuation of dry eyes (DE) through the inhibition of autophagy markers in a SS mouse model. NOD/ShiLtJ female mice with developed DE were treated with either subconjunctival or lacrimal gland injections of hMSCs (Catholic MASTER Cells). After maintenance for 14 days, clinical DE markers such as tear secretion and corneal staining were observed, as well as goblet cell counts in the conjunctiva, infiltration of inflammatory foci, B and T cells, and autophagy markers in the lacrimal glands. Proinflammatory cytokine expressions of the cornea and conjunctiva, as well as the lacrimal glands, were examined. Clinical markers, such as tear secretion and corneal stain scores, goblet cell counts in the conjunctiva, and foci infiltrations in the lacrimal glands were attenuated in mice treated with subconjunctival or lacrimal gland injections of hMSCs compared to the PBS-treated control group. B cell marker B220 decreased in the lacrimal glands of hMSCs-treated mice, as well as reduced proinflammatory cytokine expressions in the lacrimal glands and cornea. Notably, expression of autophagy markers ATG5 and LC3B-II, as well as HIF-1α and mTOR which play roles in the pathways of autophagy modulation, were shown to be attenuated in the lacrimal glands of hMSCs-treated mice compared to the PBS-treated control mice. Treatment with hMSCs by lacrimal gland or subconjunctival injection demonstrated the alleviation of DE through the repression of autophagy markers, suggesting the therapeutic potentials of hMSCs in a SS mouse model. [ABSTRACT FROM AUTHOR]

Nurses who take care of patients with hematology have more difficulty in therapeutic communication. The aim of this study is to explore the therapeutic communication experiences of nurses caring for patients with hematology and the meaning of the essential structure of therapeutic communication. Colaizzi's phenomenological method was applied to explore the essential structures and meanings of therapeutic communication in depth through a focus group interview. The interview was conducted at a tertiary care hospital with 20 nurses caring for patients with hematology. As a result of the analyses, 22 themes, 14 theme clusters, and 5 categories were derived. The categories derived from the analyses included "acquiring core competencies as nursing professionals", "improving patient-centered nursing performance", "forming a partnership treatment relationship", "obtaining clinical performance skills to solve problems", and "preparing efficient system improvement". Based on this study's results, it will be possible to provide high-quality nursing to patients by improving the therapeutic communication ability of nurses caring for patients with hematology. In addition, it will be the basis for the development of a nurses' therapeutic communication promotion program for nurses caring for such patients. [ABSTRACT FROM AUTHOR]

Background: Lupus nephritis (LN) is present in over 50% of patients with systemic lupus erythematosus (SLE) which is managed with immunosuppressive and immunomodulatory therapies. However, several novel therapeutic approaches for LN are under investigation due to the adverse effects spectrum of conventional therapy; Methods: We performed a comprehensive review of meta-analyses aggregating the comparative efficacies of various pharmacotherapies for LN. We conducted a literature search and retrieved a total of 23 meta-analyses and network meta-analyses for summarization. Pharmacotherapies were evaluated across six major outcomes: remission, relapse, mortality, end stage kidney disease (ESKD) progression, infection, and malignancy. Result: Calcineurin inhibitors (CNI), particularly tacrolimus (TAC), in combination with glucocorticoids (GC) outperformed cyclophosphamide (CPA) with GC in the rate of remission, either complete or partial remission, and in terms of infectious complications. In maintenance therapy, MMF was superior to azathioprine (AZA) as the MMF-treated patients had lower relapse rate. Interpretation: This review aggregates evidence of therapy for clinicians and sheds light on comparative efficacies of alternative LN treatments. As more promising agents are entering the market, such as voclosporin, belimumab, and obinutuzumab, LN management might undergo significant changes during the next years. [ABSTRACT FROM AUTHOR]

Significant progress has been made on the molecular biology of the severe fever with thrombopenia virus (SFTSV); however, many parts of the pathophysiological mechanisms of mortality in SFTS remain unclear. In this study, we investigated virologic and immunologic factors for fatal outcomes of patients with SFTS. We prospectively enrolled SFTS patients admitted from July 2015 to October 2020. Plasma samples were subjected to SFTSV RNA RT-PCR, multiplex microbead immunoassay for 17 cytokines, and IFA assay. A total of 44 SFTS patients were enrolled, including 37 (84.1%) survivors and 7 (15.9%) non-survivors. Non-survivors had a 2.5 times higher plasma SFTSV load than survivors at admission (p < 0.001), and the viral load in non-survivors increased progressively during hospitalization. In addition, non-survivors did not develop adequate anti-SFTSV IgG, whereas survivors exhibited anti-SFTSV IgG during hospitalization. IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF were significantly elevated in non-survivors compared to survivors and did not revert to normal ranges during hospitalization (p < 0.05). Severe signs of inflammation such as a high plasma concentration of IFN-α, IL-10, IP-10, IFN-γ, IL-6, IL-8, MCP-1, MIP-1α, and G-CSF, poor viral control, and inadequate antibody response during the disease course were associated with mortality in SFTS patients. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a mycotoxin that is potentially carcinogenic to humans. Although its mechanism remains unclear, oxidative stress has been recognized as a plausible cause for the potent renal carcinogenicity observed in experimental animals. The effect of OTA on oxidative stress parameters in two cell lines of LLC-PK1 and HK-2 derived from the kidneys of pig and human, respectively, were investigated and compared. We found that the cytotoxicity of OTA on LLC-PK1 and HK-2 cells was dose- and time-dependent in both cell lines. Furthermore, increased intracellular reactive oxygen species (ROS) induced by OTA in both cell lines were observed in a time-dependent manner. Glutathione (GSH) was depleted by OTA at >48 h in HK-2 but not in LLC-PK1 cells. While the mRNA levels of glucose-6-phosphate dehydrogenase (G6PD) and glutathione peroxidase 1 (GPX1) in LLC-PK1 were down-regulated by 0.67- and 0.66-fold, respectively, those of catalase (CAT), glutathione reductase (GSR), and superoxide dismutase 1 (SOD) in HK-2 were up-regulated by 2.20-, 2.24-, and 2.75-fold, respectively, after 72 h exposure to OTA. Based on these results, we conclude that HK-2 cells are more sensitive to OTA-mediated toxicity than LLC-PK1, and OTA can cause a significant oxidative stress in HK-2 as indicated by changes in the parameter evaluated. [ABSTRACT FROM AUTHOR]

This study aimed to analyze the concept of the "feelings of entrapment" during the COVID-19 (coronavirus disease 2019) pandemic using a systematic review. We included literature based on content and outcomes related to feelings of entrapment, such as antecedents, attributes, and consequences. The exclusion criteria were studies that did not have inappropriate subject, content, conceptual definition, and degree thesis was excluded. Walker and Avant's process of concept analysis was used in this systematic literature review. The attributes of the concept of feelings of entrapment during the COVID-19 pandemic were found to be feelings of: (1) being out of control, (2) no escape, (3) being trapped, (4) being robbed, and (5) hopelessness. The causes for these were identified as (1) the COVID-19 pandemic, (2) lockdown system, (3) restricted situation, (4) uncertain future, (5) economic hardship, and (6) poor coping abilities. Consequences of the concept were: (1) increased suicide, (2) decreased mental health, and (3) decreased well-being. In situations such as COVID-19, it is important need to know what feelings of entrapment's antecedents and attributes are to prevent suicide and enhance mental health and well-being. Based on the results of this study, counseling services, policies, and systems for relieving feelings of entrapment in the COVID-19 situation are recommended. [ABSTRACT FROM AUTHOR]

Coxiella burnetii infects humans and wild and domesticated animals. Although reported cases on Jeju Island, off the coast of South Korea, are rare, the region is considered to have a high potential for Q fever. We investigated the seroprevalence of antibodies to C. burnetii in 230 farmers living in ten rural areas on Jeju Island between January 2015 and December 2019. Blood samples were collected and examined for C. burnetii Phase I/II IgM and IgG antibodies. Trained researchers collected ticks from rural areas. Clone XCP-1 16S ribosomal RNA gene sequencing was performed to identify Coxiella species from the collected ticks. The overall seroprevalence of antibodies to C. burnetii in farmers was 35.7%. The seroprevalence was significantly higher in fruit farmers. Of the collected ticks, 5.4% (19/351) of the Haemaphysalis longicornis ticks harbored C. burnetti. A high seroprevalence of antibodies to C. burnetii was observed in this region of Jeju Island, confirming that C. burnetti is endemic. Physicians should thus consider Q fever in the differential diagnosis of patients that present with acute fever after participating in outdoor activities. [ABSTRACT FROM AUTHOR]

Spent coffee grounds (SCG) are inexpensive materials that have been used as a source of antioxidants and polysaccharides with immunostimulatory activity. In this study, we performed a microbial fermentation of SCG using Cordyceps sinensis and investigated the radical scavenging and immunostimulatory activity of fermented SCG. SCG fermentation using C. sinensis was performed at 25 °C for 8 d. The polyphenol content of the fermented SCG increased from 1022.4 to 1562.0 μg/mL. The glucosamine content of the mycelia also continuously increased during fermentation. The main polyphenol compounds of fermented SCG were chlorogenic acid and p-coumaric acid, which were increased by fermentation. Fermented SCG also showed significantly higher content of chlorogenic acid isomers than unfermented SCG. The fermented SCG exhibited significantly higher 2,2-diphenyl-2-picrylhydrazyl hydrate (half maximal inhibitory concentration: IC50, 0.37 mg/mL) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (IC50, 0.93 mg/mL) radical scavenging activities than those of the control (0.54 mg/mL and 1.20 mg/mL, respectively; p < 0.05). The fermented SCG stimulated macrophages and promoted the production of various immunostimulatory cytokines (IL-12, IL-6, and TNF-α) compared to control; therefore, microbial fermentation of SCG using C. sinensis is an effective means of generating antioxidant and immunostimulatory materials. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze the concept of the "healthcare safety net" during the COVID-19 pandemic. Walker and Avant's process of concept analysis was used in this systematic literature review. The attributes of the concept of a healthcare safety net during the COVID-19 pandemic were found to be: (a) capacity, (b) accessibility, (c) health equality, and (d) education. In consideration of these defining criteria, antecedents to the concept were identified as: (a) the COVID-19 pandemic, (b) health inequalities (internal factors and external factors), and (c) healthcare systems (health insurance, screening, protective equipment, medicine, and medical services). Consequences of the concept were: (a) meeting healthcare needs, (b) quality of life, and (c) a decrease in morbidity and mortality. A healthcare safety net is an important concept during the COVID-19 pandemic. In situations like COVID-19, healthcare safety nets are designed to meet safety needs, improve quality of life, and reduce patient turnover and mortality. Based on the results of this study, the development of standardized tools for measuring a healthcare safety net as well as that of policies and systems for resolving a healthcare safety net in the COVID-19 situation is recommended. [ABSTRACT FROM AUTHOR]

Preterm labor (PTL) is one of the obstetric complications, and is known to be associated with abnormal maternal inflammatory response and intrauterine inflammation and/or infection. However, the expression of specific miRNAs associated with PTL is not clear. In this study, we performed combination analysis of miRNA array and gene array, and then selected one miRNA (miR-373-3p) and its putative target genes (CD44 and RDX) that exhibited large expression differences in term and PTL placentas with or without inflammation. Using qRT-PCR and luciferase assays, we confirmed that miR-373-3p directly targeted CD44 and RDX. Overexpression of miR-373-3p reduced the migration and invasion of trophoblast cells, while inhibition of miR-373-3p restored the migration and invasion abilities of trophoblast cells. Finally, we validated the expression of miR-373-3p and its target genes in clinical patients' blood. miR-373-3p was increased in PTL patients' blood, and was the most expressed in PTL patients' blood with inflammation. In addition, by targeting the miR-373-3p, CD44 and RDX was decreased in PTL patients' blood, and their expression were the lowest in PTL patients' blood with inflammation. Taken together, these findings suggest that miR-373-3p and its target genes can be potential biomarkers for diagnosis of PTL. [ABSTRACT FROM AUTHOR]

Suitable scaffolds with appropriate mechanical and biological properties can improve mesenchymal stromal cell (MSC) therapy. Because silk fibroins (SFs) are biocompatible materials, they were electrospun and applied as scaffolds for MSC therapy. Consequently, interferon (IFN)-primed human bone marrow MSCs on SF nanofibers were administered into a polymicrobial sepsis murine model. The IL-6 level gradually decreased from 40 ng/mL at 6 h after sepsis to 35 ng/mL at 24 h after sepsis. The IL-6 level was significantly low as 5 ng/mL in primed MSCs on SF nanofibers, and 15 ng/mL in primed MSCs on the control surface. In contrast to the acute response, inflammation-related factors, including HO-1 and COX-2 in chronic liver tissue, were effectively inhibited by MSCs on both SF nanofibers and the control surface at the 5-day mark after sepsis. An in vitro study indicated that the anti-inflammatory function of MSCs on SF nanofibers was mediated through enhanced COX-2-PGE2 production, as indomethacin completely abrogated PGE2 production and decreased the survival rate of septic mice. Thus, SF nanofiber scaffolds potentiated the anti-inflammatory and immunomodulatory functions of MSCs, and were beneficial as a culture platform for the cell therapy of inflammatory disorders. [ABSTRACT FROM AUTHOR]

Cancer progression and migration in the tumor microenvironment are related to cell types and three-dimensional (3D) matrices. Therefore, developing biomimetic tumor models, including co-culture systems and a tunable 3D matrix, could play an essential role in understanding the cancer environment. Here, multicellular spheroids using human adipose-derived mesenchymal stem cells (hADSCs) and breast cancer cells (MDA-MB-231) within the 3D matrix were used as a tumor microenvironment (TME) mimicking platform. The amphiphilic peptide block copolymer and hyaluronic acid (HA) formed a self-assembled structure, which provides a biocompatible 3D environment for the cells. Multicellular spheroids were formed on the optimized plate and were observed as cell migration from a spheroid within a 3D matrix, such as the invasive and metastatic cancer of TME. This study suggests a new 3D platform using polymer complexes and the importance of tumor complexities, including various cell types and microenvironments. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a mycotoxin frequently found in raw and processed foods. While it is considered a possible human carcinogen, the mechanism of action remains unclear. OTA has been shown to be hepatotoxic in both in vitro and in vivo models and oxidative stress may be one of the factors contributing to its toxicity. Hence, the effect of OTA on human hepatocellular carcinoma, HepG2 cells, was investigated on oxidative stress parameters. The cytotoxicity of OTA on HepG2 was time- and dose-dependent within a range between 0.1 and 10 µM; while 100 μM of OTA increased the intracellular reactive oxygen species (ROS) in a time-dependent manner. Additionally, the levels of glutathione (GSH) were increased by 9.7% and 11.3% at 10 and 100 nM of OTA, respectively; while OTA at 100 μM depleted GSH by 40.5% after 24 h exposure compared with the control. Finally, the mRNA level of catalase (CAT) was downregulated by 2.33-, 1.92-, and 1.82-fold after cells were treated with 1, 10, and 10 μM OTA for 24 h, respectively; which was linked to a decrease in CAT enzymatic activity. These results suggest that oxidative stress is involved in OTA-mediated toxicity in HepG2 cells. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a potential human carcinogen that poses a significant concern in food safety and public health. OTA has been found in a wide variety of agricultural commodities, including cereal grains. This study investigated the reduction of OTA during the preparation of rice- and oat-based porridge by a simulated indirect steam process. The effects of sodium bicarbonate (NaHCO3) and fructose on the reduction of OTA were also investigated. During the processing, OTA in rice- and oat-porridge was decreased by 59% and 14%, respectively, from initial OTA artificially added at 20 μg/kg (dry weight basis). When 0.5% and 1% of sodium bicarbonate were added to rice porridge, increased reduction of OTA was observed as 78% and 68%, respectively. The same amounts of added sodium bicarbonate also further reduced OTA in oat porridge to 58% and 72%, respectively. In addition, increased reduction of OTA in the presence of fructose was observed. A combination of the two, i.e., 0.5% sodium bicarbonate and 0.5% fructose, resulted in a 79% and 67% reduction in rice porridge and oat porridge, respectively. These results indicate that indirect steaming may effectively reduce OTA in preparation of porridge-type products, particularly when sodium bicarbonate and/or fructose are added. [ABSTRACT FROM AUTHOR]

Background and Aims: The impact of proteinuria and its severity on the incidence of inflammatory bowel disease (IBD) has not yet been studied. We aimed to determine the association between proteinuria measured by urine dipstick tests and the development of IBD. Methods: This nationwide population-based study was conducted using the Korean National Health Insurance Service (NHIS) database. A total of 9,917,400 people aged 20 years or older who had undergone a national health examination conducted by the NHIS in 2009 were followed up until 2017. The study population was classified into four groups—negative, trace, 1+, and ≥ 2+—according to the degree of proteinuria measured by the urine dipstick test. The primary endpoint was newly diagnosed IBD, Crohn's disease (CD), or ulcerative colitis (UC) during the follow-up period. Results: Compared with the dipstick-negative group, the incidence of CD significantly increased according to the degree of proteinuria (adjusted hazard ratio [aHR] with 95% confidence interval [CI], 1.01 [0.703–1.451], 1.515 [1.058–2.162], and 2.053 [1.301–3.24] in the trace, 1+, and ≥ 2+ dipstick groups, respectively; p for trend 0.007). However, there was no significant difference in the incidence of UC according to the degree of proteinuria (aHR with 95% CI, 1.12 [0.949–1.323], 0.947 [0.764–1.174], and 1.009 [0.741–1.373] in the trace, 1+, and ≥ 2+ dipstick groups, respectively; p for trend 0.722). In the subgroup analysis, dipstick-positive proteinuria independently increased the incidence of CD regardless of the subgroup. However, dipstick-positive proteinuria was associated with the risk of UC in those with diabetes mellitus and not in those without diabetes mellitus (aHR, 1.527 vs. 0.846; interaction p-value 0.004). The risk of CD was increased or decreased according to proteinuria changes but not associated with the risk of UC. Conclusion: Proteinuria, measured by the dipstick test, is strongly associated with the development of CD. [ABSTRACT FROM AUTHOR]

Autophagy has been suggested to have an important role in the pathogenesis of Sjögren syndrome (SS). We previously identified that autophagy related 5 (ATG5) was elevated in the tear and conjunctival epithelial cells of SS dry eyes (DE) compared to non-SS DE. The purpose of this study was to investigate the role of tear ATG5 as a potential biomarker in the diagnosis of SS. To confirm this hypothesis, we evaluated the tear ATG5 concentration, and other ocular tests (Schirmer I, tear breakup time (TBUT), ocular surface staining (OSS) score, ocular surface disease index (OSDI)) in SS and non-DE, and compared their diagnostic performance to discriminate SS from non-SS DE. Tear ATG5 showed the greatest area under the curve (AUC = 0.984; 95% CI, 0.930 to 0.999) among the tests, and a 94.6% sensitivity and 93.6% specificity at a cutoff value of >4.0 ng/mL/μg. Our data demonstrated that tear ATG5 may be helpful as an ocular biomarker to diagnose and assess SS. In the future, the diagnostic power of tear ATG for SS should be validated. [ABSTRACT FROM AUTHOR]

This study investigated the effects of different aging methods on the changes in the concentrations of aroma volatiles of beef. One half (n = 15) of the beef strip loins were dry-aged, and the other half were wet-aged, and both aging processes continued for 28 days. The aroma volatiles from dry- and wet-aged samples were analyzed at seven-day intervals (n = 3 for each aging period). As the aging period increased, dry-aged beef showed higher concentrations of volatile compounds than those in wet-aged beef (p < 0.05). Most changes in the concentrations of aroma volatiles of dry-aged beef were associated with propanal, 2-methylbutanal, 2-methylpropanal, 1-butanamine, trimethylamine, 2-methyl-2-propanethiol, and ethyl propanoate, which were mainly produced by lipid oxidation and/or microbial activity (e.g., proteolysis and lipolysis) during the dry aging period. Therefore, we suggest that the differences in aroma between dry- and wet-aged beef could result from increased lipid oxidation and microbial activity in dry-aged beef possibly owing to its ambient exposure to oxygen. [ABSTRACT FROM AUTHOR]

Simple Summary: Colorectal cancer (CRC) is the third most common cancer and the second highest cause of cancer related mortality worldwide. Especially, the survival of advanced CRC patients who were failed to achieve durable remission after the anti-angiogenic and anti-epithelial growth factor receptor agents are still poor. The aim of our study was to investigate the anti-tumor activity of the CDK4/6 inhibitor, abemaciclib, as a single agent and to identify an optimal combination agent with abemaciclib in CRC cell lines. We confirmed that abemaciclib monotherapy showed anti-tumor activity and combination therapy with abemaciclib and BYL719 demonstrated synergistic effects in CRC cell lines. Moreover, our study suggested that PIK3CA mutation could be a predictive marker for efficacy of abemaciclib and BYL719 combination therapy. These findings provide novel insight into a possible therapeutic strategy for patients with relapsed and refractory CRC. Targeting cell cycle regulation in colorectal cancer has not been fully evaluated. We investigated the efficacy of the CDK4/6 inhibitor, abemaciclib, and confirmed a synergistic interaction for PI3K p110α and CDK dual inhibition in colorectal cancer cell lines. Caco-2 and SNU-C4 cell lines were selected to explore the mechanism of action for and resistance to abemaciclib. In vitro and in vivo models were used to validate the anti-tumor activity of abemaciclib monotherapy and BYL719 combination therapy. Abemaciclib monotherapy inhibited cell cycle progression and proliferation in Caco-2 and SNU-C4 cells. CDK2-mediated Rb phosphorylation and AKT phosphorylation appeared to be potential resistance mechanisms to abemaciclib monotherapy. Abemaciclib/BYL719 combination therapy demonstrated synergistic effects regardless of PIK3CA mutation status but showed greater efficacy in the PIK3CA mutated SNU-C4 cell line. Growth inhibition, cell cycle arrest, and migration inhibition were confirmed as mechanisms of action for this combination. In an SNU-C4 mouse xenograft model, abemaciclib/BYL719 combination resulted in tumor growth inhibition and apoptosis with tolerable toxicity. Dual blockade of PI3K p110α and CDK4/6 showed synergistic anti-tumor effects in vivo and in vitro in human colorectal cancer cell lines. This combination could be a promising candidate for the treatment of patients with advanced colorectal cancer. [ABSTRACT FROM AUTHOR]

Two-dimensional quantitative nuclear magnetic resonance (2D qNMR)-based metabolomics was performed to understand characteristic metabolic profiles in different aging regimes (crust from dry-aged beef, inner edible flesh of dry-aged beef, and wet-aged beef striploin) over 4 weeks. Samples were extracted using 0.6 M perchlorate to acquire polar metabolites. Partial least squares-discriminant analysis showed a good cumulative explained variation (R2 = 0.967) and predictive ability (Q2 = 0.935). Metabolites of crust and aged beef (dry- and wet-aged beef) were separated in the first week and showed a completely different aspect in the second week via NMR-based multivariable analyses. Moreover, NMR-based multivariable analyses could be used to distinguish the method, degree, and doneness of beef aging. Among them, the crust showed more unique metabolic changes that accelerated proteolysis (total free amino acids and biogenic amines) and inosine 5′-monophosphate depletion than dry-aged beef and generated specific microbial catabolites (3-indoxyl sulfate) and γ-aminobutyric acid (GABA), while asparagine, glutamine, tryptophan, and glucose in the crust were maintained or decreased. Compared to the crust, dry-aged beef showed similar patterns of biogenic amines, as well as bioactive compounds and GABA, without a decrease in free amino acids and glucose. Based on these results, the crust allows the inner dry-aged beef to be aged similarly to wet-aged beef without microbial effects. Thus, 2D qNMR-based metabolomic techniques could provide complementary information about biochemical factors for beef aging. [ABSTRACT FROM AUTHOR]

Objective: We sought to evaluate whether the 18F-fluorodeoxyglucose uptake normalization of the primary tumor to both the liver and blood pool and lymph nodes to both the liver and blood pool can enhance the discrimination for prognosis prediction in patients with cervical cancer. Methods: A total of 156 patients with cervical cancer (International Federation of Gynecology and Obstetrics stages IIB–IV) treated with concurrent chemoradiotherapy (CCRT) were enrolled. The maximum standardized uptake value (SUVmax) of tumor (tSUVmax) and the lymph node (nSUVmax) divided by the SUVmean of the liver (tumor-to-liver ratio (TLR) and node-to-liver (NLR)) and blood pool (tumor-to-blood ratio (TBR) and node-to-blood ratio (NBR)) were investigated. Univariate and multivariate analyses of disease-free survival (DFS) and overall survival (OS) were performed using clinical and metabolic parameters. A receiver operating characteristic curve analysis was performed to compare the accuracy of the metabolic parameters. Results: The multivariate analysis revealed that NLR (hazard ratio ((HR): 3.54; 95% confidence interval (CI): 1.53–8.19; p = 0.0032) and NBR (HR: 3.38; 95% CI: 1.02–11.19; p = 0.0457)) were independent prognostic factors for DFS, while TLR (HR: 4.16; 95% CI: 1.19–14.50; p = 0.0252), TBR (HR: 3.01; 95% CI: 1.04–8.70; p = 0.0415), NLR (HR: 4.84; 95% CI: 1.58–14.81; p = 0.0057), and NBR (HR: 6.87; 95% CI: 1.55–30.54; p = 0.0113) were significant prognostic factors for OS. The normalization of tSUVmax to the liver or blood pool enhanced the discrimination for prediction of recurrence (tSUVmax vs. TLR; p = 0.0056 and tSUVmax vs. TBR; p = 0.0099) and death (tSUVmax vs. TLR; p < 0.0001 and tSUVmax vs. TBR; p = 0.0001). Conclusions: The normalization of tSUVmax was an independent prognostic factor and improved the discrimination for the prediction of tumor recurrence and death in patients with locally advanced cervical cancer treated with CCRT. [ABSTRACT FROM AUTHOR]

The chemotherapeutics sorafenib and regorafenib inhibit shedding of MHC class I-related chain A (MICA) from hepatocellular carcinoma (HCC) cells by suppressing a disintegrin and metalloprotease 9 (ADAM9). MICA is a ligand for natural killer (NK) group 2 member D (NKG2D) and is expressed on tumor cells to elicit attack by NK cells. This study measured ADAM9 mRNA levels in blood samples of advanced HCC patients (n = 10). In newly diagnosed patients (n = 5), the plasma ADAM9 mRNA level was significantly higher than that in healthy controls (3.001 versus 1.00, p < 0.05). Among four patients treated with nivolumab therapy, two patients with clinical response to nivolumab showed significant decreases in fold changes of serum ADAM9 mRNA level from 573.98 to 262.58 and from 323.88 to 85.52 (p < 0.05); however, two patients with no response to nivolumab did not. Using the Cancer Genome Atlas database, we found that higher expression of ADAM9 in tumor tissues was associated with poorer survival of HCC patients (log-rank p = 0.00039), while ADAM10 and ADAM17 exhibited no such association. In addition, ADAM9 expression showed a positive correlation with the expression of inhibitory checkpoint molecules. This study, though small in sample size, clearly suggested that ADAM9 mRNA might serve as biomarker predicting clinical response and that the ADAM9-MICA-NKG2D system can be a good therapeutic target for HCC immunotherapy. Future studies are warranted to validate these findings. [ABSTRACT FROM AUTHOR]

This study aimed to develop a prognosis-predicting model based on [18F]fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and clinicopathologic factors in locally advanced cervical cancer patients treated with concurrent chemoradiotherapy (CCRT). The medical records of 270 locally advanced cervical cancer patients who were treated with CCRT were collected from three institutions and reviewed retrospectively. A nomogram was used for predicting 2-year disease-free survival (DFS) and 5-year overall survival (OS) based on Cox proportional hazards regression. Predictor variables included nodal maximum standardized uptake value (SUVmax), primary tumor SUVmax, age, tumor size, stage, serum squamous cell carcinoma antigen level, and human papillomavirus status. Internal nomogram validation was performed. A nomogram for predicting the 2-year DFS and 5-year OS was constructed using six and seven parameters, respectively. With a focus on 2-year DFS, our model found nodal SUVmax to be the highest weighted negative prognostic factor. With a focus on 5-year OS, young age was the highest weighted negative prognostic factor. The concordance index was 0.75 and 0.78 for the 2-year DFS and 5-year OS, respectively. This nomogram is a predictive tool that can be used to counsel patients for predicting survival outcomes. Moreover, our prognosis-predicting model may make it possible to personalize treatment. [ABSTRACT FROM AUTHOR]

Background and Aims: It is not known whether inflammatory bowel disease (IBD) enhances the risk of Parkinson's disease (PD) or whether PD diagnosis is the result of increased health care use. We determined the risk of developing PD among patients with IBD in terms of health care and medication use. Methods: A nationwide population-based study was conducted using claims data from the Korean National Health care Insurance service. From 2010 to 2013, patients with Crohn's disease (CD) and ulcerative colitis (UC) were identified through both International Classification of Disease, Tenth Revision (ICD-10) and national rare intractable disease (RID) registration program codes. We compared 38,861 IBD patients with age and sex-matched non-IBD individuals at a ratio of 1:3. Patients with newly diagnosed PD were identified through both ICD-10 and RID codes. Results: The incidence of PD among patients with IBD was 49 per 100,000 person-years. The risk of developing PD in patients with IBD was significantly higher than controls even after adjustment for health care use (adjusted hazard ratio (aHR), 1.87; P < 0.001). Compared to controls, the risk of PD was significantly higher in patients with CD (aHR, 2.23; P = 0.023) and UC (aHR, 1.85; P < 0.001). Corticosteroid use showed a preventive effect on developing PD in patients with CD (aHR 0.08; P < 0.001), but not UC (aHR, 0.75; P = 0.213). Among 2110 patients receiving anti-tumor necrosis factor (anti-TNF), none of the treated patients experienced PD during 9950 person-years. Conclusion: Patients with IBD are at an increased risk of PD, regardless of health care use. Corticosteroid and anti-TNF use may prevent PD in patients with IBD. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of the genera Aspergillus and Penicillium. OTA exists in a variety of foods, including rice, oats, and coffee and is hepatotoxic, with a similar mode of action as aflatoxin B1. The precise mechanism of cytotoxicity is not yet known, but oxidative damage is suspected to contribute to its cytotoxic effects. In this study, human hepatocyte HepG2 cells were treated with various concentrations of OTA (5–500 nM) for 48 h. OTA triggered oxidative stress as demonstrated by glutathione depletion and increased reactive oxygen species, malondialdehyde level, and nitric oxide production. Apoptosis was observed with 500 nM OTA treatment. OTA increased both the mRNA and protein expression of phase I and II enzymes. The same results were observed in an in vivo study using ICR mice. Furthermore, the relationship between phase I and II enzymes was demonstrated by the knockdown of the aryl hydrocarbon receptor (AhR) and NF-E2-related factor 2 (Nrf2) with siRNA. Taken together, our results show that OTA induces oxidative stress through the phase I reaction regulated by AhR and induces apoptosis, and that the phase II reaction is activated by Nrf2 in the presence of oxidative stress. [ABSTRACT FROM AUTHOR]

Background and Aims: Inflammatory bowel disease (IBD) may be associated with anxiety and depression. The aim of this study was to evaluate the incidence of anxiety and depression in patients with IBD compared to the general population. Methods: A nationwide population-based cohort study was conducted using claims data from the National Healthcare Insurance service in Korea. We compared the incidence of anxiety and depression between 15,569 IBD patients and 46,707 non-IBD controls, age and sex matched at a ratio of 1:3. Results: During a mean follow-up of six years, IBD patients experienced significantly more anxiety (12.2% vs. 8.7%; p < 0.001) and depression (8.0% vs. 4.7%; p < 0.001) compared to controls. The curves showing cumulative incidences of anxiety and depression showed a steep rise within one year following a diagnosis of IBD, leading to lines with a constant slope. The hazard ratio (HR) for new onset anxiety following a diagnosis of Crohn's disease (CD) and ulcerative colitis (UC) was 1.63 and 1.60, respectively, compared to controls (p < 0.001). Compared to controls, the HR for developing depression after a diagnosis of CD and UC was 2.09 and 2.00, respectively (p < 0.001). The risks of anxiety and depression in patients with IBD were higher compared to controls, except in those with diabetes mellitus, hypertension, and dyslipidemia, or who required immunomodulators and biologics within one year of the IBD diagnosis. Conclusions: The risk of anxiety and depression increased after a diagnosis of IBD compared to the general population. [ABSTRACT FROM AUTHOR]

We conducted a prospective cohort study at a community facility designated for the isolation of individuals with asymptomatic or mild COVID-19 between 10 January and 22 February 2021 to investigate the relationship of viral shedding with symptom changes of COVID-19. In total, 89 COVID-19 adult patients (12 asymptomatic, 16 presymptomatic, 61 symptomatic) were enrolled. Symptom scores, the genomic RNA and subgenomic RNA of SARS-CoV-2 from saliva samples with a cell culture were measured. Asymptomatic COVID-19 patients had a similar viral load to symptomatic patients during the early course of the disease, but exhibited a rapid decrease in viral load with the loss of infectivity. Subgenomic RNA and viable virus by cell culture in asymptomatic patients were detected only until 3 days after diagnosis, and the positivity of the subgenomic RNA and cell culture in symptomatic patients gradually decreased in both from 40% in the early disease course to 13% at 10 days and 4% at 8 days after the symptom onset, respectively. In conclusion, symptomatic patients have a high infectivity with high symptom scores during the early disease course and gradually lose infectivity depending on the symptom. Conversely, asymptomatic patients exhibit a rapid decrease in viral load with the loss of infectivity, despite a similar viral load during the early disease course.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that progresses into systemic inflammation and joint deformity. RA diagnosis is a complicated procedure, and early diagnostic methods are insufficient. Therefore, in this study, we attempted to identify new markers to improve the accuracy of RA prescreening. e identified differentially expressed proteins (DEPs) by using liquid chromatography tandem-mass spectrometry in health-prescreening sera with high rheumatoid factor (RF) values, and compared the findings with those from sera with normal RF values. We identified 93 DEPs; of these, 36 were upregulated, and 57 were downregulated in high-RF sera. Pathway analysis revealed that these DEPs were related to immune responses. Additionally, four DEPs were statistically analyzed by proteomic analysis; of these, SAA4 was significantly validated in individual enzyme-linked immunosorbent assays. Moreover, SAA4 was significantly upregulated in RA patients (n = 40, 66.43 ± 12.97 ng/mL) compared with normal controls (n = 40, 4.79 ± 0.95 ng/mL) and had a higher area under the curve than C-reactive protein. Thus, we identified SAA4 as a protein that was positively correlated with RF and RA. SAA4 may represent a novel prescreening marker for the diagnosis of RA.

This study aimed to investigate the effects of Phlomis umbrosa root on bone growth and growth mediators in rats. Female adolescent rats were administered P. umbrosa extract, recombinant human growth hormone or vehicle for 10 days. Tetracycline was injected intraperitoneally to produce a glowing fluorescence band on the newly formed bone on day 8, and 5-bromo-2'-deoxyuridine was injected to label proliferating chondrocytes on days 8-10. To assess possible endocrine or autocrine/paracrine mechanisms, we evaluated insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3) or bone morphogenetic protein-2 (BMP-2) in response to P. umbrosa administration in either growth plate or serum. Oral administration of P. umbrosa significantly increased longitudinal bone growth rate, height of hypertrophic zone and chondrocyte proliferation of the proximal tibial growth plate. P. umbrosa also increased serum IGFBP-3 levels and upregulated the expressions of IGF-1 and BMP-2 in growth plate. In conclusion, P. umbrosa increases longitudinal bone growth rate by stimulating proliferation and hypertrophy of chondrocyte with the increment of circulating IGFBP-3. Regarding the immunohistochemical study, the effect of P. umbrosa may also be attributable to upregulation of local IGF-1 and BMP-2 expressions in the growth plate, which can be considered as a GH dependent autocrine/paracrine pathway.