2,3-Dihydrosorbicillin and chrysopanol stimulate insulin secretion in INS-1 cells.

Pancreatic ß-cell function and insulin secretion are important in antidiabetic drug development. In an effort to discover small molecules to regulate insulin secretion, an endophytic fungus, Penicillium sp. SSP-1CLG, was selected for chemical investigation. Large scale cultures of the strain followed by extraction and chromatographic analysis led to the isolation of 10 anthraquinone and alkaloid-type compounds. The isolated compounds were identified by comprehensive analysis of NMR, MS, and ECD data. The effect of compounds 1-10 on insulin secretion in INS-1 cells was investigated. 2,3-Dihydrosorbicillin (1), chrysophanol (2), and glandicolin B (10) at non-cytotoxic concentrations resulted in an increase of glucose-stimulated insulin secretion (GSIS) in rat INS-1 pancreatic ß-cells. Furthermore, we investigated the signaling pathway involved in 2,3-dihydrosorbicillin (1) and chrysophanol (2) action in the activation of peroxisome proliferator-activated receptor γ (PPARγ), pancreatic and duodenal homeobox-1 (PDX-1), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), and Akt. Treatment of INS-1 cells with 2,3-dihydrosorbicillin (1) and chrysophanol (2) increased the expression of these proteins. Our findings indicate that 2,3-dihydrosorbicillin and chrysophanol may play roles in the regulation of insulin secretion in pancreatic ß-cells, at least in part, by targeting PPARγ and PDX-1 via the IRS-2/PI3K/Akt signaling pathway.

Preparation of inhalable N-acetylcysteine-loaded magnetite chitosan microparticles for nitrate adsorption in particulate matter.

Airborne particulate matter has been designated as a class 1 carcinogen by the World Health Organization. Nitrate is a toxic substance that accounts for a large proportion of particulate matter, and nitrate toxicity has long been reported. In this study, we aimed to optimize the adsorption and removal of particulate matter containing nitrate for effective elimination by the lungs. To this end, particles were designed to optimize the inhalation and removal efficiencies. These particles were prepared as chitosan-based particles containing N-acetylcysteine by using emulsion diffusion methods. Chitosan adsorbs nitrate, while N-acetylcysteine dissolves mucus. This removal mechanism has been found to occur in various in vitro models that mimic respiratory environments and in vivo models. In particular, the removal of exogenous substances, such as particulate matter, by the motility of respiratory cilia through mucolytic effect was investigated. This new approach for the adsorption and elimination of toxic substances entering the lungs represents an alternative defense mechanism against exposure to nitrates from air pollution.

Elucidation of protective effects of oxime derivatives against cisplatin-induced cytotoxicity in LLC-PK1 kidney cells.

This study aimed to explore the renoprotective effects of oxime derivatives against cisplatin-mediated cell death in LLC-PK1 porcine kidney epithelial cells. Treatment with compounds 161-A and 161-F improved cisplatin-mediated LLC-PK1 cell damage and increased cell viability by more than 80% of the control value when compared with that of cisplatin-treated cells. In addition, 161-A and 161-F reduced cisplatin-induced apoptosis. Analysis of the molecular mechanisms underlying the effects exerted by these compounds revealed that treatment with 161-A and 161-B inhibited the protein expression of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) and cleaved caspase-3 in cisplatin-treated LLC-PK1 cells. Thus, these findings provide in vitro scientific evidence that oxime derivatives may be useful as pharmacological candidates for the prevention of cisplatin-mediated nephrotoxicity.

Androgen Receptor as a Predictive Marker for Pathologic Complete Response in Hormone Receptor–Positive and HER-2–Negative Breast Cancer with Neoadjuvant Chemotherapy / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study investigated pathological complete response (pCR) according to androgen receptor (AR) in breast cancer patients undergoing neoadjuvant chemotherapy and estimated the relationship between AR expression and clinicopathological factors. @*Materials and Methods@#We identified 624 breast cancer patients who underwent surgery after neoadjuvant chemotherapy at the National Cancer Center in Goyang, Korea from April 2016 to October 2019. We retrospectively collected the clinicopathologic information and AR expression results and analyzed the data according to cancer stage, hormonal receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, tumor subtype, and pCR. @*Results@#Among the 624 breast cancer patients, 529 (84.8%) were AR-positive (AR+) patients and 95 (15.2%) were AR-negative (AR–) patients. AR+ patients showed more estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, HER2-positivity, and HR-positive and HER2-negative (HR+/HER2–) subtype. The rate of pCR was 31.4% (196/624). AR– patients had a significantly higher rate of pCR than AR+ patients (AR– 43.2% vs. AR+ 29.3%, p=0.007). The tumor factors associated with pCR were early stage, histologic grade 3, ER-negative, PR-negative, AR-negative, HER2-positive, and high Ki-67 values. In univariable analysis, AR+ significantly decreased the state of pCR (odds ratio, 0.546; 95% confidence interval, 0.349 to 0.853; p=0.008). According to tumor subtype, AR– tumor showed higher pCR rate in HR+/HER2– subtype (AR– 28.6% vs. AR+ 7.3%, p=0.022). @*Conclusion@#AR expression is predominant in the HR+/HER2– subtype. AR– is significantly associated with the pCR rate in breast cancer patients, especially within HR+/HER2– subtype. When determining neoadjuvant chemotherapy for the HR+/HER2– subtype, AR expression can be considered as a pCR predictive marker.

Effectiveness of protocolized management for patients sustaining maxillofacial fracture with massive oronasal bleeding: a single-center experience.

BACKGROUND: Maxillofacial fractures can lead to massive oronasal bleeding; however, surgical hemostasis and packing procedures can be challenging owing to complex facial anatomy. Only a few studies investigated maxillofacial fractures with massive oronasal hemorrhage. However, thus far, no studies have reported a protocolized management approach for maxillofacial trauma from a single center. This study aimed to evaluate the effectiveness of protocolized management for maxillofacial fractures with oronasal bleeding. METHODS: Patients were identified from the National Cheng University Hospital trauma registry from 2010 to 2020. We included patients with a face Abbreviated Injury Scale (AIS) score of > 3 and active oronasal bleeding. Patients' characteristics were compared between the angiography and non-angiography groups and between survivors and nonsurvivors. RESULTS: Forty-nine patients were included. Among them, 34 (69%) underwent angiography, of whom 21 received arterial embolization. Forty-seven patients (96%) successfully achieved hemostasis by adhering to the treatment protocol at our institution. Compared with the non-angiography group, the angiography group had significantly more patients requiring oral intubation (97% vs. 53%, P < 0.001), Glasgow Coma Scale < 9 (GCS; 79% vs. 27%, P < 0.001), head AIS > 3 (65% vs. 13%, P = 0.001), higher Injury Severity Score (ISS; 43 [33-50] vs. 22 [18-27], P < 0.001), higher incidence of cardiopulmonary resuscitation (CPR; 41% vs. 0%, P = 0.002), higher mortality rate (35% vs. 7%, P = 0.043), and more units of packed red blood cells (PRBC) transfused within 24 h (12 [6-20] vs. 2 [0-4], P < 0.001). The nonsurvivor group had significantly more patients with hypotension (62% vs. 8%; P < 0.001), higher need for CPR (85% vs. 8%; P < 0.001), head AIS > 3 (92% vs. 33%; P < 0.001), skull base fracture (100% vs. 64%; P = 0.011), GCS score < 9 (100% vs. 50%; P = 0.003), higher ISS (50 [43-57] vs. 29 [19-48]; P < 0.001), and more units of PRBC transfused within 24 h (18 [13-22] vs. 6 [2-12]; P = 0.001) than the survivor group. More patients underwent angiography in the nonsurvivor group than in the survivor group (92% vs. 61%; P = 0.043). Among embolized vessels, the internal maxillary artery (65%) was the most common bleeding site. Hypoxic encephalopathy accounted for 92% of deaths. CONCLUSIONS: Protocol-guided management effectively optimizes outcomes in patients with maxillofacial bleeding.

Spatio-temporal characterization of tropospheric ozone and its precursor pollutants NO2 and HCHO over South Asia.

In recent decades, South Asia has experienced declining air quality, with much of the attention being focused on extremely high levels of particulate matter. Here, we analyze tropospheric ozone (O3), formaldehyde (HCHO), and nitrogen dioxide (NO2) to assess other measures of air quality across South Asia from 2008 to 2018. The IASI-Forli retrieved tropospheric ozone data was validated with ozonesonde, reanalysis (ERA5), satellite (TES), and model simulation products (GEOS-Chem and TOMCAT/SLIMCAT). Space-based observations of these three trace gases were used to conduct a spatio temporal analysis over South Asia using trend analysis (Theil-Sen and linear regression), change-point detection (Pettitt's test), and hotspot identification (Getis-Ord Gi*). We used the formaldehyde-nitrogen dioxide ratio (FNR) to identify NOx limited, VOC limited, and transitional regimes in South Asia. Counter to previous studies, a statistically significant decrease of HCHO (-0.0041 DU yr-1) and O3 (-0.064 DU yr-1) was detected for South Asia; however, NO2 is increasing the 0.001 DU yr-1 over South Asia during 2008-18. The Indo-Gangetic Plains emerged as being critically affected by the three trace gases. Certain parts of southern and south-eastern India are gradually emerging as NO2 and HCHO hotpots. No significant O3 hotspots were discernible, though coldspots existed along the Himalaya belt of India, Nepal, and Bhutan and mountainous tracts of Pakistan. FNR indicates the reduction of NOx in NOx-limited regime of the Indo-Gangetic Plains reduced the formation of tropospheric O3 over South Asia.

Diagnostic value of presepsin in odontogenic infection: a retrospective study / 대한악안면성형재건외과학회지

Background@#Most head and neck infections originate from odontogenic causes; therefore, it is important to determine the severity of odontogenic infections. Since severe infection can cause sepsis, a systemic examination should be performed when evaluating a patient with odontogenic infection. C-reactive protein (CRP), white blood cell count (WBC), procalcitonin (PCT), and presepsin (PSEP) can be used to evaluate the severity of inflammatory status and sepsis in patients in the early stages of visiting the emergency room. Moreover, sepsis can be diagnosed based on the systemic inflammatory response syndrome (SIRS) classification. In relation to PSEP, significant study results on sepsis have been reported in other organ infections. However, there has been no progress in odontogenic infection; therefore, this study aimed to determine the diagnostic value of sepsis derived from odontogenic infection. @*Methods@#This study was conducted from March 2021 to October 2021 on 43 patients admitted to the Department of Oral and Maxillofacial Surgery, Dankook University Hospital, in the emergency room for odontogenic infection. All patients underwent vital sign assessment and diagnostic tests (CRP, WBC, PCT, PSEP) in the emergency room. Sepsis was classified according to the SIRS criteria, and CRP, WBC, PCT, and PSEP levels were measured. The Statistical Package for the Social Sciences was used for statistical analyses. @*Results@#The results of this study showed a moderately positive correlation between CRP and PCT, CRP and PSEP, and CT and PSEP levels. In addition, PCT and PSEP levels showed a positive correlation with sepsis. The odds ratios of sepsis and PCT and sepsis and PSEP were statistically significant. The optimal cut-off values obtained through the receiver operating characteristic curve were 0.24 and 671.5 for PCT and PSEP, respectively. Finally, there were positive correlations between CRP level and length of stay, WBC and Flynn scores, PCT level and Flynn scores, PCT level and length of stay, and PSEP level and length of stay. @*Conclusion@#WBC and CRP and PCT levels have been used in the past to determine the severity of infection and sepsis in patients with odontogenic infection, but PSEP was also found to have diagnostic value in this study. According to this study, a PSEP level of 671.5 pg/ml or higher for odontogenic infection can be considered an abnormal level.

Predicting prognosis and evaluating the benefits of adjuvant chemotherapy depending on the tumor location in intrahepatic cholangiocarcinoma: focusing on the involvement of below 2nd bile duct confluence

Purpose@#Intrahepatic cholangiocarcinoma (ICC) has various characteristics according to anatomical, histologic classifications, and its prognoses are different. This study aimed to compare oncologic outcomes according to tumor location (second bile duct confluence) and evaluate the effect of adjuvant chemotherapy. @*Methods@#Clinical data of 318 patients who underwent curative resection for ICC was reviewed. Central type ICC (C-ICC) and peripheral type ICC (P-ICC) were defined when the tumor invades the intrahepatic secondary biliary confluence and when located more peripherally, respectively. @*Results@#A larger tumor size, higher rate of elevated CA 19-9 level, vascular invasion, R1 resection, advanced T stage, and lymph node metastasis were found in C-ICC. C-ICC had poorer overall survival (median, 33 months vs. 58 months; P = 0.001), and the difference was more prominent in the early stage. C-ICC had a higher recurrence rate (68.7% vs. 55.1%, P = 0.014); otherwise, there was no difference in the recurrence patterns. There were no survival benefits of adjuvant chemotherapy in the entire cohort, but there were benefits in advanced stages (T3–4, N1 stage), especially in C-ICC. @*Conclusion@#C-ICC has more aggressive tumor characteristics and poor survival compared to P-ICC. Adjuvant chemotherapy seems to have survival benefits in the advanced stages, especially in the central type.

Automated Radiology Alert System for Pneumothorax Detection on Chest Radiographs Improves Efficiency and Diagnostic Performance.

We aimed to set up an Automated Radiology Alert System (ARAS) for the detection of pneumothorax in chest radiographs by a deep learning model, and to compare its efficiency and diagnostic performance with the existing Manual Radiology Alert System (MRAS) at the tertiary medical center. This study retrospectively collected 1235 chest radiographs with pneumothorax labeling from 2013 to 2019, and 337 chest radiographs with negative findings in 2019 were separated into training and validation datasets for the deep learning model of ARAS. The efficiency before and after using the model was compared in terms of alert time and report time. During parallel running of the two systems from September to October 2020, chest radiographs prospectively acquired in the emergency department with age more than 6 years served as the testing dataset for comparison of diagnostic performance. The efficiency was improved after using the model, with mean alert time improving from 8.45 min to 0.69 min and the mean report time from 2.81 days to 1.59 days. The comparison of the diagnostic performance of both systems using 3739 chest radiographs acquired during parallel running showed that the ARAS was better than the MRAS as assessed in terms of sensitivity (recall), area under receiver operating characteristic curve, and F1 score (0.837 vs. 0.256, 0.914 vs. 0.628, and 0.754 vs. 0.407, respectively), but worse in terms of positive predictive value (PPV) (precision) (0.686 vs. 1.000). This study had successfully designed a deep learning model for pneumothorax detection on chest radiographs and set up an ARAS with improved efficiency and overall diagnostic performance.

Necrostatins regulate apoptosis, necroptosis, and inflammation in cisplatin-induced nephrotoxicity in LLC-PK1 cells.

Acute kidney injury (AKI) is a common clinical problem that is associated with high mortality due to multiple complex mechanisms. Cisplatin is the most important and highly effective chemotherapeutic agent used for the treatment of various solid tumors; however, it is associated with dose-dependent adverse effects, particularly in the kidney where it can cause severe nephrotoxicity. The pathophysiological basis of cisplatin-induced nephrotoxicity has been investigated over the last few decades, and the key pathological occurrences in cisplatin nephrotoxicity include renal tubular cell injury and death. Necrostatin-1 (Nec-1) has been confirmed to act as a specific and potent small-molecule inhibitor of necroptosis. However, the effects of three structurally distinct necrostatins on cisplatin-induced nephrotoxicity remain ambiguous. The aim of this study was to determine if three types of necrostatins (Nec-1, Nec-3-A, and/or Nec-3-B) can exert protective effects in regard to the AKI induced by cisplatin. Our results indicated that necrostatins can prevent cisplatin induced nephrotoxicity via modulating apoptotic pathways through the suppression of cleaved caspase-3 and also by influencing the function of mitogen-activated protein kinase pathway members, including extracellular signal-regulated kinases, c-Jun N-terminal kinases, and p38, in the renal tubular epithelial cell line LLC-PK1. These findings suggest that necrostatins exert beneficial anti-apoptotic effects in the context of AKI induced by cisplatin.

Combined treatment of Taraxaci Herba and R7050 alleviates the symptoms of herpes simplex virus-induced Behçet's disease in rats.

BACKGROUND: Behçet's disease (BD) is a chronic inflammatory systemic disease that affects multiple organs. The causes of BD are still unknown, but it is primarily characterized by autoimmune reaction in the blood vessels. Current research focuses on treatments that can reduce the non-typical inflammatory responses of BD. Nevertheless, studies on improving the inflammatory effect of BD using inflammation mechanisms are still insufficient. Therefore, we conducted the integrated treatments related to inflammation modulation and achieved alleviation of symptoms in BD mice. METHODS: To understand the complex etiology of BD and compare its management, the herpes simplex virus (HSV)-induced BD mouse model was used. In order to alleviate the inflammatory response in BD mice, Taraxaci Herba (TH, herbal medicine), R7050-a TNFα inhibitor, and a mixture of TH and R7050 were injected for 2 weeks repetitively. The SCORAD index was examined to evaluate the cutaneous inflammations. In addition, histological changes and inflammatory factors were analyzed. RESULTS: Repetitive injection of TH and/or R7050 reduced the symptoms of BD and significantly decreased IL-6, IL-1ß, and TNFα in blood sera. Moreover, this treatment reduced the ulcers and the deterioration of skin. CONCLUSIONS: The results of our study showed that the down-regulation of inflammatory factors is related to the control of immune responses in BD models, suggesting that a mixed drug treatment may be more effective in improving the condition of BD.

Comparison of gait recovery patterns according to the paralyzed side in stroke patients: An observational study based on a retrospective chart review (STROBE compliant).

ABSTRACT: Gait rehabilitations have been abundantly performed for post-stroke patients, because gait is the most important factor for the return of post-stroke patients to daily life. However, conventional uniform gait rehabilitations tend to be tedious and reduce motivation. The aim of this study was to contribute to the development of personalized rehabilitation of gait by identifying differences in gait recovery pattern according to the paralyzed side of post-stroke patients.The gait analysis was performed on stroke patients who are right-handed and can walk independently. We retrospectively analyzed the results of pelvic movements and displacement of center of pressure (COP) during gait using corresponding equipments. To show the difference of gait recovery pattern according to the paralyzed side, we divided subjects into two groups, right (n = 19) and left (n = 20) hemiparesis group. The measured variables were as follows: tilt, obliquity, and rotation symmetries of pelvis; area, velocity, and lateral symmetry of COP.First, in the left hemiparesis group, obliquity (P < .01) and rotation (P < .01) symmetries of the movement of the pelvis were significantly improved in the follow-up compared to the initial gait analysis. In the right hemiparesis group, tilt (P < .001), obliquity (P < .001), and rotation (P < .05) symmetries were significantly improved in the follow-up compared to the initial gait analysis. Second, COP area and COP velocity values in the follow-up were significantly smaller than those in the initial gait analysis in the left (P < .001, P < .05) and right (P < .001, P < .01) hemiparesis groups. The positive value of lateral symmetry increased, although not a significant difference statistically, as walking ability improved in both groups. In the correlation analysis among variables obtained using Treadmill, there were significant positive linear relationships between the lateral symmetry and the COP area (P < .05), and between the COP velocity and the lateral symmetry (P < .001) of the follow-up gait analysis in the right hemiparesis group.It was confirmed that the gait recovery pattern differs according to the paralyzed side of post-stroke patients and the role of the intact side, such as moving the COP to the intact side, is important for the improvement of gait function in both groups.This study was registered with the Clinical Research Information Service (CRIS) of the Korea National Institute of Health (NIH), Republic of Korea (KCT0002984) and was approved by the Institutional Review Board (IRB) of the WKUGH (WKIRB [2018-25], November 28, 2018).

Cupping Therapy for Migraine: A PRISMA-Compliant Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Migraine is a common reason for primary headache disorders. Cupping is a frequently used traditional intervention for controlling pain including migraine. There have been no systematic reviews on the clinical effects of cupping on migraine. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the effectiveness of cupping therapy for migraine. The search strategy was built for the presence of related keywords, such as "migraine" and "cupping therapy", in the title and abstract of research articles indexed in the MEDLINE, EMBASE, CENTRAL, and other databases. The randomized controlled trials (RCTs) of cupping therapy for migraine were searched and selected from inception to May 2019. We searched eight databases including PubMed, EMBASE, Cochrane Central Register of Controlled Trials. The selection process and the quality assessment were performed by 2 authors independently. The meta-analysis was conducted and qualitative analysis was also performed. RESULTS: 218 studies were identified, and 6 RCTs were enrolled in this review. In comparison to drugs, wet cupping showed a higher total effective rate (TER). In the dry cupping plus acupuncture, the result of TER showed more effectiveness (RR 1.05, 95% CI 0.99 to 1.12, P=0.13) compared with acupuncture alone, but there was no statistically significant difference. In qualitative analysis, the results showed wet cupping plus drugs treatment could quickly relieve pain and significantly improve patients' quality of life and wet cupping could reduce headache pain. CONCLUSION: Cupping therapy could be effective for the treatment of migraine. However, the qualities of the evidence were low, so well-designed RCTs are needed to confirm the effectiveness of cupping. Systematic review registration: PROSPERO registration number is CRD42017054979.

Sentinel Lymph Node Biopsy in Breast Cancer Patients With Pathological Complete Response in the Axillary Lymph Node After Neoadjuvant Chemotherapy / 한국유방암학회지

Purpose@#Sentinel lymph node biopsy (SLNB) alone following neoadjuvant chemotherapy (NAC) remains controversial in patients with breast cancer who are initially lymph nodepositive. The present study aimed to evaluate the impact of SLNB and axillary lymph node dissection (ALND) on breast cancer recurrence and survival in patients who converted from lymph node-positive to pathological node-negative (ypN0) after NAC. @*Methods@#This single-center retrospective study included 223 patients who converted to axillary lymph node-negative status after NAC and underwent breast and axillary surgery between January 2006 and December 2015. This study compared the overall survival (OS), disease-free survival (DFS), ipsilateral axillary lymph node recurrence rates and incidence of postoperative complications, especially, arm lymphedema and shoulder stiffness between SLNB and ALND. @*Results@#This study included 223 patients with axillary pathological complete response (pCR) after NAC and surgery. The SLNB and ALND groups included 94 and 129 patients, respectively. The median follow-up time was 57 (range, 6–155) in the SLNB group and 99 (range 2–159) months in the ALND group. The corresponding 5-year OS and DFS rates were 96.3% and 94.2% (p = 0.392), and 89.2% and 86.4% (p = 0.671), respectively. Four patients (4.3%) in the SLNB group and nine (7.0%) in the ALND group developed locoregional recurrences. Ipsilateral axillary lymph node recurrence and distant metastasis were observed in one (1.1%) and three (2.3%) patients, and in 10 (10.6%) and 11 (8.5%) patients, respectively. Patients in the ALND group were more likely than their SLNB counterparts to experience complications, such as shoulder stiffness (9 [7.0%] vs. 4 [4.3%] patients, p = 0.57). The rate of lymphedema in the ALND group was three times that in the SLNB group (35 [27.1%] vs. 8 [8.5%] patients, p < 0.001). @*Conclusion@#As an alternative to ALND, SLNB has oncological safety in patients with axillary pathological complete response after NAC.

A comparative study on intraocular pressure under various anesthetics in cynomolgus monkeys (Macaca fascicularis) / 한국실험동물학회지

Background@#Nonhuman primates (NHPs) are superior model for ocular research due to its morphological and physiological similarities with humans. Thus, the effect of four different anesthetic combinations [ketamine (10 mg/ kg), ketamine + xylazine (7 + 0.6 mg/kg), zoletil (4 mg/kg), and zoletil + xylazine (4 + 0.2 mg/kg)] on intraocular pressure (IOP) was determined in cynomolgus monkeys. @*Results@#The administration of ketamine + xylazine or zoletil + xylazine resulted in lower IOP compared to ketamine or zoletil alone. Moreover, the IOP in male monkeys was higher than in females. The difference between the right and left eye was not found. @*Conclusions@#Anesthetics affected the IOP, and gender differences should be considered when measuring the IOP of nonhuman primates (NHPs).

A comparative study on intraocular pressure under various anesthetics in cynomolgus monkeys (Macaca fascicularis) / 한국실험동물학회지

Background@#Nonhuman primates (NHPs) are superior model for ocular research due to its morphological and physiological similarities with humans. Thus, the effect of four different anesthetic combinations [ketamine (10 mg/ kg), ketamine + xylazine (7 + 0.6 mg/kg), zoletil (4 mg/kg), and zoletil + xylazine (4 + 0.2 mg/kg)] on intraocular pressure (IOP) was determined in cynomolgus monkeys. @*Results@#The administration of ketamine + xylazine or zoletil + xylazine resulted in lower IOP compared to ketamine or zoletil alone. Moreover, the IOP in male monkeys was higher than in females. The difference between the right and left eye was not found. @*Conclusions@#Anesthetics affected the IOP, and gender differences should be considered when measuring the IOP of nonhuman primates (NHPs).

Development of Integrative Medicine Therapy for Gastrointestinal Autoimmune Diseases: A study protocol for a registry study.

BACKGROUND: Although the incidence of AD, including gastrointestinal AD, increases every year, there is no effective therapy for it yet. This causes high medical costs to be spent on the management of autoimmune patients every year. The aim of this study is to identify the characteristics related to the causes and symptoms of gastrointestinal autoimmune disease (AD) by collecting patients' information and to further contribute to the development of an integrative medicine therapy for gastrointestinal AD. METHODS/DESIGN: This study is a registry study of patients diagnosed with gastrointestinal AD. Subjects who voluntarily sign a written consent form after receiving a sufficient explanation will be assessed for compliance with the inclusion and exclusion criteria through a screening process on their first visit. A total of 35 subjects will be recruited; 15 will be assigned to the patient group, 10 to the control group, 8 to the caregiver group, and 2 to the medical staff group. The clinical information of the subjects will be evaluated through statistical analyses. As this study is a registry study, it will not test specific hypotheses. DISCUSSION: If this study identifies the significant characteristics of gastrointestinal AD patients, the results will be useful for the development of integrative medicine methods for the treatment of gastrointestinal AD. STUDY REGISTRATION: This study was registered with the Clinical Research Information Service (CRIS) of the Korea National Institute of Health (NIH), Republic of Korea (KCT0003976, date of registration: May 23, 2019).

Association between Relative Handgrip Strength and C-Reactive Protein in Adults / 대한스포츠의학회지

Purpose@#The purpose of this study was to investigate whether obesity indicators are mediated in the association between muscle strength and inflammation levels, and further confirm the association between muscle strength level by sex and age and inflammatory levels. @*Methods@#In this study, 3,234 adults living in rural areas were surveyed from 2007 to 2015 and the data was finally analyzed on 2,149 adults. To identify that obesity indicators are mediated in relation to the association between relative grip strength and C-reactive protein (CRP) level, odds ratio (OR) and 95% confidence interval (CI) were calculated using logistic regression analysis (p＜ 0.05). @*Results@#As confounding variables were adjusted, the odds ratio for high inflammatory conditions was lower at a high (OR, 0.58; 95% CI, 0.40–0.85) or medium (OR, 0.64; 95% CI, 0.46–0.90) level of relative grip strength than a low level of relative grip strength. However, there were no significant results if the body fat percentage was added for the confounding variable. When the association between relative grip strength and inflammatory conditions was divided by sex, for women, the odds ratio about high inflammatory conditions was gradually decreased as the relative grip level increased (medium level: OR, 0.55; 95% CI, 0.35–0.87; high level: OR, 0.49; 95% CI, 0.30–0.82). The association of relative grip strength with inflammatory conditions was shown differently in age groups. @*Conclusion@#In conclusion, improvement of muscle strength is a factor that can lower the level of inflammation, and it is important to lower the level of inflammation that can cause cardiovascular disease through resistance exercise differentiated by age and sex.

Recent Findings on the Mechanism of Cisplatin-Induced Renal Cytotoxicity and Therapeutic Potential of Natural Compounds

The efficacy and side effects associated with anticancer drugs have attracted an extensive research focus. Onconephrology is an evolving field of nephrology that deals with the study of kidney diseases in cancer patients. Most renal diseases in cancer patients are unique, and management of renal disease can be challenging especially in the presence of continuing use of the nephrotoxic drugs. Cisplatin is one of the most important chemotherapeutic agents used in the treatment of various malignancies, such as head, neck, ovarian, and cervical cancers. The major limitation in the clinical use of cisplatin is its tendency to induce adverse effects, such as nephrotoxicity. Recently, plant-derived phytochemicals have emerged as novel agents providing protection against cisplatin-induced renal cytotoxicity. Owing to the diversity of phytochemicals, they cover a wide spectrum of therapeutic indications in cancer and inflammation and have been a productive source of lead compounds for the development of novel medications. Of these agents, the effectiveness of triterpenoids, isolated from various medicinal plants, against cisplatin-induced renal cytotoxicity has been reported most frequently compared to other phytochemicals. Triterpenes are one of the most numerous and diverse groups of plant natural products. Triterpenes ameliorate cisplatin-induced renal damage through multiple pathways by inhibiting reactive oxygen species, inflammation, down-regulation of the MAPK, apoptosis, and NF-κB signaling pathways and upregulation of Nrf2-mediated antioxidant defense mechanisms. Here, we reviewed recent findings on the natural compounds with protective potential in cisplatin-induced renal cytotoxicity, provided an overview of the protective effects and mechanisms that have been identified to date, and discussed strategies to reduce renal cytotoxicity induced by anticancer drugs.

Comparison of clinical outcomes between sentinel lymph node biopsy and axillary lymph node dissection in a single-center Z0011-eligible breast cancer cohort

Purpose@#The ACOSOG Z0011 trial has proven the oncological safety of sentinel lymph node biopsy (SLBx) for node negative breast cancer. Accordingly, treatment paradigm including axilla surgery was changed. We retrospectively reviewed breast cancer patients to evaluate the clinical effect of paradigm shift in breast cancer surgery after applying the Z0011 criteria. @*Methods@#All women who underwent breast-conserving surgery at the National Cancer Center between January 1, 2000, and December 31, 2015, were enrolled and classified according to the Z0011 criteria. The primary endpoint of the study was the disease-free survival rates, and the secondary was the adverse events, especially arm lymphedema. @*Results@#Total 361 patients were enrolled the study (271 axillary lymph node dissection [ALND] group, 90 SLBx group). After the Z0011 guideline was adopted in our institute, the use of ALND decreased, and lymph node sampling (removing only a few axillary lymph nodes) replaced ALND. The total mean number of retrieved nodes were more in ALND group (13.02) than SLBx group (3.43). However, there was no difference in the mean number of positive nodes between two groups (2.34 in ALND group vs. 1.12 in SLBx group, P=0.001). During follow-up, 25 patients experienced disease recurrence: 22 from the ALND group and three from the SLBx group. All of died seven patients were from the ALND group. The ALND group had more complications than the SLBx group (P=0.02). Arm edema occurred more frequently in the ALND group (29.5%) than in the SLBx group (5.6%), although without statistical significance (P=0.07). @*Conclusion@#In our study, we concluded that SLBx can be used safely in Z0011-eligible cohort without increased risk of locoregional recurrence. Moreover, we found that omission of ALND is favored to reduce some serious complications such as arm lymphedema.