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1.
Article in English | WPRIM | ID: wpr-1043397

ABSTRACT

Objectives@#Water discharged from waterlines in dental units can cause cross-infection among dental workers and patients by various mechanisms. Therefore, we analyzed the bacterial counts in the water of dental unit chair waterlines, according to waterline flushing and related factors. @*Methods@#A total of 58 dental hospitals located in a metropolitan city participated in this study between September 2019 and January 2020. Water was collected from a high-speed handpiece and a three-way syringe of a dental unit chair and transported to the experimental lab within 4 hours;bacterial plating colony counting was performed after culturing for 72 hours. In addition, a survey was conducted with questions on the characteristics of hospitals, waterline flushing, and related factors, such as water purification systems, regular filter replacement, and backflow prevention equipment. @*Results@#The bacterial count in the water of the dental handpiece and three-way syringe in the institutions that performed waterline flushing was lower than that in the institutions that did not (P<0.001). When waterline flushing was performed on dental handpieces, the bacterial count was found to be lower when regular filter replacement and backflow prevention equipment were combined. In addition, disinfection of waterlines had a significant effect on the bacterial count when performed together with waterline flushing. However, for the three-way syringe, when waterline flushing was performed, no factors significantly affected the bacterial count. @*Conclusions@#To reduce microbial contamination of dental water, flushing of dental unit waterlines combined with regular filter replacement, backflow prevention equipment, and disinfection of waterlines may be effective in dental hospitals.

2.
Article in English | WPRIM | ID: wpr-1043526

ABSTRACT

This study measured the impact of the Decisions on Life-Sustaining Treatment Act by analyzing medical cost data from the National Health Insurance Service-National Sample Cohort. After identifying the patients who died in 2018 and 2019, the case and control groups were set using the presence of codes for managing the implementation of life-sustaining treatment with propensity score matching. Regarding medical costs, the case group had higher medical costs for all periods before death. The subdivided items of medical costs with significant differences were as follows: consultation, admission, injection, laboratory tests, imaging and radiation therapy, nursing hospital bundled payment, and special equipment.This study is the first analysis carried out to measure the impact of the Decision on LifeSustaining Treatment Act through a cost analysis and to refute the common expectation that patients who decided to withhold or withdraw life-sustaining treatment would go through fewer unnecessary tests or treatments.

3.
Article in English | WPRIM | ID: wpr-999690

ABSTRACT

Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.

4.
Article in English | WPRIM | ID: wpr-999697

ABSTRACT

Hair loss is a common condition that can have a negative impact on an individual’s quality of life. The severe side effects and the low efficacy of current hair loss medications create unmet needs in the field of hair loss treatment. Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1), one of the components of the extracellular matrix, has been shown to play a role in maintaining its integrity. HAPLN1 was examined for its ability to impact hair growth with less side effects than existing hair loss treatments. HAPLN1 was predominantly expressed in the anagen phase in three stages of the hair growth cycle in mice and promotes the proliferation of human hair matrix cells. Also, recombinant human HAPLN1 (rhHAPLN1) was shown to selectively increase the levels of transforming growth factor-β receptor II in human hair matrix cells. Furthermore, we observed concomitant activation of the ERK1/2 signaling pathway following treatment with rhHAPLN1. Our results indicate that rhHAPLN1 elicits its cell proliferation effect via the TGF-β2-induced ERK1/2 pathway. The prompt entering of the hair follicles into the anagen phase was observed in the rhHAPLN1-treated group, compared to the vehicle-treated group. Insights into the mechanism underlying such hair growth effects of HAPLN1 will provide a novel potential strategy for treating hair loss with much lower side effects than the current treatments.

5.
Article in English | WPRIM | ID: wpr-1001003

ABSTRACT

Objectives@#Rational planning and efficient management of the oral health workforce is essential for the promotion of oral health. Therefore, this study aims to analyze the distribution characteristics of dentists, using public big data. The results of this study could contribute to the development of the oral healthcare policies proposal and desirable dental services. @*Methods@#The data of dentists working in medical institutions were analyzed by type and region from 2010 to 2020 using the Korean Statistical Information Service. Python version 3.10 was employed for data analysis and visualization, and the matplotlib and seaborn libraries were used to create graphs. @*Results@#The average age of dentists working in medical institutions was 47.4 years in 2020 ― an increase by 5.3 years compared to the 2010 data. When considering different regions, the average age of dentists in major cities, including Seoul (49.7 years), was higher than in their surroundings areas (47.2-49.5 years). @*Conclusions@#A continuous increase in the average age of dentists over the past 10 years and a difference in age distribution among different regions were observed. This is probably because new dental clinics are opening predominantly in smaller cities. Therefore, institutional support for new dental clinics in these areas is necessary to promote high-quality dental healthcare within regions.Additionally, oral healthcare services to vulnerable populations should be provided through a national oral healthcare policy utilizing these local dental clinics.

6.
Health Communication ; (2): 1-8, 2023.
Article in English | WPRIM | ID: wpr-1040688

ABSTRACT

Purpose@# : We discussed what is needed for ‘Shared decision making (SDM)’ in the digital medical environment. @*Methods@# : We looked at what needs to be considered for remote SDM by examining research data on communication and remote SDM operation in existing digital environments. @*Results@# : The integration of digital technology in medicine has significantly enhanced remote communication between patients and doctors. Notably, both the quantity and quality of information exchanged among participants have markedly improved. Additionally, as patients can obtain information without relying on hospitals and doctors, the flow of information is changing from one-way (from doctor to patient) to mutual exchange between patients and doctors. SDM is a decision-making process that emphasizes patient participation, exchange of medical information and information about patient preferences, and decisions based on sufficient deliberation and consensus, and is premised on multiple meetings. To ensure effective SDM, it is necessary to understand the synchronous and asynchronous communication methods of digital technology and the exchange of expanded information. @*Conclusion@# : To facilitate successful remote Shared Decision Making (SDM), it is crucial for both patients and doctors to have digital literacy, health literacy, and maintain an attitude of respectful communication.

7.
Immune Network ; : e47-2023.
Article in English | WPRIM | ID: wpr-1040782

ABSTRACT

Scrub typhus, a mite-borne infectious disease, is caused by Orientia tsutsugamushi. Despite many attempts to develop a protective strategy, an effective preventive vaccine has not been developed. The identification of appropriate Ags that cover diverse antigenic strains and provide long-lasting immunity is a fundamental challenge in the development of a scrub typhus vaccine. We investigated whether this limitation could be overcome by harnessing the nanoparticle-forming polysorbitol transporter (PST) for an O. tsutsugamushi vaccine strategy.Two target proteins, 56-kDa type-specific Ag (TSA56) and surface cell Ag A (ScaA) were used as vaccine candidates. PST formed stable nano-size complexes with TSA56 (TSA56-PST) and ScaA (ScaA-PST); neither exhibited cytotoxicity. The formation of Ag-specific IgG2a, IgG2b, and IgA in mice was enhanced by intranasal vaccination with TSA56-PST or ScaA-PST. The vaccines containing PST induced Ag-specific proliferation of CD8 + and CD4 +T cells. Furthermore, the vaccines containing PST improved the mouse survival against O.tsutsugamushi infection. Collectively, the present study indicated that PST could enhance both Ag-specific humoral immunity and T cell response, which are essential to effectively confer protective immunity against O. tsutsugamushi infection. These findings suggest that PST has potential for use in an intranasal vaccination strategy.

8.
Article in English | WPRIM | ID: wpr-1041087

ABSTRACT

Purpose@#The study aimed to classify patient safety accident and nursing malpractice types through a content analysis of litigation cases in which nurses were found guilty. @*Methods@#Data on malpractice cases were collected from the official website of the Korean judiciary. This analysis was conducted in stages according to the systematic content analysis method. A total of 46 cases consisting of 14 criminal cases and 32 civil cases were selected for analysis, and classified based on the types of safety accident and nursing malpractice. @*Results@#Eleven categories and 14 subcategories of accidents were extracted from 71 significant statements. The 11 categories of accidents consisted of falls, medication, burns, treatment, diet, medical equipment, delivery, exams, surgery, infection, and suicide. Five categories and 14 subcategories of nursing malpractice were extracted from 71 significant statements. The five categories of malpractice were as follows: failure to take affirmative action to prevent accidents, monitor, follow guidelines, use equipment properly, and reports. @*Conclusion@#These findings highlight the importance of nurses’ independent roles as patients’ safety managers. It can be used as primary data to develop organizational and educational support for nurses seeking to perform their professional roles in ensuring patient safety.

9.
Article in English | WPRIM | ID: wpr-1041182

ABSTRACT

Purpose@#This study developed a protocol for nursing care after death for adult patients in hospitals. @*Methods@#This was a methodological study to develop a care after death protocol. The preliminary protocol was developed based on a literature review, guidelines, and practice recommendations from groups of experts and clinical nurses. Content validity was evaluated by a group of experts (n=6) and nurses (n=30) in two hospitals. @*Results@#The preliminary protocol recommendations were modified by validation and the open-question analysis results. The final protocol comprised three general recommendations and 43 recommendations in five steps that are verification and notification of a death, personal care of the body, viewing the patient, patient transfer, and documentation and self-care. @*Conclusion@#This study result provides nurses with a consensus information on patient care after death and family support in a hospital setting. This nursing protocol is expected to improve the quality of care after death for adult patients and their families, and can be used for developing educational and emotional support for nurses to accomplish their important role.

10.
Article in English | WPRIM | ID: wpr-1041357

ABSTRACT

Purpose@#Increasing levels of domestic fine dust (DFD) have emerged as a serious problem that threatens public health by causing chronic respiratory diseases and skin aging. The present study was performed to investigate the inhibitory effects of Gryllus bimaculatus (the two-spotted cricket), which has recently attracted attention as an edible insect in South Korea, on DFD-induced aging and inflammation. @*Methods@#To verify that DFD causes skin aging and investigate the anti-aging effect of an aqueous ethanolic-Gryllus bimaculatus extract (AE-GBE), human diploid fibroblasts (HDF) were treated with 100 μg/mL of European reference material (ERM)-CZ100 dust for 24 hrs in the presence or absence of 100 μg/ml AE-GBE. Aging and cellular toxicities were assessed by measuring reactive oxygen species (ROS) levels, DNA fragmentation, and β-galactosidase activity. The protein levels of cyclooxygenase (COX) 2, matrix metalloproteinase (MMP)-1, and collagen were measured by western blot, and the mRNA expressions of inflammationrelated genes were assayed by quantitative reverse transcriptase polymerase chain reaction. @*Results@#Treatment with ERM-CZ100 induced an aged phenotype in HDF cells, as evidenced by increased ROS levels, DNA fragmentation, and senescence-associated β-galactosidase activity, but cotreatment with AE-GBE significantly reduced these inductions. The mRNA expressions of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α, induced by ERM-CZ100 were also reduced by AE-GBE cotreatment, which also reduced COX2 expression. Moreover, ERM-CZ100-induced MMP-1 expression and reduced collagen type I expression were recovered by AE-GBE treatment. @*Conclusion@#These results suggest that AE-GBE is a potential treatment for domestic fine dust-induced skin inflammation and inflammaging.

11.
Article in English | WPRIM | ID: wpr-966408

ABSTRACT

Thrombin is a serine protease that participates in a variety of biological signaling through protease-activated receptors. Intestinal myofibroblasts play central roles in maintaining intestinal homeostasis. In this study, we found that thrombin-induced apoptosis is mediated by the calcium-mediated activation of cytosolic phospholipase A2 in the CCD-18Co cell. Thrombin reduced cell viability by inducing apoptosis and proteinase-activated receptor-1 antagonist attenuated thrombin-induced cell death. Endogenous ceramide did not affect the cell viability itself, but a ceramide-mediated pathway was involved in thrombin-induced cell death. Thrombin increased intracellular calcium levels and cytosolic phospholipase A2 activity. The ceramide synthase inhibitor Fumonisin B 1, intracellular calcium chelator BAPTA-AM, and cytosolic phospholipase A2 inhibitor AACOCF 3 inhibited thrombin-induced cell death. Thrombin stimulated arachidonic acid release and reactive oxygen species generation, which was blocked by AACOCF 3, BAPTA-AM, and the antioxidant reagent Trolox. Taken together, thrombin triggered apoptosis through calcium-mediated activation of cytosolic phospholipase A2 in intestinal myofibroblasts.

12.
Article in English | WPRIM | ID: wpr-937190

ABSTRACT

Purpose@#The surgical success rate for primary hyperparathyroidism (PHPT) is currently 95%–98%. However, 3%–24% of patients show persistently elevated (Pe) parathyroid hormone (PTH) levels after parathyroidectomy (PTX). This singlecenter retrospective study aimed to compare the outcomes of patients with normal PTH and PePTH levels after successful PTX and to identify the factors associated with PePTH. @*Methods@#The normal group, defined as patients with normal serum calcium and PTH levels immediately after PTX, was compared with the PePTH group (patients with normal or low serum calcium and increased serum PTH levels up to 6 months postoperatively) to determine the causes of disease in the PePTH group. @*Results@#There were no significant differences in age, sex, or preoperative estimated glomerular filtration rate between the normal PTH group (333 of 364, 91.5%) and the PePTH group (31 of 364, 8.5%). However, there were significant differences in preoperative 25-hydroxyvitamin D (17.9 and 11.8 ng/mL, respectively; P = 0.003) and PTH levels (125.5 and 212.4 pg/mL, respectively; P < 0.001) between the 2 groups. Among the 31 cases of the PePTH group, 18 were attributed to vitamin D deficiency. @*Conclusion@#Preoperative vitamin D deficiency is a predictive factor for PePTH. Therefore, preoperative administration of vitamin D supplements may reduce the probability of postoperative disease persistence. Patients with temporary laboratory abnormalities within 6 months after successful PTX should be monitored, and appropriate vitamin D and calcium supplementation may reduce the effort and cost of various examinations or reoperations.

13.
Article in English | WPRIM | ID: wpr-925867

ABSTRACT

Background@#Normocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients. @*Methods@#A total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122). @*Results@#NPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025);nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions. @*Conclusion@#We found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic.Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.

14.
Article in English | WPRIM | ID: wpr-968197

ABSTRACT

Purpose@#This cross-sectional study aimed to evaluate the mediating and moderating effects of resilience in the relationship between experience of workplace bullying and its consequences among hospital nurses. @*Methods@#The participants included 187 registered nurses working in general hospitals or a tertiary hospital in Busan and Gyeongnam Province, South Korea. Data were collected from October 25-November 30, 2019, using structured questionnaires. The moderating effects were examined using stepwise hierarchical multiple regression models. Data were analyzed using the SPSS/WIN 23.0 statistical program. @*Results@#The results demonstrated that resilience had a moderating role in the relationship between experience of workplace bullying and its consequences in hospital nurses (β=.01, p=.024). However, resilience showed no mediating effect. @*Conclusion@#To prevent and control workplace bullying, as well as to minimize its negative effects, it is necessary to develop a program that can enhance the resilience of hospital nurses.

15.
Article in English | WPRIM | ID: wpr-968806

ABSTRACT

P-glycoprotein (P-gp) is a transporter that plays an excretory role in epithelial cells. It is encoded by ABCB1, and single nucleotide polymorphisms (SNPs) in this gene can affect systemic drug exposure. Dapagliflozin and sitagliptin, used in type 2 diabetes treatment, are P-gp substrates. Here, we aimed to investigate whether ABCB1 polymorphisms affect dapagliflozin and sitagliptin pharmacokinetics (PK) in healthy Korean subjects.The study population consisted of 100 healthy Korean subjects (94 men and 6 women) who participated in four different clinical trials and received dapagliflozin and sitagliptin doses of 10 and 100 mg, respectively. We determined ABCB1 genotypes for the C3435T, C1236T, and G2677T/A SNPs. The relationship between the genotypes and dapagliflozin PKs was examined.Dapagliflozin and sitagliptin PK parameters were not statistically significantly affected by ABCB1 SNP genotypes. However, homozygous 3435TT subjects showed higher dapagliflozin PK parameters than CT and CC subjects. In subjects with the 3435TT and those with 3435CC and 3435CT genotypes, mean Cmax, AUCinf, and AUC0-1 values of dapagliflozin were 223.06 ng/mL and 194.81 ng /mL (p = 0.2767), 673.58 ng*h/mL and 573.96 ng*h/mL (p = 0.0492), and 128.53 ng*h/mL and 104.61 ng*h/mL (p = 0.2678), respectively.In summary, dapagliflozin and sitagliptin PK parameters were not significantly different between individuals with C1236T and C2677T/A ABCB1 genetic polymorphisms. Dapagliflozin exhibited higher systemic exposure in 3435TT subjects than in CC/CT subjects.

16.
Article in English | WPRIM | ID: wpr-915201

ABSTRACT

Purpose@#This study aimed to identify ICU nurses‘experiences with patient care after death. @*Methods@#The data were collected through two focus group interviews with eight nurses who had experienced the death of patients in the ICU. Giorgi’s method of descriptive phenomenology was used to interpret the data. @*Results@#Five constituents and 14 subconstituents were extracted from the 68 units of meaning. The five constituents were as follows: respect the body as a person, consideration and support for the family, dichotomy between personal courtesy and performing tasks, overcoming the patient’s death and growing, and care after death: a unique role left to the nurse. @*Conclusion@#These findings illuminate the meaning of care after death as a continuation of person-centered care and can be used as primary data for the development of organizational, educational, and emotional support for nurses to accomplish their roles in the ICU.

17.
Article in English | WPRIM | ID: wpr-891839

ABSTRACT

Objectives@#This study aimed to confirm the correlation between BMI and the prevalence of periodontal disease in adults, using data from the National Health and Nutrition Survey. @*Methods@#The data included general characteristics and oral examination results of individuals surveyed in the 7th National Health and Nutrition Survey (2016-2018). Among the variables examined, age, gender, education, income, obesity, hypertension, diabetes, high cholesterol, smoking/drinking, oral examination, and brushing habits were considered as the general characteristics of the study participants. Individuals with more than 4 mm depth of the periodontal pocket were defined as having periodontal disease. BMI was classified into underweight (BMI<18.5 kg/m2 ) and normal (18.5 kg/m2

18.
Article in English | WPRIM | ID: wpr-891841

ABSTRACT

Objectives@#This study aimed to show a correlation between periodontal disease and hypertension. @*Methods@#This study analyzed data of 6794 adults over 19 years based on results from the Korea National Health and Nutrition Examination Survey for the period 2016-2018. Complex sample analysis and propensity score matching analysis methods were conducted to determine whether a correlation between periodontal disease and hypertension existed. @*Results@#Results of the complex sample logistic regression analysis were: OR=1.4 (95% CI:1.23-1.58). However, the result of the conditional logistic regression analysis after propensity score matching yielded no correlation between periodontitis and hypertension (OR=1.03 (95% CI:0.92-1.16)). @*Conclusions@#It is difficult to conclude that a significant correlation exists between hypertension and periodontal disease, and further studies need to be performed to assess a significant correlation.

19.
Article in English | WPRIM | ID: wpr-893746

ABSTRACT

Background@#Attenuated Salmonella strain can be used as a vector to transport immunogens to the host antigen-binding sites. @*Objectives@#The study aimed to determine the protective efficacy of attenuated Salmonellastrain expressing highly conserved Brucella immunogens in goats. @*Methods@#Goats were vaccinated with Salmonella vector expressing individually lipoprotein outer-membrane protein 19 (Omp19), Brucella lumazine synthase (BLS), proline racemase subunit A (PrpA), Cu/Zn superoxide dismutase (SOD) at 5 × 10 9 CFU/mL and challenge of all groups was done at 6 weeks after vaccination. @*Results@#Among these vaccines inoculated at 5 × 10 9 CFU/mL in 1 mL, Omp19 or SOD showed significantly higher serum immunoglobulin G titers at (2, 4, and 6) weeks post-vaccination, compared to the vector control. Interferon-γ production in response to individual antigens was significantly higher in SOD, Omp19, PrpA, and BLS individual groups, compared to that in the vector control (all p < 0.05). Brucella colonization rate at 8 weeks post-challenge showed that most vaccine-treated groups exhibited significantly increased protection by demonstrating reduced numbers of Brucella in tissues collected from vaccinated groups. Realtime polymerase chain reaction revealed that Brucella antigen expression levels were reduced in the spleen, kidney, and parotid lymph node of vaccinated goats, compared to the nonvaccinated goats. Besides, treatment with vaccine expressing individual antigens ameliorated brucellosis-related histopathological lesions. @*Conclusions@#These results delineated that BLS, Omp19, PrpA, and SOD proteins achieved a definite level of protection, indicating that Salmonella Typhimurium successfully delivered Brucella antigens, and that individual vaccines could differentially elicit an antigen-specific immune response.

20.
Article in English | WPRIM | ID: wpr-902877

ABSTRACT

RESULTS@#The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. @*CONCLUSIONS@#ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.

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