Foods contributing to nutrients intake and assessment of nutritional status in pre-dialysis patients: a cross-sectional study.

BACKGROUND: For chronic kidney disease (CKD) patients, management of nutritional status is critical for delaying progression to end-stage renal disease. The purpose of this study is to provide the basis for personalized nutritional intervention in pre-dialysis patients by comparing the foods contributing to nutrients intake, nutritional status and potential dietary inflammation of CKD patients according to the diabetes mellitus (DM) comorbidity and CKD stage. METHODS: Two hundred fifty-six outpatients referred to the Department of Nephrology at SNUH from Feb 2016 to Jan 2017 were included. Subjects on dialysis and those who had undergone kidney transplantation were excluded. Bioelectrical impedance analysis (BIA), subjective global assessment (SGA), dietary intake, and biochemical parameters were collected. Subjects were classified into 4 groups according to DM comorbidity (DM or Non-DM) and CKD stage (Early or Late) by kidney function. Two-way analysis of variance and multinomial logistic regression analysis were performed for statistical analysis. RESULTS: Total number of malnourished patients was 31 (12.1%), and all of them were moderately malnourished according to SGA. The body mass index (BMI) of the DM-CKD group was significantly higher than the Non-DM-CKD group. The contribution of whole grains and legumes to protein intake in the DM-CKD group was greater than that in the Non-DM-CKD group. The DM- Early-CKD group consumed more whole grains and legumes compared with the Non-DM-Early-CKD group. The subjects in the lowest tertile for protein intake had lower phase angle, SGA score and serum albumin levels than those in the highest tertile. The potential for diet-induced inflammation did not differ among the groups. CONCLUSIONS: Significant differences in intakes of whole grains and legumes between CKD patients with or without DM were observed. Since contribution of whole grains and legumes to phosphorus and potassium intake were significant, advice regarding whole grains and legumes may be needed in DM-CKD patients if phosphorus and potassium intake levels should be controlled. The nutritional status determined by BIA, SGA and serum albumin was found to be different depending on the protein intake. Understanding the characteristics of food sources can provide a basis for individualized nutritional intervention for CKD patients depending on the presence of diabetes.

Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives as a novel selective inhibitor scaffold of JNK3.

3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives were designed and synthesised as selective inhibitors of JNK3, a target for the treatment of neurodegenerative diseases. Following previous studies, we have designed JNK3 inhibitors to reduce the molecular weight and successfully identified a lead compound that exhibits equipotent activity towards JNK3. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases. Among the derivatives, the IC50 value of 8a, (R)-2-(1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-5-(3,4-dichlorophenyl)-1H-pyrazol-3-yl)acetonitrile exhibited 227 nM, showing the highest inhibitory activity against JNK3.

Discovery of 5-methyl-N-(2-arylquinazolin-7-yl)isoxazole-4-carboxamide analogues as highly selective FLT3 inhibitors.

A series of 4-arylamido 5-methylisoxazole derivatives with quinazoline core was designed and synthesised based on conformational rigidification of a previous type II FMS inhibitor. Most of quinazoline analogues displayed activity against FLT3 and FLT3-ITD. Compound 7d, 5-methyl-N-(2-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl)quinazolin-7-yl)isoxazole-4-carboxamide, exhibited the most potent inhibitory activity against FLT3 (IC50= 106 nM) with excellent selectivity profiles over 36 other protein kinases including cKit and FMS kinase. Compound 7d was also active in FLT-ITD, with an IC50 value of 301 nM, and other FLT3 mutants showing potential as an AML therapeutics.

Dietary Assessment of Korean Non-dialysis Chronic Kidney Disease Patients with or without Diabetes.

BACKGROUND: Dietary intervention at the early stage of chronic kidney disease (CKD) is important for preventing progression to the end-stage renal disease (ESRD). However, few studies have investigated dietary intake of CKD patients in non-dialysis stage. Therefore, we investigated the dietary intake of Korean non-dialysis CKD patients and aimed to establish baseline data for the development of dietary education and intervention strategies for CKD patients. METHODS: Three hundred fifty CKD patients who visited Seoul National University Hospital outpatient clinic from February 2016 to January 2017 were recruited for this cross-sectional study. Subjects on dialysis and those who had undergone kidney transplantation were excluded. Dietary intake, demographic information, and biochemical characteristics of 256 subjects who completed three-day dietary records were analyzed. Subjects were divided into four groups based on diabetes mellitus (DM) (DM-CKD and Non-DM-CKD groups) and kidney function (Early-CKD and Late-CKD groups). RESULTS: Total energy intake was lower in the Late-CKD group compared with the Early-CKD group. In men, carbohydrate intake was higher and protein and fat intakes tended to be lower in the Late-CKD group compared with the Early-CKD group. In women, carbohydrate intake tended to be lower in the DM-CKD group than the Non-DM-CKD group. Protein intake tended to be higher in the DM-CKD groups. Phosphorus and sodium intakes were higher in the DM-CKD groups compared with the Non-DM-CKD groups in women, and tended to be higher in the DM-CKD groups in men. CONCLUSION: DM and kidney function affected energy and nutrient intakes. Subjects in the Late-CKD group consumed less energy than those in the Early-CKD group. Non-DM subjects seemed to restrict protein intake starting from the Early-CKD stage than subjects with DM. Subjects in this study had low energy and high sodium intakes compared with recommended levels. Protein intake was lower in advanced CKD patients, but their intake level was still higher than the recommendation. Dietary intervention strategies for non-dialysis CKD patients need to be customized depending on the presence of DM and kidney function.

Discovery of 1-Pyrimidinyl-2-Aryl-4,6-Dihydropyrrolo [3,4-d]Imidazole-5(1H)-Carboxamide as a Novel JNK Inhibitor.

We designed and synthesized 1-pyrimidinyl-2-aryl-4, 6-dihydropyrrolo [3,4-d] imidazole-5(1H)-carboxamide derivatives as selective inhibitors of c-Jun-N-terminal Kinase 3 (JNK3), a target for the treatment of neurodegenerative diseases. Based on the compounds found in previous studies, a novel scaffold was designed to improve pharmacokinetic characters and activity, and compound 18a, (R)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-2-(3,4-dichlorophenyl)-4,6-dihydro pyrrolo [3,4-d]imidazole-5(1H)-carboxamide, showed the highest IC50 value of 2.69 nM. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases, having mild activity against JNK2, RIPK3, and GSK3ß, which also known to involve in neuronal apoptosis.

Conformational restriction of a type II FMS inhibitor leading to discovery of 5-methyl-N-(2-aryl-1H-benzo[d]imidazo-5-yl)isoxazole-4-carboxamide analogues as selective FLT3 inhibitors.

A series of 4-arylamido 5-methylisoxazole derivatives incorporating benzimidazole was designed and synthesised by conformational restriction of an in-house type II FMS inhibitor. Kinase profiling of one compound revealed interesting features, with increased inhibitory potency towards FLT3 and concomitant loss of potency towards FMS. Several benzimidazole derivatives 5a-5g and 6a-6c containing various hydrophobic moieties were synthesised, and their inhibitory activity against FLT3 was evaluated. Specifically, 5a, 5-methyl-N-(2-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-5-yl) isoxazole-4-carboxamide, exhibited the most potent inhibitory activity against FLT3 (IC50 = 495 nM), with excellent selectivity profiles.

Discovery of novel imidazole chemotypes as isoform-selective JNK3 inhibitors for the treatment of Alzheimer's disease.

Despite innumerable efforts to develop effective therapeutics, it is difficult to achieve breakthrough treatments for Alzheimer's disease (AD), and the main reason is probably the absence of a clear target. Here, we reveal c-Jun N-terminal kinase 3 (JNK3), a protein kinase explicitly expressed in the brain and involved in neuronal apoptosis, with a view toward providing effective treatment for AD. For many years, we have worked on JNK3 inhibitors and have discovered 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile-based JNK3 inhibitors with superb potency (IC50 < 1.0 nM) and excellent selectivity over other protein kinases including isoforms JNK1 (>300 fold) and JNK2 (∼10 fold). Based on in vitro biological activity and DMPK properties, the lead compounds were selected for further in vivo studies. We confirmed that repeat administration of JNK3 inhibitors improved cognitive memory in APP/PS1 and the 3xTg mouse model. Overall, our results show that JNK3 could be a potential target protein for AD.

Distal appendiceal dilatation in equivocal appendicitis may be a useful sign for prediction of normal appendix.

Despite many efforts to reduce unnecessary appendectomy for appendicitis, the negative appendectomy rate remains relatively high. Here, we investigated predisposing factors for normal appendix by analyzing the surgical outcomes for patients with equivocal appendicitis. Over a 3-year period, 1516 patients underwent treatment for appendicitis and 148 (10%) were prospectively diagnosed with equivocal appendicitis. We defined equivocal appendicitis as a right lower quadrant pain with tenderness and an apppendiceal diameter of 6 to 9 mm without appendicolith or severe adjacent inflammation as radiological findings. We investigated normal appendix rates in relation to clinical and radiological features. Of the 148 patients, 48 (32%) had a normal appendix and 100 had appendicitis. A higher normal appendix rate was found for low white blood cell count than for leukocytosis (41% vs 23%, odds ratio (OR) = 2.48), and laparoscopic treatment was then open (42% vs 21%, OR = 2.58). Distal appendiceal dilatation, as determined by radiological imaging, was associated with a higher normal appendix rate than whole dilatation (60% vs 27%, OR = 3.96). Low white blood cell count, laparoscopic treatment, and distal appendiceal dilatation were significant predisposing factors for normal appendix after surgery. Radiologically determined distal dilatation of the appendix may be a useful sign for predicting normal appendix.

Stress, Social Support, and Sexual Adjustment in Married Female Patients with Breast Cancer in Korea.

OBJECTIVE: This study identified the level of stress, social support, and sexual adjustment in married women with breast cancer in Korea. METHODS: This study used a subgroup analysis, prospective, cross-sectional, and descriptive correlation design. Data were obtained using the perceived stress scale, multidimensional scale of perceived social support, and sexual adjustment subscale of the Korean version of the psychosocial adjustment to illness scale. From May 2015 to April 2016, 272 married female patients who had been diagnosed with breast cancer were recruited at a university hospital in Korea. Data were analyzed using SPSS Win 21.0. RESULTS: The mean score of stress level was 17.53 ± 4.13, social support was 5.37 ± 1.07, and sexual adjustment was 6.36 ± 3.29. A significant positive correlation emerged between sexual adjustment and stress (r = 0.161, P = 0.008). Significant negative correlations were observed among sexual adjustment and family support (r = -0.177, P = 0.003) and friends' support (r = -0.205, P = 0.001). CONCLUSIONS: The assessment of stress level and social support may be used in planning sexual-adjustment interventions appropriate for married female breast cancer patients in Korea.

A structural model for stress, coping, and psychosocial adjustment: A multi-group analysis by stages of survivorship in Korean women with breast cancer.

PURPOSE: Prospective studies have examined factors directly affecting psychosocial adjustment during breast cancer treatment. Survivorship stage may moderate a direct effect of stress on psychosocial adjustment. This study aimed to examine relationships between stress, social support, self-efficacy, coping, and psychosocial adjustment to construct a model of the effect pathways between those factors, and determine if survivorship stage moderates those effects. METHODS: Six hundred people with breast cancer completed questionnaires. Examined stages of survivorship after treatment were as follows: acute (i.e., <2 years), extended (2-5 years), and lasting (>5 years). Stress (Perceived Stress Scale), social support (Multidimensional Scale of Perceived Social Support), self-efficacy (New General Self Efficacy Scale), coping (Ways of Coping Checklist), and psychosocial adjustment (Psychosocial Adjustment to Illness Scale-Self-Report-Korean Version) were measured. RESULTS: Self-efficacy significantly correlated with psychosocial adjustment in the acute survival stage (γ = -0.37, P < .001). Stress inversely correlated with coping only in the extended survival stage (γ = -0.56, P < .001). Social support's benefit to psychosocial adjustment was greater in the acute (γ = -0.42, P < .001) and extended survival stages (γ = -0.56, P < .001) than in the lasting survival stage. Stress's negative correlation with psychosocial adjustment was stronger in the lasting survival stage (ß = 0.42, P < .001) than in the acute survival stage. CONCLUSIONS: Based on these results, it is necessary to improve self-efficacy, social support, and manage stress according to survival stage for psychosocial adjustment of female breast cancer patients.

In-depth Medical Nutrition Therapy for a Woman with Diabetes: From Pregnancy to Delivery.

Diabetes in pregnancy is associated with higher rates of miscarriage, pre-eclampsia, preterm labor, and fetal malformation. To prevent these obstetric and perinatal complications, women with diabetes have to control levels of blood sugar, both prior to and during pregnancy. Thus, individualized medical nutrition therapy for each stage of pregnancy is essential. We provided in-depth medical nutrition therapy to a 38-year-old pregnant woman with diabetes at all stages of pregnancy up to delivery. She underwent radiation therapy after surgery for breast cancer and was diagnosed with diabetes. At the time of diagnosis, her glycated hemoglobin level was 8.3% and she was planning her pregnancy. She started taking an oral hypoglycemic agent and received education regarding the management of diabetes and preconception care. She became pregnant while maintaining a glycated hemoglobin level of less than 6%. We provided education program for diabetes management during the pregnancy, together with insulin therapy. She experienced weight loss and ketones were detected; furthermore, she was taking in less than the recommended amount of foods for the regulation of blood sugar levels. By giving emotional support, we continued the counseling and achieved not only glycemic control but also instilled an appreciation of the importance of appropriate weight gain and coping with difficulties. Through careful diabetes management, the woman had a successful outcome for her pregnancy, other than entering preterm labor at 34 weeks. This study implicated that the important things in medical nutrition therapy for pregnant women with diabetes are frequent follow-up care and emotional approach through the pregnancy process.

Personal digital assistants: Essential tools for preparing dietetics professionals to use new generation information technology.

Rapid integration of information technology into health care systems has included the use of highly portable systems-in particular, personal digital assistants (PDAs). With their large built-in memories, fast processors, wireless connectivity, multimedia capacity, and large library of applications, PDAs have been widely adopted by physicians and nurses for patient tracking, disease management, medical references and drug information, enhancing a quality of health care. Many health-related PDA applications are available to both dietetics professionals and clients. Dietetics professionals can effectively use PDAs for client tracking and support, accessing to hospital database or information, and providing better self-monitoring tools to clients. Internship programs for dietetics professionals should include training in the use of PDAs and their dietetics applications, so that new practitioners can stay abreast of this rapidly evolving technology. Several considerations to keep in mind in selecting a PDA and its applications are discussed.