A concise synthesis of tubuphenylalanine and epi-tubuphenylalanine via a diastereoselective Mukaiyama aldol reaction of silyl ketene acetal.

We have developed a straightforward and auxiliary-free synthetic route towards tBu-tubuphenylalanine (tBu-Tup) and tBu-epi-tubuphenylalanine (tBu-epi-Tup), which are the key components of tubulysins and their analogs. A Lewis acid-mediated diastereoselective Mukaiyama aldol reaction using silyl ketene acetal and N-Boc-L-phenylalaninal provided γ-amino-ß-hydroxyl-α-methyl esters, which were deoxygenated to γ-amino-α-methyl esters under Barton-McCombie deoxygenation conditions. Notably, the desired tBu-Tup and tBu-epi-Tup were obtained in good overall yields in four steps.

Sample Size Requirements for Simple and Complex Mediation Models.

Mediation models have been widely used in many disciplines to better understand the underlying processes between independent and dependent variables. Despite their popularity and importance, the appropriate sample sizes for estimating those models are not well known. Although several approaches (such as Monte Carlo methods) exist, applied researchers tend to use insufficient sample sizes to estimate their models of interest, which might result in unstable and inaccurate estimation of the model parameters including mediation effects. In the present study, sample size requirements were investigated for four frequently used mediation models: one simple mediation model and three complex mediation models. For each model, path and structural equation modeling approaches were examined, and partial and complete mediation conditions were considered. Both the percentile bootstrap method and the multivariate delta method were compared for testing mediation effects. A series of Monte Carlo simulations was conducted under various simulation conditions, including those concerning the level of effect sizes, the number of indicators, the magnitude of factor loadings, and the proportion of missing data. The results not only present practical and general guidelines for substantive researchers to determine minimum required sample sizes but also improve understanding of which factors are related to sample size requirements in mediation models.

The Association Between Alcohol Use and Suicidal Ideation Among Employees.

OBJECTIVE: The risk of suicide is assessed by identifying the relationship between alcohol-use patterns and suicidal ideation in Korean employees. METHODS: The study involved 13,858 employees who underwent workplace mental health screening at the Workplace Mental Health Institute of Kangbuk Samsung Hospital over a 6-year period between 2014 and 2019. Analysis was performed separately for Alcohol Use Disorders Identification Test-Korea (AUDIT-K) items related to the frequency/volume of alcohol consumption (items 1 to 3, AUDIT-C) and those regarding alcohol dependence/related problems (items 4 to 10, AUDIT-D/P). Subjects were then classified into three groups on the basis of the presence or absence of clinical depression and suicidal ideation. The groups' sociodemographic factors and clinical features of depression, anxiety, and alcohol-use patterns were analyzed with a chi-square test as well as one-way analysis of variance, followed by a post hoc test using the Bonferroni correction. RESULTS: AUDIT-K and AUDIT-D/P scores were significantly associated with the presence or absence of clinical depression as well as the presence or absence of suicidal ideation (p<0.05). However, no significant differences were found among the three groups with regard to the AUDIT-C score (p=0.054). CONCLUSION: Identifying or treating alcohol dependence/related problems can help lower the occurrence of mental health problems, and suicidal ideation in particular, in employees and reduce social costs.

Asymmetric C-H functionalization of cyclopropanes using an isoleucine-NH2 bidentate directing group.

The systematic investigation of substrate-bound α-amino acid auxiliaries has resulted in catalytic asymmetric C-H functionalization of cyclopropanes enabled by amino acid amides as chiral bidentate directing groups. The use of an Ile-NH2 auxiliary embedded in the substrate provided excellent levels of asymmetric induction (diastereomeric ratio of up to 72 : 1) in the Pd(ii)-catalyzed ß-methylene C(sp3)-H bond activation of cyclopropanes and cross-coupling with aryl iodides.

[Health problems and psychosocial adaptation of children with cancer].

PURPOSE: The purpose of this study was to describe health problems and psychosocial adaptation in children with cancer and to determine the relationship between these two variables. METHOD: The data were collected from parents of 61 children with cancer, aged 4-11 years at one university hospital in Seoul. The instruments for this study were the Korea Child Behavior Check List (KCBCL) and a physical symptom checklist developed by the researchers. RESULT: The major health problems were coughing, sleeping disturbances, fatigue and weakness. The total behavior problem score for children in the cancer group was higher than the score for those in the norm group. The scores on the scales for withdrawal, somatic complaints, social immaturity, and internalizing problems were higher in the children with cancer compared to normative findings. Scores on social and school competence in the cancer group were lower than the norms for healthy children. The relationship between health problems and psychosocial adaptation was significant in the subscales of withdrawal, anxiety/depression, internalizing problems and social involvement in the off therapy group. CONCLUSIONS: This study shows the various areas that need further study in caring for children with cancer.

High frequency of gross deletions in 5' LTR/gag and nef genes in patients infected with CRF02_AG of HIV type 1 who survived for over 20 years: an association with Korean red ginseng.

Abstract We have shown that Korean red ginseng (KRG) intake is associated with gross deletions in the 5' LTR/gag (gDeltaLTR/gag) and nef genes (gDeltanef) of patients infected with subtype B of HIV-1. Here, we investigated these effects in three long-term survivors (LTSs) of subtype CRF02_AG of HIV-1. The three LTSs were diagnosed with HIV in 1987, 1988, and 1989, and have been treated with KRG for 7-15 years. Thirty-two samples of peripheral blood mononuclear cells were obtained from the subjects and used to amplify the 5' LTR/gag and nef genes via nested PCR. We obtained 88 amplicons in 5' LTR/gag and 128 amplicons in nef. The frequency of gDeltaLTR/gag was significantly higher (37.5%) in three LTSs than in control patients (8.6%, p < 0.01). Eight amplicons (9.5%) contained premature stop codon(s) in the gDeltaLTR/gag in three LTSs. Fourteen of the 128 nef amplicons (10.9%) contained the gDeltanef, which was present in only two (7.7%) of the 26 amplicons from control subjects. Interestingly, gDeltanef was detected 7 years after the reinitiation of KRG intake in an LTS and, coincidently, CD4 T cell counts and CD4/CD8 ratios rapidly increased. These data indicate that long-term intake of KRG has the therapeutic potential to induce gross deletions in HIV-1.