Prevalence and risk factors for onychomycosis in acute care dermatology wards.

We conducted a cross-sectional study on the clinical and mycological features of onychomycosis in patients in the dermatology ward of Iwate Medical University Hospital, an acute care hospital. Of the 226 hospitalized patients, 73 (32.3%) had onychomycosis and 61 (26.9%) were diagnosed after admission. The toenail was the most common site of onychomycosis (94.5%), while toenail plus fingernail and fingernail only sites were 4.1% and 1.4%, respectively. The most common clinical form of onychomycosis was distal and lateral subungual onychomycosis (79%) with Trichophyton rubrum (66.7%) and T. interdigitale (27.8%) as the main causative species. Patients who were older, or had neurological diseases, or needed stretcher transfer had onychomycosis significantly more frequently than those who were obese, had diabetes, cancer, needed an escort for moving, or could move independently. Our study suggests that there is likely to be a significant number of untreated and undiagnosed patients with onychomycosis in acute care hospitals. Therefore, it is necessary to increase awareness of onychomycosis in hospitals.

DUSP4 Inactivation Leads to Reduced Extracellular Signal‒Regulated Kinase Activity through Upregulation of DUSP6 in Melanoma Cells.

A subset of dual-specificity phosphatases is a major negative regulator of MAPKs, and their involvement in tumorigenesis remains controversial. Among them, DUSP4 is reported to preferentially dephosphorylate extracellular signal‒regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase over p38. In this study, we aimed to identify a possible role of DUSP4 in melanoma genesis. An examination of large-scale public data on gene expression and dependency revealed a considerably high DUSP4 expression and dependency of the melanoma cell lines compared with those of other tumor cell lines, which was not apparent for the other 24 dual-specificity phosphatases genes encoded in the human genome. Using two melanoma lines, we confirmed that DUSP4 depletion impaired cell growth without notably inducing apoptosis. Interestingly, immunoblotting and kinase translocation reporter data revealed that DUSP4 depletion induces a decrease in ERK1/2 phosphorylation but barely affects c-Jun N-terminal kinase phosphorylation, suggesting that neither ERK nor c-Jun N-terminal kinase is a direct target of DUSP4 in our experimental setting. Notably, DUSP4 depletion led to an increase in DUSP6 level, possibly through a post-transcriptional process, and DUSP6 knockout almost eliminated the DUSP4-depletion effect on cell growth and ERK activity. Our findings suggest that DUSP4 plays a role in maintaining a high ERK1/2 activity by negatively regulating DUSP6 and thus contributes to the survival and growth of melanoma cells.

Highly enantioselective synthesis of γ-, δ-, and ε-chiral 1-alkanols via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA)-Cu- or Pd-catalyzed cross-coupling.

Despite recent advances of asymmetric synthesis, the preparation of enantiomerically pure (≥99% ee) compounds remains a challenge in modern organic chemistry. We report here a strategy for a highly enantioselective (≥99% ee) and catalytic synthesis of various γ- and more-remotely chiral alcohols from terminal alkenes via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction)-Cu- or Pd-catalyzed cross-coupling. ZACA-in situ oxidation of tert-butyldimethylsilyl (TBS)-protected ω-alkene-1-ols produced both (R)- and (S)-α,ω-dioxyfunctional intermediates (3) in 80-88% ee, which were readily purified to the ≥99% ee level by lipase-catalyzed acetylation through exploitation of their high selectivity factors. These α,ω-dioxyfunctional intermediates serve as versatile synthons for the construction of various chiral compounds. Their subsequent Cu-catalyzed cross-coupling with various alkyl (primary, secondary, tertiary, cyclic) Grignard reagents and Pd-catalyzed cross-coupling with aryl and alkenyl halides proceeded smoothly with essentially complete retention of stereochemical configuration to produce a wide variety of γ-, δ-, and ε-chiral 1-alkanols of ≥99% ee. The MαNP ester analysis has been applied to the determination of the enantiomeric purities of δ- and ε-chiral primary alkanols, which sheds light on the relatively undeveloped area of determination of enantiomeric purity and/or absolute configuration of remotely chiral primary alcohols.