Importin-β and the small guanosine triphosphatase Ran mediate chromosome loading of the human chromokinesin Kid

Nucleocytoplasmic transport factors mediate various cellular processes, including nuclear transport, spindle assembly, and nuclear envelope/pore formation. In this paper, we identify the chromokinesin human kinesin-like DNA binding protein (hKid) as an import cargo of the importin-α/β transport pathway and determine its nuclear localization signals (NLSs). Upon the loss of its functional NLSs, hKid exhibited reduced interactions with the mitotic chromosomes of living cells. In digitonin-permeabilized mitotic cells, hKid was bound only to the spindle and not to the chromosomes themselves. Surprisingly, hKid bound to importin-α/β was efficiently targeted to mitotic chromosomes. The addition of Ran–guanosine diphosphate and an energy source, which generates Ran–guanosine triphosphate (GTP) locally at mitotic chromosomes, enhanced the importin-β–mediated chromosome loading of hKid. Our results indicate that the association of importin-β and -α with hKid triggers the initial targeting of hKid to mitotic chromosomes and that local Ran-GTP–mediated cargo release promotes the accumulation of hKid on chromosomes. Thus, this study demonstrates a novel nucleocytoplasmic transport factor–mediated mechanism for targeting proteins to mitotic chromosomes

Successful Resection of Solitary Abdominal Wall Metastasis of Sarcomatous Intrahepatic Cholangiocarcinoma

Sarcomatous intrahepatic cholangiocarcinoma (ICC) is a rare histological variant of ICC that is composed of both adenocarcinoma (ICC component) and sarcomatous components. Surgery is believed to be the primary treatment, and some reports describe primary resection. However, due to the aggressive malignancy of sarcomatous ICC, there is no report regarding resection of a metastatic lesion. In this report, we present the case of a 75-year-old woman admitted to our hospital with the chief complaint of weight loss. Various imaging techniques demonstrated a single mass in the liver and cecum. A cecal gastrointestinal stromal tumor accompanied by liver metastasis was suspected, and ileocecal resection was performed for diagnostic purposes. However, the tumor was present in the abdominal wall rather than in the cecum. The tumor was resected and diagnosed as undifferentiated sarcoma. We suspected the liver tumor was a series of lesions, so we performed hepatectomy. As the tumor was composed of both adenocarcinoma and sarcomatous components, it was diagnosed as sarcomatous ICC. The histological findings of the abdominal wall tumor were similar to those of sarcomatous ICC, so we diagnosed the abdominal wall tumor as a solitary metastasis of sarcomatous ICC. In this case, solitary metastasis was observed, and we were able to resect both the primary and metastatic lesions. This case illustrates that when solitary metastasis can be seen in sarcomatous ICC, radical resection is possible

A novel biomarker TERTmRNA is applicable for early detection of hepatoma

<p>Abstract</p> <p>Backgrounds</p> <p>We previously reported a highly sensitive method for serum human telomerase reverse transcriptase (hTERT) mRNA for hepatocellular carcinoma (HCC). α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are good markers for HCC. In this study, we verified the significance of hTERTmRNA in a large scale multi-centered trial, collating quantified values with clinical course.</p> <p>Methods</p> <p>In 638 subjects including 303 patients with HCC, 89 with chronic hepatitis (CH), 45 with liver cirrhosis (LC) and 201 healthy individuals, we quantified serum hTERTmRNA using the real-time RT-PCR. We examined its sensitivity and specificity in HCC diagnosis, clinical significance, ROC curve analysis in comparison with other tumor markers, and its correlations with the clinical parameters using Pearson relative test and multivariate analyses. Furthermore, we performed a prospective and comparative study to observe the change of biomarkers, including hTERTmRNA in HCC patients receiving anti-cancer therapies.</p> <p>Results</p> <p>hTERTmRNA was demonstrated to be independently correlated with clinical parameters; tumor size and tumor differentiation (P < 0.001, each). The sensitivity/specificity of hTERTmRNA in HCC diagnosis showed 90.2%/85.4% for hTERT. hTERTmRNA proved to be superior to AFP, AFP-L3, and DCP in the diagnosis and underwent an indisputable change in response to therapy. The detection rate of small HCC by hTERTmRNA was superior to the other markers.</p> <p>Conclusions</p> <p>hTERTmRNA is superior to conventional tumor markers in the diagnosis and recurrence of HCC at an early stage.</p

Coping Mechanisms: Exploring Strategies Utilized by Japanese Healthcare Workers to Reduce Stress and Improve Mental Health during the COVID-19 Pandemic

The COVID-19 pandemic is a major problem affecting the mental health of millions of people, including healthcare workers. In this study, we analyzed risk factors and coping mechanisms that could reduce the risk of poor mental health among healthcare workers during the COVID-19 pandemic in Japan. A cross-sectional survey was conducted for 7 days from 30 April 2020 using a web-based questionnaire. The survey assessed various outcome measures, including the General Health Questionnaire-12 (GHQ-12), health status, satisfaction with daily life activities, work, leisure, and new activities, and anxiety over COVID-19. Data from 661 participants were analyzed, and 440 participants (66.6%) showed poor mental health (GHQ-12 &ge; 4). Also, our result showed that female gender, lower levels of communication with friends, and high anxiety were associated with poorer mental health. In contrast, good health status, high work satisfaction, and high satisfaction from new activities were associated with buffering mental health problem. Most participants chose an escape-avoidance coping strategy, and participants with worse mental health were more likely to adopt seeking social support as a coping strategy. These results may support healthcare workers to cope with mental health problems associated with the COVID-19 pandemic

Effects of Lifestyle Changes on the Mental Health of Healthcare Workers with Different Sense of Coherence Levels in the Era of COVID-19 Pandemic

Sense of coherence (SOC) is a psychological factor that contributes to mental health maintenance under stressful environment. Likewise, level of SOC might affect mental health among healthcare workers during the COVID-19 pandemic differently. In this study, we investigated the relationships between lifestyle changes and mental health (General Health Questionnaire-12: GHQ-12) among different level of SOC (weak, moderate, or strong by SOC-13). The data of 898 healthcare workers from cross-sectional survey dataset were extracted and analyzed. As results, based on GHQ-12 score, 86.1% of 244 participants with weak SOC, 60.1% of 606 participants with moderate SOC, and 31.3% of 48 participants with strong SOC had poor mental health. Both SOC levels and lifestyle changes (except alcohol consumption) had significant main effects on the GHQ-12 score. Analysis on the association between lifestyle changes and mental health status stratified by SOC level reveled that among participants with weak SOC, those who increased their leisure and activity time had reduced odds of poor mental health than those who made no changes (OR: 0.08, CI: 0.01 to 0.64). Healthcare workers with weak SOC were at risk of poor mental health during the COVID-19 pandemic, and lifestyle changes may improve their mental health