TRA-1-60-positive/CD45low cells found in the peripheral blood of prostate cancer patients with metastatic disease – A proof-of-concept study

Purpose Over 90% of all cancer related deaths are due to metastasis. However, current diagnostic tools can\u27t reliably discriminate between invasive and localized cancers. Patients and methods In this proof-of-concept study, we employed the embryonic stem cell marker TRA-1-60 (TRA+) to identify TRA + cells within the blood of prostate cancer patients and searched for TRA + cells in men with metastatic and localized cancers. We isolated whole peripheral blood mononuclear cells from 26 metastatic prostate cancer patients, from 13 patients with localized prostate cancer and from 17 healthy controls. Cells were stained for DAPI, CD45 and TRA + by immunofluorescence and imaged by epi-fluorescence microscopy. Imaged-based software was used both to identify TRA + cells, and to analyze CD45 levels in TRA+ and negative cells. Results We found high numbers of TRA + cells within the blood of metastatic cancer patients, whereas healthy individuals or men with localized prostate cancer showed none or very low numbers of TRA + cells. Further analysis of the CD45 levels of TRA + cells revealed a small population of TRA + cells with almost undetectable CD45 levels that were found frequently in metastatic prostate cancer patients. By excluding CD45 positive cells from the TRA + cell pool, we were able to refine the assay to be highly specific in identifying men with metastatic disease. In fact, the difference of CD45 levels between TRA+ and negative cells was a robust measure to distinguish between men with localized and metastatic prostate cancers in this small patient cohort. Conclusions The data suggest that metastatic prostate cancer patient have significant numbers of TRA+/CD45low cells which might represent a potential tool for diagnostic assessment in the future

Sociocognitive terminology-based principles for translating the classics of traditional Chinese medicine

The classics of Traditional Chinese Medicine (TCM) contain terminology that is challenging to translate from the Ancient Chinese language into modern English and other target languages. In this paper, we introduce the main principles of sociocognitive terminology theory and examine how the application of these principles in TCM translation projects can produce superior results. To begin our study, we evaluate the salient characteristics of important TCM terms from linguistic, cognitive, diachronic, and communicative perspectives. Next, we present a model for realizing the objectives of linguistic economy, systematic relevance, conceptual retrospection, and knowledge dissemination in sociocognitive translation studies. Finally, to illustrate the practicality of this four-dimensional model, we present a case study on sociocognitive translation of the TCM classic 黄帝内经 (Huangdi Neijing or The Inner Canon of Huangdi), which was compiled during the Warring States period (475–221 BCE). In summary, we find that this model effectively addresses the complexities of TCM terminology and provides solutions to problems involving conceptual connotation, symbolic representation, and communicative context. Following this approach, translators will be better able to convey the profoundly humanistic nature of TCM concepts, significantly improve the quality of TCM translations, and promote TCM and Chinese culture internationally

Minor mental disorders in Taiwanese healthcare workers and the associations with psychosocial work conditions

Healthcare workers face multiple psychosocial work hazards intrinsic to their work, including heavy workloads and shift work. However, how contemporary adverse psychosocial work conditions, such as workplace justice and insecurity, may contribute to increased mental health risks has rarely been studied. This study aimed to search for modifiable psychosocial work factors associated with mental health disorders in Taiwanese healthcare workers. Methods: A total of 349 healthcare workers were identified from 19,641 employees who participated in a national survey of Taiwan. Minor mental disorder was assessed using the five-item brief symptom rating scale. We compared psychosocial work characteristics and the prevalence of minor mental disorder in healthcare workers with that in a sociodemographically matched sample, and examined the associations of psychosocial work conditions with mental health status. Results: Healthcare workers were found to have a higher prevalence of minor mental disorder than general workers, and they were more likely to have longer working hours, heavier psychological job demands, higher job control, more workplace violence, and a higher prevalence of shift work. Among healthcare workers, experiences of workplace violence, lower workplace justice, heavier psychological job demands, and job insecurity were associated with a higher risk for minor mental disorder, even after controlling for working hours and shift work. Conclusion: Despite the fact that healthcare workers work longer hours and shift work, there were several modifiable psychosocial work conditions that should be targeted to improve their mental health

Elucidating the Role of Lymphatics in the Pathogenesis of Chronic Inflammatory-Erosive Arthritis

Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Pathology and Laboratory Medicine, 2014.Rheumatoid arthritis (RA) is a chronic inflammatory joint disease in which patients often suffer from arthritic flare. Using longitudinal contrast-enhanced (CE)-MRI to study knee arthritis in tumor necrosis factor-transgenic (TNF-Tg) mice, we observed that the popliteal lymph nodes (PLN) firstly “expand” in size and contrast enhancement, and then suddenly “collapse” during arthritic flare. Since CE-MRI is too costly for phenotyping and longitudinal analyses of PLN, our aim was to develop ultrasound (US) methods that could replace MRI. In our initial study, we demonstrated a significant correlation between PLN volumes determined by US vs. MRI. However, since PLN collapse is more closely associated with lymphatic draining function than volume, we evaluated CE-US methods to distinguish changes in lymphatic transport, which was shown as a biomarker of arthritic flare. Unfortunately, delivery of the contrast agent prior to US significantly impairs lymphatic function, making it unsuitable for phenotyping PLNs. Thus, we went on to develop power Doppler (PD) US methods to phenotype PLN with greater accuracy and cost effectiveness vs. CE-MRI. Another important prior observation we made is that arthritic flare is associated with the loss of lymphatic pulse. From other models of inflammation, lymphatic pulse is known to be controlled by endothelial nitric oxide synthase (eNOS), and inhibited by inducible NOS (iNOS) expressed in Gr-1+ cells. To test the hypothesis that eNOS/iNOS dysregulation is responsible for the loss of lymphatic pulse during arthritic flare in TNF-Tg mice, we performed IHC and in vivo pharmacological intervention studies with selective and non-selective iNOS inhibitors. The IHC results demonstrated that large numbers of iNOS expressing Gr-1+ cells exist in collapsed PLN. By evaluating the lymphatics with NIR-ICG imaging, we observed that the specific iNOS inhibitor L-NIL increased lymphatic pulse and afferent lymphatic drainage in TNF-Tg mice. Additionally, the micro-CT results showed that bone erosions were ameliorated in L-NIL treated TNF-Tg mice compared with placebo. Collectively, these results suggest a model that the accumulation of iNOS-expressing Gr-1+ cells accelerates the onset of flare in the setting of inflammatory arthritis via inhibition of lymphatic drainage, and identifies this pathway as a potential target for RA therapy

Trends in Work Conditions and Associations with Workers’ Health in Recent 15 Years: The Role of Job Automation Probability

Job automation and associated psychosocial hazards are emerging workplace challenges. This study examined the trends in work conditions and associations with workers’ health over time in jobs with different automation probabilities. We utilized data from six waves of national questionnaire surveys of randomly selected 95,762 employees between 2001 and 2016. The Job Content Questionnaire, the Copenhagen Burnout Inventory, and the Self-Rated Health Scale were applied, and working time was self-reported. Automation probability was derived for 38 occupations and then categorized into three groups. Trends in work conditions and the associations between automation probability, work conditions and health were examined. We observed a 7% decrease in high automation probability jobs, an overall increase in job demands for and prevalence of shift work, and a decrease in job control. Workers with high automation probability jobs had low job demands, low job control and high job insecurity. Low automation probability was associated with burnout in logistic regression models. The odds ratio of job insecurity, long working hours, and shift work relating to health was higher in the later years of the surveys. In conclusion, there has been a decrease in high automation probability jobs. Workers employed in jobs with different levels of automation probability encountered different work condition challenges

Cuticular Wax Modification by <i>Epichloë</i> Endophyte in <i>Achnatherum inebrians</i> under Different Soil Moisture Availability

The cuticular wax serves as the outermost hydrophobic barrier of plants against nonstomatal water loss and various environmental stresses. An objective of this study was to investigate the contribution of the mutualistic fungal endophyte Epichloë gansuensis to leaf cuticular wax of Achnatherum inebrians under different soil moisture availability. Through a pot experiment and gas chromatography−mass spectrometry (GC−MS) analysis, our results indicated that the hydrocarbons were the dominant components of leaf cuticular wax, and the proportion of alcohols, aldehydes, amines, and ethers varied with the presence or absence of E. gansuensis and different soil moisture availability. Amines and ethers are unique in endophyte-free (EF) A. inebrians plants and endophyte-infected (EI) A. inebrians plants, respectively. By transcriptome analysis, we found a total of 13 differentially expressed genes (DEGs) related to cuticular biosynthesis, including FabG, desB, SSI2, fadD, BiP, KCS, KAR, FAR, and ABCB1. A model is proposed which provides insights for understanding cuticular wax biosynthesis in the association of A. inebrians plants with E. gansuensis. These results may help guide the functional analyses of candidate genes important for improving the protective layer of cuticular wax of endophyte-symbiotic plants

Power Doppler ultrasound phenotyping of expanding versus collapsed popliteal lymph nodes in murine inflammatory arthritis.

Rheumatoid arthritis is a chronic inflammatory disease manifested by episodic flares in affected joints that are challenging to predict and treat. Longitudinal contrast enhanced-MRI (CE-MRI) of inflammatory arthritis in tumor necrosis factor-transgenic (TNF-Tg) mice has demonstrated that popliteal lymph nodes (PLN) increase in volume and contrast enhancement during the pre-arthritic "expanding" phase of the disease, and then suddenly "collapse" during knee flare. Given the potential of this biomarker of arthritic flare, we aimed to develop a more cost-effective means of phenotyping PLN using ultrasound (US) imaging. Initially we attempted to recapitulate CE-MRI of PLN with subcutaneous footpad injection of US microbubbles (DEFINITY®). While this approach allowed for phenotyping via quantification of lymphatic sinuses in PLN, which showed a dramatic decrease in collapsed PLN versus expanding or wild-type (WT) PLN, electron microscopy demonstrated that DEFINITY® injection also resulted in destruction of the lymphatic vessels afferent to the PLN. In contrast, Power Doppler (PD) US is innocuous to and efficiently quantifies blood flow within PLN of WT and TNF-Tg mice. PD-US demonstrated that expanding PLN have a significantly higher normalized PD volume (NPDV) versus collapsed PLN (0.553 ± 0.007 vs. 0.008 ± 0.003; p0.030) and lower (<0.016) quartile NPDVs in this cohort of mice, which serve as conservative thresholds to phenotype PLN as expanding and collapsed, respectively. Interestingly, of the 12 PLN phenotyped by the two methods, there was disagreement in 4 cases in which they were determined to be expanding by CE-MRI and collapsed by PD-US. Since the adjacent knee had evidence of synovitis in all 4 cases, we concluded that the PD-US phenotyping was correct, and that this approach is currently the safest and most cost-effective in vivo approach to phenotype murine PLN as a biomarker of arthritic flare

METTL14 Regulates Intestine Cellular Senescence through m6A Modification of Lamin B Receptor

N-6-Methyladenosine (m6A) modification is involved in multiple biological processes including aging. However, the regulation of m6A methyltransferase-like 14 (METTL14) in aging remains unclear. Here, we revealed that the level of m6A modification and the expression of METTL14 were particularly decreased in the intestine of aged mice as compared to young mice. Similar results were confirmed in Drosophila melanogaster. Knockdown of Mettl14 in Drosophila resulted in a short lifespan, associated disrupted intestinal integrity, and reduced climbing ability. In human CCD-18Co cells, knockdown of METTL14 accelerated cellular senescence, and the overexpression of METTL14 rescued senescent phenotypes. We also identified the lamin B receptor (LBR) as a target gene for METTL14-mediated m6A modification. Knockdown of METTL14 decreased m6A level of LBR, resulted in LBR mRNA instability, and thus induced cellular senescence. Our findings suggest that METTL14 plays an essential role in the m6A modification-dependent aging process via the regulation of LBR and provides a potential target for cellular senescence