Accumulation of senescent cells in the adrenal gland induces hypersecretion of corticosterone via IL1ß secretion.

Aging progresses through the interaction of metabolic processes, including changes in the immune and endocrine systems. Glucocorticoids (GCs), which are regulated by the hypothalamic-pituitary-adrenal (HPA) axis, play an important role in regulating metabolism and immune responses. However, the age-related changes in the secretion mechanisms of GCs remain elusive. Here, we found that corticosterone (CORT) secretion follows a circadian rhythm in young mice, whereas it oversecreted throughout the day in aged mice >18 months old, resulting in the disappearance of diurnal variation. Furthermore, senescent cells progressively accumulated in the zF of the adrenal gland as mice aged beyond 18 months. This accumulation was accompanied by an increase in the number of Ad4BP/SF1 (SF1), a key transcription factor, strongly expressing cells (SF1-high positive: HP). Removal of senescent cells with senolytics, dasatinib, and quercetin resulted in the reduction of the number of SF1-HP cells and recovery of CORT diurnal oscillation in 24-month-old mice. Similarly, administration of a neutralizing antibody against IL1ß, which was found to be strongly expressed in the adrenocortical cells of the zF, resulted in a marked decrease in SF1-HP cells and restoration of the CORT circadian rhythm. Our findings suggest that the disappearance of CORT diurnal oscillation is a characteristic of aging individuals and is caused by the secretion of IL1ß, one of the SASPs, from senescent cells that accumulate in the zF of the adrenal cortex. These findings provide a novel insight into aging. Age-related hypersecretory GCs could be a potential therapeutic target for aging-related diseases.

Delayed bowel stenosis following subtotal resection of the small intestine for non-occlusive mesenteric ischemia.

We report herein a case of delayed bowel stenosis after surgery for non-occlusive mesenteric ischemia (NOMI), which was successfully treated with endoscopic stenting. The patient was a 78-year-old woman who underwent an emergency laparotomy for NOMI and duodeno-ileal anastomosis. Necrosis was observed in almost all areas of the small intestine except for the beginning of the jejunum and the end of the ileum. Postoperatively, the patient was discharged with central venous nutrition, but was readmitted on postoperative day 54 with a diagnosis of postoperative ileus. The patient failed to respond to conservative treatment. Fluoroscopic endoscopy revealed wall stiffness and circumferential stenosis in the ascending colon at a different site from that of the anastomosis. Based on this finding, delayed stenosis of the ascending colon after NOMI treatment was diagnosed. Bougie dilatation was performed for the stenosis, leading to temporary improvement. However, stenosis along with ileus soon recurred. To prevent restenosis, a metallic stent was endoscopically implanted at the stenotic site. Thereafter, the patient was discharged without any further episodes of restenosis. Delayed bowel stenosis may occur after a subtotal resection of the small intestine for NOMI. Endoscopic stenting is an effective treatment option if resection is difficult.

Hypoxia induces downregulation of the tumor-suppressive sST2 in colorectal cancer cells via the HIF-nuclear IL-33-GATA3 pathway.

As a decoy receptor, soluble ST2 (sST2) interferes with the function of the inflammatory cytokine interleukin (IL)-33. Decreased sST2 expression in colorectal cancer (CRC) cells promotes tumor growth via IL-33-mediated bioprocesses in the tumor microenvironment. In this study, we discovered that hypoxia reduced sST2 expression in CRC cells and explored the associated molecular mechanisms, including the expression of key regulators of ST2 gene transcription in hypoxic CRC cells. In addition, the effect of the recovery of sST2 expression in hypoxic tumor regions on malignant progression was investigated using mouse CRC cells engineered to express sST2 in response to hypoxia. Our results indicated that hypoxia-dependent increases in nuclear IL-33 interfered with the transactivation activity of GATA3 for ST2 gene transcription. Most importantly, hypoxia-responsive sST2 restoration in hypoxic tumor regions corrected the inflammatory microenvironment and suppressed tumor growth and lung metastasis. These results indicate that strategies targeting sST2 in hypoxic tumor regions could be effective for treating malignant CRC.

Body-first approach of laparoscopic cholecystectomy for minimizing vasculobiliary injury: Initial experience.

INTRODUCTION: Vasculobiliary injury (VBI) is a rare but critical complication of laparoscopic cholecystectomy (Lap-C). Dividing first the gallbladder body and then the gallbladder neck from the gallbladder bed (the "body-first approach") may decrease the possibility of VBI. METHODS: The surgical outcome of 62 patients who underwent Lap-C with a body-first approach were evaluated. In this procedure, after serosal resection of the gallbladder, the gallbladder body is divided from the cystic plate; then the gallbladder neck and cystic duct are isolated. No connective tissue of the hepatic hilum is touched. RESULTS: A total of five patients had anatomical anomalies of the biliary tract that raised concerns of cholecystectomy. Furthermore, seven patients underwent subtotal cholecystectomy. No patients required conversion to open surgery, and none developed VBI or postoperative complications of Clavien-Dindo grade 3a or worse. CONCLUSION: The body-first approach may minimize the risk of VBI during Lap-C.

Relationship between somatic symptoms with menstruation and intention to leave work among university hospital nurses in Japan: a cross-sectional study.

PURPOSE: This study investigated the association between menstrual symptoms and the intention to leave work among female nurses in Japan. METHODS: This cross-sectional study investigated female nurses (n = 317) at two university hospitals. The items measured were their characteristics (e.g., age, body mass index), "intention to leave" work, somatic symptoms related with menstruation, self-reported menstrual characteristics (e.g., pain), physical workloads (e.g., working hours and night shifts) and psychological workloads, measured with the Copenhagen Burnout Inventory (CBI), and the Job Content Questionnaire (JCQ). Participants with at least four somatic symptoms (e.g., cold, fatigue) which are present during their menstrual cycles were considered to have "somatic symptoms associated with menstruation." We also measured serum ovarian and gonadotropin-releasing hormones. RESULTS: Approximately 40% of women answered "intention to leave" work, and 17% had "somatic symptoms associated with menstruation." Multiple logistic regression analysis suggested that nurses reporting "somatic symptoms associated with menstruation" were more likely to have "intention to leave" work: the adjusted odds ratios (AOR, 95% confidence interval [CI]) were 2.15 (1.12-4.11) in the personal-burnout model, 2.23 (1.16-4.31) in the work-related burnout model, 2.91 (1.52-5.56) in the client-related burnout model; 2.96 (1.50-5.82) in the JCQ model. There was no association between serum and gonadotropin hormones and the intention to leave. CONCLUSION: Somatic symptoms with menstruation were associated with intention to leave work among female Japanese nurses. Intervention for somatic symptoms with menstruation might support nurses to continue work.

[Curative Resection after Chemotherapy for Advanced Extensive Cholangiocarcinoma-A Case Report].

A 73-year-old, male patient presented with the chief complaint of epigastric pain and received the diagnosis of extensive cholangiocarcinoma after a close examination. Extensive extension of the malignancy into the right and left hepatic ducts precluded a curative resection, and the patient received GC therapy. After 11 courses of GC over about 1 year, no new lesions or tumor progression was observed, and a bile duct mapping biopsy was performed to investigate the possibility of resection conversion. The results showed a marked decrease in atypia, and reactive atypia was diagnosed. A pancreaticoduodenectomy was performed, and histopathologically negative margins were obtained. The response to treatment was Grade Ⅱa according to the Evans classification. At 23 months after the start of treatment and 12 months after surgery, the patient is recurrence-free without adjuvant chemotherapy. Although the evidence for conversion surgery for biliary tract cancer has not been established, the long-term outcomes may be favorable.

[A Case of a Two-Stage Robotic-Assisted Surgery for a Neuroendocrine Tumor of the Pancreatic Tail with Simultaneous Single Liver Metastasis].

As medical insurance coverage for robotic surgery has been expanded in the field of gastrointestinal surgery in Japan, the number of cases undergoing robotic surgery for hepato-biliary-pancreatic disease has been increasing. Therefore, cases with malignant tumors and metastatic lesions tend to undergo robotic operation for both primary tumors and metastases. Herein, we report a case of neuroendocrine tumor(NET)in the pancreatic tail with simultaneous single liver metastasis, which was treated with two-stage robotic-assisted surgery. A 67-year-old female underwent a computed tomography scan and a hypovascularized tumor in the pancreatic tail region and liver was found. A biopsy of the pancreatic tumor by endoscopic ultrasound-guided fine needle aspiration demonstrated a NET G1-2. The liver lesion was diagnosed as a metastatic tumor, considering the other examinations. The patient underwent a robotic distal pancreatectomy(RDP)and was histopathologically diagnosed as NET G2. Sixty-three days after the RDP, a two-stage partial liver resection for the metastatic tumor was performed under robotic assistance. Curative resection was achieved through two-stage robot-assisted surgery, there were no postoperative complications.

A novel LncRNA PTH-AS upregulates interferon-related DNA damage resistance signature genes and promotes metastasis in human breast cancer xenografts.

Long noncoding RNAs (lncRNAs) are important tissue-specific regulators of gene expression, and their dysregulation can induce aberrant gene expression leading to various pathological conditions, including cancer. Although many lncRNAs have been discovered by computational analysis, most of these are as yet unannotated. Herein, we describe the nature and function of a novel lncRNA detected downstream of the human parathyroid hormone (PTH) gene in both extremely rare ectopic PTH-producing retroperitoneal malignant fibrous histiocytoma and parathyroid tumors with PTH overproduction. This novel lncRNA, which we have named "PTH-AS," has never been registered in a public database, and here, we investigated for the first time its exact locus, length, transcription direction, polyadenylation, and nuclear localization. Microarray and Gene Ontology analyses demonstrated that forced expression of PTH-AS in PTH-nonexpressing human breast cancer T47D cells did not induce the ectopic expression of the nearby PTH gene but did significantly upregulate Janus kinase-signal transducer and activator of transcription pathway-related genes such as cancer-promoting interferon-related DNA damage resistance signature (IRDS) genes. Importantly, we show that PTH-AS expression not only enhanced T47D cell invasion and resistance to the DNA-damaging drug doxorubicin but also promoted lung metastasis rather than tumor growth in a mouse xenograft model. In addition, PTH-AS-expressing T47D tumors showed increased macrophage infiltration that promoted angiogenesis, similar to IRDS-associated cancer characteristics. Although the detailed molecular mechanism remains imperfectly understood, we conclude that PTH-AS may contribute to tumor development, possibly through IRDS gene upregulation.

[Treatment Strategies for Liver Oligometastases of Esophageal Cancer].

Benefits of local therapy for liver oligometastases of esophageal cancer has not been established. There are 2 cases of resection for liver oligometastases of esophageal cancer. Case 1: A 65-year-old male diagnosed with liver metastasis of esophageal cancer 12 months after initial treatment. A tumor located in segment 7 was resected after 6 months of chemotherapy. Case 2: A 71-year-old female diagnosed with liver metastasis of esophageal cancer 14 months after initial treatment. During 6 months of chemotherapy, tumor diameter increased but there were no new lesions. The tumor located in segment 8 was resected. In both cases, R0 resection was performed without intraoperative injury to the reconstructed esophagus. They had a recurrence free survival of more than 5 months. Resection of liver metastasis of esophageal cancer may be useful in combination with drug therapy in case it was diagnosed with liver oligometastases.

Multiple Physical Symptoms Are Useful to Identify High Risk Individuals for Burnout: A Study on Faculties and Hospital Workers in Japan.

Healthcare workers have a high risk of burnout. This study aimed to investigate if the numbers of physical symptoms are associated with burnout among healthcare workers. We conducted a cross-sectional survey at a large university in Tokyo, Japan, in 2016. Participants were 1080: 525 faculties and 555 hospital workers. We investigated 16 physical symptoms perceived more than once per week and examined the association between the number of physical symptoms and Copenhagen Burnout Inventory (CBI); work-related (WBO), personal (PBO), and client-related (CBO) burnout. All CBI scores were higher among hospital workers than among faculties: WBO (43 vs. 29), PBO (50 vs. 33), CBO (33 vs. 29). Moreover, the higher the number of physical symptoms perceived, the higher the degree of burnout scores became (trend p-values < 0.001), except for CBO among faculties. Job strain (all except for CBO among hospital workers) and work-family conflict were associated with an increased risk of burnout. Being married (WBO and CBO among faculties), having a child (except for PBO and CBO among faculties), and job support (faculty and hospital workers with WBO and faculties with PBO) were associated with a decreased risk of burnout. Multiple physical symptoms might be useful for identifying high risk individuals for burnout.

Continuous Work Support Checklist for Female Healthcare Workers: Scale Development and Validation.

Healthcare jobs are very popular among women, however in Japan, women readily quit working because of gender-role responsibilities. This study aimed to develop a workplace support checklist for women to continue to work. In 2017, we investigated 780 (female 74.8%) faculty members and healthcare professionals of one medical university in Japan. We asked them to score the extent to which they considered 35 items identified by a task team, to be related to continuous work support for female workers in healthcare. We carried out an exploratory factor analysis and extracted four domains with 16 items in all: "Support for child rearing and home care" (five items), "Information dissemination" (five items), "Active promotion of women workers to higher positions" (three items), and "Consulting and counseling service" (three items), with Cronbach's alpha values ranging from 0.88 to 0.92. We found that the first three factors were generally associated with reasonably relevant characteristics of being female, in their 30s, married, and members of faculty. We also found that women with "Intention to leave" the workplace underscored the importance of "Support for child rearing and home care" and "Consulting and counseling service". These results suggest that the checklist is reliable and valid.

Workplace resources, mentorship, and burnout in early career physician-scientists: a cross sectional study in Japan.

BACKGROUND: Physician-scientists are a vital segment of the healthcare workforce, but they may face significant challenges balancing and integrating clinical responsibilities, scientific research, and domestic responsibilities. This study investigates factors associated with burnout among highly successful early career physician-researchers in Japan. METHOD: Among 1790 physician awardees of Grant-in-Aid for Young Scientists by the Japanese Ministry in 2014-2015, 490 participated in this cross-sectional survey in 2016 (usable response rate 23.8%). The primary outcome was psychological burnout, measured by the Copenhagen Burnout Inventory (i.e., personal burnout, work-related burnout, and patient-related burnout). "Workplace resources" in our study refers to the presence of career education in the workplace, promotion of gender equity, well-being consultation services on "career and work," "research," "harassment," and/or "mental health," as well as the presence of a role model in the workplace who has perceived good work-life balance. RESULTS: Among 408 physician-researchers (75% male, mean age 37 yrs), personal burnout scores were slightly higher in women than in men (mean score, 41.9 points vs. 36.7 points, difference, 5.2, 95% confidence interval, 0.5-9.9, p = 0.029), but work-related and patient-related burnout scores did not differ significantly between genders. Over half of women (64%) and men (58%) had a mentor (p = 0.374). In multivariable general linear regression models, personal burnout scores were higher for women (ß = 4.98, p = 0.045), and lower among those who had a mentor (ß = - 5.82, p = 0.010) and whose workplaces had well-being consultation services (ß = - 0.79, p = 0.022). Work-related burnout scores were lower among those with larger amounts of grant funding (ß = - 4.70, p = 0.013), a mentor (ß = - 6.12, p = 0.002), well-being consultation services (ß = - 0.78, p = 0.008) and a role model with a perceived good work-life balance (ß = - 4.00, p = 0.038). Patient-related burnout scores were higher among physician-scientists aged older than 37 years (ß = 6.25, p = 0.002) and those who had board certification (ß = 9.01, p = 0.017), while these scores were lower among those had larger amounts of funding (ß = - 5.01, p = 0.006) or a mentor (ß = - 5.35, p = 0.006). CONCLUSIONS: Workplace resources and mentorship appear to be associated with lower levels of psychological burnout for both men and women early career physician-scientists.

25(OH)D3 stimulates the expression of vitamin D target genes in renal tubular cells when Cyp27b1 is abrogated.

Recently, it was reported that 25(OH)D3 (25D3) has physiological bioactivity in certain tissues derived from Cyp27b1 knockout mice. To investigate the function of 25D3 in the kidney as an informational crossroad of various calciotropic substances, we employed the CRISPR-Cas9 system to knock out Cyp27b1 in the mouse renal distal tubular mDCT cell line. Unlike the previously reported mice in which Cyp27b1 was targeted systemically, Cyp27b1 knockout mDCT cells did not produce any measurable 1α,25(OH)2D3 (1,25D3) after 25D3 administration. As was seen with treatment of Cyp27b1 knockout mDCT cells with ≥10-8 M of 1,25D3, the administration of 10-7 M of 25D3 translocated the vitamin D3 receptor (VDR) into the nucleus and promoted the expression of the representative 1,25D3-responsive gene Cyp24a1. The exhaustive target gene profiles of 25D3 were similar to those of 1,25D3. Subsequently, we confirmed that 25D3 induced the expression of the calcium reabsorption-related gene calbindin-D9K, in a way similar to 1,25D3. We also found that 1,25D3 and 25D3 induced the expression of the megalin gene. A chromatin immunoprecipitation assay identified two vitamin D response elements in the upstream region of the megalin gene that seemed to contribute to its expression. Together, we surmise that the ability of 25D3 to stimulate VDR target genes may provide a novel perspective for its role in certain tissues.

Gender Division of Labor, Burnout, and Intention to Leave Work Among Young Female Nurses in Japan: A Cross-Sectional Study.

Women in Japan face difficulties balancing work and personal life due to the gender division of labor, and medical professions are no exception. The purpose of this study was to investigate if the gender division of labor affects the intention to leave the workplace among the nursing profession. Among 328 female nurses working for three university-affiliated hospitals in Tokyo, Japan, above 70% were in their 20s and 30s and single, and agreed with the gender division of labor that men should be the breadwinner and women should assume family responsibilities. Adjusting for three types of Copenhagen burnout inventory, stepwise multivariable logistic regression models identified that being younger (all p-values < 0.05), each domain of burnout score (each p < 0.001 for work-, personal-, and client-related burnout) increased a risk of intention to leave, and high support decreased the risk (all p < 0.001). Women who agreed with the gender division of labor were more likely to have intentions to leave (p = 0.003 but this association disappeared when adjusted. The findings of study demonstrate that perceptions toward gender division of labor are not a determinant of intention to leave the workplace but the young nurses and those who scored high on burnout were the most vulnerable population.

[Scale Development on Perception of Academic Harassment among Medical University Faculties].

OBJECTIVES: In academia, harassment may often occur and remain unrevealed in Japan, which discourages young researchers from pursuing their career. It is necessary to estimate and improve the perception of "academic harassment" among university faculties. Therefore, in this study, we aim to develop a scale of perception of academic harassment. METHODS: Prior to a quantitative survey, a task team consisting of medical doctors, researchers, nurses, hospital workers, and managers in general affairs division identified 36 items related to academic harassment. In February 2016, we sent a self-administered questionnaire to 1,126 academic faculty members who worked in a medical university located in Tokyo, Japan. We instructed them to score the extent to which they consider each item as related to academic harassment based on a Likert scale. We carried out maximum likelihood factor analyses with promax rotation and computed Cronbach's alpha to develop a scale and investigate the reliability of the scale. RESULTS: In total, 377 returned the questionnaires (response rate, 33.5%; male, 73.8%). In factor analyses, we removed 17 items owing to low factor loadings, and four factors were eventually extracted. The first factor was termed "Harassment in organization (7 items)" because it included conditions of forcing a particular person to work on chores or lectures for students that may prevent one's academic research outputs. The second factor was termed "Violence and denying personal character (4 items)". The third factor was termed "Research misconduct (5 items)" including conditions of excluding a particular person from the coauthor list of research outputs or pressuring a person to fabricate, falsify, or plagiarize research outputs. The fourth factor was termed "Research interference (3 items)" including a condition of interference with conference attendance. Cronbach's alpha values of these four factors ranged from 0.83 to 0.91, suggesting that the scale had high reliability. The means of these factors did not differ according to gender but were higher in participants aged 50 or older than in younger participants. CONCLUSIONS: The results suggest that the scale of perception on academic harassment consisting of four factors with 19 items is valid and reliable to some extent.

[Association between Job Stress and Number of Physical Symptoms among Female Nurses of Medical-university-affiliated Hospitals].

OBJECTIVES: To clarify the association between job stress and the number of physical symptoms among newly certified female nurses. METHODS: In this cross-sectional self-administered survey, we investigated 313 female nurses working at three medical-university-affiliated hospitals in February 2016. We investigated working conditions including numbers of working and on-call hours, work-life balance, Job Content Questionnaire (JCQ) scores, and 16 physical symptoms perceived more often than once a week. RESULTS: Among the 313 participants (mean age, 31.9), 57% were aged 21-29 years and 70% were single. Of the 16 physical symptoms investigated, fatigability was the most frequent complaint (66.1%), followed by lower back pain (44.7%). Univariate analysis showed that significant factors related to physical symptoms are job demands (p<0.001) and social support (p<0.001) in JCQ, binary index of supports (p<0.001), and total working hours per day (p =0.025). Multivariable-adjusted logistic regression analyses demonstrated that the likelihood of reporting a greater number (n≥3) of physical symptoms increased by 7% [95% confidence interval (CI), 2-13%] with a one-unit increase in job demand degree, and decreased by 16% (95% CI, 10-22%) in social support degree. When binary JCQ indexes were assessed, the high-support group [odds ratio (OR) 0.36; 95% CI, 0.23-0.59] was protectively associated with a greater number of physical symptoms while long working hours was significantly associated with a higher risk (OR 18%, 95% CI, 1-38%). CONCLUSIONS: Reporting a greater number of physical symptoms may be a good indicator of job stress perceived by a nurse in a university hospital setting.

Correlation between anti-thyroid peroxidase antibody levels and diffuse thyroid uptake of 18F-fluorodeoxyglucose in Hashimoto's thyroiditis: a retrospective study.

BACKGROUND: On 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET), diffuse uptake in the thyroid gland is often observed in patients with Hashimoto's thyroiditis. In this study, we evaluated the factors associated with diffuse uptake by comparing Hashimoto's thyroiditis patients with or without diffuse uptake in the thyroid. METHODS: A retrospective study was conducted of 18 patients with Hashimoto's thyroiditis who underwent blood tests, thyroid ultrasonography, and FDG-PET during the period from 2014 to 2015. The patients were divided into two groups: one with diffuse thyroid uptake (group 1, n = 13) and one without diffuse thyroid uptake (group 2, n = 5). Clinical and laboratory parameters, including maximum standardized uptake in the thyroid (SUVmax), which was defined as the higher value obtained in either the right or left thyroid lobe, were compared in the two groups. RESULTS: The frequency of abnormal findings, such as a rough or heterogeneous pattern, was significantly higher in group 1 (p <  0.01), as were anti-thyroid peroxidase (TPO) antibody titers, anti-thyroglobulin (Tg) antibody titers, and SUVmax (p <  0.01). The frequency of hypothyroidism did not differ significantly in the two groups. Anti-TPO and anti-Tg titers were positively correlated with SUVmax (r = 0.856, p <  0.01 and r = 0.821, p <  0.01, respectively); in univariate analysis, anti-TPO titer was predictive of SUVmax (p <  0.01). CONCLUSIONS: The results of the current study suggest that Hashimoto's thyroiditis patients with high titers of anti-thyroid antibodies are likely to exhibit intense diffuse FDG uptake in the thyroid, and that thyroid function may be clearly impaired, even in the presence of mild FDG uptake in the thyroid.

DNA damage response induced by Etoposide promotes steroidogenesis via GADD45A in cultured adrenal cells.

Glucocorticoid production is regulated by adrenocorticotropic hormone (ACTH) via the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway in the adrenal cortex, but the changes in steroidogenesis associated with aging are unknown. In this study, we show that cell-autonomous steroidogenesis is induced by non-ACTH- mediated genotoxic stress in human adrenocortical H295R cells. Low-dose etoposide (EP) was used to induce DNA damage as a genotoxic stress, leading to cellular senescence. We found that steroidogenesis was promoted in cells stained with γH2AX, a marker of DNA damaged cells. Among stress-associated and p53-inducible genes, the expression of GADD45A and steroidogenesis-related genes was significantly upregulated. Immunofluorescence analysis revealed that GADD45A accumulated in the nuclei. Metabolite assay using cultured media showed that EP-treated cells were induced to produce and secrete considerable amounts of glucocorticoid. Knockdown of GADD45A using small interfering RNA markedly inhibited the EP-induced upregulation of steroidogenesis-related gene expression, and glucocorticoid production. A p38MAPK inhibitor, but not a PKA inhibitor, suppressed EP-stimulated steroidogenesis. These results suggest that DNA damage itself promotes steroidogenesis via one or more unprecedented non-ACTH-mediated pathway. Specifically, GADD45A plays a crucial role in the steroidogenic processes triggered by EP-stimulated genotoxic stress. Our study sheds new light on an alternate mechanism of steroidogenesis in the adrenal cortex.

Without 1α-hydroxylation, the gene expression profile of 25(OH)D3 treatment overlaps deeply with that of 1,25(OH)2D3 in prostate cancer cells.

Recently, the antiproliferative action of 1,25(OH)2D3 (1,25D3), an active metabolite of vitamin D3, in the management of prostate cancer has been argued rigorously. In this study, we found that at a physiological concentration, 25(OH)D3 (25D3), the precursor of 1,25D3 and an inactive form of vitamin D because of its much weaker binding activity to the vitamin D receptor (VDR) compared with 1,25D3, had a gene expression profile similar to that of 1,25D3 in prostate cancer LNCaP cells. By immunocytochemistry, western blotting, and CYP27B1 and/or VDR knockdown by small interfering RNAs, we found that 10-7 M 25D3, which is within its uppermost physiological concentration in the bloodstream, induced VDR nuclear import and robustly activated its target genes in the virtual absence of CYP27B1 expression. Comprehensive microarray analyses verified 25D3 bioactivity, and we found that 25D3 target gene profiles largely matched those of 1,25D3, while the presence a small subset of 25D3- or 1,25D3-specific target genes was not excluded. These results indicated that 25D3 shares bioactivity with 1,25D3 without conversion to the latter. Metallothionein 2A was identified as a 1,25D3-specific repressive target gene, which might be a prerequisite for 1,25D3, but not 25D3, to exert its anti-proliferative action in LNCaP cells.

Direct and Indirect Harassment Experiences and Burnout among Academic Faculty in Japan.

The purpose of this study is three-fold: (1) to compare harassment (sexual, gender, and academic harassment both directly and indirectly experienced - i.e. "directly harassed" and "have seen or heard of someone who experienced harassment", respectively) experienced by males and females, (2) to investigate whether such experiences correlate with burnout, and (3) to explore whether social support might mitigate any such relationship between harassment and burnout. This cross-sectional study was conducted at a private university in Japan in February 2014 and is based on a work-life balance survey obtained from 330 academic faculty members. We investigated the association between each of the six subcategories of harassment (direct and indirect forms of each of the three types) and burnout using general linear regression models; we then evaluated interactions between harassment and social support in these models. The prevalence of direct and indirect experiences of harassment was higher in females than in males for all three types of harassment. Males showed higher burnout scores if they had direct experiences of harassment. There were significant interactions between social support and the direct experience of harassment; high social support mitigated the effect size of direct harassment on burnout among males. Females showed higher burnout scores if they had indirect experiences of harassment. However, the same buffering effect of social support on burnout as observed in males was not observed in females. Direct harassment experiences increased the risk of burnout in males, and indirect harassment experiences increased burnout in females.