Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction.

Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3ß-hydroxyl-steroid dehydrogenase (3ß-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3ß-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3ß-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3ß-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction.

[Relationship between Work Improvement and Work Engagement in Financial Industry: Examination Based on the Level of Sense of Coherence].

OBJECTIVE: In this study, we aimed to clarify the relationship between workplace improvement and work engagement based on the level of sense of coherence. METHODS: An anonymous self-administered questionnaire survey was conducted on 1,845 regular employees in a financial industry (valid response rate, 78.5%). The questionnaire included the Japanese Sense of Coherence (SOC), Japanese Utrecht Work Engagement Scale (UWES-J), and Mental Health Improvement & Reinforcement Research of Recognition (MIRROR). Multiple linear regression analysis was performed with the total score of UWES-J as the dependent variable and the MIRROR items as the independent variables for each group with high and low SOC levels. RESULTS: Two MIRROR items namely, "It is easy to take a substitute vacation after work on holidays" and "In the workplace, the abilities and ingenuity of each person are utilized", were the negative factors common to the two groups. On the other hand, in the low-SOC-level group, the items "The work policy is decided in a way that everyone is satisfied with", "When the work breaks, I can go home without worrying about other people", and "The superior gives proper explanations about everything to his subordinates" showed negative relationships. In the high-SOC-level group, "The work environment (e.g., air conditioning and lighting) can be adjusted according to the wishes of workers", "No overtime day is set or utilized", "I am allowed to commute to work avoiding crowded times and routes", and "The superiors are trying to make everyone's work proceed smoothly" showed negative relationships. CONCLUSIONS: Depending on the level of SOC, workers' desire for workplace improvement related to UWES-J scores differed.

[Factors Related to Attitudes toward Responses to Stress Survey in Stress Check Program in Financial Industry].

OBJECTIVE: The purpose of this study is to clarify the factors related to attitudes toward responses to a stress survey in the Stress Check Program, which is used to screen for workers with high psychosocial stress at the workplace. METHODS: An anonymous self-administered questionnaire survey was conducted on 1,800 regular staff member of a financial industry (valid response rate: 72.0%). The questionnaire items were the brief job stress questionnaire (BJSQ), the sense of coherence (SOC-13), the Japanese version of the Utrecht work engagement scale (UWES-J), attitudes toward responses to the stress survey, and the concerns of subjects regarding the stress check program. RESULTS: The stress in interpersonal relationships at the workplace in the BJSQ, "concerns about leaking results to the company", "concerns about receiving persistent calls for an interview", and "concerns about a disadvantageous treatment by the company" were positively related to 'writing general truths', whereas the support from the boss in the BJSQ and the subscales of SOC-13 were negatively related to 'writing general truths'. The stress in interpersonal relationships at the workplace and "concerns about receiving persistent calls for an interview" were positively related to 'writing falsehoods', but the "dedication" in UWES-J was negatively related to 'writing falsehoods'. CONCLUSIONS: To obtain authentic answers in the stress survey, it is important (1) to smooth relationships at the workplace, (2) to devise operation systems such as an interview guidance, and (3) to provide support that enhances the ability of workers to cope with stress and work engagement.

Phosphorescent Ir(III) complexes conjugated with oligoarginine peptides serve as optical probes for in vivo microvascular imaging.

Imaging the vascular structures of organ and tumor tissues is extremely important for assessing various pathological conditions. Herein we present the new vascular imaging probe BTQ-Rn (n = 8, 12, 16), a phosphorescent Ir(III) complex containing an oligoarginine peptide as a ligand. This microvasculature staining probe can be chemically synthesized, unlike the commonly used tomato lectins labeled with a fluorophore such as fluorescein isothiocyanate (FITC). Intravenous administration of BTQ-R12 to mice and subsequent confocal luminescence microscope measurements enabled in vivo vascular imaging of tumors and various organs, including kidney, liver and pancreas. Dual color imaging of hepatic tissues of living mice fed a high-fat diet using BTQ-R12 and the lipid droplet-specific probe PC6S revealed small and large lipid droplets in the hepatocytes, causing distortion of the sinusoidal structure. BTQ-R12 selectively stains vascular endothelium and thus allows longer-term vascular network imaging compared to fluorescent dextran with a molecular weight of 70 kDa that circulate in the bloodstream. Furthermore, time-gated measurements using this phosphorescent vascular probe enabled imaging of blood vessel structures without interference from autofluorescence.

Treatment of adrenal crisis in patients with primary hypoadrenalism can lead to hypertension.

Hypertension is one of the most serious side effects of glucocorticoid therapy. We retrospectively investigated the frequency of hypertension during treatment of adrenal crisis and analyzed the factors associated with its development. Patients who were admitted for primary hypoadrenalism due to diagnosed or suspected adrenal crisis were included. In the analysis, the subjects were divided into two groups: the hypertensive group (group H) and non-hypertensive group (group Non-H). The primary endpoint was the difference in the hourly therapeutic hydrocortisone (HDC) dosage between the two groups. The hourly therapeutic HDC dose in the two groups was defined as the hourly HDC dose from the start of HDC infusion until the development of hypertension in group H or until the last blood pressure measurement in group Non-H. Nine of 19 crises led to hypertension. There was no significant difference in the therapeutic HDC dosage between the groups (p = 0.108). In conclusion, hypertension developed in some patients during treatment for adrenal crisis. There was no significant difference in the therapeutic HDC dosage between groups H and Non-H.

Frequent and prolonged administration of glucocorticoid for acute adrenal insufficiency treatment can cause diabetes mellitus: A case of holoprosencephaly.

Glucocorticoid (GC)-induced diabetes mellitus (DM) is theoretically unlikely to occur in patients with adrenal insufficiency if adequate physiological replacement doses of GC are given. Herein we report a patient with holoprosencephaly who developed GC-induced DM due to frequent and prolonged administration of high-dose GC for suspected adrenal crisis (AC). GC treatment should be started whenever AC cannot be ruled out. However, the initial and subsequent doses should be adjusted to the severity of AC and to the pace of clinical recovery with treatment, respectively.

Five cases of childhood-onset Graves' disease treated with either surgery or radio-iodine therapy.

There are three major therapeutic options for the treatment of Graves' disease (GD): antithyroid drugs (ATDs), thyroidectomy, and radio-iodine (RAI) therapy. ATDs are the initial treatment option for children. However, some pediatric GD patients who are initially treated with ATDs require other type of treatments later on. We reviewed the medical records of childhood-onset GD cases retrospectively to report the clinical course of patients who received either surgery or RAI therapy subsequent to treatment with ATDs. Childhood-onset GD was successfully managed in five girls with non-ATD treatments at the age of 7-14 yr following an unfavorable outcome of initial ATD treatment. Four cases had surgery and one case was managed with RAI therapy. The reasons for switching to non-ATD treatment included poor compliance, failure to maintain remission, serious adverse events resulting from ATDs, and religious background. In conclusion, surgery and RAI therapy could be good alternative treatment options for children with GD.

A Novel Mutation in OTX2 Causes Combined Pituitary Hormone Deficiency, Bilateral Microphthalmia, and Agenesis of the Left Internal Carotid Artery.

BACKGROUND: Mutations in OTX2 cause hypopituitarism, ranging from isolated growth hormone deficiency to combined pituitary hormone deficiency (CPHD), which are commonly detected in association with severe eye abnormalities, including anophthalmia or microphthalmia. Pituitary phenotypes of OTX2 mutation carriers are highly variable; however, ACTH deficiency during the neonatal period is not common in previous reports. OBJECTIVE: We report a novel missense OTX2 (R89P) mutation in a CPHD patient with severe hypoglycemia in the neonatal period due to ACTH deficiency, bilateral microphthalmia, and agenesis of the left internal carotid artery (ICA). RESULTS: We identified a novel heterozygous mutation in OTX2 (c.266G>C, p.R89P). R89P OTX2 showed markedly reduced transcriptional activity of HESX1 and POU1F1 reporters compared with wild-type OTX2. A dominant negative effect was noted only in the transcription analysis with POU1F1 promoter. Electrophoretic mobility shift assay experiments showed that R89P OTX2 abrogated DNA-binding ability. CONCLUSION: OTX2 mutations can cause ACTH deficiency in the neonatal period. Our study also shows that OTX2 mutations are associated with agenesis of the ICA. To the best of our knowledge, this is the first report of a transcription factor gene mutation, which was identified due to agenesis of the ICA of a patient with CPHD. This study extends our understanding of the phenotypic features, molecular mechanism, and developmental course associated with mutations in OTX2.