Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3.

ABSTRACT: Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin, thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV)-mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3. In control mice, HJV overexpression increased hepatic Hamp messenger RNA (mRNA) levels, soluble HJV (sHJV), splenic iron content (SIC), as well as phosphorylated small mothers against decapentaplegic protein (pSMAD1/5/8) levels. In contrast, in Alk2fl/fl;Alb-Cre and Alk3fl/fl;Alb-Cre mice, which present with moderate and severe iron overload, respectively, the administration of AAV-HJV induced HJV and sHJV. However, it did not rescue the iron overload phenotypes of those mice. Serum iron levels were induced in Alk2fl/fl;Alb-Cre mice after HJV overexpression. In phosphate-buffered saline-injected Alk3fl/fl;Alb-Cre mice, serum iron levels and the expression of duodenal ferroportin remained high, whereas Hamp mRNA levels were decreased to 1% to 5% of the levels detected in controls. This was reduced even further by AAV-HJV overexpression. SIC remained low in mice with hepatocyte-specific Alk2 or Alk3 deficiency, reflecting disturbed iron homeostasis with high serum iron levels and transferrin saturation and an inability to induce hepcidin by HJV overexpression. The data indicate that ALK2 and ALK3 are both required in vivo for the HJV-mediated induction of hepcidin.

Infertility-related stress, social support, and coping of women experiencing infertility in Vietnam.

BACKGROUND: Women with an infertility problem living in traditional and developing countries face extensive social pressure, infertility-related stress, and distress, which possibly affect their choices of coping strategies. The present study aims to investigate the impact of infertility-related stress and social support on coping of Vietnamese women who live with an infertility diagnosis. PARTICIPANTS AND PROCEDURE: A cross-sectional study was conducted with 192 women diagnosed with infertility at two hospitals in the north and central regions of Vietnam. Participants completed a questionnaire consisting of the Multidimensional Scale of Perceived Social Support, the Copenhagen Multi-centre Psychosocial Infertility coping scales and the Fertility Problem Inventory, and questions about their sociodemographic characteristics, infertility-related history, and key social relationships. Four linear regression analyses were performed on four coping strategies: active-avoidance coping (AAC), active-confronting coping (ACC), passive-avoidance coping (PAC), and meaning-based coping (MBC). RESULTS: The findings show that high infertility-related stress significantly predicted the use of avoidance coping strategies (AAC and PAC) among these women, while those with a high level of perceived social support tended to use ACC and MBC. None of the four linear regression models support the moderating role of social support in the relationship between infertility-related stress and coping styles. CONCLUSIONS: The study findings show that levels of infertility-related stress and perceived social support have a direct effect on the choice of coping strategies among Vietnamese women diagnosed with infertility. The study results have practical implications in the Vietnamese context, including: (i) the development and adaptation of evidence-based and culturally appropriate interventions and counselling strategies; and (ii) social policy advocacy to better support women diagnosed with infertility, their husbands, and both as couples.

Paclitaxel pre-medication: A comparison of two steroid pre-medication protocols.

Purpose To evaluate and compare the rate of hypersensitivity reactions between two low-dose steroid pre-medication regimens for paclitaxel-based treatments. Methods This was a single-center, retrospective, descriptive study, comparing the incidence of hypersensitivity reactions in two different dexamethasone pre-medication regimens that took place between July 2013 to December 2014. Patients who were paclitaxel-naïve with a diagnosis of breast or gynecological cancers were included. Patients in the early termination protocol were pre-medicated with a standard pre-medication regimen and if tolerated with no hypersensitivity reaction occurrence, all pre-medications were discontinued after the first two infusions. Patients in the low-dose steroid continuation protocol were pre-medicated with lower doses of dexamethasone, and if the infusion was tolerated with no hypersensitivity reaction, dexamethasone doses were further reduced after the first two infusions. Results A total of 120 patients were included for data analysis. The hypersensitivity reaction rate in the early termination protocol group was 7% (4 out of 60 patients). The hypersensitivity reaction rate in the low-dose continuation protocol group was 5% (3 out of 60 patients). All hypersensitivity reactions occurred during the first infusion, with no hypersensitivity reactions occurring once the dexamethasone pre-medications were discontinued or dose-reduced. All of the patients who experienced a hypersensitivity reaction were successfully re-challenged with paclitaxel and were able to continue their therapy uninterrupted. Conclusion Discontinuing dexamethasone pre-medication altogether after two uneventful infusions or decreasing the dose of dexamethasone paclitaxel pre-medication are both safe alternatives to high-dose steroid pre-medications recommended in product labeling.

Artisan phakic intraocular lens for myopia:short-term results of a prospective, multicenter study.

PURPOSE: To evaluate the safety and efficiency of the Artisan iris-supported phakic intraocular lens (Ophtec BV, Groningen, Netherlands) for the correction of high myopia. STUDY DESIGN: Nonrandomized, prospective, multicenter trial conducted under a United States Food and Drug Administration (FDA) Investigational Device Exemption. PARTICIPANTS: One hundred fifty-five eyes of 155 patients with myopia from -5.5 to -22.5 diopters (D) underwent implantation of an Artisan lens, as part of a phase I, II, or III FDA trial. METHODS: Eyes were examined at 1 day (154 eyes), 2 weeks (142 eyes), 2 months (130 eyes), and 6 months (84 eyes). Intraocular pressure and presence of flare and cell on slit-lamp biomicroscopy were recorded at each visit. MAIN OUTCOME MEASURES: Achieved correction, stability of spherical equivalent refraction, change in astigmatism, postoperative uncorrected vision, change in best spectacle-corrected acuity, and change in endothelial cell count. RESULTS: Mean spherical equivalent manifest refraction stabilized on postoperative day 1. Mean difference between attempted and achieved correction at 2 months was -0.32 +/- 0.95 D (mean +/- standard deviation; range, -4.42 to +2.2 D). At 6 months, 85% of eyes saw 20/40 or better uncorrected, and 90% of eyes were within 1 D of the attempted correction. Refractive astigmatism increased in 4.8% of eyes and decreased in 17% of eyes at 6 months. At 2 months, six eyes (4.8%) lost two or more lines of best spectacle-corrected visual acuity; by 6 months, no eyes lost two or more lines of best-corrected visual acuity. Endothelial cell count was unchanged at 6 months compared with the preoperative count. Nonprogressive lens opacities developed in four eyes as a result of surgical trauma. Chronic inflammation was not detected in any eye by slit-lamp biomicroscopy, nor did any eye develop angle closure or glaucoma. CONCLUSIONS: Short-term results suggest that the Artisan lens is an accurate and safe method for the correction of high myopia. Surgical skill is important in avoiding lens opacities. Longer-term data are needed to assess the impact of the lens on the endothelium, the crystalline lens, and the iris.