Ferroportin expression and regulation in human placenta/fetal membranes: Implications for ferroptosis and adverse pregnancy outcomes.

Iron overload is associated with pregnancy complications. Ferroportin (FPN) is the only known iron exporter in mammalian cells. We hypothesize that FPN is functionally important in ferrotopsis, a process of iron-dependent non-apoptotic programmed cell death, and may have a critical role to play in pregnancy success. We investigated the expression of FPN in placenta/fetal membranes by immunohistochemistry in tissues collected from pregnancies with/without preeclampsia (PE) and spontaneous preterm birth (SPTB). FPN was highly expressed in both trophoblasts and decidual cells found in placenta/fetal membranes. Staining was significantly reduced in fetal membranes from SPTB versus healthy pregnancies (P = 0.046). FPN expression in immortalized human endometrial stromal cells (HESC) increased with in vitro decidualization induction using 1 µM of medroxyprogesterone acetate and 0.5 mM of dibutyryl-cAMP. In addition, both HESC cells and immortalized extravillous trophoblast SW71 cells with FPN knockdown showed significant sensitivity to ferroptosis inducer, erastin (P < 0.001 and P = 0.009, respectively). The survival of both HESC and SW71 cells was not negatively affected by iron supplementation with ferric ammonium citrate in the medium. However, SW71 cells were more sensitive than HESC cells to physiologic iron in the presence of a non-lethal dose of erastin (P < 0.001). Taken together, our data demonstrating increased sensitivity of FPN knockdown HESC and SW71 cells to erastin and increased sensitivity of trophoblasts to iron overload under ferroptotic stress support the hypothesis that FPN protects against ferroptosis during pregnancy.

Clinical and economic burden of benign and malignant skin lesions in renal transplant recipients.

BACKGROUND: Studies evaluating the economic burden of dermatological care in the transplant setting are currently not available in Australia. AIMS: To evaluate the clinical and economic burden of benign and malignant skin lesions in renal transplant recipients in Central Queensland. METHODS: A bottom-up approach was used to determine the clinical burden and direct costs from patient-level Medicare data obtained from Service Australia for skin lesions. RESULTS: Seventy-six percent of the renal transplant population in Central Queensland participated in this study. The median age was 57.0 years (standard deviation ± 13.6) and the majority (61.8%) of participants were men. The mean duration after transplant surgery was 99.9 months (interquartile range, 73.2-126.6 months). During a 2-year follow-up, 22 (40%) patients were diagnosed with benign skin lesions, 21 (38%) with nonmelanoma skin carcinoma (NMSC) and one (2%) with melanoma. There was a total of 231 visits to clinicians for diagnostic and therapeutic skin procedures and the direct costs to Medicare was $48 806 Australian Dollars (AUD) or $30 427 US Dollars (USD). Approximately 86% of the total direct costs was spent for nonNMSC and mean direct costs for NMSC was $763 AUD (or $476 USD). CONCLUSION: This Medicare data-based study provides further insight into the burgeoning clinical and economic burden of the care for benign and malignant skin lesions in the renal transplantation setting in Australia.

Prolotherapy injections and physiotherapy used singly and in combination for lateral epicondylalgia: a single-blinded randomised clinical trial.

BACKGROUND: Lateral epicondylalgia (tennis elbow) is a common, debilitating and often treatment-resistant condition. Two treatments thought to address the pathology of lateral epicondylalgia are hypertonic glucose plus lignocaine injections (prolotherapy) and a physiotherapist guided manual therapy/exercise program (physiotherapy). This trial aimed to compare the short- and long-term clinical effectiveness, cost effectiveness, and safety of prolotherapy used singly and in combination with physiotherapy. METHODS: Using a single-blinded randomised clinical trial design, 120 participants with lateral epicondylalgia of at least 6 weeks' duration were randomly assigned to prolotherapy (4 sessions, monthly intervals), physiotherapy (weekly for 4 sessions) or combined (prolotherapy+physiotherapy). The Patient-Rated Tennis Elbow Evaluation (PRTEE) and participant global impression of change scores were assessed by blinded evaluators at baseline, 6, 12, 26 and 52 weeks. Success rate was defined as the percentage of participants indicating elbow condition was either 'much improved' or 'completely recovered.' Analysis was by intention-to-treat. RESULTS: Eighty-eight percent completed the 12-month assessment. At 52 weeks, there were substantial, significant improvements compared with baseline status for all outcomes and groups, but no significant differences between groups. The physiotherapy group exhibited greater reductions in PRTEE at 12 weeks than the prolotherapy group (p = 0.014). CONCLUSION: There were no significant differences amongst the Physiotherapy, Prolotherapy and Combined groups in PRTEE and global impression of change measures over the course of the 12-month trial. TRIAL REGISTRATION: ACTRN12612000993897 .

Prevalence and Trends of Vitamin D Deficiency among Iranian Adults: A Longitudinal Study from 2001-2013.

Vitamin D deficiency/insufficiency is currently considered to be a re-emerging public health problem globally. This study was designed to determine the prevalence of vitamin D deficiency and insufficiency and to investigate its trend from 2001 to 2013 in a longitudinal study of Iranian adults. This study was part of a population-based, longitudinal ongoing study of Iranian healthy adults aged 35 y and older at baseline. Serum vitamin D level was assessed in a sub-sample of 370 subjects, who were apparently healthy at the time of recruitment in 2001 and were free from MetS, in three phases (2001, 2007 and 2013) during the 12-y study period. Adjusted prevalence and trend of vitamin D deficiency were calculated. Mean serum vitamin D levels increased over the time of the study (52.12, 54.27 and 62.28 nmol/L, respectively) and the prevalence of vitamin D deficiency decreased (30.5, 27.0 and 24.4, respectively). However, the prevalence of vitamin D insufficiency did not change over this time period. The risk of vitamin D deficiency decreased significantly in 2007 [OR: 0.73 (95% CI: 0.53, 0.99)] and 2013 [OR: 0.50 (95% CI: 0.36, 0.70)] compared to the baseline. The present study demonstrated some improvement in serum vitamin D levels, while the prevalence of vitamin D inadequacy was still high. Considering the possible health consequences of vitamin D deficiency, there is an urgent need for developing population-wide strategies, such as supplementation and fortification, to prevent or control vitamin D deficiency.

Exploring the impact of endometriosis on partners.

AIM: This study aimed to determine how endometriosis affects the quality of life of partners of women who suffer from this disease and how it impacts their relationships, finances, mental states, and daily living. METHODS: This was a questionnaire-based cohort study that took place at a large tertiary hospital gynecology unit, which covered two sites. Fifty-one partners of women who had surgically diagnosed endometriosis agreed to participate in the study and returned completed surveys. RESULTS: Ninety-two percent (n = 46) of partners reported negative feelings about the diagnosis of endometriosis. Seventy percent (n = 35) reported that endometriosis affected their day-to-day life either moderately or severely. Over half (52%) also felt that their finances were affected. Only 34% (n = 17) of partners felt that health professionals had engaged them in decision-making processes and had been supportive of them. Eighty percent (n = 40) of partners reported that they had received no information about the impact of endometriosis on couples. Partners reported a significant affect on their sex life (74%) and their relationship as a whole (56%). Participants whose relationships had been affected by endometriosis had also more likely had their day-to-day life (P = 0.027), sex life (P = 0.001), and finances (P = 0.002) affected. CONCLUSION: Overall, our findings suggest that endometriosis can have a significant impact on partners with respect to day-to-day living, finances, sex lives, and relationships. Improvements can be made to engage partners in the treatment process, and to provide better education, support, and holistic management to women and families who suffer with endometriosis.

Prolotherapy injections and eccentric loading exercises for painful Achilles tendinosis: a randomised trial.

OBJECTIVE: To compare the effectiveness and cost-effectiveness of eccentric loading exercises (ELE) with prolotherapy injections used singly and in combination for painful Achilles tendinosis. DESIGN: A single-blinded randomised clinical trial. The primary outcome measure was the VISA-A questionnaire with a minimum clinically important change (MCIC) of 20 points. SETTING: Five Australian primary care centres. PARTICIPANTS: 43 patients with painful mid-portion Achilles tendinosis commenced and 40 completed treatment protocols. INTERVENTIONS: Participants were randomised to a 12-week program of ELE (n=15), or prolotherapy injections of hypertonic glucose with lignocaine alongside the affected tendon (n=14) or combined treatment (n=14). MAIN OUTCOME MEASUREMENTS: VISA-A, pain, stiffness and limitation of activity scores; treatment costs. RESULTS: At 12 months, proportions achieving the MCIC for VISA-A were 73% for ELE, 79% for prolotherapy and 86% for combined treatment. Mean (95% CI) increases in VISA-A scores at 12 months were 23.7 (15.6 to 31.9) for ELE, 27.5 (12.8 to 42.2) for prolotherapy and 41.1 (29.3 to 52.9) for combined treatment. At 6 weeks and 12 months, these increases were significantly less for ELE than for combined treatment. Compared with ELE, reductions in stiffness and limitation of activity occurred earlier with prolotherapy and reductions in pain, stiffness and limitation of activity occurred earlier with combined treatment. Combined treatment had the lowest incremental cost per additional responder ($A1539) compared with ELE. CONCLUSIONS: For Achilles tendinosis, prolotherapy and particularly ELE combined with prolotherapy give more rapid improvements in symptoms than ELE alone but long-term VISA-A scores are similar. TRIAL REGISTRATION NUMBER: ACTRN: 12606000179538.

Selenium binding protein 1 in ovarian cancer.

Selenium binding protein 1 (SELENBP1) was identified to be the most significantly down-regulated protein in ovarian cancer cells by a membrane proteome profiling analysis. SELENBP1 expression levels in 4 normal ovaries, 8 benign ovarian tumors, 12 borderline ovarian tumors and 141 invasive ovarian cancers were analyzed with immunohistochemical assay. SELENBP1 expression was reduced in 87% cases of invasive ovarian cancer (122/141) and was significantly reduced in borderline tumors and invasive cancers (p<0.001). Cox multivariate analysis within the 141 invasive cancer tissues showed that SELENBP1 expression score was a potential prognostic indicator for unfavorable prognosis of ovarian cancer (hazard ratio [HR], 2.18; 95% CI=1.22-3.90; p=0.009). Selenium can disrupt the androgen pathway, which has been implicated in modulating SELENBP1 expression. We investigated the effects of selenium and androgen on normal human ovarian surface epithelial (HOSE) cells and cancer cells. Interestingly, SELENBP1 mRNA and protein levels were reduced by androgen and elevated by selenium treatment in the normal HOSE cells, whereas reversed responses were observed in the ovarian cancer cell lines. These results suggest that changes of SELENBP1 expression in malignant ovarian cancer are an indicator of aberration of selenium/androgen pathways and may reveal prognostic information of ovarian cancer.