Involvement of FSP1-CoQ10-NADH and GSH-GPx-4 pathways in retinal pigment epithelium ferroptosis.

Retinal pigment epithelium (RPE) degeneration plays an important role in a group of retinal disorders such as retinal degeneration (RD) and age-related macular degeneration (AMD). The mechanism of RPE cell death is not yet fully elucidated. Ferroptosis, a novel regulated cell death pathway, participates in cancer and several neurodegenerative diseases. Glutathione peroxidase 4 (GPx-4) and ferroptosis suppressor protein 1 (FSP1) have been proposed to be two main regulators of ferroptosis in these diseases; yet, their roles in RPE degeneration remain elusive. Here, we report that both FSP1-CoQ10-NADH and GSH-GPx-4 pathways inhibit retinal ferroptosis in sodium iodate (SIO)-induced retinal degeneration pathologies in human primary RPE cells (HRPEpiC), ARPE-19 cell line, and mice. GSH-GPx-4 signaling was compromised after a toxic injury caused by SIO, which was aggravated by silencing GPx-4, and ferroptosis inhibitors robustly protected RPE cells from the challenge. Interestingly, while inhibition of FSP1 caused RPE cell death, which was aggravated by SIO exposure, overexpression of FSP1 effectively protected RPE cells from SIO-induced injury, accompanied by a significant down-regulation of CoQ10/NADH and lipid peroxidation. Most importantly, in vivo results showed that Ferrostatin-1 not only remarkably alleviated SIO-induced RPE cell loss, photoreceptor death, and retinal dysfunction but also significantly ameliorated the compromised GSH-GPx-4 and FSP1-CoQ10-NADH signaling in RPE cells isolated from SIO-induced RPE degeneration. These data describe a distinct role for ferroptosis in controlling RPE cell death in vitro and in vivo and may provide a new avenue for identifying treatment targets for RPE degeneration.

Secreted PDZD2 exerts an insulinotropic effect on INS-1E cells by a PKA-dependent mechanism.

Secreted PDZD2 (sPDZD2) is a signaling molecule generated upon proteolytic processing of the multi-PDZ-containing protein PDZD2. Previous analysis of gene-trap mice deficient in the synthesis of full-length PDZD2, but not the secreted form, revealed a role of PDZD2 in the regulation of glucose-stimulated insulin secretion. Here, using the pancreatic INS-1E ß cells as in vitro model, we showed that depletion of PDZD2/sPDZD2 by RNA interference suppressed the expression of ß-cell genes Ins1, Glut2 and MafA whereas treatment with recombinant sPDZD2 rescued the suppressive effect. Similar to GLP-1, sPDZD2 stimulated intracellular cAMP levels, activated ß-cell gene expression in a PKA-dependent manner and induced the phosphorylation and nuclear localization of PDX1. Depletion of PDX1 inhibited the sPDZD2 insulinotropic effect, which could also be demonstrated in mouse islets. In summary, our findings are consistent with sPDZD2 serving a signaling function in regulating ß-cell gene expression.

Stop the Bleed: gap analysis and geographical evaluation of incident locations.

BACKGROUND: Trauma is a major public health issue. In 2015, the White House launched the "Stop the Bleed" (STB) campaign, which aims to equip would-be bystanders with the ability and equipment to assist in bleeding emergencies. This study sought to estimate the number of patients who might benefit from STB intervention, in an everyday setting, and their spatial injury profile. METHODS: This is a retrospective analysis of trauma registry and medical examiners' data, collected between 2013 and 2017. The majority of patients were male. The median age was 32 years. Incidents were geocoded by ZIP code, and mapped using Quantum Geographic Information System (QGIS). RESULTS: We identified 139 patients from medical examiner records and UAB's trauma registry who might have benefitted from STB intervention. The number of incidents per year ranged from 22 to 35, averaging 2.3 incidents per month. There was no evidence of geographical clustering, although the small number of incidents precluded a formal geostatistical analysis. CONCLUSION: The number of patients who might benefit from STB interventions on a daily basis is small, and incident locations are difficult to predict. Educating the public in how to stop bleeding is appealing, but providing easy and widespread access to STB kits may be difficult. Although there are parallels to the provision of cardiopulmonary resuscitation and defibrillation for cardiac arrest, there are also differences, which should not be overlooked.

A strategy for identifying circulating placental RNA markers for fetal growth assessment.

OBJECTIVE: To evaluate whether circulating placental mRNAs in maternal plasma could serve as markers for the assessment of fetal growth or intrauterine growth restriction (IUGR). METHODS: From a panel of placental transcripts detectable in maternal plasma identified by microarray previously, we chose growth-related transcripts, namely CSH1, GH2, KISS1, and ADAM12, as potential growth markers. Relationships between the maternal plasma mRNA concentrations with several fetal growth indicators were studied. Maternal plasma mRNA concentrations from IUGR pregnancies with or without pre-eclampsia (PET) were compared with gestational age matched controls cross-sectionally and longitudinally. The four transcripts were quantified by one-step real-time RT-PCR. RESULTS: Maternal plasma GH2 mRNA significantly correlated with birth weight and fetal biometric measurements. Maternal plasma ADAM12 mRNA concentration was significantly higher in IUGR with PET than normal pregnancies in the cross-sectional comparison. No significant difference was observed for all markers between IUGR without PET and controls in both the cross-sectional and longitudinal comparisons. CONCLUSION: This study presents a potential strategy in identifying surrogate markers for the study of fetal growth. Circulating GH2 mRNA in maternal plasma appeared to be associated with fetal growth. The utility of this strategy and the currently assessed markers could be explored in further studies.

Change in prevalence of group B Streptococcus maternal colonisation in Hong Kong.

OBJECTIVES: To re-examine the prevalence of group B Streptococcus colonisation in our antenatal population, and identify demographic factors associated with carriage. DESIGN: Prospective observational study. SETTING: A tertiary obstetrics unit in Hong Kong. PARTICIPANTS: A total of 1002 pregnant women were recruited at the booking clinic in a tertiary obstetrics unit in Hong Kong. High and low vaginal swabs and rectal swabs were taken for group B Streptococcus culture. Demographic data and delivery outcomes of the recruits were analysed. RESULTS: The prevalence of group B Streptococcus colonisation in our antenatal population was 10.4%. The majority of carriers were identified by low vaginal swabs (78%), while high vaginal swabs and rectal swabs only identified 31% and 30% of the carriers, respectively. Professional women yielded a higher carrier rate than housewives (21% vs 10%, P=0.03). There was no increase in preterm delivery rate in group B Streptococcus carriers. CONCLUSIONS: We noted a dramatic increase in the prevalence of group B Streptococcus colonisation in the Hong Kong pregnant population at their booking visit. Professional women had a higher colonisation rate compared to other groups.

Novel Nuclear Partnering Role of EPS8 With FOXM1 in Regulating Cell Proliferation.

One hallmark of cancer cells is sustaining proliferative signaling that leads to uncontrolled cell proliferation. Both the Forkhead box (FOX) M1 transcription factor and the Epidermal Growth Factor (EGF) receptor Pathway Substrate 8 (EPS8) are known to be activated by mitogenic signaling and their levels upregulated in cancer. Well-known to regulate Rac-mediated actin remodeling at the cell cortex, EPS8 carries a nuclear localization signal but its possible nuclear role remains unclear. Here, we demonstrated interaction of FOXM1 with EPS8 in yeast two-hybrid and immunoprecipitation assays. Immunostaining revealed co-localization of the two proteins during G2/M phase of the cell cycle. EPS8 became nuclear localized when CRM1/Exportin 1-dependent nuclear export was inhibited by Leptomycin B, and a functional nuclear export signal could be identified within EPS8 using EGFP-tagging and site-directed mutagenesis. Downregulation of EPS8 using shRNAs suppressed expression of FOXM1 and the FOXM1-target CCNB1, and slowed down G2/M transition in cervical cancer cells. Chromatin immunoprecipitation analysis indicated recruitment of EPS8 to the CCNB1 and CDC25B promoters. Taken together, our findings support a novel partnering role of EPS8 with FOXM1 in the regulation of cancer cell proliferation and provides interesting insight into future design of therapeutic strategy to inhibit cancer cell proliferation.

Creep- and fatigue-resistant, rapid piezoresistive responses of elastomeric graphene-coated carbon nanotube aerogels over a wide pressure range.

Lightweight, flexible piezoresistive materials with wide operational pressure ranges are in demand for applications such as human physical activity and health monitoring, robotics, and for functional interfacing between living systems and wearable electronics. Piezoresistivity of many elastomeric foams of polymers and carbon allotropes satisfies much of the required characteristics for these applications except creep and fatigue resistance due to their viscoelasticity, critically limiting the reliability and lifetime of integrated devices. We report the piezoresistive responses from aerogels of graphene-coated single-walled carbon nanotubes (SWCNTs), made using a facile and versatile sol-gel method. Graphene crosslinks the junctions of the underlying random network of SWCNTs, generating lightweight elastomeric aerogels with a mass density of ≈11 mg mL-1 (volume fraction ≈7.7 × 10-3) and a Young's modulus of ≈0.4 MPa. The piezoresistivity of these aerogels spans wide compressive pressures up to at least 120 kPa with sensitivity that exhibit ultrafast temporal responses of <27 ms and <3% delay ratio over 104 compressive loading-unloading cycles at rates between 0.1-10 Hz. Most importantly, the piezoresistive responses do not show any creep at least for 1 hour and 80 kPa of compressive static loading. We suggest that the fatigue- and creep-resistant, ultrafast piezoresistive responses of these elastomeric aerogels are highly attractive for use in dynamic and static lightweight, pressure sensing applications such as human activity monitoring and soft robotics.

Drastically Enhancing Moduli of Graphene-Coated Carbon Nanotube Aerogels via Densification while Retaining Temperature-Invariant Superelasticity and Ultrahigh Efficiency.

Lightweight open-cell foams that are simultaneously superelastic, possess exceptionally high Young's moduli (Y), exhibit ultrahigh efficiency, and resist fatigue as well as creep are particularly desirable as structural frameworks. Unfortunately, many of these features are orthogonal in foams of metals, ceramics, and polymers, particularly under large temperature variations. In contrast, foams of carbon allotropes including carbon nanotubes and graphene developed over the past few years exhibit these desired properties but have low Y due to low density, ρ = 0.5-10 mg/mL. Densification of these foams enhances Y although below expectation and also dramatically degrades other properties because of drastic changes in microstructure. We have recently developed size- and shape-tunable graphene-coated single-walled carbon nanotube (SWCNT) aerogels that display superelasticity at least up to a compressive strain (ε) = 80%, fatigue and creep resistance, and ultrahigh efficiency over -100-500 °C. Unfortunately, Y of these aerogels is only ∼0.75 MPa due to low ρ ≈ 14 mg/mL, limiting their competitiveness as structural foams. We report fabrication of similar aerogels but with ρ spanning more than an order of magnitude from 16-400 mg/mL through controlled isostatic compression in the presence of a polymer coating circumventing any microstructural changes in stark contrast to other foams of carbon allotropes. The compressive stress (σ) versus ε measurements show that the densification of aerogels from ρ ≈ 16 to 400 mg/mL dramatically enhances Y from 0.9 to 400 MPa while maintaining superelasticity at least up to ε = 10% even at the highest ρ. The storage (E') and loss (E″) moduli measured in the linear regime show ultralow loss coefficient, tan δ = E″/E' ≈ 0.02, that remains constant over three decades of frequencies (0.628-628 rad/s), suggesting unusually high frequency-invariant efficiency. Furthermore, these aerogels retain exceptional fatigue resistance for 106 loading-unloading cycles to ε = 2% and creep resistance for at least 30 min under σ = 0.02 MPa with ρ = 16 mg/mL and σ = 2.5 MPa with higher ρ = 400 mg/mL. Lastly, these robust mechanical properties are stable over a broad temperature range of -100-500 °C, motivating their use as highly efficient structural components in environments with extreme temperature variations.

When to induce labor for post-term? A study of induction at 41 weeks versus 42 weeks.

OBJECTIVE: To evaluate the pregnancy outcomes of two policies of timing of induction of labor for post-term pregnancies. STUDY DESIGN: It is a retrospective study in a University obstetric unit from 1997 to 2002. Five thousand eight hundred and ninety-two singleton, cephalic pregnancies with gestational age at delivery at or more than 41 completed weeks were studied. They were divided into two groups. Group A included women who delivered from January 1997 to February 1999 when the policy of the department was to induce labor for post-maturity at 42 weeks of gestation. Group B included those delivered between March 1999 and December 2002 when the timing of induction for post-term was advanced to 41 weeks. The intrapartum characteristics, delivery and perinatal outcomes were analyzed by Student's t-test and Chi-square test for continuous and categorical variables, respectively. RESULTS: Two thousand one hundred and seventy-six women were studied in Group A and 3716 in Group B. Twenty-nine percent of these pregnancies in Group A required induction of labor whereas 20.3% were for post-term. In Group B, 58% of pregnancies had labor induction and 55% for post-maturity. For the pregnancies undergoing induction of labor for post-term, both the duration of labor (P<0.001) and the need of intrapartum epidural analgesia were increased (OR 1.3, 95% CI: 1.0-1.6) in Group B. However, there was no significant difference in the mode of delivery, apgar scores and stillbirths between the two study periods. CONCLUSION: Compared to routine induction at 42 weeks, induction at 41 weeks is associated with a significantly higher risk of use of medical interventions and associated complications, with no observable benefits.

Central Forehead Reconstruction with a Simple Primary Vertical Linear Closure.

OBJECTIVE: Following Mohs surgery, medium-to-large defects on the central forehead can often be complicated to surgically reconstruct. In this paper, the authors discuss possible central forehead reconstructions and report their successful experience employing a simple primary vertical linear closure with a special technique to demarcate forehead rhytides rather than performing an overly complicated flap or graft. CASE REPORT: The patient was a 57-year-old man who presented with a broad superficial basal cell carcinoma that required treatment with Mohs surgery. For the resulting defect, the authors elected to perform a complex linear repair taking advantage of substantial side-to-side laxity in the supraperiosteal plane and carefully labeling and matching each forehead rhytide across the defect as the wound was sutured. CONCLUSION: The findings of this case demonstrate that medium-to-large wounds of the central forehead can be aesthetically repaired with a simple primary vertical linear closure. Carefully mapping and labeling horizontal forehead rhytides with a sterile surgical marking pen prior to anesthesia ensures accurate approximation during wound closure.

Effect of prostaglandin E2 for cervical priming on fetal hemodynamics.

OBJECTIVE: To assess the effect of the prostaglandin E2 (PGE2) on fetal vascular blood flow during cervical priming. STUDY DESIGN: In a prospective, observational study, 32 pregnant women > or =37 weeks of gestation requiring PGE2 for induction of labor were recruited. The resistance indices (RIs) of umbilical artery, middle cerebral artery, renal artery and ductus venosum were measured before, 2 and 4 hours after insertion of a PGE2 vaginal pessary. RESULTS: There were no significant changes in RIs of various fetal vessels during cervical priming with PGE2. CONCLUSION: There was no significant change in fetal hemodynamics after vaginal prostaglandin administration. This finding provides further evidence to support the safety of prostaglandin for normal fetuses.

Postdelivery screening for postpartum depression.

OBJECTIVE: Postpartum depression (PPD) is a serious psychiatric disorder affecting 10% to 20% of women after childbirth. Research has shown that systematic screening for PPD using self-report questionnaires helps improve the identification of PPD and expedite treatment. Most studies on PPD screening have been conducted in the second and third postpartum months; little is known about whether PPD screening can be carried out on the days immediately after delivery. METHODS: A prospective cohort of 145 women completed the Edinburgh Postnatal Depression Scale (EPDS), Beck Depression Inventory (BDI), and General Health Questionnaire (GHQ) within 2 days of delivery. Six weeks after delivery, the participants were interviewed by a psychiatrist, who used the Structured Clinical Interview for DSM-III-R (SCID, nonpatient version) to establish the diagnosis. The psychometric performance of the EPDS, BDI, and GHQ in detecting PPD was assessed using the SCID diagnosis as the gold standard. RESULTS: When the cutoffs of the EPDS, BDI, and GHQ were lowered to achieve a sensitivity of 80%, the positive predictive values of these scales were to 13%, 18%, and 21%, respectively. When the cutoffs were raised to achieve a positive predictive value of 50%, the sensitivity rates were 6% (EPDS), 14% (GHQ), and 36% (BDI). CONCLUSIONS: When commonly used depression rating scales were administered to identify PPD immediately after delivery, their psychometric properties were unsatisfactory. Healthcare providers should not screen for PPD in the first few days after delivery.

A prevalence study of antenatal depression among Chinese women.

BACKGROUND: There has thus far been no empirical research on the occurrence of antenatal psychiatric morbidity in Chinese population. Epidemiological studies in western societies generally show that depressive episodes occur in 10-20% of pregnant women. Longitudinal studies have demonstrated that antenatal depression is one of the most powerful predictors of postnatal depression. There is also a growing literature that shows that antenatal psychological distress can adversely affect maternal and foetal well being. METHODS: At 38 weeks of pregnancy, 238 consecutive women were invited to return for psychiatric assessment. The participants were interviewed using the non-patient version of the Structured Clinical Interview for DSM-IV (SCID-NP). RESULTS: Seventy women (29%) declined to participate, and another 11 (5%) defaulted the SCID interview. Among the 157 women interviewed, the 1-month prevalence of antenatal depression was 4.4%. The 1-month prevalence of all psychiatric diagnoses was 6.4%. The prevalence of antenatal depression and all psychiatric diagnoses for the entire pregnancy was 6.4% and 8.3%, respectively. LIMITATIONS: About a third of eligible subjects did not participate in the study. CONCLUSIONS: A significant proportion of Chinese women suffer from psychiatric morbidity during pregnancy. Depressive disorders are by far the commonest morbidity in the study population. Given the scope of the morbidity and the potential impact on obstetric and neonatal outcomes, early screening and treatment are warranted.

Impact of common contraceptive methods on quality of life and sexual function in Hong Kong Chinese women.

The combined oral contraceptive (COC) pills, injectables, intrauterine contraceptive device (IUCD) and female sterilization are the most common contraceptive methods used by women. Women's choice, compliance and satisfaction with specific contraceptive methods are influenced by any impact of the method on their quality of life and sexual function. Anxiety regarding possible adverse effects of the contraceptive methods on their quality of life and sexual function is one of the common concerns. The aim of this prospective observational study was to determine the impact of the abovementioned contraceptive methods on the quality of life and sexual function of the users. A sample of 361 Hong Kong Chinese women who were first-time users of the following contraceptive methods completed the study: COC pills (n=87), injectables (n=67), IUCD (n=96) and female sterilization (n=111). Quality of life and sexual function of the subjects were assessed before and 3-4 months after use of the method by a standardized questionnaire. The questions were adopted from the validated Chinese versions of the World Health Organization Quality of Life (WHOQOL) questionnaire and the Derogatis Sexual Functioning Inventory (DSFI). In the female sterilization group, we found a significantly higher score for sexual satisfaction (p=.004) and sexual drive (p=.003) 3-4 months after sterilization, as well as an improved WHOQOL social domain score (p=.009). However, the other DSFI subscale scores and WHOQOL domain scores were not significantly different (p>.05). No significant difference was demonstrated in all the WHOQOL domain scores and DSFI subscale scores after use of COC pills, injectables and IUCD (p>.05). We conclude that the COC pills, injectables, IUCD and female sterilization all do not have significant adverse impact on quality of life and sexual function. After female sterilization, there is a significant improvement in sexual satisfaction and sexual drive.

The reproductive and metabolic effect of rosiglitazone on Chinese women with polycystic ovarian syndrome--a double-blind randomized placebo-controlled study.

OBJECTIVE: To investigate whether an insulin sensitizer has any effect on amenorrhea and clinical and biochemical hyperandrogenism in Chinese women with polycystic ovarian syndrome (PCOS). DESIGN: Randomized controlled double-blind trial. SETTING: A tertiary referral center, Hong Kong. PATIENT(S): Chinese women who fulfilled the Rotterdam criteria of PCOS (n = 70). INTERVENTION(S): Rosiglitazone 4 mg daily for the first month followed by 4 mg twice daily for 11 months. MAIN OUTCOME MEASURE(S): Menstrual status as well as clinical and biochemical hyperandrogenism. RESULT(S): There is a significantly higher rate of regular menses among the treatment arm (16 [50.0%] of 32 vs 4 [11.8%] of 34) at 6 months and the improvement appeared to be sustained (10 [41.7%] of 24 vs 6 [20.0%] of 30) at 12 months. There was no change in the acne and hirsutism scores as well as serum T levels in both arms. CONCLUSION(S): We found a possible benefit in menstrual cyclicity but a lack of improvement in hyperandrogenism in our Chinese population. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-09000670 (Chinese Clinical Trial Registry).

Identification of a Streptococcus agalactiae serotype III subtype 4 clone in association with adult invasive disease in Hong Kong.

Characterization of Streptococcus agalactiae serotype III isolates revealed a subtype 4 clone that has an indistinguishable pulsed-field gel electrophoresis pattern and possesses a C-alpha protein, IS1381, and a novel sequence type (ST), ST 283, by multilocus sequence tagging. This clone was significantly associated with diseases caused by invasive strains from nonpregnant adults (P

Maternal fear associated with pregnancy and childbirth in Hong Kong Chinese women.

BACKGROUND: Women's fear toward pregnancy and childbirth is a common and important health concern. This study examined the objects, causes, and manifestations of maternal fears and their associated demographic factors in a sample of Hong Kong Chinese pregnant women. METHODS: Three hundred Chinese pregnant women were recruited in an obstetric unit in Hong Kong in 2003. Data were collected using a 73-item questionnaire. Principal components factor analysis was applied to identify the objects, causes, and manifestations of fear toward pregnancy and childbirth. RESULTS: The mean maternal age was 30 (SD 5.6) years. All participants reported some degree of fear. The main objects of fear were "fear of childbirth" and "child's and mother's wellbeing." The first factor identified for causes of fear was "negative stories," followed by "negative attitude or mood." Regarding the various manifestations of fear, "stress symptoms" and "wish to avoid pregnancy and childbirth" ranked highest. Twenty-two percent of participants had considered requesting an elective cesarean section due to fear of childbirth. CONCLUSIONS: Even in a group of low-risk pregnant women, fear toward pregnancy and childbirth was frequently experienced. Better strategies to address women's psychological needs during pregnancy are warranted.

Fetal hemodynamic changes after amniotomy.

BACKGROUND: The aim of the study was to assess fetal vascular blood flow after amniotomy. METHODS: This was a prospective observational study. Thirty-five women with singleton pregnancy beyond 36 weeks of gestation, who underwent amniotomy, were recruited. The pulsatility indices of the fetal middle cerebral artery (MCA), the renal artery, and the ductus venosum were measured before and 30 min following amniotomy. The changes in pulsatility index were compared by means of Wilcoxon signed rank test. RESULTS: There was a significant reduction in pulsatility indices of the MCA (median reduction: 0.23; interquantile range (IQR): -0.04, 0.4) and the renal artery (median reduction: 0.12; IQR: -0.12, 0.54) after amniotomy. However, there was no obvious change in the ductus venosum (median reduction: 0.00; IQR: -0.06, 0.1). CONCLUSIONS: Amniotomy is associated with significant reduction in the impedance of the fetal MCA and the renal artery. The former may be a result of fetal stress response and the latter could be related to the release of vasoactive substances after amniotomy.