Comparing Strategies for Critical Congenital Heart Disease Newborn Screening.

OBJECTIVES: An extended newborn critical congenital heart disease (CCHD) screening program using oximetry has been implemented in Taipei, Taiwan since April 2014. This study was conducted to investigate the test accuracy and efficiency of this screening protocol. METHODS: This study analyzed data from 30 birthing facilities representing 87.9% of live births in Taipei. Positive screening was defined as oxygen saturation <95% in either extremity or a preductal-postductal oxygen saturation difference of >3%. This study cohort was used to retrospectively estimate outcomes on the basis of different CCHD screening protocols. RESULTS: During the study period, 93 058 of 94 204 (98.8%) infants who had no prenatal suspicion were screened. The referral rate was 0.17% (156/93 058), and up to 90% of test-positive infants were referred within 48 hours of life. Forty-two CCHD cases without prenatal suspicion were detected and 97.6% were diagnosed within 72 hours of life. Of the screened newborns, 4 CCHD cases passed the screening. The false positive and false negative rates were 0.12% and 0.04%, respectively. In addition, applying our database to Spanish and updated American Academy of Pediatrics screening strategies led to more CCHD case detection. CONCLUSIONS: The Taipei protocol provided an efficient and effective screening referral system in a community setting. For optimal efficiency, we advocated the updated American Academy of Pediatrics algorithm/Spanish recommendation with a modification of immediate referral if oxygen saturation ≤90% in either extremity. The updated protocol would be practicable for nationwide screening in Taiwan and could also be applied to other regions with similar medical care systems.

The MAEL expression in mitochondria of human spermatozoa and the association with asthenozoospermia.

PURPOSE: The maelstrom spermatogenic transposon silencer (MAEL) function in postmeiotic germ cells remains unclear, and its protein localization in human testis and spermatozoa awaits determination. This study aims to clarify the MAEL expression in human spermatogenesis and to explore its role in sperm function. MATERIALS AND METHODS: Twenty-seven asthenozoospermic men, 40 normozoospermic controls, and three obstructive azoospermic men were enrolled. The transcripts of MAEL in the seminiferous epithelium and MAEL downstream targets were identified by bioinformatics analysis. MAEL protein expression in human testis and ejaculated sperms were examined by immunohistochemical and immunogold staining, respectively. The roles of MAEL in mitochondria function were investigated by siRNA knockdown in human H358 cells. The association between MAEL protein levels and clinical sperm features was evaluated. RESULTS: Abundant MAEL was expressed in spermatid and spermatozoa of the human testis. Remarkably, MAEL was located in the mitochondria of ejaculated sperm, and bioinformatics analysis identified GPX4 and UBL4B as MAEL's downstream targets. Knockdown of MAEL sabotaged mitochondria function and reduced adenosine triphosphate (ATP) production in H358 cells. MAEL, GPX4, and UBL4B expression levels were significantly decreased in asthenozoospermic sperms than in controls. The MAEL protein levels were positively correlated with GPX4 and UBL4B in human sperm. Total motile sperm count (TMSC) was positively correlated with protein levels of MAEL, GPX4, and UBL4B in ejaculated sperms. CONCLUSIONS: We highlight prominent MAEL expression in the intratesticular spermatid and the mitochondria of ejaculated spermatozoa. MAEL directly binds to GPX4 and UBL4B, and loss of MAEL induces mitochondrial dysfunction. MAEL-mitochondrial function-motility relationship might advance our understanding of the causes of asthenozoospermia.

Nuclear factor erythroid-2-related factor regulates LRWD1 expression and cellular adaptation to oxidative stress in human embryonal carcinoma cells.

Leucine-rich repeats and WD repeat domain-containing protein 1 (LRWD1) is implicated in the regulation of signal transduction, transcription, RNA processing and tumor development. However, LRWD1 transcriptional regulation is not fully understood. This study aimed to investigate the relationship between LRWD1 expression and reactive oxygen species (ROS) level in human embryonal carcinoma cell line, NT2/D1 cells, which will help in understanding the transcriptional regulatory role of ROS in cells. Results showed that the exposure of NT2/D1 cells to various concentrations of hydrogen peroxide (H2O2) and the nitric oxide (NO) donor sodium nitroprusside (SNP) caused a significant increase in the mRNA and protein expression of LRWD1. In addition, LRWD1 promoter luciferase reporter assay, and Chromatin Immunoprecipitation assay (CHIP assay) showed that nuclear factor erythroid-2-related factor (Nrf2) was involved in the regulation of LRWD1 expression in response to oxidative stress. The involvement of Nrf2 was confirmed by shRNA-mediated knockdown of Nrf2 in NT2/D1 cells, which caused a significant decrease in LRWD1 expression in response to oxidative stress. Similarly, LRWD1 knockdown resulted in the accumulation of H2O2 and superoxide anion radical (O2-). Blocking ROS production by N-acetyl cysteine (NAC) protected NT2/D1 shLRWD1cells from H2O2-induced cell death. Collectively, oxidative stress increased LRWD1 expression through a Nrf2-dependent mechanism, which plays an important role in cellular adaptation to oxidative stress. These results highlight an evidence, on the molecular level, about LRWD1 transcriptional regulation under oxidative stress.

Correction: Evolution of impedance field telemetry after one day of activation in cochlear implant recipients.

[This corrects the article DOI: 10.1371/journal.pone.0173367.].

Evolution of impedance field telemetry after one day of activation in cochlear implant recipients.

OBJECTIVES: Changes in impedance between 24 hours and one month after cochlear implantation have never been explored due to the inability to switch on within one day. This study examined the effect of early activation (within 24 hours) on the evolution of electrode impedance with the aim of providing information on the tissue-to-electrode interface when electrical stimulation was commenced one day post implantation. METHODS: We performed a retrospective review at a single institution. Patients who received a Nucleus 24RECA implant system (Cochlear, Sydney, Australia) and underwent initial switch-on within 24 hours postoperatively were included. Impedance measurements were obtained intraoperatively and postoperatively at 1 day, 1 week, 4 weeks, and 8 weeks. RESULTS: A significant drop in impedance was noted 1 day after an initial activation within 24 hours followed by a significant rise in impedance in all channels until 1 week, after which the impedance behaved differently in different segments. Basal and mid-portion electrodes revealed a slight increase while apical electrodes showed a slight decrease in impedance from 1 week to 8 weeks postoperatively. Impedance was relatively stable 4 weeks after surgery. CONCLUSIONS: This is the first study to report the evolution of impedance in all channels between initial mapping 1 day and 1 month after cochlear implantation. The underlying mechanism for the differences in behavior between different segments of the electrode may be associated with the combined effect of dynamics among the interplay of cell cover formation, electrical stimulation, and fibrotic reaction.

Iridium(III) complexes with orthometalated quinoxaline ligands: subtle tuning of emission to the saturated red color.

Rational design and syntheses of four iridium complexes (1-4) bearing two substituted quinoxalines and an additional 5-(2-pyridyl) pyrazolate or triazolate as the third coordinating ligand are reported. Single-crystal X-ray diffraction studies of 1 reveal a distorted octahedral geometry, in which two dpqx ligands adopt an eclipse configuration, for which the quinoxaline N atoms and the C atoms of orthometalated phenyl groups are located at the mutual trans- and cis-positions, respectively. The lowest absorption band for all complexes consists of a mixture of heavy-atom Ir(III)-enhanced 3MLCT and 3pipi* transitions, and the phosphorescent peak wavelength can be fine-tuned to cover the spectral range of 622-649 nm with high quantum efficiencies. The cyclic voltammetry was measured, showing a reversible, metal-centered oxidation with potentials at 0.76-1.03 V, as well as two reversible reduction waves with potentials ranging from -1.61 to -2.06 V, attributed to the sequential addition of two electrons to the more electron-accepting heterocyclic portion of two distinctive cyclometalated C/N ligands. Complex 1 was used as the representative example to fabricate the red-emitting PLEDs by blending it into a PVK-PBD polymer mixture. The devices exhibited the characteristic emission profile of 1 with peak maxima located at 640 nm. The maximum external quantum efficiency was 3.15% ph/el with a brightness of 1751 cd/m2 at a current density of 67.4 mA/cm2, and the maximum brightness of 7750 cd/m2 was achieved at the applied voltage of 21 V and with CIE coordinates of (0.64, 0.31).