NHA1 is a cation/proton antiporter essential for the water-conserving functions of the rectal complex in Tribolium castaneum.

More than half of all extant metazoan species on earth are insects. The evolutionary success of insects is linked with their ability to osmoregulate, suggesting that they have evolved unique physiological mechanisms to maintain water balance. In beetles (Coleoptera)-the largest group of insects-a specialized rectal ("cryptonephridial") complex has evolved that recovers water from the rectum destined for excretion and recycles it back to the body. However, the molecular mechanisms underpinning the remarkable water-conserving functions of this system are unknown. Here, we introduce a transcriptomic resource, BeetleAtlas.org, for the exceptionally desiccation-tolerant red flour beetle Tribolium castaneum, and demonstrate its utility by identifying a cation/H+ antiporter (NHA1) that is enriched and functionally significant in the Tribolium rectal complex. NHA1 localizes exclusively to a specialized cell type, the leptophragmata, in the distal region of the Malpighian tubules associated with the rectal complex. Computational modeling and electrophysiological characterization in Xenopus oocytes show that NHA1 acts as an electroneutral K+/H+ antiporter. Furthermore, genetic silencing of Nha1 dramatically increases excretory water loss and reduces organismal survival during desiccation stress, implying that NHA1 activity is essential for maintaining systemic water balance. Finally, we show that Tiptop, a conserved transcription factor, regulates NHA1 expression in leptophragmata and controls leptophragmata maturation, illuminating the developmental mechanism that establishes the functions of this cell. Together, our work provides insights into the molecular architecture underpinning the function of one of the most powerful water-conserving mechanisms in nature, the beetle rectal complex.

Laser therapy for twin-twin transfusion syndrome in a dizygotic monochorionic twin pregnancy: A case report.

OBJECTIVE: A monochorionic dizygotic (MCDZ) twin is rare, especially when complicated with twin-twin transfusion syndrome (TTTS) and treated by laser therapy. CASE REPORT: A pregnancy achieved from oocyte donation and intracytoplasmic sperm injection resulted in two embryos transferred. A monochorionic diamniotic twin pregnancy was diagnosed by an early ultrasound; however, at 16 weeks of gestation, instead of the same sex, the ultrasound suspected there was sex discrepancy between the twins. TTTS with severe polyhydramnios occurred at 22 weeks, leading to a laser therapy, which was followed with a smooth post-operation course. Then the Cesarean section was performed at the gestational age of 29 weeks due to severe preeclampsia, giving birth to two live newborns: one female and one male baby both without neurological sequelae at the time of discharge. Blood chromosomes obtained at delivery and 65 days after delivery all revealed an XX and XY chimera from both babies. CONCLUSION: Laser therapy is also effective in MCDZ twin complicated with TTTS. Determination of chorionicity in early pregnancy could timely prompt us to watch out for complications unique to monochorionic twin pregnancy.

Androgen/Androgen Receptor Signaling in Ovarian Cancer: Molecular Regulation and Therapeutic Potentials.

Ovarian cancer (OVCA) arises from three cellular origins, namely surface epithelial cells, germ cells, and stromal cells. More than 85% of OVCAs are EOCs (epithelial ovarian carcinomas), which are the most lethal gynecological malignancies. Cancer stem/progenitor cells (CSPCs) are considered to be cancer promoters due to their capacity for unlimited self-renewal and drug resistance. Androgen receptor (AR) belongs to the nuclear receptor superfamily and can be activated through binding to its ligand androgens. Studies have reported an association between AR expression and EOC carcinogenesis, and AR is suggested to be involved in proliferation, migration/invasion, and stemness. In addition, alternative AR activating signals, including both ligand-dependent and ligand-independent, are involved in OVCA progression. Although some clinical trials have previously been conducted to evaluate the effects of anti-androgens in EOC, no significant results have been reported. In contrast, experimental studies evaluating the effects of anti-androgen or anti-AR reagents in AR-expressing EOC models have demonstrated positive results for suppressing disease progression. Since AR is involved in complex signaling pathways and may be expressed at various levels in OVCA, the aim of this article was to provide an overview of current studies and perspectives regarding the relevance of androgen/AR roles in OVCA.

Prenatally diagnosed de novo segmental amplification or deletion by microarray-based comparative genomic hybridization: A retrospective study.

OBJECTIVE: Prenatal diagnosis of de novo segmental amplification or deletion by microarray-based comparative genomic hybridization (array CGH) is uncommon. The study aimed to know about the incidence, abnormal ultrasound findings, and pregnancy outcomes of prenatally diagnosed de novo segmental amplification or deletion by array CGH. MATERIALS AND METHODS: Between January 2014 and December 2017, we analyzed pregnant women who received prenatal array CGH (SurePrint G3 Human CGH Microarray Kit, 8 × 60K) at Chang Gung Memorial Hospital, Taiwan. Clinical data on maternal age, reason for fetal karyotyping, sonographic findings, gestational age at delivery, newborn birth weight, and associated anomalies, if any, were obtained by chart review. RESULTS: A total of 836 specimens (814 amniotic fluid samples, 4 cord blood samples, 18 chorionic villi samples) were analyzed by array CGH during the study period. Of the 56 cases with abnormal array CGH results, 40 had segmental amplification or deletion, 12 had trisomy, three had monosomy, and one had sex chromosome aneuploidy. Of these 40 cases with segmental amplification or deletion, 30 were inherited and 10 were de novo occurrences. The incidence of de novo segmental amplification or deletion was 1.2% (10/836). Abnormal prenatal ultrasound findings occurred in 40% (4/10) of de novo segmental amplification or deletion cases. Among these 10 pregnancies, nine were voluntarily terminated between 22 and 26 weeks of gestation and one was delivered at term. CONCLUSIONS: Prenatal diagnosis of de novo segmental amplification or deletion by array CGH raises important genetic counseling issues. In our series, the incidence of de novo segmental amplification or deletion in prenatal samples was 1.2%. Abnormal prenatal sonographic findings occurred in 40% of these de novo segmental amplification or deletion cases. Of these de novo segmental amplification or deletion pregnancies, 90% were voluntarily terminated.

Combined Immunotherapy (OK-432, IL-2) With Chemotherapy Decrease the Recurrence Rate in Advanced Ovarian Cancer.

OBJECTIVE: In advanced ovarian cancer, traditional therapy included debulking surgery and postoperative chemotherapy. We proposed immunochemotherapy (IMCT) combined with picibanil (OK-432), interleukin-2 (IL-2), and traditional platinum- and taxol-based chemotherapy as a better treatment option for advanced ovarian cancer. METHODS: We retrospectively reviewed the medical records of 51 patients with advanced ovarian cancer between 2007 and 2015 at Chang Gung Memorial Hospital Linkou Medical Center, including 26 patients who were treated with OK-432, IL-2, and platinum- and taxol-based chemotherapy (IMCT group) after debulking surgery; another 25 were treated with traditional platinum- and taxol-based chemotherapy (traditional chemotherapy group) after debulking surgery. We analyzed the difference in age, follow-up period, recurrence rate, and diagnosis-to-recurrence period between the 2 groups. We also analyzed the difference in complete blood cell counts, differentiating counts, and cancer antigen 125 (CA-125) at 1 month after treatment. RESULTS: The recurrence rate between the IMCT and traditional chemotherapy groups showed a significant difference (53.8% vs 88%; P = .0128). The diagnosis-to-recurrence duration was longer in the IMCT than in the traditional chemotherapy groups (33.21 vs 25.63 months), although no statistical significance was found ( P = .4668). In laboratory analysis at 1 month after treatment, the white blood cell, absolute neutrophil, and absolute lymphocyte counts (ALCs) were significantly higher in the IMCT group. On the other hand, CA-125 was significantly lower, and ALC was significantly higher in the nonrecurrence group. CONCLUSIONS: Combined IMCT and chemotherapy have lower recurrence rate compared to traditional chemotherapy after debulking surgery for the treatment of advanced ovarian cancer.

Laparoscopic uterine surgery as a risk factor for uterine rupture during pregnancy.

The incidence of uterine rupture through a previous cesarean scar (CS) is declining as a result of a lower parity and fewer options for vaginal birth after cesarean. However, uterine ruptures attributable to other causes that traumatize the myometrium are on the rise. To determine whether changes in the causes of uterine rupture had occurred in recent years, we retrospective retrieved the clinical records of all singletons with uterine rupture observed in the delivery room of a Taiwanese tertiary obstetric center over a 15-year period. The overall uterine rupture rate was 3.8 per 10,000 deliveries. A total of 22 cases in 20 women (with two of them experiencing two episodes). Seven uterine ruptures occurred through a previous cesarean scar (CS ruptures, 32%), 13 through a non-cesarean scar (non-CS ruptures, 59%), whereas the remaining two (9%) were in women who did not previously undergo any surgery. All of the 13 non-CS ruptures were identified in women with a history of laparoscopic procedures to the uterus. Specifically, 10 (76%) occurred after a previous laparoscopic myomectomy, one (8%) following a hysteroscopic myomectomy, and two (16%) after a laparoscopic wedge resection of cornual ectopic pregnancy. Severe bleeding (blood loss >1500 mL) requiring transfusions was more frequent in women who experienced non-CS compared with CS ruptures (10 versus 1 case, respectively, P = 0.024). Patients with a history of endoscopic uterine surgery should be aware of uterine rupture during pregnancy.

Effects of inter-twin vascular anastomoses of monochorionic twins with selective intrauterine growth restriction on the contents of placental mitochondria DNA.

BACKGROUND: Placental mitochondrial DNA (mtDNA) has been proposed to be an indicator for placental hypoxia. This study was designed to evaluate the effect of vascular anastomoses between monochorionic (MC) twins on placental mtDNA. METHODS: In this study, twin-twin transfusion syndrome (TTTS) treated with laser therapy and MC twins without TTTS (without laser therapy) resulting in two live babies were included in this study. The placental mtDNA fold changes (FC) between the small and large twins were analyzed using real-time quantitative PCR. TTTS twins with selective intrauterine growth restriction (sIUGR) are categorized as group 1, TTTS without sIUGR as group 2, MC twins without TTTS but with sIUGR as group 3, and MC twins without both TTTS and sIUGR as group 4. RESULTS: There were seven cases in group 1, eight in group 2, 26 in group 3, and 24 in group 4 cases. The placental mtDNA FC were significantly higher in group 1 (1.57 ± 0.9) compared to that of the group 3 (0.86 ± 0.6). CONCLUSION: In MC twin pregnancies with sIUGR, the placental mtDNA FC between the small and large twins are different between cases with and without inter-twin anastomoses. These findings suggest that the inter-twin anastomoses in the MC twins with sIUGR may provide rescue perfusion from the appropriate-for-gestational-age twin to the sIUGR one.

Outcome of twin-twin transfusion syndrome treated by laser therapy in Taiwan's single center: Role of Quintero staging system.

OBJECTIVE: To evaluate the outcome of twin-twin transfusion syndrome (TTTS) treated by fetoscopic laser therapy (FLT) stratified by Quintero staging. MATERIALS AND METHODS: A total of 100 TTTS cases treated by FLT, from October 2005 to August 2014, were included in this study. Cases were divided into first and second half periods to evaluate the learning effect-related outcomes, and logistic regression was applied to determine the independent factors in predicting the perinatal outcomes. RESULTS: The total fetal survival rate was 68.5%, two fetal survival rate was 55%, and at least one fetal survival rate was 82%. High Quintero stage (Stages III and IV) and small gestational age at delivery were two independent factors predicting lower two fetal survivals. Gestational age at delivery was the only independent factor predicting at least one survival. The odds ratios of high Quintero stage predicting lower two fetal survivals were 11.3 (p<0.001) and 4.8 (p=0.043) in the first and second periods, respectively. CONCLUSION: High Quintero stage and small gestational age at delivery were associated with low two survival rate in TTTS treated by FLT; after gaining experience with FLT, the effect of high Quintero stage on lower two survival rate would decrease.

Increased Fetal Plasma Erythropoietin in Monochorionic Twin Pregnancies With Selective Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler.

Hypoxia is the primary stimulus for the production of erythropoietin (EPO) in both fetal and adult life. Here, we investigated fetal plasma EPO concentrations in monochorionic (MC) twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery (UA) Doppler. We diagnosed sIUGR in presence of (1) birth-weight discordance >20% and (2) either twin with a birth weight <10th percentile. An abnormal UA Doppler was defined as a persistent absent-reverse end diastolic flow (AREDF). The intertwin EPO ratio was calculated as the plasma EPO level of the smaller (or small-for-gestational-age) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin. Thirty-two MC twin pairs were included. Of these, 17 pairs were normal twins (Group 1), seven pairs were twins with sIUGR without UA Doppler abnormalities (Group 2), and eight pairs were twins with sIUGR and UA Doppler abnormalities (Group 3). The highest EPO ratio was identified in Group 3 (p < .001) but no significant differences were observed between Groups 1 and 2. Fetal hemoglobin levels did not differ significantly in the three groups, and fetal EPO concentration did not correlate with gestational age at birth. We conclude that fetal plasma EPO concentrations are selectively increased in MC twin pregnancies with sIUGR and abnormal UA Doppler, possibly as a result of uncompensated hypoxia.

Prognostic Value of Cardiovascular Disease Risk Factors Measured in the First-Trimester on the Severity of Preeclampsia.

Recent studies have suggested that preeclampsia and cardiovascular disease may share common mechanisms. The purpose of this prospective nested case-controlled study was to characterize a variety of cardiovascular disease risk factors measured during the first trimester of pregnancy in predicting subsequent outcomes and the severity of preeclampsia.We ascertained the severity of preeclampsia at the onset of the disease, and the presence of intrauterine growth restriction (IUGR). We compared first trimester maternal serum cardiovascular disease risk factors in preeclampsia subjects versus normal pregnancies, early-onset versus late-onset preeclampsia, and preeclampsia with IUGR versus without IUGR. To identify the prognostic value of independent predictors on the severity of preeclampsia, we calculated the area under the receiver operating characteristics curve (AUC) using logistic regression analysis.There were 134 cases of preeclampsia and 150 uncomplicated pregnancies, and preeclampsia cases were classified as early-onset (53 cases) or late-onset (81 cases), or as with IUGR (44 cases) or without IUGR (90 cases). Among the cardiovascular disease risk factors, maternal serum high-sensitive C-reactive protein (hsCRP) and homocysteine were predictors of both early-onset preeclampsia and preeclampsia with IUGR. For the detection of early onset preeclampsia or preeclampsia with IUGR, the AUC for the combination model (0.943 and 0.952, respectively) was significantly higher than with serum hsCRP or serum homocysteine only.Patients with preeclampsia can be subdivided into different severities according to time of onset and fetal weight. Cardiovascular risk factors distinguish a subgroup of these patients.

Increasing postpartum rate of vaccination with tetanus, diphtheria, and acellular pertussis vaccine by incorporating pertussis cocooning information into prenatal education for group B streptococcus prevention.

BACKGROUND: To evaluate whether incorporating pertussis cocooning information into prenatal education for group B streptococcus (GBS) prevention increased postpartum rate of vaccination with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine. METHODS: We performed a retrospective pre-intervention/post-intervention study of postpartum women at a teaching hospital in Taiwan. We compared the frequency of Tdap vaccination during the pre-intervention (May 1, 2009 to December 31, 2010) and post-intervention (March 1, 2011-March 31, 2012) time periods. The clinical intervention was incorporation of pertussis cocooning information into prenatal education for GBS prevention to pregnant women presented during a prenatal visit at 35-37 weeks of gestation. Postpartum Tdap vaccination rate during the pre-intervention and post-intervention periods was compared. We also specifically examined group differences in the percentage of women who received postpartum Tdap vaccination to explore factors that influenced their decision regarding Tdap vaccine. RESULTS: Tdap vaccination was more likely during the post-intervention period compared with the pre-intervention period (2268 of 3186 [71.2%] compared with 2556 of 5030 [55.6%]; p<.001). Comparisons between each subgroup of pre-intervention and post-intervention women showed that incorporating pertussis information into prenatal education for GBS prevention was beneficial except for women of maternal age 30-34 years and women living in rural areas. CONCLUSIONS: Prenatal GBS screening activities represent an opportunity for healthcare providers to offer pertussis cocooning information to eligible pregnant women to improve rates of postpartum Tdap vaccination.

Interphase fluorescence in situ hybridization assisting in prenatal counseling for amniocentesis karyotyping-detected fetal mosaicism.

OBJECTIVE: To evaluate how interphase fluorescence in situ hybridization (FISH) played a role in genetic counseling when encountering prenatally detected fetal mosaicism cases. MATERIALS AND METHODS: We retrospectively reviewed 17 cases of amniotic fluid specimens diagnosed with Level III chromosome mosaicism using in situ coverslip culture method. Among them, seven received additional interphase FISH tests; five were related to autosomal mosaicism and two others were due to sex chromosomes. RESULTS: In the autosome group, one couple chose to terminate the pregnancy due to a high percentage of trisomy 21 cells (48.1%) shown on interphase FISH; in the gonosome group, one case chose termination as FISH exhibited as high as 80% of XXYY cells. CONCLUSION: Performing interphase FISH on uncultured amniocytes for cases detected with mosaicism by traditional amniotic fluid culture provided quick confirmation of the karyotyping results; additionally, obtaining information about the extent of the abnormality involved using interphase FISH could also play a role in counseling patients on the decision making concerning the future of their pregnancies.

Special reactive oxygen species generation by a highly photostable BODIPY-based photosensitizer for selective photodynamic therapy.

We introduce a new class of photostable, efficient photosensitizers based on boron-dipyrromethene (BODIPY) derivatives that can generate singlet oxygen and super oxide simultaneously under irradiation. For compound preparation, appropriate regulation of the reaction conditions and control of specifically substituted BODIPY derivatives have been achieved. After biologically evaluating the intracellular uptake, localization, and phototoxicity of the compounds, we conclude that 3,5-dianiline-substituted BODIPY is a potentially selective photodynamic therapy candidate because its photodamage is more efficient in cancer cells than in normal cells, without apparent dark toxicity. Furthermore, direct comparison of photodamage efficacy revealed that our compound has better efficacy than Foscan and nearly equal efficacy to that of methylene blue.

Direct visualization of the quadruplex structures in human chromosome using FRET: application of quadruplex stabilizer and duplex-binding fluorophore.

The G-quadruplex structures in the telomere of a chromosome can not only protect the internal chromosome sequences by preventing the improper activation of DNA-damage-response pathways but also become targets for cancer treatments. In this manuscript, we wish to prove the existence of G-quadruplex structure formation, rather than G-quadruplex sequence, in chromosome of human cancer cells. Based on our studies, the fluorescent mapping of G-quadruplex structures in the chromosome is possible with the combination of G-quadruplex targeting fluorophore (BMVC, 3, 6-bis-(1-methyl-4-vinylpyridinium)-carbazole diiodide) and duplex-binding fluorophores (Hoechst or propidium iodide). By means of an applicable incubation time between cell cycle period and proper staining procedure to the chromosome, FRET (fluorescence resonance energy transfer) between G-quadruplex targeting fluorophore and duplex-binding fluorophore can increase the signal contrast of the fluorescent color and the fluorescent mapping of quadruplex structures can be easily observed using fluorescence microscopy. These observations are further supported by basic spectral analysis, titration binding assay, gel electrophoresis binding competition assay and confocal microscopy.

Nonlinear analysis of movement-related changes in human subthalamic local field potentials.

Movement-related changes such as event-related desynchronizationcan (ERD) and event-related synchronization (ERS) can be found in human subthalamic nucleus (STN) with analysis on local field potentials (LFP) recorded from Parkinson's disease (PD) patients. Besides traditional time-frequency (TF) analysis, we introduced nonlinear analysis, bispectral and approximate entropy (ApEn), to measure the signal nonlinear correlation and regularity in neural activities. Movement-related changes were found in the beta band, bicoherence and ApEn, and variation during stationary movement is more available by nonlinear methods. Therefore, we suggest nonlinear analysis for further related studies.

Fluorescent organic nanoparticle formation in lysosomes for cancer cell recognition.

We present a convenient method to prepare fluorophores 3- or 3,7-divinyl substituted 10H-phenothiazines and their protonation forms can aggregate to become fluorescent organic nanoparticles (FONs) with bright fluorescent spots in the lysosomes of cancer cells but not normal cells.