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.

Individualized antiplatelet therapy for non-cardiogenic ischemic stroke.

OBJECTIVE: This research aims to investigate the impact of individualized antiplatelet therapy guided by thromboelastography with platelet mapping (TEG-PM) on the clinical outcomes of patients with non-cardiogenic ischemic stroke. METHODS: Among a total of 1264 patients, 684 individuals diagnosed with non-cardiogenic ischemic stroke underwent TEG-PM testing. Based on the adjustment of antiplatelet medication, these patients were divided into individual and control groups. Within the individual group, in accordance with the TEG-PM test results, a Maximum amplitude (MA) value greater than 47mm was defined as high residual platelet reactivity (HRPR), while an MA value less than 31mm was defined as low residual platelet reactivity (LRPR). Patients with arachidonic acid (AA) less than 50% and adenosine diphosphate (ADP) less than 30% were classified as aspirin-resistant or clopidogrel-resistant. Treatment strategies for antiplatelet medication were subsequently adjusted accordingly, encompassing increment, decrement, or replacement of drugs. Meanwhile, the control group maintained their original medication regimen without alterations. RESULTS: The individual group included 487 patients, while the control group had 197. In the individual group, approximately 175 patients (35.9%) were treated with increased medication dosages, 89 patients (18.3%) with reduced dosages, and 223 patients (45.8%) switched medications. The results showed that the incidence rate of ischemic events in the individual group was lower than that of the control group (5.54% vs. 12.6%, P = 0.001), but no significant difference was observed in bleeding events. Cox regression analysis revealed age (hazard ratio, 1.043; 95% CI, 1.01-1.078; P = 0.011) and coronary heart disease (hazard ratio, 1.902; 95% CI, 1.147-3.153; P = 0.013) as significant risk factors for adverse events. CONCLUSION: Individualized antiplatelet therapy based on TEG-PM results can reduce the risk of ischemic events in patients with non-cardiogenic ischemic stroke without increasing the risk of bleeding events or mortality. Advanced age and coronary heart disease were identified as risk factors affecting the outcomes of individualized antiplatelet therapy.

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.

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.

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.

Life threatening biphasic adverse reactions to desmopressin: case report and review of the literature.

Treatment with desmopressin diacetate arginine vasopressin (DDAVP) and its withdrawal are associated with side effects. We present a rare case of severe biphasic adverse reactions induced by DDAVP and its withdrawal in a 63-year-old female patient. A lump in the left axillary region was biopsied, and she received DDAVP after surgery. The following day, she lost consciousness, with foaming at the mouth and seizures. Hypotonic encephalopathy was considered. DDAVP was ceased, and she received electrolytes. On day 1, she displayed low blood pressure and increased urine output. She received DDAVP and dopamine as well as electrolytes. The patient was ambulatory on day 7 and was discharged without brain abnormalities on MRI. In conclusion, severe hyponatremia induced by DDAVP and massive polyuria and hypovolemic shock induced by DDAVP withdrawal are life-threatening conditions. This case underlines the need to be vigilant when administering DDAVP and to monitor for any side effects.

Risk factors for falls in Parkinson's disease: a cross-sectional observational and Mendelian randomization study.

Background: Patients with Parkinson's disease (PD) exhibit a heightened risk of falls and related fractures compared to the general population. This study aims to assess the clinical characteristics associated with falls in the patient with PD and to gain further insight into these factors through Mendelian randomization analysis. Methods: From January 2013 to December 2023, we included 591 patients diagnosed with Parkinson's disease at Shenzhen Baoan People's Hospital. Using univariate and multivariate logistic regression analyses, we identified clinical variables associated with falls. We constructed a nomogram based on these variables and evaluated the predictive efficacy of the model. Additionally, we employed summary statistics from genome-wide association studies to conduct two-sample Mendelian randomization (MR) analyses on key variables influencing falls. Results: Compared to the control group, we identified osteoporosis, motor dysfunction, higher Hoehn and Yahr scale as significant risk factors for falls in PD patients. Conversely, treatment with levodopa and a higher level of education exhibited a protective effect against the risk of falling. MR analysis further confirmed a causal relationship between osteoporosis, education level and falls in PD patients. Conclusion: Osteoporosis and educational attainment are correlated with falls in Parkinson's disease.

Clinical impact of heterogeneously distributed tumor-infiltrating lymphocytes on the prognosis of colorectal cancer.

Background: Tumor-infiltrating lymphocytes (TILs) exist in various malignancies, and have been viewed as a promising biomarker to predict the efficacy and outcome of treatment. However, the marked inter- and intra-tumor heterogeneity of TILs has resulted in some confusion regarding their impact on the prognosis of colorectal cancer (CRC). Methods: In this study, 78 CRC patients were enrolled and the CD3+ and CD8+ TILs densities at the tumor center (TC), the invasive margin (IM) and the tumor stroma (TS) were assessed by immunohistochemical staining. Their associations with clinicopathological features and progression free survival (PFS) were analyzed to evaluate the predictive and prognostic values of TILs. Results: TILs were mainly distributed along the invasive margin. High density of TILs in tumor center and invasive margin was associated with smaller tumor size (CD3+TILsIM), reduced tumor invasion (CD3+TILsIM), absence of lymph node metastasis (CD3+TILsIM and CD8+TILsTC), earlier stage (CD3+TILsIM and CD8+TILsIM), and lower tumor grade (CD3+TILsIM and CD8+TILsTC). However, stromal TILs were not associated with any clinicopathological features. Kaplan-Meier survival analysis revealed that high densities of TILs always correlated with prolonged patient survival. The pathological N stage, CD3+ TILsIM and CD8+ TILsTC were found to be independent prognostic indicators. Additionally, early-stage CRC patients who developed recurrence after surgery, showed a higher CD3+/CD8+ TILs ratio in invasive margin. In the present study, it was clarified that CD3+ and CD8+ TILs were heterogeneously distributed in tumor tissues of CRC. The increase in intratumoral and peritumoral TILs had been shown to be strongly predictive of improved clinical outcome. More importantly, the immune signatures enabled to stratify early-stage CRC patients with high risk of recurrence, highlighting the prognostic power of TILs.

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.

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.

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.

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.

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.

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.

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.