Ovarian clear cell carcinoma with uterine intramural recurrence: Case report of ovarian clear cell carcinoma with fertility sparing treatment.

OBJECTIVE: Ovarian clear cell carcinoma has a poor prognosis in comparison with other pathological types of epithelial ovarian carcinoma. It also has relative resistance to first-line platinum-based chemotherapy with a great risk of recurrence. CASE REPORT: We report a case of recurrent ovarian clear cell carcinoma status after left salpingo-oophorectomy (fertility-sparing debulking operation) and six courses of adjuvant chemotherapy (paclitaxel (175 mg/m2)/carboplatin (AUC 6)). However, two years after diagnosis, elevated CA-125 accompanied by an intrapelvic mass was noted. Uterine intramural recurrence was found during the second laparotomy. She was treated with right salpingo-oophorectomy and abdominal hysterectomy combined with systemic chemotherapy administration (paclitaxel (175 mg/m2)/carboplatin (AUC 6)) and maintenance therapy (bevacizumab (7.5 mg/kg)). There was no other recurrence until one and a half years postoperatively, and the patient was tumor free with regular follow-up. CONCLUSION: In young patients with stage I ovarian clear cell carcinoma, fertility-sparing surgery was considered. Most patients will suffer from tumor recurrence, and also intrauterine recurrence rarely happen.

Cervical pregnancy: a case report of hysteroscopic resection and balloon compression combined with systematic methotrexate treatment.

OBJECTIVE: Cervical pregnancy is a rare type of ectopic pregnancy. When the pregnancy is terminated, it will sometimes lead to persistent bleeding. In some cases, hysterectomy is inevitable and the patient loses fertility. Therefore, early diagnosis and targeted management with systemic or local injection of methotrexate is the first-line treatment. Multiple interventions of cervical pregnancy were used to prevent massive hemorrhage, including dilatation and curettage, laparoscopic resection, hysteroscopic resection combined with uterine artery embolization, or uterine artery clip. CASE REPORT: We report a case of cervical pregnancy with a high beta-hCG level accompanied by a visible fetal heartbeat that was successfully treated with hysteroscopic cervical tissue resection and balloon compression combined with systemic administration of methotrexate. CONCLUSION: Efficacy and safety with preserved fertility were important issues in the management of cervical pregnancy. We provide a safe, simple and effective treatment of cervical pregnancy.

A Novel GaN:C Millimeter-Wave HEMT with AlGaN Electron-Blocking Layer.

An AlGaN/GaN/Si high electron mobility transistor (HEMT) using a GaN:C buffer with a 2 nm AlGaN electron-blocking layer (EBL) is investigated for the first time for millimeter-wave applications. Compared with the double heterostructure field effect transistor (DHFET), the AlGaN/GaN HEMT with the GaN:C/EBL buffer has a lower vertical leakage, higher thermal stability, and better RF performance. In addition, AlGaN EBL can prevent carbon-related traps from GaN:C and improve electron confinement in 2DEG during high-frequency operation. Finally, a Pout of 31.2 dBm with PAE of 21.7% were measured at 28 GHz at 28 V. These results demonstrated the great potential of HEMTs using GaN:C with AlGaN EBL epitaxy technology for millimeter-wave applications.

Uterine leiomyoma is associated with the risk of developing endometriosis: A nationwide cohort study involving 156,195 women.

OBJECTIVE: Evidence for an association between uterine leiomyoma and increased risk of endometriosis is limited by small sample sizes and short follow-up periods. We assessed this association in a large nationwide sample with 14 years of data. DESIGN: Data were sourced from Taiwan's Longitudinal Health Insurance Database 2000 (LHID2000). MATERIALS AND METHODS: We identified 31,239 women aged ≥20 years diagnosed with uterine leiomyoma (International Classification of Disease, Ninth Revision, Clinical Modification [ICD-9-CM] code 218) between Jan 1, 2000 and Dec 31, 2012, who were matched with 124,956 controls (1:4) by 5-year age groups and year of diagnosis. Follow-up was from the date of LHID2000 entry to the first occurrence of endometriosis, loss to follow-up, insurance termination, or until December 31, 2013, whichever was earlier. RESULTS: In Cox regression analysis, the adjusted hazard ratio (aHR) for endometriosis in women with uterine leiomyoma was 6.44 (95% CI, 6.18, 6.72) compared with controls. The risk of endometriosis was significantly increased in women with uterine leiomyoma and comorbidities of tube-ovarian infection (aHR 2.86; 95% CI, 1.28, 6.36), endometritis (1.14; 1.06, 1.24), infertility (1.26; 1.16, 1.37), or allergic diseases (1.11; 1.05, 1.17). Having both uterine leiomyoma and endometritis significantly increased the risk of endometriosis (aHR 6.73; 95% CI, 6.07, 7.45) versus having only uterine leiomyoma (6.61; 6.33, 6.91) or endometritis (1.49; 1.31, 1.69). Similarly, having both uterine leiomyoma and infertility significantly increased the risk of endometriosis (aHR 6.95; 95% CI, 6.21, 7.78) versus having only uterine leiomyoma (6.66; 6.38, 6.96) or infertility (1.78; 1.57, 2.02). CONCLUSIONS: A diagnosis of uterine leiomyoma appears to increase the risk of endometriosis. Patients presenting with uterine fibroids should be encouraged to give informed consent for possible simultaneous surgical treatment of endometriosis.

Transcriptome Analysis of Dnmt3l Knock-Out Mice Derived Multipotent Mesenchymal Stem/Stromal Cells During Osteogenic Differentiation.

Multipotent mesenchymal stem/stromal cells (MSCs) exhibit great potential for cell-based therapy. Proper epigenomic signatures in MSCs are important for the maintenance and the subsequent differentiation potential. The DNA methyltransferase 3-like (DNMT3L) that was mainly expressed in the embryonic stem (ES) cells and the developing germ cells plays an important role in shaping the epigenetic landscape. Here, we report the reduced colony forming ability and impaired in vitro osteogenesis in Dnmt3l-knockout-mice-derived MSCs (Dnmt3l KO MSCs). By comparing the transcriptome between undifferentiated Dnmt3l KO MSCs and the MSCs from the wild-type littermates, some of the differentially regulated genes (DEGs) were found to be associated with bone-morphology-related phenotypes. On the third day of osteogenic induction, differentiating Dnmt3l KO MSCs were enriched for genes associated with nucleosome structure, peptide binding and extracellular matrix modulation. Differentially expressed transposable elements in many subfamilies reflected the change of corresponding regional epigenomic signatures. Interestingly, DNMT3L protein is not expressed in cultured MSCs. Therefore, the observed defects in Dnmt3l KO MSCs are unlikely a direct effect from missing DNMT3L in this cell type; instead, we hypothesized them as an outcome of the pre-deposited epigenetic signatures from the DNMT3L-expressing progenitors. We observed that 24 out of the 107 upregulated DEGs in Dnmt3l KO MSCs were hypermethylated in their gene bodies of DNMT3L knock-down ES cells. Among these 24 genes, some were associated with skeletal development or homeostasis. However, we did not observe reduced bone development, or reduced bone density through aging in vivo. The stronger phenotype in vitro suggested the involvement of potential spreading and amplification of the pre-deposited epigenetic defects over passages, and the contribution of oxidative stress during in vitro culture. We demonstrated that transient deficiency of epigenetic co-factor in ES cells or progenitor cells caused compromised property in differentiating cells much later. In order to facilitate safer practice in cell-based therapy, we suggest more in-depth examination shall be implemented for cells before transplantation, even on the epigenetic level, to avoid long-term risk afterward.

Twin reversed arterial perfusion syndrome in a monochorionic monoamniotic twin pregnancy.

OBJECTIVE: Twin-Reversed Arterial Perfusion (TRAP) sequence is a rare complication of monochorionic multiple gestation. Conservative management should be considered if there is no poor prognostic factor. CASE REPORT: This is a 35 year-old female with twin pregnancy with acardiac monster. Under the request of the patient, there was no intervention during the whole pregnancy. We keep regular and close sonography weekly follow up. There was no maternal complication and there was also no heart failure sign or polyhydramnios of the donor twin. Minimal blood flow was noted at the anastomotic vessels under the sonography at late gestational age. Due to breech presentation, cesarean section was performed at gestational age 37 + 1/7 weeks. She delivers a healthy baby smoothly. CONCLUSION: Antenatal sonography is an important tool to evaluate the fetus status. Under special condition, term pregnancy is still possible without any treatment. CASE REPORT: Twin reversed arterial perfusion syndrome in a monochorionic monoamniotic twin pregnancy.

Surgical outcomes of hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) compared with laparoscopic total hysterectomy (LTH) in women with non-prolapsed and benign uterine diseases.

OBJECTIVE: We aimed to compare the surgical outcomes between hysterectomy by transvaginal natural orifice transluminal endoscopic surgery (vNOTES) and laparoscopic total hysterectomy (LTH). MATERIALS AND METHODS: This study is a retrospective chart analysis. From January 1, 2015, to December 31, 2017, a total of 183 patients of reproductive age with an indication for hysterectomy due to non-prolapsed and benign uterine diseases were enrolled. After exclusion, 20 patients were included in the vNOTES group, and 66 patients were included in the LTH group. Various post-operative surgical outcomes such as operative time, blood loss, uterus weight, a decrease in hemoglobin level on post-operative day one, post-operative pain scale, complications, length of hospitalization, and re-admission rate were measured. RESULTS: No difference was observed between both groups regarding operative time, blood loss, uterine weight, a decrease in hemoglobin level on post-operative day one, complications, hospital stay, and re-admission rate. Patients in the vNOTES group had significantly less post-operative pain compared with those in the LTH group (p = 0.03). CONCLUSIONS: The surgical outcomes of hysterectomy by vNOTES could be similar to those of LTH. Patients undergoing hysterectomy by vNOTES may have less post-operative pain compared with those undergoing LTH. However, the sample size was small, and the results need more evidence to confirm these findings.

Transient DNMT3L Expression Reinforces Chromatin Surveillance to Halt Senescence Progression in Mouse Embryonic Fibroblast.

Global heterochromatin reduction, which is one of the hallmarks of senescent cells, is associated with reduced transposable element repression and increased risk of chromatin instability. To ensure genomic integrity, the irreparable cells in a population exit permanently from the cell cycle, and this process is termed "senescence." However, senescence only blocks the expansion of unwanted cells, and the aberrant chromatin of senescent cells remains unstable. Serendipitously, we found that the transient ectopic expression of a repressive epigenetic modulator, DNA methyltransferase 3-like (DNMT3L) was sufficient to delay the premature senescence progression of late-passage mouse embryonic fibroblasts (MEFs) associated with a tightened global chromatin structure. DNMT3L induces more repressive H3K9 methylation on endogenous retroviruses and downregulates the derepressed transposons in aging MEFs. In addition, we found that a pulse of ectopic DNMT3L resulted in the reestablishment of H3K27me3 on polycomb repressive complex 2 (PRC2)-target genes that were derepressed in old MEFs. We demonstrated that ectopic DNMT3L interacted with PRC2 in MEFs. Our data also suggested that ectopic DNMT3L might guide PRC2 to redress deregulated chromatin regions in cells undergoing senescence. This study might lead to an epigenetic reinforcement strategy for overcoming aging-associated epimutation and senescence.

Patients with uterine leiomyoma exhibit a high incidence but low mortality rate for breast cancer.

The association of uterine leiomyoma with increased risk of breast cancer is controversial. Therefore, we used the National Health Insurance Research Database of Taiwan to examine breast cancer incidence and mortality among Asian patients with and without uterine leiomyoma. We compared breast cancer incidence and mortality between 22,001 newly diagnosed uterine leiomyoma patients and 85,356 individuals without uterine leiomyoma matched by age and date of diagnosis. Adjusted hazard ratios for breast cancer were estimated using the Cox model. The incidence of breast cancer was 35% higher in the uterine leiomyoma group than the leiomyoma-free group (1.65 vs. 1.22 per 1,000 individuals, p < 0.001), with an adjusted hazard ratio of 1.31 (95% confidence interval = 1.13-1.52). Interestingly, overall mortality was lower (4.12%) in the uterine leiomyoma group (mean followed time, 3.59 ± 2.70 years) than the leiomyoma-free group (8.78%; mean followed time, 3.54 ± 2.67 years) at the endpoint of the study (p <0.05). These findings indicate the incidence of breast cancer is higher in patients with uterine leiomyoma than in those without it, but overall mortality from breast cancer was lower in the patients with uterine leiomyoma.

Risk of depression in patients with uterine leiomyoma: A nationwide population-based cohort study.

BACKGROUND: Population-based cohort study investigating the depression risk for patients with uterine leiomyoma (UL) is unavailable. This study investigated the subsequent risk of depression among patients with UL in an Asian population. METHODS: Using data from the National Health Insurance Research Database of Taiwan, we established a cohort with 21,168 patients diagnosed with UL between 2000 and 2010, and a non-UL cohort of 82,108 women without UL matched by age and year of diagnosis. The occurrence of depression and Cox method measured adjusted hazard ratios (aHRs) were monitored until the end of 2011. The depression risk altered by surgery was also evaluated. RESULTS: The overall incidence of depression was 54% higher in the UL cohort than in the non-UL cohort (7.48 vs. 4.88/1000 person-years, p<0.001), with an aHR of 1.46 [95% confidence interval (CI)=1.36-1.57] for the UL cohort. The depression risk increased with age and with comorbidity in both cohorts. Surgical intervention reduced the depression incidence to 4.76/1000 person-years for women with UL, with an aHR of 0.64 (95% CI=0.51-0.81) compared with those without a surgical treatment. CONCLUSION: The risk of depression is significantly higher in patients with UL than in those without UL. Surgical intervention for UL could significantly reduce the risk of depression. Evaluation of psychiatric status in patients with UL is strongly recommended.

New insights into Keggin-type 12-tungstophosphoric acid from 31P MAS NMR analysis of absorbed trimethylphosphine oxide and DFT calculations.

The acid and transport properties of the anhydrous Keggin-type 12-tungstophosphoric acid (H(3)PW(12)O(40); HPW) have been studied by solid-state (31)P magic-angle spinning NMR of absorbed trimethylphosphine oxide (TMPO) in conjunction with DFT calculations. Accordingly, (31)P NMR resonances arising from various protonated complexes, such as TMPOH(+) and (TMPO)(2)H(+) adducts, could be unambiguously identified. It was found that thermal pretreatment of the sample at elevated temperatures (≥423 K) is a prerequisite for ensuring complete penetration of the TMPO guest probe molecule into HPW particles. Transport of the TMPO absorbate into the matrix of the HPW adsorbent was found to invoke a desorption/absorption process associated with the (TMPO)(2)H(+) adducts. Consequently, three types of protonic acid sites with distinct superacid strengths, which correspond to (31)P chemical shifts of 92.1, 89.4, and 87.7 ppm, were observed for HPW samples loaded with less than three molecules of TMPO per Keggin unit. Together with detailed DFT calculations, these results support the scenario that the TMPOH(+) complexes are associated with protons located at three different terminal oxygen (O(d)) sites of the PW(12)O(40)(3-) polyanions. Upon increasing the TMPO loading to >3.0 molecules per Keggin unit, abrupt decreases in acid strength and the corresponding structural variations were attributed to the change in secondary structure of the pseudoliquid phase of HPW in the presence of excessive guest absorbate.

Prevalence of psychiatric morbidity and psychological adaptation of the nurses in a structured SARS caring unit during outbreak: a prospective and periodic assessment study in Taiwan.

To assess the rapidly changing psychological status of nurses during the acute phase of the 2003 SARS outbreak, we conducted a prospective and periodic evaluation of psychiatric morbidity and psychological adaptation among nurses in SARS units and non-SARS units. Nurse participants were from two SARS units (regular SARS [N=44] and SARS ICU [N=26]) and two non-SARS units (Neurology [N=15] and CCU [N=17]). Participants periodically self-evaluated their depression, anxiety, post-traumatic stress symptoms, sleep disturbance, attitude towards SARS and family support. Results showed that depression (38.5% vs. 3.1%) and insomnia (37% vs. 9.7%) were, respectively, greater in the SARS unit nurses than the non-SARS unit nurses. No difference between these two groups was found in the prevalence of post-traumatic stress symptoms (33% vs. 18.7%), yet, three unit subjects (SARS ICU, SARS regular and Neurology) had significantly higher rate than those in CCU (29.7% vs. 11.8%, respectively) (p<0.05). For the SARS unit nurses, significant reduction in mood ratings, insomnia rate and perceived negative feelings as well as increasing knowledge and understanding of SARS at the end of the study (all p<0.001) indicated that a gradual psychological adaptation had occurred. The adjustment of nurses in the more structured SARS ICU environment, where nurses care for even more severely ill patients, may have been as good or better than that of nurses in the regular SARS unit. Occurrence of psychiatric symptoms was linked to direct exposure to SARS patient care, previous mood disorder history, younger age and perceived negative feelings. Positive coping attitude and strong social and family support may have protected against acute stress. In conclusion, the psychological impact on the caring staffs facing future bio-disaster will be minimized with lowered risk factors and a safer and more structured work environment.