Towards a clinical consensus on the management of pregnancy and birth after laparoscopic and open myomectomy: A survey of obstetricians and gynaecologists.

OBJECTIVES: The primary aim was to assess if a clinical consensus regarding the management of pregnancy post myomectomy existed amongst consultant obstetricians and gynaecologists. Secondary objectives were to evaluate factors which influence the clinician's decision making in this group of women. STUDY DESIGN: Electronic survey sent to all consultants working in the North Central and East London deanery, Kent Surrey and Sussex deanery and Imperial NHS Trust to assess opinions on mode of birth post myomectomy, intervals advised to pregnancy post myomectomy, factors influencing the management of delivery in the scarred uterus post myomectomy, opinions on induction of labour and questions relating to operative notes. RESULTS: 209 consultant responses received between 07/03/2022-07/05/2022 (44% response rate); 77% (161/209) practicing obstetricians and gynaecologists, 10% (21/109) pure gynaecologists and 13% (27/209) pure obstetricians. The majority would support a vaginal birth after open myomectomy (75%) and laparoscopic myomectomy (79%). No consensus was found as to the optimal time interval between myomectomy and pregnancy. Higher frequency of performing myomectomy and a greater level of experience were significantly associated with a shorter interval to pregnancy advised. The most important operative factors influencing decision to support trial of labour post myomectomy were breach of uterine cavity; location of fibroids removed and number of incisions on the uterus. 77% believe women should be given a choice regarding mode of delivery post myomectomy in a similar way to previous LSCS. 82.8% would support enrolment of patients into a prospective trial to investigate delivery post myomectomy. CONCLUSIONS: We present a comprehensive survey of clinician opinions on pregnancy post myomectomy demonstrating that the majority of consultant obstetricians and gynaecologists sampled would support vaginal birth post myomectomy; counselling patients in a similar way to VBAC; a standardised myomectomy operation note and enrolment of patients in a future prospective trial. Wide variation in opinion regarding interval to pregnancy post myomectomy has been highlighted. We believe this information will facilitate counselling discussions and empower women with subsequent pregnancies after myomectomy to make an informed decision on mode of birth post myomectomy.

Laparoscopic management of a full-thickness uterine niche with subsequent pregnancy outcome.

BACKGROUND: Uterine niche is the consequence of impaired healing of the myometrium following a lower segment transverse caesarean section (CS). Although there is conflicting evidence on the management of these cases, laparoscopic repair is a commonly used surgical treatment modality. OBJECTIVES: To demonstrate the management and laparoscopic repair of the niche with subsequent pregnancy outcome. MATERIALS AND METHODS: We report a case of a 33-year-old patient who had a significant haematoma in the niche. The haematoma resolved after conservative management however, she remained symptomatic. Therefore, she had a laparoscopic repair. The narrated surgical video article demonstrates the dissection of the uterovesical fold overlying the niche, followed by the excision of the scar tissue and its repair with laparoscopic suturing. Ultrasound and magnetic resonance imaging images of the uterus demonstrating the haematoma at the caesarean section site, the niche after resolution of the haematoma and post-repair imaging are also provided. MAIN OUTCOME MEASURES: Repair of the niche, symptomatic relief of abnormal uterine bleeding, spontaneous conception and live birth. Ultrasonographic images also demonstrate uterine wall continuity post laparoscopic repair. RESULTS: The patient recovered uneventfully. Full-thickness of myometrium was demonstrated with post-operative imaging and confirmed at the subsequent caesarean section. Gynaecological symptoms resolved following the repair. The patient conceived spontaneously after surgery and delivered at term by caesarean section without any complications. CONCLUSION: Laparoscopic management of the niche should be considered where there is a complete myometrial defect or significant thinning of the myometrium, especially in symptomatic women who desire future pregnancy.

Overexpression of EPS8L3 promotes cell proliferation by inhibiting the transactivity of FOXO1 in HCC.

The homology of epidermal growth factor receptor pathway substrate 8 (EPS8), EPS8L3, is elevated significantly in hepatocellular carcinoma (HCC) tissues and cell lines compared with the normal liver tissues and cell lines. The MTT and colony formation assays demonstrated that overexpressing EPS8L3 enhances, while silencing reduces the proliferation of HCC cells. Further experiments illustrated that overexpressing EPS8L3 promotes the expression of p-AKT, Cyclin D1, but inhibits the transcriptional activity of FOXO1. Besides, colony formation assay demonstrated that AKT inhibitor suppresses the effect of EPS8L3 on proliferation in EPS8L3-overexpressing cells, whereas AKT restores the proliferation of EPS8L3-silenced cells, suggesting that EPS8L3 might promote proliferation by hyperactivating the AKT signaling pathway and subsequently inhibiting the FOXO1 transcriptional activity. Our results provide new view between EPS8L3 and progression of human HCC, suggesting that EPS8L3 may be a novel therapeutic target for HCC.

Ablation of Tacr2 in mice leads to gastric emptying disturbance.

BACKGROUND: Tacr2 is one of the G protein-coupled receptors(GPCRs) that mediate the biological actions of tachykinins. It is abundantly expressed in the gastrointestinal (GI) system and is thought to play an important role in GI motility, secretion, and visceral sensitivity. Previously, the physiological and pathophysiological functions of Tacr2 were mainly studied using Tacr2 selective agonists or antagonists. Here, we seek to investigate the effect of Tacr2 disruption in mice to provide further insights. METHODS: The Tacr2 knockout mice were generated by homologous recombination and the phenotypic changes of the Tacr2-null mice were analyzed and compared with their wild type (wt) littermates. KEY RESULTS: Increased food retention was detected in Tacr2-/- mice. The stomach of Tacr2-/- mice had thinner muscularis externa and less neurons in the myenteric plexus. The stomach and small intestine exhibited longer duration of electrical field stimulation (EFS)-induced inhibition in the gastric fundus and decreased frequency of migrating motor complex (MMC), respectively. Neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP) were significantly up-regulated due to Tarc2 deficiency, contributing to enhanced nitric oxide (NO) signaling in the stomach of Tacr2-/- mice. Intraperitoneal application of 7-nitroindazole (7-NI) to Tacr2-/- mice effectively relieved the gastric emptying disturbance. Moreover, Creb and NF-κB signalings were involved in the regulation of these physiological changes initiated by Tacr2 deficiency. CONCLUSIONS & INFERENCES: Tacr2 negatively regulated the expression of nNOS and VIP both in vivo and in vitro. Its ablation in mice elevated the expression of nNOS and VIP, enhanced NO signaling and changed the Creb and NF-κB signalings, finally leading to the gastric emptying disturbance of Tacr2-/- mice.

Joint effects between urinary selenium and polymorphisms in methylation related genes on breast cancer risk.

The aim of this study was to explore the associations of urinary selenium and polymorphisms in methylation related genes with breast cancer risk and the interactions on the risk. The present study involved in 240 female patients with incident breast cancer and 246 age-matched controls in two affiliated hospitals of Sun Yat-sen University in Guangzhou, China, from October 2009 to July 2010. DNMT1 rs2228611, MTHFR rs1801133, and MTR rs1805087 were genotyped using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry platform. Urinary concentration of selenium was measured by inductively coupled plasma mass spectrometry. Women with urinary selenium in the second tertile had a significant reduced breast cancer risk compared to those with urinary selenium in the lowest tertile [OR (95%CI): 0.50 (0.30, 0.81)]. DNMT1 rs2228611, MTHFR rs1801133, and MTR rs1805087 were not associated with breast cancer risk. Women with the third tertile of urinary selenium had a significant reduced breast cancer risk compared to those with the lowest tertile among women only with CC genotype [OR (95%CI): 0.55 (0.30, 1.00)] but not CT/TT genotypes [OR (95%CI): 1.58 (0.73, 3.42)] of MTHFR rs1801133 (P for interaction=0.044). Our results suggested that selenium was associated with a decreased risk of breast cancer and this beneficial effect was limited to women with CC genotype of MTHFR rs1801133.

Genistein upregulates placental corticotropin-releasing hormone expression in lipopolysaccharide-sensitized mice.

Genistein is a phytoestrogen isolated from soya beans. Although soy products are staple food of Asian, the potential effect of genistein on reproduction has not been fully addressed. Lipopolysaccharide (LPS) is an endotoxin found in the cell membrane of gram-negative bacteria. It may cause inflammation and other immune responses. Previous study has shown that LPS may induce pre-mature birth in rodents. In the present study, effect of genistein on LPS-induced preterm birth was investigated. Pregnant ICR mice were gavaged with genistein at 40, 200 and 400 mg/kg body weight/day during E13 to E16. LPS was injected i.p. on E16.5 and the animals were sacrificed at E17. Compared to the control group, an increased incidence of early delivery was observed in the pooled mice under LPS treatment. A rising trend of incidence was also demonstrated dose-dependently with genistein co-treatment. Real-time RT-PCR indicated that the placental crh expression was highly induced by the co-administration of 400 mg/kg genistein and LPS. By contrast, neither genistein nor LPS alone could alter the expression. Increased plasma CRH concentration was also seen in the co-treatment groups. In addition, the mRNA expression of placental CRH-binding protein and plasma progesterone concentration were reduced in these groups. These results indicated that genistein might exacerbate the undesirable effect of LPS on pregnant mice by altering hormonal regulations.

Incidence of right-sided colorectal cancer after breast cancer: a population-based study.

OBJECTIVES: Estrogen levels, which are involved in the development of breast cancer, may also be responsible for a higher incidence of right-sided colorectal neoplasia in women. Our objective was to determine the incidence of right-sided colorectal cancer (CRC) after the diagnosis of breast cancer. METHODS: All cases of breast cancers diagnosed between 1956 and 2006 were identified from the Manitoba Cancer Registry (MCR) and followed up until the diagnosis of any invasive cancer, death, migration out of the province, or 31 December 2006. Standardized incidence ratios (SIRs) for all CRC and right-sided CRC (cecum, ascending colon, and hepatic flexure) were calculated to compare the observed CRC incidence with that expected in the general population. Stratified analysis was performed to determine the risk at different follow-up time intervals, age at breast cancer diagnosis, and for tamoxifen use. RESULTS: There were 23,377 cases of breast cancer diagnosed between 1956 and 2006 with a total follow-up of 221,364 patient-years. The SIR for all CRC was 0.96 (95% confidence interval (CI) 0.87-1.06) and for right-sided CRC it was 1.02 (95% CI 0.87-1.20). The SIRs remained close to unity at different time intervals, for different age groups, and in analysis restricted to more recent years (1985-2006). Tamoxifen use did not alter the risk of all CRC (SIR 1.22; 95% CI 0.92-1.62) or right-sided CRC (SIR 0.90; 95% CI 0.48-1.54). CONCLUSIONS: There is no increase in the overall risk for CRC or for right-sided CRC after the diagnosis of breast cancer. CRC screening strategy for breast cancer survivors should be similar to that for the general population.

Molecular characterization of the developmental gene in eyes: through data-mining on integrated transcriptome databases.

OBJECTIVES: Our aim was to utilize publicly available and proprietary sources to discover candidate genes important for ocular development. DESIGN AND METHODS: The collated information on our 5092 non-redundant clusters was grouped and functional annotation was conducted using gene ontology (FatiGO) for categorizing them with respect to molecular function. The web-based viewer technological platform (H-InvDB) was employed for transcription analyses of in-house high quality fetal eye Expressed Sequence Tags (ESTs). Eye-specific ESTs were also analyzed across species by using EMBEST. RESULTS: According to adult eye cDNA libraries, nucleic acid binding and cell structure/cytoskeletal protein genes were the most abundant among the ESTs of fetal eyes. Using cDNA assembly in H-InvDB, 20 (80%) of the 25 most commonly expressed genes in the human eye are also expressed in extraocular tissues. The crystalline gamma S gene is highly expressed in the eye, but not in other tissues. We used EMBEST to compare human fetal eye and octopus eye ESTs and the expression similarity was low (1.6%). This indicated that our fetal eye library contains genes necessary for the developmental process and biological function of the eye, which may not be expressed in the fully developed octopus eyes. The human fetal eye cDNA library also contained highly abundant eye tissue genes, including alphaA-crystallin, eukaryotic translation elongation factor 1 alpha 1 (EEF1A1), bestrophin (VMD2), cystatin C, and transforming growth factor, beta-induced (BIGH3). CONCLUSIONS: Our annotated EST set provides a valuable resource for gene discovery and functional genomic analysis. This display will help to appreciate the strengths and weaknesses of the different technological platforms, so that in future studies the maximum amount of beneficial information can be derived from the appropriate use of each method.

The cellular mismatch repair system is able to repair mismatches within MLV retroviral double-stranded DNA at a low frequency.

Eukaryotic cells possess several distinct mismatch repair pathways. A mismatch can be introduced in retroviral double-stranded DNA by a pre-existing mutation within the primer binding site (PBS) of the viral RNA genome. In order to evaluate mismatch repair of retroviral double-stranded DNA, Moloney leukemia virus (MLV)-based vectors with a mutation in their PBS were used to infect mismatch repair-competent as well as mismatch repair-deficient cell lines. If the target cells were capable of repairing the mismatch before an infected cell divided, the mismatch within the PBS could be repaired to the wild-type or mutant PBS. If the target cells were unable to repair the mismatch, half the cells in the colony should contain the mutant PBS while the other half should contain the wild-type PBS. To evaluate these predictions, individual colonies were isolated and analyzed by PCR. Almost all mismatch-deficient cell colonies analyzed (cell lines HCT 116 and PMS2-/-) contained both the wild-type and mutated PBS, therefore, mismatches within retroviral double-strand DNA could not be repaired by the mismatch-deficient cells. In contrast, mismatches in approximately 25% of the mismatch repair-competent cell clones analyzed (cell lines HeLa and PMS2+/+) were repaired, while 75% were not. Therefore, the cellular mismatch repair system is able to repair mismatches within viral double-stranded DNA, but at a low frequency.

Most retroviral recombinations occur during minus-strand DNA synthesis.

Retroviral RNA molecules are plus, or sense in polarity, equivalent to mRNA. During reverse transcription, the first strand of the DNA molecule synthesized is minus-strand DNA. After the minus strand is polymerized, the plus-strand DNA is synthesized using the minus-strand DNA as the template. In this study, a helper cell line that contains two proviruses with two different mutated gfp genes was constructed. Recombination between the two frameshift mutant genes resulted in a functional gfp. If recombination occurs during minus-strand DNA synthesis, the plus-strand DNA will also contain the functional sequence. After the cell divides, all of its offspring will be green. However, if recombination occurs during plus-strand DNA synthesis, then only the plus-strand DNA will contain the wild-type gfp sequence and the minus-strand DNA will still carry the frameshift mutation. The double-stranded DNA containing this mismatch was subsequently integrated into the host chromosomal DNA of D17 cells, which were unable to repair the majority of mismatches within the retroviral double-strand DNA. After the cell divided, one daughter cell contained the wild-type gfp sequence and the other daughter cell contained the frameshift mutation in the gfp sequence. Under fluorescence microscopy, half the cells in the offspring were green and the other half of the cells were colorless or clear. Thus, we demonstrated that more than 98%, if not all, retroviral recombinations occurred during minus-strand DNA synthesis.

Mortality trends of elderly people in Taiwan from 1974 to 1994.

BACKGROUND: the hypothesis that disability and death will eventually be compressed to a period late in life needs empirical confirmation. OBJECTIVES: we have examined the secular trends of life expectancy and common causes of death in the aged population of Taiwan. METHOD: we compared the life expectancy, causes of death and probability of death for people at birth, at age 65 and at age 85 for both sexes from 1974 to 1994 using data from Taiwan government statistics. RESULTS: there has been a substantial gain in life expectancy, especially for men age 85 and over, in the past 20 years. . Mortality due to stroke, ischaemic heart disease, hypertension and chronic pulmonary disease has declined. There has been a steep increase in cancer deaths and deaths associated with diabetes mellitus. Tuberculosis and injury-related deaths have declined but pneumonia deaths have increased. For elderly people, the probability of dying from cancer and ischaemic heart disease increased with time. However, the probability of dying from stroke decreased. Although there was a decrease in probability of deaths associated with falls, there was an increase of deaths due to 'frailty' (as judged by falls, pneumonia and septicaemia). CONCLUSIONS: cancer is a major cause of death in the elderly population of Taiwan. This rapidly expanding elderly population seemed to suffer from poorer health in the later period of their life.

Screening of depression in patients with chronic medical diseases in a primary care setting.

BACKGROUND: Patients with chronic medical diseases may have depression that is not recognized by their primary care physicians. OBJECTIVES: We aimed to examine the application of Zung's Self-Rating Depression Scale (SDS) in the screening of depression in primary care patients with chronic medical diseases in a Chinese population. METHODS: We studied 268 patients with chronic medical diseases in the Family Medicine Outpatient Clinic using a structured questionnaire including basic demographic data, a Chinese version of the SDS and a rating for the self-perceived severity of physical condition. The severity of chronic medical diseases was assessed by the authors using the Duke University Severity of Illness Scale from a chart audit. Fifty patients were randomly selected for a diagnostic interview according to the DSM-IV criteria. The construct validity and internal consistency reliability, sensitivity and specificity of the SDS were examined. RESULTS: The results revealed that the SDS has good construct validity and internal consistent reliability in the evaluation of depression in Chinese patients with chronic medical diseases. A cut-off point of 55 had a sensitivity of 66.7% and a specificity of 90.0%. Depressed patients reported more cognitive symptoms than depressed affect and physical symptoms. Female patients had more severe depressed affect than male patients, but males had more prominent diurnal variation of mood than females. CONCLUSIONS: We concluded that SDS can be a good screening tool for depression in Chinese patients with chronic medical diseases. Owing to constraints in the expression of sexual desire in the Chinese, elderly subjects tended to report loss of libido in the response to the SDS.

Study of simplified measures for malaria surveillance in the late consolidation phase in China.

This paper presents the results of a study on simplified surveillance methods conducted in 23 pilot counties in 11 provinces and municipalities in China where reside 15 million people and malaria control has been in the late consolidation phase. Two simplified surveillance Schemes (A and B) taking treatment of clinical cases as the main measure were implemented in 1992-1994. The rate of annual blood examination for case detection was 1.0% in pilot Scheme A, while in areas of scheme B it was 0.3%. The implementation of both Scheme A and Scheme B, simplified or without treatment of infection foci and management of mobile populations, acquired satisfactory effects against malaria. Consequently, malaria incidence was declining steadily, only a few indigenous and introduced cases were detected. The parasite rate in residents and the IFA positive rate in children were very low. The results of pilot studies and cost-effectiveness analysis indicated that Scheme B is effective, rational and economic, and can be implemented to replace the routine surveillance measures in areas where malaria has been at the late consolidation phase in China.

[Growth capability of epithelial cell line of human poorly differentiated nasopharyngeal carcinoma and its response to Chinese medicinal herbs and marine drugs].

By 3H-TdR incorporation, dye exclusion and cell colony-forming tests, the capability of short-term in vitro growth of the epithelial cell line of human poorly differentiated nasopharyngeal carcinoma (CNE-2Z) was assayed. At the same time, its response to 54 kinds of Chinese medicinal herbs and marine drugs was studied. The results showed that the 3H-TdR incorporation rate of cells was 1.8 +/- 0.02%, reproduction rate was 60.9 +/- 13.0% and colony-forming rate, 40.8 +/- 3.5%. As to the ratios of the three cell growth indexes and response to medicines, the Chinese medicinal herbs and marine drugs causing the reduction of colony-forming and cell survival ratios were predominant (64.8% and 40.7%). The results indicate that the majority of drugs possess the cytotoxic and inhibitory effect on cell reproduction to different degrees. The composite cell response to every kind of drug could be divided into 6 types: descending, ascending, peaked, valley-like, depressed and stable. The depressing type drugs might inhibit or arrest the cell growth of nasopharyngeal carcinoma and are worthy of further study.