13 research outputs found
AI is a viable alternative to high throughput screening: a 318-target study
: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery
Salpingectomy and prevention of ovarian carcinoma
Advanced cases of epithelial, primary peritoneal, and primary tubal malignancies have relative poor prognosis and collectively remain the most deadly of all gynecologic malignancies. Recently, many studies have demonstrated that the fallopian tubes might be the origin of most high grade ovarian and peritoneal serous carcinoma. In this review, we describe the tubal carcinogenic pathway with the precancerous tubal lesions and the impact of salpingectomy for prevention of ovarian carcinoma
Laparoscopic management of bladder ectopic pregnancy
Ectopic pregnancy is a potentially life-threatening condition and still the major cause of maternal mortality in the first trimester of pregnancy. It accounts for approximately 10% of maternal deaths. The involvement of the urinary tract is rare, usually occurring after the rupture of an abdominal implanted ectopic embryonic sac. We herein present a case of an ectopic pregnancy implanted in the bladder and successful laparoscopic management. To the best of our knowledge, this is the first description of abdominal pregnancy on the bladder wall in a natural cycle and successful laparoscopic management
Power morcellation—An emerging risk complicating minimally invasive surgery for uterine mesenchymal neoplasms
Study objective: To determine the local incidence and clinical consequences of myoma, after intraperitoneal dissemination via morcellation.
Materials and methods: An electronic search for laparoscopic myomectomies in the computer database of the KK Women's and Children's Hospital (Singapore) and sarcomas or myomata with atypical features in the National Cancer Registry (Singapore) was performed for a 10-year study period. The identified patients had their medical records were traced and their data were extracted and studied in detail.
Results: The incidence of unexpected diagnosis (i.e., variants, atypia, and malignancy) was 0.23%, and the incidence of unexpected sarcoma was 0.10%. One of four patients who underwent a subsequent laparotomy had peritoneal dissemination. She unfortunately was also the only mortality in this study.
Conclusion: Laparoscopic surgery had proven benefits over open surgery, although the dissemination of unexpected malignancy and extrauterine seeding were major concerns. To date, morcellation in the endobag or cutting the specimen using a knife or scissors may be alternative surgical techniques
Endometriosis: A review of the diagnosis and pain management
Endometriosis is characterized by the presence of endometrial tissues outside the uterus. It affects females in their reproductive years, and may be an estrogen-dependent condition. The estimated prevalence of endometriosis in the general population is as high as 10%, and is increased in females with subfertility. The diagnosis of endometriosis is usually suspected clinically and confirmed by transvaginal ultrasound or magnetic resonance imaging of the pelvis. The gold standard of diagnosis is surgical visual inspection of the pelvic organs by an experienced surgeon during laparoscopy. A positive histology will confirm the diagnosis; however, a negative histology does not exclude it. Serum cancer antigen-125 levels may be increased in women with endometriosis, however, it is a poor diagnostic tool in comparison to laparoscopy. The management of endometriosis is dependent on whether the primary problem is pain or subfertility. The primary objectives of an intervention include removing endometriotic implants, removing nodules or cysts, restoring normal anatomy, reducing disease progression, and providing symptomatic relief. Treatment must be individualized and take into consideration the impact of the condition on quality of life. This may require a multidisciplinary approach that involves a pain clinic and counseling services
Single incision laparoscopic surgery in gynecology: Evolution, current trends, and future perspectives
Minimally invasive surgery has become the standard of care for different procedures in various subspecialties. Single-incision laparoscopic surgery (SILS) is a rapidly developing field that may mark the new frontier in laparoscopy. The ongoing and continuous efforts to decrease morbidity and improve cosmesis from laparoscopic surgery has led to minimization in number and size of ports required for these procedures. SILS is laparoscopic surgery performed through a single, small skin incision 15-20 mm in size, usually hidden in the umbilicus. SILS is not a new endeavor, but recent advances in conventional laparoscopic techniques and instrumentation has made SILS more feasible and safer for patients. Within a short span of time there has been an increase in the number of studies and clinical reports depicting the use of SILS in gynecology. As this novel field moves forward, a review of its evolution and current status is requisite. The objective of this article is to review the contemporary literature on SILS in gynecology and the recent advances in techniques and instrumentation used in SILS. The ongoing refinement of surgical techniques and instrumentation has resulted in increasing use of SILS across many subspecialties. Recently published studies have proven the feasibility, safety, and reproducibility of SILS in various gynecologic procedures
Pregnancy Outcomes in HIV-Positive Women in Singapore
Singapore had her first HIV patient tested sero-positive in 1985. Ever since then, the number of new patients being diagnosed has been on the uprising trend. Based on the current evidences in the literature, we look at how our local practice should be positioned. The objective is to study the general profile of all HIV-positive women in Singapore and to compare the difference in vertical transmission rate between women with very low viral count i.e. < 50 copies/ml who underwent caesarean section and normal vaginal deliveries. Also with proper intrapartum and postpartum advice and care, we look at the outcome of unbooked pregnancies. A ten-year retrospective review of HIV-positive women who delivered in KK Women's & Children's Hospital (Singapore) was conducted. All case notes were reviewed and data was collected and analysed using Microsoft Excel. A total of 75 deliveries by 67 women were identified. Four neonates were tested HIV-positive, amounting to a vertical transmission rate of 5.3%. Of the 12 women who were found to have viral counts of less than 50 copies/ml before their deliveries, four underwent normal vaginal deliveries while eight underwent caesarean sections. All babies were tested HIV-negative. Among the five unbooked pregnancies and two pregnancies that were booked at term, one neonate was found to be positive (14.3%). There is no difference in perinatal transmission in women with very low viral count irrespective of the mode of delivery. For those women with unbooked pregnancies, proper intrapartum care, neonatal anti-retroviral therapy together with avoidance of breastfeeding reduces vertical transmission rate and improves neonatal outcome
Limited value of pro-inflammatory oxylipins and cytokines as circulating biomarkers in endometriosis--a targeted ‘omics study
Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial-like tissues at extrauterine sites. Elevation in protein and lipid mediators of inflammation including oxylipins and cytokines within the peritoneum characterize the inflamed pelvic region and may contribute to the survival and growth of displaced endometrial tissues. The presence of a clinically silent but molecularly detectable systemic inflammation in endometriosis has been proposed. Thus, we examined serum oxylipin and immunomodulatory protein levels in 103 women undergoing laparoscopy to evaluate systematically any involvement in systemic pathophysiological inflammation in endometriosis. Oxylipin levels were similar between women with and without endometriosis. Stratification by menstrual phase or severity did not offer any difference. Women with ovarian endometriosis had significantly lower 12-HETE relative to peritoneal endometriosis (−50.7%). Serum oxylipin levels were not associated with pre-operative pain symptoms. Changes to immunomodulatory proteins were minimal, with IL-12(p70), IL-13 and VEGF significantly lower in mild endometriotic women compared to non-endometriotic women (−39%, −54% and −76% respectively). Verification using C-reactive protein as a non-specific marker of inflammation further showed similar levels between groups. The implications of our work suggest pro-inflammatory mediators in the classes studied may have potentially limited value as circulating biomarkers for endometriosis, suggesting of potentially tenuous systemic inflammation in endometriosis.Singapore. National Medical Research Council (NMRC/BNIG/2033/2015)SingHealth Foundation (SHF/FG560P/2014