Design and application of synthetic 17B-HSD13 substrates reveals preserved catalytic activity of protective human variants.

Several hydroxysteroid dehydrogenase 17-beta 13 variants have previously been identified as protective against metabolic dysfunction-associated steatohepatitis (MASH) fibrosis, ballooning and inflammation, and as such this target holds significant therapeutic potential. However, over 5 years later, the function of 17B-HSD13 remains unknown. Structure-aided design enables the development of potent and selective sulfonamide-based 17B-HSD13 inhibitors.

Multidisciplinary Obstetric Simulation Training: Experience at KK Women's and Children's Hospital (KKH), Singapore, a Tertiary Referral Centre.

Background Multidisciplinary simulation training in the management of acute obstetric emergencies has the potential to reduce both maternal and perinatal morbidity. It is a valuable tool that can be adapted for targeted audiences of different specialities at all experience levels from medical students to senior consultants. Methods In this study, pre- and post-course questionnaires of learners with varying levels of clinical experience from Obstetrics and Gynaecology (O&G), Anaesthesia, Neonatology, Emergency Medicine, midwifery, and nursing who undertook two simulation courses (namely the Combined Obstetrics Resuscitation Training course, CORE, and the CORE Lite), which comprised lectures and simulation drills with manikins and standardized patients, between 2015 and 2023 were compared.

Retrospective Study Comparing Treatment Outcomes in Obstetric Patients With Iron Deficiency Anemia Treated With and Without Intravenous Ferric Carboxymaltose.

Introduction Iron deficiency anemia is associated with an increased risk of adverse maternal and perinatal outcomes. Intravenous iron preparation containing ferric carboxymaltose has been shown to be a safe and effective way of increasing hemoglobin (Hb) and mean corpuscular volume (MCV) levels and reducing the need for blood transfusion. In our center, it used to be given as an inpatient procedure because of the risks of potential drug reactions.

Uterine Manipulation May Not Influence Ongoing Pregnancy: Case Report and Literature Review.

Abdominal pain is a very common presentation in early pregnancy. Its cause may be gynecological or totally nonpregnancy related. While acute appendicitis is the most common nonobstetric cause of pain in pregnant women, diagnosis and differentiation from other causes, including ectopic pregnancy, remain challenging.

Continuous Glucose Monitoring Feedback in the Subsequent Development of Gestational Diabetes: A Pilot, Randomized, Controlled Trial in Pregnant Women.

Objective: This study evaluated the effects of receiving glucose feedback from continuous glucose monitoring (CGM) by intermittent scanning (unblinded group), and CGM with masked feedback (blinded group) in the subsequent development of gestational diabetes mellitus (GDM).

Study Design: This was a prospective, single-center, pilot, randomized controlled trial including  = 206 pregnant women in the first trimester of pregnancy with no prior diagnosis of type 1 or type 2 diabetes. The participants were randomized into the unblinded group or blinded group and wore the CGM in the first trimester of pregnancy (9-13 weeks), the second trimester of pregnancy (18-23 weeks), and late-second to early-third trimester (24-31 weeks).

Design of Next-Generation DGAT2 Inhibitor PF-07202954 with Longer Predicted Half-Life.

Diacylglycerol O-acyltransferase 2 (DGAT2) inhibitors have been shown to lower liver triglyceride content and are being explored clinically as a treatment for non-alcoholic steatohepatitis (NASH). This work details efforts to find an extended-half-life DGAT2 inhibitor. A basic moiety was added to a known inhibitor template, and the basicity and lipophilicity were fine-tuned by the addition of electrophilic fluorines.

Management dilemma in Thoracoamniotic Shunt Migrations.

Shunt migration is a rare but significant complication of thoracoamniotic shunting, an intervention widely used for fetal pleural effusion. We describe a case of a term infant noted antenatally to have fetal hydrothorax that was managed with thoracoamniotic shunting but complicated by shunt migration. We also present the current literature on risk factors, complications and management of intrathoracic shunt migration.

Cesarean Scar Pregnancy: Current Understanding and Treatment Including Role of Minimally Invasive Surgical Techniques.

The incidence of cesarean scar pregnancy (CSP) is increasing reflecting the global increase in cesarean section (CS) rate which has almost doubled since 2000. CSP differs from other types of ectopic pregnancy in its ability to progress while still carrying a significant risk of maternal morbidity. Little is known about precise etiology or natural history although current interest in the pathology of placenta accretes spectrum disorders might be enlightening.

Scope and Suction: Hysteroscopic-guided Suction Evacuation of Cesarean Scar Pregnancy - A Safe and Efficacious Treatment for Selected Patients.

Objectives: This study aimed to evaluate hysteroscopic-guided suction evacuation for the treatment of cesarean scar pregnancy (CSP).

Materials And Methods: This was a retrospective analysis of CSP over 2 years. This study was conducted at KK Women's and Children's Hospital (KKH), Singapore, thirty-seven patients with a CSP.

Knowledge, Attitude and Perceptions Around Perinatal Mental Health Among Doctors in an Obstetrics and Gynaecology Academic Department in Singapore.

Background Frontline healthcare professionals who provide regular care to women in the antenatal and postnatal period play a critical role in the early detection and management of maternal perinatal mental health (PMH). This study aimed to assess the knowledge, attitudes, and perceptions of doctors around perinatal mental health in an obstetrics and gynaecology (O&G) department in Singapore. Methods Using an online survey, data was collected from 55 doctors who participated in the Doctor's Knowledge, Attitudes and Perceptions of Perinatal Mental Health (I-DOC) study.

Tranexamic acid, as an adjunct to oxytocin prophylaxis, in the prevention of postpartum haemorrhage in women undergoing elective caesarean section: A single-centre double-blind randomised controlled trial.

Objective: To evaluate the effectiveness of tranexamic acid (TXA) in reducing blood loss during elective caesarean sections in women with and without risk factors for postpartum haemorrhage (PPH).

Design: A double-blind, randomised placebo-controlled trial.

Setting: An academic tertiary referral centre in Singapore.

Conservative surgical approach towards placenta accreta spectrum disorders for uterine preservation.

Objective: We previously described a technique for repair of the myometrial defect at repeat Caesarean section which increases residual myometrial thickness thereby potentially reducing future niche-related complications. Here we describe how this technique can be modified for use for placenta accreta spectrum disorders, in line with emerging evidence that this is more a disorder of myometrial deficiency than morbid adherence.

Design: The surgical performance of peripartum hysterectomy was compared with that of the modified technique in all women having repeat Caesarean delivery for placenta accreta spectrum disorder in a tertiary unit in Singapore between December 2019 and October 2021.

Whooping cough complicating pulmonary hypertension in pregnancy.

We report a case of a previously fit woman who presented at 26 weeks into her fourth pregnancy with a dry cough. Following a nasopharyngeal swab, she was diagnosed with a infection, and treated with antibiotics. A chest X-ray showed right atrial dilatation and an echocardiogram was scheduled outpatient.

A comparison of antenatal prediction models for vaginal birth after caesarean section.

Introduction: An antenatal scoring system for vaginal birth after caesarean section (VBAC) categorises patients into a low or high probability of successful vaginal delivery. It enables counselling and preparation before labour starts. The current study aims to evaluate the role of Grobman nomogram and the Kalok scoring system in predicting VBAC success in Singapore.

Repair of the myometrial scar defect at repeat caesarean section: a modified surgical technique.

Background: To investigate whether the existing surgical technique for uterine closure at repeat lower segment Caesarean section (LSCS) can be modified to achieve adequate residual myometrial thickness (RMT) to ensure scar integrity and reduce complications in future pregnancy.

Methods: Women with a significant scar defect at repeat LSCS had the anterior uterine wall closed by a single experienced obstetrician with a technique focused on recognition, mobilisation and apposition of the retracted myometrial edges at the boundary of the defect. This was aimed at anatomical restoration of the lower segment.

Optimal first trimester HbA1c threshold to identify Singaporean women at risk of gestational diabetes mellitus and adverse pregnancy outcomes: A pilot study.

This pilot study examined the use of early HbA1c in screening for gestational diabetes mellitus and adverse pregnancy outcomes in Singapore. One hundred and fifty-one pregnant women with a gestational age of under 14 weeks had an HbA1c test measured with their antenatal bloods prior to a second trimester oral glucose tolerance test. Patient characteristics and pregnancy outcome data were collected.

Safety and Feasibility of Using Magnetic Resonance Imaging Criteria to Identify Patients With "Good Prognosis" Rectal Cancer Eligible for Primary Surgery: The Phase 2 Nonrandomized QuickSilver Clinical Trial.

Importance: Chemoradiotherapy (CRT), followed by surgery, is the recommended approach for stage II and III rectal cancer. While CRT decreases the risk of local recurrence, it does not improve survival and leads to poorer functional outcomes than surgery alone. Therefore, new approaches to better select patients for CRT are important.

Educational Models for the Re-Establishment of Dental Therapy Education in Canada.

With the closure of the Canadian dental therapy program in Saskatchewan in 2011 and the increasing need for oral health providers, there have been growing discussions at the national and provincial levels regarding the re-establishment of a provider with dental therapy abilities. The aims of this study were to define models for dental therapy education in Canada and explore how dental therapy abilities could best be integrated into Canadian post-secondary education. In 2017, purposeful sampling was used to invite key informants to participate in a semi-structured interview.

Which patients with heart failure should receive specialist palliative care?

Aims: We investigated which patients with heart failure (HF) should receive specialist palliative care (SPC) by first creating a definition of need for SPC in patients hospitalised with HF using patient-reported outcome measures (PROMs) and then testing this definition using the outcome of days alive and out of hospital (DAOH). We also evaluated which baseline variables predicted need for SPC and whether those with this need received SPC.

Methods And Results: PROMs assessing quality of life (QoL), symptoms, and mood were administered at baseline and every 4 months.

A comparison of in vitro cytotoxicity assays in medical device regulatory studies.

Medical device biocompatibility testing is used to evaluate the risk of adverse effects on tissues from exposure to leachates/extracts. A battery of tests is typically recommended in accordance with regulatory standards to determine if the device is biocompatible. In vitro cytotoxicity, a key element of the standards, is a required endpoint for all types of medical devices.

Late-Stage Microsomal Oxidation Reduces Drug-Drug Interaction and Identifies Phosphodiesterase 2A Inhibitor PF-06815189.

Late-stage oxidation using liver microsomes was applied to phosphodiesterase 2 inhibitor to reduce its clearance by cytochrome P450 enzymes, introduce renal clearance, and minimize the risk for victim drug-drug interactions. This approach yielded PF-06815189 () with improved physicochemical properties and a mixed metabolic profile. This example highlights the importance of C-H diversification methods to drug discovery.