Transuterine Fetal Tracheal Occlusion Model in Mice

Fetal tracheal occlusion (TO), an established treatment modality, promotes fetal lung growth and survival in severe congenital diaphragmatic hernia (CDH). Following TO, retention of the secreted epithelial fluid increases luminal pressure and induces lung growth. Various animal models have been defined to understand the pathophysiology of CDH and TO. All have their own advantages and disadvantages such as the difficulty of the technique, the size of the animal, cost, high mortality rates, and the availability of genetic tools. Herein, a novel transuterine model of murine fetal TO is described. Pregnant mice were anesthetized, and the uterus exposed via a midline laparotomy. The trachea of selected fetuses were ligated with a single transuterine suture placed behind the trachea, one carotid artery, and one jugular vein. The dam was closed and allowed to recover. Fetuses were collected just before parturition. Lung to body weight ratio in TO fetuses was higher than that in control fetuses. This model provides researchers with a new tool to study the impact of both TO and increased luminal pressure on lung development

Clinical Study Maternal Hypotension during Fetoscopic Surgery: Incidence and Its Impact on Fetal Survival Outcomes

In this retrospective cohort study, we aimed to determine the incidence of intraoperative maternal hypotension during fetoscopic surgery for twin-twin transfusion syndrome (TTTS) and to evaluate the impact of intraoperative hypotension on fetal survival. A total of 328 TTTS patients with recipient twin cardiomyopathy who underwent fetoscopic surgery under epidural anesthesia were included. The exposure of interest was maternal medical therapy with nifedipine for the treatment of fetal cardiomyopathy. We found that intraoperative hypotension occurred in 53.4% (175/328 patients). There was no statistically significant difference in incidence of hypotension between nifedipine exposure and nonexposure groups (54.8% versus 50.8%, = 0.479). However, the nifedipine exposure group received a statistically significant higher dose of phenylephrine (7.04 ± 6.38 mcg/kg versus 4.70 ± 4.14 mcg/kg, = 0.018) and higher doses of other vasopressor, as counted by number of treatments (6.06 ± 4.58 versus 4.96 ± 3.42, = 0.022). There were no statistically significant differences in acute fetal survival rate (within 5 days) and fetal survival rate at birth between hypotensive and nonhypotensive patients. We concluded that preoperative exposure to nifedipine resulted in increased intraoperative maternal vasopressor requirement during fetoscopic surgery under epidural anesthesia. In patients who had intraoperative maternal hypotension, there was no correlation between the presence of maternal hypotension and postoperative fetal survival

Prepregnancy adherence to plant-based diet indices and exploratory dietary patterns in relation to fecundability

Background Modest associations have been reported between specific food groups or nutrients and fecundability [measured by time to pregnancy (TTP)]. Examining overall diets provides a more holistic approach towards understanding their associations with fecundability. It is not known whether plant-based diets indices or exploratory dietary patterns are associated with fecundability. Objectives We examine the associations between adherence to 1) plant-based diet indices; and 2) exploratory dietary patterns and fecundability among women planning pregnancy. Methods Data were analyzed from the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) study. Prepregnancy diet was assessed using a semi-quantitative FFQ from which the overall, healthful, and unhealthful plant-based diet indices (oPDI, hPDI, and uPDI, respectively) were calculated. Exploratory dietary patterns were derived using factor analysis based on 44 predefined food groups. Participants were categorized into quintiles based on their dietary pattern scores. TTP (expressed in menstrual cycles) was ascertained within a year from the prepregnancy dietary assessment. Discrete-time proportional hazard models, adjusted for confounders, were used to estimate fecundability ratios (FRs) and 95% CIs, with FR > 1 indicating a shorter TTP. Results Among 805 women, 383 pregnancies were confirmed by ultrasound scans. Compared with women in the lowest quintile, those in the highest quintile of the uPDI had reduced fecundability (FR of Q5 compared with Q1, 0.65; 95% CI, 0.46-0.91; P trend, 0.009). Conversely, greater adherence to the hPDI was associated with increased fecundability (1.46; 95% CI, 1.02-2.07; P trend, 0.036). The oPDI was not associated with fecundability. Among the 3 exploratory dietary patterns, only greater adherence to the Fast Food and Sweetened Beverages (FFSB) pattern was associated with reduced fecundability (0.61; 95% CI, 0.40-0.91; P trend, 0.018). Conclusions Greater adherence to the uPDI or the FFSB dietary pattern was associated with reduced fecundability among Asian women. Greater adherence to the hPDI may be beneficial for fecundability, though this requires confirmation by future studies.Peer reviewe

Modifiable Risk Factor Score and Fecundability in a Preconception Cohort in Singapore

Importance: Although multiple modifiable risk factors have been identified for reduced fecundability (defined as lower probability of conception within a menstrual cycle), no scoring system has been established to systematically evaluate fecundability among females who are attempting to conceive. Objective: To examine the association of a risk score based on 6 modifiable factors with fecundability, and to estimate the percentage reduction in incidence of nonconception if all study participants achieved a minimal risk score level. Design, Setting, and Participants: This population-based cohort study obtained data from the S-PRESTO (Singapore Preconception Study of Long-Term Maternal and Child Outcomes) prospective cohort study. Females of reproductive age who were trying to conceive were enrolled from February 2015 to October 2017 and followed for 1 year, ending in November 2018. Data were analyzed from March to May 2022. Exposures: A reduced fecundability risk score was derived by giving participants 1 point for each of the following factors: unhealthy body mass index, unhealthy diet, smoking, alcohol intake, folic acid supplement nonuser, and older maternal age. Total scores ranged from 0 to 6 and were classified into 5 levels: level 1 (score of 0 or 1), level 2 (score of 2), level 3 (score of 3), level 4 (score of 4), and level 5 (score of 5 or 6). Main Outcomes and Measures: Fecundability, measured by time to conception in cycles, was analyzed using discrete-time proportional hazards models with confounder adjustment. Results: A total of 937 females (mean [SD] age, 30.8 [3.8] years) were included, among whom 401 (42.8%) spontaneously conceived within 1 year of attempting conception; the median (IQR) number of cycles before conception was 4 (2-7). Compared with participants with a level 1 risk score, those with level 2, 3, 4, and 5 risk scores had reductions in fecundability of 31% (adjusted fecundability ratio [FR], 0.69; 95% CI, 0.54-0.88), 41% (FR, 0.59; 95% CI, 0.45-0.78), 54% (FR, 0.46; 95% CI, 0.31-0.69) and 77% (FR, 0.23; 95% CI, 0.07-0.73), respectively. Assessment of the population attributable fraction showed that all participants achieving a minimal (level 1) risk level would be associated with a reduction of 34% (95% CI, 30%-39%) in nonconception within a year. Conclusions and Relevance: Results of this study revealed the co-occurrence of multiple modifiable risk factors for lowered fecundability and a substantially higher conception rate among participants with no or minimal risk factors. The risk assessment scoring system proposed is a simple and potentially useful public health tool for mitigating risks and guiding those who are trying to conceive.publishedVersionPeer reviewe

A study assessing the association of glycated hemoglobin a1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of asian ancestry

10.1371/journal.pone.0079767PLoS ONE811-POLN

De novo variants in congenital diaphragmatic hernia identify MYRF as a new syndrome and reveal genetic overlaps with other developmental disorders

Congenital diaphragmatic hernia (CDH) is a severe birth defect that is often accompanied by other congenital anomalies. Previous exome sequencing studies for CDH have supported a role of de novo damaging variants but did not identify any recurrently mutated genes. To investigate further the genetics of CDH, we analyzed de novo coding variants in 362 proband-parent trios including 271 new trios reported in this study. We identified four unrelated individuals with damaging de novo variants in MYRF (P = 5.3x10-8), including one likely gene-disrupting (LGD) and three deleterious missense (D-mis) variants. Eight additional individuals with de novo LGD or missense variants were identified from our other genetic studies or from the literature. Common phenotypes of MYRF de novo variant carriers include CDH, congenital heart disease and genitourinary abnormalities, suggesting that it represents a novel syndrome. MYRF is a membrane associated transcriptional factor highly expressed in developing diaphragm and is depleted of LGD variants in the general population. All de novo missense variants aggregated in two functional protein domains. Analyzing the transcriptome of patient-derived diaphragm fibroblast cells suggest that disease associated variants abolish the transcription factor activity. Furthermore, we showed that the remaining genes with damaging variants in CDH significantly overlap with genes implicated in other developmental disorders. Gene expression patterns and patient phenotypes support pleiotropic effects of damaging variants in these genes on CDH and other developmental disorders. Finally, functional enrichment analysis implicates the disruption of regulation of gene expression, kinase activities, intra-cellular signaling, and cytoskeleton organization as pathogenic mechanisms in CDH

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Surveillance of tobacco industry marketing strategies at retail outlets

The tobacco industry spends more money on place of sale (POS) promotions than on all other forms of cigarette marketing combined. This research monitors how the Malaysian tobacco industry promotes tobacco products at retail outlets under newly amended laws, which prohibit direct and indirect advertising, while also documenting the various consumer-based sales strategies and retailer-based incentive strategies used by the tobacco industry to maximize sales of tobacco products. Anything short of complete ban of tobacco promotion will enable the tobacco companies to shift their promotional activities from one place to another

Prenatal diagnosis of cloacal malformations

Introduction: Prenatal diagnosis of anorectal malformations currently occurs in 0-15.9% of screened cases. In cloacas, these numbers are unknown. We speculate that some images from prenatal ultrasound studies may suggest the diagnosis of cloaca, but are not recognized because of a lack of suspicion for this diagnosis. Methods: A retrospective review of the medical records of 489 patients born with cloaca was performed; 95 of them had prenatal ultrasound reports that represent the material analyzed for this study. A literature review was performed, finding 31 publications, with 68 cloaca patients detected by prenatal images. The abnormal findings of our patients were compared with those described in the literature to determine the most common abnormal prenatal images found in patients with cloaca. Results: The 95 ultrasound reports found in our patients described 270 abnormalities, the most frequent were: abdominal/pelvic cystic/mass (39), hydronephrosis (36), oligohydramnios (23), distended bowel/bowel obstruction (19), ascites (15), 2 vessel cord (14), dilated bladder (14), dilated ureter (14), polyhydramnios (10), echogenic bowel (8), multicystic kidney (8), ambiguous genitalia (7), hydrops fetalis (7), hydrocolpos (4), absent kidney (3), abnormal spine (3), and anorectal atresia (3). In spite of these findings, the radiologists who interpreted the studies only suspected a cloaca in 6 cases (6%). The literature review showed 212 abnormalities in 68 demonstrated cloaca patients. The most frequent were: abdominal/pelvic cystic/mass (46), hydronephrosis (44), ascites (21), oligohydramnios (20), distended bowel (11), multicystic dysplastic kidney (7), ambiguous genitalia (6), non-visualization of the bladder (6), two-vessel cord (5), dilated bladder (5), intraabdominal calcification (4), polyhydramnios (4), enterolithiasis (4), hydrometrocolpos (3), and dilated ureter (3). Conclusion: We conclude that it is possible to suspect the diagnosis of cloaca, prenatally, more frequently than what currently occurs, looking at the same images but with an increased index of suspicion for cystic abdominal masses and a combination of gastrointestinal and urological abnormalities. © 2010 Springer-Verlag