Implementation of First-trimester Screening and Prevention of Preeclampsia: a Stepped Wedge Cluster-randomized Trial in Asia.

BACKGROUND: This trial aimed to assess the efficacy, acceptability and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia (PE) in Asia. METHODS: Between 1st August 2019 and 28th February 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from ten regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular six-week intervals, one cluster was randomized to transit from non-intervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm PE using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm PE ≥ 1 in 100, received low-dose aspirin from <16 weeks until 36 weeks. RESULTS: Overall, 88.04% (42,897/48,725) of women agreed to undergo first-trimester screening for preterm PE. Among those identified as high-risk in the intervention phase, 82.39% (2,919/3,543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm PE between the intervention and non-intervention phases (adjusted odds ratio [aOR] 1.59; 95% confidence interval [CI] 0.91 to 2.77). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm PE (aOR 0.59; 95%CI 0.37 to 0.92). Additionally, it correlated with 54%, 55% and 64% reduction in the incidence of PE with delivery at <34 weeks (aOR 0.46; 95%CI 0.23 to 0.93), spontaneous preterm birth <34 weeks (aOR 0.45; 95%CI 0.22 to 0.92) and perinatal death (aOR 0.34; 95%CI 0.12 to 0.91), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events. CONCLUSIONS: The implementation of the screen-and-prevent strategy for preterm PE is not associated with a significant reduction in the incidence of preterm PE. However, low-dose aspirin effectively reduces the incidence of preterm PE by 41% among high-risk women. The screen-and-prevent strategy for preterm PE is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm PE on a global scale.

The properties of absorbable scaffold harvested with human amniotic fluid stem cells on rat model: an innovation for pelvic reconstruction surgery.

The current practice of restoring the anatomical structure in the treatment of pelvic floor dysfunction includes implantation of synthetic sling, which carries potential complications. This study aimed to develop biological substitutes to improve tissue function using scaffolds as a support to the host cells, through formation of new tissue. Human amniotic fluid stem cells (hAFSCs) were seeded on synthetic mesh-scaffold of AlloDerm Regenerative Tissue Matrix (RTM), Poly-DL-lactico-glycolic acid (PLGA) mesh (VICRYL) and Polydioxanone (PDS) meshes. In vitro study evaluates the metabolic activity of hAFSCs seeded mesh-scaffolds. In vivo study involving Sprague-Dawley rats was performed by assigning into 7 groups of sham control with fascia operation, AlloDerm implant, PDS implant, PLGA implant, AlloDerm harvest with hAFSC (AlloDerm-SC), PDS harvest with hAFSC(PDS-SC) and PLGS harvest with hAFSC (PGLA-SC). In vitro study reveals cell viability and proliferation of hAFSC on mesh scaffolds varies between meshes, with AlloDerm growing the fastest. The biomechanical properties of tissue-mesh-complex tension strength declined over time, showing highest tension strength on week-1, deteriorated similar to control group on week-12. All hAFSC-seeded mesh provides higher tension strength, compared to without. This study shed the potential of synthetic mesh as a scaffold for hAFSC for the surgical treatment of pelvic floor dysfunction.

Influence of gestational hypertension and maternal air pollutant exposure on birth outcomes.

The relationship between exposure to air pollutants and fetal growth outcomes has shown inconsistency, and only a limited number of studies have explored the impact of air pollution on gestational hypertension and birth outcomes. This study aimed to evaluate how maternal exposure to air pollutants and blood pressure could influence fetal birth outcomes. A total of 55 women with gestational hypertension and 131 healthy pregnant women were enrolled in this study. Data pertaining to personal characteristics, prenatal examinations, outdoor air pollutant exposure, and fetal birth outcomes were collected. The study revealed that fetal birth weight and abdominal circumference exhibited a significant reduction among women with gestational hypertension compared to healthy pregnant women, even after adjustments for body mass index, gestational age, and exposure to air pollutants had been made. Moreover, maternal exposure to outdoor air pollutants displayed a notable correlation with decreased birth length of fetuses. Consequently, the study concluded that maternal blood pressure and exposure to outdoor air pollutants during pregnancy potentially stand as pivotal factors influencing fetal birth outcomes.

Validation of the first-trimester machine learning model for predicting pre-eclampsia in an Asian population.

OBJECTIVES: To evaluate the performance of an artificial intelligence (AI) and machine learning (ML) model for first-trimester screening for pre-eclampsia in a large Asian population. METHODS: This was a secondary analysis of a multicenter prospective cohort study in 10 935 participants with singleton pregnancies attending for routine pregnancy care at 11-13+6 weeks of gestation in seven regions in Asia between December 2016 and June 2018. We applied the AI+ML model for the first-trimester prediction of preterm pre-eclampsia (<37 weeks), term pre-eclampsia (≥37 weeks), and any pre-eclampsia, which was derived and tested in a cohort of pregnant participants in the UK (Model 1). This model comprises maternal factors with measurements of mean arterial pressure, uterine artery pulsatility index, and serum placental growth factor (PlGF). The model was further retrained with adjustments for analyzers used for biochemical testing (Model 2). Discrimination was assessed by area under the receiver operating characteristic curve (AUC). The Delong test was used to compare the AUC of Model 1, Model 2, and the Fetal Medicine Foundation (FMF) competing risk model. RESULTS: The predictive performance of Model 1 was significantly lower than that of the FMF competing risk model in the prediction of preterm pre-eclampsia (0.82, 95% confidence interval [CI] 0.77-0.87 vs. 0.86, 95% CI 0.811-0.91, P = 0.019), term pre-eclampsia (0.75, 95% CI 0.71-0.80 vs. 0.79, 95% CI 0.75-0.83, P = 0.006), and any pre-eclampsia (0.78, 95% CI 0.74-0.81 vs. 0.82, 95% CI 0.79-0.84, P < 0.001). Following the retraining of the data with adjustments for the PlGF analyzers, the performance of Model 2 for predicting preterm pre-eclampsia, term pre-eclampsia, and any pre-eclampsia was improved with the AUC values increased to 0.84 (95% CI 0.80-0.89), 0.77 (95% CI 0.73-0.81), and 0.80 (95% CI 0.76-0.83), respectively. There were no differences in AUCs between Model 2 and the FMF competing risk model in the prediction of preterm pre-eclampsia (P = 0.135) and term pre-eclampsia (P = 0.084). However, Model 2 was inferior to the FMF competing risk model in predicting any pre-eclampsia (P = 0.024). CONCLUSION: This study has demonstrated that following adjustment for the biochemical marker analyzers, the predictive performance of the AI+ML prediction model for pre-eclampsia in the first trimester was comparable to that of the FMF competing risk model in an Asian population.

Multi-layered genome defences in bacteria.

Bacteria have evolved a variety of defence mechanisms to protect against mobile genetic elements, including restriction-modification systems and CRISPR-Cas. In recent years, dozens of previously unknown defence systems (DSs) have been discovered. Notably, diverse DSs often coexist within the same genome, and some co-occur at frequencies significantly higher than would be expected by chance, implying potential synergistic interactions. Recent studies have provided evidence of defence mechanisms that enhance or complement one another. Here, we review the interactions between DSs at the mechanistic, regulatory, ecological and evolutionary levels.

Short-range translocation by a restriction enzyme motor triggers diffusion along DNA.

Cleavage of bacteriophage DNA by the Type III restriction-modification enzymes requires long-range interaction between DNA sites. This is facilitated by one-dimensional diffusion ('DNA sliding') initiated by ATP hydrolysis catalyzed by a superfamily 2 helicase-like ATPase. Here we combined ultrafast twist measurements based on plasmonic DNA origami nano-rotors with stopped-flow fluorescence and gel-based assays to examine the role(s) of ATP hydrolysis. Our data show that the helicase-like domain has multiple roles. First, this domain stabilizes initial DNA interactions alongside the methyltransferase subunits. Second, it causes environmental changes in the flipped adenine base following hydrolysis of the first ATP. Finally, it remodels nucleoprotein interactions via constrained translocation of a ∼ 5 to 22-bp double stranded DNA loop. Initiation of DNA sliding requires 8-15 bp of DNA downstream of the motor, corresponding to the site of nuclease domain binding. Our data unify previous contradictory communication models for Type III enzymes.

Changing the standardised obstetric care by expanded carrier screening and counselling: a multicentre prospective cohort study.

BACKGROUND: Expanded genetic screening before conception or during prenatal care can provide a more comprehensive evaluation of heritable fetal diseases. This study aimed to provide a large cohort to evaluate the significance of expanded carrier screening and to consolidate the role of expanded genetic screening in prenatal care. METHODS: This multicentre, retrospective cohort study was conducted between 31 December 2019 and 21 July 2022. A screening panel containing 302 genes and next-generation sequencing were used for the evaluation. The patients were referred from obstetric clinics, infertility centres and medical centres. Genetic counsellors conducted consultation for at least 15 min before and after screening. RESULTS: A total of 1587 patients were screened, and 653 pairs were identified. Among the couples who underwent the screening, 62 (9.49%) had pathogenic variants detected on the same genes. In total, 212 pathogenic genes were identified in this study. A total of 1173 participants carried at least one mutated gene, with a positive screening rate of 73.91%. Among the pathogenic variants that were screened, the gene encoding gap junction beta-2 (GJB2) exhibited the highest prevalence, amounting to 19.85%. CONCLUSION: Next-generation sequencing carrier screening provided additional information that may alter prenatal obstetric care by 9.49%. Pan-ethnic genetic screening and counselling should be suggested for couples of fertile age.

Fully magnetically centrifugal left ventricular assist device and long-term outcomes: the ELEVATE registry.

BACKGROUND AND AIMS: HeartMate 3 (HM3) is a fully magnetically levitated continuous flow left ventricular assist device, which received CE marking in 2015. The ELEVATE Registry was initiated to collect real-world outcomes in patients treated with HM3 post-CE Mark approval. METHODS: A total of 540 subjects implanted at 26 centres between March 2015 and February 2017 were included in this registry. Of these, 463 received the device as a primary implant (primary implant cohort, PIC), 19 as a pump exchange (pump exchange cohort), and in 58 patients, only anonymized survival data were collected (anonymized cohort, AC). Patients in the PIC contributed to the baseline demographics, survival, adverse events, quality of life (QoL) (EuroQoL-5 Dimensions-5 Levels visual analogue scale), and functional capacity (6 min walk distance) assessments, while patients in the AC contributed only to survival. RESULTS: Primary implant cohort patients had a mean age of 56 years and were predominantly male (89%) with 48% ischaemic aetiology. The majority of subjects was designated bridge to transplant (66%) and had INTERMACS Profiles 1-3 (70%). At baseline, the subjects had poor functional capacity (104 ± 140 m) and impaired QoL (35 ± 19 points). The overall survival rate of the PIC was 63.3% and survival free of stroke was 58.1% at 5 years. Significant improvements in functional capacity and QoL were observed and maintained for 5 years (301 ± 131 m and 64 ± 20 points, respectively). CONCLUSIONS: Real-world data from the ELEVATE registry demonstrate an overall survival rate for primary implants of 63.3%. In the PIC, reductions in adverse events for patients in the extended follow-up and improved QoL and functional capacity were observed at 5 years in this patient population with advanced heart failure.

Reducing primary cesarean delivery rate through implementation of a smart intrapartum surveillance system.

The rapid changes in clinical maternity situations that occur in a labor and delivery unit can lead to unpredictable maternal and newborn morbidities. Cesarean section (CS) rate is a key indicator of the accessibility and quality of a labor and delivery unit. This retrospective cross-sectional study assesses the nulliparous, term, singleton, vertex (NTSV) cesarean delivery rates before and after the implementation of a smart intrapartum surveillance system. Research data were collected from the electronic medical records of a labor and delivery unit. The primary outcome was the CS rate of the NTSV population. The data of 3648 women admitted for delivery were analyzed. Of the studied deliveries, 1760 and 1888 occurred during the preimplementation and postimplementation periods, respectively. The CS rate for the NTSV population was 31.0% and 23.3% during the preimplementation and postimplementation periods, respectively, indicating a significant 24.7% (p = 0.014) reduction in CS rate after the implementation of the smart intrapartum surveillance system (relative risk, 0.75; 95% confidence interval, 0.71-0.80). In the NTSV population, the vaginal and CS birth groups, no significant difference in terms of newborn weight, neonatal Apgar scores, composite neonatal adverse outcome indicator, and the occurrence of the following: neonatal intensive care unit admission, neonatal meconium aspiration, chorioamnionitis, shoulder dystocia, perineal laceration, placental abruption, postpartum hemorrhage, maternal blood transfusion, and hysterectomy before and after the implementation of the smart intrapartum surveillance system. This study reveals that the use of the smart intrapartum surveillance system can effectively reduce the primary CS rate for low-risk NTSV pregnancies without significantly affecting perinatal outcomes.

Real-world management of abnormal scarring using topical silicone gel: expert consensus and case series from the Asian SCARS Expert Group.

Preventing abnormal scar formation and correcting non-aesthetic mature scars are important to prevent physical and psychosocial consequences of abnormal scarring. Evidence-based guidelines for scar management in Asian patients recommend first-line silicone-based products. Dermatix®* Ultra and Dermatix Ultra Kids are topical silicone gels containing a vitamin C ester that helps lighten scar tissue. Herein, we report a case series including patients with hypertrophic and keloid scars treated with Dermatix, showing that Dermatix is effective for scar treatment and prevention, as well as expert consensus supporting the safe and effective use of Dermatix.

Controllable branching of robust response patterns in nonlinear mechanical resonators.

In lieu of continuous time active feedback control in complex systems, nonlinear dynamics offers a means to generate desired long-term responses using short-time control signals. This type of control has been proposed for use in resonators that exhibit a plethora of complex dynamic behaviors resulting from energy exchange between modes. However, the dynamic response and, ultimately, the ability to control the response of these systems remains poorly understood. Here, we show that a micromechanical resonator can generate diverse, robust dynamical responses that occur on a timescale five orders of magnitude larger than the external harmonic driving and these responses can be selected by inserting small pulses at specific branching points. We develop a theoretical model and experimentally show the ability to control these response patterns. Hence, these mechanical resonators may represent a simple physical platform for the development of springboard concepts for nonlinear, flexible, yet robust dynamics found in other areas of physics, chemistry, and biology.

Risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic: Results of a web-based multinational cross-sectional study.

OBJECTIVE: To assess risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic using Mind-COVID, a prospective cross-sectional study that compares outcomes in middle-income economies and high-income economies. METHODS: A total of 7102 pregnant women from 12 high-income economies and nine middle-income economies were included. The web-based survey used two standardized instruments, General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). RESULT: Pregnant women in high-income economies reported higher PHQ-9 (0.18 standard deviation [SD], P < 0.001) and GAD-7 (0.08 SD, P = 0.005) scores than those living in middle-income economies. Multivariate regression analysis showed that increasing PHQ-9 and GAD-7 scales were associated with mental health problems during pregnancy and the need for psychiatric treatment before pregnancy. PHQ-9 was associated with a feeling of burden related to restrictions in social distancing, and access to leisure activities. GAD-7 scores were associated with a pregnancy-related complication, fear of adverse outcomes in children related to COVID-19, and feeling of burden related to finances. CONCLUSIONS: According to this study, the imposed public health measures and hospital restrictions have left pregnant women more vulnerable during these difficult times. Adequate partner and family support during pregnancy and childbirth can be one of the most important protective factors against anxiety and depression, regardless of national economic status.

Evaluation of Escherichia coli Inactivation at High Altitudes Using Solar Water Disinfection.

INTRODUCTION: Solar disinfection (SODIS) is an effective method for microbiologic inactivation of contaminated water using ultraviolet rays at low elevations. The aim of this study was to determine the effectiveness of SODIS at higher elevations. METHODS: The ability of SODIS to inactivate Escherichia coli bacteria was evaluated at an altitude of ≥1600 m using Nalgene bottles, disposable plastic water bottles, and Ziploc plastic bags. Bacterial viability was determined through measurement of colony forming units (CFUs). Decreases in CFUs were determined at each time point relative to those at the baseline, and a multivariable regression analysis was used to assess significant changes in CFUs. RESULTS: Bacterial CFUs in exposed containers decreased by >5 log after 6 h of exposure to sunlight. In contrast, the CFUs remained nearly unchanged in unexposed containers, showing a mean decrease of 0.3 log. By 2 h, bacterial inactivation at high altitudes was 1.7-fold greater than that at lower altitudes (P<0.05). By 6 h, nearly all bacteria were inactivated at high or low altitudes. At 6 h, no statistical difference was observed in the efficiency of inactivation between elevations. Compared with Nalgene bottles, plastic bottles had a 1.4-fold greater decrease in CFUs (P<0.05). No statistical difference in bacterial inactivation was found between plastic bottles and plastic bags. CONCLUSIONS: At high altitudes, SODIS is an effective method for inactivating E coli. Further research investigating other microorganisms is warranted to determine whether SODIS is suitable for disinfecting contaminated water at high altitudes.

The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry.

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = -0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.

Nonlinear Stiffness and Nonlinear Damping in Atomically Thin MoS2 Nanomechanical Resonators.

We report on experimental measurements and quantitative analyses of nonlinear dynamic characteristics in ultimately thin nanomechanical resonators built upon single-layer, bilayer, and trilayer (1L, 2L, and 3L) molybdenum disulfide (MoS2) vibrating drumhead membranes. This synergistic study with calibrated measurements and analytical modeling on observed nonlinear responses has led to the determination of nonlinear damping and stiffness coefficients at cubic and quintic orders for these two-dimensional (2D) resonators operating in the very high frequency (VHF) band (up to ∼90 MHz). We find that the quintic force can be ∼20% of the Duffing force at larger amplitudes, and thus, it generally cannot be ignored in a nonlinear dynamics analysis. This study provides the first quantification of nonlinear damping and frequency detuning characteristics in 2D semiconductor nanomechanical resonators and elucidates their origins and dependency on engineerable parameters, setting a foundation for future exploration and utilization of the rich nonlinear dynamics in 2D nanomechanical systems.

Combinatorial Analysis of Circulating Biomarkers and Maternal Characteristics for Preeclampsia Prediction in the First and Third Trimesters in Asia.

We aim to establish a prediction model for pregnancy outcomes through a combinatorial analysis of circulating biomarkers and maternal characteristics to effectively identify pregnant women with higher risks of preeclampsia in the first and third trimesters within the Asian population. A total of two hundred and twelve pregnant women were screened for preeclampsia through a multicenter study conducted in four recruiting centers in Taiwan from 2017 to 2020. In addition, serum levels of sFlt-1/PlGF ratio, miR-181a, miR-210 and miR-223 were measured and transformed into multiples of the median. We thus further developed statistically validated algorithmic models by designing combinations of different maternal characteristics and biomarker levels. Through the performance of the training cohort (0.848 AUC, 0.73−0.96 95% CI, 80% sensitivity, 85% specificity, p < 0.001) and the validation cohort (0.852 AUC, 0.74−0.98 95% CI, 75% sensitivity, 87% specificity, p < 0.001) from one hundred and fifty-two women with a combination of miR-210, miR-181a and BMI, we established a preeclampsia prediction model for the first trimester. We successfully identified pregnant women with higher risks of preeclampsia in the first and third trimesters in the Asian population using the established prediction models that utilized combinatorial analysis of circulating biomarkers and maternal characteristics.

Human amniotic fluid stem cell therapy can help regain bladder function in type 2 diabetic rats.

BACKGROUND: Diabetes mellitus (DM) is a serious and growing global health burden. It is estimated that 80% of diabetic patients have micturition problems such as poor emptying, urinary incontinence, urgency, and urgency incontinence. Patients with diabetic bladder dysfunction are often resistant to currently available therapies. It is necessary to develop new and effective treatment methods. AIM: To examine the therapeutic effect of human amniotic fluid stem cells (hAFSCs) therapy on bladder dysfunction in a type 2 diabetic rat model. METHODS: Sixty female Sprague-Dawley rats were divided into five groups: Group 1, normal-diet control (control); group 2, high-fat diet (HFD); group 3, HFD plus streptozotocin-induced DM (DM); group 4, DM plus insulin treatment (DM + insulin); group 5, DM plus hAFSCs injection via tail vein (DM + hAFSCs). Conscious cystometric studies were done at 4 and 12 wk after insulin or hAFSCs treatment to measure peak voiding pressure, voided volume, intercontraction interval, bladder capacity, and residual volume. Immunoreactivities and/or mRNA expression of muscarinic receptors, nerve growth factor (NGF), and sensory nerve markers in the bladder and insulin, MafA, and pancreatic-duodenal homeobox-1 (PDX-1) in pancreatic beta cells were studied. RESULTS: Compared with DM rats, insulin but not hAFSCs treatment could reduce the bladder weight and improve the voided volume, intercontraction interval, bladder capacity, and residual volume (P < 0.05). However, both insulin and hAFSCs treatment could help to regain the blood glucose and bladder functions to the levels near controls (P > 0.05). The immunoreactivities and mRNA expression of M2- and M3-muscarinic receptors (M2 and M3) were increased mainly at 4 wk (P < 0.05), while the number of beta cells in islets and the immunoreactivities and/or mRNA of NGF, calcitonin gene-related peptide (CGRP), substance P, insulin, MafA, and PDX-1 were decreased in DM rats (P < 0.05). However, insulin and hAFSCs treatment could help to regain the expression of M2, M3, NGF, CGRP, substance P, MafA, and PDX-1 to near the levels of controls at 4 and/or 12 wk (P > 0.05). CONCLUSION: Insulin but not hAFSCs therapy can recover the bladder dysfunction caused by DM; however, hAFSCs and insulin therapy can help to regain bladder function to near the levels of control.

The Exploration of miRNAs From Porcine Fallopian Tube Stem Cells on Porcine Oocytes.

Fallopian tube is essential to fertilization and embryonic development. Extracellular vesicles (EVs) from Fallopian tube containing biological regulatory factors, such as lipids, proteins and microRNAs (miRNAs) serve as the key role. At present, studies on oocytes from porcine oviduct and components from EVs remain limited. We aim to explore the effect of EVs secreted by porcine fallopian tube stem cells (PFTSCs) on oocyte. When the fifth-generation PFTSCs reached 80-90% of confluency, the pig in vitro maturation medium was utilized, and the conditioned medium collected for oocyte incubations. To realize the functions of EVs, several proteins were used to determine whether extracted EVs were cell-free. Field emission scanning electron microscope and nanoparticle tracking analyzer were used to observe the morphology. By next generation sequencing, 267 miRNAs were identified, and those with higher expression were selected to analyze the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment maps. The selected miR-152-3p, miR-148a-3p, miR-320a-3p, let-7f-5p, and miR-22-3p, were predicted to target Cepb1 gene affecting MAPK pathway. Of the five miRNAs, miR-320a-3p showed significant difference in maturation rate in vitro maturation. The blastocyst rate of pig embryos was also significantly enhanced by adding 50 nM miR-320a-3p. In vitro culture with miR-320a-3p, the blastocyst rate was significantly higher, but the cleavage rate and cell numbers were not. The CM of PFTSCs effectively improves porcine oocyte development. The miRNAs in EVs are sequenced and identified. miR-320a-3p not only helps the maturation, but also increases the blastocyst rates.

Human amniotic fluid stem cells can alleviate detrusor dysfunction caused by bladder outlet obstruction in rats.

The present study examined whether bladder detrusor dysfunction due to partial bladder outlet obstruction (pBOO) could be improved after the treatment of human amniotic fluid stem cells (hAFSCs). 72 female rats were grouped into sham operation, pBOO, and pBOO with hAFSCs treatment (pBOO + hAFSCs) for in vitro and in vivo studies. Bladder weight, bladder wall thickness, the ratio of collagen to smooth muscle and the levels of positive CD11b/c and HIS48 cells was significantly increased after pBOO but improved after hAFSCs treatment. Cystometries showed impaired bladder function after pBOO. Protein and mRNA levels of hypoxia inducible factor-1α, CCL2, interleukin-1ß, transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor (CTGF), α-smooth muscle actin, collagen I and collagen III were increased at 2 and/or 6 weeks, but proteins and mRNA expressions of protein gene product 9.5 were decreased at 2 and 6 weeks after pBOO. These abnormalities were improved after hAFSCs treatment. The expressions of TGF-ß1 and CTGF in cultured detrusor cells of pBOO rats were increased but were improved after hAFSCs treatment. The present results showed hAFSCs treatment could improve bladder detrusor dysfunction in pBOO rats, which may be related to the reduction of inflammatory and pro-fibrotic markers in detrusor muscle cells.

Engagement in digital interventions.

The notion of "engagement," which plays an important role in various domains of psychology, is gaining increased currency as a concept that is critical to the success of digital interventions. However, engagement remains an ill-defined construct, with different fields generating their own domain-specific definitions. Moreover, given that digital interactions in real-world settings are characterized by multiple demands and choice alternatives competing for an individual's effort and attention, they involve fast and often impulsive decision-making. Prior research seeking to uncover the mechanisms underlying engagement has nonetheless focused mainly on psychological factors and social influences and neglected to account for the role of neural mechanisms that shape individual choices. This article aims to integrate theories and empirical evidence across multiple domains to define engagement and discuss opportunities and challenges to promote effective engagement in digital interventions. We also propose the affect-integration-motivation and attention-context-translation (AIM-ACT) framework, which is based on a neurophysiological account of engagement, to shed new light on how in-the-moment engagement unfolds in response to a digital stimulus. Building on this framework, we provide recommendations for designing strategies to promote engagement in digital interventions and highlight directions for future research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).