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Abstract: This note provides an analytical proof of the optimal tuning of centrifugal pendulum vibration absorbers (CPVAs) to reduce in-plane translational and rotational vibration for a rotor with N cyclically symmetric substructures attached to it. The reaction forces that the substructures (helicopter or wind turbine blades, for example) exert on the rotor are first analyzed. The linearized equations of motion for the vibration are then solved by a gyroscopic system modal analysis procedure. The solutions show that the rotor translational vibrations are reduced when one group of CPVAs is tuned to order N −1 and another group is tuned to order N +1. Derivation of this result is not available in the literature. The current derivation also yields the better known result that tuning CPVAs to order N reduces rotational rotor vibration. [Copyright &y& Elsevier]

Background: The purpose of this study is to evaluate the impact of prenatal screening tests on prenatal diagnosis in Taiwan's 14 years from 2006 to 2019.Methods: The prenatal screening methods evolved from the second-trimester serum screening to combined first-trimester screening (cFTS) and then followed by the non-invasive cell-free DNA prenatal test (NIPT). The data used by the Department of Statistics, the Ministry of Health and Welfare and Department of Household Registration, Ministry of the Interior public website.Results: This regional registry-based cohort retrospective study examined a total of 2,775,792 births from January 2006 to December 2019. The proportion of advanced maternal age (AMA) pregnancies increased from 11.63% in 2006 to 30.94% in 2019. Overall, invasive diagnostic testing was used in 87.22% of AMA pregnancies. The prenatal detection rate of trisomy 21 and 18 increased from 74.1% and 83.3% in 2006 to 96.9% and 98.8% in 2019, respectively.Conclusion: During the second-trimester and cFTS periods, the percentage of AMA pregnancies increased every year and the number of invasive procedures also accompany with increased percentage of AMA. However, during the period that NIPT were implemented, the percentage of invasive procedures decreased. [ABSTRACT FROM AUTHOR]

Objective: DiGeorge syndrome (DGS) is associated with microdeletions of chromosome 22q11. It is the second most common cause of congenital heart disease and is an important consideration whenever a conotruncal cardiac anomaly is identified. The availability of noninvasive prenatal testing (NIPT) is altering the practice of prenatal genetics and maternal-fetal medicine, resulting in a decline in invasive testing. Antenatal ultrasound and other biomarkers have their own limitation. NIPT was proposed to screen DGS with cell-free DNA in Taiwan. Here, we present our experience of prenatal diagnosis of DGS in our center. Methods: This was a retrospective study between November 1, 2019, and August 31, 2020, in Taiwan. Data were collected from 7,826 pregnant women self-referred for DGS screening with massive parallel shotgun sequencing-based NIPT. High-risk cases subsequently received amniocentesis for array comparative genomic hybridization (aCGH) to confirm the diagnosis. Characteristics of pregnancies were documented when participants received the test. Report of NIPT was completed 2 weeks after the test. Follow-up on high-risk cases was completed by telephone interview on January 30, 2021. Results: Thirteen cases showed high risk by NIPT, and 7 cases were confirmed by aCGH. The sensitivity and specificity were 100% (95% confidence interval [CI] 64.57–100.00%) and 99.92% (95% CI 99.83–99.96%). The prevalence of DGS was 1 in 1,118 pregnancies. The positive predictive rate was 53.85% (95% CI 29.14–76.79%). One true positive (TP) showed US anomaly, and 5 TPs selected termination. Discussion/Conclusion: NIPT demonstrated good performance in DGS screening. Detection of 22q11.2 deletion could be combined with routine screening to facilitate proper intervention. [ABSTRACT FROM AUTHOR]

Clinical success of in utero transplantation (IUT) using allogeneic hematopoietic stem cells (HSCs) has been limited to fetuses that lack an immune response to allogeneic cells due to severe immunological defects, and where transplanted genetically normal cells have a proliferative or survival advantage. Amniotic fluid (AF) is an autologous source of stem cells with hematopoietic potential that could be used to treat congenital blood disorders. We compared the ability of congenic and allogeneic mouse AF stem cells (AFSC) to engraft the hematopoietic system of time-mated C57BL/6J mice (E13.5). At 4 and 16 weeks of age, multilineage donor engraftment was higher in congenic versus allogeneic animals. In vitro mixed lymphocyte reaction confirmed an immune response in the allogeneic group with higher CD4 and CD8 cell counts and increased proliferation of stimulated lymphocytes. IUT with congenic cells resulted in 100% of donor animals having chimerism of around 8% and successful hematopoietic long-term engraftment in immune-competent mice when compared with IUT with allogeneic cells. AFSCs may be useful for autologous cell/gene therapy approaches in fetuses diagnosed with congenital hematopoietic disorders. [ABSTRACT FROM AUTHOR]

Objective: Objective: Myelomeningocele (MMC) is the most severe type of spina bifida, with an incidence of 1.87 per 10,000 live births in Taiwan. Exposure of the lesion to amniotic fluid exacerbates neurological outcomes, while fetal surgery for MMC repair, now a routine practice, improves postnatal outcomes. However, Asian women and their families often find it difficult to accept prenatal defects, leading nearly all pregnancies with fetal MMC to opt for termination without considering fetal surgery., Materials and Methods: In Taiwan's first approved trial of fetoscopic MMC repair, we prospectively recruited 15 cases from 2020 to 2023. Final diagnoses were confirmed using MRI and ultrasound. The medical team provided non-direct consultations to discuss possible outcomes of fetal surgery with family members. For those opting for fetal surgery, we offered total percutaneous fetoscopic MMC repair., Results: Over 30 months, 14 of 15 cases (93%) chose to terminate their pregnancies between 18 and 26 weeks of gestational age. Decision factors included potential disabilities, morbidities, economic, social, and psychological aspects. Despite supportive groups in the country, the termination rate remained high among the Chinese population. One out of the 15 cases underwent fetal surgery successfully, resulting in a 30-month-old child without motor function delays, able to walk and run naturally., Conclusion: We initiated the first fetoscopic MMC repair in Taiwan with promising outcomes, though we faced a high termination rate here and similar situation in other Asian countries. Continuous social education through media could play a crucial role in changing perceptions and increasing acceptance of fetal surgery., Competing Interests: Conflicts of interest All authors declare no conflicts of interest regarding this study., (Copyright © 2024. Published by Elsevier B.V.)

Background: This trial aimed to assess the efficacy, acceptability, and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia in Asia., Methods: Between August 1, 2019, and February 28, 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from 10 regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular 6-week intervals, one cluster was randomized to transit from nonintervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm preeclampsia using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm preeclampsia ≥1 in 100, received low-dose aspirin from <16 weeks until 36 weeks., Results: Overall, 88.04% (42 897 of 48 725) of women agreed to undergo first-trimester screening for preterm preeclampsia. Among those identified as high-risk in the intervention phase, 82.39% (2919 of 3543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm preeclampsia between the intervention and non-intervention phases (adjusted odds ratio [aOR], 1.59 [95% CI, 0.91-2.77]). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm preeclampsia (aOR, 0.59 [95% CI, 0.37-0.92]). In addition, it correlated with 54%, 55%, and 64% reduction in the incidence of preeclampsia with delivery at <34 weeks (aOR, 0.46 [95% CI, 0.23-0.93]), spontaneous preterm birth <34 weeks (aOR, 0.45 [95% CI, 0.22-0.92]), and perinatal death (aOR, 0.34 [95% CI, 0.12-0.91]), 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 preeclampsia is not associated with a significant reduction in the incidence of preterm preeclampsia. However, low-dose aspirin effectively reduces the incidence of preterm preeclampsia by 41% among high-risk women. The screen-and-prevent strategy for preterm preeclampsia 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 preeclampsia on a global scale., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03941886., Competing Interests: L.C.P. has received speaker fees and consultancy payments from Roche Diagnostics and Ferring Pharmaceuticals. In addition, she has received in-kind contributions from Roche Diagnostics, Revvity Inc (formerly PerkinElmer Life and Analytical Sciences), Thermo Fisher Scientific, Ningbo Aucheer Biological Technology Co, Ltd, and GE HealthCare. D.S.S. has received in-kind contributions from Revvity Inc, Thermo Fisher Scientific, Roche Diagnostics, Diabetomics, and Ningbo Aucheer Biological Technology Co, Ltd. R.K.P. is chief executive officer of Ritz Medical Co Ltd, a genetic testing company, and holds shares in and receives executive compensation from it. The other authors report no conflicts.

This study investigates whether hAFSCs can improve bladder function in partial bladder outlet obstruction (pBOO) rats by targeting specific cellular pathways. Thirty-six female rats were divided into sham and pBOO groups with and without hAFSCs single injection into the bladder wall. Cystometry, inflammation/hypoxia, collagen/fibrosis/gap junction proteins, and smooth muscle myosin/muscarinic receptors were examined at 2 and 6 weeks after pBOO or sham operation. In pBOO bladders, significant increases in peak voiding pressure and residual volume stimulated a significant upregulation of inflammatory and hypoxic factors, TGF-β1 and Smad2/3. Collagen deposition proteins, collagen 1 and 3, were significantly increased, but bladder fibrosis markers, caveolin 1 and 3, were significantly decreased. Gap junction intercellular communication protein, connexin 43, was significantly increased, but the number of caveolae was significantly decreased. Markers for the smooth muscle phenotype, myosin heavy chain 11 and guanylate-dependent protein kinase, as well as M2 muscarinic receptors, were significantly increased in cultured detrusor cells. However, hAFSCs treatment could significantly ameliorate bladder dysfunction by inactivating the TGFβ-Smad signaling pathway, reducing collagen deposition, disrupting gap junctional intercellular communication, and modifying the expressions of smooth muscle myosin and caveolae/caveolin proteins. The results support the potential value of hAFSCs-based treatment of bladder dysfunction in BOO patients.

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., (© 2024. The Author(s).)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

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., (© 2023. UChicago Argonne, LLC, Operator of Argonne National Laboratory.)

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 (MoS 2 ) 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.

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., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fu, Wang, Lin, Shen, Chang, Lin, Chou, Yu, Yang, Huang, Shaw and Peng.)

Background: Feticide was suggested to avoid delivering children with abnormalities. Recently, twin pregnancies have increased. Selective feticide was proposed to achieve a good outcome of pregnancy. This study aimed to evaluate the performance of feticide in twin pregnancy with fetal anomaly., Methods: This was a retrospective study enrolled from 2009 to 2018. A total of 68 pregnancies with fetal anomalies received feticide. Potassium chloride was injected into the left ventricle to induce fetal asystole. Maternal and fetal characteristics of 16 dichorionic twins were documented to compare before and after 24th gestational week., Results: All pregnant women received feticide without any maternal or fetal complication. The reasons for choosing feticide were divided into four groups, including morphologic defect (61.8%), genetic-chromosomal abnormality (30.9%), obstetrical complication (5.9%), and maternal request (1.5%). Mean gestational age at delivery was significantly higher in dichorionic twins who underwent selective feticide before than after 24th gestational week (36.7 vs 33.4, p = 0.04)., Conclusion: Intracardiac injection of potassium chloride was effective for feticide and safe for mothers and fetuses. Selective feticide served as an alternative approach for twin pregnancy with fetal anomaly after sufficient discussion., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2021, the Chinese Medical Association.)

Many parents with a disabled child caused by a genetic condition appreciate the option of prenatal genetic diagnosis to understand the chance of recurrence in a future pregnancy. Genome-wide tests, such as chromosomal microarray analysis and whole-exome sequencing, have been increasingly used for prenatal diagnosis, but prenatal counseling can be challenging due to the complexity of genomic data. This situation is further complicated by incidental findings of additional genetic variations in subsequent pregnancies. Here, we report the prenatal identification of a baby with a MECP2 missense variant and 15q11.2 microduplication in a family that has had a child with developmental and epileptic encephalopathy caused by a de novo KCNQ2 variant. An extended segregation analysis including extended relatives, in addition to the parents, was carried out to provide further information for genetic counseling. This case illustrates the challenges of prenatal counseling and highlights the need to understand the clinical and ethical implications of genome-wide tests., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Ma, Chen, Li and Shaw.)

Diabetes causes vascular injury and carries a high risk of ischaemic stroke. Human amniotic fluid stem cells (hAFSCs) can enhance cerebral vascular remodelling and have the potential to improve neurological function after stroke in diabetic rats. Five groups of female rats were examined: (1) normal control, (2) type 1 diabetic (T1DM) rats induced by streptozotocin injection (DM), (3) non-DM rats receiving 60-minute middle cerebral artery occlusion (MCAO), (4) T1DM rats receiving 60-minute MCAO (DM + MCAO) and (5) T1DM rats receiving 60-minute MCAO and injection with 5 × 10 6  hAFSCs at 3 h after MCAO (DM + MCAO + hAFSCs). Neurological function was examined before, and at 1, 7, 14, 21 and 28 days, and cerebral infarction volume and haemorrhage, cerebral vascular density, angiogenesis and inflammatory were examined at 7 and 28 days after MCAO. hAFSCs treatment caused a significant improvement of neurological dysfunction, infarction volume, blood-brain barrier leakage, cerebral arterial density, vascular density and angiogenesis and a reduction of brain haemorrhage and inflammation compared with non-treatment. Our results showed that the effect of hAFSCs treatment against focal cerebral ischaemia may act through the recovery of vascular remodelling and angiogenesis and the reduction of inflammation in ischaemic brain., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Assisted reproductive technology (ART) has been widely developed over the decades. This advanced technology has shown efficacy in the conception and breeding of an animal. However, several issues such as polyspermy, low maturation rate, and low development rate in vitro remain unresolved. Fallopian tube derived cells are proposed to promote the maturation and development of oocyte. This study aims to characterize porcine (PFTSC) and bovine fallopian tube stem cell (BFTSC) while comparing allogeneic and xenogeneic paracrine effects on porcine oocyte. FTSC of Taiwan yellow cattle (B. indicus) and porcine (Landrace x Yorkshire dam x Duroc) were isolated and identified. Conditioned media (Medium 199 or PZM-3) from porcine and bovine was collected and added to porcine cells during in vitro maturation (IVM) and in vitro culture (IVC). Both PFTSC and BFTSC expressed little CD44, CD105, and CD4. Both cells were induced to transform into chondrocytes, very few cells gave rise to osteocytes and adipocytes. IVM test showed a significant elevation of maturation rate in both groups (Porcine: 66.5 ± 3.5% > 55.9 ± 1.7%, p < .05; Bovine: 68.9 ± 2.3% > 55.9 ± 1.7%, p < .05). IVC test demonstrated markedly reduction of blastocyst in both groups. In a diluted conditioned medium with different concentration, 25% and 50% PFTSC showed a decrease in blastocyst rate which is significantly different, but BFTSC demonstrated no significant difference. PFTSC and BFTSC possessed properties of stem cells. Conditioned media from both PFTSC and BFTSC could improve maturation rate but not blastocyst rate in vitro., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

"Fetus as patient" indicates fundamental concept of fetal therapy. With advance in maternal serum analysis and fetal imaging, prenatal screening has become standard of care. Accurate diagnosis in early gestation allows intervention to reverse pathophysiology and delay progression immediately. Non-invasive, minimally invasive and invasive therapies demonstrate their therapeutic potential in certain diseases. Recently, stem cell and gene therapies have been developed to avoid irreversible impairment. To elevate efficacy of treatment modality, extensive studies should be conducted according to regulatory authority. Striking a balance between scientific and ethical integrity is essential, so long-term follow up should be arranged for protecting mother and fetus., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2021. Published by Elsevier B.V.)

Spinal muscular atrophy (SMA) is a single gene disorder affecting motor function in uterus. Amniotic fluid is an alternative source of stem cell to ameliorate SMA. Therefore, this study aims to examine the therapeutic potential of Human amniotic fluid stem cell (hAFSC) for SMA. Our SMA model mice were generated by deletion of exon 7 of Smn gene and knock-in of human SMN2. A total of 16 SMA model mice were injected with 1 × 10 5 hAFSC in uterus, and the other 16 mice served as the negative control. Motor function was analyzed by three behavioral tests. Engraftment of hAFSC in organs were assessed by flow cytometry and RNA scope. Frequency of myocytes, neurons and innervated receptors were estimated by staining. With hAFSC transplantation, 15 fetuses survived (93.75% survival) and showed better performance in all motor function tests. Higher engraftment frequency were observed in muscle and liver. Besides, the muscle with hAFSC transplantation expressed much laminin α and PAX-7. Significantly higher frequency of myocytes, neurons and innervated receptors were observed. In our study, hAFSC engrafted on neuromuscular organs and improved cellular and behavioral outcomes of SMA model mice. This fetal therapy could preserve the time window and treat in the uterus.

Objective: First trimester screening is essential to preeclampsia (PE) prevention. Fetal Medicine Foundation (FMF) model combined maternal characteristics with mean arterial pressure (MAP), uterine artery pulsatility index (UtAPI) and placental growth factor (PlGF) to estimate risk. High detection rate (DR) was observed in Asia. The study aims to evaluate performance of screening in Taiwan., Materials and Methods: This was a prospective and non-interventional study between January, 2017 and June, 2018. Data was collected from 700 pregnant women at 11 +0 -13 +6 gestational week. Maternal characteristics were recorded. MAP, UtAPI and PlGF were measured and converted into Multiple of the Median (MoM). Patient-specific risks were calculated with FMF model. Performance of screening was examined by ROC curve and DR., Results: 25 women (3.57%) contracted PE, including 8 with preterm PE (1.14%). In preterm PE, mean MoM of MAP and UtAPI were higher (1.096 vs 1.000; 1.084 vs 1.035). Mean MoM of PlGF was lower (0.927 vs 1.031). DR in preterm PE achieved 12.5%, 50.0%, 50.0% and 62.5% at false-positive rate (FPR) of 5%, 10%, 15% and 20%., Conclusion: FMF model showed high DR for PE in Taiwan. Integration of PE and Down screening could set up a one-step workflow., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2021. Published by Elsevier B.V.)

Competing Interests: Dr. Steven W. Shaw, an editor at Journal of Medical Ultrasound, had no role in the peer review process of or decision to publish this article.

Background: High humidity and temperature in Taiwan have significant effects on the reproductivity of Holstein cattle, resulting in the occurrence of bovine ovarian follicular cyst (OFC). Because of economic loss from OFC, manual rupture and hormone injection have been advocated for the management of OFC. However, these incomplete treatments increase hormone resistance in cattle. Mesenchymal stem cells (MSCs) derived from placental stem cells (PSCs) demonstrate potential properties for the treatment of several diseases via promoting angiogenesis and immune modulation., Aim: To establish the possibility of cattle placental stem cells (CPSCs) as a treatment modality for OFC of cows in Taiwan., Methods: The cows with OFC were divided into three groups: control (BC1 and BC2), hormone (H1 and H2), and CPSC (PS1 and PS2) treatment groups. In the hormone treatment group, the cows were given gonadotrophin-releasing hormone (GnRH)-prostaglandin-GnRH intramuscular injection with or without drainage of follicular fluid. In the CPSC treatment group, CPSCs were isolated from the placenta after labor. With the identification of surface antigen on stem cells, the cows were administered ovarian injection of 1 × 10 6 or 6 × 10 6 CPSCs with drainage. In all groups, OFC was scanned by ultrasound once a week for a total of seven times. The concentrations of estradiol and progesterone in serum were tested in the same period. The estrus cycle was analyzed by food intake and activity. If estrus was detected, artificial insemination was conducted. Then the cow was monitored by ultrasound for confirmation of pregnancy., Results: After 7 d of culture, CPSCs were successfully isolated from placental pieces. CPSCs significantly proliferated every 24 h and had high expression of MSC markers such as cluster of differentiation 44, as determined by flow cytometry. Ultrasound showed lower numbers of OFCs with drainage of follicular fluid. We achieved recovery rates of 0%, 50%, 50%, 75%, 75% and 75% in BC1, BC2, H1, H2, PS1, and PS2, respectively. Higher concentrations of progesterone were detected in the CPSC treatment groups. However, both hormone and CPSC treatment groups had no significant difference in the concentration of estradiol. The estrus rate was 0%, 100%, 25%, 75%, 75% and 75% in BC1, BC2, H1, H2, PS1, and PS2, respectively. The two fetuses were born in H2 and PS1. In brief, cows with CPSC injection achieved higher recovery, estrus, and inseminated conception rates., Conclusion: CPSCs have efficacy in treating cows with OFC, and thus, may serve as an alternative treatment for reproductive disorders., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest regarding the publication of this paper., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Autosomal recessive renal tubular dysgenesis (ARRTD) caused by inactivation mutations in AGT , REN , ACE , and AGTR is a very rare but fatal disorder with an unknown prevalence., Methods: We report 6 Taiwanese individuals with ARRTD from 6 unrelated families diagnosed by renal histology. Clinical features, outcome, and prevalence of carrier heterozygosity were examined., Results: All patients exhibited antenatal oligohydramnios, postnatal anuria, pulmonary hypoplasia, and profound hypotension refractory to interventions. Angiotensinogen (AGT) protein levels were diminished in the liver, along with reduced serum AGT, angiotensin I (Ang I) and angiotensin II (Ang II) levels. Neonatal demise occurred in all but 1 case. All individuals carried the same homozygous E3&#95;E4 del:2870bp deletion+9bp insertion in AGT , which led to a truncated protein (1-292 amino acid). The allelic frequency of this heterozygous AGT mutation was approximately 1.2% (6/500), suggesting that ARRTD may not be exceedingly rare in Taiwan. This mutation results in skipping of exons encoding the serpin domain of AGT, which is important for renin interaction and the generation of truncated protein. In silico modeling revealed a diminished interaction between mutant AGT and renin. One patient survived after responding to high-dose hydrocortisone therapy, with resolution of profound hypotension, accompanied by an increase in serum AGT, Ang I, and Ang II levels., Conclusion: This AGT mutation may lead to the diminished interaction with renin and decreased Ang I and Ang II generation. Hydrocortisone may potentially rescue cases of ARRTD caused by this truncated AGT., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Purpose of Review: To review the advance of maternal--fetal surgery, the research of stem cell transplantation and tissue engineering in prenatal management of fetal meningomyelocele (fMMC)., Recent Findings: Advance in the imaging study provides more accurate assessment of fMMC in utero. Prenatal maternal--fetal surgery in fMMC demonstrates favourable postnatal outcome. Minimally invasive fetal surgery minimizes uterine wall disruption. Endoscopic fetal surgery is performed via laparotomy-assisted or entirely percutaneous approach. The postnatal outcome for open and endoscopic fetal surgery shares no difference. Single layer closure during repair of fMMC is preferred to reduce postnatal surgical intervention. All maternal--fetal surgeries impose anesthetic and obstetric risk to pregnant woman. Ruptured of membrane and preterm delivery are common complications. Trans-amniotic stem cell therapy (TRASCET) showed potential tissue regeneration in animal models. Fetal tissue engineering with growth factors and dura substitutes with biosynthetic materials promote spinal cord regeneration. This will overcome the challenge of closure in large fMMC. Planning of the maternal--fetal surgery should adhere to ethical framework to minimize morbidity to both fetus and mother., Summary: Combination of endoscopic fetal surgery with TRASCET or tissue engineering will be a new vision to achieve to improve the outcome of prenatal intervention in fMMC.

Background: Maternal anemia is a risk factor for poor pregnancy outcomes and threatens maternal or fetal life. Anemia increases the risk of low birth weight and preterm birth. We aimed to determine the cutoff level of hemoglobin and risk factors for maternal anemia at admission for delivery and investigate the association between maternal anemia and adverse perinatal outcomes in contemporary Taiwanese women., Methods: About 32,234 women admitted to the Taipei Chang Gung Memorial Hospital from 2001 to 2016 were enrolled in this retrospective observational cohort study. The prevalence of pre-delivery maternal anemia in Taiwan and the maternal demographic and perinatal outcomes associated with maternal anemia was assessed., Results: The 10th and 5th percentile hemoglobin levels of the test cohort (2001-2008, n = 15,602) were 10.8 g/dL and 9.9 g/dL, respectively. In the study cohort (2009-2016, n = 13,026), women who were multiparous, who were aged >34 years, with history of cesarean delivery, and with history of uterine fibroids had higher prevalence of anemia. Anemic women were at increased risk of cesarean delivery, primary cesarean delivery, premature rupture of membranes, early preterm birth <34 weeks, having very low birth weight infants (<1,500 g), having large for gestational age infants, and neonatal intensive care center transfer, but at lower risk of having small for gestational age infants., Conclusion: Maternal anemia at delivery is a risk factor for primary cesarean delivery and adverse maternal and neonatal outcomes. Furthermore, we hypothesize that maternal anemia might increase fetoplacental vasculogenesis and angiogenesis as an adaptive response.

Much is known about the nonlinear resonant response of mechanical systems, but methods for the systematic design of structures that optimize aspects of these responses have received little attention. Progress in this area is particularly important in the area of micro-systems, where nonlinear resonant behaviour is being used for a variety of applications in sensing and signal conditioning. In this work, we describe a computational method that provides a systematic means for manipulating and optimizing features of nonlinear resonant responses of mechanical structures that are described by a single vibrating mode, or by a pair of internally resonant modes. The approach combines techniques from nonlinear dynamics, computational mechanics and optimization, and it allows one to relate the geometric and material properties of structural elements to terms in the normal form for a given resonance condition, thereby providing a means for tailoring its nonlinear response. The method is applied to the fundamental nonlinear resonance of a clamped-clamped beam and to the coupled mode response of a frame structure, and the results show that one can modify essential normal form coefficients by an order of magnitude by relatively simple changes in the shape of these elements. We expect the proposed approach, and its extensions, to be useful for the design of systems used for fundamental studies of nonlinear behaviour as well as for the development of commercial devices that exploit nonlinear behaviour., (© 2015 The Author(s).)

Purpose: USP has formed Advisory Panels to ensure the integrity of laboratory procedures for non-oral routes of administration and expects that the panels will recommend performance tests (performance qualification, PQ) for these dosage forms as well as performance verification tests (PVT) for those PQ tests. An integral part of PQ is PVT, in which a standard formulation is first tested in a metrologically sound collaborative study to set acceptance criteria. Individual laboratories can then test the performance of their product by comparing their results to those obtained from the USP collaborative study. These studies are guided by metrological principles, e.g., those of the International Organization for Standardization (ISO) 43-1, which succinctly states that "one of the main uses of proficiency testing schemes is to assess laboratories' ability to perform tests competently.", Materials and Methods: Four laboratories conducted two collaborative studies to determine the reliability and reproducibility--understood in metrological terms--of release rates from semisolid dosage forms using the vertical diffusion cell (VDC)., Results: The experiments reported here from the second study found that the major contributor to variability is the interlaboratory component that may include intermediate precision considerations other than analyst. Because all laboratories used the same model equipment, one might expect that the observed reproducibility CV was lower than if the laboratories used different models or equipment made by different manufacturers. Also, more variability was observed with the creams than the other dosage forms., Conclusions: The results from the preliminary collaborative study found inconsistency among the laboratories. After operator training, the results from the second study were more consistent, suggesting the initial results were associated with variations among the laboratories in performing the methods and procedures and conducting the protocols. Those results emphasize that although the in vitro release procedure is simple and reproducible, training is needed. The data presented suggest that testing of in vitro release by VDCs should be considered as a PVT for topical semisolid dosage forms. Thus, a standard semisolid product is needed, along with a means for setting acceptance criteria. The SUPAC-SS Guidance may be helpful in the latter regard.