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Traditional object counting systems use object detection methods to count objects. However, when objects are small, crowded, and dense, object detection may fail, leading to inaccuracies in counting. To address this issue, we propose a crowded object counting system based on density map estimation. While most density map estimation models employ encoder–decoder or multi-branch approaches to generate feature maps at different scales for obtaining an accurate density map, improving the accuracy of crowded object counting remains a challenge. In this paper, we propose a novel model that can generate more accurate density maps, utilizing the context-aware network as the primary structure and integrating the self-attention mechanism. There are three main contributions in this paper. Firstly, the self-attention mechanism is employed to improve the accuracy of density map estimation. Secondly, the missing vehicle labels in the TRANCOS database are relabeled, ensuring that the ground truth data are more complete than the original TRANCOS database, thus enabling the proposed novel model to have higher crowded object counting accuracy. Thirdly, the parameters of the self-attention mechanism are analyzed to obtain the optimum parameter combination. The experimental results demonstrate that the accuracy of crowded object counting can reach 85.9%, 90.0%, 83.4%, and 92.6% for the TRANCOS, relabeled TRANCOS, ShanghaiTech Part A, and Part B datasets, respectively. Furthermore, the ablation study for the context-aware network with self-attention mechanism analyzes the optimum parameter combination.

Abstract Demand for sustainably produced biomass is expected to increase with the need to provide renewable commodities, improve resource security and reduce greenhouse gas emissions in line with COP26 commitments. Studies have demonstrated additional environmental benefits of using perennial biomass crops (PBCs), when produced appropriately, as a feedstock for the growing bioeconomy, including utilisation for bioenergy (with or without carbon capture and storage). PBCs can potentially contribute to Common Agricultural Policy (CAP) (2023–27) objectives provided they are carefully integrated into farming systems and landscapes. Despite significant research and development (R&D) investment over decades in herbaceous and coppiced woody PBCs, deployment has largely stagnated due to social, economic and policy uncertainties. This paper identifies the challenges in creating policies that are acceptable to all actors. Development will need to be informed by measurement, reporting and verification (MRV) of greenhouse gas emissions reductions and other environmental, economic and social metrics. It discusses interlinked issues that must be considered in the expansion of PBC production: (i) available land; (ii) yield potential; (iii) integration into farming systems; (iv) R&D requirements; (v) utilisation options; and (vi) market systems and the socio‐economic environment. It makes policy recommendations that would enable greater PBC deployment: (1) incentivise farmers and land managers through specific policy measures, including carbon pricing, to allocate their less productive and less profitable land for uses which deliver demonstrable greenhouse gas reductions; (2) enable greenhouse gas mitigation markets to develop and offer secure contracts for commercial developers of verifiable low‐carbon bioenergy and bioproducts; (3) support innovation in biomass utilisation value chains; and (4) continue long‐term, strategic R&D and education for positive environmental, economic and social sustainability impacts.

Abstract To help meet greenhouse gas mitigation targets perennial biomass crops will need to be planted at large scales and at a much greater pace over the coming decades. Miscanthus is a leading biomass crop but rapid upscaling is technically challenging due to costly and time‐consuming clonal propagation. Seed‐based hybrids are considered a viable route to rapid upscaling, but direct sowing has not been found feasible under temperate climate conditions due to high thermal requirements for germination and slow early plant development compared with larger seeded annuals. Seed‐based plug plants, initially propagated in greenhouses, provide a suitable route to improve field establishment. Here, we describe an input optimization experiment for seeded Miscanthus plugs raised for spring planting in a naturally lit greenhouse with the following treatments: supplemental heat to maintain a minimum of 15°C, supplemental predawn light from modern LEDs at PPFD 300–400 μmol m−2 s−1, two proprietary types of compost (known as 50k and 70k), and two compost volumes (35 and 15 cm3). Our results showed that variations in all four factors had significant effects on above‐ and belowground biomass: (i) supplemental heat increased root‐to‐shoot ratio, (ii) supplemental light increased total biomass and root‐to‐shoot ratio, (iii) compost type affected total biomass and (iv) compost volume was positively correlated with total biomass and stem base diameter. No factor had a significant effect on axillary shoot formation. We recommend nurseries in the United Kingdom use LEDs as predawn supplemental light but no supplemental heat, compost that has both good water‐holding capacity and aeration, and a larger compost volume, which provided optimized cost‐plug resilience for spring‐sown, seed‐based Miscanthus plug production.

BackgroundFew studies have addressed early-stage kidney disease and preclinical cardiac structural and functional abnormalities from a large-scale Asian population. Further, the extent to which measures of myocardial function and whether these associations may vary by testing various formulas of renal insufficiency remains largely unexplored.ObjectiveTo explore the associations among renal function, proteinuria, and left ventricular (LV) structural and diastolic functional alterations.DesignA cross-sectional, retrospective cohort study.SettingRegistered data from a cardiovascular health screening program at MacKay Memorial Hospital from June 2009 to December 2012.ParticipantsAsymptomatic individuals.MeasurementsRenal function was evaluated in terms of estimated glomerular filtration rate (eGFR) by both MDRD and CKD-EPI formulas and severity of proteinuria, which were further related to cardiac structure, diastolic function (including LV e’ by tissue Doppler), and circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) level.ResultsAmong 4942 participants (65.8% men, mean age 49.4 ± 11.2 years), the mean CKD-EPI/MDRD eGFR was 90.6 ± 15.7 and 88.5 ± 16.9 ml/min/1.73m2, respectively. Lower eGFR, estimated either by the MDRD or CKD-EPI method, and higher proteinuria were significantly associated with lower LV e’ and higher NT-proBNP (all p

As all kinds of self-contained display products have become popular, various technologies for improving printing applications have gradually been ignored or even stagnated. However, the number of printed matters in life has not decreased. Every day our lives are full of various printed materials, such as newspapers, magazines, leaflets, product packaging, and so on. The waste and pollution caused by printing technology are usually recessive, and not everyone values it. Unfortunately, people often overlook the waste of resources and environmental pollution caused by the manufacturing process, ink, toner, and printers. The method proposed in this paper uses a color difference model to find a manner that is not easy to notice by the human eye to save ink. The proposed method considers feasibility and practicability, and users can quickly find suitable settings for their applications. Also, through the actual printed pictures, the experimental results show that only 67.57% of the original ink consumption is required to obtain an equivalent print quality that is difficult to perceive by the human eye. Our proposed method will benefit the printing industry and reduce ink consumption on consumer printers, contributing to cost control and being nature-friendly.

Pulmonary fibrosis is a major public health problem with unclear mechanism and limited therapeutic options. Here the authors show that a fibroblast-enriched endoplasmic reticulum protein, TXNDC5, promotes pulmonary fibrosis by stabilizing TGFBR1 and show the potential of TXNDC5 as a therapeutic target against pulmonary fibrosis.

The existing differential item functioning (DIF) detection approaches relying on item difficulty or item discrimination are limited for understanding the associates of DIF items, and consequently, DIF items were conventionally either deleted or ignored. Given the importance of minimizing DIF items in test construction, teachers or testing practitioners need more information regarding possible associates of DIF items. Using an example of a teacher-made mathematics achievement test, this study aimed to examine how the Poly-BW indices (power, defenselessness, disturbance, and hint) contributed to the properties of gender-related DIF items. Data from a 34-item mathematics achievement test that involved 1,439 seventh-grade students from Taiwan (51.01% boys and 48.99% girls) showed that the differences of the defenselessness (mp) and power (cp) indices between men and women served as salient predictors of the DIF measures estimated by the Poly Simultaneous Item Bias Test (Poly-SIBTEST) procedure and with satisfactory accuracy of hit rates. Items with relatively large defenselessness for men were likely to present male-favoring DIFs, whereas items with relatively large power for men were likely to present female-favoring DIFs. The Poly-BW indices yielded directions for modifying items for teachers in practice.

Geosynthetics and deep cement mixed (DCM) soil columns have been widely used to improve soft soil grounds in many countries and regions. This paper presents an experimental study on a geosynthetic-reinforced sand fill over marine clay with or without DCM columns under different loadings. Two tests were conducted on the sand fill reinforced with fixed-end and free-end geosynthetics over marine clay under three-stage local loading to investigate the effects of the boundary conditions of geosynthetic reinforcement on reducing settlements. It is observed that the fixed-end geosynthetic sheet is more effective in reducing settlements than the free-end condition under identical local loading. Another test was conducted on the fixed-end geosynthetic-reinforced sand fill over the marine clay improved by DCM columns under single-stage uniform loading. The vertical stresses on the marine clay and on the DCM columns, as well as the tensile strains of the geosynthetic sheet in the overlying sand fill, were measured. The results revealed that the stress concentration ratio increases with an increase in consolidation settlements, and the maximum tensile strain of the geosynthetic sheet occurs near the edge rather than at the center of the top surface of the DCM columns. Keywords: Settlement, Geosynthetic, Reinforcement, Deep cement mixed soil columns

Cinnamomum insularimontanum is an endemic species of Taiwan. Although most Cinnamomum plants have significant biological activity, the bioactivity investment of C. insularimontanum is rare. Since inflammation plays an important role in many diseases, anti-inflammatory compounds can be developed into healthcare products. Therefore, we first conducted a study on the anti-inflammatory activity of C. insularimontanum leaves. First, we examined the antiinflammation activity of essential oil from C. insularimontanum leaves, and it revealed potent anti-inflammatory activity. A total of 23 volatile compounds were identified in C. insularimontanum leaves’ essential oil by using GC/MS analysis. Among them were 1,8-cineole (35.94%), α-eudesmol (6.17%), pinene (7.55%), sabinene (5.06%), and isobornyl acetate (4.81%). According to previous studies, 1,8-cineole might be an anti-inflammation principal compound of C. insularimontanum leaves. Next, the ethanolic extracts of C. insularimontanum leaves also exhibited good anti-inflammatory activity. Two bioactive compounds, isoburmanol (F1) and burmanol (F2), were isolated from the ethyl acetate soluble fraction by using the bioactivity-guided separation protocol and spectroscopic analysis. F1 was obtained from C. insularimontanum for the first time, and F2 was isolated for the first time from natural resources. Both F1 and F2 could inhibit the production of nitric oxide (NO), and the IC50 values were 14.0 μM and 43.8 μM, RAW 264.7 cells after induction of lipopolysaccharide. Furthermore, F1 and F2 also revealed significant inhabitation effects on iNOS and COX-2 protein expression. The anti-inflammation activity of F1 and F2 was different from the common pathway of inhibiting NF-κB. Both of them could inhibit the production of NO and PGE2 by directly inhibiting the AP-1 (c-Jun) protein and then inhibiting the downstream iNOS and COX-2. Although both F1 and F2 possessed significant anti-inflammatory activity, the activity of F1 was better than F2. Through molecular docking simulation analysis, the results show that F1 and F2 interact with AP-1, inhibit the binding of AP-1 to DNA, and cause AP-1 to fail to transcribe the related factors of inflammation. The binding ability of AP-1 and F1 was stronger than F2, and that is the reason why F1 exhibited better activities in both downstream proteins and inflammatory cytokines. Based on the results obtained in this study, the essential oil and F1 and F2 isolated from C. insularimontanum leaves have good anti-inflammatory activities, and it is expected to be used as a reference for the development of medical care products in the future.

Due to the short supply of conventional fill materials, such as sand, land reclamation using dredged marine deposits has recently been proposed, in which marine deposits with high water content are blow-filled into reclaiming areas. The strength development of the filled marine soils is of great importance during the sedimentation and consolidation to guide the filling process and construction of reclamation. In this study, a novel sensor based on optical frequency domain reflectometry (OFDR) technology with a simple design was developed for undrained shear strength measurement. The novel sensor consists of an optical fiber and a series of polyoxymethylene coins. Owing to the merits of OFDR technology on high resolution, fully distributed sensing, and immunity to electromagnetic interference, the novel sensor can be used to determine undrained shear strength profiles of very soft to soft marine sediments/soils with good accuracy. The sensor was calibrated in remolded marine deposits with different water contents. The good feasibility and performance of the novel sensor for undrained shear strength measurement were well validated in two physical model tests on marine deposits treated by horizontal drains with vacuum preloading.

Abstract Robot hands have been developing during the last few decades. There are many mechanical structures and analytical methods for different hands. But many tough problems still limit robot hands to apply in homelike environment. The ability of grasping objects covering a large range of sizes and various shapes is fundamental for a home service robot to serve people better. In this paper, a new grasping mode based on a novel sucked-type underactuated (STU) hand is proposed. By combining the flexibility of soft material and the effect of suction cups, the STU hand can grasp objects with a wide range of sizes, shapes and materials. Moreover, the new grasping mode is suitable for some situations where the force closure is failure. In this paper, we deduce the effective range of sizes of objects which our hand using the new grasping mode can grasp. Thanks to the new grasping mode, the ratio of grasping size between the biggest object and the smallest is beyond 40, which makes it possible for our robot hand to grasp diverse objects in our daily life. For example, the STU hand can grasp a soccer (220 mm diameter, 420 g) and a fountain pen (9 mm diameter, 9 g). What’s more, we use the rigid body equilibrium conditions to analysis the force condition. Experiment evaluates the high load capacity, stability of the new grasping mode and displays the versatility of the STU hand. The STU hand has a wide range of applications especially in unstructured environment.

Background: Intradialytic hypotension (IDH) is a serious complication and a major risk factor of increased mortality during hemodialysis (HD). However, predicting the occurrence of intradialytic blood pressure (BP) fluctuations clinically is difficult. This study aimed to develop an intelligent system with capability of predicting IDH. Methods: In developing and training the prediction models in the intelligent system, we used a database of 653 HD outpatients who underwent 55,516 HD treatment sessions, resulting in 285,705 valid BP records. We built models to predict IDH at the next BP check by applying time-dependent logistic regression analyses. Results: Our results showed the sensitivity of 86% and specificity of 81% for both nadir systolic BP (SBP) of

A singleton pregnant woman was found to have persistent left superior vena cava (PLSVC) of the fetus at 22 weeks by ultrasound. Follow-up scans revealed PLSVC, dilated coronary sinus, dominant right heart, some pericardial effusion, and hypertrophy of the right ventricular wall. The woman had an abdominal delivery at 34 weeks due to rupture of membranes. The baby was found to have coarctation of the aorta postnatally and had aortic reconstruction at 31 days of age. A prenatal ultrasound finding of PLSVC might be associated with coarctation of the aorta and it warrants specialist follow-ups and complete workup of echocardiography prenatally and postnatally.

Abstract Background Although the optimal timing of initiation of renal replacement therapy (RRT) in critically ill patients with acute kidney injury has been extensively studied in the past, it is still unclear. Methods In this systematic review, we searched all related randomized controlled trials (RCTs) that directly compared earlier and later RRT published prior to June 25, 2016, from PubMed, MEDLINE, and EMBASE. We extracted the study characteristics and outcomes of all-cause mortality, RRT dependence, and intensive care unit (ICU) and hospital length of stay (LOS). Results We identified 51 published relevant studies from 13,468 screened abstracts. Nine RCTs with 1627 participants were included in this meta-analysis. Earlier RRT was not associated with benefits in terms of mortality [relative risk (RR) 0.88, 95% confidence interval (CI) 0.68–1.14, p = 0.33] and RRT dependence (RR 0.81, 95% CI 0.46–1.42, p = 0.46). There were also no significant differences in the ICU and hospital LOS between patients who underwent earlier versus later RRT [standard means difference −0.08 (95% CI −0.26 to 0.09) and −0.11 (95% CI −0.37 to 0.16) day, respectively]. In subgroup analysis, earlier RRT was associated with a reduction in the in-hospital mortality among surgical patients (RR 0.78, 95% CI 0.64–0.96) and patients who underwent continuous renal replacement therapy (CRRT) (RR 0.80, 95% CI 0.67–0.96). Conclusions Compared with later RRT, earlier initiation of RRT did not show beneficial impacts on patient outcomes. However, a lower rate of death was observed among surgical patients and in those who underwent CRRT. The included literature is highly heterogeneous and, therefore, potentially subject to bias. Further high-quality RCT studies are warranted.

Objective: We present molecular cytogenetic characterization of Jacobsen syndrome (11q23.3-q25 deletion) in a fetus associated with double outlet right ventricle (DORV), hypoplastic left heart syndrome (HLHS), and ductus venosus (DV) agenesis on prenatal ultrasound. Case Report: A 26-year-old woman underwent prenatal ultrasound examination at 22 weeks of gestation, which revealed intrauterine growth restriction, short femurs, DORV, HLHS, DV agenesis, single umbilical artery, and curly fourth toe of the left foot. The parents elected to terminate the pregnancy, and a 500-g female fetus was delivered at 23 weeks of gestation with facial dysmorphism, bilateral camptodactyly, and hammertoes. The parental karyotypes were normal. Cytogenetic analysis of the cord blood and umbilical cord revealed a karyotype of 46,XX,del(11)(q23). Array comparative genomic hybridization analysis of the DNA extracted from the umbilical cord revealed a 14.38-Mb deletion of 11q23.3-q25 encompassing BSX, ETS1, FLI1, and ARHGAP32. Metaphase fluorescence in situ hybridization analysis using the probes RP11-209L12 (11q25) and RP11-25M7 (11q11) showed a distal 11q deletion in the aberrant chromosome 11 in 17/17 cells examined. Conclusion: Prenatal diagnosis of DORV, HLHS, DV agenesis associated with intrauterine growth restriction and short limbs should include a differential diagnosis of Jacobsen syndrome.

Objective: We present perinatal imaging findings and molecular genetic analysis of thanatophoric dysplasia type I (TD1) in a fetus. Case Report: A 28-year-old woman was referred for genetic counseling at 22 weeks of gestation because of abnormal prenatal ultrasound findings. Level II ultrasound examination revealed a narrow chest, shortened and curved long limbs, protrusion of the abdomen, and macrocephaly. A tentative diagnosis of TD1 was made. After genetic counseling, the pregnancy was terminated and a malformed fetus was delivered. Postnatal radiography findings were consistent with the diagnosis of TD1, with additional findings of short ribs, platyspondyly, and horizontal acetabular roofs. Molecular genetic analysis using umbilical cord tissue revealed a heterozygous mutation of c.2419T>G (p.Ter807Gly) (X807G) in the fibroblast growth factor receptor 3 gene (FGFR3). Conclusion: A second-trimester fetus with a heterozygous c.2419T>G mutation in FGFR3 may present characteristic ultrasound and X-ray findings of TD1.

Background/Aims: Indoxyl sulfate (IS) is a protein-bound uremic toxin that accumulates in patients with chronic kidney disease (CKD). We explored the effect of IS on human early endothelial progenitor cells (EPCs) and analyzed the correlation between serum IS levels and parameters of vascular function, including endothelial function in a CKD-based cohort. Methods: A cross-sectional study with 128 stable CKD patients was conducted. Flow-mediated dilation (FMD), pulse wave velocity (PWV), ankle brachial index, serum IS and other biochemical parameters were measured and analyzed. In parallel, the activity of early EPCs was also evaluated after exposure to IS. Results: In human EPCs, a concentration-dependent inhibitory effect of IS on chemotactic motility and colony formation was observed. Additionally, serum IS levels were significantly correlated with CKD stages. The total IS (T-IS) and free IS (F-IS) were strongly associated with age, hypertension, cardiovascular disease, blood pressure, PWV, blood urea nitrogen, creatine and phosphate but negatively correlated with FMD, the estimated glomerular filtration rate (eGFR), hemoglobin, hematocrit, and calcium. A multivariate linear regression analysis also showed that FMD was significantly associated with IS after adjusting for other confounding factors. Conclusions: In humans, IS impairs early EPCs and was strongly correlated with vascular dysfunction. Thus, we speculate that this adverse effect of IS may partly result from the inhibition of early EPCs.

Objective: To report prenatal diagnosis of 22q11.2 deletion syndrome with right aortic arch (RAA), left ductus arteriosus, cardiomegaly, and pericardial effusion in the fetus. Case report: A 35-year-old woman, gravida 2, para 1, was referred to the hospital at 31 weeks of gestation because of abnormal ultrasound findings and whole-genome array comparative genomic hybridization report. G-banding chromosome analysis revealed a karyotype of 46,XX. Level II ultrasound at 22 weeks of gestation revealed RAA with the presence of the aortic arch on the right side of trachea at three vessels and trachea view, left ductus arteriosus, and mild right side pyelectasis. Cardiomegaly and pericardial effusion were also found 2 months later. Array comparative genomic hybridization detected a 2.743-Mb deletion at 22q11.2 region. Multiplex ligation-dependent amplification detected deletion in the DiGeorge syndrome critical region of chromosome 22 low copy number repeat 22-A–C. Metaphase fluorescence in situ hybridization on lymphocyte in cord blood confirmed deletion in 22q11.2 region. Conclusion: Chromosome abnormalities have been found in patients with RAA. Prenatal diagnosis of RAA with or without intracardiac or extracardiac anomalies should include a diagnosis of 22q11.2 deletion syndrome.

The anti-melanogenic activity of essential oils of Alpinia nantoensis and their bioactive ingredients were investigated in vitro. Treatment with leaf (LEO) and rhizome (REO) essential oils of A. nantoensis, significantly reduced forskolin-induced melanin production followed by down-regulation of tyrosinase (TYR) and tyrosinase related protein-1 (TRP-1) expression at both transcriptional and translational levels. Further studies revealed that down-regulation TYR and TRP-1 were caused by LEO/REO-mediated suppression of Microphthalmia-associated transcription factor (MITF), as evidenced by reduced nuclear translocation of MITF. Also, we found that LEO/REO induce the sustained activation of ERK1/2, which facilitate subsequent proteasomal degradation of MITF, as confirmed by that LEO/REO failed to inhibits MITF activity in ERK1/2 inhibitor treated cells. In addition, a significant increase of ubiquitinated MITF was observed after treatment with LEO and REO. Furthermore, the chemical composition of LEO and REO were characterized by gas chromatography-mass spectrometry (GC-MS) resulted that camphor, camphene, α-pinene, β-pinene, isoborneol and D-limonene were the major compounds in both LEO and REO. Further studies revealed that α-pinene and D-limonene were the active components responsible for the anti-melanogenic properties of LEO and REO. Based on the results, this study provided a strong evidence that LEO and REO could be promising natural sources for the development of novel skin-whitening agents for the cosmetic purposes.

To interpret how the thickness of the peripapillary retinal nerve fiber layer (RNFL) changes with increasing age, axial length, or anterior chamber depth as measured by spectral domain optical coherence tomography (OCT) in the normal elderly population in Taiwan.A total of 82 volunteers (143 eyes) were enrolled. Generalized estimating equations were used to evaluate the correlation.The RNFL was significantly thinner in the superonasal (p = 0.004), inferotemporal (p = 0.046), and temporolower (p = 0.009) segments with age. The same trend was also observed in the superotemporal (p = 0.330) segment, although it was not statistically significant. The global RNFL thickness decreased by 4.97 μm per decade (β = -0.497; p = 0.021), and thinning was significant in the superonasal (-9.90 μm per decade, p < 0.001) and temporolower (-6.78 μm per decade, p < 0.001) segments; the same trend showed borderline significance in the superotemporal (-6.96 μm per decade, p = 0.073) and inferotemporal (-7.23 μm per decade, p = 0.059) segments. In eyes with longer axial length, the RNFLs significantly decreased in the non-temporal segments. Global RNFL thickness decreased by 3.086 μm for each additional millimeter of axial length (β = -3.086; p < 0.001).Changes in RNFL thickness were correlated with age in the superonasal, superotemporal, inferotemporal, and temporolower segments, and were correlated with axial length in the non-temporal segments. Anterior chamber depth was not correlated with RNFL thickness.

Postoperative acute kidney injury (AKI) is common following cardiac surgery (CS). Body weight (BW) may be an amenable variable by representing the summation of the nutritional and the fluid status. However, the predictive role of perioperative BW changes in CS patients with severe postoperative AKI is never explored. This study aimed to evaluate this association.This study was conducted using a prospectively collected multicenter cohort, NSARF (National Taiwan University Hospital Study Group on Acute Renal Failure) database. The adult CS patients with postoperative AKI requiring renal replacement therapy (RRT), who had clear initial consciousness, received CS within 14 days of hospitalization, and underwent RRT within seven days after CS in intensive care units from January 2001 to January 2014 were enrolled. With the endpoint of 30-day postoperative mortality, we evaluated the association between the clinical factors denoting fluid status and patients outcomes.A total of 188 patients (70 female, mean age 63.7 ± 15.2 years) were enrolled. Comparing with the survivors (n = 124), the non-survivors (n = 64) had a significantly higher perioperative BW change [3.6 ± 6.1% versus 0.1 ± 8.3%, p = 0.003] but not the postoperative and pre-RRT BW changes. By using multivariate Cox proportional hazards model, the independent indicators of 30-day postoperative mortality included perioperative BW change (p = 0.026) and packed red blood cells transfusion (p = 0.007), postoperative intra-aortic balloon pump (p = 0.001) and central venous pressure level (p = 0.005), as well as heart rate (p = 0.022), sequential organ failure assessment score (p < 0.001), logistic organ dysfunction score (p = 0.001), and blood total bilirubin level (p = 0.044) at RRT initiation. The generalized additive models further demonstrated, in a multivariate manner, that the mortality risk rose significantly during a perioperative BW change of 2% to 15%.Perioperative BW change was independently associated with an increased risk for 30-day postoperative mortality in CS patients with RRT-requiring AKI.

Objective: We report prenatal diagnosis of hypomethylation at KvDMR1 and Beckwith–Wiedemann syndrome (BWS) in a pregnancy conceived by intracytoplasmic sperm injection and in vitro fertilization and embryo transfer. Case report: A 34-year-old, primigravid woman was referred to the hospital at 21 weeks' gestation because of advanced maternal age and an isolated omphalocele in the fetus. Her husband had the fertility problem of oligospermia. This pregnancy was achieved by intracytoplasmic sperm injection and in vitro fertilization and embryo transfer. Prenatal ultrasound revealed a 2.1 cm × 1.6 cm isolated omphalocele. The woman underwent amniocentesis. Array comparative genomic hybridization and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were applied to the DNA extracted from the uncultured amniocytes. Conventional cytogenetic analysis and high-resolution melting analysis were performed on cultured amniocytes. Array comparative genomic hybridization revealed no genomic imbalance. MS-MLPA analysis revealed H19DMR(IC1) normal methylation and KvDMR1(IC2) hypomethylation. Conventional cytogenetic analysis revealed a karyotype of 46,XX. High-resolution melting analysis using a methylation-specific polymerase chain reaction assay confirmed normal methylation at H19DMR(IC1) and hypomethylation at KvDMR1(IC2). The altered methylation status at 11p15.5 and the phenotype of omphalocele were consistent with the diagnosis of BWS. Conclusion: In case of prenatally detected omphalocele associated with an obstetric history of assisted reproductive technology, a differential diagnosis of BWS should be considered. Methylation assays such as MS-MLPA and methylation-specific polymerase chain reaction using uncultured amniocytes are useful for rapid diagnosis of BWS under such circumstances.

Because of its high prevalence worldwide, osteoporosis is considered a serious public health concern. Many known risk factors for developing osteoporosis have been identified and are crucial if planning health care needs. Recently, an association between uric acid (UA) and bone fractures had been explored. Extracellular UA exhibits antioxidant properties by effectively scavenging free radicals in human plasma, but this benefit might be disturbed by the hydrophobic lipid layer of the cell membrane. In contrast, intracellular free oxygen radicals are produced during UA degradation, and superoxide is further enhanced by interacting with NADPH oxidase. This intracellular oxidative stress, together with inflammatory cytokines induced by UA, stimulates osteoclast bone resorption and inhibits osteoblast bone formation. UA also inhibits vitamin D production and thereby results in hyper-parathyroidism, which causes less UA excretion in the intestines and renal proximal tubules by inhibiting the urate transporter ATP-binding cassette subfamily G member 2 (ABCG2). At normal or high levels, UA is associated with a reduction in bone mineral density and protects against bone fracture. However, in hyperuricemia or gout arthritis, UA increases bone fracture risk because oxidative stress and inflammatory cytokines can increase bone resorption and decrease bone formation. Vitamin D deficiency, and consequent secondary hyperparathyroidism, can further increase bone resorption and aggravated bone loss in UA-induced osteoporosis.

Objective: To present prenatal diagnosis and molecular cytogenetic characterization of trisomy 18 in a monozygotic twin pregnancy, with one structurally abnormal living fetus and one intrauterine fetal demise. Case Report: A 38-year-old woman was referred for amniocentesis at 16 weeks of gestation because of advanced maternal age. Prenatal ultrasound revealed a monozygotic twin pregnancy, with one structurally abnormal living fetus, and one fetal demise. The body structure details of the dead fetus could not be identified, whereas holoprosencephaly and omphalocele were identified in the living fetus on prenatal ultrasound. Quantitative fluorescent polymerase chain reaction assays using polymorphic DNA markers specific for chromosome 21 and chromosome 18, were applied to the uncultured amniocytes in the amniotic cavity of the living fetus and the cultured amniocytes in the amniotic cavity of the fetus with intrauterine fetal demise. The specimen showed a dosage ratio of 2:1 (paternal:maternal) for chromosome 18-specific markers in both twins. The result was consistent with monozygosity and trisomy 18, and the trisomy 18 was possibly caused by a paternal second meiotic division non-disjunction error or a postzygotic mitotic error. Conventional cytogenetic analysis revealed a karyotype of 47,XY,+18 in both twins. The pregnancy was terminated at 19 weeks of gestation, and a 2 g small-for-date macerated twin A and a 166 g malformed twin B were delivered. Twin A manifested cebocephaly and omphalocele, and twin B manifested premaxillary agenesis and omphalocele. Conclusion: The present case provides evidence that fetal wastage may occur in one of the co-twins in monozygotic twins associated with trisomy 18, and this may in part explain the very rare occurrence of living monozygotic twins with trisomy 18.

Objective: To demonstrate perinatal imaging findings and to investigate the mutation in the NEK1 gene in a fetus with type II short rib-polydactyly syndrome (SRPS) (Majewski). Case Report: A 34-year-old woman with a past history of fetal SRPS was referred to the hospital at 16 weeks of gestation because of sonographic diagnosis of short limbs in the fetus. Fetal ultrasound revealed short ribs, short limbs, absence of tibiae, polydactyly, syndactyly and choroid plexus cysts. At 21 weeks of gestation, polycystic kidneys were found. The pregnancy was terminated, and a fetus was delivered with facial dysmorphism, a median cleft lip, a narrow chest, micromelia, aplasia of tibiae, hypoplastic nails, syndactyly and postaxial polydactyly. The karyotype was 46,XX. Molecular analysis of fetal tissues showed a paternal-origin heterozygous splice site mutation in intron 7 (c.465-1 G>A) in the NEK1 gene, but no mutations in the genes of WDR35, DYNC2H1, IFT80, EVC and EVC2. The NEK1 mutation causes an alteration of the splice acceptor site of intron 7 (IVS7-1 G>A). No second mutation was identified. Conclusion: Tibial aplasia, choroid plexus cysts and polycystic kidneys can be prominent prenatal ultrasound findings of type II SRPS. The present case provides evidence for a correlation of NEK1 mutation with type II SRPS.

Objective: To present rapid aneuploidy diagnosis (RAD) of partial trisomy 7q (7q34→qter) and partial monosomy 10q (10q26.12→qter) by array comparative genomic hybridization (aCGH) using uncultured amniocytes. Case Report: A 34-year-old, gravida 2, para 1, woman underwent amniocentesis at 20 weeks of gestation because of a previous mentally retarded child with an unbalanced reciprocal translocation inherited from the carrier father who had a karyotype of 46,XY,t(7;10) (q34;q26.12). Her first child was initially found to have a normal karyotype by routine cytogenetic analysis, but a cryptic chromosomal abnormality was subsequently diagnosed by aCGH. During this pregnancy, RAD by oligonucleotide-based aCGH using uncultured amniocytes revealed a 16.4-Mb duplication of 7q34–q36.3 and a 12.7-Mb deletion of 10q26.12–q26.3. Conventional cytogenetic analysis using cultured amniocytes revealed a karyotype of 46,XX,der(10)t(7;10)(q34;q26.12)pat. The parents elected to terminate the pregnancy. A malformed female fetus was delivered with a high prominent forehead, hypertelorism, epicanthic folds, a broad depressed nasal bridge, a prominent nose with anteverted nostrils, micrognathia, a short neck, large low-set ears, clinodactyly, small big toes, and normal female external genitalia. Conclusion: aCGH is a useful tool for RAD of subtle chromosomal rearrangements in pregnancy, especially under the circumstance of a previous abnormal child with an unbalanced translocation derived from a parental subtle reciprocal translocation.

This two-part study aimed to investigate compliance with the sepsis resuscitation bundle (SRB) and the barriers to its implementation for patients developing septic shock in the general medical wards. Methods: In the first part, medical records of patients who were admitted to the intensive care unit from the general medical wards due to septic shock were reviewed. Compliance rates with the six SRB components were assessed. In the second part, responsible junior physicians (first-year and second-year residents) in the general wards and senior physicians (third-year residents and fellows) were randomly invited for questionnaire-based interviews. Results: In the first part, during the 6-month study period, 40 patients were included. Overall compliance with the SRB within 6 h was only 2.5%, mainly due to femoral catheterization (42.5%) and the lack of measuring central venous oxygen saturation (ScvO2). Delayed completion of SRB components contributed little to the low compliance rate. In the second part, based on the questionnaire results of 71 junior physicians and 64 senior physicians, the junior physicians were less familiar with the SRB guidelines, particularly regarding the meaning of ScvO2 (p = 0.01) and management of low ScvO2 (p = 0.04). Junior physicians were also more reluctant to measure the central venous pressure (CVP; p = 0.04) and the ScvO2 (p = 0.01), and were also less confident with internal jugular vein or subclavian vein catheterization (p

Objectives: To present prenatal diagnosis and molecular cytogenetic characterization of de novo partial partial trisomy 21q (21q22.11→qter) associated with clinodactyly and hypoplastic midphalanx of the fifth fingers, midface hypoplasia, and an intracardiac echogenic focus on prenatal ultrasound. Materials, Methods, and Results: A 34-year-old gravida 2, para 1 woman underwent amniocentesis at 20 weeks of gestation because of fetal structural abnormalities on prenatal ultrasound. A level II ultrasound at 20 weeks of gestation showed polyhydramnios, clinodactyly and hypoplastic midphalanx of the fifth fingers, midface hypoplasia, and an intracardiac echogenic focus. Amniocentesis revealed an aberrant derivative chromosome 9, or der(9). Parental karyotypes were normal. Spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) analyses revealed that the der(9) contained a segment of chromosome 21 distal to chromosome 9q, and FISH analysis additionally showed that the distal subtelomeric region of 9q was not deleted. Array comparative genomic hybridization (aCGH) demonstrated a 14.8-Mb duplication of distal 21q encompassing the Down syndrome critical region (DSCR) but no genomic imbalance in the distal euchromatic region of chromosome 9. The karyotype was 46,XX,der(9)t(9;21) (q34.3;q22.11)dn. Polymorphic DNA marker analysis revealed the maternal origin of the aberrant chromosome. The pregnancy was subsequently terminated. A malformed female fetus was delivered with a characteristic phenotype of Down syndrome. Conclusion: SKY, FISH and aCGH are useful in prenatal investigation of the nature of a de novo aberrant derivative chromosome. Partial trisomy 21q encompassing the DSCR may present characteristic Down syndrome features on prenatal ultrasound.

Objective: To present the prenatal diagnosis and molecular investigation of the parental origin and mechanism of nondisjunction underlying an 48,XXY,+18 karyotype in a fetus with congenital abnormalities, and to review the literature. Materials, Methods, and Results: A 42-year-old woman was referred for amniocentesis at 18 weeks of gestation because of advanced maternal age. Prenatal ultrasound revealed bilateral choroid plexus cysts. Amniocentesis revealed a karyotype of 48,XXY,+18. The parental karyotypes were normal. Level II ultrasound revealed a flexion contracture deformity of the left wrist with absence of the thumb. The pregnancy was terminated at 22 weeks of gestation. A 332 g male fetus was delivered with clenched hands, arthrogryposis of the left wrist, aplasia of the left thumb, micrognathia, low-set ears, hypertelorism, rocker-bottom feet, and a normal penis. Quantitative fluorescent polymerase chain reaction assays using polymorphic DNA markers showed a triallelic pattern with a dosage ratio of 1:1:1 (paternal:maternal:maternal) for chromosome 18-specific markers, and a monoallelic pattern of a single maternal allele for chromosome X-specific markers. The fetus inherited two copies of two different maternal alleles on chromosome 18, and two copies of a single maternal allele on chromosome X. The molecular result, along with the karyotype of 48,XXY,+18, was consistent with the occurrence of nondisjunction of chromosome 18 in a maternal meiosis I error and nondisjunction of chromosome X in a maternal meiosis II error or less likely a postzygotic mitotic error. Conclusion: The present case provides evidence that abnormal separation of chromosomes 18 and X resulting in double aneuploidy may occur in different cell divisions, and such an occurrence is related to advanced maternal age.

Objective: To present molecular cytogenetic characterization of a de novo duplication of Xq22.1→q24 in a mentally retarded woman with short stature and premature ovarian failure. Materials and Methods: A 19-year-old woman presented with psychomotor retardation, developmental delay, mental retardation, short stature, low body weight, general muscle hypotonia, distal muscle hypotrophy of the lower extremities, elongated digits, scanty pubic and axillary hair, hypoplastic external female genitalia, and secondary amenorrhea but no clinical features of Pelizaeus-Merzbacher disease. Conventional cytogenetic analysis revealed a karyotype of 46,X,dup(X)(q22.1q24). Fluorescence in situ hybridization determined a direct duplication with a linear tandem orientation. Array comparative genomic hybridization demonstrated partial trisomy Xq [arr cgh Xq22.1q24 (101,490,234–119,070,188 bp)×3] with a 17.6-Mb duplication. Results: The duplicated region contained NXF2B, NXF4, NXF3, PLP1, and PGRMC1 genes. There was a disruption of the NXF gene cluster of Xcen-NXF5-NXF2-NXF2B-NXF4-NXF3-Xqter. Conclusion: A duplication of Xq22.1→q24 with a disruption of the NXF gene cluster in female patients can be associated with clinical manifestations of mental retardation in addition to short stature and premature ovarian failure.

Objective: To present molecular cytogenetic characterization of a prenatally detected duplication of 15q26.2→q26.3 in a fetus with overgrowth. Case Report: A 34-year-old para 0 woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 15, or der(15), with additional material at the end of the long arm of one chromosome 15. Parental karyotypes were normal. Fetal overgrowth was first noted at 21 weeks of gestation. Repeated amniocentesis was performed at 22 weeks of gestation. Array comparative genomic hybridization revealed a 4.71-Mb duplication from 15q26.2 to 15q26.3 encompassing the IGF1R gene. Fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone probes specific for 15q26.2-q26.3 and the subtelomeric region of 15q showed a direct duplication and no terminal deletion in the der(15). Polymorphic DNA marker analysis determined a paternal origin of the duplication of 15q. Level II ultrasound at 23 weeks of gestation revealed a fetal biometry equivalent to 26 weeks. The pregnancy was subsequently terminated, and a 1062-g (>99th centile) malformed fetus was delivered at 24 weeks of gestation with craniofacial dysmorphism, craniosynostosis, and overgrowth. Conclusion: The present case provides evidence for prenatal overgrowth, craniosynostosis, and characteristic facial dysmorphism in association with a duplication of 15q26.2→q26.3 and a duplication of the IGF1R gene. Prenatal diagnosis of fetal overgrowth should include a differential diagnosis of the chromosome 15q overgrowth syndrome.

Objective: To present prenatal diagnosis of chromosome 1p32-p31 deletion syndrome with NFIA haploinsufficiency, ventriculomegaly, corpus callosum hypogenesis, abnormal external genitalia, and intrauterine growth restriction and to review the literature. Materials, Methods, and Results: A 26-year-old, primigravid woman was referred for amniocentesis at 30 weeks of gestation because of hydrocephalus and short limbs. Prenatal ultrasound showed macrocephaly, prominent forehead, ventriculomegaly, corpus callosum hypogenesis, micrognathia, and ambiguous external genitalia. Amniocentesis was performed, and array comparative genomic hybridization using uncultured amniocytes revealed a 22.2-Mb deletion of 1p32.3-p31.1 [arr cgh 1p32.3p31.1 (55,500,291 bp–77,711,982 bp)×1] encompassing the genes of NFIA, GPR177, and 89 additional genes. Cytogenetic analysis revealed a karyotype of 46,XX,del(1)(p31.1p32.3)dn. At 33 weeks of gestation, a dead fetus was delivered with a body weight of 1536 g (

Objective: To present prenatal ultrasound and perinatal magnetic resonance imaging (MRI) findings of Galloway-Mowat syndrome. Case Report: A 31-year-old woman, gravida 3, para 2, was referred for genetic counseling at 29 weeks of gestation because of abnormal ultrasound findings and a previous child with Galloway-Mowat syndrome. During this pregnancy, microcephaly, intrauterine growth restriction (IUGR), and oligohydramnios were first noted at 27 weeks of gestation. Repeated ultrasounds showed microcephaly, IUGR, and oligohydramnios. MRI performed at 32 weeks of gestation showed reduced sulcation of the brain, pachygyria, poor myelination of the white matter, and cerebellar atrophy. A diagnosis of recurrent Galloway-Mowat syndrome was made. At 40 weeks of gestation, a 2,496-g female baby was delivered with microcephaly, a narrow slopping forehead, epicanthic folds, microphthalmos, a highly arched palate, a small midface, a beaked nose, thin lips, large low-set floppy ears, clenched hands, and arachnodactyly. Postnatal MRI findings were consistent with the prenatal diagnosis. Renal ultrasound showed enlarged bilateral kidneys with increased echogenicity. At the age of 2 weeks, the infant became edematous and developed nephrotic syndrome. Conclusion: Microcephaly, IUGR, and oligohydramnios are significant ultrasound triad of fetal Galloway-Mowat syndrome. Prenatal ultrasound diagnosis of microcephaly, IUGR, and oligohydramnios in late second trimester or in early third trimester should alert clinicians to the possibility of Galloway-Mowat syndrome and prompt a detailed search of abnormal sulcation, cortical gyral maldevelopment, and cerebellar atrophy by fetal ultrafast MRI.

Objective: To present array comparative genomic hybridization (aCGH) characterization of partial monosomy 13q (13q21.32→qter) and partial trisomy 8p (8p12→pter) presenting with anencephaly and increased nuchal translucency (NT). Case Report: A 34-year-old primigravid woman was referred to the hospital at 12 weeks of gestation for termination of the pregnancy because of major structural abnormalities of the fetus. Prenatal ultrasound revealed a malformed fetus with anencephaly and an increased NT thickness of 5 mm at 12 weeks of gestation. Cytogenetic analysis of the fetus revealed a derivative chromosome 13. The mother was subsequently found to carry a balanced reciprocal translocation between 8p12 and 13q21. Bacterial artificial chromosome-based aCGH using fetal DNA demonstrated partial trisomy 8p and partial monosomy 13q [arr cgh 8p23.3p12 (RP11-1150M5→RP11-1145H12)×3, 13q21.32q34 (RP11-326B4→RP11-450H16)×1]. Oligonucleotide-based aCGH showed a 36.7-Mb duplication of distal 8p and a 48.4-Mb deletion of distal 13q. The fetal karyotype was 46,XY,der(13) t(8;13)(p12;q21.32)mat. The maternal karyotype was 46,XX,t(8;13)(p12;q21.32). Conclusion: The 13q deletion syndrome can be associated with neural tube defects and increased NT in the first trimester. Prenatal sonographic detection of neural tube defects should alert chromosomal abnormalities and prompt cytogenetic investigation, which may lead to the identification of an unexpected parental translocation involving chromosomal segments associated with neural tube development.

Objective: To present prenatal diagnosis and molecular cytogenetic characterization of mosaicism for a small supernumerary marker chromosome (sSMC) derived from ring chromosome, or r(4) by spectral karyotyping (SKY), fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (aCGH). Materials, Methods, and Results: A 37-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a de novo ring-shaped sSMC in 16 of 31 amniocyte colonies. The parental karyotypes were normal. Level II ultrasound findings were unremarkable. Repeated amniocentesis revealed a karyotype of 47,XX,+mar[17]/46,XX[19]. The sSMC was characterized by SKY and FISH, which showed a chromosome 4 origin of the sSMC. aCGH demonstrated a 21.7-Mb gain in the gene dosage encompassing the region of 4p12→q13.2. The sSMC was r(4)(p12q13.2). The fetal karyotype was 47,XX,+r(4)(p12q13.2)[17]/46,XX[19]. The pregnancy was subsequently terminated. The fetus postnatally manifested hypertelorism, epicanthic folds, a prominent nose, a triangular face, low-set ears, clinodactyly of the fingers, and small big toes. Postnatal cytogenetic analyses of fetal and extraembryonic tissues revealed the karyotypes of 47,XX,+r(4)[18]/46,XX[21] in cord blood, 47,XX,+r(4)[20]/48,XX,+r(4),+r(4)[1]/46,XX[9] in umbilical cord, 47,XX,+r(4)[14]/47,XX,+dic r(4)[1]/46,XX[25] in skin, 47,XX,+r(4)[15]/46,XX[25] in amnion, and 47,XX,+r(4)[12]/47,XX,+dic r(4)[1]/46,XX[2] in placenta. Conclusion: SKY, FISH, and aCGH are helpful in genetic counseling of prenatally detected sSMCs by providing the immediate and thorough information on the origin and genetic component of the sSMC.

Objective: To present prenatal diagnosis and molecular cytogenetic characterization of a derivative chromosome der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3). Materials, Methods, and Results: A 32-year-old woman was referred for genetic counseling of prenatally detected isochromosome 18q [i(18q)]. She had undergone amniocentesis at 19 gestational weeks because of a trisomy 18 risk of 1/39 derived from abnormally low levels of maternal serum unconjugated estriol, inhibin A, α-fetoprotein, and total β-human chorionic gonadotropin. Amniocentesis revealed a karyotype of 46,XX,i(18)(q10). Parental karyotypes were normal. Prenatal ultrasound showed alobar holoprosencephaly. Repeated amniocentesis was requested and performed at 21 gestational weeks. Array-comparative genomic hybridization analyses revealed a 14-Mb deletion of 18p11.32-p11.21, a 37.8-Mb duplication of 18q12.1-q22.1, and a 6.9-Mb duplication of 18q22.3-q23. Metaphase fluorescence in situ hybridization study showed the absence of an 18q12.1-specific probe signal in one arm and the absence of an 18q22.2-specific probe signal in the other arm of the derivative chromosome. Quantitative fluorescent polymerase chain reaction analysis determined a paternal origin of the derivative chromosome. The cytogenetic result was 46,XX,der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3). The fetus postnatally manifested cebocephaly. Conclusion: Concomitant monosomy 18p and trisomy 18q can be associated with holoprosencephaly and abnormal maternal serum screening results. Array-comparative genomic hybridization, fluorescence in situ hybridization, and quantitative fluorescent polymerase chain reaction are useful in genetic counseling of prenatally detected isochromosomes by providing information on the origin and genetic components of the isochromosome.

Objective: To report five cases of major congenital malformations associated with common aneuploidies detected by rapid aneuploidy diagnosis. Case Reports: The fetus in the first case presented cebocephaly, semilobar holoprosencephaly, and tetralogy of Fallot on ultrasound at 25 gestational weeks. Cordocentesis using multiplex ligation-dependent probe amplification to detect aneuploidies of chromosomes X, Y, 13, 18, and 21 in uncultured cord blood revealed three copies of all targets on chromosome 13 consistent with the diagnosis of trisomy 13. The fetus in the second case presented bilateral choroid plexus cysts, congenital diaphragmatic hernia, and club foot on ultrasound at 18 gestational weeks. Amniocentesis using array-based comparative genomic hybridization (aCGH) in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 18 consistent with the diagnosis of trisomy 18. The fetus in the third case presented aortic stenosis and nuchal edema on ultrasound at 22 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a result of monosomy X and Turner syndrome. The fetus in the fourth case presented nuchal cystic hygroma and ventriculomegaly on ultrasound at 17 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 21 consistent with the diagnosis of trisomy 21. The fetus in the fifth case presented holoprosencephaly, omphalocele, and hydronephrosis on ultrasound at 17 gestational weeks. Amniocentesis using aCGH in uncultured amniocytes revealed a gain in the DNA dosage of chromosome 13 consistent with the diagnosis of trisomy 13. Conclusions: Prenatal diagnosis of major congenital malformations should alert one to the possibility of chromosomal abnormalities. Multiplex ligation-dependent probe amplification and aCGH have the advantage of rapid aneuploidy diagnosis of common aneuploidies in cases with major congenital malformations.

Objective: To present molecular cytogenetic characterization of prenatally detected inverted duplication and deletion of 9p, or inv dup del(9p). Materials, Methods, and Results: A 35-year-old primigravid woman underwent amniocentesis at 16 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 9, or der(9) with additional material at the end of the short arm of one chromosome 9. Parental karyotypes were normal. Level II ultrasound showed ventriculomegaly and normal male external genitalia. Repeated amniocentesis was performed at 20 weeks of gestation. Array comparative genomic hybridization revealed a 0.70-Mb deletion at 9p24.3 and an 18.36-Mb duplication from 9p24.3 to 9p22.1. The distal 9p deletion encompassed the genes of DOCK8, ANKRD15, FOXD4, DMRT1, and DMRT3. Fluorescence in situ hybridization analysis using bacterial artificial chromosome clone probes specific for 9p confirmed that the der(9) was derived from the inv dup del(9p). The karyotype of the fetus was 46,XY,inv dup del(9)(:p22.1→p24.3::p24.3→qter)dn or 46,XY,der(9) del(9)(p24.3) inv dup(9)(p22.1p24.3)dn. Polymorphic DNA marker analysis determined a maternal origin of the inv dup del(9p). A 512-g male fetus was subsequently terminated at 22 weeks of gestation with facial dysmorphism. The fetus had normal male external genitalia without sex reversal. Conclusion: Fluorescence in situ hybridization and array comparative genomic hybridization are useful to determine the nature of a prenatally detected aberrant chromosome derived from the inv dup del. Male fetuses with inv dup del(9p) and haploinsufficiency of DMRT1 and DMRT3 may present normal male external genitalia without sex reversal.

Objective: To present perinatal findings, modes of ascertainments, and modes of segregation in unbalanced reciprocal translocations detected at amniocentesis. Materials and Methods: Between January 1987 and July 2010, 40 cases with unbalanced reciprocal translocations were diagnosed by amniocentesis at Mackay Memorial Hospital, Taipei, Taiwan. The 40 cases originated from 29 families; 21 families with one case, 7 families with two cases, and 1 family with five cases. Results: Of 40 cases, 33 (82.5%) presented fetal ultrasound abnormalities and 7 (17.5%) presented no ultrasound abnormalities. Of 40 cases, 36 (90%) had a segregation mode of adjacent-1 2:2 segregation, 3 (7.5%) had a segregation mode of 3:1 segregation with tertiary trisomy, and 1 (2.5%) had a segregation mode of 3:1 segregation with tertiary monosomy. Of 29 families, 7 (24.1%) had de novo translocations and 22 (75.9%) had inherited translocations. In seven de novo cases, the main modes of ascertainments included abnormal ultrasound findings (n = 5) and advanced maternal age (n = 2). In 22 inherited families, the main modes of first ascertainment included abnormal ultrasound findings (n = 8), a previous aneuploid child (n = 8), advanced maternal age (n = 4), parental carrier status (n = 1), and abnormal maternal serum screening results (n = 1). Among 22 inherited families, 9 (40.9%) had a known parental carrier status, but 13 (59.1%) were unaware of parental carrier status at amniocentesis. Conclusion: Unbalanced reciprocal translocations detected at amniocentesis are frequently associated with abnormal ultrasound findings. Prenatal diagnosis of an unbalanced translocation may incidentally detect a balanced translocation in the family. Prenatal diagnosis of fetal structural abnormalities should alert structural chromosome rearrangements and prompt cytogenetic analysis of the fetus and parents if necessary.

Objective: To present prenatal diagnosis and molecular cytogenetic characterization of a small supernumerary marker chromosome (sSMC) derived from chromosome 8 by multiplex ligation-dependent probe amplification (MLPA), fluorescence in situ hybridization (FISH), spectral karyotyping (SKY) and array comparative genomic hybridization (aCGH). Case Report: A 42-year-old woman, gravida 6, para 3, underwent amniocentesis at 19 gestational weeks because of advanced maternal age. Amniocentesis revealed a de novo ring-shaped sSMC in all 13 colonies of the amniocytes. The karyotype was 47,XY,+mar. The MLPA showed duplications of 8p11.21-specific probes. At 24 gestational weeks, level II ultrasound revealed a left multicystic kidney in the fetus. Other internal organs were unremarkable. Repeat amniocentesis revealed a karyotype of 47,XY,+mar[25]/46,XY[2]. The sSMC was characterized by SKY and FISH, which showed a chromosome 8 origin of the sSMC. Oligonucleotide-based aCGH demonstrated a 4.4-Mb duplication of 8p11.21q11.1 [arr cgh 8p11.21q11.1 (42,637,263-47,062,180)×3]. The karyotype was 47,XY,+r(8) (p11.21q11.1)[25]/46,XY[2]. Polymorphic DNA marker analysis revealed no uniparental disomy for chromosome 8. The woman elected to continue the pregnancy and at 34 gestational weeks, a 1,820 g male baby without craniofacial dysmorphism was delivered. At the age of 1 month, the infant was apparently normal except for left multicystic kidney disease and mild ventriculomegaly. Conclusion: MLPA, SKY and aCGH are helpful in genetic counseling of prenatally detected sSMCs by providing the immediate information on the origin and the genetic contents of the sSMC.

Objective: To present perinatal findings, modes of ascertainment and parental decision in balanced reciprocal translocations detected at amniocentesis. Materials and Methods: Between January 1987 and August 2010, 82 cases with a simple reciprocal translocation, two cases with two separate simple reciprocal translocations and three cases with a complex chromosome rearrangement (CCR) were diagnosed by amniocentesis at Mackay Memorial Hospital, Taipei, Taiwan. The 87 cases originated from 76 families; 65 families with one case and 11 families with two cases. Results: In the 76 families, the main modes of ascertainment included advanced maternal age (n=38), a previous child with an unbalanced reciprocal translocation (n=11), recurrent miscarriage (n = 9), abnormal maternal serum screening results (n = 9), elective causes (n = 5), a previous child with congenital anomalies (n =2) and abnormal ultrasound findings (n = 2). In these families, there were 17 (22.4%) de novo cases including 14 simple translocations and three CCRs. Of 14 de novo cases with a simple translocation, one (7.1%) manifested a congenital malformation, which was related to an X-autosome translocation, and four (28.6%) were terminated. Of three de novo CCRs, two manifested congenital anomalies and one was terminated. In 87 cases, additional aneuploidy was noted in two cases including one inherited simple translocation with Turner syndrome, and one de novo CCR with concomitant deletions and duplication. Conclusion: Balanced reciprocal translocations detected at amniocentesis may be associated with fetal anomalies in cases of concomitant aneuploidy, de novo X-autosome translocation or de novo CCR. Genetic counseling of a de novo simple reciprocal translocation at amniocentesis remains difficult because approximately one-fourth of the parents opt for termination of the pregnancy, and detailed ultrasonography and array comparative genomic hybridization are helpful for parental counseling under such circumstances.

Objective: To present the perinatal findings and molecular genetic analysis of two siblings with Ellis-van Creveld (EvC) syndrome. Materials, Methods and Results: A 33-year-old woman, gravida 3, para 1, was referred for genetic counseling at 18 gestational weeks because of recurrent fetal skeletal dysplasia. Two years previously, she had delivered a 1,316-g dead male baby at 28 gestational weeks with a karyotype of 46,XY, postaxial polydactyly of the hands, thoracic narrowness, endocardial cushion defects, transposition of the great arteries, shortening of the long bones, malposition of the toes, and hypoplastic nails. During this pregnancy, prenatal ultrasound at 18 gestational weeks revealed shortening of the long bones (equivalent to 15 weeks), postaxial polydactyly of both hands, thoracic narrowness, and endocardial cushion defects. The pregnancy was subsequently terminated, and a 236-g female fetus was delivered with a karyotype of 46,XX, postaxial polydactyly of the hands, thoracic dysplasia, endocardial cushion defects, shortening of the long bones, and malposition of the toes and hypoplastic nails. The phenotype of each of the two siblings was consistent with EVC syndrome. Molecular analysis of the EVC and EVC2 genes revealed heterozygous mutations in the EVC2 gene. A heterozygous deletion mutation of a 26-bp deletion of c.871-2_894del26 encompassing the junction between intron 7 and exon 8 of the EVC2 gene was found in the mother and two siblings, and a heterozygous nonsense mutation of c.1195C >T, p.R399X in exon 10 of the EVC2 gene was found in the father and two siblings. Conclusion: Prenatal sonographic identification of endocardial cushion defects in association with shortening of the long bones should alert clinicians to the possibility of EvC syndrome and prompt a careful search of hexadactyly of the hands. Molecular analysis of the EVC and EVC2 genes is helpful in genetic counseling in cases with prenatally detected postaxial polydactyly, thoracic narrowness, short limbs and endocardial cushion defects.