A three-headed psoas major muscle: a case report.

BACKGROUND: Multiple anatomical variations, from anomalous courses to additional structures, have been reported in muscles from different compartments of the human body. We report an extremely rare case of a psoas major muscle presenting as a three-headed structure with variable morphology. MATERIALS AND METHODS: During a routine dissection of the posterior abdominal wall of a 82-year-old male cadaver, an anomalous PM muscle with supernumerary head was identified, photographed and subjected to further measurement. RESULTS: Although the anatomy of the dissected posterior abdominal wall structures was typical, a three-headed psoas major muscle composed of superficial, intermediate and deep heads was identified. CONCLUSIONS: It is important to be aware of morphological variability of muscles, especially those considered to be constant, since an anomalous structure might interfere not only with their functions, but also lead to further clinical consequences.

The double-headed accessory iliacus muscle: a case report.

PURPOSE: Numerous accessory muscles are present in the human body, many of which are clinically significant. We present a case of an anomalous accessory iliacus composed of two heads, whose occurrence and anatomical location indicate a high probability of causing femoral nerve compression. METHODS: During a routine dissection of the posterior abdominal wall of a xx-year-old cadaver, a double headed accessory muscle was noted, measured and photographed. RESULTS: In addition to the normal anatomy of dissected structures from the posterior abdominal wall, an accessory iliacus muscle composed of superficial and deep heads was identified. In addition, the inferior roots of the divided femoral nerve located between the heads was found to follow an unusual course. CONCLUSIONS: It is important to be aware of morphological variability around structures such as double-headed accessory iliacus muscle presented in this study, due to their association with neurovascular bundles and hip joint. The reported atypical morphology is not widely known in the literature but might be of great clinical significance, therefore knowledge of such variability might be regarded in order to diagnose properly and introduce accurate treatment.

The OsCLV2s and OsCRN1 regulate grain shape in rice.

The highly conserved CLV-WUS negative feedback pathway plays a decisive role in regulating stem cell maintenance in shoot and floral meristems in higher plants, including Arabidopsis, rice, maize, and tomato. Here, we report the discovery that CLV-like genes directly regulate grain shape in rice. We find significant natural variations in the OsCLV2c, OsCLV2d, and OsCRN1 loci in a genome-wide association study of grain shape in rice. OsCLV2a, OsCLV2c, OsCLV2d, and OsCRN1 negatively regulate grain shape and show distinctive geographical distribution, indica-japonica differentiation, and artificial selection signatures. Notably, OsCLV2a and OsCRN1 interact biochemically and genetically, suggesting that the two components function in a complex to regulate grain shape in rice. Furthermore, the genetic contributions of the haplotypes combining OsCLV2a, OsCLV2c, and OsCRN1 are significantly higher than that of each single gene alone in controlling key yield traits. These findings identify two groups of receptor-like kinases that may function as distinct co-receptors to control grain size in rice, thereby revealing a previously unrecognized role of the CLV class genes in regulating seed development and proposing a framework to understand the molecular mechanisms of the CLV-WUS pathway in rice and other crops.

Use of Adult Dry Human Mandibles to Study of Mandibular Foramen from Various Bony Landmarks.

Background: Precise knowledge of the mandibular foramen's location is essential for clinical and surgical procedures, especially the inferior alveolar nerve block. Variability in its position concerning different bony landmarks can significantly impact clinical outcomes. Materials and Methods: This study examined 30 Adult dry human mandibles to determine the mandibular foramen's positions in relation to specific bony landmarks: the occlusal plane, posterior border of the ramus, and lingula. Measurements were obtained using a calibrated digital caliper, and statistical analysis was performed. Results: The study revealed significant variations in the position of the mandibular foramen. In relation to the occlusal plane, the mandibular foramen was found at an average height of approximately 15.2 mm (±2.1 mm). Regarding the posterior border of the ramus, it was situated at an average distance of about 18.5 mm (±3.4 mm). In relation to the lingula, the average distance was approximately 21.8 mm (±4.0 mm). These results underscore the considerable individual differences and anatomical variations in the mandibular foramen's location among the studied specimens. Conclusion: The observed variations in the position of the mandibular foramen emphasize the need for clinicians and surgeons to be cognizant of these differences when performing procedures involving the inferior alveolar nerve block. Understanding these anatomical variations is crucial for enhancing clinical precision, reducing complications, and ensuring optimal outcomes.

Low C4A copy numbers and higher HERV gene insertion contributes to increased risk of SLE, with absence of association with disease phenotype and disease activity.

Low copy numbers (CNs) of C4 genes are associated with systemic autoimmune disorders and affects autoantibody diversity and disease subgroups. The primary objective of this study was to characterize diversity of complement (C4) and C4-Human Endogenous Retrovirus (HERV) gene copy numbers in SLE. We also sought to assess the association of C4 and C4-HERV CNs with serum complement levels, autoantibodies, disease phenotypes and activity. Finally, we checked the association of C4 and HERV CNs with specific HLA alleles. Genomic DNA from 70 SLE and 90 healthy controls of south Indian Tamil origin were included. Demographic, clinical and serological data was collected in a predetermined proforma. CNs of C4A and C4B genes and the frequency of insertion of 6.4kb HERV within C4 gene (C4AL, C4BL) was determined using droplet digital polymerase chain reaction (ddPCR). A four digit high resolution HLA genotyping was done using next generation sequencing. In our cohort, the total C4 gene copies ranged from 2 to 6. Compared to controls, presence of two or less copies of C4A gene was associated with SLE risk (p = 0.005; OR = 2.79; 95% CI = 1.29-6.22). Higher frequency of HERV insertion in C4A than in C4B increases such risk (p = 0.000; OR = 12.67; 95% CI = 2.80-115.3). AL-AL-AL-BS genotype was significantly higher in controls than SLE (9%vs1%, p = 0.04; OR = 0.15, 95% CI = 0.00-0.16). Distribution of HLA alleles was not different in SLE compared to controls as well as in SLE subjects with ≤ 2 copies and > 2 copies of C4A, but HLA allele distribution was diverse in subjects with C4B ≤ 2 copies and > 2 copies. Finally, there was no correlation between the C4 and the C4-HERV diversity and complement levels, autoantibodies, disease phenotypes and activity. In conclusion, our data show that, low C4A copy number and higher insertion of HERV-K in C4A increases the risk for SLE. C4 and C4-HERV CNs did not correlate with serum complements, autoantibodies, disease phenotypes and activity in SLE. Further validation in a larger homogenous SLE cohort is needed.

Prediction of heavy metal lead contamination accident in Three Gorges Reservoir Area.

Water contamination incidents have become a significant ecological and environmental threat, particularly concerning the security of drinking water source areas (DWSAs). This research aimed to address this issue by integrating Geographic Information System (GIS) into bidimensional hydrodynamic water quality mathematical model developed using C + + and FORTRAN programming languages. The focus was on the Heshangshan drinking water source area (HDWSA), and the TECPLOT360 software was utilized for visualizing pollutant migration and dispersion processes. The study specifically considered a hypothetical lead (Pb) contamination accident, which is situated in the Three Gorges Reservoir Area (TGRA). The spatio-temporal variations in Pb concentration throughout the entire DWSA were analyzed, along with a comparison of Pb concentration changes during different water seasons. The results indicate that, during the accident, the Pb concentration at the water intake in the drought season, decline season, flood season, and impounding season reached the standard limits at 76, 58, 44, and 48 min, respectively. Moreover, the entire DWSA achieved standard levels of Pb concentration at 124, 89, 71, and 74 min during the respective seasons. The study also observed an expansion and subsequent contraction of the Pb contamination area in the DWSA, with the transfer rate of Pb concentration ranked as flood season > impounding season > decline season > drought season.

Risk factors for diaphragmatic injury in subxiphoid video-assisted thoracoscopic surgery.

BACKGROUND: Subxiphoid video-assisted thoracoscopic surgery (VATS) is considered a safe and feasible operation for anterior mediastinal mass resection. However, diaphragmatic injury, presented as tearing or puncturing, may occur during subxiphoid VATS despite of low incidence. This study aims to explore risk factors for diaphragmatic injury in subxiphoid VATS, as well as strategies to reduce occurrence of the injury. METHODS: We retrospectively reviewed clinical records of 44 consecutive adult patients who underwent subxiphoid VATS. These patients were divided into two groups: diaphragmatic injury group and non-injury group. Perioperative outcomes and anatomic features derived from 3D CT reconstructions were compared between the two groups. RESULTS: Significant differences were observed in operation time (223.25 ± 92.57 vs. 136.28 ± 53.05, P = 0.006), xiphoid length (6.47 ± 0.85 vs. 4.79 ± 1.04, P = 0.001) and length of the xiphoid below the attachment point on the diaphragm (24.86 ± 12.02 vs. 14.61 ± 9.25, P = 0.029). Odds ratio for the length of the xiphoid below the attachment point on the diaphragm was 1.09 (1.001-1.186), P = 0.048 by binary logistic regression analysis. CONCLUSIONS: We identified the length of the xiphoid below the attachment point on the diaphragm as an independent risk factor for diaphragm injury during subxiphoid VATS. Prior to subxiphoid VATS, a 3D chest CT reconstruction is recommended to assess the patients' anatomic variations within the xiphoid process. For patients with longer xiphoid process, a higher incision at the middle and upper part of the xiphoid process, and partial xiphoid process resection or xiphoidectomy is preferred.

Anatomic Variations of the Calcaneofibular Ligament.

BACKGROUND: The lateral ankle joint comprises the anterior talofibular ligament (ATFL), calcaneofibular ligament (CFL), and posterior talofibular ligament (PTFL). The purpose of this study was to propose a classification of CFL morphology. METHODS: The material comprised 120 paired lower limbs from human cadavers (30 male, 30 female), mean age 62.3 years. The morphology was carefully assessed, and morphometric measurements were performed. RESULTS: A 4-part method for anatomic classification can be suggested based on our study. Type 1 (48.3%), the most common type, was characterized by a bandlike morphology. Type 2 (9.2%) was characterized by a Y-shaped band, and type 3 (21.7%) by a V-shaped band. Type 4 (20.8%) was characterized by the presence of 2 or 3 bands. Type 2 and 4 were divided into further subtypes based on origin footprint. CONCLUSION: The aim of our study was to describe variations of calcaneofibular ligament. Our proposed 4-part classification may be of value in clinical practice in future recognition of CFL injuries and in its repair or reconstruction. CLINICAL RELEVANCE: The anatomy of the CFL plays an important role in stability of the ankle. Greater recognition of anatomical variation may help improve reconstructive options for patients with chronic lateral ankle instability.

Intra-fractional geometric and dose/volume metric variations of magnetic resonance imaging-guided stereotactic radiotherapy of prostate bed after radical prostatectomy.

Background and purpose: Magnetic Resonance Imaging (MRI)-guided Stereotactic body radiotherapy (SBRT) treatment to prostate bed after radical prostatectomy has garnered growing interests. The aim of this study is to evaluate intra-fractional anatomic and dose/volume metric variations for patients receiving this treatment. Materials and methods: Nineteen patients who received 30-34 Gy in 5 fractions on a 0.35T MR-Linac were included. Pre- and post-treatment MRIs were acquired for each fraction (total of 75 fractions). The Clinical Target Volume (CTV), bladder, rectum, and rectal wall were contoured on all images. Volumetric changes, Hausdorff distance, Mean Distance to Agreement (MDA), and Dice similarity coefficient (DSC) for each structure were calculated. Median value and Interquartile range (IQR) were recorded. Changes in target coverage and Organ at Risk (OAR) constraints were compared and evaluated using Wilcoxon rank sum tests at a significant level of 0.05. Results: Bladder had the largest volumetric changes, with a median volume increase of 48.9 % (IQR 28.9-76.8 %) and a median MDA of 5.1 mm (IQR 3.4-7.1 mm). Intra-fractional CTV volume remained stable with a median volume change of 1.2 % (0.0-4.8 %). DSC was 0.97 (IQR 0.94-0.99). For the dose/volume metrics, there were no statistically significant changes observed except for an increase in bladder hotspot and a decrease of bladder V32.5 Gy and mean dose. The CTV V95% changed from 99.9 % (IQR 98.8-100 %) to 99.6 % (IQR 93.9-100 %). Conclusion: Despite intra-fractional variations of OARs, CTV coverage remained stable during MRI-guided SBRT treatments for the prostate bed.

A set of guidelines as support for the integrated geo-environmental characterization of highly contaminated coastal sites.

The knowledge of geomorphodynamic aspects is crucial for understanding marine and coastal processes/dynamics as well as for characterizing coastal environments heavily affected by anthropogenic activities. To provide a framework of analysis that can be applied in a consistent way for the geo-environmental characterization of highly contaminated coastal sites, in this paper a set of operational guidelines is proposed. Special attention is given to the role of geomorphological-based surveys and analyses in defining (i) the site-specific geological model of the investigated site, (ii) the anthropogenic impacts on marine and coastal sediments, (iii) the expected morphodynamic variations induced by climate change and anthropogenic interventions, (iv) tailored dissemination activities and community engagement plans. Then, an evaluation of the state of the art of activities already performed for the characterization of the coastal contaminated sites located in the Apulia region (southern Italy) is provided. The outcomes of this research are also provided in the form of infographics to favor their dissemination among communities and stakeholders.

[The pharmacogenetics as integral part of personalized medicine: problems and prospects].

The article considers issues of implementation into clinical practice the principles of 5P medicine in its part of individualization of therapeutic tactics considering genetic characteristics of patients. The analysis of studies concerning influence of allelic variations on metabolism, safety and tolerance of the most often prescribed medicinal preparations was implemented. The main assumptions of pharmacogenomics were considered. Despite broad perspective of applying obtained data in clinical practice, there are a number of unresolved problems related to accessibility of genetic testing to population, ambiguity of approaches to interpretation of obtaining results, ethical issues and legal regulation.

Enhancing intersex healthcare: A qualitative study of parental perspectives on the role of genetics.

Intersex individuals, encompassing people with diverse sex characteristics that do not fit binary frameworks of sex, have long faced a history of medical secrecy, discrimination, and societal stigma, contributing to their limited social visibility. In recent years, increased awareness of intersex issues and a robust advocacy movement have drawn significant attention to the experiences of intersex individuals and their families. This study contributes to the existing literature by examining the experiences and needs of parents of intersex individuals within genetic healthcare systems, bridging a critical gap, and advocating for more comprehensive and supportive healthcare practices. Semi-structured interviews were conducted with 14 parents of intersex individuals, and reflexive thematic analysis was used to inductively generate four major themes. Themes highlighted the need for improved accessibility of intersex healthcare, the importance of multidisciplinary healthcare teams, and the significance of clinical diagnosis provided by genetics professionals. Furthermore, the study highlighted the necessity of a thoughtful approach to information provision and the impact of genetic investigations on family dynamics. Genetics professionals can play a pivotal role in raising awareness about intersex variations, improving diagnostic processes, collaborating within healthcare teams, and providing specialized support to address psychosocial concerns. The study underscores the importance of treating families as a collective entity and addressing the impact of genetic investigations on the family unit. By addressing the challenges and implementing the recommendations outlined, healthcare institutions can create a more compassionate, inclusive, and effective healthcare environment for the intersex community.

[Critical Review on Heavy Metal Contamination in Urban Soil and Surface Dust].

With the rapid urbanization and industrialization, heavy metal contamination in urban soil and surface dust has received particular attention due to its negative effects on the eco-environment and human health. Contamination and spatio-temporal characteristics, contamination sources, and source apportionment methods, as well as the ecological and health risks of heavy metals in urban soil and surface dust were reviewed. The knowledge gaps in current research and prospects of future works were proposed. Four key points were presented, including improving the research on the interaction mechanism of heavy metals in urban soil and surface dust under complex conditions, enriching verification methods to improve the source apportionment reliability of anthropogenic metals by receptor models, strengthening the research on chemical forms of heavy metals from different sources and their short-term accumulation processes in surface dust, and raising the credibility of ecological and health risk forecast of heavy metals by integrating the improved exposure parameters and chemical forms.

Fine-Scale Spatial Variability of Greenhouse Gas Emissions From a Subantarctic Peatland Bog.

Peatlands are recognized as crucial greenhouse gas sources and sinks and have been extensively studied. Their emissions exhibit high spatial heterogeneity when measured on site using flux chambers. However, the mechanism by which this spatial variability behaves on a very fine scale remains unclear. This study investigates the fine-scale spatial variability of greenhouse gas emissions from a subantarctic Sphagnum peatland bog. Using a recently developed skirt chamber, methane emissions and ecosystem respiration (as carbon dioxide) were measured at a submeter scale resolution, at five specific 3 × 3 m plots, which were examined across the site throughout a single campaign during the Austral summer season. The results indicated that methane fluxes were significantly less homogeneously distributed compared with ecosystem respiration. Furthermore, we established that the spatial variation scale, i.e., the minimum spatial domain over which notable changes in methane emissions and ecosystem respiration occur, was <0.56 m2. Factors such as ground height relative to the water table and vegetation coverage were analyzed. It was observed that Tetroncium magellanicum exhibited a notable correlation with higher methane fluxes, likely because of the aerenchymatous nature of this species, facilitating gas transport. This study advances understanding of gas exchange patterns in peatlands but also emphasizes the need for further efforts for characterizing spatial dynamics at a very fine scale for precise greenhouse gas budget assessment.

Strategic control of combustion-induced ammonia emissions: A key initiative for substantial PM2.5 reduction in Tianjin, North China Plain.

Information on the temporal and spatial variations in the sources of ammonium salts (NH4+), a crucial alkaline component in PM2.5, is limited. Here, we simultaneously collected PM2.5 and gaseous ammonia (NH3) samples in both summer and winter from two sites in Tianjin: an urban site (Tianjin University, TJU) and a suburban site (Binhai New-region, BH). NH3 concentrations, the contents of major water-soluble inorganic ions in PM2.5, and the compositions of ammonium­nitrogen isotopes (δ15N-NH4+) were measured. As a result, (NH4)2SO4 and NH4NO3 were the predominant forms of NH4+ in PM2.5 during summer and winter, respectively. However, the NH4NO3 concentrations were notably greater at TJU (6.2 ± 7.3 µg m-3) than at BH (3.8 ± 4.7 µg m-3) in summer, with no regional differences observed in winter. Both sites displayed almost half the contribution of c-NH3 (combustion-related NH3) to NH4+, differing from the finding of previous isotope-based studies. This discrepancy could be attributed to the combined effects of NHx isotope fractionation and seasonal δ15N value variations in NH3 sources. The contribution fractions of v-NH3 (volatile NH3) and c-NH3 exhibited similar patterns at both sites seasonally, probably caused by coal combustion for heating in winter and temperature fluctuations. However, the contribution fraction of c-NH3 was lower at BH than at TJU in summer but greater in winter than at TJU. In summer, NH4NO3 was unstable and limited its delivery to TJU from BH, and the high contribution of c-NH3 to NH4+ at TJU could be attributed to local vehicle emissions. In winter, the stable particulate NH4NO3 that formed from the c-NH3 in the upwind area could be transported to the downwind area, increasing the NH4+ concentration at BH. Our study provides valuable insights for devising emission mitigation strategies to alleviate the increasing burden of NH3 in the local atmosphere.

Seasonal variations of profiles of antibiotic resistance genes and virulence factor genes in household dust from Beijing, China revealed by the metagenomics.

Household-related microbiome is closely related with human health. However, the knowledge about profiles of antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) which are carried by microbes inside homes and their temporal dynamics are rather limited. Here we monitored the seasonal changes of bacterial community (especially pathogenic bacteria), ARGs, and VFGs in household dust samples during two years. Based on metagenomic sequencing, the dust-related bacterial pathogenic community, ARGs, and VFGs all harbored the lowest richness in spring among four seasons. Their structure (except that of VFGs) also exhibited remarkable differences among the seasons. The structural variations of ARGs and VFGs were almost explained by mobile genetic elements (MGEs), bacterial pathogens, and particulate matter-related factors, with MGEs explaining the most. Moreover, the total normalized abundance of ARGs or VFGs showed no significant change across the seasons. Results of metagenomic binning and microbial network both showed that several pathogenic taxa (e.g., Ralstonia pickettii) were strongly linked with numerous ARGs (mainly resistant to multidrug) and VFGs (mainly encoding motility) simultaneously. Overall, these findings underline the significance of MGEs in structuring ARGs and VFGs inside homes along with seasonal variations, suggesting that household dust is a neglected reservoir for ARGs and VFGs.

Building Haplotype-Resolved 3D Genome Maps of Chicken Skeletal Muscle.

Haplotype-resolved 3D chromatin architecture related to allelic differences in avian skeletal muscle development has not been addressed so far, although chicken husbandry for meat consumption has been prevalent feature of cultures on every continent for more than thousands of years. Here, high-resolution Hi-C diploid maps (1.2-kb maximum resolution) are generated for skeletal muscle tissues in chicken across three developmental stages (embryonic day 15 to day 30 post-hatching). The sequence features governing spatial arrangement of chromosomes and characterize homolog pairing in the nucleus, are identified. Multi-scale characterization of chromatin reorganization between stages from myogenesis in the fetus to myofiber hypertrophy after hatching show concordant changes in transcriptional regulation by relevant signaling pathways. Further interrogation of parent-of-origin-specific chromatin conformation supported that genomic imprinting is absent in birds. This study also reveals promoter-enhancer interaction (PEI) differences between broiler and layer haplotypes in skeletal muscle development-related genes are related to genetic variation between breeds, however, only a minority of breed-specific variations likely contribute to phenotypic divergence in skeletal muscle potentially via allelic PEI rewiring. Beyond defining the haplotype-specific 3D chromatin architecture in chicken, this study provides a rich resource for investigating allelic regulatory divergence among chicken breeds.

Mesenteric sparing approach for advanced nodal extent in small intestinal neuroendocrine tumors. Is there a limit to the vascular resection in order to avoid creating a short small bowel syndrome? An anatomic research study.

PURPOSE: By selectively perfusing the first three jejunal arteries (JA), we aim to assess the individual perfusion length of small bowel (SB) and its impact on nodal resection in stage III-up small-intestinal neuroendocrine tumors (SI-NET). METHODS: Our anatomical research protocol implies a midline laparotomy and three measures of the SB length. We then perform a classical anterior approach of the superior mesenteric vessels. We carry on with the complete dissection and checking of the superior mesenteric artery (SMA) in order to identify the first three JA. Then we selectively perfuse each artery with colored latex solutions and measure the length of small bowel perfused respectively. RESULTS: We conducted our protocol on six cadaveric subjects. Mean(SD) SB length was 413(5.7), 535(13.2), 485(15), 353(25.1), 730(17.3) and 525(16° cm respectively from subject one to six. Most JA originated from the left side of the SMA. The first JA originated from its posterior wall in two subjects. Mean(SD) distance of origin of the first three JA was 4.6(1.3)cm, 6(1.1)cm and 7.1(0.9)cm respectively. Mean(SD) diameter of SMA was 10.8(3.3)mm. Mean diameter of the three first JA was 4(1.4)mm, 4(1.5)mm and 5(1.2)mm respectively. Mean(SD) SB length perfused by first and second JA was 224(14.9)cm, 175(8.6)cm, 238.3(7.6)cm, 84.3(5.1)cm, 233.3(5.8)cm and 218.3(10.4)cm respectively from subject one to six. CONCLUSION: We observed a trend suggesting that the first and second JA may sustain a SB length beyond the viable 1.5 m limit, implying the feasibility of stage III-up SI-NET resection with just two JA.

Are enlarged peroneal tubercle and accessory anterolateral talar facet associated with calcaneal spur?

BACKGROUND: As the anatomical variations of the foot, enlarged peroneal tubercle (EPT) and accessory anterolateral talar facet (AALTF) have attracted the attention of foot surgeons in recent years. However, EPT and AALTF have not been examined for a relationship with calcaneus spur (CS) as a common osteophyte. METHODS: The subjects were 369 individuals who died in northeastern Thailand and were preserved as skeletal specimens. The authors examined for the presence of left and right EPT, AALTF, and calcaneus spur (CS). We divided the EPT (+) group with EPT and the EPT (-) group without it and also divided the AALTF (+) group with AALTF and the AALTF (-) group without it. The age at death and the presence of CS were compared statistically between the EPT (+) and EPT (-) groups and between the AATLF (+) and AALTF (-) groups. RESULTS: Out of the total 369 cases, EPT was found in 117 cases (31.7%), AALTF was positive in 91 cases (24.7%), and CS was found in 194 cases (52.3%). In comparison between EPT (+) and EPT (-) groups, CS was significantly higher (p < 0.0001) in the EPT (+) group, but there was no significant difference in age at death. In comparison between AALTF (+) and AALTF (-) groups, there was no significant difference in age at death or CS. CONCLUSION: This study showed a strong relationship between EPT and CS, and the prevalence of EPT and AALTF by age in Thailand was first reported. We believe it helps to know the pathogenesis and biomechanism of EPT and AALTF. TRIAL REGISTRATION: Not applicable.

Combined first-trimester screening and invasive diagnostics for atypical chromosomal aberrations: Danish nationwide data on prenatal profiles and detection compared with NIPT.

OBJECTIVE: To examine the prenatal profiles of pregnancies affected by an atypical chromosomal aberration, focusing on pathogenic copy number variants (pCNVs). Further, we wanted to quantify the performance of combined first-trimester screening (cFTS) and a second-trimester anomaly scan in detecting these conditions. Finally, we aimed to estimate the consequences of a policy of using non-invasive prenatal testing (NIPT) rather than invasive testing with chromosomal microarray (CMA) to manage pregnancies identified as high risk from cFTS. METHODS: A retrospective review of the Danish fetal medicine database identified all pregnant women who had cFTS and a trisomy 21 risk-assessment between January 1, 2008, and December 31, 2018. Chromosomal aberrations diagnosed prenatally, postnatally, or from fetal tissue following pregnancy loss or termination of pregnancy (TOP) were identified. Chromosomal aberrations were grouped into one of six categories: 1) Triploidy; 2) Common trisomies (trisomies 21, 18, and 13); 3) Monosomy X; 4) Other sex chromosome aberrations (SCAs); 5) pCNVs; and 6) Rare autosomal trisomies (RATs) and mosaicisms. The prevalence of each aberration-category was stratified by the individual cFTS markers and risk estimate, and the size of each pCNV diagnosed from CMA was calculated. RESULTS: We included data on 565,708 pregnancies of which 3,982 were diagnosed with a fetal chromosomal aberration (0.70%). cFTS performed well in identifying triploidies (86%), monosomy X (92%), atypical SCAs (58%), and RATs and mosaicisms (70%). pCNVs comprised 28% (n = 1,091) of the chromosomal aberrations diagnosed overall, and the prevalence increased during the study period with more prenatal chromosomal microarray analysis being performed. In pregnancies with maternal age <30 years, NT <95th percentile, PAPP-A MoM ≥ 1, or trisomy 21 risk ≥1 in 1000, the prevalence of pCNVs significantly exceeded the prevalence of trisomies 21, 18, and 13. Pregnancies affected by a pCNV had significantly increased nuchal translucency thickness (NT) and decreased maternal biomarkers pregnancy associated plasma protein-A (PAPP-A) and ß-human chorionic gonadotropin (ß-hCG) compared with unaffected pregnancies. However, only 23% of these pregnancies screened positive from cFTS and 51% were not detected until after birth. Amongst high-risk pregnancies diagnosed with a chromosomal aberration, pCNVs comprised 14% and when other atypical aberrations were considered, conventional NIPT (screening for trisomies 21, 18, and 13, and monosomy X) would miss 28% of all pathogenic aberrations diagnosed following a high-risk cFTS result. Thus, 1 in 26 pregnancies at high-risk following cFTS would be affected by a chromosomal aberration despite a normal conventional NIPT result. In a contingent screening model with NIPT provided for the "intermediate" risk group (T21 risk of 1 in 100-300), 50% of the aberrations would be missed. In our cohort, 80% of the pCNVs diagnosed were <5Mb and therefore not detectable using current forms of "genome wide" NIPT. CONCLUSION: As a by-product to screening for trisomies 21, 18, and 13, most triploidies and the majority of atypical SCAs, RATs, and mosaicisms are detected before birth. However, only 23% of pCNVs are high-risk from cFTS and only half are diagnosed before birth. Replacing invasive testing with NIPT for high-risk pregnancies would substantially decrease the first-trimester detection of pathogenic chromosomal anomalies. This article is protected by copyright. All rights reserved.