Numerical Abnormalities Research Articles

Challenging diagnoses of tetraploidy/diploidy and trisomy 12: utility of first-tier prenatal testing methods.

Introduction: Chromosome mosaicism and low-grade mosaicism present a challenge for diagnosis in the era of SNP array and NGS. Tetraploidy is a rare numerical chromosomal abnormality characterized by the presence of four copies of each chromosome. The prevalence of tetraploidy/diploidy mosaicism cases is extremely rare in the human population. Accurate estimates of the frequency of this chromosomal anomaly are lacking due to its classification as an extremely rare and difficult-to-detect condition. Methods: In this report, we describe two cases involving challenging diagnoses of tetraploidy/diploidy and trisomy 12. We utilized advanced genetic testing techniques, including SNP array, to examine the chromosomal abnormalities in these cases. We compared the results from SNP array to conventional G band karyotyping to assess the utility of first-tier prenatal testing methods. Results:Our analysis revealed two cases of tetraploidy/diploidy and trisomy 12 with atypical presentations. SNP array analysis provided higher resolution and more precise information about the chromosomal anomalies in these cases compared to conventional G band karyotyping. Additionally, the prevalence of tetraploidy/diploidy mosaicism was confirmed to be extremely rare in the population. Discussion: Low-level mosaicism is difficult to diagnose, and in many cases, it has traditionally been identified through techniques such as G band karyotype or FISH. Microarray has become an invaluable diagnostic tool for detecting chromosomal abnormalities, offering high-resolution insights. However, it may not always be able to detect rare occurrences of tetraploidy or tetraploidy/diploidy mosaicism. As a result, it is recommended to perform a G band karyotype analysis after obtaining a negative microarray result before considering other diagnostic methods with a potentially higher yield of diagnosis. For the detection of low-level mosaicism, combined diagnostic methods should be considered. The diagnosis of mosaicism is a multistep process that can be time-consuming, often requiring the application of more than one diagnostic technique. This approach is crucial for accurate diagnosis and comprehensive patient care. Further research is warranted to better understand the underlying mechanisms of these rare chromosomal anomalies and to develop more effective diagnostic strategies for challenging cases.

Heavy water coupling gel for short-wave infrared photoacoustic imaging.

Changes in lipid, water, and collagen (LWC) content in tissue are associated with numerous medical abnormalities (cancer, atherosclerosis, and Alzheimer's disease). Standard imaging modalities are limited in resolution, specificity, and/or penetration for quantifying these changes. Short-wave infrared (SWIR) photoacoustic imaging (PAI) has the potential to overcome these challenges by exploiting the unique optical absorption properties of . This study's aim is to harness SWIR PAI for mapping LWC changes in tissue. The focus lies in devising a reflection-mode PAI technique that surmounts current limitations related to SWIR light delivery. To enhance light delivery for reflection-mode SWIR PAI, we designed a deuterium oxide (, "heavy water") gelatin (HWG) interface for opto-acoustic coupling, intended to significantly improve light transmission above 1200nm. HWG permits light delivery up to 1850nm, which was not possible with water-based coupling ( light delivery up to 1350nm). PAI using the HWG interface and the Visualsonics Vevo LAZR-X reveals a signal increase up to 24dB at 1720nm in lipid-rich regions. By overcoming barriers related to light penetration, the HWG coupling interface enables accurate quantification/monitoring of biomarkers like LWC using reflection-mode PAI. This technological stride offers potential for tracking changes in chronic diseases (in vivo) and evaluating their responses to therapeutic interventions.

Anomalies du récepteur de l’hormone de croissance hypophysaire et de son effecteur de l’axe somatotrope, l’Insulin-Like Growth Factor I

Postnatal statural growth is under the hormonal control of the somatotropic axis: hypothalamus-pituitary-liver-bone. Numerous gene abnormalities have been described, located at the hypothalamus and especially at the pituitary levels. Rarer damages are located downstream at the level of the pituitary growth hormone (GH) receptor, as in Laron's syndrome or in post-receptor signaling, Stat5b or the terminal effector of growth, the Insulin-Like Growth Factor I (IGF I). For several decades now, these severe statural growth retardations can benefit from recombinant IGF I treatment, with variable efficacy depending on the genetic abnormality.

Zinc As an Erythrocyte Stimulating Agent in Myelodysplastic Syndrome

Background: The anemia highly associated with myelodysplastic syndrome (MDS) has been linked to numerous transcriptional factor regulation abnormalities, specifically SMAD 2/3 upregulation that forms an inhibitory feedback loop to downregulate erythrocyte stimulation (ESA), which can have therapeutic implications. There is evidence that zinc contributes to erythropoiesis through multifactorial mechanisms involving regulation and transportation of necessary micronutrients including copper and iron. Zinc is involved in cell signaling pathways for erythropoiesis including acting as a cofactor in the SMAD 2/3 complex, TGF-β signaling, and incorporation of zinc into GATA-1 (Zinc finger transcription factor). The interaction with zinc in signaling cascades such as the growth hormone and insulin-like growth factor-1 pathways also result in increased erythropoietin transcription and therefore increased erythropoiesis. In addition, zinc is regarded as an important erythroid differentiation factor which progress maturation of erythrocytes. Due to the multifactorial role of zinc in erythropoiesis, including acting as a cofactor in the SMAD 2/3 complex, it may represent an inexpensive, and well tolerated ESA or additional micronutrient to test and supplement in MDS. This descriptive, retrospective study describes zinc deficient patients with MDS, who underwent zinc supplementation, and their changes in hemoglobin (HGB) over a 12-month period in an academic outpatient hematology center in California, United States of America. Objectives: Primary endpoints: determine if zinc supplementation in zinc deficient MDS patients will improve HGB by at least 1.0 g.dL by 1, 3, 6, and 12 month time points. Methods: Eight adult patients with MDS were identified to have zinc deficiency (plasma zinc concentration <65 ug/dL). Patients were not started on ESAs or their treatments were not changed for the management of their MDS. Patients were supplemented with Zinc Sulfate 50 mg daily and their HGB was followed over 12 months. A retrospective analysis for medical history and lab data at time of zinc deficiency diagnosis and at 1, 3, 6 and 12 month following initiation of zinc supplementation was completed. ANOVA, Wilcoxon rank-sum, and unpaired Students and t tests were performed to determine significant differences where p <0.05 is considered statistically significant. Results: Prior to supplementation, average HGB among patients was 8.01 g/dL, WBC was 3.65 g/dL, MCV was 97.6 fl, PLTS were 140g/dL. Following 1 month of supplementation average HGB was 8.5 g/dL (p = 0.5, n = 7), at 3 months average HGB was 9.27 g/dL (p = 0.087, n = 7), at 6 months average HGB was 10.3 g/dL (p= 0.006, n = 7), and at 12 months average HGB was 10.28 g/dL (p = 0.04, n= 7). Primary endpoint of HGB improvement by at least 1.0 g/dL was reached in 29% of patients at 1 month, 43% of patients at 3 months, 86% of patients at 6 months and 71% of patients at 12 months. Resolution of anemia was reached in 1 patient (12.5%) of patients within 12 months. Conclusions: Zinc supplementation improved anemia in MDS patients with incremental improvement in HGB over a 1 year time frame. There was statistically significant improvement from baseline HGB at the 3, 6, and 12 month time markers. Further study is warranted to determine the specific mechanism of zinc deficiency in MDS and its mechanism as an erythrocyte stimulating agent as well as further study in non-zinc deficient patients, various zinc supplementation doses, monitoring, and toxicity.

Ketogenic diet influence on the elemental homeostasis of internal organs is gender dependent

The ketogenic diet (KD) is a low-carbohydrate and high-fat diet that gains increasing popularity in the treatment of numerous diseases, including epilepsy, brain cancers, type 2 diabetes and various metabolic syndromes. Although KD is effective in the treatment of mentioned medical conditions, it is unfortunately not without side effects. The most frequently occurring undesired outcomes of this diet are nutrient deficiencies, the formation of kidney stones, loss of bone mineral density, increased LDL (low-density lipoprotein) cholesterol levels and hormonal disturbances. Both the diet itself and the mentioned adverse effects can influence the elemental composition and homeostasis of internal organs. Therefore, the objective of this study was to determine the elemental abnormalities that appear in the liver, kidney, and spleen of rats subjected to long-term KD treatment. The investigation was conducted separately on males and females to determine if observed changes in the elemental composition of organs are gender-dependent. To measure the concentration of P, S, K, Ca, Fe, Cu, Zn and Se in the tissues the method of the total reflection X-ray fluorescence (TXRF) was utilized. The obtained results revealed numerous elemental abnormalities in the organs of animals fed a high-fat diet. Only some of them can be explained by the differences in the composition and intake of the ketogenic and standard diets. Furthermore, in many cases, the observed anomalies differed between male and female rats.

Analysis of copy number variations and possible candidate genes in spontaneous abortion by copy number variation sequencing.

Embryonic chromosomal abnormalities represent a major causative factor in early pregnancy loss, highlighting the importance of understanding their role in spontaneous abortion. This study investigates the potential correlation between chromosomal abnormalities and spontaneous abortion using copy number variation sequencing (CNV-seq), a Next-Generation Sequencing (NGS) technology. We analyzed Copy Number Variations (CNVs) in 395 aborted fetal specimens from spontaneous abortion patients by CNV-seq. And collected correlated data, including maternal age, gestational week, and Body Mass Index (BMI), and analyzed their relationship with the CNVs. Out of the 395 cases, 67.09% of the fetuses had chromosomal abnormalities, including numerical abnormalities, structural abnormalities, and mosaicisms. Maternal age was found to be an important risk factor for fetal chromosomal abnormalities, with the proportion of autosomal trisomy in abnormal karyotypes increasing with maternal age, while polyploidy decreased. The proportion of abnormal karyotypes with mosaic decreased as gestational age increased, while the frequency of polyploidy and sex chromosome monosomy increased. Gene enrichment analysis identified potential miscarriage candidate genes and functions, as well as pathogenic genes and pathways associated with unexplained miscarriage among women aged below or over 35 years old. Based on our study, it can be inferred that there is an association between BMI values and the risk of recurrent miscarriage caused by chromosomal abnormalities. Overall, these findings provide important insights into the understanding of spontaneous abortion and have implications for the development of personalized interventions for patients with abnormal karyotypes.

The value of non-invasive prenatal testing for the identification of numerical and structural chromosomal abnormalities and copy number variations in the fetuses

To assess the value of non-invasive prenatal testing (NIPT) for the identification of numerical and structural chromosomal abnormalities and copy number variations (CNVs) in fetuses. 46 197 pregnant women undergoing NIPT at the Prenatal Diagnosis Center of Chenzhou First People's Hospital from January 2018 to December 2021 were selected as the study subjects. Positive cases were subjected to chromosomal karyotyping and copy number variation sequencing (CNV-seq) following amniocentesis. Nearly 50% of common chromosomal aneuploidies were found in the elder pregnant women. Among these, sex chromosome aneuploidies were mainly found in pregnant women with advanced age as well as borderline risks by serological screening. Rare autosomal aneuploidies and CNVs were mainly found in those with borderline or high risks by serological screening. The positive predictive values (PPV) for fetal chromosomal abnormalities indicated by NIPT were as follows: T21 (92.37%, 109/118), T18 (53.85%, 14/26), sex chromosome aneuploidies (45.04%, 59/131), T13 (34.62%, 9/26), CNVs (29.17%, 14/48), and rare autosomal aneuploidies (2.60%, 2/77). NIPT has a high detection rate for T21, T18, T13 and sex chromosome aneuploidies. It can also detect rare autosomal aneuploidies and CNVs, including some rare structural abnormalities, though verification is required by analyzing amniotic fluid samples.

Adenylate kinase 9 is essential for sperm function and male fertility in mammals

Despite passing routine laboratory tests for semen quality, bulls used in artificial insemination exhibit significant variation in fertility. Routine analysis of fertility data identified a dairy bull with extreme subfertility (10% pregnancy rate). To characterize the subfertility phenotype, a range of in vitro, in vivo, and molecular assays were carried out. Sperm from the subfertile bull exhibited reduced motility and severely reduced caffeine-induced hyperactivation compared to controls. Ability to penetrate the zona pellucida, cleavage rate, cleavage kinetics, and blastocyst yield after IVF or AI were significantly lower than in control bulls. Whole-genome sequencing from semen and RNA sequencing of testis tissue revealed a critical mutation in adenylate kinase 9 (AK9) that impaired splicing, leading to a premature termination codon and a severely truncated protein. Mice deficient in AK9 were generated to further investigate the function of the gene; knockout males were phenotypically indistinguishable from their wild-type littermates but produced immotile sperm that were incapable of normal fertilization. These sperm exhibited numerous abnormalities, including a low ATP concentration and reduced motility. RNA-seq analysis of their testis revealed differential gene expression of components of the axoneme and sperm flagellum as well as steroid metabolic processes. Sperm ultrastructural analysis showed a high percentage of sperm with abnormal flagella. Combined bovine and murine data indicate the essential metabolic role of AK9 in sperm motility and/or hyperactivation, which in turn affects sperm binding and penetration of the zona pellucida. Thus, AK9 has been found to be directly implicated in impaired male fertility in mammals.

Flow Cytometric Ploidy Analysis in Acute Lymphoblastic Leukemia and Plasma Cell Myeloma

AbstractIdentification of underlying cytogenetic (CG) aberrancies plays a significant role in risk stratification of hematological malignancies. These abnormalities can be due to aberrancies that affect the number or structure of chromosomes. Numerical chromosomal abnormalities are called aneuploidies, which result from either gain or loss of whole chromosomes. Ploidy assessment by CG is a laborious and less sensitive technique. With the aid of fluorescent nucleic acid binding dyes, the total DNA content and different phases of the cell cycle specific to any population of interest can be deciphered and analyzed by flow cytometry (FCM). DNA index (DI), a parameter derived by FCM DNA analysis, is equivalent to conventional CG-based ploidy assessment. In this study, the technical aspects and implications of FCM DNA assessment among patients diagnosed with acute lymphoblastic leukemia and plasma cell myeloma are discussed.

KaryoNet: Chromosome Recognition with End-to-End Combinatorial Optimization Network.

Chromosome recognition is a critical way to diagnose various hematological malignancies and genetic diseases, which is however a repetitive and time-consuming process in karyotyping. To explore the relative relation between chromosomes, in this work, we start from a global perspective and learn the contextual interactions and class distribution features between chromosomes within a karyotype. We propose an end-to-end differentiable combinatorial optimization method, KaryoNet, which captures long-range interactions between chromosomes with the proposed Masked Feature Interaction Module (MFIM) and conducts label assignment in a flexible and differentiable way with Deep Assignment Module (DAM). Specially, a Feature Matching Sub-Network is built to predict the mask array for attention computation in MFIM. Lastly, Type and Polarity Prediction Head can predict chromosome type and polarity simultaneously. Extensive experiments on R-band and G-band two clinical datasets demonstrate the merits of the proposed method. For normal karyotypes, the proposed KaryoNet achieves the accuracy of 98.41% on R-band chromosome and 99.58% on G-band chromosome. Owing to the extracted internal relation and class distribution features, KaryoNet can also achieve state-of-the-art performances on karyotypes of patients with different types of numerical abnormalities. The proposed method has been applied to assist clinical karyotype diagnosis. Our code is available at: https://github.com/xiabc612/KaryoNet.

Autoimmune Disease in Turner Syndrome in Sweden: An up to 25 Years' Controlled Follow-up Study.

Turner syndrome (TS) is the most common chromosomal aberration in women; it is the result of structural or numeric abnormalities in the X chromosome. Autoimmune hypothyroidism has been recognized as one of the more prominent disorders associated with TS. This work aimed to study the prevalence of autoimmune diseases in TS. A cross-sectional, longitudinal, 25-year follow-up study was conducted of patients from adult Turner centers at the University Hospitals, Sweden. During 1994 to 2020, a total of 503 women aged 16 to 71 years with TS were evaluated consecutively every fifth year according to national guidelines. A random population sample of women, n = 401, aged 25 to 44 years, from the World Health Organization Monitoring of Trends and Determinants for Cardiovascular Disease (MONICA) project served as controls. Serum thyrotropin, free thyroxine, vitamin B12, antithyroid peroxidase (anti-TPO), and antitransglutaminase antibodies were measured. Mean follow-up time (years) was 16 ± 7 for patients and 13 ± 1 for controls. From study start, the prevalence increased in TS for hypothyroidism 40% to 58%, vitamin B12 deficiency 5% to 12%, celiac disease 4% to 7%, positive anti-TPO 26% to 41%, and antitransglutaminase antibodies 6% to 8% (P < .0001 vs controls). Type 1 diabetes and Addison disease were rare. The only interrelationship was between hypothyroidism and vitamin B12 deficiency, both in TS and controls. No association between autoimmune disease and karyotype, antecedent growth hormone treatment, or ongoing estrogen hormone replacement, was seen in TS. In women with TS up to older than 80 years, more than half developed hypothyroidism, mainly autoimmune, during follow-up. Awareness of vitamin B12 deficiency and celiac disease throughout life is also recommended in women with TS.

Deep immunophenotypic analysis of the bone marrow progenitor cells in myelodysplastic syndromes

BackgroundDiagnosis of myelodysplastic syndromes (MDS) is often challenging and requires integration of clinical, morphologic, cytogenetics and molecular information. Flow cytometry immunophenotyping (FCIP) can support the diagnosis by demonstration of numerical and immunophenotypic abnormalities of progenitor and maturing myelomonocytic and erythroid populations. We have previously shown that comprehensive immunophenotypic analysis of the progenitor population is valuable in the diagnosis of MDS and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). This study was designed to improve the analysis method and confirm its value in a larger cohort of patients. MethodsFCIP of bone marrow samples from 105 patients with cytopenia(s) (with or without leukocytosis) and clinical concern for MDS or MDS/MPN was performed using a single-tube/10-color/13-marker assay. A modified analysis approach was used to obtain 11 progenitor parameters and 2 myelomonocytic parameters. ResultsSignificantly higher number of abnormalities were identified in MDS and MDS/MPN cases when compared to cytopenic patients not meeting the diagnostic criteria for MDS (Non-MDS). A FCIP score that combined the 13 parameters showed a sensitivity of 89.8% and specificity of 93.5% for the diagnosis of MDS and MDS/MPN. The sensitivity was 100% for both MDS/MPN and higher-risk MDS, and 81.3% for lower-risk MDS. ConclusionThis study confirms that detailed immunophenotypic analysis of the progenitor population is powerful in the diagnosis of MDS and MDS/MPN. The combination of markers used in the panel allowed for evaluation of two relatively new parameters, namely myeloid progenitor heterogeneity and stem cell aberrancy, which improved the sensitivity of the assay for lower-risk MDS.

Chromosomal aneuploidy and pregnancy outcomes for D5/D6 blastocysts from patients undergoing PGT-A treatment

To compare the prevalence of chromosomal aneuploidies and pregnancy outcomes of D5 and D6 blastocysts subjected to preimplantation genetic testing for aneuploidy (PGT-A). Clinical and laboratory data of 268 couples who underwent PGT-A at the Reproductive Center of the First Affiliated Hospital of Zhengzhou University from September 2018 to September 2020 were collected. The prevalence of chromosomal aneuploidies and pregnancy outcomes of D5/D6 biopsied blastocysts were compared. Compared with D6 blastocysts, the euploidy rate of D5 blastocysts was significantly higher (49.1% vs. 41.1%, P = 0.001 1), whilst their aneuploidy rate was significantly lower (50.9% vs. 58.9%, P = 0.001 1). The rate of numerical abnormalities of D6 blastocysts was significantly higher than that of D5 blastocysts (27.9% vs. 20.2%, P = 0.000 5). For patients under 35 years old, the euploidy rate of D5 blastocysts was significantly higher than that of D6 blastocysts (53.8% vs. 44.3%, P = 0.001), whilst the numerical abnormality rate was significantly lower (16.3% vs. 23.9%, P = 0.001). For both D5 and D6 blastocysts, the euploidy rates for patients <= 35 were significantly higher than those for > 35. The elder group had the lowest rates for aneuploidies and live births. Compared with those receiving D6 blastocysts transplantation, the pregnancy rate, implantation rate and live birth rate for those receiving thawed D5 blastocysts transplantation were significantly higher (60.2% vs.37.0%, P = 0.000 3; 59.1% vs.37.0%, P = 0.000 6; 47.7% vs. 28.3%, P = 0.002). For patients undergoing PGT-A, the chromosomal euploidy rate for D5 blastocysts is higher than that for D6 blastocysts, and the clinical outcome of D5 blastocysts with normal signal is better than that of D6 blastocysts. Elder patients have a higher rate of aneuploidies.

Absence of long-term structural and functional cardiac abnormalities on multimodality imaging in a multi-ethnic group of COVID-19 survivors from the early stage of the pandemic.

Many patients with coronavirus disease-2019 (COVID-19), particularly from the pandemic's early phase, have been reported to have evidence of cardiac injury such as cardiac symptoms, troponinaemia, or imaging or ECG abnormalities during their acute course. Cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) have been widely used to assess cardiac function and structure and characterize myocardial tissue during COVID-19 with report of numerous abnormalities. Overall, findings have varied, and long-term impact of COVID-19 on the heart needs further elucidation. We performed TTE and 3 T CMR in survivors of the initial stage of the pandemic without pre-existing cardiac disease and matched controls at long-term follow-up a median of 308 days after initial infection. Study population consisted of 40 COVID-19 survivors (50% female, 28% Black, and 48% Hispanic) and 12 controls of similar age, sex, and race-ethnicity distribution; 35% had been hospitalized with 28% intubated. We found no difference in echocardiographic characteristics including measures of left and right ventricular structure and systolic function, valvular abnormalities, or diastolic function. Using CMR, we also found no differences in measures of left and right ventricular structure and function and additionally found no significant differences in parameters of tissue structure including T1, T2, extracellular volume mapping, and late gadolinium enhancement. With analysis stratified by patient hospitalization status as an indicator of COVID-19 severity, no differences were uncovered. Multimodal imaging of a diverse cohort of COVID-19 survivors indicated no long-lasting damage or inflammation of the myocardium.

Cytogenetic studies in reproductive function disorders: a retrospective analysis

Aim. Fertility disorders are one of the most common problems of reproductive medicine. Chromosomal abnormalities play a crucial role in reproductive failure. The main purpose of our study was to determine the types and frequency of chromosomal aberrations in couples with history of infertility. Methods. Karyotyping was performed in 652 couples with reproductive failure between 2004 and 2022, including 203 couples with primary infertility (PI), 240 couples with recurrent pregnancy loss (RPL) and 209 – with sporadic pregnancy loss (SPL). Results. Numerical and structural karyotype abnormalities were detected in 37 (2.84 %) of 1304 individuals with infertility, most frequently in group with PI – 3.4 % and RPL – 3.3 %. Chromosomal abnormalities were detected in 3.1 % woman and 2.6 % men. The most common cytogenetic abnormalities (26 cases of 37; 2 %) are translocations, reciprocal – 18 cases (1.4 %) and Robertsonian – 8 cases (0.6 %). Numerical and structural gonosomal abnormalities were detected in 9 individuals (0.7 %), supernumerary marker chromosome – in 2 (0.14 %). Conclusions. Karyotype abnormalities are most common in individuals with PI and RPL and a occur with the same frequency among women and men. Numerical gonosomal abnormalities were detected only as mosaic form.

Pesticide use and Their Impacts on Health of Farmers: A Study in Rajapur Area, Bardiya (Nepal)

A study was conducted in the Rajapur municipality and Geruwa Rural municipality to determine the types of pesticides used in agriculture and their potential effects on farmers' health. Interviews were conducted with 240 farmers from 12 villages in the study area, and the information provided suo moto by the farmers were analyzed. This study found that the farmers frequently use pesticides in the extremely risky to highly deadly categories, such as carbamates, pyrethroids, organophosphides, and organophosphates. It has been discovered that the majority of farmers in the study area are ignorant of the dangers to human health presented by the mentioned pesticides and the consequences of their careless handling. Farmers cover their faces with cloth fabric masks and smoke tobacco to protect them. In addition, it was noticed that after spraying the pesticides, other typical farming activities continued in the agricultural fields. So, there is also a possibility that these pesticides will directly come into touch with women, children, and other field employees. There were numerous illnesses and physiological abnormalities with various indications and symptoms. A significant relative risk (RR) was also noted. It was discovered that the farmers of the study area have poor state of health which was aggravated by the lack of awareness and failure to implement suitable preventive measures regarding use of pesticides.

The Value of Using a Quality Assurance Follow-Up Team to Address Incidental Findings After Emergency Department or Urgent Care Discharge: A Cost Analysis

BackgroundIncidental finding (IF) follow-up is of critical importance for patient safety and is a source of malpractice risk. Laboratory, imaging, or other types of IFs are often uncovered incidentally and are missed, not addressed, or only result after hospital discharge. Despite a growing IF notification literature, a need remains to study cost-effective non–electronic health record (EHR)–specific solutions that can be used across different types of IFs and EHRs. ObjectiveThe objective of this study was to evaluate the utility and cost-effectiveness of an EHR-independent emergency medicine–based quality assurance (QA) follow-up program in which an experienced nurse reviewed laboratory and imaging studies and ensured appropriate follow-up of results. MethodsA QA nurse reviewed preceding-day abnormal studies from a tertiary care hospital, a community hospital, and an urgent care center. Laboratory values outside preset parameters or radiology over-reads resulting in clinically actionable changes triggered contact with an on-call emergency physician to determine an appropriate intervention and its implementation. ResultsOf 104,125 visits with 1,351,212 laboratory studies and 95,000 imaging studies, 6530 visits had IFs, including 2659 laboratory and 4004 imaging results. The most common intervention was contacting a primary care physician (5783 cases [88.6%]). Twenty-one cases resulted in a patient returning to the ED, at an average cost of $28,000 per potential life-/limb-saving intervention. ConclusionsAlthough abnormalities in laboratory results and imaging are often incidental to patient care, a dedicated emergency department QA follow-up program resulted in the identification and communication of numerous laboratory and imaging abnormalities and may result in changes to patients’ subsequent clinical course, potentially increasing patient safety.

Efficacy of Systematic Early-Second-Trimester Ultrasound Screening for Facial Anomalies: A Comparison between Prenatal Ultrasound and Postmortem Findings.

Second-trimester 2D ultrasound (US) assessment of the fetal anatomy, as proposed by worldwide guidelines, allows detecting the majority of fetal malformation. However, the detection rates of fetal facial anomalies seem to still be low, mostly in cases of isolated facial malformation. The purpose of this research was to assess and analyze the concordance between the antenatal imaging findings from second-trimester US screening and the results of fetal postmortem autopsy. Between January 2010 and January 2020, there were 43 cases where fetuses with prenatal ultrasound diagnosis of a face abnormality, associated or not with a genetic syndrome or chromosomal disorder, following intrauterine death (IUD) or termination of pregnancy (TOP) after the 13 weeks of pregnancy, underwent autopsy in the Pathological Anatomy section of Bari Polyclinic specializing in feto-placental autopsies. The diagnosis of the fetal facial defects at ultrasound was compared with the findings at autopsy in all cases. A very high level of agreement between prenatal ultrasound and autopsy findings was found for facial abnormalities associated with genetic syndromes or numerical abnormality of chromosomes. A lower level of concordance was instead found in isolated facial defects or those associated with other organ anomalies, but not associated with genetic syndrome or numerical chromosome anomaly. A detailed examination of aborted fetuses led to successful quality control of early-second-trimester ultrasound detection of facial anomalies; however, it was less accurate for the isolated ones. It is, thus, reasonable to propose a systematic early-second-trimester prenatal ultrasound screening for facial anatomy by operators specialized in fetal medicine field, using 2D, 3D, and 4D techniques (two-, three-, and four-dimensional ultrasound).

Genotoxicity assessment of titanium dioxide nanoparticles using a standard battery of in vivo assays

As one representative of nanometal oxides, titanium dioxide nanoparticles (TiO2-NPs) have been widely used, particularly in the food industry. The genotoxicity of TiO2-NPs has attracted great attention over the years. This study was undertaken to investigate the chromosome and DNA damage effects of TiO2-NPs (0, 50, 150, and 500 mg/kg BW) using rodent models. After a comprehensive characterization, we conducted a standard battery of in vivo genotoxicity tests, including the chromosomal aberration test (CA), micronucleus (MN) test, and the comet test. The results of all these tests were negative. There were no structural or numerical chromosomal abnormalities in mice bone marrow cells, no increase in the frequency of micronucleated polychromatic erythrocytes in mice bone marrow cells, and no elevation in % tail DNA in rat hepatocytes. This indicated that TiO2-NPs did not cause chromosomal damage or have a direct impact on DNA. These findings suggested that TiO2-NPs did not exhibit genotoxicity and provided valuable data for risk assessment purposes.

Chromosomal Abnormalities of Interest in Turner Syndrome: An Update.

Turner syndrome (TS) is caused by the total or partial loss of the second sex chromosome; it occurs in 1 every 2,500-3,000 live births. The clinical phenotype is highly variable and includes short stature and gonadal dysgenesis. In 1959, the chromosomal origin of the syndrome was recognized; patients had 45 chromosomes with a single X chromosome. TS presents numerical and structural abnormalities in the sex chromosomes, interestingly only 40% have a 45, X karyotype. The rest of the chromosomal abnormalities include mosaics, deletions of the short and long arms of the X chromosome, rings, and isochromosomes. Despite multiple studies to establish a relationship between the clinical characteristics and the different chromosomal variants in TS, a clear association cannot yet be established. Currently, different mechanisms involved in the phenotype have been explored. This review focuses to analyze the different chromosomal abnormalities and phenotypes in TS and discusses the possible mechanisms that lead to these abnormalities.