The Study of Alternative Splicing Events in Human Induced Pluripotent Stem Cells From a Down's Syndrome Patient

Down's syndrome (DS) is one of the most commonly known disorders with multiple congenital disabilities. Besides severe cognitive impairment and intellectual disability, individuals with DS also exhibit additional phenotypes of variable penetrance and severity, with one or more comorbid conditions, including Alzheimer's disease, congenital heart disease, or leukemia. Various vital genes and regulatory networks had been studied to reveal the pathogenesis of the disease. Nevertheless, very few studies have examined alternative splicing. Alternative splicing (AS) is a regulatory mechanism of gene expression when making one multi-exon protein-coding gene produce more than one unique mature mRNA. We employed the GeneChip Human Transcriptome Array 2.0 (HTA 2.0) for the global gene analysis with hiPSCs from DS and healthy individuals. Examining differentially expressed genes (DEGs) in these groups and focusing on specific transcripts with AS, 466 up-regulated and 722 down-regulated genes with AS events were identified. These genes were significantly enriched in biological processes, such as cell adhesion, cardiac muscle contraction, and immune response, through gene ontology (GO) analysis of DEGs. Candidate genes, such as FN1 were further explored for potentially playing a key role in DS. This study provides important insights into the potential role that AS plays in DS.

Prevalence of Neural Tube Defects (NTDs) In And Around Varanasi Region: Some Observations

Congenital anomalies are one of the primary causes of infant mortality and disability in the world. Neural Tube Defects (NTDs) are the most typical type of birth defect resulting from the failure of Neural tube closure. In this retrospective hospital-based study, the data of the children affected byneural tube defects (NTDs) were analyzed. Prevalence of Hydrocephalous, Myelomeningocele (MMC), Encephalocele, Lipo MMC, Meningocele, Spina Bifida Occulta among children with more or less than one year of age and their occurrence in males and females was studied. The frequency of occurrence of cases of neural tube defects was significantly less among all the congenital disabilities, i.e., 5% of total cases studied. The prevalence of myelomeningocele, hydrocephalous, and Encephalocele was higher than other types of NTDs. This study concludes that the prevalence of hydrocephalous and myelomeningocele in this area raises a concern to have more research of their etiology.

Health Risks Associated with the Consumption of Legumes Contaminated with Pesticides and Heavy Metals

Legumes have high nutritional value and they are important sources of protein, carbohydrates, fats and dietary fiber. The contamination of legumes with pesticides and heavy metals has been reported in scientific literature. Human beings are mainly exposed to the residues of pesticides and heavy metals through the dietary route. The purpose of this review chapter is to highlight the acute and chronic health risks that human beings may be exposed to as a result of the ingestion of legumes polluted with pesticides and heavy metals. Additionally, the mechanisms through which pesticides and heavy metals engender different undesirable health outcomes in human beings were stated. Scientific literature were perused and the information contained in them were collated to derive this chapter. Pesticides cause short-term health effects including hypersensitivity and mortality, while heavy metals induce acute effects like seizures and death. Some chronic untoward effects of pesticides are congenital disabilities and neurological damage. Heavy metals elicit disorders like anemia, hypertension and cancer. It is envisaged that the findings documented in this review will create awareness of the health risks posed by the contamination of legumes with the residues of pesticides and heavy metals so that food safety measures can be enforced globally.

P–554 Reproductive risks and preimplantation genetic testing intervention for X-autosome translocation carriers

Study question For X-autosome translocation [t(X-A)] carriers, is it a more applicable preimplantation genetic testing (PGT) strategy, that distinguishing noncarrier from euploid/ balanced embryos and prioritized transfer? Summary answer Noncarrier and carrier embryos discrimination in PGT is an applicable strategy to avoid transferring genetic and reproductive risks to the offspring of t(X-A) carriers. What is known already Balanced t(X-A) is a specific reciprocal translocation, with a higher risk of detrimental phenotype and fertility issues compared to individuals with autosomal translocation. Alternative X-chromosome inactivation (XCI) is a specific pathogenic mechanism in this population. For carrier offspring of couples with t(X-A), the genetic counseling is challenged in both the prenatal and postpartum stages, because of the complexity and severity of phenotype outcomes that are unpredictable and associated with the complex XCI mechanism. Therefore, caution is necessary when designing a PGT strategy for couples with t(X-A). Study design, size, duration A retrospective study. We collected a 3-year-old girl with maternal translocation 46,X,t(X;1)(q28;p31.1) presenting with multiple congenital disabilities. Three couples with female t(X-A) carrier requesting for PGT. Participants/materials, setting, methods Karyotype analysis, whole-exome sequencing (WES), and X inactivation analysis were performed for the girl with congenital cardiac anomaly, language defect, and mild neurodevelopmental delay. PGT based on next-generation sequencing following the microdissecting junction region to distinguish noncarrier and carrier embryos were used in three couples with female t(X-A) carrier (Cases 1–3). Main results and the role of chance The girl carried a maternal balanced translocation 46,X,t(X;1)(q28;p31.1). WES revealed none monogenic mutation related to her phenotype, but she carried a rare skewed inactivation of the translocation X chromosome and spread to the adjacent interstitial 1p segment, contrary to her mother. All translocation breakpoints of Cases 1–3 were successfully identified and each couple underwent one PGT cycle. Thirty oocytes were retrieved, and 13 blastocysts were eligible for biopsy, of which 6 (46.15%) embryos were balanced and only 4 were noncarriers. Three frozen embryo transfers with noncarrier embryos resulted in the birth of two healthy children (one girl and one boy), who were subsequently confirmed to have normal karyotypes. We reported a girl with multiple congenital disabilities resulting from maternally balanced t(X-A) and validated that noncarrier and carrier embryo discrimination is an effective and applicable strategy for avoiding transferring genetic and reproductive risks to the offspring from t(X-A) carriers. Limitations, reasons for caution Here, we reported a girl with multiple congenital disabilities resulting from maternally balanced t(X-A) found different XCI patterns, while we did not further determine the mechanism causing the different XCI patterns between the girl and her mother. Wider implications of the findings: We demonstrated passing on a balanced t(X-A) may result in clinical manifestations associated with the X-inactivation, and verified the PGT strategy, that distinguishing normal and carrier embryos in can widely applied in t(X-A) carrier couples to avoid the genetic and reproductive risk of transferring t(X-A) to the next generation. Trial registration number the National Key Research & Developmental Program of China (2018YFC1004900), the National Natural Science Foundation of China (81771645 and 81971447), the Key Grant of Prevention and Treatment of Birth Defect from Hunan Province (2019SK1012), Hunan Provincial Grant for Innovative Province Construction (2019SK4012) and the Research Grant of CITIC-Xiangya (YNXM–201916).

A Label and Probe-Free Zika Virus Immunosensor Prussian Blue@carbon Nanotube-Based for Amperometric Detection of the NS2B Protein

Zika virus (ZIKV) is a mosquito-borne infection, predominant in tropical and subtropical regions causing international concern due to the ZIKV disease having been associated with congenital disabilities, especially microcephaly and other congenital abnormalities in the fetus and newborns. Development of strategies that minimize the devastating impact by monitoring and preventing ZIKV transmission through sexual intercourse, especially in pregnant women, since no vaccine is yet available for the prevention or treatment, is critically important. ZIKV infection is generally asymptomatic and cross-reactivity with dengue virus (DENV) is a global concern. An innovative screen-printed electrode (SPE) was developed for amperometric detection of the non-structural protein (NS2B) of ZIKV by exploring the intrinsic redox catalytic activity of Prussian blue (PB), incorporated into a carbon nanotube–polypyrrole composite. Thus, this immunosensor has the advantage of electrochemical detection without adding any redox-probe solution (probe-less detection), allowing a point-of-care diagnosis. It was responsive to serum samples of only ZIKV positive patients and non-responsive to negative ZIKV patients, even if the sample was DENV positive, indicating a possible differential diagnosis between them by NS2B. All samples used here were confirmed by CDC protocols, and immunosensor responses were also checked in the supernatant of C6/36 and in Vero cell cultures infected with ZIKV.

Disability, Embodiment, and Slavery in the Old South

Centering on disabled people’s experiences of complex embodiment under slavery, this chapter highlights the shifting boundaries of “unsoundness.” Enslaved people experienced congenital disabilities but also acquired impairments as a result of labor accidents, punishments, and aging. Bondpeople were valuable “property” as laborers and potential reproducers of future generations of slaves, so the condition of their bodies and minds were central to slaveholders’ pursuit of economic gain. This emphasis on sound bodies and minds dominated the historical record left by slaveholders and, in turn, shaped scholarship about the institution. Clinical and detached assessments of “slave health” and assumptions about labor potential obscure the point that many people navigated a lifetime of enslavement with various disabilities.

A comparison of the clinical effects of thinning and drilling on laser-assisted hatching

To systematically investigate the effects of two methods used for laser-assisted hatching (LAH) on clinical outcomes after day 4 (D4) on frozen-embryo-transfer (FET) cycles. Data from 11471 infertile patients who underwent FET cycles between January 2014 and October 2018 was retrospectively analyzed. The 1410 patients who met the inclusion criteria were further categorized into two groups based on the hatching procedure used: the thinning laser-assisted hatching group (T-LAH, 716 patients), and the drilling laser-assisted hatching group (D-LAH, 694 patients). The baseline characteristics of the patients were consistent between the two groups. However, the rates of implantation and clinical pregnancy were significantly higher in the T-LAH group compared to the D-LAH group (32.73% vs. 29.09%, P < 0.01, and 50.98% vs. 43.95%, P < 0.01). The proportion of live birth was also higher in the T-LAH group, but the difference was insignificant (39.11% vs. 36.89%, P > 0.05). Moreover, there were no significant differences in rates of miscarriages, multiple pregnancies, ectopic pregnancies, preterm births, and congenital disabilities between the two groups. Nonetheless, significantly higher rates of implantation and pregnancy were reported in the T-LAH group compared to the D-LAH group among patients aged <35 years, patients with at least one previously failed cycle, and patients with an endometrial thickness of 8–10 mm. T-LAH is superior to D-LAH in improving clinical implantation and pregnancy outcomes in D4 FET, particularly in patients aged <35 years with at least one previously failed cycle or an endometrial thickness of 8–10 mm. The findings of this study provide theoretical support for clinical individualized diagnosis and treatment of patients with infertility.