Apparently isolated ventricular septal defect, prenatal diagnosis, association with chromosomal aberrations, spontaneous closure rate in utero and during the first year of life: a systematic review

Aim: To evaluate the incidence of chromosomal aberrations in apparently isolated ventricular septal defects (VSD), quantify the timing of diagnosis of prenatally diagnosed VSDs, and define the spontaneous closure rate prenatally both in utero and during the first year of life. Materials and methods: Medline, PubMed, and the Cochrane Database Library were searched to identify studies published between January 2013 and January 2023 using keywords and word variant combinations for isolated ventricular septal defect, fetal echocardiography, karyotype, genetics, array CGH, spontaneous closure, and outcome. Inclusion criteria: studies reporting apparently isolated ventricular septal defect. Primary outcomes: to find the incidence of chromosomal aberrations in apparently isolated ventricular septal defects, and quantify the timing of diagnosis. Secondary outcome: to define the spontaneous closure rate in utero and in the first year of life. Statistical analysis was performed using Jamovi Meta-Analysis major package 2.3.21 Solid. To combine data, we used proportions and maximum likelihood ratios. Results: Overall, the maximum likelihood ratio of chromosomal aberrations in antenatally diagnosed apparently isolated VSD was 2.7%. The different types of defects showed substantially different rates of chromosomal aberrations. Muscular VSDs had a chromosomal aberrations rate of 0.4% vs. 4.8% for perimembranous VSDs. Mean gestational age of diagnosis was 25+4 days. Spontaneous closure rate maximum likelihood ratio in utero was 28.6%. Higher closure rate in utero was observed for the perimembranous type while muscular VSDs showed higher closure rates after birth. Closure in utero was observed in 28.9% of the perimembranous VSDs and in 14.5% of the muscular VSDs. Closure after 12 months was found in 22% for the perimembranous defects and in 53.8% for the muscular defects. The presented results could be of use in informed prenatal counseling and of great help in parental decision making. Conclusions: This systematic study included 740 isolated ventricular septal defects, of which 422 were muscular and 165 were perimembranous. Other types were not specified. One hundred fifty-nine perimembranous and 384 muscular VSDs were available for a follow-up after 12 months of life. Chromosomal aberrations were detected in 4.8% of the perimembranous VSDs and in 0.4% of the muscular VSDs

Synthesis and Pharmacological Evaluation of Novel Schiff Base Analogues of 3-(4-amino) Phenylimino) 5-fluoroindolin-2-one

In our study, a series of novel 3-(4-(benzylideneamino) phenylimino) 4-fluoroindolin-2-one derivatives were synthesized and characterized by spectral (I.R, 1H NMR, mass) and elemental analysis. The title compounds (N1-N10) were evaluated for analgesic, anti-inflammatory, and ulcerogenic index activities. Results displayed that compound N3 exhibited significant analgesic activity. Among the title compounds studied, N2, N3, and N8 exhibited significant anti- inflammatory activity comparable to reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic side effect when compared to aspirin

Sequence analysis of the Epstein-Barr virus (EBV) BRLF1 gene in nasopharyngeal and gastric carcinomas

<p>Abstract</p> <p>Background</p> <p>Epstein-Barr virus (EBV) has a biphasic infection cycle consisting of a latent and a lytic replicative phase. The product of immediate-early gene BRLF1, Rta, is able to disrupt the latency phase in epithelial cells and certain B-cell lines. The protein Rta is a frequent target of the EBV-induced cytotoxic T cell response. In spite of our good understanding of this protein, little is known for the gene polymorphism of BRLF1.</p> <p>Results</p> <p>BRLF1 gene was successfully amplified in 34 EBV-associated gastric carcinomas (EBVaGCs), 57 nasopharyngeal carcinomas (NPCs) and 28 throat washings (TWs) samples from healthy donors followed by PCR-direct sequencing. Fourteen loci were found to be affected by amino acid changes, 17 loci by silent nucleotide changes. According to the phylogenetic tree, 5 distinct subtypes of BRLF1 were identified, and 2 subtypes BR1-A and BR1-C were detected in 42.9% (51/119), 42.0% (50/119) of samples, respectively. The distribution of these 2 subtypes among 3 types of specimens was significantly different. The subtype BR1-A preferentially existed in healthy donors, while BR1-C was seen more in biopsies of NPC. A silent mutation A/G was detected in all the isolates. Among 3 functional domains, the dimerization domain of Rta showed a stably conserved sequence, while DNA binding and transactivation domains were detected to have multiple mutations. Three of 16 CTL epitopes, NAA, QKE and ERP, were affected by amino acid changes. Epitope ERP was relatively conserved; epitopes NAA and QKE harbored more mutations.</p> <p>Conclusions</p> <p>This first detailed investigation of sequence variations in BRLF1 gene has identified 5 distinct subtypes. Two subtypes BR1-A and BR1-C are the dominant genotypes of BRLF1. The subtype BR1-C is more frequent in NPCs, while BR1-A preferentially presents in healthy donors. BR1-C may be associated with the tumorigenesis of NPC.</p

The Death of Sperm Cells

A major factor affecting male fertility is excessive death of germ cells, both immature germ cells and mature spermatozoa. It can be due to various factors causing testicular and/or post-testicular damage, such as infections, obstructive conditions, toxins, oxidative stress, hormonal imbalance, hyperthermia, and anti-sperm antibodies. Massive death of spermatozoa leads to a high proportion of dead sperm cells in the ejaculate (necrozoospermia or necrospermia) while death of immature germ cells can lead to low sperm count (oligozoospermia or oligospermia). Cell death can occur both by necrosis and by apoptosis; in recent decades, it has been found that apoptosis of mature spermatozoa is not only possible but quite common, and can contribute to infertility. Treatment approaches are primarily directed to the underlying condition, i.e. removing the cause(s) of sperm cell death whenever possible, but include also attempts to bypass the cell death event by intracytoplasmic sperm injection with testicular spermatozoa