The potential protective effects of melatonin and omega-3 on the male rat optic nerve exposed to 900 MHz electromagnetic radiation during the prenatal period.

BACKGROUND: Due to children and adolescents' widespread use of electronic devices, researchers have focused on pre-and early postnatal electromagnetic field (EMF) exposure. However, little is known about the effects of EMF exposure on the optic nerve. The aim of study was to investigate the changes occurring in the optic nerve and the protective effects of melatonin (mel) and omega 3 (ω-3) in rats. METHODS: Thirty-five pregnant rats were divided into seven groups, Cont, Sham, EMF, EMF + melatonin (EMF + Mel), EMF + ω3, Mel, and ω3. The EMF groups were exposed to 900 megahertz (MHz) EMF daily for two hours during pregnancy. After the experiment, the right optic nerve of each offspring rat was removed and fixed in glutaraldehyde. Thin and semi-thin sections were taken for electron microscopic and stereological analyses. Myelinated axon numbers, myelin sheath thicknesses, and axonal areas were estimated using stereological methods. RESULTS: The groups had no significant differences regarding mean numbers of axons, mean axonal areas, or mean myelin sheath thicknesses (p > 0.05). Histological observations revealed impaired lamellae in the myelin sheath of most axons, and vacuolization was frequently observed between the myelin sheath and axon in the EMF-exposed group. The Mel and ω-3-treated EMF groups exhibited well-preserved myelinated nerve fibers and intact astrocytes and oligodendrocytes. CONCLUSIONS: At the ultrastructural level, Mel and ω3 exhibits a neuroprotective effect on the optic nerve exposed to prenatal EMF. The protective effects of these antioxidants on oligodendrocytes, which play an essential role in myelin formation in the central nervous system, now require detailed investigation.

Primary antibody deficiencies in Turkey: molecular and clinical aspects.

Primary antibody deficiencies (PAD) are the most common subtype of primary immunodeficiencies, characterized by increased susceptibility to infections and autoimmunity, allergy, or malignancy predisposition. PAD syndromes comprise of immune system genes highlighted the key role of B cell activation, proliferation, migration, somatic hypermutation, or isotype switching have a wide spectrum from agammaglobulinemia to selective Ig deficiency. In this study, we describe the molecular and the clinical aspects of fifty-two PAD patients. The most common symptoms of our cohort were upper and lower respiratory infections, bronchiectasis, diarrhea, and recurrent fever. Almost all patients (98%) had at least one of the symptoms like autoimmunity, lymphoproliferation, allergy, or gastrointestinal disease. A custom-made next-generation sequencing (NGS) panel, which contains 24 genes, was designed to identify well-known disease-causing variants in our cohort. We identified eight variants (15.4%) among 52 PAD patients. The variants mapped to BTK (n = 4), CD40L (n = 1), ICOS (n = 1), IGHM (n = 1), and TCF3 (n = 1) genes. Three novel variants were described in the BTK (p.G414W), ICOS (p.G60*), and IGHM (p.S19*) genes. We performed Sanger sequencing to validate pathogenic variants and check for allelic segregation in the family. Targeted NGS panel sequencing can be beneficial as a suitable diagnostic modality for diagnosing well-known monogenic PAD diseases (only 2-10% of PADs); however, screening only the coding regions of the genome may not be adequately powered to solve the pathogenesis of PAD in all cases. Deciphering the regulatory regions of the genome and better understanding the epigenetic modifications will elucidate the molecular basis of complex PADs.

Lymphoma Predisposing Gene in an Extended Family: CD70 Signaling Defect.

Genome-wide sequencing studies in pediatric cancer cohorts indicate that about 10% of patients have germline mutations within cancer predisposition genes. Within this group, primary immune deficiencies take the priority regarding the vulnerability of the patients to infectious agents and the difficulties of cancer management. On the other hand, early recognition of these diseases may offer specific targeted therapies and hematopoietic stem cell transplantation as an option. Besides therapeutic benefits, early diagnosis will provide genetic counseling for the family members. Within this context, an extended family with multiple consanguineous marriages and affected individuals, who presented with combined immune deficiency (CID) and/or Hodgkin lymphoma phenotype, were examined by exome sequencing. A pathogenic homozygous missense CD70 variation was detected (NM_001252.5:c332C>T) in concordance with CD70 phenotype and familial segregation was confirmed. CD70 variations in patients with CID and malignancy have very rarely been reported. This paper reports extended family with multiple affected members with CID and malignancy carrying a missense CD70 variation, and reviews the rare cases reported in the literature. Primary immune deficiencies appear to be a potential cause for pediatric cancers. Better focusing on these inborn disorders to prevent or make an early diagnosis of malignant transformation and reduce mortalities is important.

Mutational landscape of severe combined immunodeficiency patients from Turkey.

Severe combined immunodeficiency (SCID) has a diverse genetic aetiology, where a clinical phenotype, caused by single and/or multiple gene variants, can give rise to multiple presentations. The advent of next-generation sequencing (NGS) has recently enabled rapid identification of the molecular aetiology of SCID, which is crucial for prognosis and treatment strategies. We sought to identify the genetic aetiology of various phenotypes of SCIDs and assessed both clinical and immunologic characteristics associated with gene variants. An amplicon-based targeted NGS panel, which contained 18 most common SCID-related genes, was contumely made to screen the patients (n = 38) with typical SCID, atypical SCID or OMENN syndrome. Allelic segregations were confirmed for the detected gene variants within the families. In total, 24 disease-causing variants (17 known and 7 novel) were identified in 23 patients in 9 different SCID genes: RAG1 (n = 5), RAG2 (n = 2), ADA (n = 3), DCLRE1C (n = 2), NHEJ1 (n = 2), CD3E (n = 2), IL2RG (n = 3), JAK3 (n = 4) and IL7R (n = 1). The overall success rate of our custom-made NGS panel was 60% (39.3% for NK+ SCID and 100% for NK- SCID). Incidence of autosomal-recessive inherited genes is more frequently found in our cohort than the previously reported populations probably due to the high consanguineous marriages in Turkey. In conclusion, the custom-made sequencing panel was able to identify and confirm the previously known and novel disease-causing variants with high accuracy.

Wheezing, asthma, and atopy in premature infants at 2 years of age.

BACKGROUND/AIM: We aimed to evaluate wheezing, bronchial asthma (BA), and atopy in premature infants at 2 years of age via a cross-sectional study. MATERIALS AND METHODS: Premature infants at <37 weeks of gestational age (GA) were assessed for atopy by skin-prick test and serum immunoglobulin E level at 2 years of age. The family's and infant's histories of allergy, BA, atopy, and wheezing were obtained by questionnaire and from hospital records. RESULTS: There were 98 infants, with mean birth weight (BW) 1517.4 ± 486.5 g and GA 30.8 ± 2.9 weeks. The frequencies of wheezing, asthma, and bronchopulmonary dysplasia (BPD) were 32.7%, 16.3%, and 14.3%, respectively. Skin-prick tests were positive for 11 subjects, with allergy to cereals for 7 infants, egg for 3, and peanut for 1. Wheezing was related to GA, BW, respiratory distress syndrome, mechanical ventilation, sepsis, asphyxia, smoking, antenatal steroid, BA, palivizumab prophylaxis, number of people in the household, and duration of hospitalization (P < 0.05). Wheezing was negatively correlated to GA. Family history of BA, smoking, and number of people in the household were linked to BA (P < 0.05). CONCLUSION: Wheezing was related to degree of premature birth, but BA was linked to BA in the family and smoking. Increased gestation should improve the infant's respiratory health up to 2 years of age.

Cytokine concentrations in pediatric patients with Crimean-Congo hemorrhagic fever.

Crimean-Congo hemorrhagic fever is a zoonotic disease that can be a severe illness in humans. We investigated concentrations of interleukin (IL)-6, tumor necrosis factor-α and IL-10 in serum samples obtained from 25 pediatric Crimean-Congo hemorrhagic fever cases and 35 control children with no signs of infection. Lower cytokine values in our patients could be a good prognostic factor to for a better outcome.

Follicular fluid concentrations of IGF-I, IGF-II, IGFBP-3, VEGF, AMH, and inhibin-B in women undergoing controlled ovarian hyperstimulation using GnRH agonist or GnRH antagonist.

OBJECTIVE: To compare follicular fluid concentrations of IGF-I, IGF-II, IGFBP-3, inhibin-B, VEGF, and AMH in women undergoing controlled ovarian hyperstimulation with a long-luteal GnRH agonist protocol or multiple-dose GnRH antagonist protocol. STUDY DESIGN: A total of 80 cycles were included; long-luteal GnRH agonist group (n=40) and multiple dose GnRH antagonist group (n=40). All follicular fluid samples were obtained from mature follicles during oocyte retrieval. IGF-I and IGFBP-3 concentrations were measured by immunoradiometric assay. IGF-II, VEGF, AMH, and inhibin-B concentrations were measured by enzyme-linked immunosorbent assay. RESULTS: There were no significant differences in the concentrations of the studied follicular fluid markers, cycle parameters, and treatment outcomes between GnRH agonist and GnRH antagonist protocols. CONCLUSIONS: The long-luteal GnRH agonist protocol and multiple-dose GnRH antagonist protocol seem to have similar effects on the follicular microenvironment in women undergoing controlled ovarian hyperstimulation.