Lactobacillus GG is associated with mucin genes expressions in type 2 diabetes mellitus: a randomized, placebo-controlled trial.

PURPOSE: Recent studies indicate that dysbiosis of gut microbiota and low-grade inflammation are important pathogenic determinants of type two diabetes mellitus (T2DM). The aim of this study is to investigate the effects of Lactobacillus GG on glycemic control, lipid profile, inflammatory parameters, and some gene expression levels in individuals with T2DM. METHODS: In a randomized, placebo-controlled trial, 34 women, aged 30-60 years with T2DM consumed daily probiotics or placebo for 8 weeks. The probiotic group consumed 10 × 109 Cfu/day Lactobacillus rhamnosus GG ATCC 53,103 (LGG), approved by the TR Ministry of Food, Agriculture, and Livestock. Anthropometric measurements, food diary, fasting blood, and fecal samples were taken at baseline and post-treatment. RESULTS: Fasting blood glucose was significantly decreased in probiotic (p = 0.049) and placebo (p = 0.028), but there was no difference between the groups. In the probiotic group, no significant difference was observed in HbA1c, fructosamine, lipid profile, and inflammatory variables compared to baseline. In this group, with LGG supplementation, mucin 2 and 3A (MUC2 and MUC3A) gene expressions increased more than ninefolds (p = 0.046 and p = 0.008, respectively) at post-treatment. Meanwhile, there was no significant change in any of the gene expressions in the placebo group. There was no significant difference in energy, protein, dietary fiber, and cholesterol intakes between placebo and probiotic groups during the study. However, daily fat intake (p = 0.003), body weight (p = 0.014), and body fat (p = 0.015) in the probiotic group were significantly decreased. CONCLUSION: In this study, the effects of a single probiotic strain were investigated for 8 weeks. At the end of the study, although there was no finding that clearly reflected on the glycemic parameters of T2DM, its beneficial effects on the expression of mucin genes, which are responsible for weight loss and protection of intestinal barrier functions, cannot be denied. Further studies are needed to reveal the importance of these findings. CLINICAL TRIAL REGISTRATION: ID: NCT05066152, October 4, 2021 retrospectively registered in ClinicalTrials.gov PRS web site.

Is there a relationship between ACTN3 R577X gene polymorphism and sarcopenia?

BACKGROUND AND AIMS: The alpha-actinin (ACTN) genes are important structural components of the sarcomere. Sarcopenia is a common geriatric syndrome characterized by morbidity and mortality. Our study aimed to examine the relationship between the ACTN3 R577X gene and sarcopenia in community-dwelling Turkish adults. METHODS: We designed a cross-sectional study among the patients aged ≥ 65 years admitted to the geriatric outpatient clinic. We recorded the general characteristics of the patients. We used the Jamar hand dynamometer to evaluate handgrip strength. Body composition was estimated using bioimpedance analysis. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People2 criteria with population-specific cutoffs. We performed analyses of low muscle mass (LMM) with skeletal muscle mass index adjusted for body mass index [SMMI(BMI)]. We further categorized the SMMI(BMI) cutoffs into tenths. The analyzes were performed according to the 90th percentile SMMI(BMI) cutoffs. Peripheral blood samples were collected to determine the ACTN3 genotypes. RESULTS: 197 participants were included [mean age: 76.3 ± 6.1 years, 151 (76.6%) women]. The proportions of the ACTN3 genotypes were as follows: RX (45.1%) > RR (31%) > XX (23.9%). The significant difference between genotypes was found only for low SMMI(BMI) according to the 90th percentile (p = 0.025). In multivariate analysis, only gender (female) was independently associated with LMM. CONCLUSION: We did not find any association between ACTN3 R577X gene polymorphism and probable sarcopenia, confirmed sarcopenia and LMM. Besides, much more research is needed to reveal how ethnicity affects the muscles of older adults with ACTN3 R577X gene polymorphism.

Cytogenetic and molecular characterization of a patient having infertility and mild intellectual disability with a very rare unstable ring chromosome 13.

INTRODUCTION: Ring chromosomes arise from breakage and fusion at distal regions of short and long arms of the chromosomes. The effect of the ring chromosome on the phenotype may vary widely depending on the amount of the deletion in the chromosomal areas and genes implicated in these regions. CASE PRESENTATION: We present a 35-year-old male patient with infertility and mild intellectual disability (MID) who has de novo ring 13 (r(13)) chromosomes. To determine chromosomal abnormality, we performed karyotype analysis, Y chromosome microdeletion analysis, FISH, and aCGH techniques. CONCLUSION: The patient's karyotype analysis result was mos46,XY,r(13)(p13q34)[75]/45,XY,-13[14]/46,XY,dic (13;13)[8]/47,XY,r(13), + r(13)[2]/46,XY,tetrac r(13;13;13;13)[1]. FISH analysis supported the findings of the cytogenetic analysis. Y microdeletion analysis showed that the AZF region was intact. On aCGH analysis, we detected a 1.5 megabase deletion at the end of chromosome 13, including the CHAMP1 gene. The loss of the CHAMP1 gene, in particular, may explain our patient's MID, and the other deleted genes at 13q34 may explain our patient's infertility.

Skeletal and molecular findings in 51 Cleidocranial dysplasia patients from Turkey.

Loss or decrease of function in runt-related transcription factor 2 encoded by RUNX2 is known to cause a rare autosomal-dominant skeletal disorder, cleidocranial dysplasia (CCD). Clinical spectrum and genetic findings in 51 CCD patients from 30 unrelated families are herein presented. In a majority of the patients, facial abnormalities, such as delayed fontanel closure (89%), parietal and frontal bossing (80%), metopic groove (77%), midface hypoplasia (94%), and abnormal mobility of shoulders (90%), were recorded following clinical examination. In approximately one-half of the subjects, wormian bone (51%), short stature (43%), bell-shaped thorax (42%), wide pubic symphysis (50%), hypoplastic iliac wing (59%), and chef's hat sign (44%) presented in available radiological examinations. Scoliosis was identified in 28% of the patients. Investigation of RUNX2 revealed small sequence alterations in 90% and gross deletions in 10% of the patients; collectively, 23 variants including 11 novel changes (c.29_30insT, c.203delAinsCG, c.423 + 2delT, c.443_454delTACCAGATGGGAinsG, c.505C > T, c.594_595delCTinsG, c.636_637insC, c.685 + 5G > A, c.1088G > T, c.1281delC, Exon 6-9 deletion) presented high allelic heterogeneity. Novel c.29_30insT is unique in affecting the P1-driven long isoform of RUNX2, which is expected to disrupt the N-terminal region of RUNX2; this was shown in two unrelated phenotypically discordant patients. The clinical findings highlighted mild intra-familial genotype-phenotype correlation in our CCD cohort.

REST Final-Exon-Truncating Mutations Cause Hereditary Gingival Fibromatosis.

Hereditary gingival fibromatosis (HGF) is the most common genetic form of gingival fibromatosis that develops as a slowly progressive, benign, localized or generalized enlargement of keratinized gingiva. HGF is a genetically heterogeneous disorder and can be transmitted either as an autosomal-dominant or autosomal-recessive trait or appear sporadically. To date, four loci (2p22.1, 2p23.3-p22.3, 5q13-q22, and 11p15) have been mapped to autosomes and one gene (SOS1) has been associated with the HGF trait observed to segregate in a dominant inheritance pattern. Here we report 11 individuals with HGF from three unrelated families. Whole-exome sequencing (WES) revealed three different truncating mutations including two frameshifts and one nonsense variant in RE1-silencing transcription factor (REST) in the probands from all families and further genetic and genomic analyses confirmed the WES-identified findings. REST is a transcriptional repressor that is expressed throughout the body; it has different roles in different cellular contexts, such as oncogenic and tumor-suppressor functions and hematopoietic and cardiac differentiation. Here we show the consequences of germline final-exon-truncating mutations in REST for organismal development and the association with the HGF phenotype.

WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects.

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.

Mutations in RAD21 disrupt regulation of APOB in patients with chronic intestinal pseudo-obstruction.

BACKGROUND & AIMS: Chronic intestinal pseudo-obstruction (CIPO) is characterized by severe intestinal dysmotility that mimics a mechanical subocclusion with no evidence of gut obstruction. We searched for genetic variants associated with CIPO to increase our understanding of its pathogenesis and to identify potential biomarkers. METHODS: We performed whole-exome sequencing of genomic DNA from patients with familial CIPO syndrome. Blood and lymphoblastoid cells were collected from patients and controls (individuals without CIPO); levels of messenger RNA (mRNA) and proteins were analyzed by quantitative reverse-transcription polymerase chain reaction, immunoblot, and mobility shift assays. Complementary DNAs were transfected into HEK293 cells. Expression of rad21 was suppressed in zebrafish embryos using a splice-blocking morpholino (rad21a). Gut tissues were collected and analyzed. RESULTS: We identified a homozygous mutation (p.622, encodes Ala>Thr) in RAD21 in patients from a consanguineous family with CIPO. Expression of RUNX1, a target of RAD21, was reduced in cells from patients with CIPO compared with controls. In zebrafish, suppression of rad21a reduced expression of runx1; this phenotype was corrected by injection of human RAD21 mRNA, but not with the mRNA from the mutated p.622 allele. rad21a Morpholino zebrafish had delayed intestinal transit and greatly reduced numbers of enteric neurons, similar to patients with CIPO. This defect was greater in zebrafish with suppressed expression of ret and rad21, indicating their interaction in the regulation of gut neurogenesis. The promoter region of APOB bound RAD21 but not RAD21 p.622 Ala>Thr; expression of wild-type RAD21 in HEK293 cells repressed expression of APOB, compared with control vector. The gut-specific isoform of APOB (APOB48) is overexpressed in sera from patients with CIPO who carry the RAD21 mutation. APOB48 also is overexpressed in sporadic CIPO in sera and gut biopsy specimens. CONCLUSIONS: Some patients with CIPO carry mutations in RAD21 that disrupt the ability of its product to regulate genes such as RUNX1 and APOB. Reduced expression of rad21 in zebrafish, and dysregulation of these target genes, disrupts intestinal transit and the development of enteric neurons.

Turmeric Inhibits MDA-MB-231 Cancer Cell Proliferation, Altering miR-638-5p and Its Potential Targets.

Objective: Recent research suggests curcumin extracted from the turmeric plant may inhibit the proliferation of cancer cells by controlling the expression of microRNAs (miRNAs). The effect of phenolic curcumin on miR-638-5p and potential target gene expressions in the triple negative breast cancer (TNBC) cell line MDA-MB-231 was investigated in this study. Materials and Methods: GSE154255 and GSE40525 datasets were downloaded and analyzed using GEO2R to identify dysregulated miRNAs in TNBC. To find differently expressed genes in breast cancer (BRCA), The Cancer Genome Atlas Program data was examined. Utilizing in silico tools, KEGG, GO, and other enrichment analyses were performed. The databases miRNet, miRTarBase v8.0, and TarBase v.8 were used for miRNA and mRNA matching. Real-time quantitative reverse transcription polymerase chain reaction was used to examine the levels of miRNA and its targets in miRNA mimic transfected/curcumin-treated MDA-MB-231 cultures and controls. The cell viability detection kit-8 method was used to assess cell viability, and the scratch assay was used to conduct migration assessment. Results: Bioinformatics analysis showed that miR-638-5p was significantly reduced in TNBC patients. Experimental results showed that miR-638-5p was upregulated in MDA-MB-231 treated with curcumin, while the potential target genes of miR-638-5p, CFL1, SIX4, MAZ, and CDH1 were downregulated. Mimic miR-638-5p transfection inhibited MDA-MB-231 cell proliferation and reduced migration and expression of CFL1, SIX4, and MAZ genes was decreased in mimic miR-638-5p transfected cells. Conclusion: These findings suggest that curcumin exerts its anticancer effects on MDA-MB-231 cells by modulating the expression of miR-638-5p and its possible target genes.

Overexpression of CDC25A, AURKB, and TOP2A Genes Could Be an Important Clue for Luminal A Breast Cancer.

Objective: Breast cancer (BC) is highly heterogeneous and one of the most common cancers. Luminal A (LUM A) is a subtype of BC with a better prognosis than other BC subtypes. The molecular mechanisms underlying the initiation and progression of the LUM A subtype are still unclear. Big data generated from microarray and sequencing systems can be re-analyzed, especially with the help of various in silico tools developed in recent years, and made applicable for in vitro and in vivo research. This work aimed to identify genes that may play a role in the progression of LUM A subtype of BC using both computational and laboratory-based methods. Materials and Methods: Overlapping genes associated with BC were identified from the The Cancer Genome Atlas database, GSE233242, GSE100925 geodata sets, and the geneshot tool. The network functional analysis between overlapping genes was determined with STRING 12.0. Expression levels of overlapping genes in BC were investigated with the TNMplot (https://tnmplot.com/analysis/) in silico tool. The effect of overlapping genes on the overall survival of LUM A cancer patients was defined using the Kaplan-Meier plotter tool. Expressions of genes identified using bioinformatics data were investigated via quantitative real-time -polymerase chain reaction (qRT-PCR) in LUM A tumor and adjacent tissue samples. The data were evaluated using the t-test. Both the sensitivity and specificity of selected genes have been determined using the receiver operating characteristic curve. Results: In silico investigation showed that eleven genes were possibly associated with BC. Among them CDC25A, AURKB, and TOP2A were considerably increased in LUM A samples according to qRT-PCR results. An overall survival analysis also showed that overexpression of these three genes could reduce the overall survival of LUM A patients. Conclusion: The genes CDC25A, AURKB, and TOP2A may play crucial functions in LUM A pathogenesis. Therapeutic strategies that diminish the expression of these connected genes may enhance the prognosis of LUM A patients.

Genotoxicity of fixation devices analyzed by the frequencies of sister chromatid exchange.

BACKGROUND: Metal alloys utilized in the management of jaw fractures may exert genotoxic effects. Our purpose was to compare the genotoxicity of intermaxillary fixation devices containing nickel and chromium to that of titanium miniplates utilized in treatment of jaw fractures through the analysis of sister chromatid exchange. METHODS: In this prospective study, in a total of 28 non-smoker patients (10 females, 18 males; mean age 33.43±10.76; range 15 to 60 years) with jaw fractures, 14 were treated with intermaxillary fixation by administration of nickel-chromium wire and arch bar and 14 with titanium miniplates to investigate the genotoxicity of different metal alloys. The outcome variable was the frequency of sister chromatide exchange in peripheral lymphoctyes, determined through the analysis of venous blood samples obtained preoperatively and 4 to 6 weeks postoperatively. RESULTS: The frequency of the average sister chromatid exchange was found to be significantly higher in patients treated with the nickel-chromium intermaxillary fixation devices than those treated by titanium miniplates (1.29±0.29 vs. 0.46±0.39, p<0.001). CONCLUSION: Although titanium miniplate osteosynthesis is an invasive technique in comparison with the nickel-chromium-containing intermaxillary fixation devices, titanium seems to exert less genotoxic effect than the nickel-chromium alloy. However, this finding should be supported in clinical studies with a larger sampling size.

Prostaglandin transporter mutations cause pachydermoperiostosis with myelofibrosis.

Pachydermoperiostosis, or primary hypertrophic osteoarthropathy (PHO), is an inherited multisystem disorder, whose features closely mimic the reactive osteoarthropathy that commonly accompanies neoplastic and inflammatory pathologies. We previously described deficiency of the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (HPGD) as a cause of this condition, implicating elevated circulating prostaglandin E(2) (PGE(2)) as causative of PHO, and perhaps also as the principal mediator of secondary HO. However, PHO is genetically heterogeneous. Here, we use whole-exome sequencing to identify recessive mutations of the prostaglandin transporter SLCO2A1, in individuals lacking HPGD mutations. We performed exome sequencing of four probands with severe PHO, followed by conventional mutation analysis of SLCO2A1 in nine others. Biallelic SLCO2A1 mutations were identified in 12 of the 13 families. Affected individuals had elevated urinary PGE(2), but unlike HPGD-deficient patients, also excreted considerable quantities of the PGE(2) metabolite, PGE-M. Clinical differences between the two groups were also identified, notably that SLCO2A1-deficient individuals have a high frequency of severe anemia due to myelofibrosis. These findings reinforce the key role of systemic or local prostaglandin excess as the stimulus to HO. They also suggest that the induction or maintenance of hematopoietic stem cells by prostaglandin may depend upon transporter activity.

OCT-1 Expression in Patients with Chronic Myeloid Leukemia: A Comparative Analysis with Respect to Response to Imatinib Treatment.

The introduction of tyrosine kinase inhibitors (TKI) has resulted in a significant improvement in the treatment of CML patients. However, some CML patients are resistant to imatinib therapy, the initial TKI therapy in the CML. Therefore, it is important to find prognostic markers for resistance. The OCT-1 gene involved in imatinib uptake is also suspected to cause imatinib resistance. The aim of this study was to investigate the role of OCT-1 in imatinib resistance by comparing OCT-1 expression levels in imatinib resistant and imatinib sensitive patients with chronic myeloid leukemia (CML). This study was conducted on 101 patients with CML [imatinib sensitive (n = 51) and imatinib resistant (n = 50)] who were treated with imatinib. Gene expression analysis was done using QRT-PCR. The relative expression levels of OCT-1 were calculated using 2(-ΔΔCT) method. OCT1 mRNA expression levels were 0.149 (0.011-2.532) and 0.119 (0.008-2.868) in imatinib-sensitive group and imatinib-resistant group, respectively. OCT-1 expression levels were not significantly different in the imatinib-sensitive group when compared to imatinib resistant group (p > 0.05). OCT-1 expression was also similar in BCR-ABL1 kinase domain mutation positive and negative cases (p > 0.05). The imatinib-resistant group had a higher rate of hydroxyurea or interferon-alpha treatment prior to imatinib therapy and a lower rate for first-line imatinib as the only treatment than the imatinib-sensitive group (p = 0.002 and p = 0.002, respectively). According to the results of our study, OCT-1 does not have a biomarker feature in the evaluation of imatinib response. In addition, the study should be performed in larger patient groups.

The effect of Anzer honey on X-ray induced genotoxicity in human lymphocytes: An in vitro study.

Anzer honey is well known in Turkey and used for its medicinal properties, especially for pharyngitis, tonsillitis, ulcers and cancer. In this study, we investigated whether Anzer honey, which is shown to have antioxidant, anti-tumoral, and anti-inflammatory properties, has a protective effect against X-ray induced genotoxic damage by cytogenetic methods. Peripheral blood lymphocytes isolated from 20 healthy volunteers were divided into two groups and cultivated by conventional methods. Study group lymphocytes were treated with 10% diluted honey while those in the control group were not. Both groups were exposed to a high dose (2 Gy) X-ray at the 48th hour of culture. Conventional cytogenetic staining and Giemsa banding methods were applied to evaluate chromosomal breakage and ring formation. Micronucleus frequencies were determined by the cytokinesis-block micronucleus (CBMN) assay. Paired sample t test was used to compare groups. Anzer honey, which was analyzed melissopalynologically, was used. Micronucleus frequency was significantly decreased in the study group (CI = 348.75 ± 31, median 326, min. 98, max. 704) compared to the control group (CI = 489.10 ± 27, median 500, min. 216, max. 645) (p = .001). Chromosomal breakage was also significantly decreased in the study group (CI = 118.70 ± 16, median 109, min. 12, max. 316) compared to the control group (CI = 233.60 ± 25, median 225, min. 65, max. 492) (p < .0001). This is the first study indicating that genotoxic damage in the peripheral blood lymphocytes of healthy volunteers induced by X-radiation may be prevented or alleviated by adding Anzer honey in vitro. These results encourage further research about the protective effects of honey. RESEARCH HIGHLIGHTS: Anzer honey has a genoprotective effect against radiation-induced genotoxicity, probably by preventing oxidation damage.

Clinical Characteristics and Mutation Spectrum of Neurofibromatosis Type 1 in 27 Turkish Families.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder that results in a predisposition to the growth of multiple tumors in the central nervous system, the peripheral nervous system, and the skin. The clinical manifestations of neurofibromatosis are associated with loss of neurofibromin expression which causes the upregulation of the RAS pathway. Although neurofibromatosis type 1 can be diagnosed based on the National Institutes of Health criteria, sometimes the diagnosis is difficult, in cases where the characteristic features do not develop. Moreover, other RAS-related disorders may present with significantly overlapping clinical features. AIMS: To determine the clinical and molecular genetic characteristics of Turkish patients with neurofibromatosis type 1. STUDY DESIGN: Cross-sectional study. METHODS: For the genetic analysis of 27 Turkish families clinically diagnosed with NF1 between 1990 and 2019, we used a multi-step process consisting of next-generation sequencing, multiplex ligation-dependent probe amplification, and array-comparative genomic hybridization. RESULTS: In this study, we identified 11 novel and 11 previously reported single-nucleotide variants in 22 families. Whole gene deletions were detected by multiplex ligation-dependent probe amplification analysis in 3 families. Of those, array comparative genomic hybridization analysis defined a 17q11.2 deletion in 4 patients from 2 families and 1.2-Mb involving 1 unrelated patient. All patients with a deletion had facial dysmorphism, suggesting a peculiar phenotype in this group. We could not find any pathogenic variant in the 2 families that met the National Institutes of Health criteria. CONCLUSION: The novel pathogenic variants identified in this study broaden the spectrum of pathogenic variants in NF1 and provide better clinical characterization of NF1. RNA-seq experiments are recommended in patients who meet the National Institutes of Health diagnostic criteria for NF but have not identified any variants in nextgeneration sequencing, multiplex ligation-dependent probe amplification, or array-comparative genomic hybridization analysis.

Overview of clinical and genetic features of CML patients with variant Philadelphia translocations involving chromosome 7: A case series.

Variant Philadelphia (Ph) translocations involving chromosome 7 are rarely seen in Chronic Myeloid Leukemia (CML) patients. It is aimed to contribute new cases to the literature by reviewing the cases in our archive and shed light into the understanding of the role of chromosome 7 in CML. This study was carried out in 237 newly diagnosed CML patients with variant Ph translocations. Among the patients, those with variant Ph translocation involving chromosome 7 were evaluated in terms of clinical and genetic characteristics. Chromosome analysis was performed on 24 and 48 h of bone marrow cultures. FISH analysis was performed with BCR-ABL1 dual color dual fusion translocation probes. BCR-ABL1 transcript levels were analysed by QRT-PCR and results were reported as BCR-ABL1/ABL1 (BCR-ABL1 (IS) %) according to international scale. Four of the patients had variant Ph translocations including chromosome 7. The karyotypes were 46,XX,t(7;9;22)(p13;q34;q11); 46,XX,t(7;9;22)(p21;q34;q11); 46,XX,t(7;9;22)(q22;q34;q11) and 46,XY,t(7;9;22)(q22;q34;q11). The breakpoints demonstrated by cytogenetic analysis were confirmed by FISH analysis. Monitoring by QRT-PCR showed that patients with variant Ph translocation including 7p13 and 7p21 had a dramatic decrease in BCR-ABL1 levels resulting in complete hematological, complete cytogenetic and deep molecular responses. Despite achieving complete hematological, complete cytogenetic response in two patients with variant Philadelphia translocation, including 7q22, no major molecular response was achieved and both patients are still in the warning category. Response to tyrosine kinase inhibitör therapy may be associated with both the variant translocation mechanism and new gene interactions that occur due to the breakpoints of additional chromosomes involved in translocation.

Indication for Y Chromosome Microdeletion Analysis in Infertile Men: Is a New Sperm Concentration Threshold Needed?

OBJECTIVE: To describe the prevalence of Y-chromosome deletions in patients with a sperm concentration of less than 5 million/mL. To also determine a new sperm threshold for Y-chromosome analysis in men with infertility. METHODS: A total of 3023 patients who had a semen concentration of less than 5 million/mL included in this retrospective study. All of these patients had a genetic evaluation, hormonal evaluation, and 2 abnormal semen analyses. RESULTS: Y-chromosome deletions were present in 116 (3.8 %) patients with sperm concentration <5 million/mL. The frequency of a Y-chromosome deletions was 6.8%, 1.0%, 0.15% in azoospermic men, in men with sperm concentrations of 0-1 million /mL, in men with sperm concentrations of 1-5 million/mL. Patients were divided into 2 groups regarding the determined new sperm threshold. The sensitivity and specificity of the Y-chromosome deletions test were 92.2.7% and 49.3 %, 99.1%, and 22.1% in patients with azoospermia and sperm concentrations <1 million/mL, respectively. If the sperm concentration thresholds of azoospermia or <1 million/mL, are applied, the number of tests decreased to 50.5% (1442 tests) and 23.1% (643 tests), respectively. Approximately $108,150 and $48,225 would be saved if the sperm thresholds were azoospermia and <1 million/mL, respectively CONCLUSION: The current threshold of sperm concentration for Y-chromosome deletions is controversial. The new proposed sperm threshold for genetic testing of 1 million/mL would increase sensitivity and more cost-effective compared to the current threshold.

Left ventricular thickness is increased in nonhypertensive Turner's syndrome.

BACKGROUND: Turner's syndrome (TS), the most frequent congenital anomaly in newborn girls, is associated with various cardiovascular abnormalities, predominantly bicuspid aortic valves and aortic coarctation. The causes of the left ventricular hypertrophy (LVH) and ECG findings associated with TS are unknown. We used echocardiography to assess cardiac structure and function in normotensive patients with TS. METHOD: Thirty-one patients with TS and 30 healthy women were enrolled in this comparative study. Twelve-lead ECG, 24-hour-ambulatory ECG recording, and echocardiography were performed. RESULTS: With 24-hour-ambulatory ECG recording, the mean heart rate (HR) of TS women was higher than non-TS women. With echocardiographic examination, the interventricular septum diastolic thickness, left ventricle posterior wall diastolic thickness (LVPW), the LV mass index (LVMI), and left atrial diameter index (LADi) were significantly higher in TS women compared with controls. Mitral flow A velocity was significantly higher and the ratio of early to late diastolic filling was significantly lower in TS patients. CONCLUSION: HR, LV wall thicknesses, LVMI and the LADi are significantly increased in normohypertensive TS women. There is also subclinical diastolic dysfunction in these patients.

Case Report: a novel chromosomal insertion, 46, XY, inv ins(18;2)(q11.2;q13q22), in a patient with infertility and mild intellectual disability.

Infertility is an important health problem affecting 15% of couples worldwide. Intellectual disability (ID) is characterized with significant impairment of intellectual function, adaptive daily life skills and social skills. Insertion is a rare chromosomal rearrangement causing infertility and ID. Here, we report a 39-year-old man presenting with primary infertility and mild ID. The patient's spermiogram was consistent with azoospermia. Conventional cytogenetic analysis showed a novel inversion/insertion type of chromosomal aberration involving chromosomes 18 and 2: 46, XY, inv ins(18;2)(q11.2;q13q22). We carried out the array comparative genomic hybridization analysis to confirm the cytogenetic findings. Y micro-deletion analysis demonstrated that the AZF region as intact. We suggest that the novel insertion found in this case [46, XY, inv ins(18;2)(q11.2;q13q22)] may have caused infertility and mild ID in our patient. To the best of our knowledge, this chromosomal insertion has not previously been reported.

Investigation of Gene Expressions of Myeloma Cells in the Bone Marrow of Multiple Myeloma Patients by Transcriptome Analysis

Background: Multiple myeloma is a plasma cell dyscrasia characterized by transformation of B cells into malignant cells. Although there are data regarding the molecular pathology of multiple myeloma, the molecular mechanisms of the disease have not been fully elucidated. Aims: To investigate the gene expression profiles in bone marrow myeloma cells via RNA-sequencing technology. Study Design: Cell study. Methods: Myeloma cells from four patients with untreated multiple myeloma and B cells from the bone marrow of four healthy donors were sorted using a FACSAria II flow cytometer. The patient pool of myeloma cells and the control pool of B cells were the two comparative groups. A transcriptome analysis was performed and the results were analyzed using bioinformatics tools. Results: In total, 18.806 transcripts (94.4%) were detected in the pooled multiple myeloma patient cells. A total of 992 regions were detected as new exon candidates or alternative splicing regions. In addition, 490 mutations (deletions or insertions), 1.397 single nucleotide variations, 415 fusion transcripts, 132 frameshift mutations, and 983 fusions, which were reported before in the National Center for Biotechnology Information, were detected with unknown functions in patients. A total of 35.268 transcripts were obtained (71%) (25.355 transcripts were defined previously) in the control pool. In this preliminary study, the first 50 genes were analyzed with the MSigDB, Enrichr, and Panther gene set enrichment analysis programs. The molecular functions, cellular components, pathways, and biological processes of the genes were obtained and statistical values were determined using bioinformatics tools and are presented as a supplemental file. Conclusion: EEF1G, ITM2C, FTL, CLPTM1L, and CYBA are identified as possible candidate genes associated with myelomagenesis.

DNA damage effects of inhalation anesthetics in human bronchoalveolar cells.

BACKGROUND: The main objective was to evaluate and compare the local genotoxicity of sevoflurane and desflurane in bronchoalveolar cells, while the secondary outcome was to detect systemic oxidative DNA damage. To our knowledge, our study is the first one to evaluate the local effects of inhalation anesthetics in human bronchoalveolar cells in patients. METHODS: American Society of Anesthesiologists group I-II patients scheduled for lumbar discectomy surgery were enrolled in this randomized prospective study. Patients were randomized to sevoflurane or desflurane for anesthesia maintenance. Bronchoalveolar lavage samples and peripheral blood samples were taken at 2-time points: the first point (baseline, T1); and the second point (postexposure, T2). Final number of 48 samples were the sevoflurane (n = 22) and desflurane (n = 26) groups. Comet assay was applied to examine genotoxic properties. Oxidative DNA damage in plasma was measured with 8-hydroxy-2'-deoxyguanosine (8-OHdG). RESULTS: T2 values were higher than baseline values in both the desflurane group (tail-length: 66 ±â€Š24, %DNA in tail: 72 ±â€Š60, tail moment: 47.52 ±â€Š14.4; P = .001, P = .005, P = .001, respectively) and the sevoflurane group (tail-length: 58 ±â€Š33, %DNA in tail: 88 ±â€Š80, tail moment: 51.04 ±â€Š26.4; P = .001, P = .012, P = .001, respectively). T2 plasma 8-OHdG levels were also higher than baseline levels in the desflurane group (3.91 ±â€Š0.19 ng/ml vs 1.32 ±â€Š0.20 ng/ml, P = .001) and sevoflurane group (3.98 ±â€Š0.18 ng/ml vs 1.31 ±â€Š0.11 ng/ml, P = .001). There were no differences between the 2 groups in comet parameters and 8-OHdG levels. CONCLUSION: Our results indicate that both inhalation agents cause DNA damage in the bronchoalveolar cells. Also, we detected increases in plasma 8-OHdG concentrations. Local genotoxicity and systemic oxidized DNA damage were similar in both groups.