Fecundity in an infertile man with r(15) - a challenge to the current paradigm.

Ring chromosome 15 [r(15)] is a rare condition with a mild-to-severe growth failure, mental disabilities, café-au-lait spots, specific facial features, fertility difficulties and other minor dysmorphic stigmata. Of almost 50 affected individuals reported in the literature, none were assessed for the precise breakpoint positioning, which creates uncertainty in defining a specific phenotype for the deleted segment. This study reports for the first time the vertical transmission of r(15) in three consecutive generations of a family, including a subfertile man, his mother and his newborn infant. Array comparative genomic hybridization results revealed a 563 kb deletion of 15q26.3, overlapping the OMIM genes SNRP1, PCSK6 and TM2D3. The hemizygosity was confirmed with real-time quantitative PCR. Regarding haploinsufficiency in 15q26.3, based on phenotypic characteristics of the carriers, the only rational conclusion is that SNRPA1, PCSK6 and TM2D3 are not gene-dosage sensitive and are probably inherited in an autosomal-recessive manner. Given growth deficiency in r(15) carriers, this shows that the growth retardation cannot be attributed entirely to IGF1R. The predominance of female patients with r(15) is the next as yet unanswered question; incomplete penetrance and/or variable expression of gene(s) in different genders may be involved, but further evidence is needed to support this idea.

The impact of inspiratory pressure level on prevention of ventilator-associated pneumonia: A double-blind, randomized clinical trial.

BACKGROUND: Atelectasis and pneumonia are highly prevalent in patients under mechanical ventilation. Studies indicate that using ventilation with an open lung concept improves recovery, decreases ventilator-related pneumonia, decreases mortality and leads to faster weaning from the ventilator. Therefore, this study investigated the effect of higher airway pressure on ventilator-associated pneumonia. METHODS: This randomized clinical trial was conducted on 120 patients under mechanical ventilation. The patients were divided into two groups based on ventilator pressure: the control group (pressure level 20) and the intervention group (pressure level 30). Demographic data, disease severity, the incidence of ventilator-associated pneumonia, organ damage, days connected to the ventilator, length of hospitalization in ICU, and mortality were compared between the two groups. RESULTS: There was no significant difference in demographic data and disease severity between the two groups. The average Clinical Pulmonary Infection Score in the intervention group was significantly lower than the control group (P = 0.02). The intervention group's average Sequential Organ Failure Assessment score was significantly lower than the control group (p = 0.016). CONCLUSIONS: High-pressure levels can decrease ventilator-associated pneumonia and organ failure. It is recommended that the study be repeated with a larger, more diverse population.

Gene Alterations and Expression Spectrum of NANOS3 in Nonobstructive Azoospermia.

Nanos3, a zinc finger RNA-binding protein, suppresses the apoptosis in primordial germ cells (PGCs) during migration to gonads and maintains the PGC population. The genetic variations and expression of NANOS3 in patients with non-obstructive azoospermia (NOA) were evaluated in this study. The study included 100 idiopathic infertile men with NOA and 100 fertile men as the as the case and control groups, respectively. NANOS3 gene variations were analyzed using the standard polymerase chain reaction (PCR) and sequencing. For mRNA and protein expression analysis, testicular biopsy specimens from 27 patients including 9 obstructive azoospermia (OA), 9 maturation arrest (MA), and 9 Sertoli cell-only syndromes (SCOS) were collected and evaluated using the real-time PCR technique and immunohistochemistry. Although the evaluation of the 5`UTR regulatory region has shown the significant difference in the numbers of TG repeats in rs11182456 between groups, the odd ratio was not strong enough to consider that as a certain risk factor lead to azoospermia and infertility. Meanwhile, NANOS3 expression at mRNA level had a significant difference among OA, SCOS, and MA groups.

Supplementation of extender with coenzyme Q10 improves the function and fertility potential of rooster spermatozoa after cryopreservation.

The effects of coenzyme Q10 (CoQ10) has not yet been assessed for cryopreservation of rooster semen. The aim of this study was to evaluate the effect of different concentrations of CoQ10 in Lake extender for cryopreservation of rooster semen. The viability and apoptosis status, DNA fragmentation, abnormal morphology, motion parameters, membrane functionality, mitochondrial activity, acrosome integrity, lipid peroxidation, and fertility potential were evaluated after the freeze-thaw process. Semen samples were collected from ten roosters, twice a week, and then diluted in extender contained different concentrations of CoQ10 as follows: Lake without CoQ10 (control, Q 0), Lake containing 1 µM (Q 1), 2 µM (Q 2), 5 µM (Q 5), and 10 µM (Q 10) CoQ10. Supplementation of Lake with 1 and 2 µM CoQ10 resulted in greater sperm viability, total motility, progressive motility, membrane functionality, mitochondrial activity, acrosome integrity, and fertility rate. Furthermore, the extent of lipid peroxidation in thawed spermatozoa treated with 1 and 2 µM CoQ10 was less than with the other groups. Different concentrations of CoQ10 had no effect on DNA fragmentation and sperm morphology. Results of the present study indicate that supplementation of Lake extender with 1 and 2 µM CoQ10 enhances the quality of rooster sperm after the freeze-thaw process.

De novo complex chromosomal rearrangement of 46, XY, t (3; 16; 8) (p26; q13; q21.2) in a non-obstructive azoospermic male.

Complex Chromosomal Rearrangements (CCRs) are rare structural abnormalities that are usually associated with infertility or subfertility in male carriers. We described clinical and chromosomal features of a non-obstructive azoospermic male that has been referred for infertility. Cytogenetic analysis showed three chromosomes, i.e. 3, 8 and 16, which have been involved and caused spermatogenesis failure.

Impact of pericentric inversion of Chromosome 9 [inv (9) (p11q12)] on infertility.

BACKGROUND: One of the frequent occurrences in chromosome rearrangements is pericentric inversion of the Chromosome 9; inv (9) (p11q12), which is consider to be the variant of normal karyotype. Although it seems not to correlate with abnormal phenotypes, there have been many controversial reports indicating that it may lead to abnormal clinical conditions such as infertility. The incidence is found to be about 1.98% in the general population. MATERIALS AND METHODS: We investigated the karyotypes of 300 infertile couples (600 individuals) being referred to our infertility clinic using standard GTG banding for karyotype preparation. RESULTS: The chromosomal analysis revealed a total of 15 (2.5%) inversions, among these, 14 male patients were inversion 9 carriers (4.69%) while one female patient was affected (0.33%). The incidence of inversion 9 in male patients is significantly higher than that of normal population and even than that of female patients (P< 0.05). CONCLUSIONS: This result suggests that inversion 9 may often cause infertility in men due to spermatogenic disturbances, which are arisen by the loops or acentric fragments formed in meiosis.

A Rare Case of Klinefelter Syndrome Patient with Quintuple Mosaic Karyotype, Diagnosed by GTG-Banding and FISH.

Klinefelter syndrome (KS) is the most common sex chromosomal disorder in men. Most of these patients show the 47,XXY karyotype, whereas approximately 15% of them are mosaics with variable phenotype. A 39-year-old male investigated for primary infertility, was clinically normal with small firm testes and elevated levels of FSH, LH and low level of testosterone. Total azoospermia was confirmed on semen analysis. Testicular histopathology revealed no spermatogenesis and absence of germ cells. Karyotype from whole blood culture showed cells with 47,XXY/46,XX/ 45,X/48,XXXY/ 46,XY mosaicism. The predominant cell line was 47,XXY (83.67%). This was confirmed by fluorescence in situ hybridization (FISH). Also the presence of a small population of cells with the 48,XXXY and 45,X karyotypes was detected by FISH. This case illustrates the utility of FISH as an adjunct to conventional cytogenetics in assess the chromosome copy number in each cell line of a mosaic.

Impact of pericentric inversion of Chromosome 9 [inv (9) (p11q12)] on infertility.

BACKGROUND: One of the frequent occurrences in chromosome rearrangements is pericentric inversion of the Chromosome 9; inv (9) (p11q12), which is consider to be the variant of normal karyotype. Although it seems not to correlate with abnormal phenotypes, there have been many controversial reports indicating that it may lead to abnormal clinical conditions such as infertility. The incidence is found to be about 1.98% in the general population. MATERIALS AND METHODS: We investigated the karyotypes of 300 infertile couples (600 individuals) being referred to our infertility clinic using standard GTG banding for karyotype preparation. RESULTS: The chromosomal analysis revealed a total of 15 (2.5%) inversions, among these, 14 male patients were inversion 9 carriers (4.69%) while one female patient was affected (0.33%). The incidence of inversion 9 in male patients is significantly higher than that of normal population and even than that of female patients (P< 0.05). CONCLUSIONS: This result suggests that inversion 9 may often cause infertility in men due to spermatogenic disturbances, which are arisen by the loops or acentric fragments formed in meiosis.