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Background Recent guidelines support more aggressive surgery for aneurysms of the ascending aorta and root in patients with bicuspid aortic valve. However, the fate of the arch after surgery of the root and ascending aorta is unknown. We set out to assess outcomes following root and ascending aortic surgery and subsequent growth of the arch. Methods Between 2005 and 2016, 536 consecutive patients underwent surgery for aneurysm of the root and ascending aorta; 168 had bicuspid aortic valve. Patients with dissection were excluded. Arch diameter was measured before and after surgery, at 6 months and then annually. Results Of 168 patients, 127 (75.6%) had aortic root replacement and 41 (24.4%) had ascending replacement. Mean age was 57 ± 12.8 years, 82.7% were men, and 5 operations were performed during pregnancy. There was 1 (0.6%) hospital death. One (0.6%) patient had a stroke and 1 (0.6%) had resternotomy for bleeding. Median intensive care unit and hospital stays were 1 and 6 days, respectively. Follow-up was complete for 94% at a median of 5.9 years (range, 1 to 139 months). Aortic arch diameter was 2.9 cm preoperatively and 3.0 cm at follow-up. There was 97% freedom from reoperation and none of the patients required surgery on the arch. Conclusions Prophylactic arch replacement during aortic root and ascending aortic surgery in patients with bicuspid aortic valve is not supported. Our data do not support long-term surveillance of the rest of the aorta in this population. [ABSTRACT FROM AUTHOR]

Abstract: Infertile men have poorer sperm DNA integrity than do fertile men, and this damage may contribute to reducing male reproductive potential. However, the etiology of this damage has not been fully characterized. We sought to examine the relationship, if any, between anti-sperm antibodies and sperm DNA damage in a consecutive series of non-azoospermic, infertile men in order to determine whether anti-sperm antibodies (ASAs) may contribute to sperm DNA damage. We conducted a prospective study on consecutive semen samples obtained from men (n =75) presenting for infertility evaluation. Sperm concentration, motility, strict morphology, ASA levels (by direct mixed agglutination reaction, expressed as the percentage of spermatozoa with IgG or IgA antibodies) and sperm DNA damage (by sperm chromatin structure assay) were evaluated. Mean (±SD) sperm concentration and progressive motility were significantly lower in ASA-positive (>40% of sperm coated with ASAs) compared to ASA-negative samples (23.4±13.1×106/mL and 27±15% vs. 74.6±61.2×106/mL and 46±18%, respectively, P <0.05). Sperm progressive motility was inversely correlated with the percentage of IgG-bound (r =−0.33) and IgA-bound spermatozoa (r =−0.25). In contrast, sperm %DNA fragmentation index and percent normal forms were not significantly different in ASA-positive compared to ASA-negative samples (17.5±17.9% and 7.5±3.0% vs. 17.4±13.5% and 6.5±2.6%, respectively). The data indicate that ASAs are not associated with sperm DNA damage and suggest that ASAs are unlikely to have a significant direct or indirect effect on sperm DNA integrity. [Copyright &y& Elsevier]

Objective: To examine the relationship between sperm strict morphology and sperm chromatin integrity. Design: Prospective study. Setting: Infertility clinic. Patient(s): Eighty-seven consecutive semen samples from non-azoospermic men presenting for infertility evaluation and 6 samples from fertile donors. Intervention(s): Assessment of standard semen parameters and sperm chromatin structure assay (SCSA) parameters (%DFI [DNA fragmentation index] and %HDS [high DNA stainability]). Evaluation of %HDS and %DFI after treatment with dithiothreitol (a thiol-reducing agent used to decondense sperm nuclei) was also undertaken. Main Outcome Measure(s): Relationship between sperm strict morphology defects and SCSA parameters (%DFI and %HDS). Result(s): We observed significant relationships between the percentage of normal sperm forms and both %HDS (r = −0.40) and sperm motility (r = 0.32). We also found significant relationships between sperm head defects and both %HDS (r = 0.40) and sperm concentration (r = −0.39). Sperm tail, midpiece, and neck defects were not significantly related to the SCSA parameters. Treatment of spermatozoa with dithiothreitol (to induce decondensation) resulted in a substantial increase in %HDS but no measurable change in %DFI. Conclusion(s): The observed relationship between sperm head defects and %HDS suggests that sperm head abnormalities may, in part, be due to incomplete sperm chromatin condensation. [Copyright &y& Elsevier]

The use of modified natural-cycle in vitro fertilization (IVF) is a valuable alternative to controlled ovarian hyperstimulation in young poor responders and should be considered in patients who require IVF and demonstrate endocrinologic evidence of ovarian aging and in those who have had one or two canceled controlled ovarian hyperstimulation cycles. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate and compare sperm retrieval outcomes by testicular sperm aspiration (TESA) and micro-dissection testicular sperm extraction (micro-TESE) in non-azoospermic men.Methods: We conducted a retrospective study of 145 consecutive testicular sperm retrievals in men with cryptozoospermia (n = 56) or severe oligozoospermia (n = 84). The decision to perform a TESA or a micro-TESE was made after thorough discussion of the pros and cons of these procedures with the couple. Final assessment of sperm recovery, on the day of ICSI, was reported either as successful (available sperm for ICSI) or unsuccessful (no sperm for ICSI).Results: Mean sperm concentration, sperm motility, testicular volume and serum FSH level of men undergoing TESA were not significantly different from those of men undergoing micro-TESE. In men with severe oligozoospermia (<5 million/ml), sperm recovery was successful in 95% (18/19) of those who underwent micro-TESE and in 92% (60/65) of those who underwent TESA (P > 0.05). In men with cryptozoospermia, sperm recovery was successful in 88% (42/48) of men who underwent micro-TESE and 25% (2/8) of men who underwent TESA (P < .001).Conclusions: These data indicate that in men with severe oligozoospermia, TESA and micro-TESE are equally successful sperm retrieval techniques. However, in men with cryptozoospermia, sperm retrieval rates are significantly higher with micro-TESE than TESA. [ABSTRACT FROM AUTHOR]

Do live birth rates (LBR) following modified natural IVF (mnIVF) differ according to serum anti-Müllerian hormone (AMH) concentration? Retrospective cohort study including 638 women aged ≤39 years starting their first mnIVF cycle at a university-affiliated private IVF centre. Patients were divided into three groups, by concentration of AMH: ≤0.5 ng/ml (25th percentile), 0.51–2.03 ng/ml (25–75th percentile, reference) and 2.04–6.56 ng/ml (75th percentile). Analyses were stratified by AMH percentile and the age of patients (<35, 35–39 years). Logistic regression assessed the impact of age and AMH percentile on outcomes. LBR was the primary outcome measure. LBR per started cycle were comparable across AMH percentiles (11.6%, 12.4% and 17.0% for the 25th, 25–75th and 75th percentile, respectively). No statistically significant difference was found between the three AMH groups with respect to cancellation, successful egg retrieval, embryo transfer, or biochemical and clinical pregnancy rates. Logistic regression analysis did not identify AMH percentile as a significant predictor of live birth. Compared with the reference group, the odds ratios (OR [95% confidence interval, CI]) for live birth in the <25th and >75th AMH percentile groups were 0.97 (0.54–1.76) and 1.41 (0.82–2.41), respectively. The results were the same regardless of age group (<35 years, 35–39 years). Serum AMH cannot be used to predict mnIVF outcomes. Patients in lower/upper AMH percentiles showed pregnancy and LBR comparable to patients with normal AMH. [ABSTRACT FROM AUTHOR]

Eukaryotic Initiation Factor 4G forms the core of the translation initiation complex. Bellsolell et al. report the structure of its C-terminal region as two HEAT domains that define a new class and map binding sites for its regulatory factors (). [Copyright &y& Elsevier]

Monozygotic multiple pregnancies are three times more common after assisted reproduction (with or without IVF) than after spontaneous conception (1.2% versus 0.4%). These pregnancies are associated with multiple maternal and fetal risks. This article is a description of nine cases of monozygotic pregnancies following IVF at the OVO Clinic (Montreal) between January 2007 and August 2011 and a scientific review of the literature on monozygotic multiple pregnancies after assisted reproductive treatment found in the MEDLINE and Cochrane Databases. In this retrospective series, 3522 embryos were transferred and 1033 pregnancies were obtained, of which there were nine monozygotics (0.87%). The exact mechanism behind this increased frequency remains uncertain. Possible explanations associated with fertility treatments include alterations of the zona pellucida, transfers at the blastocyst stage, prolonged culture, preimplantation genetic diagnosis, ovarian stimulation and maternal age. Assisted reproduction treatment appears to increase monozygotic pregnancies; however, the rate is still low and therefore it is difficult to exactly conclude the real mechanism. [ABSTRACT FROM AUTHOR]

• This study is the first to use follitropin delta as a stimulatory medication in intrauterine insemination. • It provides validation of an original personalized intrauterine insemination dosing regimen based on anti-Müllerian hormone values and weight. • A total of 258 cycles led to 43 clinical pregnancies (16.7%), with six multiple pregnancies. • Only four live twin births were observed, representing 1.6% of the total cycles. What is the efficacy and safety of individualized follitropin delta dosing for ovarian stimulation in intrauterine insemination (IUI)? This single-centre, prospective, open-label, single-cohort study involving 106 patients established an original dosing regimen based on body weight and anti-Müllerian hormone (AMH) concentrations, with adjustments based on the ovarian response from the previous IUI cycle. Each participant was enrolled in a maximum of three IUI cycles. Mean age was 34.5 ± 4.5 years, mean weight 69.2 ± 11.2 kg, mean AMH 15.7 ± 8.6 pmol/l, mean FSH 6.3 ± 2.6 IU/l and mean antral follicle count 16.4 ± 8.2. The percentage of patients who produced more than three mature follicles was 1.9%, 0% and 1.5%, respectively, for the three IUI cycles. The percentage of patients with two or three mature follicles was 34.0%, 36.9% and 47.1% for the three IUI cycles. The clinical pregnancy rate per IUI cycle was 17.9%, 14.3% and 17.6% for the three cycles, with a cumulative clinical pregnancy rate of 40.6%. Out of 258 cycles, 43 (16.7%) resulted in clinical pregnancy, with six of those resulting in multiple pregnancies (14.0%). Two resulted in spontaneous reduction within the first trimester and four resulted in live twin births, representing only 1.6% of the total cycles. This study is the first to utilize follitropin delta for stimulation in IUI. It demonstrates that individualized dosing is both effective and safe, resulting in satisfactory cumulative pregnancy rates and an acceptable multiple pregnancy rate, thus achieving the primary objectives of the research. [ABSTRACT FROM AUTHOR]

Abstract Research question Does autologous endometrial cell co-culture (AECC) improve the number of good-quality blastocysts obtained by IVF/intracytoplasmic sperm injection (ICSI), compared with conventional embryo culture medium in a broad group of patients referred to assisted reproductive technology (ART)? Design This interventional, randomized, double-blind study took place at Clinique Ovo from March 2013 to October 2015 and included 207 healthy patients undergoing an IVF or ICSI protocol, of which 71 were excluded before randomization. On the previous cycle, all participants underwent an endometrial biopsy at D5 to D7 post-ovulation, following which the endometrial cells were prepared for AECC. Results The data demonstrated that AECC significantly increased the incidence of good-quality blastocysts compared with culture in conventional media (42.6% vs 28.4%, P < 0.001). No significant differences were found in pregnancy and live birth rates. Conclusion This study demonstrated the benefits of AECC on blastocyst quality compared with conventional embryo culture medium, in a broader category of patients referred to ART as opposed to other studies that concentrated on specific causes of infertility only. However, limitations of the study design should be taken into consideration; the analysis was performed using embryos rather than patients and a follow-up of children born following the treatments could not be conducted. [ABSTRACT FROM AUTHOR]

Objective To evaluate testicular sperm aspiration (TESA) sperm retrieval rates and intracytoplasmic sperm injection outcomes in nonazoospermic men. Materials and Methods Data were collected retrospectively from 54 consecutive, nonazoospermic, infertile men who underwent TESA between March 2007 and September 2012. Sperm retrieval rates and clinical pregnancy outcomes were recorded. Patients were subgrouped based on clinical diagnosis: group 1, anejaculation (primary, situational); group 2, idiopathic severe oligoasthenozoospermia; and group 3, severe oligoasthenozoospermia after vasovasostomy. Results Mean (±standard deviation) paternal and maternal ages were 39 ± 7 and 35 ± 5 years, respectively. Using TESA, sperm recovery was successful in 94% (51 of 54) of the men overall and in 100% (17 of 17) of the men in group 1, 90% (28 of 31) in group 2, and 100% (6 of 6) in group 3. Overall, 35% of the couples achieved a clinical pregnancy using TESA sperm (with a mean of 1.7 ± 0.9 embryos transferred per cycle). The clinical pregnancy rates were 40% in group 1, 33% in group 2, and 33% in group 3 with no significant difference in paternal or maternal age between groups. Conclusion The data indicate that TESA yields high sperm retrieval rates in select groups of nonazoospermic infertile men, and this approach results in acceptable pregnancy rates regardless of the male infertility etiology. Randomized controlled trials comparing ejaculated vs testicular sperm are needed to assess the true benefit of TESA-intracytoplasmic sperm injection in these couples. [ABSTRACT FROM AUTHOR]

A retrospective cohort study was performed to evaluate the outcome of modified natural IVF-intracytoplasmic sperm injection {mnlVF-ICSI) cycles to compare 81 mnlVF- ICSI first cycles using ejaculated spermatozoa with 44 mnlVF-ICSI first cycles using surgically retrieved spermatozoa. There were no differences between the two groups in terms of number of oocytes retrieved, oocyte maturity or female age. However, male age was significantly higher in the surgically retrieved compared with the ejaculated group (41.5 versus 36.5 years, P= 0.001). There were no significant differences in fertilization rate or cleavage rate between the ejaculated and the surgically retrieved groups; however the prevalence of embryo transfer was higher in the surgically retrieved group (65.9% versus 45.7%, P = 0.03). Only single-embryo transfer was performed. Biochemical (34.5% versus 37.8%) and clinical (31.0% versus 35.1%) pregnancy rates per embryo transfer were similar between the ejaculated and the surgically retrieved groups. The data suggest that mnlVF-ICSI is an alternative treatment option in couples with severe male factor infertility where surgical sperm retrieval is required. [ABSTRACT FROM AUTHOR]

Interfering intracellular antibodies are valuable for biological studies as drug surrogates and as potential macromolecular drugs per se. Their application is still limited because of the difficulty of acquisition of functional intracellular antibodies. We describe the use of the new intracellular antibody capture procedure (IAC³) to facilitate direct isolation of functional single domain antibody fragments using four independent target molecules (LMO2, TPS3, CRAF1, and Hoxa9) from a set of diverse libraries. Initially, these have variability in only one of the three antigen-binding CDR regions of VH or VL and first round single domains are affinity matured by iterative randomization of the two other CDRs and reselection. We highlight the approach using a single domain binding to LMO2 protein. Our results show that interfering with LMO2 protein function demonstrates a role specifically in erythroid differentiation, confirm a necessary and sufficient function for LMO2 as a cancer therapy target in T-cell neoplasia and allowed for the first time production of soluble recombinant LMO2 protein by co-expression with intracellular domain antibodies. Cocrystallization of LMO2 and the anti-LMO2 VH protein was successful. These results demonstrate that this third generation IAC³ offers a robust toolbox for various biomedical applications and consolidates functional features of the LMO2 protein complex, which includes the importance of Lmo2-Ldb1 protein interaction. [ABSTRACT FROM AUTHOR]

Abstract: Seminal antisperm antibodies (ASAs) have been associated with male infertility and a reduced probability of achieving a spontaneous pregnancy. However, the impact of ASAs on reproductive outcomes after assisted reproductive technologies (ARTs) remains controversial. We sought to further examine the relationship between ASAs and reproductive outcomes after in vitro fertilization (IVF) or IVF with intracytoplasmic sperm injection (ICSI). We conducted a retrospective study of consecutive IVF and IVF/ICSI cycles where the male partner had had direct ASA testing in the six months preceding the ART cycle. We examined the relationship between semen parameters (sperm concentration, motility, strict morphology, ASA levels [by direct mixed agglutination reaction and expressed as the percentage of spermatozoa with IgG or IgA antibodies]) and reproductive outcomes (fertilization and clinical pregnancy rate) after IVF and IVF/ICSI. There was no significant relationship between direct ASA levels and reproductive outcomes after IVF and IVF/ICSI. Similarly, we found no significant relationships between sperm parameters (concentration, motility, strict morphology) and reproductive outcomes after IVF and IVF/ICSI. Clinical pregnancy rates were not significantly different in ASA-positive (>50% of sperm coated with ASAs) compared with ASA-negative samples (42% vs. 52% respectively, odds ratio: 1.45 (95% CI 0.63, 3.30, P >0.05). The data indicate that ASAs in semen are not associated with reproductive outcomes (fertilization and clinical pregnancy rate) after IVF or IVF/ICSI. [Copyright &y& Elsevier]

Abstract: Several 2-aminotetralones were identified as novel inhibitors of the bacterial enzymes MurA and MurZ. A number of these inhibitors demonstrated antibacterial activity against Staphylococcus aureus and Escherichia coli with MICs in the range 8–128μg/ml. Based on structure–activity relationships we propose that the α-aminoketone functionality is responsible for the inhibitory activity and evidence is provided to support a covalent mode of action involving the C115 thiol group of MurA/MurZ. [Copyright &y& Elsevier]

Objective: To localize foci of single-stranded (ss) DNA in sperm nuclei of fertile and infertile men. Design: Prospective, observational study. Setting: University infertility clinic. Patient(s): Semen samples from 12 consecutive asthenoteratospermic men presenting for infertility evaluation and 5 consecutive fertile men presenting for vasectomy. Intervention(s): Semen analysis, semen processing, and immunocytochemistry using an antibody targeting ssDNA. Main Outcome Measure(s): Sperm nuclear ssDNA immunostaining pattern in whole and processed semen samples. Result(s): Immunocytochemistry (using ssDNA antibody) demonstrated one of two sperm nuclear staining patterns: [1] faint punctated staining, and [2] diffuse nuclear staining. Infertile men had a higher proportion of spermatozoa exhibiting diffuse ssDNA staining than did fertile men (52 ± 19 vs. 14 ± 13, respectively). The proportion of spermatozoa exhibiting diffuse ssDNA staining was significantly higher in whole compared with processed semen. Positive (DNAse-treated nuclei) and negative controls (S1 nuclease-treated nuclei) were obtained to validate the specificity of the antibody. Conclusion(s): Human sperm nuclei generally exhibit discrete (presumably peripheral) foci of ssDNA. The data also show that infertile men have a higher proportion of sperm nuclei with diffuse areas of ssDNA than do fertile men, and suggest that spermatozoa with diffuse nuclear staining are abnormal. [Copyright &y& Elsevier]

Summary: Sequence-specific interactions between RNA stem-loops and coat protein (CP) subunits play vital roles in the life cycles of the RNA bacteriophages, e.g., by allowing translational repression of their replicase cistrons and tagging their own RNA genomes for encapsidation. The CPs of bacteriophages Qβ and MS2 each discriminate in favor of their cognate translational operators, even in the presence of closely related operators from other phages in vivo. Discrete mutations within the MS2 CP have been shown to relax this discrimination in vitro. We have determined the structures of eight complexes between such mutants and both MS2 and Qβ stem-loops with X-ray crystallography. In conjunction with previously determined in vivo repression data, the structures enable us to propose the molecular basis for the discrimination mechanism. [Copyright &y& Elsevier]

Computer-based molecular design has been used to produce a series of new macrocyclic systems targeted against the bacterial cell wall biosynthetic enzyme MurD. Following their preparation, which involved a novel metathesis-based cyclisation as the key step, these systems were found to show good inhibition when assayed against the MurD enzyme. [Copyright &y& Elsevier]