Prevalence of chromosomal abnormalities in 2078 infertile couples referred for assisted reproductive techniques

BACKGROUND: This study analyses the prevalence of karyotype changes and Yq11 microdeletions among couples referred for assisted reproduction techniques. METHODS: Prior to receiving either IVF or ICSI treatment, each partner of 2078 infertile couples was screened for karyotype changes by GTG-banding technique on peripheral lymphocytes. No subject presented with obvious phenotype of chromosomal rearrangement. All the oligo/azoospermic men with normal karyotype were further investigated by PCR for Yq11 microdeletions. RESULTS: Eighty-two out of 2078 couples (3.95%) had one partner carrying a chromosomal change, and 10 out of 202 (4.95%) men showed Yq11 microdeletions. The chromosomal rearrangements were 44 (2.1%) translocations, 23 (1.1%) gonosomal mosaics, six (0.3%) 47,XXY, five (0.24%) marker chromosomes, three (0.14%) inversions and one (0.05%) duplication. Frequency of anomalies in men and women were similar: 42 and 40 cases respectively. CONCLUSIONS: Partners of infertile couples requiring IVF or ICSI treatment appear to be affected by higher frequency of chromosomal rearrangements than the general population. Categories with greater risk were represented by men with sperm cell count <20 x 10(6) sperm/ml, and women with history of pregnancy loss.     

Optical Coherence Angiographic Demonstration of Retinal Changes From Chronic Optic Neuropathies

Glaucoma causes a decrease in peripapillary perfused capillary density on optical coherence tomography (OCT) angiography. However, other chronic optic neuropathies have not been explored with OCT angiography to see if these changes were specific to glaucoma. The authors evaluated OCT angiography in 10 patients who suffered various kinds of chronic optic neuropathies, including optic neuritis and ischaemic optic neuropathy, and found that all optic neuropathies showed a decrease in peripapillary vessel density on OCT angiography, regardless of the aetiology of the optic neuropathy. The peripapillary vessel loss on OCT angiography correlated well with the areas of retinal nerve fibre layer thinning seen on OCT.     

Synthesis and kinetics of disassembly for silyl-containing ethoxycarbonyls using fluoride ions

In this study, a series of silyl-containing ethoxycarbonates and ethoxycarbamates on electron poor anilines and phenols were synthesized and their kinetics of disassembly determined in real-time upon exposure to fluoride ion sources at room temperature. The results provide a greater understanding of stability and kinetics for silyl-containing protecting groups that eliminate volatile molecules upon removal, which will allow for simplification of orthogonal protection in complex organic molecules.

Rate constants of disassembly for synthesized silyl-containing ethoxycarbonyls were significantly faster than TEOC, a common protecting group.

Silicon-based groups have demonstrated wide utility in organic syntheses, ranging from orthogonal protection of amine, hydroxyl and acid functionalities in complex drug molecules^1–3 to utilization as a trigger in self-immolative polymers and dendrimers.^4–6 One of the commonly used silicon-based protecting groups is 2-(trimethylsilyl)ethoxycarbonyl (TEOC),⁷ which was originally developed and later optimized for N-protection of amino acids to prevent formation of oligopeptides, but has since been utilized for protection of other functionalities.⁸ The uniqueness of TEOC is that it can be preferentially removed with a mild de-blocking agent, such as fluoride ion, in the presence of other base-sensitive groups to produce low molecular weight and volatile by-products via cascading bond cleavage, thereby easing purification of complex mixtures and enabling greater product yields.During our course of utilizing TEOC to protect amine and hydroxyl functionality on aliphatic oligomers we discovered there was a severe lack of kinetic data in the literature for removal of TEOC using fluoride ion, as most papers generally stated the times for removal as occurring within hours at elevated temperatures⁷ to days at room temperature.^9,10 Furthermore, similar silyl-containing protecting groups, such as (2-phenyl-2-trimethylsilyl)ethoxycarbonyl (PSOC)¹¹ and 2-(triphenylsilyl)ethoxycarbonyl (TPSEOC),¹² were reported to be removed under milder fluoride ion conditions and/or faster times than TEOC due to a more readily formed fluoro-containing penta-coordinated intermediate as a result of phenyl group incorporation. However, while these groups were reported to be removed within minutes to hours at room temperature the studies provide minimal details on the actual kinetics compared to TEOC. As a result, we aimed to generate quantitative kinetic data for the removal of TEOC and other silyl-containing ethoxycarbonyl groups from functionality by performing disassembly experiments with fluoride ion sources at room temperature, as this information is relevant to those utilizing orthogonal protecting group chemistry in multi-step synthesis and potentially in the processing of pharmaceuticals.Herein, we report the kinetics of disassembly (i.e., rate constants (k) for removal) for a series of silyl-terminated ethoxycarbonyl protecting groups, such as TEOC, 2-(methyldiphenylsilyl)ethoxycarbonyl (MDPSEOC), and several extended chain versions of these molecules, from electron poor hydroxyl and amine functionalities. To do this, we utilized non-substituted and para-substituted phenols and anilines, as these molecules provided a UV-visible chromophore for real-time detection during removal of the protecting groups. We also synthesized and determined the kinetics of disassembly for several novel silyl-centered bis(ethoxycarbonyls), as we were interested in studying the reaction of multiple fluoride ions with silicon and their influence on the resulting kinetics.Our study of these molecules commenced by attempting to determine the rate constants of disassembly for 4-nitrophenyl (2-(trimethylsilyl)ethyl) carbonate (1a), a commercially available control,¹³ and synthesized 2-(trimethylsilyl)ethyl (4-nitrophenyl)carbamate (1b), using solutions of different fluoride salts in organic solvents and water. It was initially found that tetrahydrofuran (THF), dichloromethane, and acetonitrile provided good solubility of these organic molecules, with water and water/solvent combinations providing limited solubility. Furthermore, fluoride ion sources, such as tetrabutylammonium fluoride trihydrate (TBAF·3H₂O) and a 1 : 1 molar ratio of TBAF/CsF, provided good solubility in the aforementioned solvents and several solvent/water combinations, whereas solubility of cesium fluoride (CsF), sodium fluoride (NaF), potassium fluoride (KF), and stannous fluoride (SnF₂) were limited. It should be noted that a 1 : 1 TBAF/CsF mixture in THF provided nearly identical rate constants of disassembly during initial studies as TBAF in THF. However, to maintain fluoride ion solution consistency it was determined that all kinetic experiments would be conducted in THF using commercially available TBAF in THF.Kinetic experiments for 1a and 1b were conducted as 0.1 mM solutions in THF using 1 ml cuvettes and an Agilent 8453 UV-Visible Spectrophotometer. To initiate disassembly, 4 molar equivalents of 1.0 M TBAF in THF were added separately to 1a and 1b at room temperature (Scheme 1), then the absorbance of the solutions were recorded up to 120 minutes. The cuvettes were not stirred upon addition of the fluoride salt solution in effort to prevent an increase in the rate of disassembly due to turbidity. Silyl-terminated carbonate 1a, which has a maximum absorbance (λ_max) at 270 nm, decreased within minutes as a new absorbance at λ_max of 423 nm appeared, corresponding to 4-nitrophenolate (2a).¹⁴ Ethylene and carbon dioxide were detected via gas chromatography/mass spectrometry (GC-MS), thereby supporting the proposed mechanism of disassembly as shown in Scheme 1.⁷ The rate constant of disassembly for 1a was found to be 2196 ± 1380 M⁻¹ min⁻¹ for the second order reaction (15 although this peak quickly decreased as a new absorbance at λ_max of 366 nm was formed. The latter corresponded to 4-nitroaniline (2c),¹⁶ the conjugate acid of 2b, and is proposed to have resulted from beta-elimination of a proton on the tetrabutylammonium cation, thereby forming tributylamine and 1-butene as side products via a Hofmann elimination.¹⁷¹H-NMR and GC-MS analysis of the solution after disassembly supports this hypothesis. The rate constant of disassembly for 1b was determined to be 38.5 ± 0.3 M⁻¹ min⁻¹, and the slower rate compared to 1a is consistent with substituted anilines possessing a larger pKa value than substituted phenols. 2-(methyldiphenylsilyl)ethyl (4-nitrophenyl) carbonate 1c and 2-(methyldiphenylsilyl)ethyl (4-nitrophenyl)carbamate 1d were subsequently synthesized and their rate constants of disassembly determined. Although similar to the triphenylsilyl and 2-phenyl-2-trimethylsilyl ethoxycarbonyl protecting groups reported in the literature,^11,12 we chose the methyldiphenylsilyl group because it was a hybrid of the aforementioned groups, the kinetics of phenyl-containing silyl groups had not been reported, and the lone methyl group provided a basis for larger aliphatic groups, which are discussed in subsequent paragraphs.Open in a separate windowScheme 1Products and proposed mechanism of disassembly for reaction of silyl-terminated carbonates and carbamates with TBAF.Rate constants of disassembly and percentage of silyl-terminated carbonates and carbamates remaining once treated with TBAF under non-stirred conditions

A torque-measuring micromotor provides operator independent measurements marking four different density areas in maxillae

PURPOSE

Bone density at implant placement site is a key factor to obtain the primary stability of the fixture, which, in turn, is a prognostic factor for osseointegration and long-term success of an implant supported rehabilitation. Recently, an implant motor with a bone density measurement probe has been introduced. The aim of the present study was to test the objectiveness of the bone densities registered by the implant motor regardless of the operator performing them.

MATERIALS AND METHODS

A total of 3704 bone density measurements, performed by means of the implant motor, were registered by 39 operators at different implant sites during routine activity. Bone density measurements were grouped according to their distribution across the jaws. Specifically, four different areas were distinguished: a pre-antral (between teeth from first right maxillary premolar to first left maxillary premolar) and a sub-antral (more distally) zone in the maxilla, and an interforaminal (between and including teeth from first left mandibular premolar to first right mandibular premolar) and a retroforaminal (more distally) zone in the lower one. A statistical comparison was performed to check the inter-operators variability of the collected data.

RESULTS

The device produced consistent and operator-independent bone density values at each tooth position, showing a reliable bone-density measurement.

CONCLUSION

The implant motor demonstrated to be a helpful tool to properly plan implant placement and loading irrespective of the operator using it.     

Bone‐to‐Implant Contact Around Immediately Loaded Direct Laser Metal‐Forming Transitional Implants in Human Posterior Maxilla

Objective: Direct laser metal forming (DLMF) is a procedure in which a high‐power laser beam is directed onto a metal powder bed and programmed to fuse particles according to a computer‐aided design file, generating a thin metal layer. This histologic study evaluated the bone‐to‐implant contact (BIC%) around immediately loaded DLMF transitional implants retrieved after 2 months from posterior human maxillae. Methods: Twelve totally edentulous individuals (mean age, 66.14 ± 2.11 years) received DLMF transitional implants divided in twelve immediately loaded (IL) and twelve unloaded (UI) implants. These transitional implants were placed between conventional implants to support the interim complete maxillary denture during the healing period. After 8 weeks, the transitional implants and the surrounding tissue were removed and prepared for histomorphometric analysis. Results: Mature woven preexisting bone lined by newly formed bone in early stages of maturation were found around all retrieved implants. Histometric evaluation indicated that the mean BIC% was 45.20 ± 7.68% and 34.10 ± 7.85% for IL and UI, respectively (P <0.05). Conclusion: The present data obtained in humans showed that, although both IL and UI presented good BIC%, IL DLMF implants had a higher BIC% in the posterior maxilla.     

Augmentation of the floor of the maxillary sinus with recombinant human bone morphogenetic protein-7: a pilot radiological and histological study in humans

The aim of this study was to evaluate the quantity and quality of bony regeneration after we had used recombinant human bone morphogenetic protein-7 (rhBMP-7 to augment the floor of the maxillary sinus. Nine consecutive patients with bilateral posterior maxillary atrophy who required augmentation of the sinus for interposition of implants were treated simultaneously with rhBMP-7 (Osigraft) with deproteinised bone substitute (0.5 g on the test side) and with deproteinised bone alone (2.0 g on the control side). Computed tomographic images preoperatively, immediately postoperatively, and at 4 months postoperatively showed a mean (SD) postoperative gain of 10.8 (3.0) mm on the test side and of 10.2 (1.8) mm on the control side. Histological and histomorphometric analyses of biopsy specimens showed that there was significantly more new bone on the control side (19.9 (6.8)%) than on the test side (6.6 (4.8)%). In this pilot controlled trial of the use of rhBMP-7, histological analyses showed that it resulted in the formation of less bone than treatment with inorganic bovine hydroxyapatite.