Photocatalytic ATRA reaction promoted by iodo-Bodipy and sodium ascorbate.

Using ascorbate as a sacrificial reductant, iodo-Bodipy dye 1b is able to promote the ATRA reaction between bromoderivatives and alkenes. This finding expands the possibility of using Bodipy dyes to promote photocatalytic reactions in efficient ways.

Carotenoids co-localize with hydroxyapatite, cholesterol, and other lipids in calcified stenotic aortic valves. Ex vivo Raman maps compared to histological patterns.

Unlike its application for atherosclerotic plaque analysis, Raman microspectroscopy was sporadically used to check the sole nature of bioapatite deposits in stenotic aortic valves, neglecting the involvement of accumulated lipids/lipoproteins in the calcific process. Here, Raman microspectroscopy was employed for examination of stenotic aortic valve leaflets to add information on nature and distribution of accumulated lipids and their correlation with mineralization in the light of its potential precocious diagnostic use. Cryosections from surgically explanted stenotic aortic valves (n=4) were studied matching Raman maps against specific histological patterns. Raman maps revealed the presence of phospholipids/triglycerides and cholesterol, which showed spatial overlapping with one another and Raman-identified hydroxyapatite. Moreover, the Raman patterns correlated with those displayed by both von-Kossa-calcium- and Nile-blue-stained serial cryosections. Raman analysis also provided the first identification of carotenoids, which co-localized with the identified lipid moieties. Additional fit concerned the distribution of collagen and elastin. The good correlation of Raman maps with high-affinity staining patterns proved that Raman microspectroscopy is a reliable tool in evaluating calcification degree, alteration/displacement of extracellular matrix components, and accumulation rate of different lipid forms in calcified heart valves. In addition, the novel identification of carotenoids supports the concept that valve stenosis is an atherosclerosis-like valve lesion, consistently with their previous Raman microspectroscopical identification inside atherosclerotic plaques.

Immunolocalization of interleukin-1 receptor antagonist in healthy and infarcted myocardium.

Ischemic heart disease is a widespread cause of death. During infarction, myocardial injury is mediated by release of several pro-inflammatory cytokines including multifunctional interleukin-1 (IL-1). In various tissues, IL-1-mediated deleterious effects are known to be attenuated via the over-expression of natural anti-inflammatory cytokine IL-1 receptor antagonist (IL-1ra). In the present investigation, IL-1ra distribution in healthy and infarcted myocardium was studied by light and electron microscopy. After immunostaining, weak positivity resulted for cardiomyocytes in normal myocardium and, at higher degrees, in infarction border areas and ischemic ones. In ischemic areas, additional reactivity was displayed by the extracellular matrix and intravascular plasma. Immunogold labelling provided further details on intracytoplasmatic and extracellular distribution; in particular, noticeable gold particle distribution appeared on intercalated discs in normal and hypertrophic cardiomyocytes, as well as on thickened Z-lines for these latter. The present results suggest that cardiomyocytes represent a major source of IL-1ra in vivo, even though additional contribution by blood derived IL-1ra is to be taken in account in ischemic areas. In addition, ischemia-associated intracytoplasmic IL-1ra increase and its additional presence in the extracellular matrix is consistent with the concept that this cytokine plays a cardioprotective role at different levels and by distinct mechanisms.

Opposed independent effects and epistasis in the complex association of IRF5 to SLE.

Genetic variation in the interferon regulatory factor 5 (IRF5) gene affects systemic lupus erythematosus (SLE) susceptibility. However, association is complex and incompletely defined. We obtained fourteen European sample collections with a total of 1383 SLE patients and 1614 controls to better define the role of the different IRF5 variants. Eleven polymorphisms were studied, including nine tag single nucleotide polymorphisms (SNPs) and two extra functional polymorphisms. Two tag SNPs showed independent and opposed associations: susceptibility (rs10488631, P<10(-17)) and protection (rs729302, P<10(-6)). Haplotype analyses showed that the susceptibility haplotype, identified by the minor allele of rs10488631, can be due to epistasis between three IRF5 functional polymorphisms. These polymorphisms determine increased mRNA expression, a splice variant with a different exon 1 and a longer proline-rich region in exon 6. This result is striking as none of the three polymorphisms had an independent effect on their own. Protection was independent of these polymorphisms and seemed to reside in the 5' side of the gene. In conclusion, our results help to understand the role of the IRF5 locus in SLE susceptibility by clearly separating protection from susceptibility as caused by independent polymorphisms. In addition, we have found evidence for epistasis between known functional polymorphisms for the susceptibility effect.

Bias in association studies of systemic lupus erythematosus susceptibility due to geographical variation in the frequency of a programmed cell death 1 polymorphism across Europe.

We obtained eight collections of DNA samples from ethnically matched systemic lupus erythematosus (SLE) patients and controls from five European countries totaling 783 patients and 1210 controls. A highly significant cline in the frequency of the PD1.3 A allele was found among controls but not among SLE patients. The frequency of the PD1.3 A allele increased from the Northeast to the Southwest of Europe. The cline was clearly apparent (P=1.2 x 10(-6)) when data from controls of other five SLE susceptibility studies were included in the analysis. This variation has severely biased SLE association studies owing to the lack of parallel changes in SLE patients. As a consequence, the PD1.3 A allele was more common in SLE patients than in controls in the Northeast and Center of Europe, similar to controls in Southeast Europe, and less frequent than in the controls in the Southwest of the Continent. This dissociation in allele frequencies between SLE patients and controls in different subpopulations indicated that programmed cell death 1 variation and disease susceptibility are not independent but the type of relationship is currently unclear. As allele frequency clines are common in other polymorphisms their impact in genetic epidemiology studies should be carefully considered.

Ultrastructural characterization of calcification onset and progression in subdermally implanted aortic valves. Histochemical and spectrometric data.

Detailed characterization of the subdermal model is a significant tool for better understanding of calcification mechanisms occurring in heart valves. In previous ultrastructural investigation on six-week-implantated aortic valve leaflets, modified pre-embedding glutaraldehyde-cuprolinic-blue reactions (GA-CB) enabled sample decalcification with concurrent retention/staining of lipid-containing polyanionic material, which lined cells and cell-derived matrix-vesicle-like bodies (phthalocyanin-positive layers: PPLs) co-localizing with the earliest apatite nucleation sites. Additional post-embedding silver staining (GA-CB-S) revealed PPLs to contain calcium-binding sites. This investigation concerns valve leaflets subjected to shorter implantation times to shed light on the modifications associated with PPLs generation and calcification onset/progression. Spectrometric estimations revealed time-dependent calcium increase, for unreacted samples, and copper modifications indicating an increase in acidic, non-glycanic material, for GA-CB-reacted samples. Two-day-implant thin sections showed emission and subsequent reabsorption of lamellipodium-like protrusions by cells, originating ECM-containing vacuoles, and/or degeneration stages characterized by the appearance of GA-CB-S-reactive, organule-derived dense bodies and progressive dissolution of all cell membranes. In one-week-implants, the first PPL-lined cells were found to co-exist with cells where GA-CB-S-reactive material accumulated, or exudated towards their edges, or outcropped at the ECM milieu, so acquiring PPL features. PPL-derived material was observed increasingly to affect the ECM on thin sections of one-week- to six-week-implants. These results show an endogenous source for PPLs and reveal that a peculiar cascade of cell degenerative steps is associated with valve mineralization in the subdermal model, providing new useful parameters for more reliable comparison of this experimental calcification process versus the physiological and pathological processes.

Two single-nucleotide polymorphisms in the 5' and 3' ends of the osteopontin gene contribute to susceptibility to systemic lupus erythematosus.

OBJECTIVE: To test the association of osteopontin (OPN) polymorphisms with systemic lupus erythematosus (SLE). METHODS: The coding 5' and 3' flanking regions of the OPN gene were scanned for polymorphisms by denaturing high-performance liquid chromatography. A case-control association study was performed in 394 Italian SLE patients and 479 matched controls. OPN serum levels were determined by enzyme-linked immunosorbent assay in 40 patients and 124 controls, and the mean levels were compared between the different OPN genotypes. RESULTS: Among the 13 detected single-nucleotide polymorphisms (SNPs), alleles -156G (frequency 0.714 versus 0.651; P = 0.006, corrected P [P(corr)] = 0.036) and +1239C (0.377 versus 0.297; P = 0.00094, P(corr) = 0.0056) were significantly increased in the SLE patients compared with the controls. The presence of the associated allele in single or double dose conferred an odds ratio (OR) of 2.35 (95% confidence interval [95% CI] 1.38-4.02) for SNP -156 and an OR of 1.57 (95% CI 1.16-2.13) for SNP +1239. These effects were independent of each other, i.e., not a consequence of linkage disequilibrium between the 2 alleles. The risk associated with a double dose of susceptibility alleles at both SNPs was 3.8-fold higher (95% CI 2.0-7.4) relative to the complete absence of susceptibility alleles. With regard to individual clinical and immunologic features, a significant association was seen between lymphadenopathy and -156 genotypes (overall P = 0.0011, P(corr) = 0.046). A significantly increased OPN serum level was detected in healthy individuals carrying +1239C (P = 0.002), which is indicative of an association between the SLE susceptibility allele and OPN levels. CONCLUSION: These data suggest the independent effect of a promoter (-156) and a 3'-untranslated region (+1239) SNP in SLE susceptibility. We can speculate that these sequence variants (or others in perfect linkage disequilibrium) create a predisposition to high production of OPN, and that this in turn may confer susceptibility to SLE.

Isolation of intact aortic valve scaffolds for heart-valve bioprostheses: extracellular matrix structure, prevention from calcification, and cell repopulation features.

Extracellular matrix (ECM) scaffolds isolated from valvulated conduits can be useful in developing durable bioprostheses by tissue engineering provided that anatomical shape, architecture, and mechanical properties are preserved. As evidenced by SEM, intact scaffolds were derived from porcine aortic valves by the combined use of Triton X-100 and cholate (TRI-COL) or N-cetylpyridinium (CPC) and subsequent nucleic acid removal by nuclease. Both treatments were effective in removing most cells and all the cytomembranes, with preservation of (1) endothelium basal membranes, (2) ECM texture, including the D-periodical interaction of small proteoglycans with normally D-banded collagen fibrils, and (3) mechanical properties of the treated valves. Ultrastructural features agreed with DNA, hexosamine, and uronic acid biochemical estimations. Calcification potential, assessed by a 6-week rat subdermal model, was significantly reduced by TRI-COL/nuclease treatment. This was not true for CPC only, despite better proteoglycan preservation, suggesting that nucleic acids also are involved in calcification onset. Human fibroblasts, used to repopulate TRI-COL samples, formed mono- or multilayers on surfaces, and groups of cells also were scattered within the valve leaflet framework. A biocompatible scaffolds of this kind holds promise for production of durable valve bioprostheses that will be able to undergo probable turnover and/or remodeling by repopulating recipient cells.

Malachite green and phthalocyanine-silver reactions reveal acidic phospholipid involvement in calcification of porcine aortic valves in rat subdermal model.

Subdermal implant models are helpful in the study of calcification "in vivo" and for testing anticalcific treatments. After implantation of porcine aortic valve leaflets in rat subcutis, we previously found that glutaraldehyde-Cuprolinic blue reactions (GA-CB) at low pH induce favourable tissue unmasking from mineral deposits, and visualize peculiar, electrondense layers that outline the calcifying cells and matrix vesicle-like structures. The layer-forming material seemed to consist of acidic phospholipids because of its anionic nature and differential susceptibility to chemical/enzymatic extractivity. In the present investigation, pre-embedding glutaraldehyde-Malachite green (GA-MG) reactions and subsequent osmium post-fixation were compared with pre-embedding GA-CB reactions, combined with post-embedding von Kossa silver staining (GA-CB-S), to assess whether the layer-forming material is actually composed of acidic phospholipids and exhibits calcium-binding properties. After lowering standard pH, GA-MG reactions also caused sample demineralization and the appearance of pericellular osmium-MG-reactive layers comparable to CB-reactive ones. Moreover, GA-CB-S reactions showed that major silver precipitation was superimposed to the CB-reactive layers, whereas minor metal extra-precipitation occurred at three distinct, additional sites. These results demonstrate that a unique process of cell degeneration occurs in this calcification model, in which acidic phospholipids accumulate at cell surface, replacing cell membrane and acting as major apatite nucleator. However, the overall observations are consistent with the hypothesis that certain phases are common to the various types of normal and/or abnormal calcification.

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5' regulatory region.

Many lines of evidence suggest that IL10 is a strong candidate gene for systemic lupus erythematosus (SLE) susceptibility. In our previously reported study an allele (IL10.G-140bp) of the microsatellite IL10.G located at position -1100 was significantly increased in Italian SLE patients in comparison with controls. Starting from this observation, we tested if sequence variations in the vicinity of IL10.G were more strongly associated with SLE. We performed a comprehensive association study including 26 SNPs (of which four were newly identified in the present study by DHPLC analysis) spanning 8.5 Kb of the 5' flanking and the transcribed region of the IL10 gene. The association study was performed by the DNA pool method on an extended panel of Italian patients (205) and controls (631). Haplotypic associations were studied by individual typing of seven selected markers surrounding IL10.G. Gene, genotype and haplotype frequencies were not significantly different in patients and controls. Thus the IL10.G microsatellite remains to date the only IL10 marker associated with SLE in our population. A meta-analysis of all published results indicates a possible direct role of the IL10.G repeat number in SLE susceptibility.

Ab-interno trabeculo-canalectomy: surgical approach and histological examination.

PURPOSE: To evaluate, on eye bank eyes, a new surgical approach aimed at removing a quadrant of the trabecular meshwork (TM), with an ab interno approach. METHODS: Gonioscopically controlled ab interno removal of the TM was done with a subretinal forcep on six human bank eyes. Serial histological sections were obtained from the treated and untreated part of each globe to assess the effect of the technique on intraocular tissues. RESULTS: Under the gonioscope, the TM was easily removed in strings of varying length. Histological examination showed, unexpectedly, that this resulted in a well-defined deep furrow in the middle of the trabecular region involving both the TM and the inner wall of Schlemm's canal. The operation created a direct communication between the anterior chamber and Schlemm's canal lumen without any evident damage to the outer canal wall and adjacent ocular structures such as the iris base and corneal endothelium. CONCLUSIONS: Our small series on human bank eyes showed that the procedure involves both the TM and the inner wall of Schlemm's canal and is therefore called ab interno trabeculocanalectomy (AITC). The intraoperative findings and the histological evidence are encouraging, and suggest that the procecedure could have potential clinical application.

Copper retention, calcium release and ultrastructural evidence indicate specific Cuprolinic Blue uptake and peculiar modifications in mineralizing aortic valves.

Previously, reactions with copper phthalocyanines at 0.05 M critical electrolyte concentration were found to cause demineralization in calcifying porcine aortic valves after subdermal implantation in rat, as well as simultaneous visualization of peculiar phthalocyanine-positive layers around cells and cell-derived matrix vesicles. In the present investigation, an appraisal was made of the mechanism and specificity of reactions with Cuprolinic Blue by comparing quantitatively calcium release and copper retention by calcified aortic valves reacted with this phthalocyanine under different critical electrolyte concentration conditions, and the corresponding ultrastructural patterns. It was found that (i) decalcifying properties are inversely proportional to salt molarity; (ii) reactivity to Cuprolinic Blue is critical electrolyte concentration-dependent, since the greatest copper retention occurred in 0.05 M critical electrolyte concentration Cuprolinic Blue-reacted samples, the only ones that also exhibited phthalocyanine-positive layers; (iii) the appearance of phthalocyanine-positive layers depends on Cuprolinic Blue uptake, revealing pericellular clustering of calcium-binding, anionic molecules; and (iv) minor Cuprolinic Blue uptake occurs by residual proteoglycans which still remain in the extracellular matrix after 6-week-long subdermal implantation. The present results indicate that this method is appropriate for the study of mineralized tissues and illustrate peculiar tissue modifications occurring at least in the experimental conditions used here.

Novel ultrastructural features as revealed by phthalocyanine reactions indicate cell priming for calcification in subdermally implanted aortic valves.

The roles played by various determinants in physiological, pathological or experimental calcification are still unclear. In this investigation, new insights were gained into structural changes occurring in porcine aortic valves undergoing mineralization in the rat subdermal model and then subjected to reactions with cationic phthalocyanines (PHTs), at salt-critical electrolyte concentrations (CEC). PHT reactions showed decalcifying effects, depending on both acidic pH in the media employed and mineral substitution by Cuprolinic Blue (CB) itself, as well as specific reactivity which enabled the ultrastructural detection of unusual, PHT-positive layers (PPLs) encircling cells and matrix vesicles, at 0.05 M CEC conditions. Other reactions at different CEC conditions, or subsequent to enzymatical or specific extractive treatments, suggest PPL appearance is due to PHT uptake by clustered anionic phospholipids, which seem to be involved in mineral precipitation. PPLs present as a novel, reliable ultrastructural parameter indicating cell propensity in priming experimental and, possibly, pathological calcification.

[Human olfactory mucosa biopsy with endoscopic technique: clinical and structural observations on neurosensory epithelium rearrangement]. / Biopsia di mucosa olfattiva con tecnica endoscopica: rilievi clinici e osservazioni strutturali sul rinnovamento tissutale.

Optical and electron microscopy have been widely used to study the structural features of olfactory epithelium in several Vertebrate species. To date, however, understanding of histopathological alterations in the human olfactory neuroepithelium has been quite limited due to the difficulty in obtaining well preserved, intact fragments of mucosa. The recent introduction of endoscopic biopsy techniques has made it possible to analyze this epithelium in greater detail. In the present work, endoscopic biopsy has been performed on samples from 10 rhinologically healthy subjects. The technique used proved quite simple and did not present any risks or complications. Moreover, all samples were well preserved, as confirmed by histology. In addition, the histological pictures suggest that normal rearrangement of neuroepithelium is not an uniform process but takes place following a zone pattern with distinct dynamics between neurosensorial and support cells. Greater diffusion of this technique would not only make it possible to use different techniques to gain more detailed knowledge of tissue structure, ultrastructure and dynamics in human neuroepithelium, but it would also provide improved diagnostic and forensic evaluation in cases of anosmia, disosmia and hyposmia.

A model for type II collagen fibrils: distinctive D-band patterns in native and reconstituted fibrils compared with sequence data for helix and telopeptide domains.

The periodical D-band pattern is generally considered a unique ultrastructural feature shared by all fibril-forming collagens, which correlates with the intrafibril, paracrystalline array of tropocollagen monomers. Distinct band patterns have been reported, however, for collagen stained long-spacing (SLS) crystallites of genetic types I, II, and III. Moreover, D-band patterns of negatively stained, native type II collagen fibrils were found to be not identical to those of type I in our previous research. Because of (a) these distinctive features, (b) tropocollagen heterotrimeric conditions (type I) vs homotrimeric conditions (type II), and (c) different lengths and poor homology between extrahelical telopeptides, the molecular array or telopeptide conformation within the extensively studied type I collagen fibrils could be not the same as those in the very much less intensively studied type II collagen fibrils. In this investigation, a distinctive positive-staining D-band pattern was found for type II collagen fibrils obtained from human cartilages. A fibril model was developed by analyzing actual D-band patterns, and matching them against simulated patterns based on the primary structure of extrahelical and helical domains in human type II tropocollagen. In particular, a more prominent b(1) band was apparent in native type II collagen fibrils than in type I. This distinctive feature was also observed for native-type collagen fibrils reconstituted from purified type II collagen, i.e., free from associated minor type XI collagen. On modeling possible monomer arrays, the best fit between microdensitograms and simulation traces was found for 234 amino acid staggering, as is also the case for type I collagen fibrils. On comparing this model with an analogous one for type I collagen fibrils, there was a higher intraband distribution of charged residues for band b(1), consistent with the higher electrondensity observed for this band in type II collagen fibrils. N- and C-telopeptide displacement in the model corresponded to D-locations of a c(2) subband, which we named c(2.0), and band a(3), respectively. In simulation profiles, c(2.0) -like and a(3) -like peaks mimicked the corresponding peaks in microdensitograms when molecular reversals were adopted at positions 10N-12N, 12C-14C, and 17C-19C for N- and C-telopeptides. Hydrophobic interactions and algorithmic predictions of protein secondary structure, according to Chou and Fasman and Rost and Sander criteria, were consistent with these conformational models, and suggest that an additional molecular reversal may occur at positions 3N-5N. These telopeptide "S-fold" conformations, interpreted as axial projections of tridimensional conformation, may represent starting points for further investigation into the still unresolved tridimensional conformation of telopeptides in monomers arrayed within type II collagen fibrils.

The sacrospinous vaginal vault suspension: Critical analysis of outcomes.

One hundred and three women with a preoperative diagnosis of a pelvic support defect underwent right sacrospinous fixation of the vaginal apex. The procedure was performed either therapeutically (in 63 subjects with vaginal vault eversion) or prophylactically (40 patients with severe uterovaginal prolapse), and was associated with other reconstructive procedures to repair the coexisting cystocele, enterocele or rectocele. Preoperative and postoperative assessments of each vaginal site were compared and the results in the cure of stress urinary incontinence, if present, were evaluated with regard to the type of surgery performed. The overall rate of satisfactory results in the repair of the superior vaginal defect was 94%, and good anatomic results were achieved in the repair of either enterocele or rectocele. Conversely, the repair of the anterior vaginal wall was not as good as in the posterior and superior vaginal sites. Stress urinary incontinence was successfully managed in 72% of the women using different anti-incontinence procedures.

Dietary habits, reproductive and menstrual factors and risk of dysmenorrhoea.

In order to analyze risk factors for dysmenorrhoea, we conducted a case-control study. Cases were 106 women (median age 27 years) with moderate or severe dysmenorrhoea lasting 12 months or more. Controls were 145 women (median age 26 years) without dysmenorrhoea, admitted for routine gynecological examination at the outpatient gynecological services of the same clinic where cases had been identified. In comparison with women reporting short menstrual cycles (every 25 days or less) the relative risk (RR) of dysmenorrhoea was 2.0 and 2.6, respectively, in those reporting their menstrual cycles of 26-30 days and of 31 days or more, and the RR was 3.6 (95% confidence interval (CI): 1.0-13.4) for women reporting totally irregular menstrual cycles. The estimated RRs were, in comparison with women reporting menstrual flows lasting 4 days or less, respectively 2.2 and 1.9 in those reporting menstrual flows lasting 5 and 6 days or more. Fourty-four (58%) cases but only seven (5%) controls reported heavy menstrual flows (RR in comparison with women reporting slight or normal menstrual flow 12.6, 95% CI: 5.0-32.1). As regards dietary factors, no associations emerged between the various food items, with the exception of cheese and eggs, which tended to be more frequently consumed by cases than controls. The results of this study suggest that the risk of dysmenorrhoea is higher in women with irregular, long and heavy menstrual flows. No association emerged between reproductive history and dysmenorrhoea. Likewise, no clear relationship emerged between intake of several dietary factors and risk dysmenorrhoea.

Superovulation and intrauterine insemination vs. superovulation alone in the treatment of unexplained infertility. A randomized study.

OBJECTIVE: To assess whether intrauterine insemination (IUI) improves the fertility rates in women with unexplained infertility. STUDY DESIGN: We recruited 68 women with unexplained infertility and allocated them randomly to treatment with three to five cycles of superovulation plus IUI (36 patients) or superovulation alone (32 patients). Superovulation was obtained with clomiphene citrate, human menopausal gonadotropins and human chorionic gonadotropins. RESULTS: The cycle fecundity rate was 10% in patients who underwent superovulation alone and 19% in those treated with superovulation plus IUI (P < .05). CONCLUSION: Our results demonstrate that superovulation plus IUI is more effective than superovulation alone in the treatment of unexplained infertility.

Residual uterine septum of less than 1 cm after hysteroscopic metroplasty does not impair reproductive outcome.

The objective of this study was to ascertain if incomplete correction leaving a residual uterine septum of < or = 1 cm affects fertility outcome. Reproductive outcome in 17 women with a residual septum of between 0.5 cm and 1 cm after hysteroscopic metroplasty was compared to that in 51 women with no residual septum or one of < 0.5 cm. Septal lysis was performed with microscissors or resectoscope. One month after operative hysteroscopy, abdominal ultrasonography was performed on all the women and those with a residual septum of > 1 cm then underwent a second operative hysteroscopy to complete the lysis. The cumulative pregnancy and birth rates were calculated and the curves compared using the log-rank test. The cumulative 18 month probability of becoming pregnant was 44.5% in the patients with residual septum and 52.7% in those with no residual septum (not significantly different), and the cumulative 18 month probability of giving birth to a child was 27.5 and 36% respectively (also not significant). The presence of a residual uterine septum of between 0.5 and 1 cm as shown by ultrasonography appears not to worsen the reproductive prognosis compared with that in women in whom the septum has been completely or almost completely corrected.