Recurrence of keratoconus characteristics: a clinical and histologic follow-up analysis of donor grafts.

PURPOSE: To report on clinical corneal topography, histopathologic analysis, and fine structure findings in failed grafts after penetrating keratoplasty (PK) for keratoconus (KC). DESIGN: Retrospective, consecutive, interventional case series with histologic and clinical correlation. PARTICIPANTS: Twelve corneal buttons were obtained from consecutive patients undergoing repeated PK 10 to 28 years after the initial PK for KC. The indication for regrafting was endothelial deficiency in seven cases, irreversible immune graft rejection in two cases, and corneal ectasia in three cases. METHODS: Removed corneal buttons were examined by light and transmission electron microscopy. A potential correlation between the clinical and videokeratoscopic findings and the microscopic structural observations was analyzed. RESULTS: Preoperative simulated keratometry measured by TMS-1 (Tomey, New York, NY) or EyeSys CAS (EyeSys Technology, Houston, TX) ranged from 49.8 to 66.1 diopters. A pattern compatible with KC characteristics was observed in all cases. Fine structure analysis revealed Bowman's layer disruption or folds and stromal deposits in all corneal buttons. However, central corneal thinning was not present in any of the removed buttons. CONCLUSIONS: Structure changes compatible with the diagnosis of KC were observed in all donor buttons many years after PK on KC recipients. Recurrence of the KC characteristics may result from graft repopulation by recipients' keratocytes, aging of the grafted tissue, or both.

The predation cost of being a male: implications for sex-specific rates of ageing

Evolutionary theory predicts that the rate of extrinsic (i.e. age- and condition-independent) mortality should affect important life history traits such as the rate of ageing and maximum lifespan. Sex-specific differences in mortality rates due to predation may therefore result in the evolution of important differences in life history traits between males and females. However, quantifying the role of predators as a factor of extrinsic mortality is notoriously difficult in natural populations. We took advantage of the unusual prey caching behaviour of the barn owl Tyto alba and the tawny owl Strix aluco to estimate the sex ratio of their five most common preys. For all prey species, there was a significant bias in the sex ratio of remains found in nests of both these owls. A survey of literature revealed that sex-biased predation is a common phenomenon. These results demonstrate that predation, a chief source of extrinsic mortality, was strongly sex-biased. This may select for alternate life history strategies between males and females, and account for a male life span being frequently lower than female lifespan in many animal species.

Sex steroids and gender differences in nonmuscle invasive bladder cancer.

PURPOSE OF REVIEW: To review and summarize current knowledge on gender differences and sex steroid hormones in nonmuscle invasive bladder cancer. RECENT FINDINGS: Beyond the proven role of gender as a risk factor for the development of bladder cancer, recent studies indicate that women present with more advanced bladder cancer tumor stages than men, which may be due to differences in both bladder cancer care and biology. In addition, female gender has been identified as an independent prognostic factor for both recurrence and progression and may be associated with worse response to Bacillus Calmette-Guérin instillation therapy. Overall, sex steroid hormones and their receptors impact bladder carcinogenesis, recurrence and progression. Basic and transitional research evidence suggests that estrogens may initially protect against bladder cancer development, but later promote bladder cancer progression. Androgens, in contrast, seem to initiate and drive bladder cancer with its receptor playing a central role. Promising novel research shows a potential role of sex steroid hormones as therapeutic targets. SUMMARY: Whereas men are more likely to develop bladder cancer, women present generally with more advanced disease and have worse oncologic outcomes even after adjusting for tumor stage. Sex steroid hormones and their receptors play an active role in bladder cancer development and progression and represent attractive therapeutic targets for gender-specific care.

Genetic clusters and sex-biased gene flow in a unicolonial Formica ant.

BACKGROUND: Animal societies are diverse, ranging from small family-based groups to extraordinarily large social networks in which many unrelated individuals interact. At the extreme of this continuum, some ant species form unicolonial populations in which workers and queens can move among multiple interconnected nests without eliciting aggression. Although unicoloniality has been mostly studied in invasive ants, it also occurs in some native non-invasive species. Unicoloniality is commonly associated with very high queen number, which may result in levels of relatedness among nestmates being so low as to raise the question of the maintenance of altruism by kin selection in such systems. However, the actual relatedness among cooperating individuals critically depends on effective dispersal and the ensuing pattern of genetic structuring. In order to better understand the evolution of unicoloniality in native non-invasive ants, we investigated the fine-scale population genetic structure and gene flow in three unicolonial populations of the wood ant F. paralugubris. RESULTS: The analysis of geo-referenced microsatellite genotypes and mitochondrial haplotypes revealed the presence of cryptic clusters of genetically-differentiated nests in the three populations of F. paralugubris. Because of this spatial genetic heterogeneity, members of the same clusters were moderately but significantly related. The comparison of nuclear (microsatellite) and mitochondrial differentiation indicated that effective gene flow was male-biased in all populations. CONCLUSION: The three unicolonial populations exhibited male-biased and mostly local gene flow. The high number of queens per nest, exchanges among neighbouring nests and restricted long-distance gene flow resulted in large clusters of genetically similar nests. The positive relatedness among clustermates suggests that kin selection may still contribute to the maintenance of altruism in unicolonial populations if competition occurs among clusters.

MsrR contributes to cell surface characteristics and virulence in Staphylococcus aureus.

MsrR, a factor contributing to methicillin resistance in Staphylococcus aureus, belongs to the LytR-CpsA-Psr family of cell envelope-associated proteins. Deletion of msrR increased cell size and aggregation, and altered envelope properties, leading to a temporary reduction in cell surface hydrophobicity, diminished colony-spreading ability, and an increased susceptibility to Congo red. The reduced phosphorus content of purified cell walls of the msrR mutant suggested a reduction in wall teichoic acids, which may explain some of the observed phenotypes. Microarray analysis of the msrR deletion mutant revealed only minor changes in the global transcriptome, suggesting that MsrR has structural rather than regulatory functions. Importantly, virulence of the msrR mutant was decreased in a nematode-killing assay as well as in rat experimental endocarditis. MsrR is therefore likely to play a role in cell envelope maintenance, cell separation, and pathogenicity of S. aureus.

Characteristics of eyes with secondary loss of visual acuity receiving variable dosing ranibizumab for neovascular age-related macular degeneration.

PURPOSE: The aim of this work is to investigate the characteristics of eyes failing to maintain visual acuity (VA) receiving variable dosing ranibizumab for neovascular age-related macular degeneration (nAMD) after three initial loading doses. METHODS: A consecutive series of patients with nAMD, who, after three loading doses of intravitreal ranibizumab (0.5 mg each), were re-treated for fluid seen on optical coherence tomography. After exclusion of eyes with previous treatment, follow-up less than 12 months, or missed visits, 99 patients were included in the analysis. The influence of baseline characteristics, initial VA response, and central retinal thickness (CRT) fluctuations on the VA stability from month 3 to month 24 were analyzed using subgroups and multiple regression analyses. RESULTS: Mean follow-up duration was 21.3 months (range 12-40 months, 32 patients followed-up for ≥24 months). Secondary loss of VA (loss of five letters or more) after month 3 was seen in 30 patients (mean VA improvement from baseline +5.8 letters at month 3, mean loss from baseline -5.3 letters at month 12 and -9.7 at final visit up to month 24), while 69 patients maintained vision (mean gain +8.9 letters at month 3, +10.4 letters at month 12, and +12.8 letters at final visit up to month 24). Secondary loss of VA was associated with the presence of pigment epithelial detachment (PED) at baseline (p 0.01), but not with baseline fibrosis/atrophy/hemorrhage, CRT fluctuations, or initial VA response. Chart analysis revealed additional individual explanations for the secondary loss of VA, including retinal pigment epithelial tears, progressive fibrosis, and atrophy. CONCLUSIONS: Tissue damage due to degeneration of PED, retinal pigment epithelial tears, progressive fibrosis, progressive atrophy, or massive hemorrhage, appears to be relevant in causing secondary loss of VA despite vascular endothelial growth factor suppression. PED at baseline may represent a risk factor.

Music and felt emotions: how systematic pitch level variations affect the experience of pleasantness and arousal

Pitch is a fundamental musical factor; however, findings about its contribution to the elicitation of emotions are contradictory. The purpose of this work was to assess the effect of systematic pitch variations on self-reports of felt valence and arousal. In a within-subject design, 49 subjects listened to four 1-minute classical piano excerpts, each presented at three different pitch levels (one octave lower than the original version, the original version and one octave higher than the original version). Compared to excerpts both without octave modification and in the +1 octave variant, pleasantness of excerpts in the -1 octave variant was significantly lower. This main effect was stronger for women than men and, importantly, was modulated by the specific characteristics of the stimuli. There was also a significant, yet smaller, negative relationship between pitch level and arousal, moderated by gender: Compared to higher pitch, lower pitch was associated with higher arousal in men only. Regarding the complex outcomes of this study, future studies should investigate to which extent our findings can be generalized to other musical works. The ultimate goal might be to demonstrate how pitch level interacts with other musical features and listeners' characteristics in eliciting diverse affective experiences.

Effects of ploidy and sex-locus genotype on gene expression patterns in the fire ant Solenopsis invicta.

Males in many animal species differ greatly from females in morphology, physiology and behaviour. Ants, bees and wasps have a haplodiploid mechanism of sex determination whereby unfertilized eggs become males while fertilized eggs become females. However, many species also have a low frequency of diploid males, which are thought to develop from diploid eggs when individuals are homozygous at one or more sex determination loci. Diploid males are morphologically similar to haploids, though often larger and typically sterile. To determine how ploidy level and sex-locus genotype affect gene expression during development, we compared expression patterns between diploid males, haploid males and females (queens) at three developmental timepoints in Solenopsis invicta. In pupae, gene expression profiles of diploid males were very different from those of haploid males but nearly identical to those of queens. An unexpected shift in expression patterns emerged soon after adult eclosion, with diploid male patterns diverging from those of queens to resemble those of haploid males, a pattern retained in older adults. The finding that ploidy level effects on early gene expression override sex effects (including genes implicated in sperm production and pheromone production/perception) may explain diploid male sterility and lack of worker discrimination against them during development.

Coronary arteriography rates in Switzerland: how do they vary?

Coronary heart disease is a leading cause of death for both sexes in developed countries. Controversy has arisen about the health benefits and risks of coronary surgery and, more recently of coronary angioplasty. As a clinical prerequisite to these interventions, coronary arteriography can be considered an indicator of invasive services offered to coronary heart disease patients. We collected data on characteristics of all patients subjected to coronary arteriography during 1984 in Switzerland. A total of 4921 coronary arteriographies were performed among 4359 patients; this corresponds to 77 procedures/100,000 residents and 68 patients/100,000 residents. Rates for men are 4.2 times women's rates, and the highest utilization rate for both sexes are observed in the group aged 40-64. Large variations characterize cantonal and regional coronary arteriography rates. Similarly, the distribution of centers practising this procedure is not uniform. These observations are placed in the context of the general practice of coronary angiography, changes expected in the face of by-pass surgery and angioplasty expansion, and coronary heart disease data.

Polymorphism at a sex-linked transcription cofactor in European tree frogs (Hyla arborea): Sex-antagonistic selection or neutral processes?

Nascent sex chromosomes offer a unique opportunity to investigate the evolutionary fate of genesrecently trapped in non-recombining segments. A housekeeping gene (MED15) was recently shown to lie on the nascent sex-chromosomes of the European tree frog (Hyla arborea), with different alleles fixed on the X and the Y chromosomes. Here we document a polymorphism (glutamine deletion) in the X copy of the gene, and use population surveys and experimental crosses to test whether this polymorphism is neutral or maintained by sex-antagonistic selection. Tadpoles from parents of known genotypes revealed significant discrepancies from Mendelian inheritance, suggesting possible sex-antagonistic effects under laboratory conditions. Quantitatively, however, these effects did not meet the conditions for polymorphism maintenance. Furthermore, field estimates of female genotypic frequencies did not differ from Hardy-Weinberg equilibrium and allelic frequencies on the X chromosome did not differ between sexes. In conclusion, although sex antagonistic effects cannot be excluded given the laboratory conditions, the X-linked polymorphism under study appears neutral in the wild. Alternatively, sex-antagonistic selection might still account for the fixation of a male specific allele on the Y chromosome.

Low rates of X-Y recombination, not turnovers, account for homomorphic sex chromosomes in several diploid species of Palearctic green toads (Bufo viridis subgroup).

Contrasting with birds and mammals, most ectothermic vertebrates present homomorphic sex chromosomes, which might be due either to a high turnover rate or to occasional X-Y recombination. We tested these two hypotheses in a group of Palearctic green toads that diverged some 3.3 million years ago. Using sibship analyses of sex-linked markers, we show that all four species investigated share the same pair of sex chromosomes and a pattern of male heterogamety with drastically reduced X-Y recombination in males. Phylogenetic analyses of sex-linked sequences show that X and Y alleles cluster by species, not by gametolog. We conclude that X-Y homomorphy and fine-scale sequence similarity in these species do not stem from recent sex-chromosome turnovers, but from occasional X-Y recombination.