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Background:. This study aimed to measure the impact of insurance type on access to pediatric surgical care, clinical and surgical scheduling decisions, provider-driven cancelations, and missed care opportunities (MCOs). We hypothesize that patients with public health insurance experience longer scheduling delays and more frequently canceled surgical appointments compared with patients with private health insurance. Methods:. This retrospective study reviewed the demographics and clinical characteristics of patients who underwent a surgical procedure within the plastic and oral surgery department at our institution in 2019. Propensity score matching and linear regressions were used to estimate the effect of insurance type on hospital scheduling and patient access outcomes while controlling for procedure type and sex. Results:. A total of 457 patients were included in the demographic and clinical characteristics analyses; 354 were included in propensity score matching analyses. No significant differences in the number of days between scheduling and occurrence of initial consultation or number of clinic cancelations were observed between insurance groups (P > 0.05). However, patients with public insurance had a 7.4 times higher hospital MCO rate (95% CI [5.2–9.7]; P < 0.001) and 4.7 times the number of clinic MCOs (P = 0.007). Conclusions:. No significant differences were found between insurance groups in timely access to surgical treatment or cancelations. Patients with public insurance had more MCOs than patients with private insurance. Future research should investigate how to remove barriers that impact access to care for marginalized patients.

Carotid artery stenosis typically causes hemispheric neurologic effects by atheroembolism. Nonhemispheric symptoms, such as syncope, are generally not attributable to extracranial carotid disease. This report describes a 62-year-old woman with severe bilateral carotid artery stenosis, right vertebral artery occlusion, and severe left vertebral artery stenosis who presented with transient loss of consciousness and unilateral weakness when upright. Her symptoms resolved after right carotid endarterectomy. Whereas vertebrobasilar insufficiency alone can cause syncope, in the case of severe multivessel cerebrovascular disease, unilateral carotid revascularization was successful in treating the patient's transient loss of consciousness, suggesting global cerebral hypoperfusion as the cause. Keywords: Carotid stenosis, Vertebrobasilar, Hypoperfusion, Positional

Eukaryotic energy production requires tight coordination between nuclear and mitochondrial gene products. Because males and females often have different energetic strategies, optimal mitonuclear coordination may be sex-specific. Previous work found evidence for sex-specific mitonuclear effects in the copepod Tigriopus californicus by comparing two parental lines and their reciprocal F1 crosses. However, an alternative hypothesis is that the patterns were driven by the parental source of nuclear alleles. Here we test this alternative hypothesis by extending the same cross to F2 hybrids, who receive both maternal and paternal nuclear alleles from F1 hybrids. Results confirm mitonuclear effects on sex ratio, with distorted ratios persisting from the F1 to F2 generations, despite reduced fitness in F2 hybrids. No sex by cross interactions were found for other phenotypic traits measured. Mitochondrial DNA content was higher in females. Both routine metabolic rate and oxidative DNA damage were lower in F2 hybrids than in parentals. The persistence of sex-specific mitonuclear effects, even in the face of F2 hybrid breakdown, attests to the magnitude of these effects, which contribute to the maintenance of within-population mitochondrial DNA polymorphisms., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Evolutionary Biology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Mitochondria perform an array of functions, many of which involve interactions with gene products encoded by the nucleus. These mitochondrial functions, particularly those involving energy production, can be expected to differ between sexes and across ages. Here, we measured mitochondrial effects on sex- and age-specific gene expression in parental and reciprocal F1 hybrids between allopatric populations of Tigriopus californicus with over 20% mitochondrial DNA divergence. Because the species lacks sex chromosomes, sex-biased mitochondrial effects are not confounded by the effects of sex chromosomes. Results revealed pervasive sex differences in mitochondrial effects, including effects on energetics and aging involving nuclear interactions throughout the genome. Using single-individual RNA sequencing, sex differences were found to explain more than 80% of the variance in gene expression. Males had higher expression of mitochondrial genes and mitochondrially targeted proteins (MTPs) involved in oxidative phosphorylation (OXPHOS), while females had elevated expression of non-OXPHOS MTPs, indicating strongly sex-dimorphic energy metabolism at the whole organism level. Comparison of reciprocal F1 hybrids allowed insights into the nature of mito-nuclear interactions, showing both mitochondrial effects on nuclear expression, and nuclear effects on mitochondrial expression. While based on a small set of crosses, sex-specific increases in mitochondrial expression with age were associated with longer life. Network analyses identified nuclear components of strong mito-nuclear interactions and found them to be sexually dimorphic. These results highlight the profound impact of mitochondria and mito-nuclear interactions on sex- and age-specific gene expression., Competing Interests: Competing interests statement:The authors declare no competing interest.

Strict maternal inheritance of mitochondria favours the evolutionary accumulation of sex-biased fitness effects, as mitochondrial evolution occurs exclusively in female lineages. The 'mother's curse' hypothesis proposes that male-harming mutations should accumulate in mitochondrial genomes when they have neutral or beneficial effects on female fitness. Rigorous empirical tests have largely focused on Drosophila , where support for the predictions of mother's curse has been mixed. We investigated the impact of mother's curse mutations in Tigriopus californicus, a minute crustacean. Using non-recombinant backcrosses, we introgressed four divergent mitochondrial haplotypes into two nuclear backgrounds and recorded measures of fertility and longevity. We found that the phenotypic effects of mitochondrial mutations were context dependent, being influenced by the nuclear background in which they were expressed, as well as the sex of the individual and rearing temperature. Mitochondrial haplotype effects were greater for fertility than longevity, and temperature effects were greater for longevity. However, in opposition to mother's curse expectations, females had higher mitochondrial genetic variance than males for fertility and longevity, little evidence of sexual antagonism favouring females was found, and the impacts of mitonuclear mismatch harmed females but not males. Together, this indicates that selection on mitochondrial variation has not resulted in the accumulation of male mutation load in Tigriopus californicus .

As organisms age, cellular function declines in a time-dependent manner. Oxidative stress induced by reactive oxygen species damages cellular machinery and contributes to senescence which narrows the homeostatic window needed to maintain function and survive stress. Sex differences in longevity are apparent in many species and may be related to sex-specific homeostatic responses. Here we use the emerging aging model system Tigriopus californicus, the splashpool copepod, to estimate sex- and age-specific tolerances to two chemical oxidants, hydrogen peroxide and paraquat. Sex-specific tolerance was estimated for both oxidants simultaneously for 15 age-classes. As animals aged, hydrogen peroxide tolerance decreased but paraquat tolerance increased. Also, we observed no sex difference for hydrogen peroxide tolerance, while females were more tolerant of paraquat. Our results demonstrate that oxidative stressors can have dramatically different sex and age effects in Tigriopus californicus. These findings underscore the challenges ahead in understanding relationships among oxidative stressors, sex, and aging., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Long life is standardly assumed to be associated with high stress tolerance. Previous work shows that the copepod Tigriopus californicus breaks this rule, with longer life span under benign conditions found in males, the sex with lower stress tolerance. Here, we extended this previous work, raising animals from the same families in food-replete conditions until adulthood and then transferring them to food-limited conditions until all animals perished. As in previous work, survivorship under food-replete conditions favored males. However, under food deprivation life span strongly favored females in all crosses. Compared to benign conditions, average life span under nutritional stress was reduced by 47% in males but only 32% in females. Further, the sex-specific mitonuclear effects previously found under benign conditions were erased under food limited conditions. Results thus demonstrate that sex-specific life span, including mitonuclear interactions, are highly dependent on nutritional environment., Competing Interests: All authors declare no competing interests., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Impaired mitochondrial function can lead to senescence and the ageing phenotype. Theory predicts degenerative ageing phenotypes and mitochondrial pathologies may occur more frequently in males due to the matrilineal inheritance pattern of mitochondrial DNA observed in most eukaryotes. Here, we estimated the sex-specific longevity for parental and reciprocal F1 hybrid crosses for inbred lines derived from two allopatric Tigriopus californicus populations with over 20% mitochondrial DNA divergence. T. californicus lacks sex chromosomes allowing for more direct testing of mitochondrial function in sex-specific ageing. To better understand the ageing mechanism, we estimated two age-related phenotypes (mtDNA content and 8-hydroxy-20-deoxyguanosine (8-OH-dG) DNA damage) at two time points in the lifespan. Sex differences in lifespan depended on the mitochondrial and nuclear backgrounds, including differences between reciprocal F1 crosses which have different mitochondrial haplotypes on a 50 : 50 nuclear background, with nuclear contributions coming from alternative parents. Young females showed the highest mtDNA content which decreased with age, while DNA damage in males increased with age and exceed that of females 56 days after hatching. The adult sex ratio was male-biased and was attributed to complex mitonuclear interactions. Results thus demonstrate that sex differences in ageing depend on mitonuclear interactions in the absence of sex chromosomes.

The genomic variation of an invasive species may be affected by complex demographic histories and evolutionary changes during the invasion. Here, we describe the relative influence of bottlenecks, clonality, and population expansion in determining genomic variability of the widespread red macroalga Agarophyton vermiculophyllum. Its introduction from mainland Japan to the estuaries of North America and Europe coincided with shifts from predominantly sexual to partially clonal reproduction and rapid adaptive evolution. A survey of 62,285 SNPs for 351 individuals from 35 populations, aligned to 24 chromosome-length scaffolds indicate that linkage disequilibrium (LD), observed heterozygosity (H o ), Tajima's D, and nucleotide diversity (Pi) were greater among non-native than native populations. Evolutionary simulations indicate LD and Tajima's D were consistent with a severe population bottleneck. Also, the increased rate of clonal reproduction in the non-native range could not have produced the observed patterns by itself but may have magnified the bottleneck effect on LD. Elevated marker diversity in the genetic source populations could have contributed to the increased H o and Pi observed in the non-native range. We refined the previous invasion source region to a ~50 km section of northeastern Honshu Island. Outlier detection methods failed to reveal any consistently differentiated loci shared among invaded regions, probably because of the complex A. vermiculophyllum demographic history. Our results reinforce the importance of demographic history, specifically founder effects, in driving genomic variation of invasive populations, even when localized adaptive evolution and reproductive system shifts are observed., (© 2021 John Wiley & Sons Ltd.)

For many taxa, including isomorphic haplodiplontic macroalgae, determining sex and ploidy is challenging, thereby limiting the scope of some population demographic and genetic studies. Here, we used double-digest restriction site-associated DNA sequencing (ddRAD-seq) to identify sex-linked molecular markers in the widespread red alga Agarophyton vermiculophyllum. In the ddRAD-seq library, we included 10 female gametophytes, 10 male gametophytes, and 16 tetrasporophytes from one native and one non-native site (N = 40 gametophytes and N = 32 tetrasporophytes total). We identified seven putatively female-linked and 19 putatively male-linked sequences. Four female- and eight male-linked markers amplified in all three life cycle stages. Using one female- and one male-linked marker that were sex-specific, we developed a duplex PCR and tested the efficacy of this assay on a subset of thalli sampled at two sites in the non-native range. We confirmed ploidy based on the visual observation of reproductive structures and previous microsatellite genotyping at 10 polymorphic loci. For 32 vegetative thalli, we were able to assign sex and confirm ploidy in these previously genotyped thalli. These markers will be integral to ongoing studies of A. vermiculophyllum invasion. We discuss the utility of RAD-seq over other approaches previously used, such as RAPDs (random amplified polymorphic DNA), for future work designing sex-linked markers in other haplodiplontic macroalgae for which genomes are lacking., (© 2020 Phycological Society of America.)

Background: Patterns of gene expression can be dramatically different between males and females of the same species, in part due to genes on sex chromosomes. Here we test for sex differences in early transcriptomic response to oxidative stress in a species which lacks heteromorphic sex chromosomes, the copepod Tigriopus californicus., Results: Male and female individuals were separately exposed to control conditions and pro-oxidant conditions (hydrogen peroxide and paraquat) for periods of 3 hours and 6 hours. Variance partitioning showed the greatest expression variance among individuals, highlighting the important information that can be obscured by the common practice of pooling individuals. Gene expression variance between sexes was greater than that among treatments, showing the profound effect of sex even when males and females share the same genome. Males exhibited a larger response to both pro-oxidants, differentially expressing more than four times as many genes, including up-regulation of more antioxidant genes, heat shock proteins and protease genes. While females differentially expressed fewer genes, the magnitudes of fold change were generally greater, indicating a more targeted response. Although females shared a smaller fraction of differentially expressed genes between stressors and time points, expression patterns of antioxidant and protease genes were more similar between stressors and more GO terms were shared between time points., Conclusions: Early transcriptomic responses to the pro-oxidants H 2 O 2 and paraquat in copepods revealed substantial variation among individuals and between sexes. The finding of such profound sex differences in oxidative stress response, even in the absence of sex chromosomes, highlights the importance of studying both sexes and the potential for developing sex-specific strategies to promote optimal health and aging in humans.

The rapid evolution of non-native species can facilitate invasion success, but recent reviews indicate that such microevolution rarely yields expansion of the climatic niche in the introduced habitats. However, because some invasions originate from a geographically restricted portion of the native species range and its climatic niche, it is possible that the frequency, direction, and magnitude of phenotypic evolution during invasion have been underestimated. We explored the utility of niche shift analyses in the red seaweed Gracilaria vermiculophylla , which expanded its range from the northeastern coastline of Japan to North America, Europe, and northwestern Africa within the last 100 years. A genetically informed climatic niche shift analysis indicates that native source populations occur in colder and highly seasonal habitats, while most non-native populations typically occur in warmer, less seasonal habitats. This climatic niche expansion predicts that non-native populations evolved greater tolerance for elevated heat conditions relative to native source populations. We assayed 935 field-collected and 325 common-garden thalli from 40 locations, and as predicted, non-native populations had greater tolerance for ecologically relevant extreme heat (40°C) than did Japanese source populations. Non-native populations also had greater tolerance for cold and low-salinity stresses relative to source populations. The importance of local adaptation to warm temperatures during invasion was reinforced by evolution of parallel clines: Populations from warmer, lower-latitude estuaries had greater heat tolerance than did populations from colder, higher-latitude estuaries in both Japan and eastern North America. We conclude that rapid evolution plays an important role in facilitating the invasion success of this and perhaps other non-native marine species. Genetically informed ecological niche analyses readily generate clear predictions of phenotypic shifts during invasions and may help to resolve debate over the frequency of niche conservatism versus rapid adaptation during invasion.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant disorder. The disease has been formally characterized with epistaxis, cutaneous and mucosal telangiectases, a first-degree relative with HHT, and visceral lesions such as arteriovenous malformations (AVMs). Hereditary hemorrhagic telangiectasia has been underreported for many years. Wider recognition of this disorder in recent years has prompted researchers and physicians to recognize milder cases and focus on earlier treatment. This article highlights different treatments used to control epistaxis and screen for other complications associated with HHT.