Low concentrations of carbon monoxide (CO) can protect tissues against ischemia–reperfusion (I–R) injury. We have recently identified a novel class of compounds, CO-releasing molecules (CO-RMs), ...which exert important pharmacological activities by carrying and delivering CO to biological systems. Here, we examined the possible beneficial effects of CO liberated from CO-RMs on the damage inflicted by cold storage and I–R in isolated perfused kidneys. Hemodynamic and biochemical parameters as well as mitochondrial respiration were measured in isolated perfused rabbit kidneys that were previously flushed with CO-RMs and stored at 4°C for 24 h. Two water-soluble CO-RMs were tested: (1) sodium boranocarbonate (CORM-A1), a boron-containing carbonate that releases CO at a slow rate, and (2) tricarbonylchloro(glycinato)ruthenium(II) (CORM-3), a transition metal carbonyl that liberates CO very rapidly in solution. Kidneys flushed with Celsior solution supplemented with CO-RMs (50 μM) and stored at 4°C for 24 h displayed at reperfusion a significantly higher perfusion flow rate (PFR), glomerular filtration rate, and sodium and glucose reabsorption rates compared to control kidneys flushed with Celsior solution alone. Addition of 1H-1,2,4oxadiazolo4,3-alphaquinoxalin-1-one (ODQ), a guanylate cyclase inhibitor, prevented the increase in PFR mediated by CO-RMs. The respiratory control index from kidney mitochondria treated with CO-RMs was also markedly increased. Notably, renal protection was lost when kidneys were flushed with Celsior containing an inactive compound (iCO-RM), which had been deliberately depleted of CO. CO-RMs are effective therapeutic agents that deliver CO during kidney cold preservation and can be used to ameliorate vascular activity, energy metabolism and renal function at reperfusion.
Obesity hypoventilation and obstructive sleep apnea are common complications of obesity linked to defects in respiratory pump and upper airway neural control. Leptin-deficient ob/ob mice have ...impaired ventilatory control and inspiratory flow limitation during sleep, which are both reversed with leptin. We aimed to localize central nervous system (CNS) site(s) of leptin action on respiratory and upper airway neuroventilatory control.
We localized the effect of leptin to medulla versus hypothalamus by administering intracerbroventricular leptin (10 μg/2 μL) versus vehicle to the lateral (n = 14) versus fourth ventricle (n = 11) of ob/ob mice followed by polysomnographic recording. Analyses were stratified for effects on respiratory (nonflow-limited breaths) and upper airway (inspiratory flow limitation) functions. CNS loci were identified by (1) leptin-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation and (2) projections of respiratory and upper airway motoneurons with a retrograde transsynaptic tracer (pseudorabies virus).
Both routes of leptin administration increased minute ventilation during nonflow-limited breathing in sleep. Phrenic motoneurons were synaptically coupled to the nucleus of the solitary tract, which also showed STAT3 phosphorylation, but not to the hypothalamus. Inspiratory flow limitation and obstructive hypopneas were attenuated by leptin administration to the lateral but not to the fourth cerebral ventricle. Upper airway motoneurons were synaptically coupled with the dorsomedial hypothalamus, which exhibited STAT3 phosphorylation.
Leptin relieves upper airway obstruction in sleep apnea by activating the forebrain, possibly in the dorsomedial hypothalamus. In contrast, leptin upregulates ventilatory control through hindbrain sites of action, possibly in the nucleus of the solitary tract.
Although epidemiological cutoff values (ECVs) have been established for Candida spp. and the triazoles, they are based on MIC data from a single laboratory. We have established ECVs for eight Candida ...species and fluconazole, posaconazole, and voriconazole based on wild-type (WT) MIC distributions for isolates of C. albicans (n=11,241 isolates), C. glabrata (7,538), C. parapsilosis (6,023), C. tropicalis (3,748), C. krusei (1,073), C. lusitaniae (574), C. guilliermondii (373), and C. dubliniensis (162). The 24-h CLSI broth microdilution MICs were collated from multiple laboratories (in Canada, Brazil, Europe, Mexico, Peru, and the United States). The ECVs for distributions originating from ≥6 laboratories, which included ≥95% of the modeled WT population, for fluconazole, posaconazole, and voriconazole were, respectively, 0.5, 0.06 and 0.03 μg/ml for C. albicans, 0.5, 0.25, and 0.03 μg/ml for C. dubliniensis, 8, 1, and 0.25 μg/ml for C. glabrata, 8, 0.5, and 0.12 μg/ml for C. guilliermondii, 32, 0.5, and 0.25 μg/ml for C. krusei, 1, 0.06, and 0.06 μg/ml for C. lusitaniae, 1, 0.25, and 0.03 μg/ml for C. parapsilosis, and 1, 0.12, and 0.06 μg/ml for C. tropicalis. The low number of MICs (<100) for other less prevalent species (C. famata, C. kefyr, C. orthopsilosis, C. rugosa) precluded ECV definition, but their MIC distributions are documented. Evaluation of our ECVs for some species/agent combinations using published individual MICs for 136 isolates (harboring mutations in or upregulation of ERG11, MDR1, CDR1, or CDR2) and 64 WT isolates indicated that our ECVs may be useful in distinguishing WT from non-WT isolates.
Little information is available on the prevalence and determinants of valvular regurgitation in the general population. This study sought to assess the prevalence and clinical determinants of mitral ...(MR), tricuspid (TR), and aortic (AR) regurgitation in a population-based cohort. Color Doppler echocardiography was performed in 1,696 men and 1,893 women (aged 54 ± 10 years) attending a routine examination at the Framingham Study. After excluding technically poor echocardiograms, MR, TR, and AR were qualitatively graded from trace to severe. Multiple logistic regression analysis was used to examine the association of clinical variables with MR and TR (more than or equal to mild severity) and AR (more than or equal to trace severity). MR and TR of more than or equal to mild severity was seen in 19.0% and 14.8% of men and 19.1% and 18.4% of women, respectively, and AR of more than or equal to trace severity in 13.0% of men and 8.5% of women. The clinical determinants of MR were age (odds ratio OR 1.3/9.9 years, 95% confidence interval CI 1.2 to 1.5), hypertension (OR 1.6; 95% CI 1.2 to 2.0), and body mass index (OR 0.8/4.3 kg/m
2; 95% CI 0.7 to 0.9). The determinants of TR were age (OR 1.5/9.9 years; 95% CI 1.3 to 1.7), body mass index (OR 0.7/4.3 kg/m
2; 95% CI 0.6 to 0.8), and female gender (OR 1.2; 95% CI 1.0 to 1.6). The determinants of AR were age (OR 2.3/9.9 years; 95% CI 2.0 to 2.7) and male gender (OR 1.6; 95% CI 1.2 to 2.1). A substantial proportion of healthy men and women had detectable valvular regurgitation by color Doppler echocardiography. These data provide population-based estimates for comparison with patients taking anorectic drugs.
There is robust evidence that sex (biological) and gender (behavioral/social) differences influence hearing loss risk and outcomes. These differences are noted for animals and humans-in the ...occurrence of hearing loss, hearing loss progression, and response to interventions. Nevertheless, many studies have not reported or disaggregated data by sex or gender. This article describes the influence of sex-linked biology (specifically sex-linked hormones) and gender on hearing and hearing interventions, including the role of sex-linked biology and gender in modifying the association between risk factors and hearing loss, and the effects of hearing loss on quality of life and functioning. Most prevalence studies indicate that hearing loss begins earlier and is more common and severe among men than women. Intrinsic sex-linked biological differences in the auditory system may account, in part, for the predominance of hearing loss in males. Sex- and gender-related differences in the effects of noise exposure or cardiovascular disease on the auditory system may help explain some of these differences in the prevalence of hearing loss. Further still, differences in hearing aid use and uptake, and the effects of hearing loss on health may also vary by sex and gender. Recognizing that sex-linked biology and gender are key determinants of hearing health, the present review concludes by emphasizing the importance of a well-developed research platform that proactively measures and assesses sex- and gender-related differences in hearing, including in understudied populations. Such research focus is necessary to advance the field of hearing science and benefit all members of society.
The presence of stable color polymorphisms within populations begs the question of how genetic variation is maintained. Consistent variation among populations in coloration, especially when ...correlated with environmental variation, raises questions about whether environmental conditions affect either the fulcrum of those balanced polymorphisms, the plastic expression of coloration, or both. Color patterns in male bluefin killifish provoke both types of questions. Red and yellow morphs are common in all populations. Blue males are more common in tannin‐stained swamps relative to clear springs. Here, we combined crosses with a manipulation of light to explore how genetic variation and phenotypic plasticity shape these patterns. We found that the variation in coloration is attributable mainly to two axes of variation: (1) a red‐yellow axis with yellow being dominant to red, and (2) a blue axis that can override red‐yellow and is controlled by genetics, phenotypic plasticity, and genetic variation for phenotypic plasticity. The variation among populations in plasticity suggests it is adaptive in some populations but not others. The variation among sires in plasticity within the swamp population suggests balancing selection may be acting not only on the red‐yellow polymorphism but also on plasticity for blue coloration.
Stereo videography is a powerful technique for quantifying the kinematics and behavior of animals, but it can be challenging to use in an outdoor field setting. We here present a workflow and ...associated software for performing calibration of cameras placed in a field setting and estimating the accuracy of the resulting stereoscopic reconstructions. We demonstrate the workflow through example stereoscopic reconstructions of bat and bird flight. We provide software tools for planning experiments and processing the resulting calibrations that other researchers may use to calibrate their own cameras. Our field protocol can be deployed in a single afternoon, requiring only short video clips of light, portable calibration objects.
An emerging literature suggests that sleep may play an important role in moderating the association between discrimination and mental health problems among adolescents. However, few if any studies ...have considered this topic among adults. Addressing this knowledge gap, the current study examined multiple sleep parameters as moderating variables in the association between discrimination and mental health problems among adults.
Participants were 874 adults residing in small towns and semirural contexts within the Southeastern region of the United States ( Mage = 41 years, SD = 7; 57% female; 31% Black, 69% White; 52% income-to-needs < 2). Sleep duration and night-to-night variability in duration were assessed using wrist actigraphy. Established self-report measures were used to assess global sleep problems, experiences of discrimination, and mental health problems (anxiety, depression, and externalizing symptoms).
Experiences of discrimination were associated with more depression, anxiety, and externalizing problems. Two out of three sleep parameters were found to moderate the effects of discrimination on mental health. The association between discrimination and externalizing problems (but not anxiety or depression) was attenuated among those with less night-to-night variability in sleep duration. The associations between discrimination and anxiety and externalizing problems (but not depression) were attenuated among those with fewer global sleep problems. Less variability in sleep duration and fewer global sleep problems were also directly associated with lower levels of depression, anxiety, and externalizing problems.
Greater consistency in sleep duration from night-to-night, and fewer overall sleep problems appear to mitigate risk of mental health problems among adults, particularly in contexts where discrimination is prevalent.
To examine social class discrimination as a mediator of socioeconomic disparities in sleep outcomes in an adolescent sample.
Sleep was assessed from established actigraphy (efficiency, long wake ...episodes, duration) and self-report (sleep/wake problems, daytime sleepiness) measures among 272 high school students in the Southeastern region of the United States (35% low income; 59% White, 41% Black, 49% female, Mean age = 17.3, SD = 0.8). Social class discrimination was assessed using a new measure, the Social Class Discrimination Scale (SCDS; 22-items), and an established measure, the Experiences of Discrimination Scale (EODS; 7-items). Socioeconomic disadvantage (SED) was measured as an aggregate of six indicators.
The SCDS was associated with sleep efficiency, long wake episodes, sleep/wake problems and daytime sleepiness (but not sleep duration), and significantly mediated the socioeconomic gradient in each sleep outcome. Black males experienced higher levels of social class discrimination than Black females, White males, or White females. A race by gender moderation effect was evident for two of the five sleep outcomes (sleep efficiency and long wake episodes) suggesting a stronger association between social class discrimination and sleep problems for Black females than White females but no clear race differences among males. The EODS was not associated with objective sleep outcomes or SED but was associated with self-reported sleep and showed a similar pattern of moderation effects.
Findings suggest that social class discrimination may contribute to socioeconomic disparities in sleep problems, with some variability across measures and demographic groups. Results are discussed in light of evolving trends in socioeconomic health disparities.
•Socioeconomically disadvantaged adolescents had poorer sleep.•Social class discrimination was linked to worse actigraphy-assessed sleep quality.•Social class discrimination predicted more self-reported sleep problems.•Social class discrimination partially explained socioeconomic disparities in sleep.
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