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Recessive X-linked ichthyosis (RXLI), a genetic disorder caused by deletion or point mutations of the steroid sulfatase (STS) gene, is the second most common form of ichthyosis. It is a disorder of keratinocyte cholesterol sulfate retention and the mechanism of extracutaneous phenotypes such as corneal opacities and attention deficit hyperactivity disorder are poorly understood. To understand the pathomechanisms of RXLI, the transcriptome of differentiated primary keratinocytes with STS knockdown was sequenced. The results were validated in a stable knockdown model of STS, to confirm STS specificity, and in RXLI skin. The results show that there was significantly reduced expression of genes related to epidermal differentiation and lipid metabolism, including ceramide and sphingolipid synthesis. In addition, there was significant downregulation of aldehyde dehydrogenase family members and the oxytocin receptor which have been linked to corneal transparency and behavioural disorders respectively, both of which are extracutaneous phenotypes of RXLI. These data provide a greater understanding of the causative mechanisms of RXLI’s cutaneous phenotype, and show that the keratinocyte transcriptome and lipidomics can give novel insights into the phenotype of patients with RXLI.

Competing Interests: The authors report no conflicts of interest.

Purpose: Neurogenic orthostatic hypotension (nOH) is the hallmark of neurodegenerative forms of autonomic failure, including pure autonomic failure, multiple system atrophy, and Parkinson's disease. Studies have shown autonomic physiological differences in Africans Americans (AA) such as lower heart rate variability, enhanced blood pressure reactivity, and blunted sympathetic neural response compared to non-Hispanic whites. However, the clinical characteristics and neurohormonal profile of autonomic failure in AA is unknown., Methods: A total of 65 patients with nOH participated in this study (9 AA and 56 non-Hispanic whites). Both groups were of similar age and comorbidity status, and they underwent standardized autonomic testing and assessment of neurohormonal levels and renin activity and aldosterone in supine and upright positions., Results: There were no significant differences in baseline autonomic clinical characteristics between non-Hispanic whites and AA with nOH. Non-Hispanic whites demonstrated a significant increase in upright renin activity compared to AA (295 ± 88% vs. 13 ± 13%, respectively). AA showed a blunted increase in aldosterone compared to non-Hispanic whites (188 ± 27% vs. 59 ± 38%, respectively). These results indicated persistent suppression of the renin-angiotensin system in AA, particularly during upright posture., Conclusion: Our findings demonstrate that AA with nOH have similar clinical characteristics and hemodynamic autonomic profiles, but lower upright renin activity and aldosterone levels, compared to non-Hispanic whites. Renin suppression persists in AA with severe autonomic failure and can potentially contribute to postural changes and supine hypertension.

This review summarizes the current literature on the epidemiology of orthostatic hypotension (OH) in the elderly and in patients with autonomic impairment also known as neurogenic OH (nOH); these two conditions have distinct pathophysiologies and affect different patient populations. The prevalence of OH in the elderly varies depending on the study population. In community dwellers, OH prevalence is estimated at 16%, whereas in institutionalized patients, it may be as high as 60%. The prevalence of OH increases exponentially with age, particularly in those 75 years and older. Multiple epidemiological studies have identified OH as a risk factor for all-cause mortality and cardiovascular disease including heart failure and stroke. Real-world data from administrative databases found polypharmacy, multiple co-morbid conditions, and high health-care utilization as common characteristics in OH patients. A comprehensive evaluation of medications associated with OH is discussed with particular emphasis on the use of anti-hypertensive therapy from two large clinical trials on high-intensive versus standard blood pressure management. Finally, we also review the epidemiology of nOH based on the underlying neurodegenerative disorder (either Parkinson's disease or multiple system atrophy), and the presence of co-morbid conditions such as hypertension and cognitive impairment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Racial and ethnic differences in cardiovascular morbidity and mortality persist despite advances in risk factor identification and implementation of evidence-based treatment strategies. African American men and women are disproportionately affected by cardiovascular risk factors, particularly hypertension. In this context, previous studies have identified sex and racial differences in autonomic cardiovascular regulation which may contribute to the development of hypertension and its high morbidity burden among African Americans. In this review, we provide a comprehensive evaluation of the potential pathophysiological mechanisms of blood pressure control and their differences based on sex and race. These mechanisms include obesity-induced sympathetic activation, sympatho-vascular transduction, baroreflex sensitivity and adrenoreceptor vascular sensitivity, which have been the subjects of prior investigation in this field. Understanding the racial differences in the pathophysiology of hypertension and its co-morbid conditions would allow us to implement better treatment strategies tailored to African Americans, with the ultimate goal of reducing cardiovascular mortality in this population.

Three key steps in meiosis allow diploid organisms to produce haploid gametes: (1) homologous chromosomes (homologs) pair and undergo crossovers; (2) homologs segregate to opposite poles; and (3) sister chromatids segregate to opposite poles. The XX/XO sex determination system found in many nematodes [1] facilitates the study of meiosis because variation is easily recognized [2-4]. Here we show that meiotic segregation of X chromosomes in the trioecious nematode Auanema rhodensis [5] varies according to sex (hermaphrodite, female, or male) and type of gametogenesis (oogenesis or spermatogenesis). In this species, XO males exclusively produce X-bearing sperm [6, 7]. The unpaired X precociously separates into sister chromatids, which co-segregate with the autosome set to generate a functional haplo-X sperm. The other set of autosomes is discarded into a residual body. Here we explore the X chromosome behavior in female and hermaphrodite meioses. Whereas X chromosomes segregate following the canonical pattern during XX female oogenesis to yield haplo-X oocytes, during XX hermaphrodite oogenesis they segregate to the first polar body to yield nullo-X oocytes. Thus, crosses between XX hermaphrodites and males yield exclusively male progeny. During hermaphrodite spermatogenesis, the sister chromatids of the X chromosomes separate during meiosis I, and homologous X chromatids segregate to the functional sperm to create diplo-X sperm. Given these intra-species, intra-individual, and intra-gametogenesis variations in the meiotic program, A. rhodensis is an ideal model for studying the plasticity of meiosis and how it can be modulated., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The majority of drug abusing offenders who need substance abuse treatment do not receive it. Although interventions like drug court increase the probability of offender success, little is known about how co-occurring psychological symptoms impact drug court treatment outcomes. Based on previous research, we hypothesized that co-occurring psychological symptoms would have a significant relationship with successful drug court completion. Using a sample of suburban drug court enrollees (n = 122), multivariate logistic regression was conducted with successful drug court completion as the outcome variable. Predictor variables included symptom counts of depression, post-traumatic stress, obsessive-compulsive disorder, panic disorder, psychosis, generalized anxiety, and social phobia. Results indicated that participants with fewer symptoms of depression were more likely to successfully complete drug court than participants with more symptoms. The present study extends previous research by demonstrating that symptoms of depression are related to poorer outcomes for drug court enrollees. Accordingly, drug courts need to address participants' symptoms of depression to maximize success.

The demand for high-quality patient care in the current complex health care environment and the variety of today's available nursing education programs dictate a need to differentiate nursing practice into technical and professional roles. These roles are based on competencies acquired in ADN and BSN degree programs and implemented in practice settings where the contributions of all nurses are valued. To create a preferred future, AACN has developed a model for differentiated nursing practice in critical care. The model is a guideline for those nurses and institutions who may be or will be involved in changing practice patterns. The model does not support or encourage the elimination or disenfranchisement of any individual or groups of nurses. These statements were developed to address specific behavior that reflects the valuable contributions of each category of nurses within critical care nursing. The statements provide a model for creating efficient and effective practice patterns that may contribute to high-quality outcomes for critically ill patients and their families.