The developmental expression of the multiple isozymes of Na,K-ATPase in rat brain, heart, lung, kidney, and skeletal muscle from fetal (14 days gestation) to adult (55 days) was investigated at the ...molecular level with cDNA probes specific for the multiple catalytic alpha isoform (alpha 1, alpha 2, alpha 3) and beta subunit mRNAs. Northern and RNA slot blot analyses revealed that these mRNAs are regulated in a tissue-specific manner. The multiple alpha isoform and beta subunit mRNAs appear to be regulated coordinately during ontogenesis with maximum expression occurring between 15 and 25 days of age for brain, heart, kidney, and skeletal muscle, whereas peak expression in lung was observed between 2 and 4 days of neonatal life. Brain tissue showed between 10- and 17-fold increases in the levels of expression for the three individual alpha isoform mRNAs. The alpha 3 mRNA was found to be the predominant alpha isoform transcript in fetal as well as adult brain. Examination of heart tissue showed alpha 1 mRNA to be the major catalytic subunit during development. However, a developmentally regulated transition in alpha 2 and alpha 3 mRNA expression was observed in heart between 7 and 14 days after birth. The alpha 3 mRNA was expressed primarily in fetal and neonatal heart tissue, while alpha 2 mRNA was expressed in juvenile and adult tissue. In kidney and lung, alpha 1 mRNA was the predominant alpha isoform transcript showing temporary increases in expression of 2- and 4-fold, respectively, during development. In contrast to the other tissues, muscle expressed predominantly alpha 2 mRNA following birth, the levels increasing approximately 89-fold during myogenesis. Thus, each tissue examined exhibits a distinct pattern of expression for the Na,K-ATPase catalytic alpha isoforms during ontogenesis.
Abstract
Introduction
Christianson Syndrome (CS), a recently identified X-linked neurodevelopmental disorder, is caused by mutations in the human gene SLC9A6 encoding the recycling endosomal alkali ...cation/proton exchanger NHE6. CS may be among the most common X-linked developmental brain disorders. Individuals with CS have pronounced limitations in cognitive ability, motor skills and adaptive behaviour. Clinically significant sleep problems are prevalent in individuals with neurodevelopmental disorders such as autism and Angelman syndrome which share some phenotypic similarities with CS. There are two reports in the literature pertaining to the association of CS with electrical status epilepticus during slow-wave sleep, but there is currently no information that describes sleep disturbances in individuals with CS. The objective of this study was to characterize, for the first time, sleep disturbances in individuals with CS.
Methods
13 boys with confirmed mutations in NHE6 (Mean Age=12.33 years, SD=6.2) were recruited through the CS Association. Information on age, gender, and patients’ medical history was collected using a short questionnaire completed by parents. Sleep disturbances were assessed using the Sleep Disturbance Scale for Children, which investigates the occurrence of sleep problems or disorders during the previous 6 months. The scale includes the following six factors: (1) disorders of initiating and maintaining sleep; (2) sleep-breathing disorders; (3) disorders of arousal, including sleepwalking, sleep terrors, and nightmares; (4) sleep-wake transition disorders, including hypnic jerks, rhythmic movement disorders, hypnagogic hallucinations, nocturnal hyperkinesias, and bruxism; (5) disorders of excessive somnolence; and (6) sleep hyperhidrosis. A T score > 70 is considered abnormal.
Results
The most typical sleep problems were disturbances of initiating or maintain sleep (46%) and sleep-wake transition (31%). In addition, arousal or breathing problems occurred in 7% of the participants.
Conclusion
We present results from the largest sample reported in the literature regarding individuals with CS to date. Our findings suggest that disturbances of initiating or maintaining sleep and sleep wake transition are prevalent in this population, and emphasise the need for assessing sleep in individuals with CS.
Support (If Any):
To determine the prevalence of, and factors associated with, burnout among pediatric intensivists across a variety of practice settings.
A population-based survey, using a mailed questionnaire that ...included a previously validated Burnout Scale.
Private and academic pediatric critical care practices.
Respondents from among all members of the Pediatric Section of the Society of Critical Care Medicine and all physicians certified in pediatric critical care medicine by the American Board of Pediatrics.
The questionnaire consisted of demographic items, variables noted in the literature as being associated with burnout (e.g., the individual's perception of how others valued their work, and the use of preventive measures such as regular exercise to relieve stress), and a validated Burnout Scale. The questionnaire also included questions pertaining to past training, practice of other primary specialties or subspecialties, practice settings, admission responsibilities, actual and preferred practice activities, total work effort, academic activities, and causes of stress at work. The Burnout Scale of Pines and Aronson is a self-diagnosis instrument, consisting of 21 questions using a 7-point frequency scale. The total Burnout Score represents an average of the scores for the individual components. Scores of < or = 3 in our study were classified as "not burned out." Scores of > 3 and < or = 4 were classified as "at risk." Scores of > 4 were classified as "burned out." A total of 883 questionnaires were mailed; 474 (56%) were respondent returns and 35 questionnaires could not be delivered. Primary analyses focused on the 389 respondent attending physicians presently practicing pediatric critical care medicine at the time of the survey. The average Burnout Score of these attending physicians was 3.1 +/- 0.8; 36% were classified as being at risk for burnout, and 14% were classified as burned out. There was no association between burnout status and the following work conditions: having fellows; having protected time for research and publications; frequency of being called at home; frequency of returning to the hospital when called at home; or call schedule. Respondents classified as burned out were significantly more likely than respondents who were classified as not burned out to feel that their work was not valued by others. Burned out respondents were less likely than respondents who were not burned out to give the following description: feeling very successful; feeling that their peers viewed them as very successful; feeling satisfied in their professional life; and routinely exercising or having some other outside interest.
We found that a high degree of burnout exists in pediatric critical care medicine, with 50% of pediatric intensivists at risk or burned out. Overall, there was no association between Burnout Scores and training, practice specialties, or practice settings, nor was there an association with aspects of practice that are physically taxing. However, perceptions about the value of their work and feelings of success and satisfaction were highly associated with those respondents classified as burned out. Routine exercise (a strategy used by some for stress reduction) was associated with lower Burnout Scores. Further studies are necessary to evaluate the trends that we have reported and to identify causal factors.
Barn owls are effective nocturnal predators. We tested their visual performance at low light levels and determined visual acuity and contrast sensitivity of three barn owls by their behavior at ...stimulus luminances ranging from photopic to fully scotopic levels (23.5 to 1.5 × 10⁻⁶). Contrast sensitivity and visual acuity decreased only slightly from photopic to scotopic conditions. Peak grating acuity was at mesopic (4 × 10⁻² cd/m²) conditions. Barn owls retained a quarter of their maximal acuity when luminance decreased by 5.5 log units. We argue that the visual system of barn owls is designed to yield as much visual acuity under low light conditions as possible, thereby sacrificing resolution at photopic conditions.
The luminal pH of organelles along the secretory and endocytic pathways of mammalian cells is acidic and tightly regulated, with the H+ varying up to 100-fold between compartments. Steady-state ...organellar pH is thought to reflect a balance between the rates of H+ pumping by the vacuolar-type H+-ATPase and H+ efflux through ill-defined pathways. Here, we describe the cloning of a novel gene (NHE7) in humans that is homologous to Na+/H+ exchangers, is ubiquitously expressed, and localizes predominantly to the trans-Golgi network. Significantly, NHE7 mediates the influx of Na+ or K+ in exchange for H+. The activity of NHE7 was also found to be relatively insensitive to inhibition by amiloride but could be antagonized by the analogue benzamil and the unrelated compound quinine. Thus, NHE7 displays unique functional and pharmacological properties and may play an important role in maintaining cation homeostasis of this important organelle.
The Organ Procurement and Transplantation Network (OPTN) Deceased Donor Potential Study, funded by the Health Resources and Services Administration, characterized the current pool of potential ...deceased donors and estimated changes through 2020. The goal was to inform policy development and suggest practice changes designed to increase the number of donors and organ transplants. Donor estimates used filtering methodologies applied to datasets from the OPTN, the National Center for Health Statistics, and the Agency for Healthcare Research and Quality and used these estimates with the number of actual donors to estimate the potential donor pool through 2020. Projected growth of the donor pool was 0.5% per year through 2020. Potential donor estimates suggested unrealized donor potential across all demographic groups, with the most significant unrealized potential (70%) in the 50–75‐year‐old age group and potential Donation after Circulatory Death (DCD) donors. Actual transplants that may be realized from potential donors in these categories are constrained by confounding medical comorbidities not identified in administrative databases and by limiting utilization practices for organs from DCD donors. Policy, regulatory, and practice changes encouraging organ procurement and transplantation of a broader population of potential donors may be required to increase transplant numbers in the United States.
Findings from the OPTN Deceased Donor Potential Study suggest possible transplant center and organ procurement organization practice changes, as well as potential transplant system regulatory changes, which may expand the donor pool.
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