Birthweight, early passive respiratory system mechanics, and ventilator requirements as predictors of outcome in premature infants with respiratory failure.

Early respiratory mechanics have been reported to predict outcome in newborns with respiratory failure. However, it remains unknown whether measurements of pulmonary function add significantly to the predictive value of more readily available variables The present study was designed to answer this question. Passive respiratory system mechanics were measured by an airway occlusion technique in 104 ventilator-dependent premature infants between 6 and 48 hours of life and corrected for infant size. A ventilation index [FiO2 x mean airway pressure (MAP)] was calculated at the time of pulmonary function testing. Poor outcome was defined as death from respiratory failure or need for supplemental oxygen at 28 days. Stepwise logistic function regression examined whether ventilation index and respiratory mechanics added predictive power over and above birthweight. Five infants died, and 45 patients required supplemental oxygen at 28 days. Birthweight was a strong predictor and would have entered the logistic model first in any case. Ventilation index added significantly to the predictive model (P = 0.038). Respiratory system conductance (P = 0.15) and compliance (P = 0.93) entered on the third and last step, respectively. We conclude that in premature infants with respiratory failure, birthweight is a strong predictor of outcome. Early ventilator requirements but not respiratory system mechanics, add significantly to this predictive model.     

Reassessing Medical Risk in Living Kidney Donors

The short- and long-term effects of unilateral nephrectomy on living donors have been important considerations for 60 years. Short-term risk is well established (0.03% mortality and <1% risk of major morbidity), but characterization of long-term risk is evolving. Relative to the general population, risk of mortality, ESRD, hypertension, proteinuria, and cardiovascular disease is comparable or lower. However, new studies comparing previous donors with equally healthy controls indicate increased risk of metabolic derangements (particularly involving calcium homeostasis), renal failure, and possibly, mortality. We discuss how these results should be interpreted and their influence on the practice of living donor kidney transplantation.     

Coexistence of phosphotyrosine-dependent and -independent interactions between Cbl and Bcr-Abl

Cbl is one of the major tyrosine-phosphorylated proteins in Bcr-Abl-expressing cells. A direct association between the SH2 domain of Bcr-Abl and tyrosine-phosphorylated Cbl has been demonstrated. The purpose of this study was to determine if and how unphosphorylated Cbl and Bcr-Abl may associate.Interactions between Cbl and Bcr-Abl were investigated in yeast two- and three-hybrid systems, gel overlay assays, and immunoprecipitates from mammalian cells expressing wild-type and the Y177F mutant of Bcr-Abl.No direct interaction between Bcr-Abl and unphosphorylated Cbl was observed. Bcr-Abl did, however, associate with Grb2, an adaptor protein that binds tyrosine 177 of Bcr-Abl. Additionally, Grb2 interacted with Cbl. In a yeast three-hybrid assay, Grb2 mediated an interaction between Cbl and Bcr-Abl that was dependent on a functional Grb2 binding site. This interaction was confirmed in vitro using purified proteins. In cells expressing Bcr-Abl with a mutation in the Grb2 binding site, binding of Cbl to Bcr-Abl was significantly reduced, but Cbl tyrosine phosphorylation was maintained. Imatinib treatment of these cells further reduced but did not abrogate Cbl binding, reflecting residual kinase activity.Multiple phosphotyrosine-dependent and -independent interactions stabilize the interaction between Cbl and Abl. Grb2 or another, yet unidentified, protein may mediate an initial interaction between Cbl and Bcr-Abl that is independent of Cbl tyrosine phosphorylation. Following this initial interaction, Cbl can then become tyrosine phosphorylated and interact with the SH2 domain of Bcr-Abl, further stabilizing the complex.     

A proposal for the addressing the needs of the pediatric pulmonary work force

Unprecedented opportunities and daunting difficulties are anticipated in the future of pediatric pulmonary medicine. To address these issues and optimize pediatric pulmonary training, a group of faculty from various institutions met in 2019 and proposed specific, long‐term solutions to the emerging problems in the field. Input on these ideas was then solicited more broadly from faculty with relevant expertise and from recent trainees. This proposal is a synthesis of these ideas. Pediatric pulmonology was among the first pediatric specialties to be grounded deliberately in science, requiring its fellows to demonstrate expertise in scientific inquiry (1). In the future, we will need more training in science, not less. Specifically, the scope of scientific inquiry will need to be broader. The proposal outlined below is designed to help optimize the practices of current providers and to prepare the next generation to be leaders in pediatric care in the future. We are optimistic that this can be accomplished. Our broad objectives are (a) to meet the pediatric subspecialty workforce demand by increasing interest and participation in pediatric pulmonary training; (b) to modernize training to ensure that future pediatric pulmonologists will be prepared clinically and scientifically for the future of the field; (c) to train pediatric pulmonologists who will add value in the future of pediatric healthcare, complemented by advanced practice providers and artificial intelligence systems that are well‐informed to optimize quality healthcare delivery; and (d) to decrease the cost and improve the quality of care provided to children with respiratory diseases.     

Biogeography of time partitioning in mammals

Many animals regulate their activity over a 24-h sleep–wake cycle, concentrating their peak periods of activity to coincide with the hours of daylight, darkness, or twilight, or using different periods of light and darkness in more complex ways. These behavioral differences, which are in themselves functional traits, are associated with suites of physiological and morphological adaptations with implications for the ecological roles of species. The biogeography of diel time partitioning is, however, poorly understood. Here, we document basic biogeographic patterns of time partitioning by mammals and ecologically relevant large-scale patterns of natural variation in “illuminated activity time” constrained by temperature, and we determine how well the first of these are predicted by the second. Although the majority of mammals are nocturnal, the distributions of diurnal and crepuscular species richness are strongly associated with the availability of biologically useful daylight and twilight, respectively. Cathemerality is associated with relatively long hours of daylight and twilight in the northern Holarctic region, whereas the proportion of nocturnal species is highest in arid regions and lowest at extreme high altitudes. Although thermal constraints on activity have been identified as key to the distributions of organisms, constraints due to functional adaptation to the light environment are less well studied. Global patterns in diversity are constrained by the availability of the temporal niche; disruption of these constraints by the spread of artificial lighting and anthropogenic climate change, and the potential effects on time partitioning, are likely to be critical influences on species’ future distributions.Natural cycles of light and darkness structure the environment of the majority of eukaryotic organisms. The rotation of the Earth partitions time into regular cycles of day and night, and although all points on the Earth’s surface receive roughly equal durations of light and darkness over the course of a year, at mid to high latitudes seasonal variation in day length imposes an uneven distribution throughout the annual cycle. During the hours when the sun is below the horizon, there is seasonal and latitudinal variation in the duration of “biologically useful semidarkness” in the form of twilight and moonlight (1), modified by both the lunar cycle and variable cloud cover, providing changing opportunities for animals able to use visual cues for key behaviors including foraging, predator avoidance, and reproduction (2–6). Activity during both daylight and semidarkness may be further constrained by covariance between the natural cycles of light and temperature; the metabolic costs of thermoregulation place constraints on the time available for activity (7). Thermal constraints may limit nocturnal activity when nighttime temperatures are low, and diurnal activity when temperatures are high. Furthermore, energetic constraints may force some species to be active throughout hours of both light and darkness (8). Where energetic and thermal costs are not prohibitive, temporal niche partitioning may occur as species specialize and avoid competition by concentrating their activity within a particular section along the light gradient (9, 10). Behavioral traits are associated with a range of specialized adaptations, particularly in visual systems and eye morphology (11) and energetics and resource use (6, 12). Thus, some species are apparently obligately diurnal in their peak activity patterns, some obligately nocturnal, obligately crepuscular (active primarily during twilight), or obligately cathemeral (significant activity both during daylight and night), and others make facultative use of both daylight and night (13), or show seasonal and/or geographical variation in their strategy. Strict nocturnality and diurnality are hence two ends of a continuum of possible strategies for partitioning time over the 24-h cycle. As properties of organisms that strongly influence performance within a particular environment, these strategies can be considered functional traits in themselves (14), but are also associated with suites of adaptations, with implications for the ecological roles of species and individuals. Crepuscular and cathemeral species may have intermediate adaptations (15), and behavior may be flexible to vary within species and among individuals according to factors such as time of year, habitat structure, food availability, age, temperature, and the presence or absence of predators (16–18).The ecology of diel time partitioning by organisms remains rather poorly understood (19, 20). Studies have considered the adaptive mechanisms behind strategies within a single ecosystem, including predator avoidance, energetic constraints, diet quality, and interspecific competition (9, 21). Meanwhile, although mapping functional traits has become a core technique in functional biogeography (22, 23), surprisingly little is known about the biogeography of diel activity patterns, and the extent to which they are determined by geographic gradients in light and climate. Addressing such issues has become more pressing with growth in the evidence for a wide range of ecological impacts of both anthropogenic climatic change and nighttime light pollution (24–28). Natural cycles of light have remained consistent for extremely long geological periods, providing a rather invariant context, and a very reliable set of potential environmental cues. The continued spread of electric lighting has caused substantial disruption to how these cycles are experienced by many organisms, exerting a novel environmental pressure (29). Direct illumination of the environment has quite localized effects, but sky glow—the amplified night sky brightness that is produced by upwardly emitted and reflected electric light being scattered by water, dust, and gas molecules in the atmosphere—can alter light regimes over extensive areas. Indeed, under cloudy conditions in urban areas, sky glow has been shown to be of an equivalent or greater magnitude than high-elevation summer moonlight (30). Understanding the biogeography of time partitioning by organisms provides a first step toward determining where such changes are likely to have the greatest impact.In this paper, we (i) document basic biogeographic patterns of time partitioning by organisms, using terrestrial mammals as a case study; (ii) document ecologically relevant large-scale patterns of natural variation in “biologically useful” natural light, constrained by temperature; and (iii) determine how well the first of these are predicted by the second. Mammals provide an interesting study group, being globally distributed, occupying a broad range of environments, and exhibiting a wide diversity of time-partitioning behavior. Much concern has also been expressed as to the potential impacts of nighttime light pollution on the group, and there are many studies documenting significant influences (31, 32). Due to the global nature of this study, and the paucity of detailed information on time partitioning reported for many species, our focus is on a high-level categorization, allocating species to one of four temporal niches: nocturnal, diurnal, cathemeral, and crepuscular (Fig. 1), albeit with the acknowledgment that in many species behavior occurs along a continuum of possible strategies that may be more flexible and complex.Open in a separate windowFig. 1.Examples of recorded diel activity patterns illustrating the four main time-partitioning strategies used to classify terrestrial mammals in this study (64–67).     

Atrial fibrosis quantified using late gadolinium enhancement MRI is associated with sinus node dysfunction requiring pacemaker implant

Atrial Fibrosis and Sinus Node Dysfunction . Introduction: Sinus node dysfunction (SND) commonly manifests with atrial arrhythmias alternating with sinus pauses and sinus bradycardia. The underlying process is thought to be because of atrial fibrosis. We assessed the value of atrial fibrosis, quantified using Late Gadolinium Enhanced‐MRI (LGE‐MRI), in predicting significant SND requiring pacemaker implant. Methods: Three hundred forty‐four patients with atrial fibrillation (AF) presenting for catheter ablation underwent LGE‐MRI. Left atrial (LA) fibrosis was quantified in all patients and right atrial (RA) fibrosis in 134 patients. All patients underwent catheter ablation with pulmonary vein isolation with posterior wall and septal debulking. Patients were followed prospectively for 329 ± 245 days. Ambulatory monitoring was instituted every 3 months. Symptomatic pauses and bradycardia were treated with pacemaker implantation per published guidelines. Results: The average patient age was 65 ± 12 years. The average wall fibrosis was 16.7 ± 11.1% in the LA, and 5.3 ± 6.4% in the RA. RA fibrosis was correlated with LA fibrosis (R²= 0.26; P < 0.01). Patients were divided into 4 stages of LA fibrosis (Utah I: <5%, Utah II: 5–20%, Utah III: 20–35%, Utah IV: >35%). Twenty‐two patients (mean atrial fibrosis, 23.9%) required pacemaker implantation during follow‐up. Univariate and multivariate analysis identified LA fibrosis stage (OR, 2.2) as a significant predictor for pacemaker implantation with an area under the curve of 0.704. Conclusions: In patients with AF presenting for catheter ablation, LGE‐MRI quantification of atrial fibrosis demonstrates preferential LA involvement. Significant atrial fibrosis is associated with clinically significant SND requiring pacemaker implantation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 44‐50, January 2012)