The outlook for those with cystic fibrosis (CF) has never been brighter with ever increasing life expectancy and the approval of the highly effective CFTR modulators, such as ...elexacaftor/tezacaftor/ivacaftor. With that being said, the progressive pulmonary decline and importance of lung health, infection, and inflammation in CF remains. This review is the second part in a three‐part CF Year in Review 2020. Part one focused on the literature related to CFTR modulators while part three will feature the multisystem effects related to CF. This review focuses on articles from Pediatric Pulmonology, including articles from other journals that are of particular interest to clinicians. Herein, we highlight studies published during 2020 related to CF pulmonary disease, infection, treatment, and diagnostics.
Here, a search for the exotic meson X(5568) decaying into the B$0\atop{s}$π± final state is performed using data corresponding to 9.6 fb-1 from $p\bar{p}$ collisions at $\sqrt{s}$ = 1960 GeV recorded ...by the Collider Detector at Fermilab. No evidence for this state is found and an upper limit of 6.7% at the 95% confidence level is set on the fraction of B$0\atop{s}$ produced through the X(5568)→B$0\atop{s}$π± process.
We examined changes in understory vegetation under an intact forest canopy during the first decade following the deposition of tephra (aerially transported volcanic ejecta) during the 1980 eruption ...of Mount St. Helens, Washington State, USA. Objectives were (1) to document vegetation response to a major disturbance that has received little attention but is widespread and relatively frequent in the northwestern United States, and (2) to analyze vegetation responses in terms of characteristics of the disturbance, responses of growth forms as well as those of species, components of vegetation change, and species autecology. We used permanent plots at four study sites, representing two tephra depths (≈ 4.5 and 15 cm), to examine understory vegetation change in old-growth, subalpine conifer forests. The two sites at each tephra depth differed in understory vegetation and amount of snowpack at the time of disturbance. At each site, plant cover and density were measured in 100 1-m2plots with undisturbed tephra covering the soil surface, in 50 1-m2plots from which the tephra was removed in 1980 (cleared plots), and, at 1 site, in 50 1-m2plots from which the tephra was removed in 1982. Values in cleared plots were used to estimate pre-eruption vegetation composition and to calculate inertia and components of resilience. After a decade, the impact of the tephra was still pronounced: cover was reduced for bryophytes at all sites, for herbs in deep tephra, and for shrubs where deep tephra had fallen on snow. Most cover was contributed by plants that survived the eruption. Vascular species initially absent from the site contributed little to the vegetation. Seedlings of most herb and shrub species did not survive, and many surviving species produced no seedlings. In contrast, at least two species of weedy, widespread mosses (Ceratodon purpureus and Pohlia annotina) extensively colonized the tephra surface. Although cover of surviving small trees changed little after the eruption, many seedlings of the shade-tolerant conifer species that dominated the canopy established and survived well, with the most germinants and highest survival on undisturbed deep tephra. Tsuga spp. constituted a higher proportion of the new seedlings than of the pre-eruption seedling population. A dense layer of conifer saplings appeared to be developing, unlike any present before the eruption. We calculated inertia (the percentage of pre-eruption importance remaining after the eruption) and four measures of resilience for each understory growth form. For shrubs, herbs, and bryophytes combined, inertia and one measure of resilience, the importance of the growth form at the end of the decade as a percentage of pre-eruption importance (called "c/a"), were highly correlated; both components increased as tephra depth decreased, as plant size increased, and where the snowpack had melted before the eruption, and both were higher for species richness and shoot density than for cover. Inertia for species density decreased with tephra depth and increased with plant height. Regressions predicting inertia for single growth forms included only a single, and different, environmental factor for each growth form: for shrubs, cover of snowpack; for herbs, tephra depth; and for bryophytes, light intensity. Other measures of resilience were less variable than c/a. Although this disturbance did not generally favor establishment of new species or totally eliminate species from the system, it did modify greatly the structure, species composition, and overall abundance of the forest understory. Recovery to the original state will not occur soon. Even for this example of vegetation recovery in a single stratum, generalities are difficult to state, because the relationships of inertia and resilience to growth form and variation in the disturbance were so complex. Because the initial damage played the dominant role in determining understory patterns a decade later, it is critical to focus attention on details of the disturbance and mechanisms of survival in order to understand early vegetation recovery following tephra deposition.
Mortality of canopy trees is an important process in forest dynamics, and can be sudden without relationship to past events or the culmination of a long decline. For three Engelmann spruce (
Picea ...engelmannii Parry)-subalpine fir (
Abies lasiocarpa Hook. Nutt.) forests, we reconstructed growth of canopy-size
A. lasiocarpa snags using dendrochronological procedures. We compared both the magnitude and rate of growth prior to death to a control (i.e., living) group of trees. Basal area increment averaged substantially less during the last 10 years before death than for control trees. Trees that died started diverging in growth, on average, 20–40 years before death. About 50% of trees that died had chronically slow growth, 30% had pronounced declines in growth, whereas 20% had good growth up to death. The rate of change in growth indicated a decline relative to the control group of trees but overlap was extensive between the two groups. Although some trees die abruptly without evidence in their ring patterns of impending mortality, overall our results indicate that mortality of canopy
A. lasiocarpa in these old forests is a gradual process related to long periods of low growth or long-term declines in growth.
A new transition metal-based reaction has been developed for the selective modification of tryptophan residues on protein substrates. After activation of vinyl-substituted diazo compounds by ...Rh2(OAc)4, the resulting metallocarbenoid intermediates were found to modify indoles in aqueous media despite competing reactions with water. Both N- and 2-substituted indole products were observed in the reaction. Following initial small-molecule studies, the reaction was performed on two protein substrates. Both myoglobin and subtilisin Carlsberg were modified readily in aqueous solution, and the tryptophan selectivity of the reactions was confirmed through MS analyses of trypsin digest fragments. It was also demonstrated that myoblobin concentrations as low as 10 μM still led to appreciable levels of modification. Reconstitution experiments confirmed that myoglobin retained its ability to bind heme following modification.
We report a measurement of single top quark production in proton-antiproton collisions at a center-of-mass energy of s=1.96TeV using a data set corresponding to 7.5fb super(-1) of integrated ...luminosity collected by the Collider Detector at Fermilab. We select events consistent with the single top quark decay process tarrowrightWbscriptlnub by requiring the presence of an electron or muon, a large imbalance of transverse momentum indicating the presence of a neutrino, and two or three jets including at least one originating from a bottom quark. An artificial neural network is used to discriminate the signal from backgrounds. We measure a single top quark production cross section of (ProQuest: Formulae and/or non-USASCII text omitted) pb and set a lower limit on the magnitude of the coupling between the top quark and bottom quark V sub(t)b0.78 at the 95% credibility level.
Studies of succession have a long history in ecology, but rigorous tests of general, unifying principles are rare. One barrier to these tests of theory is the paucity of longitudinal studies that ...span the broad gradients of disturbance severity that characterize large, infrequent disturbances. The cataclysmic eruption of Mount St. Helens (Washington, USA) in 1980 produced a heterogeneous landscape of disturbance conditions, including primary to secondary successional habitats, affording a unique opportunity to explore how rates and patterns of community change relate to disturbance severity, post‐eruption site conditions and time.
In this novel synthesis, we combined data from three long‐term (c. 30‐year) studies to compare rates and patterns of community change across three ‘zones’ representing a gradient of disturbance severity: primary successional blast zone, secondary successional tree blowdown/standing snag zone and secondary successional intact forest canopy/tephra deposit zone.
Consistent with theory, rates of change in most community metrics (species composition, species richness, species gain/loss and rank abundance) decreased with time across the disturbance gradient. Surprisingly, rates of change were often greatest at intermediate‐severity disturbance and similarly low at high‐ and low‐severity disturbance. There was little evidence of compositional convergence among or within zones, counter to theory. Within zones, rates of change did not differ among ‘site types’ defined by pre‐ or post‐eruption site characteristics (disturbance history, legacy effects or substrate characteristics).
Synthesis. The hump‐shaped relationships with disturbance severity runs counter to the theory predicting that community change will be slower during primary than during secondary succession. The similarly low rates of change after high‐ and low‐severity disturbance reflect differing sets of controls: seed limitation and abiotic stress in the blast zone vs. vegetative re‐emergence and low light in the tephra zone. Sites subjected to intermediate‐severity disturbance were the most dynamic, supporting species with a greater diversity of regenerative traits and seral roles (ruderal, forest and non‐forest). Succession in this post‐eruption landscape reflects the complex, multifaceted nature of volcanic disturbance (including physical force, heating and burial) and the variety of ways in which biological systems can respond to these disturbance effects. Our results underscore the value of comparative studies of long‐term, ecological processes for testing the assumptions and predictions of successional theory.
We combined data from three 36‐year studies to compare rates and patterns of community change across a gradient of disturbance severity on Mount St. Helens volcano. We found community change relationships with disturbance severity run counter to theory predicting that change will be slower during primary than during secondary succession. Rather, the similarly low rates of change after high‐ and low‐severity disturbance reflect differing sets of controls. Sites subjected to intermediate‐severity disturbance were the most dynamic. Succession in this post‐eruption landscape reflects the complex, multifaceted nature of volcanic disturbance and the variety of ways in which biological systems can respond to these disturbance effects.
Silver nanoparticles (AgNPs) have been shown to promote wound healing and to exhibit antimicrobial properties against a broad range of bacteria. In our previous study, we prepared tannic acid ...(TA)-modified AgNPs showing a good toxicological profile and immunomodulatory properties useful for potential dermal applications.
In this study, in vitro scratch assay, antimicrobial tests, modified lymph node assay as well as a mouse splint wound model were used to access the wound healing potential of TA-modified and unmodified AgNPs.
TA-modified but not unmodified AgNPs exhibited effective antibacterial activity against
,
and
and stimulated migration of keratinocytes in vitro. The tests using the mouse splint wound model showed that TA-modified 33 and 46 nm AgNPs promoted better wound closure, epithelialization, angiogenesis and formation of the granulation tissue. Additionally, AgNPs elicited expression of VEGF-α, PDGF-β and TGF-β1 cytokines involved in wound healing more efficiently in comparison to control and TA-treated wounds. However, both the lymph node assay and the wound model showed that TA-modified AgNPs sized 13 nm can elicit strong inflammatory response not only during wound healing but also when applied to the damaged skin.
TA-modified AgNPs sized >26 nm promote wound healing better than TA-modified or unmodified AgNPs. These findings suggest that TA-modified AgNPs sized >26 nm may have a promising application in wound management.
Background and Objectives
There are limited data on cystic fibrosis (CF) transmembrane conductance regulator‐related metabolic syndrome (CRMS) outcomes beyond infancy. The goal of this study was to ...analyze outcomes of infants with CRMS up to the age of 9–10 years using the CF Foundation Patient Registry (CFFPR).
Methods
We analyzed data from the CFFPR for individuals with CF and CRMS born between 2010 and 2020. We classified all patients based on the clinical diagnosis reported by the CF care center and the diagnosis using CFF guideline definitions for CF and CRMS, classifying children into groups based on agreement between clinical report and guideline criteria. Descriptive statistics for the cohort were calculated for demographics, nutritional outcomes, and microbiology for the first year of life and lung function and growth outcomes were summarized for ages 6–10 years.
Results
From 2010 to 2020, there were 8765 children with diagnosis of CF or CRMS entered into the CFFPR with sufficient diagnostic data for classification, of which 7591 children had a clinical diagnosis of CF and 1174 had a clinical diagnosis of CRMS. CRMS patients exhibited normal nutritional indices and pulmonary function up to age 9–10 years. The presence of respiratory bacteria associated with CF, such as Pseudomonas aeruginosa from CRMS patients ranged from 2.1% to 9.1% after the first year of life.
Conclusions
Children with CRMS demonstrate normal pulmonary and nutritional outcomes into school age. However, a small percentage of children continue to culture CF‐associated respiratory pathogens after infancy.
In response to numerous pathologic stimuli, the myocardium undergoes a hypertrophic response characterized by increased myocardial cell size and activation of fetal cardiac genes. We show that ...cardiac hypertrophy is induced by the calcium-dependent phosphatase calcineurin, which dephosphorylates the transcription factor NF-AT3, enabling it to translocate to the nucleus. NF-AT3 interacts with the cardiac zinc finger transcription factor GATA4, resulting in synergistic activation of cardiac transcription. Transgenic mice that express activated forms of calcineurin or NF-AT3 in the heart develop cardiac hypertrophy and heart failure that mimic human heart disease. Pharmacologic inhibition of calcineurin activity blocks hypertrophy in vivo and in vitro. These results define a novel hypertrophic signaling pathway and suggest pharmacologic approaches to prevent cardiac hypertrophy and heart failure.
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