Cystic Fibrosis Mortality in Childhood : Data from European Cystic Fibrosis Society Patient Registry

Data collected in the European Cystic Fibrosis Society Patient Registry (ECFSPR) database were used to investigate whether risk factors for death in childhood and adolescents CF patients have different impact in countries of different income. In this way, it is possible to recognize where interventions could improve the quality of care and survival in these patients. We matched deceased and alive patients by age, country, year of follow-up. Multivariable logistic models were developed. In the years of this study, the ECFSPR collected information on 24,416 patients younger than 18 years: 7830 patients were from countries with low/middle income and 16,586 from countries with high income; among these the dead are 102 and 107 (p 60%). Evaluation of mortality in pediatric age may reflect the availability of resources for CF diagnosis and treatment in some countries

Latest Triassic onset of the Central Atlantic Magmatic Province (CAMP) volcanism in the Fundy Basin (Nova Scotia): New stratigraphic constraints

In this paper we investigate the stratigraphic relationship between the emplacement of the CAMP basalts and the Triassic–Jurassic (Tr–J) boundary in the Fundy Basin (Nova Scotia, Canada). This is one of the best exposed of the synrift basins of eastern North America (ENA) formed as a consequence of the rifting that led to the formation of the Atlantic Ocean. The Triassic palynological assemblages found in the sedimentary rocks below (uppermost Blomidon Formation) and just above the North Mountain Basalt (Scots Bay Member of the McCoy Brook Formation) indicate that CAMP volcanism, at least in Nova Scotia, is entirely of Triassic age, occurred in a very short time span, and may have triggered the T–J boundary biotic and environmental crisis. The palynological assemblage from the Blomidon Formation is characterised by the dominance of the Circumpolles group (e.g. Gliscopollis meyeriana, Corollina murphyae, Classopollis torosus) which crosses the previously established Tr–J boundary.The Triassic species Patinasporites densus disappears several centimetres below the base of the North Mountain basalt, near the previously interpreted Tr–J boundary. The lower strata of the Scots Bay Member yielded a palynological assemblage dominated by Triassic bisaccate pollens (e.g Lunatisporites acutus, L. rhaeticus Lueckisporites sp., Alisporites parvus) with minor specimens of the Circumpolles group. Examination of the state of preservation and thermal alteration of organic matter associated with the microfloral assemblages precludes the possibility of recycling of the Triassic sporomorphs from the older strata. Our data argue against the previous definition of the Tr–J boundary in the ENA basins, which was based mainly on the last occurrence of P. densus. Consequently, it follows that the late Triassic magnetostratigraphic correlations should be revised considering that chron E23r, which is correlated with the last occurrence of P. densus in the Newark basin, does not occur at the Tr–J boundary but marks rather a late Triassic (probably Rhaetian) reversal

Cystic Fibrosis Defective Response to Infection Involves Autophagy and Lipid Metabolism

Cystic fibrosis (CF) is a hereditary disease, with 70% of patients developing a proteinopathy related to the deletion of phenylalanine 508. CF is associated with multiple organ dysfunction, chronic inflammation, and recurrent lung infections. CF is characterized by defective autophagy, lipid metabolism, and immune response. Intracellular lipid accumulation favors microbial infection, and autophagy deficiency impairs internalized pathogen clearance. Myriocin, an inhibitor of sphingolipid synthesis, significantly reduces inflammation, promotes microbial clearance in the lungs, and induces autophagy and lipid oxidation. RNA-seq was performed in Aspergillusfumigatus-infected and myriocin-treated CF patients' derived monocytes and in a CF bronchial epithelial cell line. Fungal clearance was also evaluated in CF monocytes. Myriocin enhanced CF patients' monocytes killing of A. fumigatus. CF patients' monocytes and cell line responded to infection with a profound transcriptional change; myriocin regulates genes that are involved in inflammation, autophagy, lipid storage, and metabolism, including histones and heat shock proteins whose activity is related to the response to infection. We conclude that the regulation of sphingolipid synthesis induces a metabolism drift by promoting autophagy and lipid consumption. This process is driven by a transcriptional program that corrects part of the differences between CF and control samples, therefore ameliorating the infection response and pathogen clearance in the CF cell line and in CF peripheral blood monocytes

The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers

There remain many treatment uncertainties in cystic fibrosis (CF). With limited resources, research should focus on questions which are most important to the CF community. We conducted a James Lind Alliance Priority Setting Partnership in CF. Research questions were elicited and then prioritised in successive surveys. A workshop agreed the final top 10. Online methods avoided cross infection and widened participation. The elicitation survey had 482 respondents (1080 questions) and prioritisation survey 677 respondents. Participants were drawn equally from the patient and clinical communities globally. We have achieved a consensus on 10 research priorities which will be attractive to funders

Trans-heterozygosity for mutations enhances the risk of recurrent/chronic pancreatitis in patients with Cystic Fibrosis

Background: Recurrent (RP) and chronic pancreatitis (CP) may complicate Cystic Fibrosis (CF). It is still unknown if mutations in genes involved in the intrapancreatic activation of trypsin (IPAT) or in the pancreatic secretion pathway (PSP) may enhance the risk for RP/CP in patients with CF.Methods: We enrolled: 48 patients affected by CF complicated by RP/CP and, as controls 35 patients with CF without pancreatitis and 80 unrelated healthy subjects. We tested a panel of 8 genes involved in the IPAT, i.e. PRSS1, PRSS2, SPINK1, CTRC, CASR, CFTR, CTSB and KRT8 and 23 additional genes implicated in the PSP.Results: We found 14/48 patients (29.2%) with mutations in genes involved in IPAT in the group of CF patients with RP/CP, while mutations in such genes were found in 2/35 (5.7%) patients with CF without pancreatitis and in 3/80 (3.8%) healthy subjects (p < 0.001). Thus, we found mutations in 12 genes of the PSP in 11/48 (22.9%) patients with CF and RP/CP. Overall, 19/48 (39.6%) patients with CF and RP/CP showed one or more mutations in the genes involved in the IPAT and in the PSP while such figure was 4/35 (11.4%) for patients with CF without pancreatitis and 11/80 (13.7%) for healthy controls (p < 0.001).Conclusions: The trans-heterozygous association between CFTR mutations in genes involved in the pathways of pancreatic enzyme activation and the pancreatic secretion may be risk factors for the development of recurrent or chronic pancreatitis in patients with CF

First observation of the KS->pi0 gamma gamma decay

Using the NA48 detector at the CERN SPS, 31 KS->pi0 gamma gamma candidates with an estimated background of 13.7 +- 3.2 events have been observed. This first observation leads to a branching ratio of BR(KS->pi0 gamma gamma) = (4.9 +- 1.6(stat) +- 0.9(syst)) x 10^-8 in agreement with Chiral Perturbation theory predictions.Comment: 10 pages, 4 figures submitted to Phys. Lett.

Evolution of the Family Equidae, Subfamily Equinae, in North, Central and South America, Eurasia and Africa during the Plio-Pleistocene

Studies of horse evolution arose during the middle of the 19th century, and several hypotheses have been proposed for their taxonomy, paleobiogeography, paleoecology and evolution. The present contribution represents a collaboration of 19 multinational experts with the goal of providing an updated summary of Pliocene and Pleistocene North, Central and South American, Eurasian and African horses. At the present time, we recognize 114 valid species across these continents, plus 4 North African species in need of further investigation. Our biochronology and biogeography sections integrate Equinae taxonomic records with their chronologic and geographic ranges recognizing regional biochronologic frameworks. The paleoecology section provides insights into paleobotany and diet utilizing both the mesowear and light microscopic methods, along with calculation of body masses. We provide a temporal sequence of maps that render paleoclimatic conditions across these continents integrated with Equinae occurrences. These records reveal a succession of extinctions of primitive lineages and the rise and diversification of more modern taxa. Two recent morphological-based cladistic analyses are presented here as competing hypotheses, with reference to molecular-based phylogenies. Our contribution represents a state-of-the art understanding of Plio-Pleistocene Equus evolution, their biochronologic and biogeographic background and paleoecological and paleoclimatic contexts. © 2022 by the authors.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]