Investigating the association between obesity and asthma in 6- to 8-year-old Saudi children:a matched case-control study

Background: Previous studies have demonstrated an association between obesity and asthma, but there remains considerable uncertainty about whether this reflects an underlying causal relationship. Aims: To investigate the association between obesity and asthma in pre-pubertal children and to investigate the roles of airway obstruction and atopy as possible causal mechanisms. Methods: We conducted an age- and sex-matched case–control study of 1,264 6- to 8-year-old schoolchildren with and without asthma recruited from 37 randomly selected schools in Madinah, Saudi Arabia. The body mass index (BMI), waist circumference and skin fold thickness of the 632 children with asthma were compared with those of the 632 control children without asthma. Associations between obesity and asthma, adjusted for other potential risk factors, were assessed separately in boys and girls using conditional logistic regression analysis. The possible mediating roles of atopy and airway obstruction were studied by investigating the impact of incorporating data on sensitisation to common aeroallergens and measurements of lung function. Results: BMI was associated with asthma in boys (odds ratio (OR)=1.14, 95% confidence interval (CI), 1.08–1.20; adjusted OR=1.11, 95% CI, 1.03–1.19) and girls (OR=1.37, 95% CI, 1.26–1.50; adjusted OR=1.38, 95% CI, 1.23–1.56). Adjusting for forced expiratory volume in 1 s had a negligible impact on these associations, but these were attenuated following adjustment for allergic sensitisation, particularly in girls (girls: OR=1.25; 95% CI, 0.96–1.60; boys: OR=1.09, 95% CI, 0.99–1.19). Conclusions: BMI is associated with asthma in pre-pubertal Saudi boys and girls; this effect does not appear to be mediated through respiratory obstruction, but in girls this may at least partially be mediated through increased risk of allergic sensitisation

KAP Degradation by Calpain Is Associated with CK2 Phosphorylation and Provides a Novel Mechanism for Cyclosporine A-Induced Proximal Tubule Injury

The use of cyclosporine A (CsA) is limited by its severe nephrotoxicity that includes reversible vasoconstrictor effects and proximal tubule cell injury, the latter associated whith chronic kidney disease progression. The mechanisms of CsA-induced tubular injury, mainly on the S3 segment, have not been completely elucidated. Kidney androgen-regulated protein (KAP) is exclusively expressed in kidney proximal tubule cells, interacts with the CsA-binding protein cyclophilin B and its expression diminishes in kidneys of CsA-treated mice. Since we reported that KAP protects against CsA toxicity in cultured proximal tubule cells, we hypothesized that low KAP levels found in kidneys of CsA-treated mice might correlate with proximal tubule cell injury. To test this hypothesis, we used KAP Tg mice developed in our laboratory and showed that these mice are more resistant to CsA-induced tubular injury than control littermates. Furthermore, we found that calpain, which was activated by CsA in cell cultures and kidney, is involved in KAP degradation and observed that phosphorylation of serine and threonine residues found in KAP PEST sequences by protein kinase CK2 enhances KAP degradation by calpain. Moreover, we also observed that CK2 inhibition protected against CsA-induced cytotoxicity. These findings point to a novel mechanism for CsA-induced kidney toxicity that might be useful in developing therapeutic strategies aimed at preventing tubular cell damage while maintaining the immunosuppressive effects of CsA

Molecular Characterization of the Region 7q22.1 in Splenic Marginal Zone Lymphomas

Splenic marginal zone lymphomas (SMZL) are an uncommon type of B-cell non-Hodgkin's lymphoma (NHL-B) in which no specific chromosomal translocations have been described. In contrast, the most frequent cytogenetic abnormality is the loss of the long arm of chromosome 7 (7q). Previous reports have located this loss in the 7q32 region. In order to better characterize the genomic imbalances in SMZL, molecular studies were carried out in 73 patients with SMZL. To gain insight into the mapping at 7q a tiling array was also used. The results confirmed the loss of 7q as the most frequent change. In addition, several abnormalities, including 4q22.1, 1q21.3–q22, 6q25.3, 20q13.33, 3q28, 2q23.3–q24.1 and 17p13, were also present. A loss of 7q22.1 at 99925039–101348479 bp was observed in half of the cases. The region of 7q22.1 has not previously been characterised in SMZL. Our results confirmed the presence of a new region of loss on chromosome 7 in these NHL

Knowledge systems, health care teams, and clinical practice: a study of successful change

Clinical teams are of growing importance to healthcare delivery, but little is known about how teams learn and change their clinical practice. We examined how teams in three US hospitals succeeded in making significant practice improvements in the area of antimicrobial resistance. This was a qualitative cross-case study employing Soft Knowledge Systems as a conceptual framework. The purpose was to describe how teams produced, obtained, and used knowledge and information to bring about successful change. A purposeful sampling strategy was used to maximize variation between cases. Data were collected through interviews, archival document review, and direct observation. Individual case data were analyzed through a two-phase coding process followed by the cross-case analysis. Project teams varied in size and were multidisciplinary. Each project had more than one champion, only some of whom were physicians. Team members obtained relevant knowledge and information from multiple sources including the scientific literature, experts, external organizations, and their own experience. The success of these projects hinged on the teams' ability to blend scientific evidence, practical knowledge, and clinical data. Practice change was a longitudinal, iterative learning process during which teams continued to acquire, produce, and synthesize relevant knowledge and information and test different strategies until they found a workable solution to their problem. This study adds to our understanding of how teams learn and change, showing that innovation can take the form of an iterative, ongoing process in which bits of K&I are assembled from multiple sources into potential solutions that are then tested. It suggests that existing approaches to assessing the impact of continuing education activities may overlook significant contributions and more attention should be given to the role that practical knowledge plays in the change process in addition to scientific knowledge

Decadal slowdown of a land-terminating sector of the Greenland Ice Sheet despite warming

Ice flow along land-terminating margins of the Greenland Ice Sheet (GIS) varies considerably in response to fluctuating inputs of surface meltwater to the bed of the ice sheet. Such inputs lubricate the ice-bed interface, transiently speeding up the flow of ice. Greater melting results in faster ice motion during summer, but slower motion over the subsequent winter, owing to the evolution of an efficient drainage system that enables water to drain from regions of the ice-sheet bed that have a high basal water pressure. However, the impact of hydrodynamic coupling on ice motion over decadal timescales remains poorly constrained. Here we show that annual ice motion across an 8,000-km2 land-terminating region of the west GIS margin, extending to 1,100 m above sea level, was 12 slower in 2007-14 compared with 1985-94, despite a 50 increase in surface meltwater production. Our findings suggest that, over these three decades, hydrodynamic coupling in this section of the ablation zone resulted in a net slowdown of ice motion (not a speed-up, as previously postulated). Increases in meltwater production from projected climate warming may therefore further reduce the motion of land-terminating margins of the GIS. Our findings suggest that these sectors of the ice sheet are more resilient to the dynamic impacts of enhanced meltwater production than previously thought. © 2015 Macmillan Publishers Limited. All rights reserved

Environmental sensing and response genes in cnidaria : the chemical defensome in the sea anemone Nematostella vectensis

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Cell Biology and Toxicology 24 (2008): 483-502, doi:10.1007/s10565-008-9107-5.The starlet sea anemone Nematostella vectensis has been recently established as a new model system for the study of the evolution of developmental processes, as cnidaria occupy a key evolutionary position at the base of the bilateria. Cnidaria play important roles in estuarine and reef communities, but are exposed to many environmental stressors. Here I describe the genetic components of a ‘chemical defensome’ in the genome of N. vectensis, and review cnidarian molecular toxicology. Gene families that defend against chemical stressors and the transcription factors that regulate these genes have been termed a ‘chemical defensome,’ and include the cytochromes P450 and other oxidases, various conjugating enyzymes, the ATP-dependent efflux transporters, oxidative detoxification proteins, as well as various transcription factors. These genes account for about 1% (266/27200) of the predicted genes in the sea anemone genome, similar to the proportion observed in tunicates and humans, but lower than that observed in sea urchins. While there are comparable numbers of stress-response genes, the stress sensor genes appear to be reduced in N. vectensis relative to many model protostomes and deuterostomes. Cnidarian toxicology is understudied, especially given the important ecological roles of many cnidarian species. New genomic resources should stimulate the study of chemical stress sensing and response mechanisms in cnidaria, and allow us to further illuminate the evolution of chemical defense gene networks.WHOI Ocean Life Institute and NIH R01-ES01591

Observation of B(s)0→J/ψpp¯ decays and precision measurements of the B(s)0 masses

The first observation of the decays B 0 ( s ) → J / ψ p ¯ p is reported, using proton-proton collision data corresponding to an integrated luminosity of 5.2     fb − 1 , collected with the LHCb detector. These decays are suppressed due to limited available phase space, as well as due to Okubo-Zweig-Iizuka or Cabibbo suppression. The measured branching fractions are B ( B 0 → J / ψ p ¯ p ) = [ 4.51 ± 0.40 ( stat ) ± 0.44 ( syst ) ] × 10 − 7 , B ( B 0 s → J / ψ p ¯ p ) = [ 3.58 ± 0.19 ( stat ) ± 0.39 ( syst ) ] × 10 − 6 . For the B 0 s meson, the result is much higher than the expected value of O ( 10 − 9 ) . The small available phase space in these decays also allows for the most precise single measurement of both the B 0 mass as 5279.74 ± 0.30 ( stat ) ± 0.10 ( syst )     MeV and the B 0 s mass as 5366.85 ± 0.19 ( stat ) ± 0.13 ( syst )     MeV

Test of lepton universality in b→sℓ+ℓ−b \rightarrow s \ell^+ \ell^- decays

The first simultaneous test of muon-electron universality using $B^{+}\rightarrow K^{+}\ell^{+}\ell^{-}$ and $B^{0}\rightarrow K^{*0}\ell^{+}\ell^{-}$ decays is performed, in two ranges of the dilepton invariant-mass squared, $q^{2}$. The analysis uses beauty mesons produced in proton-proton collisions collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of 9 $\mathrm{fb}^{-1}$. Each of the four lepton universality measurements reported is either the first in the given $q^{2}$ interval or supersedes previous LHCb measurements. The results are compatible with the predictions of the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-046.html (LHCb public pages