A blinded comparison of fluticasone propionate with budesonide via powder devices in adult patients with moderate-to-severe asthma: a clinical evaluation

In Vitro and in vivo data have demonstrated that there are detectable differences between inhaled corticosteroids commonly used to treat asthma. However, controversy still remains as to whether these differences translate into clinical benefits. This 12-week, international, randomized, doubleblind, parallel-group study was undertaken to compare the efficacy and safety of fluticasone propionate (FP) 800 μg daily, administered as a powder via the Diskhaler®, and budesonide (BUD) 1600 μg daily, administered using the Turbuhaler®, in adult patients with moderate-tosevere asthma. A total of 518 patients participated in the study, 256 of whom received FP and 262 BUD. Assessment of mean morning peak expiratory flow (PEF) over the 12-week treatment period revealed a statistically significant difference in efficacy between FP 800 μg daily and BUD 1600 μg daily in favour of FP (p = 0.003), with an overall improvement of 20.9 l/min with FP compared with 12.4 l/min on BUD. Statistically significant differences in favour of FP were seen over the 12 weeks for mean evening PEF (p = 0.04), diurnal PEF variation (p = 0.03) and percentage predicted PEF (p = 0.003), as well as forced expiratory volume (p = 0.008), forced vital capacity (p = 0.02) and PEF (p = 0.005) measured at clinic visits. The median percentage of symptom-free nights increased over the 12-week study period in both treatment groups, with similar changes seen for the median percentage of days with symptom score < 2, rescue medication use and exacerbations of asthma. The incidence of adverse events was found to be comparable in the two treatment groups. The geometric mean ratios of serum cortisol levels were found to be 1.03 for FP, indicating no mean hypothalamic-pituitary-adrenal axis suppression from baseline, and 0.93 for BUD (p = 0.0002 compared with FP). In summary, FP 800 μg daily showed a greater efficacy/safety ratio in the treatment of moderate-to-severe asthma than BUD 1600 μg daily

Biochemical markers of type II collagen breakdown and synthesis are positioned at specific sites in human osteoarthritic knee cartilage

SummaryObjectiveTo investigate whether type II collagen turnover markers used for osteoarthritis (OA) activity evaluation in body fluids can be detected at the level of specific histological features of OA cartilage tissue, as well as how they relate with each other at this level.MethodsAdjacent sections were obtained from full-depth cartilage biopsies from 32 OA knees. Immunohistochemistry was performed for Helix-II and CTX-II, which are type II collagen fragments originating from the triple helix and the telopeptide region, respectively, and believed to reflect distinct breakdown events, as well as for type IIA N propeptide (PIIANP), a biochemical marker reflecting synthesis of type IIA collagen.ResultsHelix-II and CTX-II were detected in areas where collagen damage was reported previously, most frequently around chondrocytes, but also frequently in regions not previously investigated such as the margin area and close to subchondral bone, including vascularization sites and bone–cartilage interface. The latter is CTX-II's prevailing position and shows rarely Helix-II. PIIANP co-localized with Helix-II and CTX-II on a limited number of features, mainly in deep zone cartilage. Overall, our analysis highlights clear patterns of association of the markers with specific histological features, and shows that they spread to these features in an ordered way.ConclusionHelix-II and CTX-II show to some degree differential selectivity for specific features in cartilage tissue. CTX-II detection close to bone may be relevant to the possible role of subchondral bone in OA. The restricted co-localization of breakdown markers and PIIANP suggests that collagen fragments can result only partially from newly synthesized collagen. Our study strengthens the interest for the question whether combining several markers reflecting different regional cartilage contributions or metabolic processes should allow a broader detection of OA activity

Effectiveness of Saturated Buffers on Water Pollutant Reduction from Agricultural Drainage

It is a pivotal time in the development of saturated buffers as a conservation drainage practice. Field data have demonstrated that this practice can effectively reduce nitrate loads in subsurface drainage. The compilation and assessment of current knowledge for this relatively new practice is timely to help identify future opportunities. This review summarizes the state of the science for saturated buffers in the US within the context of this special collection‘s emphasis on performance and cost. Suggested research areas are identified to improve understanding of saturated buffer function and performance and to refine design processes and criteria to accelerate adoption. As currently designed, saturated buffers removed an average of 46 ± 24% (mean ± sd) of the N load that would have otherwise entered receiving waters (9.4 ± 5.9 kg N removed/ha-y; n = 30 site-years). Cost efficiencies, which generally trended around $3 to$5/kg N removed per year, were considered relatively efficient compared to similar nitrate removal practices (range: $1.20 to$9.20/kg N/y), with planning level costs between $25 and$66/ha treated/y. As adoption is scaled, engineering design costs need to be considered unless the design model can be simplified. Future research should refine design processes, management, and siting criteria to facilitate scaled adoption for water quality goals. Additional studies on nutrient cycling within saturated buffers are needed to fill gaps about nitrogen and phosphorus dynamics and the role of buffer vegetation. Saturated buffers have significant nitrate reduction potential for tile-drained landscapes, but design adaptations may be needed to facilitate adoption in varied landscapes.This article is published as Johnson, Gabriel, Laura Christianson, Reid Christianson, Morgan Davis, Carolina Díaz-García, Tyler Groh, Thomas Isenhart et al. "Effectiveness of saturated buffers on water pollutant reduction from agricultural drainage." Journal of Natural Resources and Agricultural Ecosystems 1 (2023): 49-62. doi: 10.13031/jnrae.15516. Works produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted

Selenoamides modulate dipole-dipole interactions in hydrogen bonded supramolecular polymers of 1,3,5-substituted benzenes

We report the synthesis and self-assembly behavior of a chiral C3-symmetrical benzene-tricarboselenoamide. The introduction of the selenoamide moiety enhances the dipolar character of the supramolecular interaction and confers a remarkable thermal stability to the supramolecular polymers obtained

A classification method for neurogenic heterotopic ossification of the hip

Background: Existing classifications for heterotopic ossification (HO) do not include all HO types; nor do they consider the anatomy of the involved joint or the neurological injury. Therefore, we performed this study to propose and evaluate a classification according to the location of neurogenic HO and the neurological injury. Materials and methods: We studied the files of 24 patients/33 hips with brain or spinal cord injury and neurogenic HO of the hip treated with excision, indomethacin, and radiation therapy. We classified patients according to the Brooker classification scheme as well as ours. Four types of neurogenic HO were distinguished according to the anatomical location of HO: type 1, anterior; type 2, posterior; type 3, anteromedial; type 4, circumferential. Subtypes of each type were added based on the neurological injury: a, spinal cord; b, brain injury. Mean follow-up was 2.5 years (1-8 years). Results: The Brooker classification scheme was misleading - all hips were class III or IV, corresponding to ankylosis, even though only 14 hips had ankylosis. On the other hand, our classification was straightforward and easy to assign in all cases. It corresponded better to the location of the heterotopic bone, and allowed for preoperative planning of the appropriate surgical approach and evaluation of the prognosis; recurrence of neurogenic HO was significantly higher in patients with brain injury (subtype b), while blood loss was higher for patients with anteromedial (type 3) and circumferential (type 4) neurogenic HO. Conclusions: Our proposed classification may improve the management and evaluation of the prognosis for patients with neurogenic HO

CUX1-related neurodevelopmental disorder: deep insights into phenotype-genotype spectrum and underlying pathology

Heterozygous, pathogenic CUX1 variants are associated with global developmental delay or intellectual disability. This study delineates the clinical presentation in an extended cohort and investigates the molecular mechanism underlying the disorder in a Cux1+/− mouse model. Through international collaboration, we assembled the phenotypic and molecular information for 34 individuals (23 unpublished individuals). We analyze brain CUX1 expression and susceptibility to epilepsy in Cux1+/− mice. We describe 34 individuals, from which 30 were unrelated, with 26 different null and four missense variants. The leading symptoms were mild to moderate delayed speech and motor development and borderline to moderate intellectual disability. Additional symptoms were muscular hypotonia, seizures, joint laxity, and abnormalities of the forehead. In Cux1+/− mice, we found delayed growth, histologically normal brains, and increased susceptibility to seizures. In Cux1+/− brains, the expression of Cux1 transcripts was half of WT animals. Expression of CUX1 proteins was reduced, although in early postnatal animals significantly more than in adults. In summary, disease-causing CUX1 variants result in a non-syndromic phenotype of developmental delay and intellectual disability. In some individuals, this phenotype ameliorates with age, resulting in a clinical catch-up and normal IQ in adulthood. The post-transcriptional balance of CUX1 expression in the heterozygous brain at late developmental stages appears important for this favorable clinical course.CAG was supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number P50 HD103525. This work was funded by PID2020-112831GB-I00 AEI /10.13039/501100011033 (MN). SS was supported by a grant from the NIH/NINDS (K23NS119666). SWS is supported by the Hospital for Sick Children Foundation, Autism Speaks, and the University of Toronto McLaughlin Center. EM-G was supported by a grant from MICIU FPU18/06240. EVS. was supported by a grant from the NIH (EY025718). CRF was supported by the fund to support clinical research careers in the Region of Southern Denmark (Region Syddanmarks pulje for kliniske forskerkarriereforløb).Peer reviewe