Influenza epidemics cause substantial morbidity. The seasonal vaccine, an important control measure, is not completely efficacious. This trial assessed the efficacy of a recombinant seasonal vaccine ...(made in a cell culture rather than with viruses grown in eggs).
Reducing the burden of influenza disease requires improved vaccines, and a recombinant influenza vaccine may contribute to this public-health goal.
1
This vaccine contains recombinant hemagglutinin (HA) proteins produced in a serum-free medium by
expres
SF+ cells. These cells contain recombinant baculovirus vectors carrying genes that code for HA. The process yields recombinant HA that is genetically identical to the selected influenza strains without extraneous egg proteins, formaldehyde, antibiotics, or preservatives. Influenza viruses are grown in eggs to produce the inactivated influenza vaccine (IIV); these viruses typically contain mutations in the genes that code for HA that may reduce vaccine effectiveness. . . .
Langerhans cell histiocytosis (LCH) can affect children and adults with a wide variety of clinical manifestations, including unifocal, single-system multifocal, single-system pulmonary ...(smoking-associated), or multisystem disease. The existing paradigms in the management of LCH in adults are mostly derived from the pediatric literature. Over the last decade, the discovery of clonality and MAPK-ERK pathway mutations in most cases led to the recognition of LCH as a hematopoietic neoplasm, opening the doors for treatment with targeted therapies. These advances have necessitated an update of the existing recommendations for the diagnosis and treatment of LCH in adults. This document presents consensus recommendations that resulted from the discussions at the annual Histiocyte Society meeting in 2019, encompassing clinical features, classification, diagnostic criteria, treatment algorithm, and response assessment for adults with LCH. The recommendations favor the use of 18F-Fluorodeoxyglucose positron emission tomography-based imaging for staging and response assessment in the majority of cases. Most adults with unifocal disease may be cured by local therapies, while the first-line treatment for single-system pulmonary LCH remains smoking cessation. Among patients not amenable or unresponsive to these treatments and/or have multifocal and multisystem disease, systemic treatments are recommended. Preferred systemic treatments in adults with LCH include cladribine or cytarabine, with the emerging role of targeted (BRAF and MEK inhibitor) therapies. Despite documented responses to treatments, many patients struggle with a high symptom burden from pain, fatigue, and mood disorders that should be acknowledged and managed appropriately.
When it comes to Confederate monuments, there is no common ground.
Polarizing debates over their meaning have intensified into
legislative maneuvering to preserve the statues, legal battles to
remove ...them, and rowdy crowds taking matters into their own hands.
These conflicts have raged for well over a century--but they've
never been as intense as they are today. In this eye-opening
narrative of the efforts to raise, preserve, protest, and remove
Confederate monuments, Karen L. Cox depicts what these statues
meant to those who erected them and how a movement arose to force a
reckoning. She lucidly shows the forces that drove white
southerners to construct beacons of white supremacy, as well as the
ways that antimonument sentiment, largely stifled during the Jim
Crow era, returned with the civil rights movement and gathered
momentum in the decades after the Voting Rights Act of 1965.
Monument defenders responded with gerrymandering and "heritage"
laws intended to block efforts to remove these statues, but hard as
they worked to preserve the Lost Cause vision of southern history,
civil rights activists, Black elected officials, and movements of
ordinary people fought harder to take the story back. Timely,
accessible, and essential, No Common Ground is the story
of the seemingly invincible stone sentinels that are just beginning
to fall from their pedestals.
From the late nineteenth century through World War II, popular culture portrayed the American South as a region ensconced in its antebellum past, draped in moonlight and magnolias, and represented by ...such southern icons as the mammy, the belle, the chivalrous planter, white-columned mansions, and even bolls of cotton.InDreaming of Dixie, Karen Cox shows that the chief purveyors of this constructed nostalgia for the Old South were outsiders of the region, especially advertising agencies, musicians, publishers, radio personalities, writers, and filmmakers playing to consumers' anxiety about modernity by marketing the South as a region still dedicated to America's pastoral traditions. Cox examines how southerners themselves embraced the imaginary romance of the region's past, particularly in the tourist trade as southern states and cities sought to capitalize on popular perceptions by showcasing their Old South heritage. Only when television emerged as the most influential medium of popular culture did views of the South begin to change, as news coverage of the civil rights movement brought images of violence, protest, and conflict in the South into people's living rooms. Until then, Cox argues, most Americans remained content with their romantic vision of Dixie.
Once upon a time, it was impossible to drive through the South without coming across signs to "See Rock City" or similar tourist attractions. From battlegrounds to birthplaces, and sites in between, ...heritage tourism has always been part of how the South attracts visitors--and defines itself--yet such sites are often understudied in the scholarly literature.
As the contributors to this volume make clear, the narrative of southern history told at these sites is often complicated by race, influenced by local politics, and shaped by competing memories. Included are essays on the meanings of New Orleans cemeteries; Stone Mountain, Georgia; historic Charleston, South Carolina; Yorktown National Battlefield; Selma, Alabama, as locus of the civil rights movement; and the homes of Mark Twain, Margaret Mitchell, and other notables.
Destination Dixie reveals that heritage tourism in the South is about more than just marketing destinations and filling hotel rooms; it cuts to the heart of how southerners seek to shape their identity and image for a broader touring public--now often made up of northerners and southerners alike.
Background:
Artificial intelligence (AI) has the potential to revolutionize nursing education. This study compared NCLEX-RN questions generated by AI and those created by nurse educators.
Method:
...Faculty of accredited baccalaureate programs were invited to participate. Likert-scale items for grammar and clarity of the item stem and distractors were compared using Mann-Whitney U, and yes/no questions about clinical relevance and complex terminology were analyzed using chi-square. A one-sample binomial test with confidence intervals evaluated participants' question preference (AI-generated or educator-written). Qualitative responses identified themes across faculty.
Results:
Item clarity, grammar, and difficulty were similar for AI and educator-created questions. Clinical relevance and use of complex terminology was similar for all question pairs. Of the four sets with preference for one item, three were generated by AI.
Conclusion:
AI can assist faculty with item generation to prepare nursing students for the NCLEX-RN examination. Faculty expertise is necessary to refine questions written using both methods.
J Nurs Educ
. 2023;62(12):679–687.
Protein-coding genetic variants that strongly affect disease risk can yield relevant clues to disease pathogenesis. Here we report exome-sequencing analyses of 20,791 individuals with type 2 diabetes ...(T2D) and 24,440 non-diabetic control participants from 5 ancestries. We identify gene-level associations of rare variants (with minor allele frequencies of less than 0.5%) in 4 genes at exome-wide significance, including a series of more than 30 SLC30A8 alleles that conveys protection against T2D, and in 12 gene sets, including those corresponding to T2D drug targets (P = 6.1 × 10
) and candidate genes from knockout mice (P = 5.2 × 10
). Within our study, the strongest T2D gene-level signals for rare variants explain at most 25% of the heritability of the strongest common single-variant signals, and the gene-level effect sizes of the rare variants that we observed in established T2D drug targets will require 75,000-185,000 sequenced cases to achieve exome-wide significance. We propose a method to interpret these modest rare-variant associations and to incorporate these associations into future target or gene prioritization efforts.
A rare lysosomal disease resembling a mucopolysaccharidosis with unusual systemic features, including renal disease and platelet dysfunction, caused by the defect in a conserved region of the VPS33A ...gene on human chromosome 12q24.31, occurs in Yakuts-a nomadic Turkic ethnic group of Southern Siberia. VPS33A is a core component of the class C core vacuole/endosome tethering (CORVET) and the homotypic fusion and protein sorting (HOPS) complexes, which have essential functions in the endocytic pathway. Here we show that cultured fibroblasts from patients with this disorder have morphological changes: vacuolation with disordered endosomal/lysosomal compartments and-common to sphingolipid diseases-abnormal endocytic trafficking of lactosylceramide. Urine glycosaminoglycan studies revealed a pathological excess of sialylated conjugates as well as dermatan and heparan sulphate. Lipidomic screening showed elevated β-D-galactosylsphingosine with unimpaired activity of cognate lysosomal hydrolases. The 3D crystal structure of human VPS33A predicts that replacement of arginine 498 by tryptophan will de-stabilize VPS33A folding. We observed that the missense mutation reduced the abundance of full-length VPS33A and other components of the HOPS and CORVET complexes. Treatment of HeLa cells stably expressing the mutant VPS33A with a proteasome inhibitor rescued the mutant protein from degradation. We propose that the disease is due to diminished intracellular abundance of intact VPS33A. Exposure of patient-derived fibroblasts to the clinically approved proteasome inhibitor, bortezomib, or inhibition of glucosylceramide synthesis with eliglustat, partially corrected the impaired lactosylceramide trafficking defect and immediately suggest therapeutic avenues to explore in this fatal orphan disease.
The Human Epigenome Project aims to identify, catalogue, and interpret genome-wide DNA methylation phenomena. Occurring naturally on cytosine bases at cytosine-guanine dinucleotides, DNA methylation ...is intimately involved in diverse biological processes and the aetiology of many diseases. Differentially methylated cytosines give rise to distinct profiles, thought to be specific for gene activity, tissue type, and disease state. The identification of such methylation variable positions will significantly improve our understanding of genome biology and our ability to diagnose disease. Here, we report the results of the pilot study for the Human Epigenome Project entailing the methylation analysis of the human major histocompatibility complex. This study involved the development of an integrated pipeline for high-throughput methylation analysis using bisulphite DNA sequencing, discovery of methylation variable positions, epigenotyping by matrix-assisted laser desorption/ionisation mass spectrometry, and development of an integrated public database available at http://www.epigenome.org. Our analysis of DNA methylation levels within the major histocompatibility complex, including regulatory exonic and intronic regions associated with 90 genes in multiple tissues and individuals, reveals a bimodal distribution of methylation profiles (i.e., the vast majority of the analysed regions were either hypo- or hypermethylated), tissue specificity, inter-individual variation, and correlation with independent gene expression data.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Randomized comparison of immunogenicity and safety of quadrivalent recombinant versus inactivated vaccine in young adults showed overall comparable antibody titers to vaccine strains, including ...higher responses to influenza A/H3N2 consistent with better efficacy previously reported in adults 50 or older.
Abstract
Background
Seasonal influenza vaccines are transitioning to quadrivalent formulations including the hemagglutinins of influenza A subtypes H1N1 and H3N2 and B lineages Yamagata and Victoria.
Methods
A new quadrivalent recombinant influenza vaccine (RIV4) was compared directly with a standard-dose, egg-grown, quadrivalent-inactivated influenza vaccine (IIV4) for immunogenicity and safety in adults 18–49 years of age. The coprimary endpoints for noninferiority were hemagglutination inhibition seroconversion rates and postvaccination geometric mean titer ratios for each antigen using US regulatory criteria. Reactogenicity solicited for 7 days, other safety events collected for 28 days, and serious or medically attended adverse events collected for 6 months after vaccination comprised the safety evaluation.
Results
The immunogenicity of RIV4 was comparable to that of IIV4; the coprimary noninferiority criteria were met for 3 antigens, and the antibody responses to the fourth antigen, influenza B/Brisbane/60/2008, were low in each group, making comparisons uninterpretable. Systemic and injection site reactions were mild, transient, and similar in each group, whereas none of the spontaneously reported adverse events, serious or nonserious, were considered related to study vaccine.
Conclusions
This first head-to-head comparison of recombinant versus inactivated quadrivalent influenza vaccines in 18–49 year old adults showed comparable immunogenicity, safety, and tolerability for both vaccines.
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