SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with ...Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing titers against D614G were 4,760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (preboost), respectively, and 320 and 110 for Omicron. 2 weeks after the boost, titers against D614G and Omicron increased to 5,360 and 2,980 for mRNA-1273 boost and 2,670 and 1,930 for mRNA-Omicron, respectively. Similar increases against BA.2 were observed. Following either boost, 70%–80% of spike-specific B cells were cross-reactive against WA1 and Omicron. Equivalent control of virus replication in lower airways was observed following Omicron challenge 1 month after either boost. These data show that mRNA-1273 and mRNA-Omicron elicit comparable immunity and protection shortly after the boost.
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•mRNA-1273 prime induces cross-reactive B cells to Omicron and ancestral strains•Boosting with mRNA-1273 or mRNA-Omicron enhances neutralization of Omicron•Either boost expands B cells cross-reactive to Omicron and ancestral strains•mRNA-1273 or mRNA-Omicron boost is protective against Omicron replication in the lungs
Boosting previously vaccinated nonhuman primates with either the mRNA-1273 or mRNA-Omicron vaccine expands cross-reactive memory B cells and elicits similar levels of protection upon challenge with SARS-CoV-2 Omicron.
Abstract Tuberculosis remains a large global disease burden for which treatment regimens are protracted and monitoring of disease activity difficult. Existing detection methods rely almost ...exclusively on bacterial culture from sputum which limits sampling to organisms on the pulmonary surface. Advances in monitoring tuberculous lesions have utilized the common glucoside 18 FFDG, yet lack specificity to the causative pathogen Mycobacterium tuberculosis ( Mtb ) and so do not directly correlate with pathogen viability. Here we show that a close mimic that is also positron-emitting of the non-mammalian Mtb disaccharide trehalose – 2- 18 Ffluoro-2-deoxytrehalose ( 18 FFDT) – is a mechanism-based reporter of Mycobacteria-selective enzyme activity in vivo. Use of 18 FFDT in the imaging of Mtb in diverse models of disease, including non-human primates, successfully co-opts Mtb -mediated processing of trehalose to allow the specific imaging of TB-associated lesions and to monitor the effects of treatment. A pyrogen-free, direct enzyme-catalyzed process for its radiochemical synthesis allows the ready production of 18 FFDT from the most globally-abundant organic 18 F-containing molecule, 18 FFDG. The full, pre-clinical validation of both production method and 18 FFDT now creates a new, bacterium-selective candidate for clinical evaluation. We anticipate that this distributable technology to generate clinical-grade 18 FFDT directly from the widely-available clinical reagent 18 FFDG, without need for either custom-made radioisotope generation or specialist chemical methods and/or facilities, could now usher in global, democratized access to a TB-specific PET tracer.
Chromosome 22, particularly band 22q11.2, is predisposed to rearrangements due to misalignments of low-copy repeats (LCRs). DiGeorge/velocardiofacial syndrome (DG/VCFS) is a common disorder resulting ...from microdeletion within the same band. Although both deletion and duplication are expected to occur in equal proportions as reciprocal events caused by LCR-mediated rearrangements, very few microduplications have been identified. We have identified 13 cases of microduplication 22q11.2, primarily by interphase fluorescence in situ hybridization (FISH). The size of the duplications, determined by FISH probes from bacterial artificial chromosomes and P
1 artificial chromosomes, range from 3–4 Mb to 6 Mb, and the exchange points seem to involve an LCR. Molecular analysis based on 15 short tandem repeats confirmed the size of the duplications and indicated that at least 1 of 15 loci has three alleles present. The patients’ phenotypes ranged from mild to severe, sharing a tendency for velopharyngeal insufficiency with DG/VCFS but having other distinctive characteristics, as well. Although the present series of patients was ascertained because of some overlapping features with DG/VCF syndromes, the microduplication of 22q11.2 appears to be a new syndrome.
Background
In single-center studies, both preterm birth and low birth weight (LBW) are associated with worse outcomes in childhood nephrotic syndrome. Using the Nephrotic Syndrome Study Network ...(NEPTUNE) observational cohort, we tested the hypothesis that in patients with nephrotic syndrome, hypertension, proteinuria status, and disease progression would be more prevalent and more severe in subjects with LBW and prematurity singly or in combination (LBW/prematurity).
Methods
Three hundred fifty-nine adults and children with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) and available birth history were included. Estimated glomerular filtration rate (eGFR) decline and remission status were primary outcomes, and secondary outcomes were kidney histopathology, kidney gene expression, and urinary biomarkers. Logistic regression was used to identify associations with LBW/prematurity and these outcomes.
Results
We did not find an association between LBW/prematurity and remission of proteinuria. However, LBW/prematurity was associated with greater decline in eGFR. This decline in eGFR was partially explained by the association of LBW/prematurity with
APOL1
high-risk alleles, but the association remained after adjustment. There were no differences in kidney histopathology or gene expression in the LBW/prematurity group compared to normal birth weight/term birth.
Conclusion
LBW and premature babies who develop nephrotic syndrome have a more rapid decline in kidney function. We did not identify clinical or laboratory features that distinguished the groups. Additional studies in larger groups are needed to fully ascertain the effects of (LBW) and prematurity alone or in combination on kidney function in the setting of nephrotic syndrome.
Aims
The aim of the study was to examine the content and impact of interventions that have been used to increase the uptake of pre‐pregnancy care for women with type 2 diabetes, and their impact on ...maternal and fetal outcomes.
Methods
A systematic search of multiple databases was conducted in November 2021, and updated July 2022, to identify studies assessing interventions to enhance pre‐pregnancy care for women with type 2 diabetes. Over 10% of articles were screened by two reviewers at title and phase, after which all selected full‐text articles were screened by two reviewers. Quality assessment was conducted using the Critical Appraisal Skills Programme checklist for cohort studies. Meta‐analysis was not possible due to study heterogeneity; therefore, narrative synthesis was conducted.
Results
Four eligible cohort studies were identified. The conclusions able to be drawn by this review were limited as women with type 2 diabetes (n = 800) were in the minority in all four studies (35%–40%) and none of the interventions were exclusively tailored for them. The uptake of pre‐pregnancy care was lower in women with type 2 diabetes (8%–10%) compared with other participant groups in the studies. Pregnancy preparation indicators generally improved among all groups exposed to pre‐pregnancy care, with varying impact on pregnancy outcomes.
Conclusions
This review demonstrates that previous interventions have had a limited impact on pre‐pregnancy care uptake in women with type 2 diabetes. Future studies should focus on tailored interventions for improving pre‐pregnancy care for women with type 2 diabetes, particularly those from ethnic minorities and living in poorer communities.
Background
In the current study, longitudinal BP and lipid measurements were examined in a NEPTUNE cohort of children with newly diagnosed nephrotic syndrome (cNEPTUNE). We hypothesized that ...hypertensive BP and dyslipidemia would persist in children with nephrotic syndrome, regardless of steroid treatment response.
Methods
A multi-center longitudinal observational analysis of data obtained from children < 19 years of age with new onset nephrotic syndrome enrolled in the Nephrotic Syndrome Study Network (cNEPTUNE) was conducted. BP and lipid data were examined over time stratified by disease activity and steroid exposure. Generalized estimating equation regressions were used to find determinants of hypertensive BP and dyslipidemia.
Results
Among 122 children, the prevalence of hypertensive BP at any visit ranged from 17.4% to 57.4%, while dyslipidemia prevalence ranged from 40.0% to 96.2% over a median of 30 months of follow-up. Hypertensive BP was found in 46.2% (116/251) of study visits during active disease compared with 31.0% (84/271) of visits while in remission. Dyslipidemia was present in 88.2% (120/136) of study visits during active disease and in 66.0% (101/153) while in remission. Neither dyslipidemia nor hypertensive BP were significantly different with/without medication exposure (steroids and/or CNI). In regression analysis, male sex and urine protein:creatinine ratio (UPC) were significant determinants of hypertensive BP over time, while eGFR was found to be a determinant of dyslipidemia over time.
Conclusions
Results demonstrate persistent hypertensive BPs and unfavorable lipid profiles in the cNEPTUNE cohort regardless of remission status or concurrent steroid or calcineurin inhibitor treatment.
Graphical abstract
A higher resolution version of the Graphical abstract is available as
Supplementary information
Modern paints and coatings are designed for a variety of applications, ranging from fine art to extraterrestrial thermal control. These systems can be engineered to provide lasting color, but there ...are a limited number of materials that can undergo transient changes in their visual appearance in response to external stimuli without requirements for advanced fabrication strategies. The authors describe color-changing paint formulations that leverage the redox-dependent absorption profile of xanthommatin, a small-molecule colorant found throughout biology, and the electronic properties of titanium dioxide, a ubiquitous whitening agent in commercial coatings. This combination yields reversible photoreduction upon exposure to sunlight, shifting from the oxidized (yellow) form of xanthommatin, to the reduced (red) state. The extent of photoreduction is dependent on the loading density and size of titanium dioxide particles, generating changes in hue angle as large as 77% upon irradiation. These coatings can be blended with non-responsive supplemental colorants to expand the accessible color palette, and irradiated through masks to create transient, disappearing artwork. These formulations demonstrate energy-efficient photochromism using a simple combination of a redox-active dye and metal oxide semiconductor, highlighting the utility of these materials for the development of optically dynamic light-harvesting materials.
Machines of protein destruction—including energy-dependent proteases and disassembly chaperones of the AAA+ ATPase family—function in all kingdoms of life to sculpt the cellular proteome, ensuring ...that unnecessary and dangerous proteins are eliminated and biological responses to environmental change are rapidly and properly regulated. Exciting progress has been made in understanding how AAA+ machines recognize specific proteins as targets and then carry out ATP-dependent dismantling of the tertiary and/or quaternary structure of these molecules during the processes of protein degradation and the disassembly of macromolecular complexes.
Workers, particularly outdoor workers, are among the populations most disproportionately affected by climate-related hazards. However, scientific research and control actions to comprehensively ...address these hazards are notably absent. To assess this absence, a seven-category framework was developed in 2009 to characterize the scientific literature published from 1988-2008. Using this framework, a second assessment examined the literature published through 2014, and the current one examines literature from 2014-2021. The objectives were to present literature that updates the framework and related topics and increases awareness of the role of climate change in occupational safety and health. In general, there is substantial literature on worker hazards related to ambient temperatures, biological hazards, and extreme weather but less on air pollution, ultraviolet radiation, industrial transitions, and the built environment. There is growing literature on mental health and health equity issues related to climate change, but much more research is needed. The socioeconomic impacts of climate change also require more research. This study illustrates that workers are experiencing increased morbidity and mortality related to climate change. In all areas of climate-related worker risk, including geoengineering, research is needed on the causality and prevalence of hazards, along with surveillance to identify, and interventions for hazard prevention and control.
Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive ...deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP.
This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project.
Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90(th) percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject's BP/95(th) percentile BP) correlated inversely with Performance IQ score (systolic, r = -0.13, P = 0.01; diastolic, r = -0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = -3.7, 95% confidence interval CI: -7.3 to -0.06; systolic BP index, β = -1.16 to 95% CI: -2.1, -0.21; diastolic BP index, β = -1.17, 95% CI: -1.8 to -0.55).
Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD.
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