We analyze the transport of light in the bulk and at the edge of photonic Lieb lattices, whose unique feature is the existence of a flat band representing stationary states in the middle of the band ...structure that can form localized bulk states. We find that transport in bulk Lieb lattices is significantly affected by the particular excitation site within the unit cell, due to overlap with the flat band states. Additionally, we demonstrate the existence of new edge states in anisotropic Lieb lattices. These states arise due to a virtual defect at the lattice edges and are not described by the standard tight-binding model.
Natural molecular machines contain protein components that undergo motion relative to each other. Designing such mechanically constrained nanoscale protein architectures with internal degrees of ...freedom is an outstanding challenge for computational protein design. Here we explore the de novo construction of protein machinery from designed axle and rotor components with internal cyclic or dihedral symmetry. We find that the axle-rotor systems assemble in vitro and in vivo as designed. Using cryo-electron microscopy, we find that these systems populate conformationally variable relative orientations reflecting the symmetry of the coupled components and the computationally designed interface energy landscape. These mechanical systems with internal degrees of freedom are a step toward the design of genetically encodable nanomachines.
Studies evaluating sputum quality and Xpert
MTB/RIF positivity in the context of active case finding are scarce. We aimed to determine whether sputum quality is associated with Xpert positivity and ...whether the association differed according to demographic and clinical characteristics.
A cross-sectional analysis using data from a mass screening programme in Brazilian prisons was conducted from 2017 to 2021. We administered a standardised questionnaire, obtained a chest X-ray and collected a spot sputum sample for Xpert testing. Sputum quality was classified as 'salivary', 'mucoid/mucopurulent' or 'blood-stained'. We used log binomial regressions to estimate the relationship between sputum quality and Xpert positivity, assessing interactions with participant characteristics.
Among 4,368 participants for whom sputum quality was assessed, 957 (21.9%) produced salivary specimens, 3,379 (77.4%) had mucoid/mucopurulent sputum and 32 (0.7%) had blood-stained sputum. Xpert positivity was higher among those with mucoid/mucopurulent sputum than among those with salivary samples (12.0% vs. 3.7%). Mucopurulent sputum independently predicted Xpert positivity among individuals with and without symptoms, current smoking and abnormal chest radiographs on CAD4TB.
In our study, sputum appearance independently predicted Xpert positivity, and could be used together with chest X-ray and symptom screening to inform use of Xpert in individual or pooled testing.
Exercise training reduces renin-angiotensin system (RAS) activation, decreases plasma and tissue oxidative stress and inflammation in hypertension. However, the temporal nature of these phenomena in ...response to exercise is unknown. We sought to determine in spontaneously hypertensive rats (SHR) and age-matched WKY controls the weekly effects of training on blood pressure (BP), plasma and left ventricle (LV) Ang II and Ang-(1-7) content (HPLC), LV oxidative stress (DHE staining), gene and protein expression (qPCR and WB) of pro-inflammatory cytokines, antioxidant enzymes and their consequence on hypertension-induced cardiac remodeling. SHR and WKY were submitted to aerobic training (T) or maintained sedentary (S) for 8 weeks; measurements were made at weeks 0, 1, 2, 4 and 8. Hypertension-induced cardiac hypertrophy was accompanied by acute plasma Ang II increase with amplified responses during the late phase of LV hypertrophy. Similar pattern was observed for oxidative stress markers, TNF alpha and interleukin-1β, associated with cardiomyocytes' diameter enlargement and collagen deposition. SHR-T exhibited prompt and marked decrease in LV Ang II content (T1 vs T4 in WKY-T), normalized oxidative stress (T2), augmented antioxidant defense (T4) and reduced both collagen deposition and inflammatory profile (T8), without changing cardiomyocytes' diameter and LV hypertrophy. These changes were accompanied by decreased plasma Ang II content (T2-T4) and reduced BP (T8). SHR-T and WKY-T showed parallel increases in LV and plasma Ang-(1-7) content. Our data indicate that early training-induced downregulation of LV ACE-AngII-AT1 receptor axis is a crucial mechanism to reduce oxidative/pro-inflammatory profile and improve antioxidant defense in SHR-T, showing in addition this effect precedes plasma RAS deactivation.
Recent proteomic studies have identified multiple proteins that coisolate with human HDL. We hypothesized that distinct clusters of protein components may distinguish between ...physicochemically-defined subpopulations of HDL particles, and that such clusters may exert specific biological function(s).
We investigated the distribution of proteins across 5 physicochemically-defined particle subpopulations of normolipidemic human HDL (HDL2b, 2a, 3a, 3b, 3c) fractionated by isopycnic density gradient ultracentrifugation. Liquid chromatography/electrospray mass spectrometry identified a total of 28 distinct HDL-associated proteins. Using an abundance pattern analysis of peptide counts across the HDL subfractions, these proteins could be grouped into 5 distinct classes. A more in-depth correlational network analysis suggested the existence of distinct protein clusters, particularly in the dense HDL3 particles. Levels of specific HDL proteins, primarily apoL-I, PON1, and PON3, correlated with the potent capacity of HDL3 to protect LDL from oxidation.
These findings suggest that HDL is composed of distinct particles containing unique (apolipo)protein complements. Such subspeciation forms a potential basis for understanding the numerous observed functions of HDL. Further work using additional separation techniques will be required to define these species in more detail.
The demand for insect-pollinated crops is increasing. Conventional agricultural intensification heavily relies on increased input of fertilizers, which can have negative effects on local ...biodiversity. Such effects may be particularly accentuated in biodiversity hotspots that are naturally nutrient-poor. Ecological intensification of farming, i.e. practices that increase production through the increase of ecosystem services, emerges as an alternative to conventional intensification. For example, practices that boost abundance and diversity of crop pollinators can lead to substantial increases in cropland productivity. However, little is known about the synergisms and trade-offs between fertilizer input and such ecological intensification practices. Here we investigate interactive effects between fertilization practices and the provision of ecosystem services in a biodiversity hotspot where conventional agriculture is rapidly expanding (Brazilian savannas). We focus on a highly nitrogen-demanding crop species that benefits from pollinators (the common bean, Phaseolus vulgaris L.), for which nitrogen input greatly varies in the study region. Our findings show that positive effects of native pollinators on crop yield are most accentuated under low inputs of nitrogen (e.g. equal to or below 72kg ha-1). This interactive effect could be due to changes in flower visitor community composition or behaviour. Our study also suggests that landscape management practices that minimize isolation from patches of natural vegetation and maximize its cover nearby (within 500 meters) of production areas can increase pollinator and biocontrol agent abundance and richness. Overall, these results suggest that ecological intensification is a valuable alternative for common bean production in Brazil, and potentially other regions of the world. Land productivity can be enhanced if an adequate balance of chemical inputs and landscape management is achieved.
Food allergy can have significant effects on morbidity and quality of life and can be costly in terms of medical visits and treatments. There is therefore considerable interest in generating ...efficient approaches that may reduce the risk of developing food allergy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Prevention and is part of the EAACI Guidelines for Food Allergy and Anaphylaxis. It aims to provide evidence‐based recommendations for primary prevention of food allergy. A wide range of antenatal, perinatal, neonatal, and childhood strategies were identified and their effectiveness assessed and synthesized in a systematic review.
Based on this evidence, families can be provided with evidence‐based advice about preventing food allergy, particularly for infants at high risk for development of allergic disease. The advice for all mothers includes a normal diet without restrictions during pregnancy and lactation. For all infants, exclusive breastfeeding is recommended for at least first 4–6 months of life. If breastfeeding is insufficient or not possible, infants at high‐risk can be recommended a hypoallergenic formula with a documented preventive effect for the first 4 months. There is no need to avoid introducing complementary foods beyond 4 months, and currently, the evidence does not justify recommendations about either withholding or encouraging exposure to potentially allergenic foods after 4 months once weaning has commenced, irrespective of atopic heredity. There is no evidence to support the use of prebiotics or probiotics for food allergy prevention.
Most concrete produced today includes either chemical additions to the cement, chemical admixtures in the concrete, or both. These chemicals alter a number of properties of cementitious systems, ...including hydration behavior, and it has been long understood by practitioners that these systems can differ widely in response to such chemicals.
In this paper the impact on hydration of several classes of chemicals is reviewed with an emphasis on the current understanding of interactions with cement chemistry. These include setting retarders, accelerators, and water reducing dispersants. The ability of the chemicals to alter the aluminate–sulfate balance of cementitious systems is discussed with a focus on the impact on silicate hydration. As a key example of this complex interaction, unusual behavior sometimes observed in systems containing high calcium fly ash is highlighted.
Drug‐induced liver injury (DILI) is a major cause of acute liver failure (ALF), where hepatocyte necrotic products trigger liver inflammation, release of CXC chemokine receptor 2 (CXCR2) ligands ...(IL‐8) and other neutrophil chemotactic molecules. Liver infiltration by neutrophils is a major cause of the life‐threatening tissue damage that ensues. A GRPR (gastrin‐releasing peptide receptor) antagonist impairs IL‐8‐induced neutrophil chemotaxis in vitro. We investigated its potential to reduce acetaminophen‐induced ALF, neutrophil migration, and mechanisms underlying this phenomenon. We found that acetaminophen‐overdosed mice treated with GRPR antagonist had reduced DILI and neutrophil infiltration in the liver. Intravital imaging and cell tracking analysis revealed reduced neutrophil mobility within the liver. Surprisingly, GRPR antagonist inhibited CXCL2‐induced migration in vivo, decreasing neutrophil activation through CD11b and CD62L modulation. Additionally, this compound decreased CXCL8‐driven neutrophil chemotaxis in vitro independently of CXCR2 internalization, induced activation of MAPKs (p38 and ERK1/2) and downregulation of neutrophil adhesion molecules CD11b and CD66b. In silico analysis revealed direct binding of GRPR antagonist and CXCL8 to the same binding spot in CXCR2. These findings indicate a new potential use for GRPR antagonist for treatment of DILI through a mechanism involving adhesion molecule modulation and possible direct binding to CXCR2.
Drug‐induced liver injury is expanded by neutrophil recruitment. Here, we describe that a GRPR antagonist protects from extended liver damage by reducing neutrophil activation and motility. An unexpected interaction between GRPR antagonist and CXCR2 competes for the binding site of CXCL8, preventing neutrophil chemotaxis.
Dental implants have become an increasingly popular treatment choice for replacing missing teeth. Yet, little is known about the prevalence and sociodemographic distribution of dental implant use in ...the United States. To address this knowledge gap, we analyzed data from 7 National Health and Nutrition Examination Surveys from 1999 to 2016. We estimated dental implant prevalence among adults missing any teeth for each survey period overall as stratified by sociodemographic characteristics. We calculated absolute and relative differences from 1999–2000 to 2015–2016 and fit logistic regression models to estimate changes over time. We also used multivariable logistic regression to estimate independent associations of sociodemographic covariates with the presence of any implant. We projected the proportion of patients treated with dental implants into the year 2026 under varying assumptions of how the temporal trend would continue. There has been a large increase in the prevalence of dental implants, from 0.7% in 1999 to 2000 to 5.7% in 2015 to 2016. The largest absolute increase in prevalence (12.9%) was among individuals 65 to 74 y old, whereas the largest relative increase was ~1,000% among those 55 to 64 y old. There was an average covariate-adjusted increase in dental implant prevalence of 14% per year (95% CI, 11% to 18%). Having private insurance (vs. none or public insurance) or more than a high school education (vs. high school or less) was each associated with a 2-fold increase in prevalence, with an almost 13-fold (95% CI, 8 to21) increase for older adults. Dental implant prevalence projected to 2026 ranged from 5.7% in the most conservative scenario to 23% in the least. This study demonstrates that dental implant prevalence among US adults with missing teeth has substantially increased since 1999. Yet access overall is still very low, and prevalence was consistently higher among more advantaged groups.
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