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Summary: The current focus on the use phase in automotive carbon dioxide (CO2) legislation bares a risk of unintended consequences as often reductions in the use phase come along with increasing CO2 emissions in other life cycle (LC) phases. This study presents voluntary policy options in form of LC‐based CO2 emission credits. They were developed by desk research considering existing applications of LCA in practice (e.g., environmental reports) and feedback obtained in a structured stakeholder dialogue. A variety of credit options were identified, including rather simple ones based on life cycle thinking (LCT) and more advanced options which rely on quantitative LCA: LCT options that reward innovations leading to CO2 reductions, for example, in the production phase. LCA‐based options reward CO2 reductions along the LC (credits for an International Organization for Standardization [ISO] 14044 conforming externally reviewed LCA showing a continuous improvement) or reductions of other environmental impacts. It was shown that the credit options can be implemented throughout a simplified and robust methodology, for example, with defined rules for conducting the LCA based on international standards and established industry practice, and for calculating the credits (e.g., a credit of 1 gram [g] of CO2/km [kilometer] for savings of 10 g of CO2/km). Voluntary credit options as a complementary modality to the current automotive tailpipe‐based CO2 regulations would help to improve its efficiency and effectiveness and support and reward efforts on achieving real net CO2 emission reductions. The credit options were developed with a first focus on CO2 and automotive industry, but can generally be transferred to other environmental impacts and sectors as well. [ABSTRACT FROM AUTHOR]

The supply of water, food, and energy in our global economy is highly interlinked. Virtual blue water embedded into internationally traded food crops has therefore been extensively researched in recent years. This study focuses on the often neglected energy needed to supply this blue irrigation water. It provides a globally applicable and spatially explicit approach to the watershed level for water source specific quantification of energy consumption and related greenhouse gas (GHG) emissions of irrigation water supply. The approach is applied to Israel's total domestic and imported food crop supply of 105 crops by additionally including import‐related transportation energy and emissions. Total energy use and related emissions of domestic crop production were much lower (551 GWh/422 kt CO2‐equivalents [CO2e]) than those embedded into crop imports (1639 GWh/649 kt CO2e). Domestic energy and emissions were mainly attributable to the irrigation water supply with artificial water sources (treated domestic wastewater and desalinated water, 84%). Transport accounted for 79% and 66% of virtually imported energy and emissions, respectively. Despite transport, specific GHG emissions (CO2e per ton of crop) were significantly lower for several crops (e.g., olives, almonds, chickpeas) compared to domestic production. This could be attributed to the high share of energy‐intensive artificial water supply in combination with higher irrigation water demands in Israel. In the course of an increasing demand for artificial water supply in arid and semi‐arid regions, our findings point to the importance of including "energy for water" into comparative environmental assessment of crop supply to support decision‐making related to the water–energy–food nexus. [ABSTRACT FROM AUTHOR]

This work identifies shortcomings in water footprinting and discusses whether the water footprint should be a volumetric or impact-oriented index. A key challenge is the current definition of water consumption according to which evaporated water is regarded as lost for the originating watershed per se. Continental evaporation recycling rates of up to 100% within short time and length scales show that this definition is not generally valid. Also, the inclusion of land use effects on the hydrological balance is questionable, as land transformation often leads to higher water availability due to locally increased runoff. Unless potentially negative consequences, such as flooding or waterlogging, and adverse effects on the global water cycle are considered, water credits from land transformation seem unjustified. Most impact assessment methods use ratios of annual withdrawal or consumption to renewability rates to denote local water scarcity. As these ratios are influenced by two metrics-withdrawal and availability-arid regions can be regarded as uncritical if only small fractions of the limited renewable supplies are used. Besides neglecting sensitivities to additional water uses, such indicators consider neither ground nor surface water stocks, which can buffer water shortages temporally. Authors favoring volumetric indicators claim that global freshwater appropriation is more important than local impacts, easier to determine, and less error prone than putting complex ecological interaction into mathematical models. As shown in an example, volumetric water footprints can be misleading without additional interpretation because numerically smaller footprints can cause higher impacts. [ABSTRACT FROM AUTHOR]

N -Acetylglucosamine is a major component of complex carbohydrates. The mammalian salvage pathway of N -acetylglucosamine recruitment from glycoconjugate degradation or nutritional sources starts with phosphorylation by N -acetylglucosamine kinase. In this study we describe the identification of two active site cysteines of the sugar kinase by site-directed mutagenesis and computer-based structure prediction. Murine N -acetylglucosamine kinase contains six cysteine residues, all of which were mutated to serine residues. The strongest reduction of enzyme activity was found for the mutant C131S, followed by C143S. Determination of the kinetic properties of the cysteine mutants showed that the decreased enzyme activities were due to a strongly decreased affinity to either N -acetylglucosamine for C131S, or ATP for C143S. A secondary structure prediction of N -acetylglucosamine kinase showed a high homology to glucokinase. A model of the three-dimensional structure ofN -acetylglucosamine kinase based on the known structure of glucokinase was therefore generated. This model confirmed that both cysteines are located in the active site of N -acetylglucosamine kinase with a potential role in the binding of the transfered γ-phosphate group of ATP within the catalytic mechanism. [ABSTRACT FROM AUTHOR]

N-Acetylglucosamine is produced by the endogenous degradation of glycoconjugates and by the degradation of dietary glycoconjugates by glycosidases. It enters the pathways of aminosugar metabolism by the action of N-acetylglucosamine kinase. In this study we report the isolation and characterization of a cDNA clone encoding the murine enzyme. An open reading frame of 1029 base pairs encodes 343 amino acids with a predicted molecular mass of 37.3 kDa. The deduced amino-acid sequence contains matches of the sequences of eight peptides derived from tryptic cleavage of rat N-acetylglucosamine kinase. The recombinant murine enzyme was functionally expressed in Escherichia coli BL21 cells, where it displays N-acetylglucosamine kinase activity as well as N-acetylmannosamine kinase activity. The complete cDNA sequence of human N-acetylglucosamine kinase was derived from the nucleotide sequences of several expressed sequence tags. An open reading frame of 1032 base pairs encodes 344 amino acids and a protein with a predicted molecular mass of 37.4 kDa. Similarities between human and murine N-acetylglucosamine kinase were 86.6% on the nucleotide level and 91.6% on the amino-acid level. Amino-acid sequences of murine and human N-acetylglucosamine kinase show sequence similarities to other sugar kinases, and all five sequence motifs necessary for the binding of ATP by sugar kinases are present. Tissue distribution of murine N-acetylglucosamine kinase revealed an ubiquitous occurrence of the enzyme and a very high expression in testis. The size of the murine mRNA was 1.35 kb in all tissues investigated, with the exception of testis, where it was 1.45 kb mRNA of the murine enzyme was continuously expressed during mouse development. mRNA of the human enzyme was expressed in all investigated human tissues, as well as in cancer cell lines. In both the tissues and the cancer cell lines, the human mRNA was 1.35 kb in size. [ABSTRACT FROM AUTHOR]

Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real‐time, real‐world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK‐air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients. [ABSTRACT FROM AUTHOR]

Background: We investigated the biological function of the mould allergen Alt a 1 as a carrier of micronutrients, such as the vitamin A metabolite retinoic acid (RA) and the influence of RA binding on its allergenicity in vitro and in vivo. Methods: Alt a 1‐RA complex formation was analyzed in silico and in vitro. PBMCs from Alternaria‐allergic donors were stimulated with Alt a 1 complexed with RA (holo‐Alt a 1) or empty apo‐Alt a 1 and analyzed for cytokine production and CD marker expression. Serum IgE‐binding and crosslinking assays to apo‐ and holo‐protein were correlated to B‐cell epitope analysis. Female BALB/c mice already sensitized to Alt a 1 were intranasally treated with apo‐Alt a 1, holo‐Alt a 1 or RA alone before measuring anaphylactic response, serum antibody levels, splenic cytokines and CD marker expression. Results: In silico docking calculations and in vitro assays showed that the extent of RA binding depended on the higher quaternary state of Alt a 1. Holo‐Alt a 1 loaded with RA reduced IL‐13 released from PBMCs and CD3+CD4+CRTh2 cells. Complexing Alt a 1 to RA masked its IgE B‐cell epitopes and reduced its IgE‐binding capacity. In a therapeutic mouse model of Alternaria allergy nasal application of holo‐Alt a 1, but not of apo‐Alt a 1, significantly impeded the anaphylactic response, impaired splenic antigen‐presenting cells and induced IL‐10 production. Conclusion: Holo‐Alt a 1 binding to RA was able to alleviate Th2 immunity in vitro, modulate an ongoing Th2 response and prevent anaphylactic symptoms in vivo, presenting a novel option for improving allergen‐specific immunotherapy in Alternaria allergy. [ABSTRACT FROM AUTHOR]

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person‐centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision‐making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried‐over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)—Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)—on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally‐enabled PCC in AIT. [ABSTRACT FROM AUTHOR]

Dupilumab reduces symptom burden in allergic rhinitis and suppresses allergen-specific IgE production Keywords: allergen-specific; allergy; birch pollen; dupilumab; grass pollen EN allergen-specific allergy birch pollen dupilumab grass pollen 1687 1691 5 06/02/23 20230601 NES 230601 To the Editor, Type 2 immune responses underlie many respiratory diseases including allergy and chronic rhinosinusitis. In some patients, allergen-specific IgE levels in nMLF dropped even below the detection limit (e.g. patient #1, 2 and #3 for selected allergens). Male patients experienced on average a larger reduction in total IgE in nMLF but not in serum and the percentage reduction in serum IgE levels correlated negatively with the number of allergens a patient was sensitised to (Tables S2 and S3). [Extracted from the article]

Summary: The diversity of raw materials used in modern products, compounded by the risk of supply disruptions—due to uneven geological distribution of resources, along with socioeconomic factors like production concentration and political (in)stability of raw material producing countries—has drawn attention to the subject of raw material "criticality." In this article, we review the state of the art regarding the integration of criticality assessment, herein termed "product‐level supply risk assessment," as a complement to environmental life cycle assessment. We describe and compare three methods explicitly developed for this purpose—Geopolitical Supply Risk (GeoPolRisk), Economic Scarcity Potential (ESP), and the Integrated Method to Assess Resource Efficiency (ESSENZ)—based on a set of criteria including considerations of data sources, uncertainties, and other contentious methodological aspects. We test the methods on a case study of a European‐manufactured electric vehicle, and conclude with guidance for appropriate application and interpretation, along with opportunities for further methodological development. Although the GeoPolRisk, ESP, and ESSENZ methods have several limitations, they can be useful for preliminary assessments of the potential impacts of raw material supply risks on a product system (i.e., "outside‐in" impacts) alongside the impacts of a product system on the environment (i.e., "inside‐out" impacts). Care is needed to not overlook critical raw materials used in small amounts but nonetheless important to product functionality. Further methodological development could address regional and firm‐level supply risks, multiple supply‐chain stages, and material recycling, while improving coverage of supply risk characterization factors. [ABSTRACT FROM AUTHOR]

Glycyrrhizin, a saponin, and its aglycone glycyrrhetinic acid are natural products found in the Liquorice ( Glycyrrhiza glabra L.) root extract. This saponin is known for its in vitro and in vivo thrombin inhibitory activity. The design and synthesis of five glycyrrhizin derivatives were carried out to improve the natural product activity. Compound 3b, a phthalic ester derivative of glycyrrhizin, presented a more pronounced thrombin inhibition ( IC50 = 114.4 ± 1.3 μ m) than the saponin ( IC50 = 235.7 ± 1.4 μ m). Molecular docking simulations performed to investigate the molecular interaction between compound 3b and the enzyme indicate that this product is, as previously determined for glycyrrhizin, an allosteric thrombin inhibitor. [ABSTRACT FROM AUTHOR]

Background Rib cage mobility decreases in various health conditions, for example neuromuscular diseases. A decrease in rib cage mobility reduces respiratory function and therefore increases the risk of respiratory complications. To evaluate the effects of interventions aiming at increasing rib cage mobility, changes should be calculated from measurements before and after such interventions. Therefore, an accurate and easy to perform method is needed. Objective To assess rib cage mobility using computed tomography ( CT). Methods We analysed single-image CT scans of the chest to assess its reproducibility at maximal inspiration and expiration in ten able-bodied individuals and ten subjects with tetraplegia. CT scans were taken twice in the supine position, with a repositioning of subjects in-between. At maximal inspiration and expiration, two images at the fourth and ninth vertebral body were recorded. Intra-costal areas, anterior-posterior distances from the sternum to the vertebral body as well as transversal distances of the chest were measured manually by three independent testers, each of them analysing all data twice. Intra-class correlation coefficients ( ICCs) and Bland and Altman plots were calculated for intra-subject reproducibility at maximal inspiration and expiration as well as for intra- and inter-tester reproducibility. Results Mean differences between the two intra-subject measurements expressed as percentage of their mean were 2·3 ± 1·3% in able-bodied individuals and 2·1 ± 1·3% in subjects with tetraplegia. All ICCs were above 0·95 and thus showed very high reproducibility. Conclusion Assessing rib cage mobility by analysing CT scans of the chest is a simple and highly reproducible method. [ABSTRACT FROM AUTHOR]

Abstract: The addition of N-glycans to clinically used proteins enhances their therapeutic features. Here we report the design of a novel peptide tag with an unnatural N-glycosylation site, which may increase the N-glycan content of generally any protein. The designed GlycoTags were attached to A1AT, EPO and AGP and constructs were expressed in HEK293 or CHO cells. Hereby we could prove that the attached unnatural N-glycosylation site is decorated with complex-type N-glycans and that the spacer as well as the C-terminal “tail” sequence are critical for the usage of the novel N-glycosylation site. This demonstrates that the novel GlycoTag is a convenient tool to provide proteins with extra N-glycan moieties by simply adding a peptide tag sequence as small as 22 amino acids. [Copyright &y& Elsevier]