Mechanism and clinical implication of gut dysbiosis in degenerative abdominal aortic aneurysm: A systematic review.

The gut microbiome is the entirety of microorganisms and their genomes residing in the gut, characterised by diversity, stability, and resilience. Disrupted gut microbiome has been implicated in multiple disease entities. The aim of this paper is to summarise the rapidly evolving contemporary evidence of gut dysbiosis on the development and progression of abdominal aortic aneurysm (AAA), discuss possible mechanisms, and explore potential microbiota-targeted interventions and prognostic markers for AAA. A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, using PubMed, ScienceDirect, Web of Science, Ovid, Embase. Search terms of "microbiome" OR "dysbiosis" OR "microorganism"; AND "aneurysm" OR "dilatation" OR "aorta" were used. Study endpoints included effects of microbiota on AAA formation, effects of specific type of bacteria and its metabolite on AAA formation, and pre- or post-treatment by novel small-molecules/inhibitors. From May to August 2023, a total of twelve animal studies and eight human studies were included. Akkermansia muciniphila, Lactobacillus acidophilus and species from the Bacteroidetes phylum were associated with lower AAA incidence in both animal and human studies, while Proteobacteria phylum, Campylobacter, Fusobacterium and Faecalibacterium prausnitzii were found to be in abundance in the AAA group and were associated with larger aneurysms. The diversity of gut microbiota was inversely correlated with AAA diameter. Three important mechanisms were identified: including trimethylamine N-oxide pathway, butyric acid pathway, and aberrant tryptophan metabolism. With our expanding knowledge of the downstream pathogenic mechanisms of gut dysbiosis, novel therapeutics such as short-chain fatty acids and spermidine, as well as prognostic biomarkers such as TMAO have yielded promising preclinical results. In conclusion, there is strong evidence corroborating the role of gut dysbiosis in the pathogenesis of AAA, wherein its therapeutic and prognostic potential deserves further exploration.

Dissecting components of the Campylobacter jejuni fetMP-fetABCDEF gene cluster under iron limitation.

IMPORTANCE: Campylobacter jejuni is a bacterium that is prevalent in the ceca of farmed poultry such as chickens. Consumption of ill-prepared poultry is thus the most common route by which C. jejuni infects the human gut to cause a typically self-limiting but severe gastrointestinal illness that can be fatal to very young, old, or immunocompromised people. The lack of a vaccine and an increasing resistance to current antibiotics highlight a need to better understand the mechanisms that make C. jejuni a successful human pathogen. This study focused on the functional components of one such mechanism-a molecular system that helps C. jejuni thrive despite the restriction on growth-available iron by the human body, which typically defends against pathogens. In providing a deeper understanding of how this system functions, this study contributes toward the goal of reducing the enormous global socioeconomic burden caused by C. jejuni.

Disrupted Structural White Matter Network in Alzheimer's Disease Continuum, Vascular Dementia, and Mixed Dementia: A Diffusion Tensor Imaging Study.

BACKGROUND: Dementia presents a significant burden to patients and healthcare systems worldwide. Early and accurate diagnosis, as well as differential diagnosis of various types of dementia, are crucial for timely intervention and management. However, there is currently a lack of clinical tools for accurately distinguishing between these types. OBJECTIVE: This study aimed to investigate the differences in the structural white matter (WM) network among different types of cognitive impairment/dementia using diffusion tensor imaging, and to explore the clinical relevance of the structural network. METHODS: A total of 21 normal control, 13 subjective cognitive decline (SCD), 40 mild cognitive impairment (MCI), 22 Alzheimer's disease (AD), 13 mixed dementia (MixD), and 17 vascular dementia (VaD) participants were recruited. Graph theory was utilized to construct the brain network. RESULTS: Our findings revealed a monotonic trend of disruption in the brain WM network (VaD > MixD > AD > MCI > SCD) in terms of decreased global efficiency, local efficiency, and average clustering coefficient, as well as increased characteristic path length. These network measurements were significantly associated with the clinical cognition index in each disease group separately. CONCLUSION: These findings suggest that structural WM network measurements can be utilized to differentiate between different types of cognitive impairment/dementia, and these measurements can provide valuable cognition-related information.

Dissecting components of the Campylobacter jejuni fetMP-fetABCDEF gene cluster in iron scavenging.

Campylobacter jejuni is a leading cause of bacterial gastroenteritis worldwide. Acute infection can be antecedent to highly debilitating long-term sequelae. Expression of iron acquisition systems is vital for C. jejuni to survive the low iron availability within the human gut. The C. jejuni fetMP-fetABCDEF gene cluster is known to be upregulated during human infection and under iron limitation. While FetM and FetP have been functionally linked to iron transport in prior work, here we assess the contribution by each of the downstream genes ( fetABCDEF ) to C. jejuni growth during both iron-depleted and iron-replete conditions. Significant growth impairment was observed upon disruption of fetA , fetB, fetC , and fetD , suggesting a role in iron acquisition for each encoded protein. FetA expression was modulated by iron-availability but not dependent on the presence of FetB, FetC, FetD, FetE or FetF. Functions of the putative thioredoxins FetE and FetF were redundant in iron scavenging, requiring a double deletion (Δ fetEF ) to exhibit a growth defect. C. jejuni FetE was expressed and the structure solved to 1.50 Å, revealing structural similarity to thiol-disulfide oxidases. Functional characterization in biochemical assays showed that FetE reduced insulin at a slower rate than E. coli Trx and that together, FetEF promoted substrate oxidation in cell extracts, suggesting that FetE (and presumably FetF) are oxidoreductases that can mediate oxidation in vivo . This study advances our understanding of the contributions by the fetMP-fetABCDEF gene cluster to virulence at a genetic and functional level, providing foundational knowledge towards mitigating C. jejuni -related morbidity and mortality.

A new member of the flavodoxin superfamily from Fusobacterium nucleatum that functions in heme trafficking and reduction of anaerobilin.

Fusobacterium nucleatum is an opportunistic oral pathogen that is associated with various cancers. To fulfill its essential need for iron, this anaerobe will express heme uptake machinery encoded at a single genetic locus. The heme uptake operon includes HmuW, a class C radical SAM-dependent methyltransferase that degrades heme anaerobically to release Fe2+ and a linear tetrapyrrole called anaerobilin. The last gene in the operon, hmuF encodes a member of the flavodoxin superfamily of proteins. We discovered that HmuF and a paralog, FldH, bind tightly to both FMN and heme. The structure of Fe3+-heme-bound FldH (1.6 Å resolution) reveals a helical cap domain appended to the ⍺/ß core of the flavodoxin fold. The cap creates a hydrophobic binding cleft that positions the heme planar to the si-face of the FMN isoalloxazine ring. The ferric heme iron is hexacoordinated to His134 and a solvent molecule. In contrast to flavodoxins, FldH and HmuF do not stabilize the FMN semiquinone but instead cycle between the FMN oxidized and hydroquinone states. We show that heme-loaded HmuF and heme-loaded FldH traffic heme to HmuW for degradation of the protoporphyrin ring. Both FldH and HmuF then catalyze multiple reductions of anaerobilin through hydride transfer from the FMN hydroquinone. The latter activity eliminates the aromaticity of anaerobilin and the electrophilic methylene group that was installed through HmuW turnover. Hence, HmuF provides a protected path for anaerobic heme catabolism, offering F. nucleatum a competitive advantage in the colonization of anoxic sites of the human body.

Level of Amyloid-ß (Aß) Binding Leading to Differential Effects on Resting State Functional Connectivity in Major Brain Networks.

INTRODUCTION: Amyloid-ß protein (Aß) is one of the biomarkers for Alzheimer's disease (AD). The recent application of interhemispheric functional connectivity (IFC) in resting-state fMRI has been used as a non-invasive diagnostic tool for early dementia. In this study, we focused on the level of Aß accumulated and its effects on the major functional networks, including default mode network (DMN), central executive network (CEN), salience network (SN), self-referential network (SRN) and sensory motor network (SMN). METHODS: 58 participants (27 Hi Aß (HiAmy) and 31 low Aß (LowAmy)) and 25 healthy controls (HC) were recruited. [18F]flutemetamol PET/CT was performed for diseased groups, and MRI scanning was done for all participants. Voxel-by-voxel correlation analysis was done for both groups in all networks. RESULTS: In HiAmy, IFC was reduced in all networks except SN. A negative correlation in DMN, CEN, SRN and SMN suggests high Aß related to IFC reduction; However, a positive correlation in SN suggests high Aß related to an increase in IFC. In LowAmy, IFC increased in CEN, SMN, SN and SRN. Positive correlation in all major brain networks. CONCLUSION: The level of Aß accumulated demonstrated differential effects on IFC in various brain networks. As the treatment to reduce Aß plaque deposition is available in the market, it may be an option for the HiAmy group to improve their IFC in major brain networks.

Sequence Divergence in the Arginase Domain of Ornithine Decarboxylase/Arginase in Fusobacteriacea Leads to Loss of Function in Oral Associated Species.

A number of species within the Fusobacteriaceae family of Gram-negative bacteria uniquely encode for an ornithine decarboxylase/arginase (ODA) that ostensibly channels l-ornithine generated by hydrolysis of l-arginine to putrescine formation. However, two aspartate residues required for coordination to a catalytically obligatory manganese cluster of arginases are substituted for a serine and an asparagine. Curiously, these natural substitutions occur only in a clade of Fusobacterium species that inhabit the oral cavity. Herein, we expressed and isolated full-length ODA from the opportunistic oral pathogen Fusobacterium nucleatum along with the individual arginase and ornithine decarboxylase components. The crystal structure of the arginase domain reveals that it adopts the classical α/ß arginase-fold, but metal ions are absent in the active site. As expected, the ureohydrolase activity with l-arginine was not detected for wild-type ODA or the isolated arginase domain. However, engineering of the complete metal coordination environment through site-directed mutagenesis restored Mn2+ binding capacity and arginase activity, although the catalytic efficiency for l-arginine was low (60-100 M-1 s-1). Full-length ODA and the isolated ODC component were able to decarboxylate both l-ornithine and l-arginine to form putrescine and agmatine, respectively, but kcat/KM of l-ornithine was ∼20-fold higher compared to l-arginine. We discuss environmental conditions that may have led to the natural selection of an inactive arginase in the oral associated species of Fusobacterium.

Sachet water in Ghana: A spatiotemporal analysis of the recent upward trend in consumption and its relationship with changing household characteristics, 2010-2017.

The consumption of packaged water in Ghana has grown significantly in recent years. By 2017, "sachet water"-machine-sealed 500ml plastic bags of drinking water-was consumed by 33% of Ghanaian households. Reliance on sachet water has previously been associated with the urban poor, yet recent evidence suggests a customer base which crosses socioeconomic lines. Here, we conduct a repeated cross-sectional analysis of three nationally representative datasets to examine the changing demography of sachet water consumers between 2010 and 2017. Our results show that over the course of the study period sachet water has become a ubiquitous source of drinking water in Ghana, with relatively wealthy households notably increasing their consumption. In 2017, the majority of sachet water drinking households had access to another improved water source. The current rate and form of urbanisation, inadequate water governance, and an emphasis on cost recovery pose significant challenges for the expansion of the piped water supply network, leading us to conclude that sachet water will likely continue to be a prominent source of drinking water in Ghana for the foreseeable future. The main challenge for policymakers is to ensure that the growing sachet water market enhances rather than undermines Ghana's efforts towards achieving universal and equitable access to clean drinking water and sanitation.

Radiomics-Based Artificial Intelligence Differentiation of Neurodegenerative Diseases with Reference to the Volumetry.

This study aimed to build automated detection models-one by brain regional volume (V-model), and the other by radiomics features of the whole brain (R-model)-to differentiate mild cognitive impairment (MCI) from cognitive normal (CN), and Alzheimer's Disease (AD) from mild cognitive impairment (MCI). The objectives are to compare the models and identify whether radiomics or volumetry can provide a better prediction for differentiating different types of dementia. METHOD: 582 MRI T1-weighted images were retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, which is a multicenter operating open source database for AD. In total, 97 images of AD, 293 images of MCI patient and 192 images of cognitive normal were divided into a training, a validation and a test group at a ratio of 70:15:15. For each T1-weighted image, volumetric segmentation was performed with the image analysis software FreeSurfer, and radiomics features were retrieved by imaging research software 3D slicers. Brain regional volume and radiomics features were used to build the V-model and R-model, respectively, using the random forest algorithm by R. The receiver operating characteristics (ROC) curve of both models were used to evaluate their diagnostic accuracy and reliability to differentiate AD, MCI and CN. RESULTS: To differentiate MCI and CN, both V-model and R-model achieved excellent performance, with an AUC of 0.9992 ± 0.0022 and 0.9850 ± 0.0032, respectively. No significant difference was found between the two AUCs, indicating both models attained similar good performance. In MCI and AD differentiation, the V-model and R-model yielded AUC of 0.9986 ± 0.0013 and 0.9714 ± 0.0175, respectively. The best performance was to differentiate AD from CN, where the V-model and R-model yielded AUC of 0.9994 ± 0.0019 and 0.9830 ± 0.009, respectively. The results suggested that both volumetry and radiomics approaches could be used in differentiating AD, MCI and CN, based on T1 weighted MR images using random forest algorithm successfully. CONCLUSION: This study showed that the radiomics features from T1-weighted MR images achieved excellence performance in differentiating AD, MCI and CN. Compared to the volumetry method, the accuracy, sensitivity and specificity are slightly lower in using radiomics, but still attained very good and reliable classification of the three stages of neurodegenerations. In view of the convenience and operator independence in feature extraction, radiomics can be a quantitative biomarker to differentiate the disease groups.

Characterization of a phylogenetically distinct extradiol dioxygenase involved in the bacterial catabolism of lignin-derived aromatic compounds.

The actinobacterium Rhodococcus jostii RHA1 grows on a remarkable variety of aromatic compounds and has been studied for applications ranging from the degradation of polychlorinated biphenyls to the valorization of lignin, an underutilized component of biomass. In RHA1, the catabolism of two classes of lignin-derived compounds, alkylphenols and alkylguaiacols, involves a phylogenetically distinct extradiol dioxygenase, AphC, previously misannotated as BphC, an enzyme involved in biphenyl catabolism. To better understand the role of AphC in RHA1 catabolism, we first showed that purified AphC had highest apparent specificity for 4-propylcatechol (kcat/KM ∼106 M-1 s-1), and its apparent specificity for 4-alkylated substrates followed the trend for alkylguaiacols: propyl > ethyl > methyl > phenyl > unsubstituted. We also show AphC only poorly cleaved 3-phenylcatechol, the preferred substrate of BphC. Moreover, AphC and BphC cleaved 3-phenylcatechol and 4-phenylcatechol with different regiospecificities, likely due to the substrates' binding mode. A crystallographic structure of the AphC·4-ethylcatechol binary complex to 1.59 Å resolution revealed that the catechol is bound to the active site iron in a bidentate manner and that the substrate's alkyl side chain is accommodated by a hydrophobic pocket. Finally, we show RHA1 grows on a mixture of 4-ethylguaiacol and guaiacol, simultaneously catabolizing these substrates through meta-cleavage and ortho-cleavage pathways, respectively, suggesting that the specificity of AphC helps to prevent the routing of catechol through the Aph pathway. Overall, this study contributes to our understanding of the bacterial catabolism of aromatic compounds derived from lignin, and the determinants of specificity in extradiol dioxygenases.

A scoping review of resting-state brain functional alterations in Type 2 diabetes.

Resting-state functional magnetic resonance imaging (rs-fMRI) has been actively used in the last decade to investigate brain functional connectivity alterations in Type 2 Diabetes Mellitus (T2DM) to understand the neuropathophysiology of T2DM in cognitive degeneration. Given the emergence of new analysis techniques, this scoping review aims to map the rs-fMRI analysis techniques that have been applied in the literature and reports the latest rs-fMRI findings that have not been covered in previous reviews. Graph theory, the contemporary rs-fMRI analysis, has been used to demonstrate altered brain topological organisations in people with T2DM, which included altered degree centrality, functional connectivity strength, the small-world architecture and network-based statistics. These alterations were correlated with T2DM patients' cognitive performances. Graph theory also contributes to identify unbiased seeds for seed-based analysis. The expanding rs-fMRI analytical approaches continue to provide new evidence that helps to understand the mechanisms of T2DM-related cognitive degeneration.

Soft-Dielectron Excess in Proton-Proton Collisions at sqrt[s]=13 TeV.

A measurement of dielectron production in proton-proton (pp) collisions at sqrt[s]=13 TeV, recorded with the ALICE detector at the CERN LHC, is presented in this Letter. The data set was recorded with a reduced magnetic solenoid field. This enables the investigation of a kinematic domain at low dielectron (ee) invariant mass m_{ee} and pair transverse momentum p_{T,ee} that was previously inaccessible at the LHC. The cross section for dielectron production is studied as a function of m_{ee}, p_{T,ee}, and event multiplicity dN_{ch}/dη. The expected dielectron rate from hadron decays, called hadronic cocktail, utilizes a parametrization of the measured η/π^{0} ratio in pp and proton-nucleus collisions, assuming that this ratio shows no strong dependence on collision energy at low transverse momentum. Comparison of the measured dielectron yield to the hadronic cocktail at 0.15

Structural and functional analysis of lignostilbene dioxygenases from Sphingobium sp. SYK-6.

Lignostilbene-α,ß-dioxygenases (LSDs) are iron-dependent oxygenases involved in the catabolism of lignin-derived stilbenes. Sphingobium sp. SYK-6 contains eight LSD homologs with undetermined physiological roles. To investigate which homologs are involved in the catabolism of dehydrodiconiferyl alcohol (DCA), derived from ß-5 linked lignin subunits, we heterologously produced the enzymes and screened their activities in lysates. The seven soluble enzymes all cleaved lignostilbene, but only LSD2, LSD3, and LSD4 exhibited high specific activity for 3-(4-hydroxy-3-(4-hydroxy-3-methoxystyryl)-5-methoxyphenyl) acrylate (DCA-S) relative to lignostilbene. LSD4 catalyzed the cleavage of DCA-S to 5-formylferulate and vanillin and cleaved lignostilbene and DCA-S (∼106 M-1 s-1) with tenfold greater specificity than pterostilbene and resveratrol. X-ray crystal structures of native LSD4 and the catalytically inactive cobalt-substituted Co-LSD4 at 1.45 Å resolution revealed the same fold, metal ion coordination, and edge-to-edge dimeric structure as observed in related enzymes. Key catalytic residues, Phe-59, Tyr-101, and Lys-134, were also conserved. Structures of Co-LSD4·vanillin, Co-LSD4·lignostilbene, and Co-LSD4·DCA-S complexes revealed that Ser-283 forms a hydrogen bond with the hydroxyl group of the ferulyl portion of DCA-S. This residue is conserved in LSD2 and LSD4 but is alanine in LSD3. Substitution of Ser-283 with Ala minimally affected the specificity of LSD4 for either lignostilbene or DCA-S. By contrast, substitution with phenylalanine, as occurs in LSD5 and LSD6, reduced the specificity of the enzyme for both substrates by an order of magnitude. This study expands our understanding of an LSD critical to DCA catabolism as well as the physiological roles of other LSDs and their determinants of substrate specificity.

Elliptic Flow of Electrons from Beauty-Hadron Decays in Pb-Pb Collisions at sqrt[s_{NN}]=5.02 TeV.

The elliptic flow of electrons from beauty hadron decays at midrapidity (|y|<0.8) is measured in Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV with the ALICE detector at the LHC. The azimuthal distribution of the particles produced in the collisions can be parametrized with a Fourier expansion, in which the second harmonic coefficient represents the elliptic flow, v_{2}. The v_{2} coefficient of electrons from beauty hadron decays is measured for the first time in the transverse momentum (p_{T}) range 1.3-6 GeV/c in the centrality class 30%-50%. The measurement of electrons from beauty-hadron decays exploits their larger mean proper decay length cτ≈500 µm compared to that of charm hadrons and most of the other background sources. The v_{2} of electrons from beauty hadron decays at midrapidity is found to be positive with a significance of 3.75 σ. The results provide insights into the degree of thermalization of beauty quarks in the medium. A model assuming full thermalization of beauty quarks is strongly disfavored by the measurement at high p_{T}, but is in agreement with the results at low p_{T}. Transport models including substantial interactions of beauty quarks with an expanding strongly interacting medium describe the measurement within uncertainties.

Peptidoglycan binding by a pocket on the accessory NTF2-domain of Pgp2 directs helical cell shape of Campylobacter jejuni.

The helical morphology of Campylobacter jejuni, a bacterium involved in host gut colonization and pathogenesis in humans, is determined by the structure of the peptidoglycan (PG) layer. This structure is dictated by trimming of peptide stems by the LD-carboxypeptidase Pgp2 within the periplasm. The interaction interface between Pgp2 and PG to select sites for peptide trimming is unknown. We determined a 1.6 Å resolution crystal structure of Pgp2, which contains a conserved LD-carboxypeptidase domain and a previously uncharacterized domain with an NTF2-like fold (NTF2). We identified a pocket in the NTF2 domain formed by conserved residues and located ∼40 Å from the LD-carboxypeptidase active site. Expression of pgp2 in trans with substitutions of charged (Lys257, Lys307, Glu324) and hydrophobic residues (Phe242 and Tyr233) within the pocket did not restore helical morphology to a pgp2 deletion strain. Muropeptide analysis indicated a decrease of murotripeptides in the deletion strain expressing these mutants, suggesting reduced Pgp2 catalytic activity. Pgp2 but not the K307A mutant was pulled down by C. jejuni Δpgp2 PG sacculi, supporting a role for the pocket in PG binding. NMR spectroscopy was used to define the interaction interfaces of Pgp2 with several PG fragments, which bound to the active site within the LD-carboxypeptidase domain and the pocket of the NTF2 domain. We propose a model for Pgp2 binding to PG strands involving both the LD-carboxypeptidase domain and the accessory NTF2 domain to induce a helical cell shape.

A qualitative exploration of the experiences of school nurses during COVID-19 pandemic as the frontline primary health care professionals.

BACKGROUND: It is widely acknowledged that the experiences of frontline primary health care professionals during COVID-19 are important to understand how they respond and act under situations of pandemic as the gatekeepers in primary health care system. School nurses are primary health care professionals who lead health care in schools and practice in a holistic manner to address the needs of schoolchildren and school personnel. There are rising mental health concerns of frontline health care professionals with anxiety and panic disorders, somatic symptoms, and feeling isolated. No studies use a qualitative study approach to document community frontline school nursing professionals' experiences and challenges during the COVID-19 pandemic. Hence, understanding the school nurses' experiences and challenges to fight against COVID-19 in the communities is important. PURPOSE: This study aims to explore the experiences of school nurses during the COVID-19 pandemic in Hong Kong. METHODS: A qualitative study design adopted the principles of thematic analysis. Nineteen school nurses were recruited to participate in individual semistructured interviews and shared their roles and responsibilities during the COVID-19 pandemic. FINDINGS: Three themes indicated the school nurses' expand professional responsibilities to fight against COVID-19 emerged from the data analysis. These were "Managing Stress," "Navigating the School Through the Pandemic," and "Raising the Profile of the School Nurse Professional," DISCUSSION: Findings reveal the important role of school nursing professionals in minimizing the community-wide risk posed by pandemics and the need to integrate them into planning and implementation of school health policies and guidelines in the primary health care system. This essential role in schools is necessary to assess, implement, monitor, prevent, and reduce the spread of virus in school communities and to minimize the burden to and extra health care resources utilized in the acute care setting during COVID-19 pandemic.

Heterogeneity of Amyloid Binding in Cognitively Impaired Patients Consecutively Recruited from a Memory Clinic: Evaluating the Utility of Quantitative 18F-Flutemetamol PET-CT in Discrimination of Mild Cognitive Impairment from Alzheimer's Disease and Other Dementias.

BACKGROUND: With the more widespread use of 18F-radioligand-based amyloid-ß (Aß) PET-CT imaging, we evaluated Aß binding and the utility of neocortical 18F-Flutemetamol standardized uptake value ratio (SUVR) as a biomarker. OBJECTIVE: 18F-Flutemetamol SUVR was used to differentiate 1) mild cognitive impairment (MCI) from Alzheimer's disease (AD), and 2) MCI from other non-AD dementias (OD). METHODS: 109 patients consecutively recruited from a University memory clinic underwent clinical evaluation, neuropsychological test, MRI and 18F-Flutemetamol PET-CT. The diagnosis was made by consensus of a panel consisting of 1 neuroradiologist and 2 geriatricians. The final cohort included 13 subjective cognitive decline (SCD), 22 AD, 39 MCI, and 35 OD. Quantitative analysis of 16 region-of-interests made by Cortex ID software (GE Healthcare). RESULTS: The global mean 18F-Flutemetamol SUVR in SCD, MCI, AD, and OD were 0.50 (SD-0.08), 0.53 (SD-0.16), 0.76 (SD-0.10), and 0.56 (SD-0.16), respectively, with SUVR in SCD and MCI and OD being significantly lower than AD. Aß binding in SCD, MCI, and OD was heterogeneous, being 23%, 38.5%, and 42.9% respectively, as compared to 100% amyloid positivity in AD. Using global SUVR, ROC analysis showed AUC of 0.868 and 0.588 in differentiating MCI from AD and MCI from OD respectively. CONCLUSION: 18F-Flutemetamol SUVR differentiated MCI from AD with high efficacy (high negative predictive value), but much lower efficacy from OD. The major benefit of the test was to differentiate cognitively impaired patients (either SCD, MCI, or OD) without AD-related-amyloid-pathology from AD in the clinical setting, which was under-emphasized in the current guidelines proposed by Amyloid Imaging Task Force.

Measurement of the Low-Energy Antideuteron Inelastic Cross Section.

In this Letter, we report the first measurement of the inelastic cross section for antideuteron-nucleus interactions at low particle momenta, covering a range of 0.3≤p<4 GeV/c. The measurement is carried out using p-Pb collisions at a center-of-mass energy per nucleon-nucleon pair of sqrt[s_{NN}]=5.02 TeV, recorded with the ALICE detector at the CERN LHC and utilizing the detector material as an absorber for antideuterons and antiprotons. The extracted raw primary antiparticle-to-particle ratios are compared to the results from detailed ALICE simulations based on the geant4 toolkit for the propagation of (anti)particles through the detector material. The analysis of the raw primary (anti)proton spectra serves as a benchmark for this study, since their hadronic interaction cross sections are well constrained experimentally. The first measurement of the inelastic cross section for antideuteron-nucleus interactions averaged over the ALICE detector material with atomic mass numbers ⟨A⟩=17.4 and 31.8 is obtained. The measured inelastic cross section points to a possible excess with respect to the Glauber model parametrization used in geant4 in the lowest momentum interval of 0.3≤p<0.47 GeV/c up to a factor 2.1. This result is relevant for the understanding of antimatter propagation and the contributions to antinuclei production from cosmic ray interactions within the interstellar medium. In addition, the momentum range covered by this measurement is of particular importance to evaluate signal predictions for indirect dark-matter searches.

A copper site is required for iron transport by the periplasmic proteins P19 and FetP.

Campylobacter jejuni is a leading cause of food-borne gastrointestinal disease in humans and uropathogenic Escherichia coli is a leading cause of urinary tract infections. Both human pathogens harbour a homologous iron uptake system (termed cjFetM-P19 in C. jejuni and ecFetM-FetP in E. coli). Although these systems are important for growth under iron limitation, the mechanisms by which these systems function during iron transport remain undefined. The copper ions bound to P19 and FetP, the homologous periplasmic proteins, are coordinated in an uncommon penta-dentate manner involving a Met-Glu-His3 motif and exhibit positional plasticity. Here we demonstrate the function of the Met and Glu residues in modulating copper binding and controlling copper positioning through site-directed variants, binding assays, and crystal structures. Growth of C. jejuni strains with these p19 variants is impaired under iron limited conditions as compared to the wild-type strain. Additionally, an acidic residue-rich secondary site is required for binding iron and function in vivo. Finally, western blot analyses demonstrate direct and specific interactions between periplasmic P19 and FetP with the large periplasmic domain of their respective inner membrane transporters cjFetM and ecFetM.