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1.
Proc Natl Acad Sci U S A ; 121(27): e2406032121, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38913904

ABSTRACT

The Toarcian Oceanic Anoxic Event (T-OAE; ~183 Mya) was a globally significant carbon-cycle perturbation linked to widespread deposition of organic-rich sediments, massive volcanic CO2 release, marine faunal extinction, sea-level rise, a crisis in carbonate production related to ocean acidification, and elevated seawater temperatures. Despite recognition of the T-OAE as a potential analog for future ocean deoxygenation, current knowledge on the severity of global ocean anoxia is limited largely to studies of the trace element and isotopic composition of black shales, which are commonly affected by local processes. Here, we present the first carbonate-based uranium isotope (δ238U) record of the T-OAE from open marine platform limestones of the southeastern Tethys Ocean as a proxy for global seawater redox conditions. A significant negative δ238U excursion (~0.4‰) is recorded just prior to the onset of the negative carbon isotope excursion comprised within the T-OAE, followed by a long-lived recovery of δ238U values, thus confirming that the T-OAE represents a global expansion of marine anoxia. Using a Bayesian inverse isotopic mass balance model, we estimate that anoxic waters covered ~6 to 8% of the global seafloor during the peak of the T-OAE, which represents 28 to 38 times the extent of anoxia in the modern ocean. These data, combined with δ238U-based estimates of seafloor anoxic area for other CO2-driven Phanerozoic OAEs, suggest a common response of ocean anoxia to carbon release, thus improving prediction of future anthropogenically induced ocean deoxygenation.

2.
ACS Earth Space Chem ; 7(11): 2222-2238, 2023 Nov 16.
Article in English | MEDLINE | ID: mdl-38026809

ABSTRACT

Rare earth elements (REEs) have been found to have numerous uses to trace geological and cosmochemical processes through analyses of elemental patterns, radioactive decay, nucleosynthetic anomalies, and cosmogenic effects. Stable isotopic fractionation is one aspect of REE geochemistry that has been seldom studied, with most publications focusing on the development of analytical methodologies for individual REEs, and most applications concerning terrestrial igneous rocks. In this study, we present a method to systematically analyze stable isotopic fractionations of 8 REEs, including Ce, Nd, Sm, Eu, Gd, Dy, Er, and Yb, using sample-standard bracketing (SSB) and double-spike (DS) approaches. All REEs are separated and purified using a fluoropolymer pneumatic liquid chromatography (FPLC) system. We introduce procedures for identifying and correcting some isobaric interferences in double-spike data reduction. Several geostandards, including igneous rocks and sediments, are analyzed using SSB and DS methods. The results indicate that REE isotopic fractionation in igneous processes is limited, except for Eu. Other REEs can still be isotopically fractionated by low-temperature processes and kinetic effects at a high temperature.

3.
Metallomics ; 15(11)2023 11 02.
Article in English | MEDLINE | ID: mdl-37804184

ABSTRACT

Relative to healthy controls, lighter copper isotopic compositions have been observed in the serum of breast cancer and end-stage liver disease patients, raising the possibility that Cu isotope ratios could be used as a tracer for disease progression. Here, we assess the potential of natural Cu isotopic variations (expressed as δ65Cu) as diagnostic tools for cancer progression and/or liver failure by performing a first-order analysis of Cu isotopic cycling in the human body. Using a box model, we simulate the kinetics of Cu mass transfer throughout significant reservoirs in the body, allowing isotopic fractionation to occur during Cu uptake/release from these reservoirs. With this model, we determine under which conditions the serum δ65Cu values would reflect perturbation related to cancer growth and/or liver failure at a level resolvable with modern mass spectrometry. We find that tumor growth alone is unable to explain the light isotopic signature observed in serum. Instead, we find that metabolic changes to the liver function resulting in a ∼1‰ isotope fractionation during Cu uptake from the blood into the liver can readily explain the long-term serum isotopic shift of ∼0.2‰ observed in cancer patients. A similar fractionation (∼1.3‰) during Cu uptake into the liver also readily explains the -1.2‰ shift observed in the serum of cirrhosis patients with ascites, suggesting a potentially common driver of isotopic fractionation in both cases. Using this model, we then test hypotheses put forward by previous studies and begin to probe the mechanisms behind the measured isotopic compositions.


Subject(s)
Breast Neoplasms , Liver Failure , Humans , Female , Copper/metabolism , Isotopes/metabolism
4.
Sci Adv ; 9(27): eadg9213, 2023 Jul 07.
Article in English | MEDLINE | ID: mdl-37406123

ABSTRACT

The observation that mid-ocean ridge basalts had ~3× higher iodine/plutonium ratios (inferred from xenon isotopes) compared to ocean island basalts holds critical insights into Earth's accretion. Understanding whether this difference stems from core formation alone or heterogeneous accretion is, however, hindered by the unknown geochemical behavior of plutonium during core formation. Here, we use first-principles molecular dynamics to quantify the metal-silicate partition coefficients of iodine and plutonium during core formation and find that both iodine and plutonium partly partition into metal liquid. Using multistage core formation modeling, we show that core formation alone is unlikely to explain the iodine/plutonium difference between mantle reservoirs. Instead, our results reveal a heterogeneous accretion history, whereby predominant accretion of volatile-poor differentiated planetesimals was followed by a secondary phase of accretion of volatile-rich undifferentiated meteorites. This implies that Earth inherited part of its volatiles, including its water, from late accretion of chondrites, with a notable carbonaceous chondrite contribution.

5.
Environ Sci Pollut Res Int ; 30(9): 23386-23397, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36323968

ABSTRACT

The River Thurso, North Scotland, receives substantial terrestrial deliveries of dissolved organic matter (DOM) leached from Europe's most extensive blanket bogs. The relatively short distance between peatlands and coastal ocean offers potential for research to investigate source-to-sea processing of terrigenous dissolved organic carbon (DOC). Here, we determined DOC concentrations in the bulk (< 0.4 µm), truly dissolved (< 5 kDa), and colloidal fraction (5 kDa - 0.4 µm) as well as DOM absorbance and fluorescence spectra during two river catchment surveys and two corresponding coastal plume surveys, in early spring (1st sampling period) and late spring (2nd sampling period). DOC concentrations ranged from 79 to 3799 µM in early spring and from 115 to 5126 µM in late spring. DOM exhibited conservative mixing across the plume in both surveys, but the plume extended further offshore in the second survey due to a pulse of freshwater caused by recent rainfall. Fluorescence excitation-emission matrices (EEMs) and fluorescence indices revealed that the flushed DOM was humic-like, recently synthesized DOM. Coupled with C/N ratio analyses and molecular weight fractionation, the fluorescence indices also provided evidence for the gradual altering of DOM characteristics along the bog - headstream - loch - river continuum. The same analytical tools revealed that seasonal variations occurred within the DOM pool of marine origin, i.e., greater abundance of low-molecular weight bacterial or algal DOM in the late spring survey. The time scale of such variations relative to the flushing time of water through the aquatic continuum should be taken into account when interpreting the DOM property-salinity distributions of major river plumes.


Subject(s)
Dissolved Organic Matter , Fresh Water , Rivers , Scotland , Spectrometry, Fluorescence
6.
Neurourol Urodyn ; 42(2): 478-499, 2023 02.
Article in English | MEDLINE | ID: mdl-36478202

ABSTRACT

AIMS: To discuss the advantages and limitation of the different pelvic floor muscle (PFM) dynamometers available, both in research and industry, and to present the extent of variation between them in terms of structure, functioning, psychometric properties, and assessment procedures. METHODS: We identified relevant studies from four databases (MEDLINE, Compendex, Web of Science, and Derwent Innovations Index) up to December 2020 using terms related to dynamometry and PFM. In addition, we conducted a hand search of the bibliographies of all relevant reports. Peer-reviewed papers, conference proceedings, patents and user's manuals for commercial dynamometers were included and assessed by two independent reviewers. RESULTS: One hundred and one records were included and 23 PFM dynamometers from 15 research groups were identified. From these, 20 were considered as clinical dynamometers (meant for research settings) and three as personal dynamometers (developed by the industry). Overall, significant heterogeneity was found in their structure and functioning, which limits development of normative data for PFM force in women. Further research is needed to assess the psychometric properties of PFM dynamometers and to standardize assessment procedures. CONCLUSION: This review points up to the heterogeneity of existing dynamometers and methods of assessing PFM function. It highlights the need to better document their design and assessment protocol methods. Additionally, this review recommends standards for new dynamometers to allow the establishment of normalized data.


Subject(s)
Muscle Contraction , Pelvic Floor Disorders , Female , Humans , Muscle Contraction/physiology , Pelvic Floor , Pelvic Floor Disorders/diagnosis
7.
Viruses ; 14(12)2022 11 22.
Article in English | MEDLINE | ID: mdl-36560603

ABSTRACT

The organization and dynamics of plasma membrane receptors are a critical link in virus-receptor interactions, which finetune signaling efficiency and determine cellular responses during infection. Characterizing the mechanisms responsible for the active rearrangement and clustering of receptors may aid in developing novel strategies for the therapeutic treatment of viruses. Virus-receptor interactions are poorly understood at the nanoscale, yet they present an attractive target for the design of drugs and for the illumination of viral infection and pathogenesis. This study utilizes super-resolution microscopy and related techniques, which surpass traditional microscopy resolution limitations, to provide both a spatial and temporal assessment of the interactions of human JC polyomavirus (JCPyV) with 5-hydroxytrypamine 2 receptors (5-HT2Rs) subtypes during viral entry. JCPyV causes asymptomatic kidney infection in the majority of the population and can cause fatal brain disease, and progressive multifocal leukoencephalopathy (PML), in immunocompromised individuals. Using Fluorescence Photoactivation Localization Microscopy (FPALM), the colocalization of JCPyV with 5-HT2 receptor subtypes (5-HT2A, 5-HT2B, and 5-HT2C) during viral attachment and viral entry was analyzed. JCPyV was found to significantly enhance the clustering of 5-HT2 receptors during entry. Cluster analysis of infected cells reveals changes in 5-HT2 receptor cluster attributes, and radial distribution function (RDF) analyses suggest a significant increase in the aggregation of JCPyV particles colocalized with 5-HT2 receptor clusters in JCPyV-infected samples. These findings provide novel insights into receptor patterning during viral entry and highlight improved technologies for the future development of therapies for JCPyV infection as well as therapies for diseases involving 5-HT2 receptors.


Subject(s)
JC Virus , Leukoencephalopathy, Progressive Multifocal , Polyomavirus Infections , Humans , JC Virus/physiology , Serotonin , Virus Attachment
9.
J Addict Med ; 16(1): 101-109, 2022.
Article in English | MEDLINE | ID: mdl-33534276

ABSTRACT

OBJECTIVES: Child and adolescent psychiatric (CAP) inpatient admissions have increased since 2009 and the clinical profile of these patients has become more complex. Unrecognized dual diagnosis, that is, comorbid substance use or substance use disorder (SUD) may contribute to this problem, but the prevalence of dual diagnosis in this population is inadequately understood. The goal of this scoping review was to summarize the range and content of research on this topic. METHODS: MEDLINE, EMBASE, and PsychINFO databases were systematically searched for studies published from 2008 to 2019 containing information on rates of comorbid substance use or SUD in CAP inpatients. RESULTS: A total of 23,326 abstracts were located. After removing duplicates, screening abstracts and full-text papers, and extracting data with full-text reviews, fourteen studies meeting our criteria remained. Rates of substance use or SUD ranged from 0.9% to 54.8%, differing on the basis of: (1) type of outcome; (2) type of data source; and (3) whether samples had a specific diagnostic focus or not. Rates of any type of SUD were reported in approximately 25% of samples from administrative databases, in 17.7% to 38.5% of chart reviews, and in 55% of studies with data from clinical research examinations. The highest rates of substance-specific substance use or SUD were for alcohol, cannabis, and nicotine. CONCLUSIONS: We located 14 studies, but methodologic heterogeneity precluded quantitative calculation of a single estimate for the prevalence of dual diagnosis. However, most of the rates suggest that this is an important problem in CAP inpatients, meriting further research. We suggest ways to improve future studies.


Subject(s)
Inpatients , Substance-Related Disorders , Adolescent , Child , Comorbidity , Diagnosis, Dual (Psychiatry) , Humans , Prevalence , Substance-Related Disorders/diagnosis
10.
Soc Psychiatry Psychiatr Epidemiol ; 57(3): 575-581, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34374826

ABSTRACT

BACKGROUND: Spinal pain and major depression are prevalent conditions in adult populations and are particularly impactful in the military. However, the temporal relationship between these two conditions remains poorly understood. METHODS: Using data extracted from electronic medical records, we assessed the association between incident diagnoses of spinal pain and major depression in a cohort of 48,007 Canadian Armed Forces personnel followed from January 2017 to August 2018. We used multivariate Poisson regression to measure the association between the period prevalence of these two conditions. We used probabilistic bias modelling to correct our estimates for misclassification of spinal pain and major depression. RESULTS: After correcting for misclassification with probabilistic bias modelling, subjects newly diagnosed with spinal pain during the study period were 1.41 times (95% interval 1.25, 1.59) more likely also to be diagnosed with incident major depression, and personnel newly diagnosed with major depression were 1.28 times (95% interval 1.17, 1.39) more likely also to be diagnosed with spinal pain, compared to undiagnosed counterparts of the same age and sex. Without bias corrections, we would have overestimated the magnitude of the association between major depression and spinal pain by a factor of approximately 2.0. CONCLUSION: Our results highlight a moderate and bi-directional association between two of the most prevalent disorders in military populations. Our results also highlight the importance of correcting for misclassification in electronic medical record data research.


Subject(s)
Back Pain , Depressive Disorder, Major , Electronic Health Records , Military Personnel , Adult , Back Pain/diagnosis , Back Pain/epidemiology , Bias , Canada/epidemiology , Cohort Studies , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/epidemiology , Electronic Health Records/standards , Humans , Military Personnel/psychology , Military Personnel/statistics & numerical data
11.
Eur Radiol ; 32(4): 2620-2628, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34792635

ABSTRACT

OBJECTIVES: Deep-learning image reconstruction (DLIR) offers unique opportunities for reducing image noise without degrading image quality or diagnostic accuracy in coronary CT angiography (CCTA). The present study aimed at exploiting the capabilities of DLIR to reduce radiation dose and assess its impact on stenosis severity, plaque composition analysis, and plaque volume quantification. METHODS: This prospective study includes 50 patients who underwent two sequential CCTA scans at normal-dose (ND) and lower-dose (LD). ND scans were reconstructed with Adaptive Statistical Iterative Reconstruction-Veo (ASiR-V) 100%, and LD scans with DLIR. Image noise (in Hounsfield units, HU) and quantitative plaque volumes (in mm3) were assessed quantitatively. Stenosis severity was visually categorized into no stenosis (0%), stenosis (< 20%, 20-50%, 51-70%, 71-90%, 91-99%), and occlusion (100%). Plaque composition was classified as calcified, non-calcified, or mixed. RESULTS: Reduction of radiation dose from ND scans with ASiR-V 100% to LD scans with DLIR at the highest level (DLIR-H; 1.4 mSv vs. 0.8 mSv, p < 0.001) had no impact on image noise (28 vs. 27 HU, p = 0.598). Reliability of stenosis severity and plaque composition was excellent between ND scans with ASiR-V 100% and LD scans with DLIR-H (intraclass correlation coefficients of 0.995 and 0.974, respectively). Comparison of plaque volumes using Bland-Altman analysis revealed a mean difference of - 0.8 mm3 (± 2.5 mm3) and limits of agreement between - 5.8 and + 4.1 mm3. CONCLUSION: DLIR enables a reduction in radiation dose from CCTA by 43% without significant impact on image noise, stenosis severity, plaque composition, and quantitative plaque volume. KEY POINTS: •Deep-learning image reconstruction (DLIR) enables radiation dose reduction by over 40% for coronary computed tomography angiography (CCTA). •Image noise remains unchanged between a normal-dose CCTA reconstructed by ASiR-V and a lower-dose CCTA reconstructed by DLIR. •There is no impact on the assessment of stenosis severity, plaque composition, and quantitative plaque volume between the two scans.


Subject(s)
Computed Tomography Angiography , Deep Learning , Algorithms , Coronary Angiography , Drug Tapering , Humans , Image Processing, Computer-Assisted , Prospective Studies , Radiation Dosage , Radiographic Image Interpretation, Computer-Assisted/methods , Reproducibility of Results
12.
Eur Rev Med Pharmacol Sci ; 25(23): 7317-7322, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34919231

ABSTRACT

OBJECTIVE: This pilot study aimed at evaluating the effect of tonotopic (basal) stimulation on the Subjective Visual Vertical (SVV) in patients unilaterally treated with a Cochlear Implant (CI). MATERIALS AND METHODS: Ten adult subjects with severe to profound sensorineural hearing loss, who were implanted with a CI from Advanced Bionics (AB, Stäfa, Switzerland), model HiRes 90KTM or newer, were included in this prospective pilot study between September and December 2020. A specific CI processor (Naída CI Q90) was used to generate five different stimulation modes: simulation of either basal, medial, or apical electrodes, all electrodes on and all electrodes off. The examination of the verticality was carried out by means of SVV goggles both in the upright body position (head position 0 degrees) and with the head tilted sideways (-30°, -15°, +15°, +30°). RESULTS: In each stimulation mode, there was a significant difference (p < 0.05) in SVV between the straight head orientation and the tilted head position. There were, however, no significant differences between the five CI settings in any given head position (p > 0.05). No significant differences could be found regarding the direction of SVV deviation relative to the operated ear (p > 0.05). CONCLUSIONS: SVV could not be influenced by tonotopic CI stimulation. Different stimulation settings, patterns and intensity other than the auditory strategy may have to be developed to provide an adequate stimulus to the otolith organs.


Subject(s)
Cochlear Implants , Electric Stimulation/methods , Hearing Loss, Sensorineural/therapy , Visual Perception/physiology , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Patient Acuity , Pilot Projects , Prospective Studies
13.
Sci Rep ; 11(1): 21180, 2021 10 27.
Article in English | MEDLINE | ID: mdl-34707152

ABSTRACT

Recent research has revealed that shrimp sensory quality may be affected by ocean acidification but we do not exactly know why. Here we conducted controlled pH exposure experiments on adult tiger shrimp, which were kept in 1000-L tanks continuously supplied with coastal seawater. We compared survival rate, carapace properties and flesh sensory properties and amino acid composition of shrimp exposed to pH 7.5 and pH 8.0 treatments for 28 days. Shrimp reared at pH 7.5 had a lower amino acid content (17.6% w/w) than those reared at pH 8.0 (19.5% w/w). Interestingly, the amino acids responsible for the umami taste, i.e. glutamate and aspartic acid, were present at significantly lower levels in the pH 7.5 than the pH 8.0 shrimp, and the pH 7.5 shrimp were also rated as less desirable in a blind quality test by 40 volunteer assessors. These results indicate that tiger shrimp may become less palatable in the future due to a lower production of some amino acids. Finally, tiger shrimp also had a lower survival rate over 28 days at pH 7.5 than at pH 8.0 (73% vs. 81%) suggesting that ocean acidification may affect both the quality and quantity of future shrimp resources.


Subject(s)
Aspartic Acid/metabolism , Crassostrea/metabolism , Glutamic Acid/metabolism , Seawater/chemistry , Animals , Aspartic Acid/analysis , Climate Change , Crassostrea/chemistry , Glutamic Acid/analysis , Hydrogen-Ion Concentration , Seafood/standards
14.
Mol Cancer Ther ; 20(10): 1820-1835, 2021 10.
Article in English | MEDLINE | ID: mdl-34253596

ABSTRACT

Protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of apoptosis, proliferation, and DNA-damage response, is overexpressed in many cancers, including small cell lung cancer (SCLC). Here we report that LB100, a small molecule inhibitor of PP2A, when combined with platinum-based chemotherapy, synergistically elicited an antitumor response both in vitro and in vivo with no apparent toxicity. Using inductively coupled plasma mass spectrometry, we determined quantitatively that sensitization via LB100 was mediated by increased uptake of carboplatin in SCLC cells. Treatment with LB100 alone or in combination resulted in inhibition of cell viability in two-dimensional culture and three-dimensional spheroid models of SCLC, reduced glucose uptake, and attenuated mitochondrial and glycolytic ATP production. Combining LB100 with atezolizumab increased the capacity of T cells to infiltrate and kill tumor spheroids, and combining LB100 with carboplatin caused hyperphosphorylation of the DNA repair marker γH2AX and enhanced apoptosis while attenuating MET signaling and invasion through an endothelial cell monolayer. Taken together, these data highlight the translational potential of inhibiting PP2A with LB100 in combination with platinum-based chemotherapy and immunotherapy in SCLC.


Subject(s)
Gene Expression Regulation, Enzymologic/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Lung Neoplasms/drug therapy , Piperazines/pharmacology , Protein Phosphatase 2/antagonists & inhibitors , Small Cell Lung Carcinoma/drug therapy , Antineoplastic Agents/pharmacology , Apoptosis , Cell Proliferation , Humans , Lung Neoplasms/enzymology , Lung Neoplasms/pathology , Small Cell Lung Carcinoma/enzymology , Small Cell Lung Carcinoma/pathology , Tumor Cells, Cultured
15.
Sci Adv ; 7(28)2021 Jul.
Article in English | MEDLINE | ID: mdl-34244141

ABSTRACT

The 87Rb-87Sr radiochronometer provides key insights into the timing of volatile element depletion in planetary bodies, yet the unknown nucleosynthetic origin of Sr anomalies in Ca-Al-rich inclusions (CAIs, the oldest dated solar system solids) challenges the reliability of resulting chronological interpretations. To identify the nature of these Sr anomalies, we performed step-leaching experiments on nine unmelted CAIs from Allende. In six CAIs, the chemically resistant residues (0.06 to 9.7% total CAI Sr) show extreme positive µ84Sr (up to +80,655) and 87Sr variations that cannot be explained by decay of 87Rb. The extreme 84Sr but more subdued 87Sr anomalies are best explained by the presence of a presolar carrier enriched in the p-nuclide 84Sr. We argue that this unidentified carrier controls the isotopic anomalies in bulk CAIs and outer solar system materials, which reinstates the chronological significance of differences in initial 87Sr/86Sr between CAIs and volatile-depleted inner solar system materials.

16.
Elife ; 102021 04 19.
Article in English | MEDLINE | ID: mdl-33871352

ABSTRACT

The HIV-1 gp120/gp41 trimer undergoes a series of conformational changes in order to catalyze gp41-induced fusion of viral and cellular membranes. Here, we present the crystal structure of gp41 locked in a fusion intermediate state by an MPER-specific neutralizing antibody. The structure illustrates the conformational plasticity of the six membrane anchors arranged asymmetrically with the fusion peptides and the transmembrane regions pointing into different directions. Hinge regions located adjacent to the fusion peptide and the transmembrane region facilitate the conformational flexibility that allows high-affinity binding of broadly neutralizing anti-MPER antibodies. Molecular dynamics simulation of the MPER Ab-stabilized gp41 conformation reveals a possible transition pathway into the final post-fusion conformation with the central fusion peptides forming a hydrophobic core with flanking transmembrane regions. This suggests that MPER-specific broadly neutralizing antibodies can block final steps of refolding of the fusion peptide and the transmembrane region, which is required for completing membrane fusion.


Subject(s)
Broadly Neutralizing Antibodies/metabolism , HIV Antibodies/metabolism , HIV Envelope Protein gp41/antagonists & inhibitors , HIV-1/immunology , Single-Domain Antibodies/metabolism , Antibody Specificity , Binding Sites, Antibody , Broadly Neutralizing Antibodies/immunology , HEK293 Cells , HIV Antibodies/immunology , HIV Envelope Protein gp41/immunology , HIV Envelope Protein gp41/metabolism , Humans , Lipid Bilayers , Membrane Fusion , Molecular Dynamics Simulation , Protein Binding , Protein Conformation , Protein Folding , Protein Stability , Single-Domain Antibodies/immunology , Structure-Activity Relationship
17.
Curr Pharm Des ; 27(29): 3229-3234, 2021.
Article in English | MEDLINE | ID: mdl-33438532

ABSTRACT

Office white-coat effect tail (OWCET) is defined as a decrease of ≥10 mmHg in systolic blood pressure (SBP) between successive measurements after its waxing during an office visit. The influence of sex on the incidence of long-term major fatal and non-fatal cardiovascular events was studied in two Italian populational cohorts [from the Gubbio Study and the Italian Rural Areas of the Seven Countries Study (IRA)]. OWCET increased risk of cardiovascular disease (CVD) [HR: 1.591 (95% CI: 1.204-2.103)], coronary heart disease (CHD) [HR: 1.614 (95% CI: 1.037-2.512)] and stroke (STR) [HR: 1.696 (95% CI: 1.123-2.563)] events independently of age, serum and high density lipoprotein (HDL) cholesterol, cigarettes, body mass index (BMI) and SBP in women included in Gubbio study over an almost 20-year follow-up. However, risks of CVD, CHD or STR increased in men with OWCET neither in the Gubbio 20-year follow-up nor in the IRA 50-year follow-up. The correction of the regression dilutions bias between the first and the subsequent SBP measurements did not significantly change these outcomes. Primary care physicians should evaluate OWCET, especially in women, to improve stratification of long-term CVD, CHD and STR risks.


Subject(s)
Cardiovascular Diseases , Coronary Disease , Hypertension , Blood Pressure , Cardiovascular Diseases/epidemiology , Female , Humans , Incidence , Male , Risk Factors
18.
ACS Appl Mater Interfaces ; 12(50): 55795-55808, 2020 Dec 16.
Article in English | MEDLINE | ID: mdl-33274910

ABSTRACT

Metallic lithium deposition on graphite anodes is a critical degradation mode in lithium-ion batteries, which limits safety and fast charge capability. A conclusive strategy to mitigate lithium deposition under fast charging yet remains elusive. In this work, we examine the role of electrode microstructure in mitigating lithium plating behavior under various operating conditions, including fast charging. The multilength scale characteristics of the electrode microstructure lead to a complex interaction of transport and kinetic limitations that significantly governs the cell performance and the occurrence of Li plating. We demonstrate, based on a comprehensive mesoscale analysis, that the performance and degradation can be significantly modulated via systematic design improvements at the hierarchy of length scales. It is found that the improvement in kinetic and transport characteristics achievable at disparate scales can dramatically affect Li plating propensity.

19.
FEMS Yeast Res ; 20(5)2020 08 01.
Article in English | MEDLINE | ID: mdl-32584995

ABSTRACT

Candida albicans is the most common human fungal pathogen that can cause superficial and deep-seated infections in susceptible individuals. Despite its medical importance, the vast majority of C. albicans genes remain of unknown function. Here, we report a role for the lineage-specific gene, MRV8, in host pathogen interactions, mycelial microcolony maturation and biofilm formation. In silico analysis indicated that MRV8 encodes a four-pass transmembrane protein unique to the closely related pathogens C. albicans and Candida dubliniensis. Deletion of MRV8 did not affect C. albicans adherence to, or initial invasion into human oral epithelia, but inhibited mycelial development and strongly reduced epithelial damage. mrv8Δ/Δ cells exhibited a media-dependent defect in biofilm formation and mutant biofilm metabolic activity was enhanced by cyclosporin A. mrv8Δ/Δ biofilms were more tolerant to treatment with caspofungin, but not to fluconazole or amphotericin B. Co-stimulation with calcium chloride and calcofluor white rescued biofilm growth in the presence of caspofungin, and this rescue-effect was Mrv8-dependent. Together, our data demonstrate an important role for a lineage-specific gene (MRV8) in C. albicans biofilm formation, drug tolerance and host-pathogen interactions.


Subject(s)
Biofilms , Candida albicans/pathogenicity , Fungal Proteins/metabolism , Mouth Mucosa/microbiology , Antifungal Agents/pharmacology , Biofilms/drug effects , Candida albicans/drug effects , Cell Line, Tumor , Fungal Proteins/genetics , Host-Pathogen Interactions , Humans
20.
Mil Med ; 185(7-8): e1255-e1262, 2020 08 14.
Article in English | MEDLINE | ID: mdl-32073617

ABSTRACT

INTRODUCTION: Major depression is a leading cause of morbidity in military personnel and an important impediment to operational readiness in military organizations. Although treatment options are available, a large proportion of individuals with depression do not access mental health services. Quantifying and closing this treatment gap is a public health priority. However, the scientific literature on the major depression treatment gap in military organizations has never been systematically reviewed. METHODS: We systematically searched the EMBASE, MEDLINE, and PsychINFO databases for studies measuring recent mental health service use in personnel serving in the armed forces of a Five-Eye country (Australia, Canada, New Zealand, the United Kingdom, or the United States). We excluded studies conducted with retired veterans. Because of the substantial heterogeneity in included studies, we did not pool their results. Instead, we computed median period prevalence of mental health service use. RESULTS: Twenty-eight studies were included in the systematic review; 12 had estimated mental health service use in personnel with depression, and another 16 had estimated mental health service use in personnel with depression or another mental health disorder. The period prevalence of mental health service use in depressed military personnel ranged from 20 to 75% in 12 included studies, with a median of 48%, over 2-12 months. The other 16 studies yielded similar conclusions; they reported period prevalence of mental health service use in personnel with any mental health disorder ranging from 14 to 75%, with a median of 36%, over 1-12 months. The median was higher in studies relying on diagnostic interviews to identify depressed personnel, compared to studies relying on screening tools (60% vs. 44%). CONCLUSIONS: There is a large treatment gap for major depression in particular, and for mental health disorders in general, among military personnel. However, our results highlight the association between the use of measurement tools and treatment gaps: estimated treatment gaps were larger when depressed patients were identified by screening tools instead of diagnostic interviews. Researchers should be wary of overestimating the mental health treatment gap when using screening tools in future studies.


Subject(s)
Mental Health Services , Military Personnel , Humans , Mental Disorders , Veterans
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