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1.
bioRxiv ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39149290

RESUMO

Protein Tyrosine Phosphatase 1B (PTP1B) is a negative regulator of leptin signaling whose disruption protects against diet-induced obesity in mice. We investigated whether structural characterization of human PTP1B variant proteins might reveal precise mechanisms to target for weight loss therapy. We selected 12 rare variants for functional characterization from exomes from 997 people with persistent thinness and 200,000 people from UK Biobank. Seven of 12 variants impaired PTP1B function by increasing leptin-stimulated STAT3 phosphorylation in cells. Using room-temperature X-ray crystallography, hydrogen-deuterium exchange mass spectrometry, and computational modeling, we determined that human variants modulate the 3-dimensional structure of PTP1B through distinct allosteric conduits that energetically link distal, highly ligandable structural regions to the active site. These studies inform the design of allosteric PTP1B inhibitors for the treatment of obesity.

2.
PNAS Nexus ; 3(8): pgae260, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39108306

RESUMO

As on land, oceans exhibit high temporal and spatial temperature variation. This "ocean weather" contributes to the physiological and ecological processes that ultimately determine the patterns of species distribution and abundance, yet is often unrecognized, especially in tropical oceans. Here, we tested the paradigm of temperature stability in shallow waters (<12.5 m) across different zones of latitude. We collated hundreds of in situ, high temporal-frequency ocean temperature time series globally to produce an intuitive measure of temperature variability, ranging in scale from quarter-diurnal to annual time spans. To estimate organismal sensitivity of ectotherms (i.e. microbes, algae, and animals whose body temperatures depend upon ocean temperature), we computed the corresponding range of biological rates (such as metabolic rate or photosynthesis) for each time span, assuming an exponential relationship. We found that subtropical regions had the broadest temperature ranges at time spans equal to or shorter than a month, while temperate and tropical systems both exhibited narrow (i.e. stable) short-term temperature range estimates. However, temperature-dependent biological rates in tropical regions displayed greater ranges than in temperate systems. Hence, our results suggest that tropical ectotherms may be relatively more sensitive to short-term thermal variability. We also highlight previously unexplained macroecological patterns that may be underpinned by short-term temperature variability.

3.
Sci Total Environ ; 946: 174434, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38960154

RESUMO

Air pollution and greenness are environmental determinants of mental health, though existing evidence typically considers each exposure in isolation. We evaluated relationships between co-occurring air pollution and greenspace levels and depression and anxiety. We estimated cross-sectional associations among 9015 Gulf Long-term Follow-up Study participants living in the southeastern U.S. who completed the Patient Health Questionnaire-9 (depression: score ≥ 10) and Generalized Anxiety Disorder Questionnaire-7 (anxiety: score ≥ 10). Participant residential addresses were linked to annual average concentrations of particulate matter (1 km PM2.5) and nitrogen dioxide (1 km NO2), as well as satellite-based greenness (2 km Enhanced Vegetation Index (EVI)). We used adjusted log-binomial regression to estimate prevalence ratios (PR) and 95 % confidence intervals (CI) for associations between exposures (quartiles) and depression and anxiety. In mutually adjusted models (simultaneously modeling PM2.5, NO2, and EVI), the highest quartile of PM2.5 was associated with increased prevalence of depression (PR = 1.17, 95 % CI: 1.06-1.29), whereas the highest quartile of greenness was inversely associated with depression (PR = 0.89, 95 % CI: 0.80-0.99). Joint exposure to greenness mitigated the impact of PM2.5 on depression (PRPM only = 1.20, 95 % CI: 1.06-1.36; PRPM+green = 0.98, 95 % CI: 0.83-1.16) and anxiety (PRPM only = 1.10, 95 % CI: 1.00-1.22; PRPM+green = 0.95, 95 % CI: 0.83-1.09) overall and in subgroup analyses. Observed associations were stronger in urbanized areas and among nonwhite participants, and varied by neighborhood deprivation. NO2 exposure was not independently associated with depression or anxiety in this population. Relationships between PM2.5, greenness, and depression were strongest in the presence of characteristics that are highly correlated with lower socioeconomic status, underscoring the need to consider mental health as an environmental justice issue.


Assuntos
Poluição do Ar , Depressão , Exposição Ambiental , Saúde Mental , Material Particulado , Humanos , Poluição do Ar/estatística & dados numéricos , Saúde Mental/estatística & dados numéricos , Material Particulado/análise , Exposição Ambiental/estatística & dados numéricos , Depressão/epidemiologia , Feminino , Masculino , Seguimentos , Pessoa de Meia-Idade , Adulto , Poluentes Atmosféricos/análise , Ansiedade/epidemiologia , Estudos Transversais , Sudeste dos Estados Unidos/epidemiologia , Dióxido de Nitrogênio/análise
4.
Environ Sci Technol ; 58(31): 13820-13832, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39038214

RESUMO

Numerous US drinking water aquifers have been contaminated with per- and polyfluoroalkyl substances (PFAS) from fire-fighting and fire-training activities using aqueous film-forming foam (AFFF). These sites often contain other organic compounds, such as fuel hydrocarbons and methane, which may serve as primary substrates for cometabolic (i.e., nongrowth-linked) biotransformation reactions. This work investigates the abilities of AFFF site relevant bacteria (methanotrophs, propanotrophs, octane, pentane, isobutane, toluene, and ammonia oxidizers), known to express oxygenase enzymes when degrading their primary substrates, to biotransform perfluoroalkyl acid (PFAA) precursors to terminal PFAAs. Microcosms containing AFFF-impacted groundwater, 6:2 fluorotelomer sulfonate (6:2 FTS), or N-ethylperfluorooctane sulfonamidoethanol (EtFOSE) were inoculated with the aerobic cultures above and incubated for 4 and 8 weeks at 22 °C. Bottles were sacrificed, extracted, and subjected to target, nontarget, and suspect screening for PFAS. The PFAA precursors 6:2 FTS, N-sulfopropyldimethyl ammoniopropyl perfluorohexane sulfonamide (SPrAmPr-FHxSA), and EtFOSE transformed up to 99, 71, and 93%, respectively, and relevant daughter products, such as the 6:1 fluorotelomer ketone sulfonate (6:1 FTKS), were identified in quantities previously not observed, implicating oxygenase enzymes. This is the first report of a suite of site relevant PFAA precursors being transformed in AFFF-impacted groundwater by bacteria grown on substrates known to induce specific oxygenase enzymes. The data provide crucial insights into the microbial transformation of these compounds in the subsurface.


Assuntos
Biotransformação , Água Subterrânea , Oxigenases , Poluentes Químicos da Água , Água Subterrânea/química , Água Subterrânea/microbiologia , Oxigenases/metabolismo , Poluentes Químicos da Água/metabolismo , Bactérias/metabolismo , Fluorocarbonos/metabolismo , Biodegradação Ambiental
5.
Nat Med ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886623

RESUMO

PI3K-δ inhibitors have shown impressive activity in lymphoid malignancies but have been hampered by autoimmune and infectious toxicities, leading to market withdrawals. We previously demonstrated activity of the PI3K-δγ inhibitor duvelisib in T cell lymphomas (TCLs) that was associated with inflammatory adverse events. As reported here, we conducted a phase 1b/2a study of duvelisib in combination with either romidepsin (n = 66) or bortezomib (n = 32) in patients with relapsed/refractory TCL and found that the addition of romidepsin, but not bortezomib, appeared to increase efficacy while attenuating PI3K inhibitor-driven toxicity. The primary endpoint of the study was to determine the safety and maximum tolerated dose of duvelisib, which was 75 mg twice daily when combined with romidepsin versus 25 mg twice daily when combined with bortezomib. The most common adverse events were neutropenia (42%, 25/59) and fatigue (37%, 22/59) in patients treated with duvelisib and romidepsin and diarrhea (48%, 11/23) and neutropenia (30%, 7/23) in patients treated with duvelisib and bortezomib. Duvelisib and romidepsin resulted in less grade 3/4 hepatotoxicity (14%, 8/59) compared to 40% (14/35) in our previous study with duvelisib monotherapy. This was associated with reductions in circulating inflammatory mediators and myeloid cell inflammatory gene expression. Secondary endpoints of overall and complete response rates were 55% (35/64) and 34% (22/64) for patients treated with duvelisib and romidepsin and 34% (11/32) and 13% (4/32) for patients treated with duvelisib and bortezomib. Among patients with peripheral T cell lymphomas (PTCLs), overall and complete response rates of duvelisib and romidepsin were 56% (27/48) and 44% (21/48), respectively, with exploratory analyses showing increased response rates in patients with a follicular helper T cell subtype. These findings support further development of combined PI3K and histone deacetylase (HDAC) inhibition in TCLs and suggest a unique strategy to enable PI3K inhibitor-based combinations for additional patient populations. ClinicalTrials.gov identifier: NCT02783625 .

6.
Membranes (Basel) ; 14(6)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38921494

RESUMO

To date, life support systems on the International Space Center (ISS) or those planned for upcoming moon/Mars missions have not included biological reactors for wastewater treatment, despite their ubiquitous use for the treatment of terrestrial wastewaters. However, the new focus on partial gravity habitats reduces the required complexity of treatment systems compared with those operating in micro-gravity, and the likely addition of large-volume wastewaters with surfactant loads (e.g., laundry and shower) makes the current ISS wastewater treatment system inappropriate due to the foaming potential from surfactants, increased consumable requirements due to the use of non-regenerative systems (e.g., mixed adsorbent beds), the complexity of the system, and sensitivity to failures from precipitation and/or biological fouling. Hybrid systems that combine simple biological reactors with desalination (e.g., Reverse Osmosis (RO)) could reduce system and consumable mass and complexity. Our objective was to evaluate a system composed of a membrane-aerated bioreactor (MABR) coupled to a low-pressure commercial RO system to process partial gravity habitat wastewater. The MABR was able to serve as the only wastewater collection tank (variable volume), receiving all wastewaters as they were produced. The MABR treated more than 20,750 L of graywater and was able to remove more than 90% of dissolved organic carbon (DOC), producing an effluent with DOC < 14 mg/L and BOD < 12 mg/L and oxidizing >90% of the ammoniacal nitrogen into NOx-. A single RO membrane (260 g) was able to process >3000 L of MABR effluent and produced a RO permeate with DOC < 5 mg/L, TN < 2 mg/L, and TDS < 10 mg/L, which would essentially meet ISS potable water standards after disinfection. The system has an un-optimized mass and volume of 128.5 kg. Consumables include oxygen (~4 g/crew-day), RO membranes, and a prefilter (1.7 g/crew-day). For a one-year mission with four crew, the total system + consumable mass are ~141 kg, which would produce ~15,150 kg of treated water, resulting in a pay-back period of 13.4 days (3.35 days for a crew of four). Given that the MABR in this study operated for 500 days, while in previous studies, similar systems operated for more than 3 years, the total system costs would be exceedingly low. These results highlight the potential application of hybrid treatment systems for space habitats, which may also have a direct application to terrestrial applications where source-separated systems are employed.

7.
BMC Public Health ; 24(1): 1220, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38698385

RESUMO

BACKGROUND: Minoritized racial/ethnic groups and women in the United States (US) are disproportionately burdened by food insecurity, which likely contributes to disparities in cardiovascular health (CVH). Disparities are projected to widen due to the worsening climate crisis that is straining the agricultural system including food supplies. Nonetheless, studies have not investigated the relationship between food security status and 'ideal' CVH in a large, nationally-representative and racially/ethnically diverse US sample. METHODS AND RESULTS: We investigated household food security status in relation to 'ideal' CVH among US adults (N = 157,001) using 2014-2018/2020 National Health Interview Survey data. Food security status was defined as very low, low, marginal, or high. A summed score of 4 health behaviors and 3 clinical factors totaling 7 different measures was dichotomized (yes/no) to assess modified 'ideal' CVH (mICVH). Using Poisson regression with robust variance, we estimated prevalence ratios (PRs) and 95% CIs of mICVH by household food security status. We stratified models by sex/gender and race/ethnicity. Very low food security prevalence was higher among non-Hispanic (NH)-Black (8.0%) compared to Hispanic/Latinx (5.1%), NH-White (3.1%) and NH-Asian (1.7%) adults. The association between very low versus high food security and mICVH was stronger among women (PR = 0.23 [95% CI: 0.17-0.31]) than men (PR = 0.48 [95% CI: 0.35-0.66]). Compared to NH-White adults with high food security, racially/ethnically minoritized groups with very low to high food security were generally less likely (range: [PRvery low = 0.25[95% CI: 0.14-0.44] - [PRhigh = 0.88 [95% CI: 0.79-0.97]) to meet mICVH criteria. CONCLUSIONS: Food insecurity was associated with lower mICVH prevalence and racially/ethnically minoritized groups were disproportionately burdened.


Assuntos
Segurança Alimentar , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Doenças Cardiovasculares/etnologia , Doenças Cardiovasculares/epidemiologia , Etnicidade/estatística & dados numéricos , Segurança Alimentar/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Inquéritos Epidemiológicos , Grupos Raciais/estatística & dados numéricos , Fatores Sexuais , Estados Unidos/epidemiologia , Negro ou Afro-Americano , Asiático , Hispânico ou Latino , Brancos
8.
Sci Total Environ ; 935: 173387, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38788945

RESUMO

BACKGROUND: Research on metal-associated neurodegeneration has largely focused on single metals. Since metal exposures typically co-occur as combinations of both toxic and essential elements, a mixtures framework is important for identifying risk and protective factors. This study examined associations between toenail levels of an eight-metal mixture and attention and memory in men living in US Gulf states. METHODS: We measured toenail concentrations of toxic (arsenic, chromium, lead, and mercury) and essential (copper, manganese, selenium, and zinc) metals in 413 non-smoking men (23-69 years, 46 % Black) from the Gulf Long-Term Follow-Up (GuLF) Study. Sustained attention and working memory were assessed at the time of toenail sample collection using the continuous performance test (CPT) and digit span test (DST), respectively. Associations between toenail metal concentrations and performance on neurobehavioral tests were characterized using co-pollutant adjusted general linear models and Bayesian Kernel Machine Regression. RESULTS: Adjusting for other metals, one interquartile range (IQR) increase in toenail chromium was associated with a 0.19 (95 % CI: -0.31, -0.07) point reduction in CPT D Prime score (poorer ability to discriminate test signals from noise). One IQR increase in toenail manganese was associated with a 0.20 (95 % CI, -0.41, 0.01) point reduction on the DST Reverse Count (fewer numbers recalled). Attention deficits were greater among Black participants compared to White participants for the same increase in toenail chromium concentrations. No evidence of synergistic interaction between metals or adverse effect of the overall metal mixture was observed for either outcome. CONCLUSIONS: Our findings support existing studies of manganese-related memory deficits and are some of the first to show chromium related attention deficits in adults. Longitudinal study of cognitive decline is needed to verify chromium findings. Research into social and chemical co-exposures is also needed to explain racial differences in metal-associated neurobehavioral deficits observed in this study.


Assuntos
Unhas , Humanos , Unhas/química , Masculino , Pessoa de Meia-Idade , Adulto , Atenção/efeitos dos fármacos , Idoso , Adulto Jovem , Seguimentos , Exposição Ambiental/estatística & dados numéricos , Memória/efeitos dos fármacos , Metais/análise , Poluentes Químicos da Água/análise
9.
J Appl Physiol (1985) ; 136(6): 1488-1495, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38722754

RESUMO

Advancing age increases cardiovascular disease risk, in part, because of impaired glycocalyx thickness and endothelial dysfunction. Glycocalyx-targeted therapies, such as Endocalyx Pro, could improve both glycocalyx thickness and endothelial function in older adults; however, this has yet to be tested. We hypothesized that Endocalyx Pro supplementation would increase glycocalyx thickness and endothelial function in older adults. Twenty-three older adults aged 66 ± 7 yr (52% female) were enrolled in a randomized, double-blind, placebo-controlled, parallel-arms study to investigate the effect of 12-wk Endocalyx Pro supplementation (3,712 mg/day) on glycocalyx thickness and endothelial function. Glycocalyx thickness was assessed using the GlycoCheck, and endothelial function was determined via brachial artery flow-mediated dilation (FMD). Between-group comparisons revealed Endocalyx Pro did not increase glycocalyx thickness in microvessels 4-25 µm (P = 0.33), 4-7 µm (P = 0.07), or 10-25 µm (P = 0.47) in diameter when compared with placebo. In addition, Endocalyx Pro did not significantly improve FMD [mean ratio (95%) confidence interval [CI]) for between-group comparisons, 1.16 (0.77-1.74); P = 0.48]. However, Endocalyx Pro improved FMD normalized to shear rate (SR) area under the curve [mean ratio (95% CI) for between-group comparisons, 2.41 (1.14,4.13); P = 0.001]. Moreover, Endocalyx Pro increased capillary glycocalyx thickness more than placebo in individuals not taking antihypertensive medication [mean difference (95% CI) for between-group comparison, -0.08 (-0.15, -0.01); P = 0.02]. Our pilot study suggests that Endocalyx Pro supplementation is feasible in older adults but has no measurable effect on overall glycocalyx thickness and FMD. However, Endocalyx Pro may have select effects on capillary glycocalyx thickness and FMD normalized to shear rate among older adults, but further investigation is warranted.NEW & NOTEWORTHY Endothelial glycocalyx thickness and vascular endothelial function decline with advancing age. Endocalyx Pro is a glycocalyx-targeted therapy that may improve endothelial glycocalyx thickness and vascular endothelial function in older adults. This study demonstrated that 12-wk Endocalyx Pro supplementation did not improve overall endothelial glycocalyx thickness or flow-mediated dilation in older adults; however, Endocalyx Pro did increase capillary glycocalyx thickness in individuals not taking antihypertensive medication and improve flow-mediated dilation normalized to the shear stimulus.


Assuntos
Artéria Braquial , Endotélio Vascular , Glicocálix , Humanos , Glicocálix/efeitos dos fármacos , Glicocálix/metabolismo , Feminino , Masculino , Idoso , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Endotélio Vascular/fisiopatologia , Método Duplo-Cego , Artéria Braquial/efeitos dos fármacos , Artéria Braquial/fisiologia , Artéria Braquial/diagnóstico por imagem , Vasodilatação/efeitos dos fármacos , Vasodilatação/fisiologia , Pessoa de Meia-Idade , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/fisiopatologia
10.
Sci Data ; 11(1): 370, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605078

RESUMO

Freshwater ecosystems are biologically important habitats that provide many ecosystem services. Calcium concentration and pH are two key variables that are linked to multiple chemical processes in these environments, influence the biology of organisms from diverse taxa, and can be important factors affecting the distribution of native and non-native species. However, it can be challenging to obtain high-resolution data for these variables at regional and national scales. To address this data gap, water quality data for lakes and rivers in Canada and the continental USA were compiled and used to generate high-resolution (10 × 10 km) interpolated raster layers, after comparing multiple spatial interpolation approaches. This is the first time that such data have been made available at this scale and resolution, providing a valuable resource for research, including projects evaluating risks from environmental change, pollution, and invasive species. This will aid the development of conservation and management strategies for these vital habitats.

11.
Environ Health Perspect ; 132(2): 27013, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38416540

RESUMO

BACKGROUND: Studies are increasingly examining the relationship between the neighborhood environment and cognitive decline; yet, few have investigated associations between multiple neighborhood features and Alzheimer's disease and related dementias (ADRD). OBJECTIVE: We investigated the relationship between neighborhood features and ADRD cumulative incidence from 2010 to 2014 in the South Carolina Alzheimer's Disease Registry (SCADR). METHODS: Diagnosed ADRD cases ≥50 years of age were ascertained from the SCADR by ZIP code and census tract. Neighborhood features from multiple secondary sources included poverty, air pollution [particulate matter with a diameter of 2.5 micrometers or less (PM2.5)], and rurality at the census-tract level and access to healthy food, recreation facilities, and diabetes screening at the county level. In addition to using Poisson generalized linear regression to estimate ADRD incident rate ratios (IRR) with 95% confidence intervals (CIs), we applied integrated nested Laplace approximations and stochastic partial differential equations (INLA-SPDE) to address disparate spatial scales. We estimated associations between neighborhood features and ADRD cumulative incidence. RESULTS: The average annual ADRD cumulative incidence was 690 per 100,000 people per census tract (95% CI: 660, 710). The analysis was limited to 98% of census tracts with a population ≥50 years old (i.e., 1,081 of 1,103). The average percent of families living below the federal poverty line per census tract was 18.8%, and ∼20% of census tracts were considered rural. The average percent of households with limited access to healthy food was 6.4%. In adjusted models, every 5µg/m3) increase of PM2.5 was associated with 65% higher ADRD cumulative incidence (IRR=1.65; 95% CI: 1.30, 2.09), where PM2.5 at or below 12 µg/m3 is considered healthy. Compared to large urban census tracts, rural and small urban tracts had 10% (IRR=1.10; 95% CI: 1.00, 1.23) and 5% (IRR=1.05; 95% CI: 0.96, 1.16) higher ADRD, respectively. For every percent increase of the county population with limited access to healthy food, ADRD was 2% higher (IRR=1.02; 95% CI: 1.01, 1.04). CONCLUSIONS: Neighborhood environment features, such as higher air pollution levels, were associated with higher neighborhood ADRD incidence. The INLA-SPDE method could have broad applicability to data collected across disparate spatial scales. https://doi.org/10.1289/EHP13183.


Assuntos
Poluição do Ar , Doença de Alzheimer , Disfunção Cognitiva , Humanos , Doença de Alzheimer/epidemiologia , South Carolina/epidemiologia , Características da Vizinhança
12.
J Appl Physiol (1985) ; 136(2): 330-336, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38126088

RESUMO

The endothelial glycocalyx is a dynamic, gel-like layer that is critical to normal vascular endothelial function. Heparin impairs the endothelial glycocalyx and reduces vascular endothelial function in a murine model; however, this has yet to be tested in healthy humans. We hypothesized that a single bolus dose of heparin would increase circulating glycocalyx components and decrease endothelial glycocalyx thickness resulting in blunted brachial artery vasodilation in healthy younger adults. Healthy adults (n = 19, aged 18-39 yr, 53% female) underwent measurements of the endothelial glycocalyx and vascular endothelial function at baseline and after a single bolus 5,000 U dose of heparin. The glycocalyx components syndecan-1 and heparan sulfate were measured from plasma samples using enzyme-linked immunosorbent assays. Glycocalyx thickness was determined as perfused boundary region (PBR) in sublingual microvessels using the GlycoCheck. Endothelial function was measured via ultrasonography and quantified as brachial artery flow-mediated dilation (FMD). Following acute heparin administration, there was no increase in syndecan-1 or heparan sulfate (P = 0.90 and P = 0.49, respectively). In addition, there was no change in PBR 4-7 µm (P = 0.55), PBR 10-25 µm (P = 0.63), or 4-25 µm (P = 0.49) after heparin treatment. Furthermore, we did not observe a change in FMDmm (P = 0.23), FMD% (P = 0.35), or plasma nitrite concentrations (P = 0.10) in response to heparin. Finally, time to peak dilation and peak FMD normalized to shear stress were unchanged following heparin (P = 0.59 and P = 0.21, respectively). Our pilot study suggests that a single bolus intravenous dose of heparin does not result in endothelial glycocalyx degradation or vascular endothelial dysfunction in healthy younger adults.NEW & NOTEWORTHY The endothelial glycocalyx's role in modulating vascular endothelial dysfunction with aging and disease is becoming increasingly recognized. This study presents novel findings that acute heparin administration is not a feasible method to experimentally degrade the endothelial glycocalyx and measure concurrent changes in vascular endothelial function in healthy humans. Alternative approaches will be needed to translate findings from preclinical studies and test the effects of acute endothelial glycocalyx degradation on vascular endothelial function in humans.


Assuntos
Heparina , Sindecana-1 , Adulto , Humanos , Feminino , Camundongos , Animais , Masculino , Heparina/farmacologia , Heparina/metabolismo , Glicocálix/metabolismo , Projetos Piloto , Endotélio Vascular , Heparitina Sulfato/metabolismo , Heparitina Sulfato/farmacologia
13.
J Phys Chem A ; 127(51): 10838-10850, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38109706

RESUMO

The ligand binding energies (LBEs) of N-heterocyclic carbenes (NHCs) and CH2 and CF2 adducts with group 1, 2, 10, and 11 metals and complexes with metals from these groups are predicted at the coupled cluster CCSD(T) level of theory by using density functional theory optimized geometries. The differences in LBEs as a function of the metal and the types of bonding interactions as well as the type of carbene are described. The bonding between the alkali cations and alkaline earth dications is predominantly ionic with a linear correlation between the LBEs and the cation hardness. In contrast, the bonding behaviors of the group 10 and 11 metals and metal complexes have only a weak, indirect correlation between the LBEs and the metal hardness. The difference in bonding behavior between the groups of metals arises due to the accessibility of electron donation between the ligand and the metal in the transition metal complexes, which results in more covalent-like bonding behavior. The presence of the methyl groups on the NHC nitrogen results in only slightly more delocalized charge from the metal onto the ring, but there is significant redistribution of the charge on the ring. Saturation of the NHC ring had a much smaller effect on how the charge was distributed on the ring. The analysis of the bonding behavior of NHCs with various metal groups enables improved understanding of carbene-metal interactions to inform rational design of NHC-based systems.

14.
Front Glob Womens Health ; 4: 1286142, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38415184

RESUMO

Introduction: Pregnant women and their offspring are particularly vulnerable to food insecurity and its adverse effects during critical periods of fetal development. Racially/ethnically minoritized women in the United States (US) who are pregnant are additionally burdened by food insecurity, which may exacerbate cardiovascular health (CVH) disparities. Despite heightened social vulnerability, few studies have employed an intersectional framework, including race and gender, to assess the food insecurity and CVH relationship. Methods: We used 2012-2018 and 2020 National Health Interview Survey data among US pregnant women aged 18-49 years old (N = 1,999) to assess the prevalence of food insecurity status by race/ethnicity and to investigate household food security status in relation to ideal CVH, using a modified ideal CVH (mICVH) metric. We categorized food security status as "very low/low", "marginal", or "high". To assess mICVH, a summary score of 7 clinical characteristics and health behaviors was dichotomized as yes [(7)] vs. no [<7]. Prevalence ratios (PRs) and 95% confidence intervals (CIs) of associations between food security status and mICVH were estimated using Poisson regression with robust variance. Models were adjusted for age, household income, educational attainment, geographic region, marital status, alcohol consumption, survey year, and race/ethnicity (in overall model). Results: The mean age ± standard error was 29.0 ± 0.2 years. Among pregnant women, 12.7% reported "very low/low", 10.6% reported "marginal", and 76.7% reported "high" food security. "Very low/low" food security prevalence was higher among NH-Black (16.2%) and Hispanic/Latina (15.2%) pregnant women compared to NH-White (10.3%) and NH-Asian (3.2%) pregnant women. The mICVH prevalence was 11.6% overall and 14.5% for NH-White, 4.1% for NH-Black, 5.0% for Hispanic/Latina, and 26.7% for NH-Asian pregnant women. Among all pregnant women, "very low/low" and "marginal" vs. "high" food security status was associated with a lower prevalence of mICVH {[PRvery low/low = 0.26 (95% CI: 0.08-0.75)]; [PRmarginal = 0.47 (95% CI: 0.23 -0.96)]}. Conclusion: Household food insecurity was higher among pregnant women in minoritized racial/ethnic groups and was associated with lower mICVH prevalence. Given the higher burden of food insecurity among minoritized racial/ethnic groups, food security may be an important intervention target to help address disparities in poor CVH among pregnant women.

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