Tag: pubmed

Cardiovasc Res. 2022 Jan 10:cvab375. doi: 10.1093/cvr/cvab375. Online ahead of print.

ABSTRACT

 : Cardiac electrophysiological heterogeneity includes: (i) regional differences in action potential (AP) waveform, (ii) AP waveform differences in cells isolated from a single region, (iii) variability of the contribution of individual ion currents in cells with similar APDs.

AIMS: To assess intra-regional AP waveform differences, to quantify the contribution of specific ion channels to the APD via drug responses and to generate a population of mathematical models to investigate the mechanisms underlying heterogeneity in rabbit ventricular cells.

METHODS AND RESULTS: APD in ∼50 isolated cells from subregions of the LV free wall of rabbit hearts were measured using a voltage-sensitive dye. When stimulated at 2 Hz, average APD90 value in cells from the basal epicardial region was 254 ± 25ms (mean±SD) in 17 hearts with a mean inter-quartile range (IQR) of 53 ± 17ms. Endo-epicardial and apical-basal APD90 differences accounted for ∼10% of the IQR value. Highly variable changes in APD occurred after IK(r) or ICa(L) block that included a sub-population of cells (HR) with an exaggerated (hyper) response to IK(r) inhibition. A set of 4,471 AP models matching the experimental APD90 distribution was generated from a larger population of models created by random variation of the maximum conductances (Gmax) of 8 key ion channels/exchangers/pumps. This set reproduced the pattern of cell-specific responses to ICa(L) and IK(r) block, including the HR sub-population. The models exhibited a wide range of Gmax values with constrained relationships linking ICa(L) with IK(r), ICl, INCX and INaK.

CONCLUSIONS: Modelling the measured range of inter-cell APDs required a larger range of key Gmax values indicating that ventricular tissue has considerable inter-cell variation in channel/pump/exchanger activity. AP morphology is retained by relationships linking specific ionic conductances. These interrelationships are necessary for stable repolarisation despite large inter-cell variation of individual conductances and this explains the variable sensitivity to ion channel block.

TRANSLATIONAL PERSPECTIVE: We show that single myocytes from the same region of a heart have highly variable electrophysiology and different responses to ion-channel blocking drugs because of even higher inter-cell variation in ion-channel activity. Our data demonstrate that it is the relative activity of a single ion channel comparted to others that determines electrophysiological stability in the heart. Therefore, predisposition to arrhythmias from genetic or environmental causes is not due to up- or down-regulation of single ion-channels, but instead disrupted patterns of co-expression. An alternative treatment strategy therefore is to manipulate other ion-channels in the network to restore a stable co-expression pattern.

PMID:35020837 | DOI:10.1093/cvr/cvab375

Am J Epidemiol. 2022 Jan 7:kwab300. doi: 10.1093/aje/kwab300. Online ahead of print.

ABSTRACT

Rural-urban differences in maternal mortality ratios (MMR) in the United States have been difficult to measure in recent years due to the incremental adoption of a pregnancy status checkbox on death certificates. Using 1999-2017 mortality and birth data, we examined the impact of the pregnancy checkbox on MMRs by rural-urban residence (large urban, medium/small urban, rural), using log-binomial regression models to predict trends as if all states had adopted the checkbox as of 1999. Implementation of the checkbox resulted in an average estimated increase of 7.5 maternal deaths per 100,000 live births (95% CI: 6.3, 8.8) in large urban areas (76% increase), 11.6 (95% CI: 9.6, 13.6) in medium/small urban areas (113% increase), and 16.6 (95% CI: 12.9, 20.3) in rural areas (107% increase), compared with MMRs prior to the checkbox. Assuming all states had the checkbox as of 1999, demographic-adjusted predicted MMRs increased in rural, declined in large urban, and did not change in medium/small urban areas. However, trends and urban-rural differences were substantially attenuated when analyses were limited to direct/specific causes of maternal death, which are likely subject to less misclassification. Accurate ascertainment of maternal deaths, particularly in rural areas, is important for reducing disparities in maternal mortality.

PMID:35020799 | DOI:10.1093/aje/kwab300

Am J Epidemiol. 2022 Jan 11:kwab297. doi: 10.1093/aje/kwab297. Online ahead of print.

ABSTRACT

Racial residential segregation is associated with multiple adverse health outcomes in Black individuals. Yet, the influence of structural racism and racial residential segregation on brain aging is less understood. In this study, we investigate the association between cumulative exposure to racial residential segregation over 25 years (1985-2010) of young adulthood, measured by the Getis-Ord Gi*-statistic, and year 25 measures of brain volume in midlife (cerebral, gray matter, white matter, and hippocampal volumes). We studied 290 Black participants with available brain imaging data who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) prospective cohort study. CARDIA originally recruited 2637 Black participants aged 18 to 30 years old from 4 field centers across the United States. We conducted analyses using marginal structural models, incorporating inverse probability weighting and inverse censoring weighting. We found that compared to low/medium segregation, greater cumulative exposure to residential segregation throughout young adulthood was associated with smaller brain volumes in general (e.g. β for cerebral volume: -0.08 [95% CI]: [-0.15, -0.02]) and with a more pronounced reduction in hippocampal volume, though results were not statistically significant. Our findings suggest that exposure to segregated neighborhoods may be associated with worse brain aging.

PMID:35020781 | DOI:10.1093/aje/kwab297

Am J Clin Nutr. 2022 Jan 10:nqab428. doi: 10.1093/ajcn/nqab428. Online ahead of print.

ABSTRACT

BACKGROUND: Longer-term consumption of saturated fatty acid (SFA)-reduced, monounsaturated fatty acid (MUFA)-enriched dairy products have been reported to improve fasting flow-mediated vasodilation (FMD). Yet, their impact on endothelial function in the postprandial state warrants investigation.

OBJECTIVES: To compare the impact of a fatty acid (FA)-modified with a conventional (control) dairy diet on the postprandial %FMD (primary outcome) and systemic cardiometabolic responses to representative meals, and retrospectively explore whether treatment effects differ by apolipoprotein (APO)E or endothelial nitric oxide synthase (eNOS) Glu298Asp gene polymorphisms.

METHODS: In a crossover-design randomized controlled study, 52 adults with moderate cardiovascular disease risk consumed dairy products [38% total energy intake (%TE) from fat: FA-modified (target: 16%TE SFAs; 14%TE MUFAs) or control (19%TE SFAs; 11%TE MUFAs)] for 12-wk, separated by an 8-wk washout. Blood sampling and FMD measurements (0-480 min) were performed pre- and post-intervention after sequential mixed meals that were representative of the assigned dairy diets (0 min; ∼50 g fat; 330 min; ∼30 g fat).

RESULTS: Relative to pre-intervention (∆), the FA-modified dairy diet and meals (treatment) attenuated the increase in the incremental AUC (iAUC), but not AUC, for the %FMD response observed with the conventional treatment (-135 ± 69 vs + 199 ± 82% x min; P = 0.005). The ∆ iAUC, but not AUC, for the apoB response decreased after FA-modified yet increased after the conventional treatment (-4 ± 3 vs + 3 ± 3 mg/mL × min; P = 0.004). The ∆ iAUC decreased for total plasma SFAs (P = 0.003) and trans 18:1 (P < 0.0001) and increased for cis-MUFAs (P < 0.0001) following conventional, relative to the FA-modified treatment. No treatment x APOE- or eNOS-genotype interactions were evident for any outcome.

CONCLUSIONS: This study provides novel insights into the longer-term effects of FA-modified dairy food consumption on postprandial cardiometabolic responses. Clinical Trial Registry: Unique identifier: NCT02089035. URL: https://clinicaltrials.gov/ct2/show/NCT02089035.

PMID:35020795 | DOI:10.1093/ajcn/nqab428

PLoS One. 2022 Jan 12;17(1):e0262236. doi: 10.1371/journal.pone.0262236. eCollection 2022.

ABSTRACT

Wild birds can be colonized by bacteria, which are often resistant to antibiotics and have various virulence profiles. The aim of this study was to analyze antibiotic resistance mechanisms and virulence profiles in relation to the phylogenetic group of E. coli strains that were isolated from the GI tract of wildfowl. Out of 241 faecal samples, presence of E. coli resistant to a cephalosporin (ESBL/AmpC) was estimated for 33 isolates (13,7%). Based on the analysis of the coexistence of 4 genes encoding ESBLs/AmpC (blaCTX-M, blaTEM, blaSHV, blaAmpC) and class 1 and 2 integrons genes (intI1, intI2) a subset of two resistance profiles was observed among the investigated E. coli isolates carrying blaAmpC, blaSHV, and blaCTX-M, blaTEM, class 1 and 2 integrons, respectively. The E. coli isolates were categorized into 4 phylogenetic groups A (39.4%), B2 (24.25%), D (24.25%) and B1 (12.1%). The pathogenic B2 and D groups were mainly typical for the Laridae family. Among the 28 virulence factors (Vfs) detected in pathogenic phylogenetic groups B2 and D, 7 were exclusively found in those groups (sfa, vat, tosA, tosB, hly, usp, cnf), while 4 VFs (fecA, fyuA, irp2, kspMTII) showed a statistically significant association (P≤0.05) with phylogroups A and B1. Our results indicated that strains belonging to commensal phylogroups A/B1 possess extensive iron acquisition systems (93,9%) and autotransporters (60,6%), typical for pathogens, hence we suggest that these strains evolve towards higher levels of virulence. This study, which is a point assessment of the virulence and drug resistance potential of wild birds, confirms the importance of taking wild birds as a reservoir of strains that pose a growing threat to humans. The E. coli analyzed in our study derive from different phylogenetic groups and possess an arsenal of antibiotic resistance genes and virulence factors that contribute to their ability to cause diseases.

PMID:35020771 | DOI:10.1371/journal.pone.0262236

PLoS One. 2022 Jan 12;17(1):e0262404. doi: 10.1371/journal.pone.0262404. eCollection 2022.

ABSTRACT

The utility of chest x-ray examination (CXR) in mandatory annual health examinations for occupational health is debatable in Japan. This study aimed to provide basic data to consider future policies for mandatory annual health examinations in the workplace. A nationwide descriptive survey was performed to determine the rate of detection of tuberculosis, lung cancer, and other diseases through CXR in organizations associated with National Federation of Industrial Health Association. The rate of finding on CXR conducted during annual health examinations in FY2016 was evaluated. Data regarding diagnosis based on follow-up examination findings were obtained and compared with the national statistics. In addition, CXR findings were compared with the results of low-dose lung computed tomography performed at the Hitachi Health Care Center. From 121 surveyed institutions, 88 institutions with 8,669,403 workers were included. For all ages, 1.0% of examinees required follow-up examination. Among 4,764,985 workers with diagnosis data, the tuberculosis detection rate was 1.8-5.3 per 100,000 persons. For Lung cancer, 3,688,396 workers were surveyed, and 334 positive cases were detected. The lung cancer detection rate using CXR was 9.1-24.4 per 100,000 persons. From 164 cases with information regarding the clinical stage, 72 (43.9%) had Stage I lung cancer. From 40,045 workers who underwent low-dose computed tomography multiple times, 31 lung cancer cases, all with Stage I disease, were detected (detection rate: 77.4 per 100,000 persons). Our findings suggest that CXR plays a little role in the detection of active tuberculosis. With regard to LC screening, the detection rate of LC by CXR was lower, approximately 50%, than the expected rate (41.0 per 100,000 persons) of LC morbidity based on the age-sex distribution of this study population. However, the role of CXR for LC screening cannot be mentioned based on this result, because assessment of mortality reduction is essential to evaluate the role.

PMID:35020766 | DOI:10.1371/journal.pone.0262404

PLoS One. 2022 Jan 12;17(1):e0261946. doi: 10.1371/journal.pone.0261946. eCollection 2022.

ABSTRACT

Obesity is the most common nutritional disorder in dogs and it is associated with many comorbidities. Some obesity risk factors have already been established, however, the evaluation of the effect of different individual variables on weight loss induced by calorie restriction, although very important, is still poorly explored. The weight loss protocol can be updated and improved by more precise and adjusted equations throughout the weight loss program in the clinical routine practice. Therefore, the objective of this study was to analyze weight loss program dynamics in groups according to reproductive status, age, body size, and breed, as well as to define more accurately the amount of calories per target metabolic weight throughout the program. Data of 1,053 cases, presented between 2012 and 2019 at the Veterinary Hospital of the School of Veterinary Medicine and Animal Science of the University of São Paulo (FMVZ-USP) were retrospectively analyzed. A total of 77 obese dogs (body condition scores 8/9 or 9/9) of different ages, breeds, sizes, and reproductive status were selected. These dogs did not have any concomitant illnesses and successfully completed the weight loss program. Statistical analysis was performed and values of p≤0.05 were considered significant. The proposed weight loss program was based on an energy restriction protocol where daily energy intake (in kcal) was estimated as 70 kcal × target weight0.75. The target weight (TW) was defined as 80% of the animal’s current weight. The average calorie intake for weight loss (calories x target weight0.75) was lower for spayed females (62.36), differing from intact males (66.14) and neutered males (65.41), while intact females (63.66) showed intermediate values without differing between groups (p = 0.015). There were no differences between weight loss calories according to age (p = 0.473) or body size (p = 0.084), allowing the use of the same mathematical equation for intact and neutered dogs; for dogs older than 1 year and of different body sizes. Regarding the breed, the average calorie intake was lower (p = 0.002) in mixed breed dogs (61.54xTW0.75) when compared to obesity-prone purebred dogs (64.17xTW0.75) and other purebreds (65.27xTW0.75). It was concluded that spayed females and mixed breed dogs have greater difficulty in losing weight, that is, they need fewer calories per metabolic body weight for the weight loss program to succeed. A more accurate equation for energy requirement for weight loss can improve chances of success, therefore improving compliance and helping clinical management of obesity in dogs.

PMID:35020762 | DOI:10.1371/journal.pone.0261946

PLoS One. 2022 Jan 12;17(1):e0262160. doi: 10.1371/journal.pone.0262160. eCollection 2022.

ABSTRACT

Advanced analytical methods play an important role in quantifying serum disease biomarkers. The problem of separating thousands of proteins can be reduced by analyzing for a ‘sub-proteome’, such as the ‘metalloproteome’, defined as all proteins that contain bound metals. We employed size exclusion chromatography (SEC) coupled to an inductively coupled plasma atomic emission spectrometer (ICP-AES) to analyze plasma from multiple sclerosis (MS) participants (n = 21), acute ischemic stroke (AIS) participants (n = 17) and healthy controls (n = 21) for Fe, Cu and Zn-metalloproteins. Using ANOVA analysis to compare the mean peak areas among the groups revealed no statistically significant differences for ceruloplasmin (p = 0.31), α2macroglobulin (p = 0.51) and transferrin (p = 0.31). However, a statistically significant difference was observed for the haptoglobin-hemoglobin (Hp-Hb) complex (p = 0.04), being driven by the difference between the control group and AIS (p = 0.012), but not with the MS group (p = 0.13), based on Dunnes test. A linear regression model for Hp-Hb complex with the groups now adjusted for age found no statistically significant differences between the groups (p = 0.95), but was suggestive for age (p = 0.057). To measure the strength of association between the Hp-Hb complex and age without possible modifications due to disease, we calculated the Spearman rank correlation in the healthy controls. The latter revealed a positive association (r = 0.39, 95% Confidence Interval = (-0.05, 0.83), which suggests that either the removal of Hp-Hb complexes from the blood circulation slows with age or that the release of Hb from red blood cells increases with age. We also observed that the Fe-peak corresponding to the Hp-Hb complex eluted ~100 s later in ~14% of all study samples, which was not correlated with age or disease diagnosis, but is consistent with the presence of the smaller Hp (1-1) isoform in 15% of the population.

PMID:35020753 | DOI:10.1371/journal.pone.0262160

PLoS One. 2022 Jan 12;17(1):e0261650. doi: 10.1371/journal.pone.0261650. eCollection 2022.

ABSTRACT

The Effective Reproduction Number Rt provides essential information for the management of an epidemic/pandemic. Projecting Rt into the future could further assist in the management process. This article proposes a methodology based on exposure scenarios to perform such a procedure. The method utilizes a compartmental model and its adequate parametrization; a way to determine suitable parameters for this model in México’s case is detailed. In conjunction with the compartmental model, the projection of Rt permits estimating unobserved variables, such as the size of the asymptomatic population, and projecting into the future other relevant variables, like the active hospitalizations, using scenarios. The uses of the proposed methodologies are exemplified by analyzing the pandemic in a Mexican state; the main quantities derived from the compartmental model, such as the active and total cases, are included in the analysis. This article also presents a national summary based on the methodologies to illustrate how these procedures could be further exploited. The supporting information includes an application of the proposed methods to a metropolitan area to show that it also works well at other demographic disaggregation levels. The procedures developed in this article shed light on how to develop an effective surveillance system when information is incomplete and can be applied in cases other than México’s.

PMID:35020745 | DOI:10.1371/journal.pone.0261650

PLoS One. 2022 Jan 12;17(1):e0262218. doi: 10.1371/journal.pone.0262218. eCollection 2022.

ABSTRACT

Public lands in the United States are those land areas managed by federal, state, and county governments for public purposes such as preservation and recreation. Protecting carbon resources and increasing carbon sequestration capacity are compatible with public land management objectives for healthy and resilient habitats, i.e., managing habitats for the benefit of wildlife and ecosystem services can simultaneously capture and store carbon. To evaluate the effect of public land management on carbon storage and review carbon management as part of the land management objectives, we used existing data of carbon stock and net ecosystem carbon balance in a study of the National Wildlife Refuge System (NWRS), a public land management program of the U.S. Fish and Wildlife Service (Service). Total carbon storage of the 364 refuges studied was 16.6 PgC, with a mean value 42,981 gCm-2. We used mixed modeling with Bonferroni adjustment techniques to analyze the effect of time since refuge designation on carbon storage. In general, older refuges store more carbon per unit area than younger refuges. In addition to the age factor, carbon resources are variable by regions and habitat types protected in the refuges. Mean carbon stock and the rate of sequestration are higher within refuges than outside refuges, but the statistical comparison of 364 refuges analyzed in this study was not significant. We also used the social cost of carbon to analyze the annual benefits of sequestrating carbon in these publicly managed lands in the United States, which is over $976 million per year in avoided CO2 emissions via specific conservation management actions. We examine case studies of management, particularly with respect to Service cooperation activities with The Conservation Fund (TCF) Go Zero® Program, Trust for Public Land (TPL) and individuals. Additional opportunities exist in improving techniques to maximize carbon resources in refuges, while continuing to meet the core purpose and need of the NWRS.

PMID:35020751 | DOI:10.1371/journal.pone.0262218