Subclinical Atherosclerosis to Guide Treatment in Dyslipidemia and Diabetes Mellitus.

PURPOSE OF REVIEW: Dyslipidemia and type 2 diabetes mellitus are two common conditions that are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). In this review, we aimed to provide an in-depth and contemporary review of non-invasive approaches to assess subclinical atherosclerotic burden, predict cardiovascular risk, and guide appropriate treatment strategies. We focused this paper on two main imaging modalities: coronary artery calcium (CAC) score and computed tomography coronary angiography. RECENT FINDINGS: Recent longitudinal studies have provided stronger evidence on the relationship between increased CAC, thoracic aorta calcification, and risk of cardiovascular events among those with primary hypercholesterolemia, highlighting the beneficial role of statin therapy. Interestingly, resilient profiles of individuals not exhibiting atherosclerosis despite dyslipidemia have been described. Non-conventional markers of dyslipidemia have also been associated with increased subclinical atherosclerosis presence and burden, highlighting the contribution of apolipoprotein B-100 (apoB)-rich lipoprotein particles, such as remnant cholesterol and lipoprotein(a), to the residual risk of individuals on-target for low-density lipoprotein cholesterol (LDL-C) goals. Regarding type 2 diabetes mellitus, variability in atherosclerotic burden has also been found, and CAC testing has shown significant predictive value in stratifying cardiovascular risk. Non-invasive assessment of subclinical atherosclerosis can help reveal the continuum of ASCVD risk in those with dyslipidemia and diabetes mellitus and can inform personalized strategies for cardiovascular disease prevention in the primary prevention setting.

Digital Health Interventions for Hypertension Management in US Populations Experiencing Health Disparities: A Systematic Review and Meta-Analysis.

Importance: Hypertension remains a leading factor associated with cardiovascular disease, and demographic and socioeconomic disparities in blood pressure (BP) control persist. While advances in digital health technologies have increased individuals' access to care for hypertension, few studies have analyzed the use of digital health interventions in vulnerable populations. Objective: To assess the association between digital health interventions and changes in BP and to characterize tailored strategies for populations experiencing health disparities. Data Sources: In this systematic review and meta-analysis, a systematic search identified studies evaluating digital health interventions for BP management in the Cochrane Library, Ovid Embase, Google Scholar, Ovid MEDLINE, PubMed, Scopus, and Web of Science databases from inception until October 30, 2023. Study Selection: Included studies were randomized clinical trials or cohort studies that investigated digital health interventions for managing hypertension in adults; presented change in systolic BP (SBP) or baseline and follow-up SBP levels; and emphasized social determinants of health and/or health disparities, including a focus on marginalized populations that have historically been underserved or digital health interventions that were culturally or linguistically tailored to a population with health disparities. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Data Extraction and Synthesis: Two reviewers extracted and verified data. Mean differences in BP between treatment and control groups were analyzed using a random-effects model. Main Outcomes and Measures: Primary outcomes included mean differences (95% CIs) in SBP and diastolic BP (DBP) from baseline to 6 and 12 months of follow-up between digital health intervention and control groups. Shorter- and longer-term follow-up durations were also assessed, and sensitivity analyses accounted for baseline BP levels. Results: A total of 28 studies (representing 8257 participants) were included (overall mean participant age, 57.4 years [range, 46-71 years]; 4962 [60.1%], female). Most studies examined multicomponent digital health interventions incorporating remote BP monitoring (18 [64.3%]), community health workers or skilled nurses (13 [46.4%]), and/or cultural tailoring (21 [75.0%]). Sociodemographic characteristics were similar between intervention and control groups. Between the intervention and control groups, there were statistically significant mean differences in SBP at 6 months (-4.24 mm Hg; 95% CI, -7.33 to -1.14 mm Hg; P = .01) and SBP changes at 12 months (-4.30 mm Hg; 95% CI, -8.38 to -0.23 mm Hg; P = .04). Few studies (4 [14.3%]) reported BP changes and hypertension control beyond 1 year. Conclusions and Relevance: In this systematic review and meta-analysis of digital health interventions for hypertension management in populations experiencing health disparities, BP reductions were greater in the intervention groups compared with the standard care groups. The findings suggest that tailored initiatives that leverage digital health may have the potential to advance equity in hypertension outcomes.

Sacubitril-Valsartan (LCZ696) in the Treatment of Systemic Hypertension: An Updated Review of Neprilysin Inhibition Combined with Angiotensin II Receptor Blockade.

Sacubitril-valsartan (LCZ696) has been demonstrated to be a highly effective treatment for heart failure with preserved ejection fraction since its Food and Drug Administration approval in 2015, and a growing body of evidence suggests its emergence as a hypertensive medication. It acts as an inhibitor of both neprilysin and the renin-angiotensin-aldosterone system, approaching the control of a multi-faceted pathology in multiple unique ways. Because 48% of US adults are affected by hypertension, with less than half of patients achieving controlled blood pressure, and the high correlation between uncontrolled hypertension and cardiovascular mortality, it is crucial to investigate new pharmacotherapies for managing this disease. This review discusses the current evidence of sacubitril-valsartan trials in hypertension management, with a focus on distinct populations and hypertension subsets. Asian populations are predisposed to salt-sensitive hypertension and have been shown to benefit from sacubitril-valsartan more than olmesartan, an angiotensin receptor blocker (ARB). Systolic hypertension from stiff, aging arteries commonly affects individuals over the age of 65 years, and responds demonstrably better to sacubitril-valsartan than ARB monotherapy. Patients with treatment-resistant hypertension, especially those with heart failure, also show significantly improved blood pressure when treated with sacubitril-valsartan over ARBs. We conclude with a discussion of sacubitril-valsartan's potential role in managing noncardiac disease.

Assessing SSU rDNA Barcodes in Foraminifera: A Case Study using Bolivina quadrata.

The Small Subunit Ribosomal RNA gene (SSU rDNA) is a widely used tool to reconstruct phylogenetic relationships among foraminiferal species. Recently, the highly variable regions of this gene have been proposed as DNA barcodes to identify foraminiferal species. However, the resolution of these barcodes has not been well established, yet. In this study, we evaluate four SSU rDNA hypervariable regions (37/f, 41/f, 43/e, and 45/e) as DNA barcodes to distinguish among species of the genus Bolivina, with particular emphasis on Bolivina quadrata for which ten new sequences (KY468817-KY468826) were obtained during this study. Our analyses show that a single SSU rDNA hypervariable sequence is insufficient to resolve all Bolivina species and that some regions (37/f and 41/f) are more useful than others (43/e and 45/e) to distinguish among closely related species. In addition, polymorphism analyses reveal a high degree of variability. In the context of barcoding studies, these results emphasize the need to assess the range of intraspecific variability of DNA barcodes prior to their application to identify foraminiferal species in environmental samples; our results also highlight the possibility that a longer SSU rDNA region might be required to distinguish among species belonging to the same taxonomic group (i.e. genus).

Impact ejecta at the Paleocene-Eocene boundary.

Extraterrestrial impacts have left a substantial imprint on the climate and evolutionary history of Earth. A rapid carbon cycle perturbation and global warming event about 56 million years ago at the Paleocene-Eocene (P-E) boundary (the Paleocene-Eocene Thermal Maximum) was accompanied by rapid expansions of mammals and terrestrial plants and extinctions of deep-sea benthic organisms. Here, we report the discovery of silicate glass spherules in a discrete stratigraphic layer from three marine P-E boundary sections on the Atlantic margin. Distinct characteristics identify the spherules as microtektites and microkrystites, indicating that an extraterrestrial impact occurred during the carbon isotope excursion at the P-E boundary.

Impact of Antarctic Circumpolar Current development on late Paleogene ocean structure.

Global cooling and the development of continental-scale Antarctic glaciation occurred in the late middle Eocene to early Oligocene (~38 to 28 million years ago), accompanied by deep-ocean reorganization attributed to gradual Antarctic Circumpolar Current (ACC) development. Our benthic foraminiferal stable isotope comparisons show that a large δ(13)C offset developed between mid-depth (~600 meters) and deep (>1000 meters) western North Atlantic waters in the early Oligocene, indicating the development of intermediate-depth δ(13)C and O(2) minima closely linked in the modern ocean to northward incursion of Antarctic Intermediate Water. At the same time, the ocean's coldest waters became restricted to south of the ACC, probably forming a bottom-ocean layer, as in the modern ocean. We show that the modern four-layer ocean structure (surface, intermediate, deep, and bottom waters) developed during the early Oligocene as a consequence of the ACC.

The Phanerozoic record of global sea-level change.

We review Phanerozoic sea-level changes [543 million years ago (Ma) to the present] on various time scales and present a new sea-level record for the past 100 million years (My). Long-term sea level peaked at 100 +/- 50 meters during the Cretaceous, implying that ocean-crust production rates were much lower than previously inferred. Sea level mirrors oxygen isotope variations, reflecting ice-volume change on the 10(4)- to 10(6)-year scale, but a link between oxygen isotope and sea level on the 10(7)-year scale must be due to temperature changes that we attribute to tectonically controlled carbon dioxide variations. Sea-level change has influenced phytoplankton evolution, ocean chemistry, and the loci of carbonate, organic carbon, and siliciclastic sediment burial. Over the past 100 My, sea-level changes reflect global climate evolution from a time of ephemeral Antarctic ice sheets (100 to 33 Ma), through a time of large ice sheets primarily in Antarctica (33 to 2.5 Ma), to a world with large Antarctic and large, variable Northern Hemisphere ice sheets (2.5 Ma to the present).

The rise of oxygen over the past 205 million years and the evolution of large placental mammals.

On the basis of a carbon isotopic record of both marine carbonates and organic matter from the Triassic-Jurassic boundary to the present, we modeled oxygen concentrations over the past 205 million years. Our analysis indicates that atmospheric oxygen approximately doubled over this period, with relatively rapid increases in the early Jurassic and the Eocene. We suggest that the overall increase in oxygen, mediated by the formation of passive continental margins along the Atlantic Ocean during the opening phase of the current Wilson cycle, was a critical factor in the evolution, radiation, and subsequent increase in average size of placental mammals.

Climatically driven macroevolutionary patterns in the size of marine diatoms over the Cenozoic.

Numerous taxonomic groups exhibit an evolutionary trajectory in cell or body size. The size structure of marine phytoplankton communities strongly affects food web structure and organic carbon export into the ocean interior, yet macroevolutionary patterns in the size structure of phytoplankton communities have not been previously investigated. We constructed a database of the size of the silica frustule of the dominant fossilized marine planktonic diatom species over the Cenozoic. We found that the minimum and maximum sizes of the diatom frustule have expanded in concert with increasing species diversity. In contrast, the mean area of the diatom frustule is highly correlated with oceanic temperature gradients inferred from the delta18O of foraminiferal calcite, consistent with the hypothesis that climatically induced changes in oceanic mixing have altered nutrient availability in the euphotic zone and driven macroevolutionary shifts in the size of marine pelagic diatoms through the Cenozoic.

The evolution of modern eukaryotic phytoplankton.

The community structure and ecological function of contemporary marine ecosystems are critically dependent on eukaryotic phytoplankton. Although numerically inferior to cyanobacteria, these organisms are responsible for the majority of the flux of organic matter to higher trophic levels and the ocean interior. Photosynthetic eukaryotes evolved more than 1.5 billion years ago in the Proterozoic oceans. However, it was not until the Mesozoic Era (251 to 65 million years ago) that the three principal phytoplankton clades that would come to dominate the modern seas rose to ecological prominence. In contrast to their pioneering predecessors, the dinoflagellates, coccolithophores, and diatoms all contain plastids derived from an ancestral red alga by secondary symbiosis. Here we examine the geological, geochemical, and biological processes that contributed to the rise of these three, distantly related, phytoplankton groups.