Obesity and related metabolic diseases show clear sex-related differences. The growing burden of these diseases calls for better understanding of the age- and sex-related metabolic consequences. ...High-throughput lipidomic analyses of population-based cohorts offer an opportunity to identify disease-risk-associated biomarkers and to improve our understanding of lipid metabolism and biology at a population level. Here, we comprehensively examined the relationship between lipid classes/subclasses and molecular species with age, sex, and body mass index (BMI). Furthermore, we evaluated sex specificity in the association of the plasma lipidome with age and BMI. Some 747 targeted lipid measures, representing 706 molecular lipid species across 36 classes/subclasses, were measured using a high-performance liquid chromatography coupled mass spectrometer on a total of 10,339 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), with 563 lipid species being validated externally on 4,207 participants of the Busselton Health Study (BHS). Heat maps were constructed to visualise the relative differences in lipidomic profile between men and women. Multivariable linear regression analyses, including sex-interaction terms, were performed to assess the associations of lipid species with cardiometabolic phenotypes. Associations with age and sex were found for 472 (66.9%) and 583 (82.6%) lipid species, respectively. We further demonstrated that age-associated lipidomic fingerprints differed by sex. Specific classes of ether-phospholipids and lysophospholipids (calculated as the sum composition of the species within the class) were inversely associated with age in men only. In analyses with women alone, higher triacylglycerol and lower lysoalkylphosphatidylcholine species were observed among postmenopausal women compared with premenopausal women. We also identified sex-specific associations of lipid species with obesity. Lysophospholipids were negatively associated with BMI in both sexes (with a larger effect size in men), whilst acylcarnitine species showed opposing associations based on sex (positive association in women and negative association in men). Finally, by utilising specific lipid ratios as a proxy for enzymatic activity, we identified stearoyl CoA desaturase (SCD-1), fatty acid desaturase 3 (FADS3), and plasmanylethanolamine Δ1-desaturase activities, as well as the sphingolipid metabolic pathway, as constituent perturbations of cardiometabolic phenotypes. Our analyses elucidate the effect of age and sex on lipid metabolism by offering a comprehensive view of the lipidomic profiles associated with common cardiometabolic risk factors. These findings have implications for age- and sex-dependent lipid metabolism in health and disease and suggest the need for sex stratification during lipid biomarker discovery, establishing biological reference intervals for assessment of disease risk.
How do landscapes—defined in the broadest sense to incorporate the physical contours of the built environment, the aesthetics of form, and the imaginative reflections of spatial ...representations—contribute to the making of politics? Shifting through the archaeological, epigraphic, and artistic remains of early complex societies, this provocative and far-reaching book is the first systematic attempt to explain the links between spatial organization and politics from an anthropological point of view.
The Classic-period Maya, the kingdom of Urartu, and the cities of early southern Mesopotamia provide the focal points for this multidimensional account of human polities. Are the cities and villages in which we live and work, the lands that are woven into our senses of cultural and personal identity, and the national territories we occupy merely stages on which historical processes and political rituals are enacted? Or do the forms of buildings and streets, the evocative sensibilities of architecture and vista, the aesthetics of place conjured in art and media constitute political landscapes—broad sets of spatial practices critical to the formation, operation, and overthrow of polities, regimes, and institutions? Smith brings together contemporary theoretical developments from geography and social theory with anthropological perspectives and archaeological data to pursue these questions.
Nitrogen heterocycles are among the most significant structural components of pharmaceuticals. Analysis of our database of U.S. FDA approved drugs reveals that 59% of unique small-molecule drugs ...contain a nitrogen heterocycle. In this review we report on the top 25 most commonly utilized nitrogen heterocycles found in pharmaceuticals. The main part of our analysis is divided into seven sections: (1) three- and four-membered heterocycles, (2) five-, (3) six-, and (4) seven- and eight-membered heterocycles, as well as (5) fused, (6) bridged bicyclic, and (7) macrocyclic nitrogen heterocycles. Each section reveals the top nitrogen heterocyclic structures and their relative impact for that ring type. For the most commonly used nitrogen heterocycles, we report detailed substitution patterns, highlight common architectural cores, and discuss unusual or rare structures.
To quantify and contextualize the risk for coronavirus disease 2019 (COVID-19)-related hospitalization and illness severity in type 1 diabetes.
We conducted a prospective cohort study to identify ...case subjects with COVID-19 across a regional health care network of 137 service locations. Using an electronic health record query, chart review, and patient contact, we identified clinical factors influencing illness severity.
We identified COVID-19 in 6,138, 40, and 273 patients without diabetes and with type 1 and type 2 diabetes, respectively. Compared with not having diabetes, people with type 1 diabetes had adjusted odds ratios of 3.90 (95% CI 1.75-8.69) for hospitalization and 3.35 (95% CI 1.53-7.33) for greater illness severity, which was similar to risk in type 2 diabetes. Among patients with type 1 diabetes, glycosylated hemoglobin (HbA
), hypertension, race, recent diabetic ketoacidosis, health insurance status, and less diabetes technology use were significantly associated with illness severity.
Diabetes status, both type 1 and type 2, independently increases the adverse impacts of COVID-19. Potentially modifiable factors (e.g., HbA
) had significant but modest impact compared with comparatively static factors (e.g., race and insurance) in type 1 diabetes, indicating an urgent and continued need to mitigate severe acute respiratory syndrome coronavirus 2 infection risk in this community.
Two-photon calcium imaging provides an optical readout of neuronal activity in populations of neurons with subcellular resolution. However, conventional two-photon imaging systems are limited in ...their field of view to ∼1 mm(2), precluding the visualization of multiple cortical areas simultaneously. Here, we demonstrate a two-photon microscope with an expanded field of view (>9.5 mm(2)) for rapidly reconfigurable simultaneous scanning of widely separated populations of neurons. We custom designed and assembled an optimized scan engine, objective, and two independently positionable, temporally multiplexed excitation pathways. We used this new microscope to measure activity correlations between two cortical visual areas in mice during visual processing.
Benzene is a ubiquitous chemical in our environment that causes acute leukemia and probably other hematological cancers. Evidence for an association with childhood leukemia is growing. Exposure to ...benzene can lead to multiple alterations that contribute to the leukemogenic process, indicating a multimodal mechanism of action. Research is needed to elucidate the different roles of multiple metabolites in benzene toxicity and the pathways that lead to their formation. Studies to date have identified a number of polymorphisms in candidate genes that confer susceptibility to benzene hematotoxicity. However, a genome-wide study is needed to truly assess the role of genetic variation in susceptibility. Benzene affects the blood-forming system at low levels of occupational exposure, and there is no evidence of a threshold. There is probably no safe level of exposure to benzene, and all exposures constitute some risk in a linear, if not supralinear, and additive fashion.
Ample evidence suggests that sleep and pain are related. However, many questions remain about the direction of causality in their association, as well as mechanisms that may account for their ...association. The prevailing view has generally been that they are reciprocally related. The present review critically examines the recent prospective and experimental literature (2005-present) in an attempt to update the field on emergent themes pertaining to the directionality and mechanisms of the association of sleep and pain. A key trend emerging from population-based longitudinal studies is that sleep impairments reliably predict new incidents and exacerbations of chronic pain. Microlongitudinal studies employing deep subjective and objective assessments of pain and sleep support the notion that sleep impairments are a stronger, more reliable predictor of pain than pain is of sleep impairments. Recent experimental studies suggest that sleep disturbance may impair key processes that contribute to the development and maintenance of chronic pain, including endogenous pain inhibition and joint pain. Several biopsychosocial targets for future mechanistic research on sleep and pain are discussed, including dopamine and opioid systems, positive and negative affect, and sociodemographic factors.
This critical review examines the recent prospective and experimental research (2005-present) on the association of sleep and pain in an attempt to identify trends suggestive of directionality and potential mechanisms. An update on this literature is needed to guide future clinical efforts to develop and augment treatments for chronic sleep disturbance and chronic pain.
Environment and Disease Risks Rappaport, Stephen M.; Smith, Martyn T.
Science (American Association for the Advancement of Science),
10/2010, Letnik:
330, Številka:
6003
Journal Article
Recenzirano
Odprti dostop
A new paradigm is needed to assess how a lifetime of exposure to environmental factors affects the risk of developing chronic diseases.
Although the risks of developing chronic diseases are ...attributed to both genetic and environmental factors, 70 to 90% of disease risks are probably due to differences in environments (
1
–
3
). Yet, epidemiologists increasingly use genome-wide association studies (GWAS) to investigate diseases, while relying on questionnaires to characterize “environmental exposures.” This is because GWAS represent the only approach for exploring the totality of any risk factor (genes, in this case) associated with disease prevalence. Moreover, the value of costly genetic information is diminished when inaccurate and imprecise environmental data lead to biased inferences regarding gene-environment interactions (
4
). A more comprehensive and quantitative view of environmental exposure is needed if epidemiologists are to discover the major causes of chronic diseases.
The response properties, connectivity and function of the cingulate sulcus visual area (CSv) are reviewed. Cortical area CSv has been identified in both human and macaque brains. It has similar ...response properties and connectivity in the two species. It is situated bilaterally in the cingulate sulcus close to an established group of medial motor/premotor areas. It has strong connectivity with these areas, particularly the cingulate motor areas and the supplementary motor area, suggesting that it is involved in motor control. CSv is active during visual stimulation but only if that stimulation is indicative of self-motion. It is also active during vestibular stimulation and connectivity data suggest that it receives proprioceptive input. Connectivity with topographically organized somatosensory and motor regions strongly emphasizes the legs over the arms. Together these properties suggest that CSv provides a key interface between the sensory and motor systems in the control of locomotion. It is likely that its role involves online control and adjustment of ongoing locomotory movements, including obstacle avoidance and maintaining the intended trajectory. It is proposed that CSv is best seen as part of the cingulate motor complex. In the human case, a modification of the influential scheme of Picard and Strick (Picard and Strick, Cereb Cortex 6:342–353, 1996) is proposed to reflect this.
Oxygen heterocycles are the second most common type of heterocycles that appear as structural components of U.S. Food and Drug Administration (FDA) approved pharmaceuticals. Analysis of our database ...of drugs approved through 2017 reveals 311 distinct pharmaceuticals containing at least one oxygen heterocycle. Most prevalent among these are pyranoses, with furanoses, macrolactones, morpholines, and dioxolanes rounding off the top five. The main body of this Perspective is organized according to ring size, commencing with three- and four-membered rings and ending with macrocycles, polymers, and unusual oxygen-containing heterocycles. For each section, all oxygen heterocycle-containing drugs are presented along with a brief discussion about structural and drug application patterns.
PDF
