Social networks and inflammatory markers in the Framingham Heart Study

Lack of social integration predicts coronary heart disease mortality in prospective studies; however, the biological pathways that may be responsible are poorly understood. The specific aims of this study were to examine whether social networks are associated with serum concentrations of the inflammatory markers interleukin-6 (IL-6), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1). Participants in the Framingham Study attending examinations from 1998 to 2001 (n=3267) were eligible for inclusion in the study. Social networks were assessed using the Berkman-Syme Social Network Index (SNI). Concentrations of IL-6, CRP, sICAM-1 and MCP-1 were measured in fasting serum samples. Multivariable linear regression analyses were used to assess the association of social networks with inflammatory markers adjusting for potential confounders including age, smoking, blood pressure, total:HDL cholesterol ratio, body mass index, lipid-lowering and antihypertensive medication, diabetes, cardiovascular disease, depression and socioeconomic status. Results found that the SNI was significantly inversely associated with IL-6 in men (p=0.03) after adjusting for potential confounders. In age-adjusted analyses, social networks also were significantly inversely associated with IL-6 for women (p=0.03) and were marginally to modestly associated with CRP and sICAM-1 for men (p=0.08 and 0.02, respectively), but these associations were not significant in the multivariate analyses. In conclusion, social networks were found to be inversely associated with interleukin-6 levels in men. The possibility that inflammatory markers may be potential mediators between social integration and coronary heart disease merits further investigation.     

Key factors associated with social distress after prostate cancer: Results from the United Kingdom Life after Prostate Cancer diagnosis study

BackgroundMore men are living following a prostate cancer (PCa) diagnosis. They may need support to maximize the quality of their survival. Physical and psychological impacts of PCa are widely documented. Less is known about social impacts. We aimed to identify key factors associated with social distress following PCa.MethodsThe Life After Prostate Cancer Diagnosis study is a UK national cross-sectional survey of men 18–42 months post diagnosis of PCa. Men (n = 58 930) were invited to participate by their diagnosing cancer centre including 82% of English NHS Trusts (n = 111) and 100% of all Health Boards in Northern Ireland (n = 5), Scotland (n = 14) and Wales (n = 6). Social distress was measured using the Social Difficulties Inventory (SDI-21), 16 item Social Distress scale with men assigned to ‘socially distressed’/‘not socially distressed’ groups, according to published guidelines. Clinical and sociodemographic variables were collected from self-report and cancer registries.ResultsResponse rate 60.8% (n = 35 823) of whom 97% (n = 29 351) completed the Social Distress scale (mean age = 71.2; SD = 7.88). The proportion of ‘socially distressed’ men was 9.4%. Multivariable logistic regression analysis revealed unemployment versus employment (odds ratio (OR): 11.58 [95% CI 9.16–14.63]) and ≥3 co-morbidities versus none (OR: 5.37 [95% CI 4.61–6.27]) as key associations. Others were Androgen Deprivation Therapy, External Beam Radiotherapy in combination with another treatment, age, prior mental health problems and living in a socio-economically deprived area.ConclusionMost men following PCa are socially resilient. A simple checklist could help clinicians identify men at risk of social distress.     

Blood mercury concentrations in common bottlenose dolphins from the Indian River Lagoon,Florida: Patterns of social distribution

Social network analysis has been shown to be effective in studying the social structure of cetacean populations. Common bottlenose dolphins (Tursiops truncatus) inhabiting the Indian River Lagoon (IRL), Florida, have among the highest concentrations of total mercury (THg) in blood reported worldwide. The purpose of this study was to examine the relationship between THg concentrations in IRL dolphins and their social affiliations. Whole blood samples from 98 dolphins with photo‐identification sighting histories were collected between 2003–2007 and 2010–2012. Dolphins were categorized into approximate tertiles of low (mean 199.7 μg/L), medium (mean 366.8 μg/L), and high (mean 990.5 μg/L) THg exposure. Social associations between individual dolphins were defined by the proportion of sightings documented with another known individual. Social network measures of individuals and associations between dyads were examined to determine differences among THg categories. Strong social affiliations of individuals within the highest category of THg were found (P = 0.04), suggesting shared exposures among dolphins foraging in specific areas of the estuary. Network measures of strength and affinity were significantly higher in the highest exposure category. This report used social network analysis as a novel way to examine patterns of exposure to an environmental contaminant in a cetacean population.     

Insulin Sensitivity in African‐American and White Women: Association With Inflammation

Whether the contribution of inflammation to risk for chronic metabolic disease differs with ethnicity is not known. The objective of this study was to determine: (i) whether ethnic differences exist in markers of inflammation and (ii) whether lower insulin sensitivity among African Americans vs. whites is due to greater inflammatory status. Subjects were African‐American (n = 108) and white (n = 105) women, BMI 27–30 kg/m². Insulin sensitivity was assessed with intravenous glucose tolerance test and minimal modeling; fat distribution with computed tomography; body composition with dual‐energy X‐ray absorptiometry; markers of inflammation (tumor necrosis factor (TNF)‐α, soluble tumor necrosis factor receptor (sTNFR)‐1, sTNFR‐2, C‐reactive protein (CRP), and interleukin (IL)‐6) with enzyme‐linked immunosorbent assay (ELISA). Whites had greater intra‐abdominal adipose tissue (IAAT), insulin sensitivity, and concentrations of TNF‐α, sTNFR‐1, and sTNFR‐2 than African Americans. Greater TNF‐α in whites vs. African Americans was attributed to greater IAAT in whites. Among whites, but not African Americans, CRP was independently and inversely associated with insulin sensitivity, after adjusting for IAAT (r = ?0.29 P < 0.05, and r = ?0.13 P = 0.53, respectively). Insulin sensitivity remained lower in African Americans after adjusting for CRP (P < 0.001). In conclusion, greater IAAT among whites may be associated with greater inflammation. Insulin sensitivity was lower among African Americans, independent of obesity, fat distribution, and inflammation.     

Common bottlenose dolphin (Tursiops truncatus) social structure and distribution changes following the 2008 Unusual Mortality Event in the Indian River Lagoon,Florida

In animal societies with fission-fusion dynamics, demographic disturbances can influence the social and spatial structure of the population. Within the Indian River Lagoon (IRL), Florida, common bottlenose dolphins (Tursiops truncatus) have experienced recurrent unusual mortality events (UMEs) providing an opportunity to examine postdisturbance population and social cluster restructuring. This study investigates the impact of the potentially nonepizootic 2008 UME on the IRL dolphin population. Photo-identification surveys conducted from August 2006 to May 2010 were stratified into pre- (August 2006–April 2008) and post-UME (September 2008–May 2010) time periods. Social network and spatial (univariate kernel density) analyses were limited to individuals sighted 5+ times per period (pre-UME = 183, post-UME = 134), and indicated a change from 11 to ten social clusters, although individuals did not always reassociate with pre-UME cluster associates. Despite the social and spatial disconnect between IRL proper and Mosquito Lagoon clusters, both network density and core area spatial overlap increased post-UME allowing for increased intercluster interactions. However, intracluster associations increased as well, allowing the population to maintain multiple social clusters within a loosely connected network. This study shows the important role sociality may play in the adaptability of cetaceans to environmental and demographic changes.     

BMI,Waist Circumference,and Mortality According to Health Status in the Older Adult Population of Spain

Among the explanations proposed for the weak and inconsistent association between BMI and mortality in the elderly are the lack of adjustment for waist circumference (WC) and that the association varies with health status. This work examines the independent association of BMI and WC with mortality in older adults, and the influence of health status on this association. A cohort of 3,536 persons representative of the Spanish population aged ≥60 years was selected in 2000 and 2001, and followed prospectively until 2007. The analyses were performed with Cox models and adjusted for the main confounders. During follow‐up, 659 persons died (18.6% of the cohort). Before adjusting for WC, mortality in the upper quartile of BMI was 15% lower than in the lower quartile (hazard ratio (HR): 0.85; 95% confidence interval (CI): 0.66–1.08; P for linear trend = 0.076). After adjusting for WC, the association was even stronger, so that mortality in the upper quartile of BMI was 37% lower than in the lower quartile (HR: 0.63; 95% CI: 0.45–0.88; P for linear trend < 0.003). Before adjusting for BMI, no association was observed between WC and mortality. After adjusting for BMI, WC was positively associated with mortality (HR for upper vs. lower quartile of WC: 1.48; 95% CI: 1.07–2.05; P for linear trend = 0.008). These associations were mainly observed in those with limitations in mobility and agility. BMI has an inverse, and WC has a direct, independent association with mortality in older adults, particularly in those with worse health status.     

Dynamic changes of platelet-related parameters and their associations with clinical outcomes in COVID-19 patients during hospitalization

This paper aims to analyze dynamic changes in platelet-related indicators and their associations with clinical outcomes in COVID-19 patients. 220 COVID-19 patients hospitalized in the General Hospital of Central Theater Command the PLA from January 21, 2020 to March 25, 2020, were enrolled. These patients were firstly divided into non-severe and severe groups in accordance with disease severity on admission. The patients of the severe group were further divided into survivors and non-survivors according to whether the patient was discharged or deceased. The results demonstrated that IL-6 had negative correlations with PLT (R=?0.318, P<0.001) and PCT (R=?0.323, P<0.001). However, no significant correlations or only weak correlations were found between the platelet-related parameters (PLT, MPV, PDW, PCT, and P-LCR) and other indexes of coagulation and inflammation (PT, APTT, FIB, D-D, and CRP). The dynamic changes of platelet-related parameters in non-severe patients and survivors during hospitalization showed very similar trends and changing rules, while those in the non-survivor group were considerably different. After adjusting for demographic variables and coexisting disorders, the patients with nadir platelet counts of (100–150), (50–100), and (0–50), respectively, possessed a significantly increased risk of mortality [(OR=1.81, 95% CI, 0.2–16.44, P>0.05), (OR=9.91, 95% CI, 1.36–72.2, P<0.05), and (OR=53.81, 95% CI, 5.85–495.22, P<0.001)] with (150–) as the reference. This study suggests that changing trends of the platelet-related parameterrs during hospitalization especially in the first week after admission, are of great significance for predicting clinical outcomes.     

Factors associated with inflammation markers, a cross-sectional analysis

Epidemiological studies have reported associations between circulating inflammation markers and risk of chronic diseases. It is of interest to examine whether risk factors for these diseases are associated with inflammation. We conducted a cross-sectional analysis to evaluate whether reproductive and lifestyle factors and circulating vitamin D were associated with inflammation markers, including C-reactive protein, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα), and cytokine modulators (IL-1RA, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1/R2), among 616 healthy women. We confirmed associations of several inflammation markers with age and BMI. We also observed significantly higher levels of certain inflammation markers in postmenopausal vs. premenopausal women (TNFα, sIL-1RII, sIL-2Ra), with increasing parity (IL-12p40), and with higher circulating 25(OH) vitamin D (IL-13) and lower levels among current users of non-steroidal anti-inflammatory drugs (NSAIDs) (IL-1β, IL-2, IL-10, IL-12p70, and IL-12p40), current smokers (IL-4, IL-13, IL-12p40), and women with a family history of breast or ovarian cancer (IL-4, IL-10, IL-13). Our findings suggest that risk factors for chronic diseases (age, BMI, menopausal status, parity, NSAID use, family history of breast and ovarian cancer, and smoking) are associated with inflammation markers in healthy women.     

Unraveling the metabolic underpinnings of frailty using multicohort observational and Mendelian randomization analyses

Identifying metabolic biomarkers of frailty, an age-related state of physiological decline, is important for understanding its metabolic underpinnings and developing preventive strategies. Here, we systematically examined 168 nuclear magnetic resonance-based metabolomic biomarkers and 32 clinical biomarkers for their associations with frailty. In up to 90,573 UK Biobank participants, we identified 59 biomarkers robustly and independently associated with the frailty index (FI). Of these, 34 associations were replicated in the Swedish TwinGene study (n = 11,025) and the Finnish Health 2000 Survey (n = 6073). Using two-sample Mendelian randomization, we showed that the genetically predicted level of glycoprotein acetyls, an inflammatory marker, was statistically significantly associated with an increased FI (β per SD increase = 0.37%, 95% confidence interval: 0.12–0.61). Creatinine and several lipoprotein lipids were also associated with increased FI, yet their effects were mostly driven by kidney and cardiometabolic diseases, respectively. Our findings provide new insights into the causal effects of metabolites on frailty and highlight the role of chronic inflammation underlying frailty development.     

Common Genetic Variants in Fatty Acid–Binding Protein‐4 (FABP4) and Clinical Diabetes Risk in the Women's Health Initiative Observational Study

Adipocypte fatty acid–binding protein‐4 (FABP4/adipocyte P2) may play a central role in energy metabolism and inflammation. In animal models, defects of the aP2 gene (aP2^?/?) partially protected against the development of obesity‐related insulin resistance, dyslipidemia, and atherosclerosis. However, it is unclear whether common genetic variation in FABP4 gene contributes to risk of type 2 diabetes (T2D) or diabetes‐related metabolic traits in humans. We comprehensively assess the genetic associations of variants in the FABP4 gene with T2D risk and diabetes‐associated biomarkers in a prospective study of 1,529 cases and 2,147 controls among postmenopausal women aged 50–79 years who enrolled in the Women's Health Initiative Observational Study (WHI‐OS). We selected and genotyped a total of 11 haplotype‐tagging single‐nucleotide polymorphisms (tSNPs) spanning 41.3 kb across FABP4 in all samples. None of the SNPs and their derived haplotypes showed significant association with T2D risk. There were no significant associations between SNPs and plasma levels of inflammatory and endothelial biomarkers, including C‐reactive protein, tumor necrosis factor (TNF), interleukin‐6 (IL‐6), E‐selectin, and intercellular adhesion molecule (ICAM‐1). Among African‐American women, several SNPs were significantly associated with lower levels of vascular cell adhesion molecule‐1 (VCAM‐1), especially among those with incident T2D. On average, plasma levels of VCAM‐1 were significantly lower among carriers of each minor allele at rs1486004(C/T; ?1.08 ng/ml, P = 0.01), rs7017115(A/G; ?1.07 ng/ml, P = 0.02), and rs2290201(C/T; ?1.12 ng/ml, P = 0.002) as compared with the homozygotes of the common allele, respectively. After adjusting for multiple testing, carriers of the rs2290201 minor allele remained significantly associated with decreasing levels of plasma VCAM‐1 in these women (P = 0.02). In conclusion, our finding from a multiethnic cohort of postmenopausal women did not support the notion that common genetic variants in the FABP4 gene may trigger increased risk of T2D. The observed significant association between reduced VCAM‐1 levels and FABP4 genotypes in African‐American women warrant further confirmation.     

Male–female associations and female olfactory neurogenesis with pair bonding in Mus spicilegus

Mound‐building mice Mus spicilegus exhibit life‐history traits that are unique among the Mus species complex, such as the cooperative mound‐building behaviour that gives the species its common name. In this and other socially coordinated activities, such as those associated with reproduction, these mice should be able to recognize individuals (via discrimination based on kinship, population and species) to mediate their interactions. Our previous studies have provided evidence of population and species recognition in M. spicilegus. The aims of the present study were: (i) to study associations of mice during their reproductive period (in outdoor enclosures), (ii) to investigate whether there is an influence of relatedness of females in these associations, (iii) to determine whether female M. spicilegus are able to make kin vs. non‐kin discriminations, and (iv) to study certain neurobiological correlates of male–female bonds. Stable male–female associations were found in almost all the experimental groups, both those with unrelated and unfamiliar females and those with unfamiliar sisters. Kinship between females did not affect female associations in our enclosure experiment, but in our kin discrimination experiment females did distinguish between unfamiliar sisters and unfamiliar unrelated females. Shared kinship may not encourage cooperative rearing of pups but could enhance cooperation in building mounds where mice over‐winter. Male–female associations could be based on a social bond, as hypothesized from previous laboratory experiments. This was substantiated in this study by increased olfactory bulbar neurogenesis in females that preferred (in two choice tests) their sexual partner 3 weeks after their first mating. Based on these results there is clear evidence to suggest that the mating system of M. spicilegus is social monogamy. © 2005 The Linnean Society of London, Biological Journal of the Linnean Society, 2005, 84 , 323–334.     

Genetic variants in telomere‐maintenance genes are associated with ovarian cancer risk and outcome

Most ovarian cancer patients present at an advanced stage with poor prognosis. Telomeres play a critical role in protecting chromosomes stability. The associations of genetic variants in telomere maintenance genes and ovarian cancer risk and outcome are unclear. We genotyped 137 single nucleotide polymorphisms (SNPs) in telomere‐maintenance genes in 417 ovarian cancer cases and 417 matched healthy controls to evaluate their associations with cancer risk, survival and therapeutic response. False discovery rate Q‐value was calculated to account for multiple testing. Eleven SNPs from two genes showed nominally significant associations with the risks of ovarian cancer. The most significant SNP was TEP1: rs2228026 with participants carrying at least one variant allele exhibiting a 3.28‐fold (95% CI: 1.72‐6.29; P < 0.001, Q = 0.028) increased ovarian cancer risk, which remained significant after multiple testing adjusting. There was also suggested evidence for the associations of SNPs with outcome, although none of the associations had a Q < 0.05. Seven SNPs from two genes showed associations with ovarian cancer survival (P < 0.05). The strongest association was found in TNKS gene (rs10093972, hazard ratio = 1.88; 95% CI: 1.20‐2.92; P = 0.006, Q = 0.076). Five SNPs from four genes showed suggestive associations with therapeutic response (P < 0.05). In a survival tree analysis, TEP1:rs10143407 was the primary factor contributing to overall survival. Unfavourable genotype analysis showed a cumulative effect of significant SNPs on ovarian cancer risk, survival and therapeutic response. Genetic variations in telomere‐maintenance genes may be associated with ovarian cancer risk and outcome.     

Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function

Chronic inflammation in older individuals is thought to contribute to inflammatory, age‐related diseases. Human monocytes are comprised of three subsets (classical, intermediate and nonclassical subsets), and despite being critical regulators of inflammation, the effect of age on the functionality of monocyte subsets remains to be fully defined. In a cross‐sectional study involving 91 healthy male (aged 20–84 years, median 52.4) and 55 female (aged 20–82 years, median 48.3) individuals, we found age was associated with an increased proportion of intermediate and nonclassical monocytes (P = 0.002 and 0.04, respectively) and altered phenotype of specific monocyte subsets (e.g. increased expression of CD11b and decreased expression of CD38, CD62L and CD115). Plasma levels of the innate immune activation markers CXCL10, neopterin (P < 0.001 for both) and sCD163 (P = 0.003) were significantly increased with age. Whilst similar age‐related changes were observed in both sexes, monocytes from women were phenotypically different to men [e.g. lower proportion of nonclassical monocytes (P = 0.002) and higher CD115 and CD62L but lower CD38 expression] and women exhibited higher levels of CXCL10 (P = 0.012) and sCD163 (P < 0.001) but lower sCD14 levels (P < 0.001). Monocytes from older individuals exhibit impaired phagocytosis (P < 0.05) but contain shortened telomeres (P < 0.001) and significantly higher intracellular levels of TNF both at baseline and following TLR4 stimulation (P < 0.05 for both), suggesting a dysregulation of monocyte function in the aged. These data show that aging is associated with chronic innate immune activation and significant changes in monocyte function, which may have implications for the development of age‐related diseases.     

Differences in DNA methylation by extent of breast cancer family history in unaffected women

Breast cancer clusters within families but genetic factors identified to date explain only a portion of this clustering. Lower global DNA methylation in white blood cells (WBC) has been associated with increased breast cancer risk. We examined whether WBC DNA methylation varies by extent of breast cancer family history in unaffected women from high-risk breast cancer families. We evaluated DNA methylation levels in LINE-1, Alu and Sat2 in 333 cancer-free female family members of the New York site of the Breast Cancer Family Registry, the minority of which were known BRCA1 or BRCA2 mutation carriers. We used generalized estimated equation models to test for differences in DNA methylation levels by extent of their breast cancer family history after adjusting for age. All unaffected women had at least one sister affected with breast cancer. LINE-1 and Sat2 DNA methylation levels were lower in individuals with 3 or more (3+) first-degree relatives with breast cancer relative to women with only one first-degree relative. For LINE-1, Alu, and Sat2, having 3+ affected first-degree relatives was associated with a decrease of 23.4% (95%CI = ?46.8%, 0.1%), 17.9% (95%CI = ?39.5%, 3.7%) and 11.4% (95% CI = ?20.3%, ?2.5%), respectively, relative to individuals with only one affected first-degree relative, but the results were only statistically significant for Sat2. Individuals having an affected mother had 17.9% lower LINE-1 DNA methylation levels (95% CI = ?28.8%, ?7.1%) when compared with those not having an affected mother. No associations were observed for Alu or Sat2 by maternal breast cancer status. If replicated, these results indicate that lower global WBC DNA methylation levels in families with extensive cancer histories may be one explanation for the clustering of cancers in these families. Family clustering of disease may reflect epigenetic as well as genetic and shared environmental factors.     

Overweight is associated with decreased cognitive functioning among school-age children and adolescents

Objective: Childhood overweight and obesity have increased substantially in the past two decades, raising concerns about their psychosocial and cognitive consequences. We examined the associations between academic performance (AP), cognitive functioning (CF), and increased BMI in a nationally representative sample of children. Methods and Procedures: Participants were 2,519 children aged 8–16 years, who completed a brief neuropsychological battery and measures of height and weight as a part of the Third National Health and Nutrition Examination Survey, a cross‐sectional survey conducted between 1988 and 1994. Z‐scores were calculated for each neuropsychological test, and poor performance was defined as z‐score <2. Results: The association between BMI and AP was not significant after adjusting for parental/familial characteristics. However, the associations between CF remained significant after adjusting for parental/familial characteristic, sports participation, physical activity, hours spent watching TV, psychosocial development, blood pressure, and serum lipid profile. Z‐scores on block design (a measure of visuospatial organization and general mental ability) among overweight children and children at risk of overweight were below those of normal‐weight children by 0.22 (s.e. = 0.16) and 0.10 (s.e. = 0.10) unit, respectively (P for trend <0.05). The odds of poor performance on block design were 1.97 (95% confidence interval: 1.01–3.83) and 2.80 (1.16–6.75), respectively, among children at risk or overweight compared to normal‐weight peers. Discussion: Increased body weight is independently associated with decreased visuospatial organization and general mental ability among children. Future research is needed to determine the nature, persistence, and functional significance of this association.     

Effect of Shiftwork on Systemic Markers of Inflammation

Shiftwork is associated with an increased risk of cardiovascular diseases, but the possible role of inflammation in this relationship is not well known. We tested the hypothesis that shiftwork would be associated with higher levels of C-reactive protein (CRP) and increased leukocyte count. We analyzed the cross-sectional associations between work arrangements and low-grade inflammation in 1877 airline-company employees separately for men (n?=?1037) and women (n?=?840). The participants were classified into five categories according to their work schedule: day workers who have not worked in shifts (referent group), former shiftworkers, 2-shift workers, 3-shift workers, and in-flight workers. In models adjusted for age and recent infectious diseases, CRP levels were higher among male 3-shift workers (p = .002) and marginally higher in male 2-shift workers (p = .076). In addition, leukocyte count was higher in 2-shift (p = .005) and 3-shift (p = .021) working men. In women, CRP level was higher in 2-shift workers (p = .028), whereas leukocyte count was lower in flight workers (p = .005). Any separate adjustment additionally for smoking, education, alcohol consumption, physical activity, and obesity did not substantially affect the results of 2- and 3-shift work. In the fully adjusted model, only the association between 3-shift work and CRP in men (p = .021) and 2-shift work and leukocyte count in men (p = .020) and leukocyte count in 3-shift-working women (p = .044) were significant. Our results suggest that 2- and 3-shift work is associated with increased systemic inflammation and the relationship is relatively independent of the considered risk factors of cardiovascular disease. (Author correspondence: Sampsa.Puttonen@ttl.fi)     

Matrix metalloproteinase-9 and plasminogen activator inhibitor-1 are associated with right ventricular structure and function: The MESA-RV Study

Elevated resistance and reduced compliance of the pulmonary vasculature increase right ventricular (RV) afterload. Local and systemic inflammation and haemostatic abnormalities are prominent in pulmonary vascular diseases. We hypothesized that plasma biomarker levels indicating greater inflammation and coagulability associated with pulmonary vascular disease would be associated with RV structure and function measured by cardiac magnetic resonance imaging (MRI). The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac MRI among participants aged 45–84 years without clinical cardiovascular disease. We assessed the associations of RV mass, RV end-diastolic volume (RVEDV), RV stroke volume (RVSV) and RV ejection fraction (RVEF) with plasma measures of inflammation (matrix metalloproteinase (MMP)-3 and -9, intercellular adhesion molecule (ICAM)-1, tumour necrosis factor receptor (TNF-R1), and E-selectin) and thrombosis (plasminogen activator inhibitor (PAI)-1, tissue factor, tissue factor pathway inhibitor and CD40 ligand).The study sample included 731 subjects. Higher MMP-9 levels were associated with lower RV mass before and after adjustment for left ventricular (LV) mass (p?=?0.008 and p?=?0.044, respectively). Higher levels of MMP-9 and PAI-1 were also associated with smaller RVEDV (p<0.05). Higher PAI-1 levels were associated with lower RVEF even after adjustment for LV ejection fraction (p?=?0.017). In conclusion, MMP-9 and PAI-1 are associated with changes in RV structure and function which could be potentially related to a subclinical increase in pulmonary vascular resistance.     

A Network Based Method for Analysis of lncRNA-Disease Associations and Prediction of lncRNAs Implicated in Diseases

Increasing evidence has indicated that long non-coding RNAs (lncRNAs) are implicated in and associated with many complex human diseases. Despite of the accumulation of lncRNA-disease associations, only a few studies had studied the roles of these associations in pathogenesis. In this paper, we investigated lncRNA-disease associations from a network view to understand the contribution of these lncRNAs to complex diseases. Specifically, we studied both the properties of the diseases in which the lncRNAs were implicated, and that of the lncRNAs associated with complex diseases. Regarding the fact that protein coding genes and lncRNAs are involved in human diseases, we constructed a coding-non-coding gene-disease bipartite network based on known associations between diseases and disease-causing genes. We then applied a propagation algorithm to uncover the hidden lncRNA-disease associations in this network. The algorithm was evaluated by leave-one-out cross validation on 103 diseases in which at least two genes were known to be involved, and achieved an AUC of 0.7881. Our algorithm successfully predicted 768 potential lncRNA-disease associations between 66 lncRNAs and 193 diseases. Furthermore, our results for Alzheimer''s disease, pancreatic cancer, and gastric cancer were verified by other independent studies.     

Dominance rank predicts social network position across developmental stages in rhesus monkeys

Social network analysis is increasingly common in studying complex interactions among individuals. Across a range of primates, high-ranking adults are generally more socially connected, which results in better fitness outcomes. However, it still remains unclear whether this relationship between social network position and dominance rank emerges in infancy and whether, in species with a social transmission of dominance rank, social network positions are driven by the presence of the mother. To fill this gap, we first explored whether dominance ranks were related to social network position, measured via eigenvector centrality, in infants, juveniles, and adults in a troop of semi-free-ranging rhesus macaques (Macaca mulatta). We then examined relationships between dominance rank and eigenvector centrality in a peer-only group of yearlings who were reared with their mothers in either a rich, socially complex environment of multigenerational (MG) kin support or a unigenerational group of mothers and their infants from birth through 8 months. In Experiment 1, we found that mother's network position predicted offspring network position and that dominants across all age categories were more central in affiliative networks (social contact, social grooming, and social play). Experiment 2 showed that high-ranking yearlings in a peer-only group were more central only in the social contact network. Moreover, yearlings reared in a socially complex environment of MG kin support were more central. Our findings suggest that the relationship between dominance rank and social network position begins early in life, and that complex early social environments can promote later social competency. Our data add to the growing body of evidence that the presence/absence of the mother and kin influence how dominance rank affects social network position. These findings have important implications for the role of caregivers in the social status of developing primates, which ultimately ties to health and fitness outcomes.     

Clinicopathological and prognostic value of lncRNA PANDAR expression in solid tumors: Evidence from a systematic review and meta-analysis

PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) has been shown to be aberrantly expressed in many types of cancer. Considering conflicting data, the current study was aimed to assess its potential role as a prognostic marker in malignant tumors. A comprehensive literature search of PubMed, Medline, and Web of Science was performed to identify all eligible studies describing the use of PANDAR as a prognostic factor for different types of cancer. Data related to overall survival (OS) and clinicopathologic features were collected and analyzed. The pooled hazard ratio (HR) and odds radio (OR) with a 95% confidence interval (CI) were used to estimate associations. Ten original studies containing 1,231 patients were included. The results showed that in patients with cancer, high PANDAR expression is correlated with lymph node metastasis (LNM; OR = 2.57; 95% CI, 1.76–3.81; p < 0.001), tumor stage (OR = 2.90; 95% CI, 1.25–6.75; p = 0.013), and tumor size (OR = 1.79; 95% CI, 1.11–2.91; p = 0.018). However, sensitivity analysis further demonstrated a significant association between high PANDAR expression and OS, both in multivariate and univariate analysis models (pooled HR 2.01; 95% CI, 1.17–3.44 and pooled HR 2.62; 95% CI, 1.98–3.47, respectively), after omitting one study. These results suggested that PANDAR expression might be indicative of advanced disease and poor prognosis in patients with cancer. Further studies are necessary to determine the value of this risk stratification biomarker in clinical management of patients with cancer.