Search

Abstract Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40–80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was − 0.91 standard-deviations lower in women than men (95%CI − 0.98; − 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p

ObjectiveWe suggested cervical cancer screening strategies for women living with HIV (WLHIV) by comparing their precancer risks to general population women, and then compared our suggestions with current Centers for Disease Control and Prevention (CDC) guidelines.DesignWe compared risks of biopsy-confirmed cervical high-grade squamous intraepithelial neoplasia or worse (bHSIL+), calculated among WLHIV in the Women's Interagency HIV Study, to 'risk benchmarks' for specific management strategies in the general population.MethodsWe applied parametric survival models among 2423 WLHIV with negative or atypical squamous cell of undetermined significance (ASC-US) cytology during 2000-2015. Separately, we synthesized published general population bHSIL+ risks to generate 3-year risk benchmarks for a 3-year return (after negative cytology, i.e. 'rescreening threshold'), a 6-12-month return (after ASC-US), and immediate colposcopy [after low-grade squamous intraepithelial lesion (LSIL)].ResultsAverage 3-year bHSIL+ risks among general population women ('risk benchmarks') were 0.69% for a 3-year return (after negative cytology), 8.8% for a 6-12-month return (after ASC-US), and 14.4% for colposcopy (after LSIL). Most CDC guidelines for WLHIV were supported by comparing risks in WLHIV to these benchmarks, including a 3-year return with CD4 greater than 500 cells/μl and after either three negative cytology tests or a negative cytology/oncogenic human papillomavirus cotest (all 3-year risks≤1.3%); a 1-year return after negative cytology with either positive oncogenic human papillomavirus cotest (1-year risk = 1.0%) or CD4 cell count less than 500 cells/μl (1-year risk = 1.1%); and a 6-12-month return after ASC-US (3-year risk = 8.2% if CD4 cell count at least 500 cells/μl; 10.4% if CD4 cell count = 350-499 cells/μl). Other suggestions differed modestly from current guidelines, including colposcopy (vs. 6-12 month return) for WLHIV with ASC-US and CD4 cell count less than 350 cells/μl (3-year risk = 16.4%) and a lengthened 2-year (vs. 1-year) interval after negative cytology with CD4 cell count at least 500 cells/μl (2-year risk = 0.98%).ConclusionsCurrent cervical cancer screening guidelines for WLHIV are largely appropriate. CD4 cell count may inform risk-tailored strategies.

PurposePersistent oral human papillomavirus (HPV) infection increases risk for oropharyngeal carcinoma, and people living with HIV have higher rates of oral HPV infection and related cancers. Some prescription medications have immunomodulatory effects, but the impact of medication use on oral HPV natural history is unknown.MethodsScope® oral rinse-and-gargle samples were collected semi-annually from 1,666 participants and tested for 37 types of oral HPV DNA using PCR; 594 HPV-infected participants with 1,358 type-specific oral HPV infections were identified. Data were collected on recent (past 6 months) use of medications. The relationship between medication use and oral HPV clearance was evaluated using Wei-Lin-Weissfeld regression, adjusting for biologic sex, prevalent versus incident infection, age, HIV status and CD4+ T cell count.ResultsOut of 11 medications examined, oral HPV clearance was significantly reduced in participants reporting recent use of antipsychotics (HR 0.75, 95% CI 0.57-0.99), anxiolytics/sedatives (HR 0.78, 95% CI 0.63-0.96) and antidepressants (HR 0.82, 95% CI 0.67-0.999). Among antipsychotics users, effect modification by HIV status was observed, with reduced clearance in HIV-infected (HR 0.67, 95% CI 0.49-0.91), but not HIV-uninfected participants (p-interaction = 0.009). After adjusted analysis, antipsychotic use remained significantly associated with reduced oral HPV clearance overall (aHR 0.75, 95% CI 0.57-0.99), and when restricted to only HIV-infected participants (aHR 0.66, 95% CI 0.48-0.90). After adjustment, anxiolytic/sedative use and antidepressant use were no longer significantly associated with reduced oral HPV clearance.ConclusionsSome medications were associated with decreased oral HPV clearance, most notably antipsychotic medications. These medications are prescribed for conditions that may have immunomodulating effects, so characteristics of underlying illness may have partially contributed to reduced oral HPV clearance.

Understanding adolescent climate change concern (CCC) may be a key strategy for building a citizenry that supports climate change action, as adolescents are likely less influenced by ideological polarization than adults. Prior research shows that climate education may build concern among adolescents, but other factors such as peer pressure may also be important. We investigated the relationships between CCC, acceptance of anthropogenic global warming (AGW), perceived level of acceptance among friends and family, and frequency of discussion of the issue among 426 middle school students in North Carolina, USA, and developed a novel instrument to measure each of these constructs. Acceptance of AGW had the strongest association with CCC. Frequency of discussion with friends and family was the second strongest predictor. Perceived level of acceptance among family and friends was the third strongest predictor. Model selection results suggest family had more influence than friends in this study. Girls perceived climate change as a higher risk than boys. In addition to building acceptance of AGW, leveraging discussions with peers and especially family may help build concern for climate change among future generations.

Abstract Significantly increased risks of cardiovascular disease occur in testicular cancer survivors given cisplatin-based chemotherapy. The postulated mechanism of platinum-based chemotherapy’s vascular toxicity has been thought secondary to its different early- and late- effects on vascular injury, endothelial dysfunction, and induction of a hypercoagulable state. We highlight for the first time the similarities between platinum-associated vascular adverse events and the vascular toxicity associated with other xenobiotic-metal contaminants. The vascular toxicity seen in large epidemiologic studies of testicular cancer survivors may in part be similar and mechanistically linked to the risk seen in environmental heavy metal contaminants linked to cardiovascular disease. Future research should be directed to better understand the magnitude of the adverse cardiovascular effects of platinum and to elucidate the underlying mechanisms of action.

Metabolomics has been used extensively to capture the exposome. We investigated whether prospectively measured metabolites provided predictive power beyond well-established risk factors among 758 women with adjudicated cancers [n = 577 breast (BC) and n = 181 colorectal (CRC)] and n = 758 controls with available specimens (collected mean 7.2 years prior to diagnosis) in the Women's Health Initiative Bone Mineral Density subcohort. Fasting samples were analyzed by LC-MS/MS and lipidomics in serum, plus GC-MS and NMR in 24 h urine. For feature selection, we applied LASSO regression and Super Learner algorithms. Prediction models were subsequently derived using logistic regression and Super Learner procedures, with performance assessed using cross-validation (CV). For BC, metabolites did not increase predictive performance over established risk factors (CV-AUCs~0.57). For CRC, prediction increased with the addition of metabolites (median CV-AUC across platforms increased from ~0.54 to ~0.60). Metabolites related to energy metabolism: adenosine, 2-hydroxyglutarate, N-acetyl-glycine, taurine, threonine, LPC (FA20:3), acetate, and glycerate; protein metabolism: histidine, leucic acid, isoleucine, N-acetyl-glutamate, allantoin, N-acetyl-neuraminate, hydroxyproline, and uracil; and dietary/microbial metabolites: myo-inositol, trimethylamine-N-oxide, and 7-methylguanine, consistently contributed to CRC prediction. Energy metabolism may play a key role in the development of CRC and may be evident prior to disease development. [ABSTRACT FROM AUTHOR]

This article discusses a case of a newborn male with a vascular mass on the posterior neck, which was identified on a prenatal ultrasound and confirmed to be a congenital hemangioma (CH). The patient experienced transient thrombocytopenia, which was resolved with treatment. The article provides information on the diagnosis and characteristics of CH, as well as other types of vascular anomalies that can occur in newborns. It emphasizes the importance of early diagnosis and intervention for larger and more invasive anomalies like arteriovenous malformations (AVMs) to prevent complications. The information is sourced from a book and medical journal articles. [Extracted from the article]

We develop a fast and accurate approach to approximate posterior distributions in the Bayesian empirical likelihood framework. Bayesian empirical likelihood allows for the use of Bayesian shrinkage without specification of a full likelihood but is notorious for leading to several computational difficulties. By coupling the stochastic variational Bayes procedure with an adjusted empirical likelihood framework, the proposed method overcomes the intractability of both the exact posterior and the arising evidence lower bound objective, and the mismatch between the exact posterior support and the variational posterior support. The optimization algorithm achieves fast algorithmic convergence by using the variational expected gradient of the log adjusted empirical likelihood function. We prove the consistency of the proposed approximate posterior distribution and an empirical likelihood analogue of the variational Bernstein-von-Mises theorem. Through several numerical examples, we confirm the accuracy and quick algorithmic convergence of our proposed method. for this article are available online. [ABSTRACT FROM AUTHOR]

Simple Summary: Improvements in lung cancer risk assessment to inform on the need for screening may be achieved through the use of biomarkers. Here, we report the findings of a validation study of a panel of four circulating protein biomarkers for the risk prediction of lung cancer in a cohort of pre-diagnostic plasmas obtained from the Physician's Health Study (PHS). We demonstrate that the protein panel can identify individuals at high risk of lung cancer up to two years prior to clinical diagnosis. This study aimed to assess a four-marker protein panel (4MP)'s performance, including the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19, for predicting lung cancer in a cohort enriched with never- and ever-smokers. Blinded pre-diagnostic plasma samples collected within 2 years prior to a lung cancer diagnosis from 25 cases and 100 sex-, age-, and smoking-matched controls were obtained from the Physicians' Health Study (PHS). The 4MP yielded AUC performance estimates of 0.76 (95% CI: 0.61–0.92) and 0.69 (95% CI: 0.56–0.82) for predicting lung cancer within one year and within two years of diagnosis, respectively. When stratifying into ever-smokers and never-smokers, the 4MP had respective AUCs of 0.77 (95% CI: 0.63–0.92) and 0.72 (95% CI: 0.17–1.00) for a 1-year risk of lung cancer. The AUCs of the 4MP for predicting metastatic lung cancer within one year and two years of the blood draw were 0.95 (95% CI: 0.87–1.00) and 0.78 (95% CI: 0.62–0.94), respectively. Our findings indicate that a blood-based biomarker panel may be useful in identifying ever- and never-smokers at high risk of a diagnosis of lung cancer within one-to-two years. [ABSTRACT FROM AUTHOR]

The evolution of behavioral isolation is often the first step toward speciation. While past studies show that behavioral isolation will sometimes evolve as a by-product of divergent ecological selection, we lack a more nuanced understanding of factors that may promote or hamper its evolution. The environment in which mating occurs may be important in mediating whether behavioral isolation evolves for two reasons. Ecological speciation could occur as a direct outcome of different sexual interactions being favored in different mating environments. Alternatively, mating environments may vary in the constraint they impose on traits underlying mating interactions, such that populations evolving in a "constraining" mating environment would be less likely to evolve behavioral isolation than populations evolving in a less constraining mating environment. In the latter, mating environment is not the direct cause of behavioral isolation but rather permits its evolution only if other drivers are present. We test these ideas with a set of 28 experimental fly populations, each of which evolved under one of two mating environments and one of two larval environments. Counter to the prediction of ecological speciation by mating environment, behavioral isolation was not maximal between populations evolved in different mating environments. Nonetheless, mating environment was an important factor as behavioral isolation evolved among populations from one mating environment but not among populations from the other. Though one mating environment was conducive to the evolution of behavioral isolation, it was not sufficient: assortative mating only evolved between populations adapting to different-larval environments within that mating environment, indicating a role for ecological speciation. Intriguingly, the mating environment that promoted behavioral isolation is characterized by less sexual conflict compared to the other mating environment. Our results suggest that mating environments play a key role in mediating ecological speciation via other axes of divergent selection. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) includes a group of disorders of the heart and blood vessels that includes numerous problems, many of which are related to the process called atherosclerosis. The present work is aimed to analyze the most relevant studies examining the potentially beneficial effects of tomato products on both CVD prevention and antiplatelet aggregation as well as an European Food Safety Authority health claims evaluation on tomato and tomato products. To date, only one health claim has been approved for a concentrated extract of tomato soluble in water (WSTC) marketed under the patented name of Fruitflow® with two forms of presentation: WSTC I and II, with the following claim “helping to maintain normal platelet aggregation, which contributes to healthy blood flow.” Other studies also demonstrate similar beneficial effects for fresh tomatoes, tomato products and tomato pomace extracts.