Osajin and Pomiferin, Two Isoflavones Purified from Osage Orange Fruits, Tested for Repellency to the Maize Weevil (Coleoptera: Curculionidae)

The fruit of the osage orange tree, Maclura pomifera (Raf.) Schneid (Moraceae), has long been thought to be repellent to insects. A preliminary study reported here confirmed repellency of fruit extracts to the maize weevil, Sitophilus zeamais Motschulsky. Two isoflavones, osajin and pomiferin, were isolated from the mature fruit of M. pomifera in high purity (≥95%). Testing of purified osajin and pomiferin failed to show repellency. Repellency is likely caused by factors other than isoflavones in the fruit

A Practical Guide of the Southwest Oncology Group to Measure Malignant Pleural Mesothelioma Tumors by RECIST and Modified RECIST Criteria

Abstract:Malignant pleural mesothelioma (MPM) is difficult to measure radiographically due to the nonradial and variable pattern of growth and response to therapy. Inaccurate and inconsistent tumor measurements often compromise results from clinical trials that are dependent on identifying response rate and progression-free survival. In this article, we sought to provide a practical guide through the Southwest Oncology Group on how to measure MPM by the updated RECIST version 1.1 and by modified RECIST. We hope that these steps will provide a simple means by which computed tomography measurements can be consistently performed, minimizing intra- and interobserver variability. With this consistency, we may be able to better estimate the prognosis and response to therapy. With greater utilization, we will be able to better understand the biology of MPM

Two Boundaries Separate Borrelia burgdorferi Populations in North America

Understanding the spread of infectious diseases is crucial for implementing effective control measures. For this, it is important to obtain information on the contemporary population structure of a disease agent and to infer the evolutionary processes that may have shaped it. Here, we investigate on a continental scale the population structure of Borrelia burgdorferi, the causative agent of Lyme borreliosis (LB), a tick-borne disease, in North America. We test the hypothesis that the observed d population structure is congruent with recent population expansions and that these were preceded by bottlenecks mostly likely caused by the near extirpation in the 1900s of hosts required for sustaining tick populations. Multilocus sequence typing and complementary population analytical tools were used to evaluate B. burgdorferi samples collected in the Northeastern, Upper Midwestern, and Far-Western United States and Canada. The spatial distribution of sequence types (STs) and inferred population boundaries suggest that the current populations are geographically separated. One major population boundary separated western B. burgdorferi populations transmitted by Ixodes pacificus in California from Eastern populations transmitted by I. scapularis; the other divided Midwestern and Northeastern populations. However, populations from all three regions were genetically closely related. Together, our findings suggest that although the contemporary populations of North American B. burgdorferi now com- prise three geographically separated subpopulations with no or limited gene flow among them, they arose from a common ancestral population. A comparative analysis of the B. burgdorferi outer surface protein C (ospC) gene revealed novel linkages and provides additional insights into the genetic characteristics of strains

Encorafenib plus binimetinib in patients with BRAFV600-mutant non-small cell lung cancer: phase II PHAROS study design

BRAF V600 mutation; Binimetinib; EncorafenibMutació de BRAF V600; Binimetinib; EncorafenibMutación de BRAF V600; Binimetinib; EncorafenibBRAFV600 oncogenic driver mutations occur in 1–2% of non-small-cell lung cancers (NSCLCs) and have been shown to be a clinically relevant target. Preclinical/clinical evidence support the efficacy and safety of BRAF and MEK inhibitor combinations in patients with NSCLC with these mutations. We describe the design of PHAROS, an ongoing, open-label, single-arm, phase II trial evaluating the BRAF inhibitor encorafenib plus the MEK inhibitor binimetinib in patients with metastatic BRAFV600-mutant NSCLC, as first- or second-line treatment. The primary end point is objective response rate, based on independent radiologic review (per RECIST v1.1); secondary objectives evaluated additional efficacy end points and safety. Results from PHAROS will describe the antitumor activity/safety of encorafenib plus binimetinib in patients with metastatic BRAFV600-mutant NSCLC

Adolescent Psychological Assets and Cardiometabolic Health Maintenance in Adulthood: Implications for Health Equity

Background Positive cardiometabolic health (CMH) is defined as meeting recommended levels of multiple cardiometabolic risk factors in the absence of manifest disease. Prior work finds that few individuals—particularly members of minoritized racial and ethnic groups—meet these criteria. This study investigated whether psychological assets help adolescents sustain CMH in adulthood and explored interactions by race and ethnicity. Methods and Results Participants were 3478 individuals in the National Longitudinal Study of Adolescent Health (49% female; 67% White, 15% Black, 11% Latinx, 6% other [Native American, Asian, or not specified]). In Wave 1 (1994–1995; mean age=16 years), data on 5 psychological assets (optimism, happiness, self‐esteem, belongingness, and feeling loved) were used to create a composite asset index (range=0–5). In Waves 4 (2008; mean age=28 years) and 5 (2016–2018; mean age=38 years), CMH was defined using 7 clinically assessed biomarkers. Participants with healthy levels of ≥6 biomarkers at Waves 4 and 5 were classified as maintaining CMH over time. The prevalence of CMH maintenance was 12%. Having more psychological assets was associated with better health in adulthood (odds ratio [OR]linear trend, 1.12 [95% CI, 1.01–1.25]). Subgroup analyses found substantive associations only among Black participants (OR, 1.35 [95% CI, 1.00–1.82]). Additionally, there was some evidence that racial and ethnic disparities in CMH maintenance may be less pronounced among participants with more assets. Conclusions Youth with more psychological assets were more likely to experience favorable CMH patterns 2 decades later. The strongest associations were observed among Black individuals. Fostering psychological assets in adolescence may help prevent cardiovascular disease and play an underappreciated role in shaping health inequities

The Social Determinants of Ideal Cardiovascular Health: A Global Systematic Review

This systematic review synthesizes research published from January 2010-July 2022 on the social determinants of ideal cardiovascular health (CVH) carried out around the world and compares trends in high-income countries (HICs) to those in low- and middle-income countries (LMICs). 41 studies met inclusion criteria (n = 28 HICs, n = 13 LMICs). Most were from the United States (n = 22) and cross-sectional (n = 33), and nearly all evaluated associations among adults. Among studies conducted in LMICs, nearly all were from middle-income countries and only one was carried out in low-income country. Education (n = 24) and income/wealth (n = 17) were the most frequently examined social determinants in both HICs and LMICs. Although most studies assessed ideal CVH using reliable and valid methods (n = 24), only 7 used criteria pre-defined by the American Heart Association to characterize ideal levels of each CVH metric. Despite heterogeneity in how outcome measures were derived and analyzed, consistent associations were evident between multiple markers of higher social status (i.e. greater education, income/wealth, socioeconomic status, racial/ethnic majority status) and greater levels of ideal CVH across both country contexts. Gaps in the literature include evidence from LMICs and HICs other than the United States, longitudinal research, and investigations of a wider array of social determinants beyond education and income/wealth

Mechanisms of FUS1/TUSC2 deficiency in mesothelioma and its tumorigenic transcriptional effects

<p>Abstract</p> <p>Background</p> <p>FUS1/TUSC2 is a novel tumor suppressor located in the critical 3p21.3 chromosomal region frequently deleted in multiple cancers. We previously showed that Tusc2-deficient mice display a complex immuno-inflammatory phenotype with a predisposition to cancer. The goal of this study was to analyze possible involvement of TUSC2 in malignant pleural mesothelioma (MPM) - an aggressive inflammatory cancer associated with exposure to asbestos.</p> <p>Methods</p> <p>TUSC2 insufficiency in clinical specimens of MPM was assessed via RT-PCR (mRNA level), Representational Oligonucleotide Microarray Analysis (DNA level), and immunohistochemical evaluation (protein level). A possible link between TUSC2 expression and exposure to asbestos was studied using asbestos-treated mesothelial cells and ROS (reactive oxygen species) scavengers. Transcripional effects of TUSC2 in MPM were assessed through expression array analysis of TUSC2-transfected MPM cells.</p> <p>Results</p> <p>Expression of TUSC2 was downregulated in ~84% of MM specimens while loss of TUSC2-containing 3p21.3 region observed in ~36% of MPMs including stage 1 tumors. Exposure to asbestos led to a transcriptional suppression of TUSC2, which we found to be ROS-dependent. Expression array studies showed that TUSC2 activates transcription of multiple genes with tumor suppressor properties and down-regulates pro-tumorigenic genes, thus supporting its role as a tumor suppressor. In agreement with our knockout model, TUSC2 up-regulated IL-15 and also modulated more than 40 other genes (~20% of total TUSC2-affected genes) associated with immune system. Among these genes, we identified CD24 and CD274, key immunoreceptors that regulate immunogenic T and B cells and play important roles in systemic autoimmune diseases. Finally, clinical significance of TUSC2 transcriptional effects was validated on the expression array data produced previously on clinical specimens of MPM. In this analysis, 42 TUSC2 targets proved to be concordantly modulated in MM serving as disease discriminators.</p> <p>Conclusion</p> <p>Our data support immuno-therapeutic potential of TUSC2, define its targets, and underscore its importance as a transcriptional stimulator of anti-tumorigenic pathways.</p

Phase II Study of Cediranib in Patients with Malignant Pleural Mesothelioma: SWOG S0509

IntroductionMalignant pleural mesothelioma (MPM) tumors express vascular epithelial growth factor (VEGF) and VEGF receptors. We conducted a phase II study of the oral pan-VEGF receptor tyrosine kinase inhibitor, cediranib, in patients with MPM after platinum-based systemic chemotherapy.MethodsPatients with MPM previously treated with a platinum-containing chemotherapy regimen and a performance status 0 to 2 were eligible for enrollment. Cediranib 45 mg/d was administered until progression or unacceptable toxicity. The primary end point was response rate. Tumor measurements were made by RECIST criteria, with a subset analysis conducted using modified RECIST. A two-stage design with an early stopping rule based on response rate was used.ResultsFifty-four patients were enrolled. Of 47 evaluable patients, 4 patients (9%) had objective responses, 16 patients (34%) had stable disease, 20 patients (43%) had disease progression, 2 patients (4%) had symptomatic deterioration, and 1 patient (2%) had early death. The most common toxicities were fatigue (64%), diarrhea (64%), and hypertension (70%); 91% of patients required a dose reduction. Median overall survival was 9.5 months, 1-year survival was 36%, and median progression-free survival was 2.6 months.ConclusionCediranib monotherapy has modest single-agent activity in MPM after platinum-based therapy. However, some patient tumors were highly sensitive to cediranib. This study provides a rationale for further testing of cediranib plus chemotherapy in MPM and highlights the need to identify a predictive biomarker for cediranib