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Purpose: Functional capacity and cardiac function can decline during breast cancer (BC) therapy. In non-cancer populations, higher physical activity (PA) is associated with better physical function and cardiac health. This study compared baseline PA, functional capacity, and cardiac function between women with and without BC and tested if greater PA participation was related to higher functional capacity and/or better heart function after three months of BC therapy. Methods: Data was collected in 104 women without BC (82% Caucasian, baseline only) and 110 women with stage I-III BC (82% Caucasian) before therapy and after three months of treatment. Participants self-reported PA and underwent six-minute walk distance (6MWD) testing to measure functional capacity and cardiovascular magnetic resonance to assess left ventricular ejection fraction (LVEF). Analyses were adjusted for age, race, body mass index (BMI), and medication use. Results: The BC group was older (56.2 ± 10.7 vs 52.1 ± 14.7 yrs, P=0.02) with a higher average BMI than the non-cancer group (30.3 ± 6.8 vs 27.7 ± 6.2 kg/m2, P<0.01). Pre-treatment, BC participants reported lower PA scores (27.9 ± 2.8 vs 34.9 ± 2.8, P=0.04) with similar 6MWD and LVEF relative to those without cancer (485 ± 11 vs 496 ± 11 m, P=0.4 and 59.7 ± 0.7 vs 58.9 ± 0.8%, P=0.37, respectively). After three months of BC therapy, declines were observed for PA scores (27.9 ± 2.8 vs 18.3 ± 2.5, P=0.02), 6MWD (485 ± 11 vs 428 ± 10 m, P<0.001), and LVEF (59.7 ± 0.7 vs 56.1 ± 0.7%, P<0.001). Compared to BC participants who reported no PA at three months (n=24, 22%), BC women who reported any PA (n=78, 86%) had higher 6MWD (442 ± 11 vs 389 ± 17 m, P=0.006) but similar LVEF (56.5 ± 0.9 vs 55.3 ± 1.5%, p=0.5). Women who reported any PA were less likely to exhibit an LVEF below normal (<50%) or decline in LVEF of â•10 points compared to inactive women (BMI-adjusted, OR [95% CI]: 0.27 [0.09, 0.85]). Conclusions: These preliminary results indicate that self-reported PA, LVEF and 6MWD decline in the first three months of BC treatment, but PA participation during BC treatment may mitigate declines in functional capacity and cardiac function. Further research is needed to identify barriers and facilitators of PA participation during BC therapy. Funding: Data collection was funded by the Wake Forest NCORP Research Base grant 2UG1CA189824 with support of the NCI Community Oncology Research Program (NCORP). Additional funding for this study was provided by grants from the National Institutes of Health, National Cancer Institute (1R01CA199167 and 5T32CA093423). Clinical Trial ID: NCT02791581 for WF97415 UPBEAT. [ABSTRACT FROM AUTHOR]

Social subordination in female macaques represents a well-described model of chronic psychosocial stress. Additionally, a length polymorphism (5- HTTLPR) in the regulatory region of the serotonin (5- HT) transporter (5- HTT) gene ( SLC6A4) is present in rhesus macaques, which has been linked to adverse outcomes similar to that described in humans with an analogous 5- HTTLPR polymorphism. The present study determined the effects of social status and the 5- HTTLPR genotype on 5- HT1 A receptor binding potential (5- HT1 A BPND) in brain regions implicated in emotional regulation and stress reactivity in ovariectomised female monkeys, and then assessed how these effects were altered by 17β-oestradiol ( E2) treatment. Areas analysed included the prefrontal cortex [anterior cingulate ( ACC); medial prefrontal cortex (m PFC); dorsolateral prefrontal cortex; orbitofrontal prefrontal cortex], amygdala, hippocampus, hypothalamus and raphe nucleui. Positron emission tomography using p-[18 F] MPPF was performed to determine the levels of 5- HT1 A BPND under a non- E2 and a 3-week E2 treatment condition. The short variant (s-variant) 5- HTTLPR genotype produced a significant reduction in 5- HT1A BPND in the m PFC regardless of social status, and subordinate s-variant females showed a reduction in 5- HT1 A BPND within the ACC. Both these effects of 5- HTTLPR were unaffected by E2. Additionally, E2 reduced 5- HT1 A BPND in the dorsal raphe of all females irrespective of psychosocial stress or 5- HTTLPR genotype. Hippocampal 5- HT1 A BPND was attenuated in subordinate females regardless of 5- HTTLPR genotype during the non- E2 condition, an effect that was normalised with E2. Similarly, 5- HT1 A BPND in the hypothalamus was significantly lower in subordinate females regardless of 5- HTTLPR genotype, an effect reversed with E2. Taken together, the data indicate that the effect of E2 on modulation of central 5 HT1 A BPND may only occur in brain regions that show no 5- HTTLPR genotype-linked control of 5- HT1 A binding. [ABSTRACT FROM AUTHOR]

Examines the relationship between selected variables and successful performance in an accounting program at a large midwestern university. Previous research; Method; Data analysis; Results; Conclusion; More.

Highlights: [•] Social subordination alters GABAARs binding in estradiol-treated female monkeys. [•] Status effect on GABAAR is site specific, only seen in the prefrontal cortex. [•] CRH receptor antagonism reverses status differences in GABAAR binding. [•] Implicates the stress axis in the dysregulation of GABAAR in subordinate females. [•] Provides mechanism by which subordination alters the actions of estradiol. [ABSTRACT FROM AUTHOR]

The division of the insect embryo into repeated units - segments - is a fundamental feature of the body plan. The genes controlling this process in Drosophila melanogaster were identified in genetic screens and characterized in that species in numerous studies in the 1980s and 1990s. These genes form a well-established hierarchy and have been leveraged to examine gene regulation, transcriptional machinery, chromatin structure and more. Much of the genetic toolkit identified in Drosophila is highly conserved throughout the animal kingdom, spearheading the field of evolutionary developmental biology or Evo-Devo. Accordingly, a 'Drosophila-centric' approach has examined the evolutionary conservation of orthologs of Drosophila segmentation genes in closely and distantly related insects. Here, we report on progress in both Drosophila and emerging model insects in recent years (2022 - present), with much of the new research related to the pair-rule subset of segmentation genes. We highlight new findings on 'classic' Drosophila genes, revealing unexpected roles of genes and cis-regulatory elements in this species. We further report on the expanding knowledge about mechanisms regulating segmentation in emerging model insects that are distantly related to Drosophila, including those that pattern segments sequentially. We also describe technical advances in both Drosophila and non-model species that are currently progressing research in this field., Competing Interests: Declaration of Competing Interest The authors, Katie Reding and Leslie Pick, declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Morphological features of organismal body plans are often highly conserved within large taxa. For example, segmentation is a shared and defining feature of all insects. Screens in Drosophila identified genes responsible for the development of body segments, including the "pair-rule" genes (PRGs), which subdivide embryos into double-segment units in a previously unexpected pre-patterning step. Here we show that the milkweed bug Oncopeltus fasciatus also uses a pair rule for embryo subdivision but Oncopeltus employs different genes for this process. We identified the gene Blimp1 as an Oncopeltus PRG based on its expression pattern, tested its function with RNA interference and CRISPR-Cas9, and generated the first PR mutant in this species. Although it does not have PR function in Drosophila , like Drosophila PRGs, Blimp1 encodes a transcription factor required for embryonic viability. Thus, pair-rule subdivision of the insect body plan is more highly conserved than the factors mediating this process, suggesting a developmental constraint on this pre-patterning step.

Background: Relationships between lifestyle risk factors and cardiovascular disease (CVD) risk in women with breast cancer (BC) are underexplored., Objectives: To evaluate the incidence of CVD in relation to the Life's Essential 8 (LE8) score among women with BC., Methods: Data from the Women's Health Initiative were utilized. The primary exposure was the LE8 score assessed prior to BC diagnosis. The LE8 score was stratified into low (0-59), moderate (60-79), and high (80-100) cardiovascular health (CVH). The primary endpoint was a composite of incident CVD events, which included coronary heart disease, defined as myocardial infarction along with coronary revascularization, CVD death, and stroke. We calculated the cumulative incidence of CVD and estimated hazard ratios., Results: Among 7,165 participants, the median age was 70.1 years at BC diagnosis. The mean LE8 score was 62.0 ± 12.2. Over a median follow-up period of 6 years, 490 composite CVD events occurred. The risk of CVD events was highest for low CVH compared with moderate and high CVH. Compared with low CVH, the hazard ratio for incident CVD was 0.57 (95% CI: 0.46-0.69) for moderate CVH and 0.34 (95% CI: 0.20-0.59) for high CVH. LE8, in conjunction with age, provided a C-statistic of 0.74 for the composite risk of CVD., Conclusions: Higher LE8 scores were associated with a lower risk of incident CVD among women with BC in the United States., Competing Interests: The WHI program is funded by National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. This manuscript was partially funded by a grant from Alpha Phi. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background and Objective Postmenopausal women tend to experience significant changes in body composition, particularly abdominal adipose tissue (AAT) deposition patterns, which are hypothesized to be critical factors influencing future cardiometabolic disease risk. Physical activity has a demonstrable effect on body composition and overall health. However, there is little evidence for how different intensities and durations of physical activity over a sustained period of time influence AAT patterns and other measures of body composition in postmenopausal women. We emulated a target trial of physical activity interventions, including the 2018 Physical Activity Guidelines for Americans recommendations, on 3-year changes in AAT and body composition. Methods We analyzed observational data from 4,451 postmenopausal women aged 50-79 years in the Women's Health Initiative (WHI) to emulate a three-year target trial of adhering to increasing minutes of moderate (at least 15, 30, 75, 150, 300 minutes/week) and vigorous (at least 15, 30, 75, 150 minutes/week) physical activity aligned with the physical activity guidelines. All participants had repeated whole body Dual X-Ray Absorptiometry (DXA) scans with derived abdominal visceral (VAT) and subcutaneous adipose tissue (SAT). The measured differences in average levels of VAT, SAT, and other body composition measures determined at end of follow-up were estimated with the parametric-g formula. Results Over 3 years, interventions of increasing minutes of moderate activity would result in dose-dependent reductions in abdominal VAT, SAT, and overall body fat, and increases in lean soft tissue, with the greatest estimated benefit at the 2018 physical activity guideline recommendation of 150 mins/wk or more. Compared to no intervention, if all participants had adhered to at least 150 mins/wk of moderate physical activity, they would have 16.8 cm2 lower VAT (95% CI -23.1, -10.4), 26.8 cm2 lower SAT (95% CI -36.3, -17.3), 1.3% lower total body fat% (95% CI -1.8, -0.7), 1.2 % higher total lean soft tissue% (95% CI 0.7, 1.8), and 2.6 kg lower total bodyweight (95% CI -3.6, -1.5). We saw similar patterns in our vigorous-intensity activity interventions - if all participants adhered to at least 150 mins/wk, they would have experienced 6.7 cm2 lower VAT (95% CI -17.7, 4.3), 13.3 cm2 lower SAT (95% CI -28.8, 2.1), 1.0 % lower total body fat percent (95% CI -2.0, 0.0 ), % higher total lean soft tissue percent (95% CI) and a 0.9 kg lower total bodyweight (95% CI -2.7, 0.8). Conclusion This hypothetical emulated intervention indicated that postmenopausal women who adhere to physical activity guideline recommendations would experience beneficial changes in abdominal VAT, SAT, and overall body composition over 3 years. The study results underscore the imperative to explore further how physical activity may serve as a potential determinant of body composition., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Lower income is associated with high incident cardiovascular disease (CVD) and mortality. CVD is an important cause of morbidity and mortality in cancer survivors. However, there is limited research on the association between income, CVD, and mortality in this population., Methods: This study utilized nationally representative data from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional survey evaluating the health and nutritional status of the US population. Our study included NHANES participants aged ≥20 years from 2003-2014, who self-reported a history of cancer. We evaluated the association between income level, prevalence of CVD, and all-cause mortality. All-cause mortality data was obtained through public use mortality files. Income level was assessed by poverty-income ratio (PIR) that was calculated by dividing family (or individual) income by poverty guideline. We used multivariable-adjusted Cox proportional hazard models through a backward elimination method to evaluate associations between PIR, CVD, and all-cause mortality in cancer survivors., Results: This cohort included 2,464 cancer survivors with a mean age of 62 (42% male) years. Compared with individuals with a higher PIR tertiles, those in the lowest PIR tertile had a higher rate of pre-existing CVD and post-acquired CVD. In participants with post-acquired CVD, the lowest PIR tertile had over two-fold increased risk mortality (Hazard Ratio (HR) = 2.17; 95% CI: 1.27-3.71) when compared to the highest PIR tertile. Additionally, we found that PIR was as strong a predictor of mortality in cancer survivors as CVD. In patients with no CVD, the lowest PIR tertile continued to have almost a two-fold increased risk of mortality (HR = 1.72; 95% CI: 1.69-4.35) when compared to a reference of the highest PIR tertile., Conclusions: In this large national study of cancer survivors, low PIR is associated with a higher prevalence of CVD. Low PIR is also associated with an increased risk of mortality in cancer survivors, showing a comparable impact to that of pre-existing and post-acquired CVD. Urgent public health resources are needed to further study and improve screening and access to care in this high-risk population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yogeswaran et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: To understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the association between baseline body mass index (BMI), intra-abdominal adipose tissue (IAT) and subcutaneous adipose tissue (SAT) with baseline to 3-month left ventricular ejection fraction (LVEF) change among women receiving potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or sarcoma., Methods: Women underwent potentially cardiotoxic chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, for treatment of breast cancer, lymphoma, or sarcoma. We obtained magnetic resonance images (MRIs) of body composition and cardiac function prior to treatment, and then a repeat MRI for cardiac function assessment at three months into treatment. Analyses and assessment of abdominal adipose tissue volumes and LVEF outcomes were conducted by independent reviewers blinded to all patient identifiers. A general linear model was created to examine associations between adipose tissue depots, BMI, and 3-month LVEF change., Results: Women (n = 210) aged 56 ± 11 years with breast cancer, lymphoma, and sarcoma were enrolled (n = 195, 14, 1 respectively). Baseline BMI, IAT, and SAT fat were independently associated with 3-month LVEF declines (p = 0.001 to 0.025 for all). After adjusting for baseline cardiovascular disease risk factors, BMI, IAT, and SAT, BMI remained the only variable associated with 3-month LVEF decline (p = 0.047)., Conclusions: These results suggest that factors other than abdominal adipose tissue or traditional cardiovascular risk factors may contribute to 3-month declines in LVEF among women with elevated BMI receiving potentially cardiotoxic chemotherapy. Further investigation should be conducted on psychosocial stress, physical activity, sleep, or diet., Trial Registration: DETECTIV&#95;NCT01719562, WF99112, & WF97415-NCT02791581., (© 2024. The Author(s).)

Post-transplantation revaccination uptake of childhood vaccines in adult hematopoietic stem cell transplantation (HSCT) survivors is suboptimal, increasing the risk of infectious morbidity and mortality within this population. We systematically reviewed the literature for factors related to revaccination uptake, as well as the barriers and facilitators that affect successful revaccination. We conducted a scoping review searching PubMed, CINAHL, Embase, and Web of Science in March 2023. Two independent reviewers performed study selection using the complete dual review process. Data were extracted using a standard form. Factors were characterized as demographic, clinical, or social determinants of health that affected revaccination uptake. Barriers and facilitators were categorized using the constructs from the World Health Organization Behavioural and Social Drivers Framework. Our searches yielded 914 sources, from which 15 publications were selected (5 original research and 10 quality improvement initiatives). More than one-half of the reports listed factors associated with poorer uptake, predominately clinical factors, followed by social determinants of health, then demographic factors. Nearly all the reports described barriers to successful revaccination uptake, with most of these falling into the "practical issues" construct. Most of the reports described facilitators, nearly all related to health care system improvements associated with improved revaccination uptake. Although this review provides a good starting point for understanding impediments to successful revaccination after HSCT, this review reveals that we lack sufficient evidence to drive targeted interventions to improve uptake. More research is needed, focusing on survivors' voices to inform our knowledge of barriers and facilitators to complete revaccination after HSCT, exploring behavioral and social drivers within this population, and examining the care delivery models that may complicate vaccine delivery in this population., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. All rights reserved.)

While biomarkers have been proposed to identify individuals at risk for radiation-induced cardiovascular disease (RICVD), little is known about long-term associations with cardiac events. We examined associations of biomarkers of oxidative stress (myeloperoxidase, growth differentiation factor-15, 8-hydroxy-2'-deoxyguanosine [8-OH-dG], placental growth factor), cardiac injury (troponin I, cystatin-C), inflammation (interleukin-6, C-reactive protein), and myocardial fibrosis (transforming growth factor-ß) with long-term RICVD in breast cancer (BC) survivors. We conducted a nested case-control study within the Women's Health Initiative of postmenopausal women with incident BC stages I-III, who received radiation and had pre- and post-BC diagnosis serum samples. Cases (n = 55) were defined as developing incident, physician-adjudicated myocardial infarction, coronary heart disease death, other CVD death, heart failure, or stroke after BC. Cases were matched to three controls (n = 158). After adjustment, a higher 8-OH-dG ratio was significantly associated with an elevated long-term risk of RICVD, suggesting oxidative DNA damage may be a putative pathway for RICVD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Insects display a vast array of eye and body colors. Genes encoding products involved in biosynthesis and deposition of pigments are ideal genetic markers, contributing, for example, to the power of Drosophila genetics. Oncopeltus fasciatus is an emerging model for hemimetabolous insects, a member of the piercing-sucking feeding order Hemiptera, that includes pests and disease vectors. To identify candidate visible markers for O. fasciatus, we used parental and nymphal RNAi to identify genes that altered eye or body color while having no deleterious effects on viability. We selected Of-vermilion for CRISPR/Cas9 genome editing, generating three independent loss-of-function mutant lines. These studies mapped Of-vermilion to the X-chromosome, the first assignment of a gene to a chromosome in this species. Of-vermilion homozygotes have bright red, rather than black, eyes and are fully viable and fertile. We used these mutants to verify a role for Of-xdh1, ortholog of Drosophila rosy, in contributing to red pigmentation using RNAi. Rather than wild-type-like red bodies, bugs lacking both vermilion and xdh1 have bright yellow bodies, suggesting that ommochromes and pteridines contribute to O. fasciatus body color. Our studies generated the first gene-based visible marker for O. fasciatus and expanded the genetic toolkit for this model system., (© 2023. The Author(s).)

We investigated cross-sectional relationships between the Mediterranean diet and overall fatigue, energy, and weariness scores among 4,563 women aged 65+ from the Women's Health Initiative study. We also used the Isocaloric Substitution approach to explore whether the substitution of fish for red and processed meat, whole for non-whole grains, and whole fruit for fruit juice relate to RAND-36 measured overall fatigue and its subdomains. The alternate Mediterranean Diet (aMED) Index quintiles (Q1-Q5) and selected Mediterranean foods available on a Food Frequency Questionnaire were exposure measures. Results showed aMED Q5 was associated with 2.99 (95% CI: 0.88, 5.11), 4.01 (95% CI: 1.51, 6.53), and 2.47 (95% CI: 0.24, 4.70) point improvements in fatigue, energy, and weariness scores, respectively, compared with aMED Q1. Substituting fish for red and processed meat and whole for non-whole grains was associated with more favorable fatigue scores, whereas substituting whole fruit for juice was not.

Fatigue is a common age-related symptom among community-dwelling adults aged 65 years and older. Yet, a systematic approach has rarely been applied to review definitions, measures, related factors, and consequences of fatigue in this population. A scoping review was conducted in December 2020 to fill the gap, and 36 articles met the inclusion criteria. Definitions, albeit diverse, included at least one of the following attributes: an early indicator of disablement, subjective, a lack of energy, multidimensional, impaired daily activities, and temporal. A summary of fatigue measures used in this population was provided, including a brief overview, number of items, reliability, and validity. In general, different measures were used with considerable variability in the content. Additionally, most measures had limited information on test-retest reliability and validity. Fatigue-related factors mapped into biological, psychological, social, and behavioral factors. Fatigue consequences were primarily declines in physical and cognitive functions. (100-150 words)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: In the Women's Health Initiative (WHI) dietary modification (DM) randomised trial, the low-fat dietary intervention reduced deaths from breast cancer (P = 0.02). Extending these findings, secondary analysis examined dietary intervention influence on breast cancer mortality by metabolic syndrome (MS) components., Methods: In total, 48,835 postmenopausal women with no prior breast cancer were randomised to a low-fat dietary intervention or comparison groups. Four MS components were determined at entry in 45,833 participants: (1) high waist circumference, (2) high blood pressure, (3) high cholesterol and (4) diabetes history. Forest plots of hazard ratios (HRs) were generated with P-values for interaction between randomisation groups and MS component score. Primary outcome was death from breast cancer by metabolic syndrome score., Results: HRs and 95% confidence intervals (CI) for dietary intervention influence on death from breast cancer were with no MS components (n = 10,639), HR 1.09, 95% CI 0.63-1.87; with 1-2 MS components (n = 30,948), HR 0.80, 95% CI 0.62-1.02; with 3-4 MS components (n = 4,246), HR 0.31, 95% CI 0.14-0.69 (interaction P = 0.01)., Conclusions: While postmenopausal women with 3-4 MS components were at higher risk of death from breast cancer, those randomised to a low-fat dietary intervention more likely had reduction in this risk., Registry: ClinicalTrials.gov (NCT00000611)., (© 2021. The Author(s), under exclusive licence to Cancer Research UK.)

Despite the strong link between childhood maltreatment and psychopathology, the underlying neurodevelopmental mechanisms are poorly understood and difficult to disentangle from heritable and prenatal factors. This study used a translational macaque model of infant maltreatment in which the adverse experience occurs in the first months of life, during intense maturation of amygdala circuits important for stress and emotional regulation. Thus, we examined the developmental impact of maltreatment on amygdala functional connectivity (FC) longitudinally, from infancy through the juvenile period. Using resting state functional magnetic resonance imaging (MRI) we performed amygdala-prefrontal cortex (PFC) region-of-interest and exploratory whole-brain amygdala FC analyses. The latter showed (a) developmental increases in amygdala FC with many regions, likely supporting increased processing of socioemotional-relevant stimuli with age; and (b) maltreatment effects on amygdala coupling with arousal and stress brain regions (locus coeruleus, laterodorsal tegmental area) that emerged with age. Maltreated juveniles showed weaker FC than controls, which was negatively associated with infant hair cortisol concentrations. Findings from the region-of-interest analysis also showed weaker amygdala FC with PFC regions in maltreated animals than controls since infancy, whereas bilateral amygdala FC was stronger in maltreated animals. These effects on amygdala FC development may underlie the poor behavioral outcomes associated with this adverse experience.

Cardiovascular disease is one of the leading causes of morbidity and mortality in persons with cancer. The elevated risk is thought to derive from the combination of cardiovascular risk factors and direct cardiotoxicity from cancer therapies. Exercise may be a potential strategy to counteract these toxicities and maintain cardiovascular reserve. In this article, we review the evidence for the potential cardioprotective effects of exercise training in cancer patients before, during, and following treatment. We also propose a patient-tailored approach for the development of targeted prescriptions based on individual exercise capacity and cardiovascular reserve., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

In this manuscript, we report that clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 is highly efficient in the hemipteran Oncopeltus fasciatus The white gene is well characterized in Drosophila where mutation causes loss of eye pigmentation; white is a reliable marker for transgenesis and other genetic manipulations. Accordingly, white has been targeted in a number of nonmodel insects to establish tools for genetic studies. Here, we generated mutations in the Of-white ( Of-w ) locus using CRISPR/Cas9. We found that Of-w is required for pigmentation throughout the body of Oncopeltus , not just the ommatidia. High rates of somatic mosaicism were observed in the injected generation, reflecting biallelic mutations, and a high rate of germline mutation was evidenced by the large proportion of heterozygous G1s. However, Of-w mutations are homozygous lethal; G2 homozygotes lacked pigment dispersion throughout the body and did not hatch, precluding the establishment of a stable mutant line. Embryonic and parental RNA interference (RNAi) were subsequently performed to rule out off-target mutations producing the observed phenotype and to evaluate the efficacy of RNAi in ablating gene function compared to a loss-of-function mutation. RNAi knockdowns phenocopied Of-w homozygotes, with an unusual accumulation of orange granules observed in unhatched embryos. This is, to our knowledge, the first CRISPR/Cas9-targeted mutation generated in Oncopeltus While we were unable to establish white as a useful visible marker for Oncopeltus , these findings are instructive for the selection of visible markers in nonmodel species and reveal an unusual role for an ortholog of a classic Drosophila gene., (Copyright © 2020 by the Genetics Society of America.)

Background: Much has been learned about basic biology from studies of insect model systems. The pre-eminent insect model system, Drosophila melanogaster , is a holometabolous insect with a derived mode of segment formation. While additional insect models have been pioneered in recent years, most of these fall within holometabolous lineages. In contrast, hemimetabolous insects have garnered less attention, although they include agricultural pests, vectors of human disease, and present numerous evolutionary novelties in form and function. The milkweed bug, Oncopeltus fasciatus (order: Hemiptera)-close outgroup to holometabolous insects-is an emerging model system. However, comparative studies within this order are limited as many phytophagous hemipterans are difficult to stably maintain in the lab due to their reliance on fresh plants, deposition of eggs within plant material, and long development time from embryo to adult., Results: Here we present the harlequin bug, Murgantia histrionica , as a new hemipteran model species. Murgantia -a member of the stink bug family Pentatomidae which shares a common ancestor with Oncopeltus  ~ 200 mya-is easy to rear in the lab, produces a large number of eggs, and is amenable to molecular genetic techniques. We use Murgantia to ask whether Pair-Rule Genes (PRGs) are deployed in ways similar to holometabolous insects or to Oncopeltus . Specifically, PRGs even - skipped, odd - skipped, paired and sloppy - paired are initially expressed in PR-stripes in Drosophila and a number of holometabolous insects but in segmental-stripes in Oncopeltus . We found that these genes are likewise expressed in segmental-stripes in Murgantia, while runt displays partial PR-character in both species. Also like Oncopeltus , E75A is expressed in a clear PR-pattern in blastoderm- and germband-stage Murgantia embryos, although it plays no role in segmentation in Drosophila . Thus, genes diagnostic of the split between holometabolous insects and Oncopeltus are expressed in an Oncopeltus -like fashion during Murgantia development., Conclusions: The similarity in gene expression between Murgantia and Oncopeltus suggests that Oncopeltus is not a sole outlier species in failing to utilize orthologs of Drosophila PRGs for PR-patterning. Rather, strategies deployed for PR-patterning, including the use of E75A in the PRG-network, are likely conserved within Hemiptera, and possibly more broadly among hemimetabolous insects., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)

Background: Halyomorpha halys (Stål), the brown marmorated stink bug, is a highly invasive insect species due in part to its exceptionally high levels of polyphagy. This species is also a nuisance due to overwintering in human-made structures. It has caused significant agricultural losses in recent years along the Atlantic seaboard of North America and in continental Europe. Genomic resources will assist with determining the molecular basis for this species' feeding and habitat traits, defining potential targets for pest management strategies., Results: Analysis of the 1.15-Gb draft genome assembly has identified a wide variety of genetic elements underpinning the biological characteristics of this formidable pest species, encompassing the roles of sensory functions, digestion, immunity, detoxification and development, all of which likely support H. halys' capacity for invasiveness. Many of the genes identified herein have potential for biomolecular pesticide applications., Conclusions: Availability of the H. halys genome sequence will be useful for the development of environmentally friendly biomolecular pesticides to be applied in concert with more traditional, synthetic chemical-based controls.

Context: Limited evidence suggests that patients with gastrointestinal (GI) cancers receiving chemotherapy (CTX) experience an average of 13 co-occurring symptoms. An alternative to counting symptoms is to evaluate for symptom clusters., Objectives: In a sample of patients with GI cancers receiving CTX (n = 399), we evaluated the occurrence, severity, and distress of 38 symptoms in the week before patients' second or third cycle of CTX (Time 1 [T1]), approximately one week after CTX (Time 2 [T2]), and approximately two weeks after CTX (Time 3 [T3]); evaluated for differences in the number and types of symptom clusters at each of these three assessments using ratings of occurrence, severity, and distress; and evaluated for changes in symptom clusters over time., Methods: Modified version of the Memorial Symptom Assessment Scale collected data on 38 common symptoms. Exploratory factor analyses were used to create the symptom clusters., Results: Five distinct symptom clusters were identified across the three symptom dimensions and the three assessments (i.e., psychological, CTX-related, weight change, GI, and epithelial). Psychological, CTX-related, and weight change clusters were relatively stable across all three symptom dimensions and time. Across all three symptom dimensions, GI cluster was identified only at T1 and epithelial cluster was identified at T2 and T3., Conclusion: The number and types of symptom clusters appear to be relatively stable over time and across the symptom dimensions. Ongoing assessment and management of these clusters is warranted across the entire course of CTX. The underlying mechanism for these clusters warrants investigation., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

The discovery of pair-rule genes (PRGs) in Drosophila revealed the existence of an underlying two-segment-wide prepattern directing embryogenesis. The milkweed bug Oncopeltus fasciatus , a hemimetabolous insect, is a more representative arthropod: most of its segments form sequentially after gastrulation. Here, we report the expression and function of orthologs of the complete set of nine Drosophila PRGs in Oncopeltus Seven Of -PRG-orthologs are expressed in stripes in the primordia of every segment, rather than every other segment; Of-runt is PR-like and several orthologs are also expressed in the segment addition zone. RNAi-mediated knockdown of Of-odd-skipped , paired and sloppy-paired impacted all segments, with no indication of PR-like register. We confirm that Of - E75A is expressed in PR-like stripes, although it is not expressed in this way in Drosophila , demonstrating the existence of an underlying PR-like prepattern in Oncopeltus These findings reveal that a switch occurred in regulatory circuits, leading to segment formation: while several holometabolous insects are ' Drosophila -like', using PRG orthologs for PR patterning, most Of- PRGs are expressed segmentally in Oncopeltus , a more basally branching insect. Thus, an evolutionarily stable phenotype - segment formation - is directed by alternate regulatory pathways in diverse species., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2019. Published by The Company of Biologists Ltd.)

Background: Epidemiologic studies regarding weight loss and subsequent cancer risk are sparse. The study aim was to evaluate the association between weight change by intentionality and obesity-related cancer incidence in the Women's Health Initiative Observational Study. Eleven cancers were considered obesity related: breast, ovary, endometrium, colon and rectum, esophagus, kidney, liver, multiple myeloma, pancreas, stomach, and thyroid., Methods: Postmenopausal women (n = 58 667) aged 50-79 years had body weight and waist circumference (WC) measured at baseline and year 3. Weight or WC change was categorized as stable (change < ±5%), loss (≥5%), and gain (≥5%). Self-report at year 3 characterized weight loss as intentional or unintentional. During the subsequent 12 years (mean) of follow-up, 6033 incident obesity-related cancers were identified. Relationships were evaluated using multivariable Cox proportional hazards regression models., Results: Compared to women with stable weight, women with intentional weight loss had lower obesity-related cancer risk (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.80 to 0.98). A similar result was observed for intentional WC reduction (HR = 0.88, 95% CI = 0.80 to 0.96). Among all cancers, intentional weight loss was most strongly associated with endometrial cancer (HR = 0.61, 95% CI = 0.42 to 0.88). Intentional WC loss was also associated with lower colorectal cancer risk (HR = 0.79, 95% CI = 0.63 to 0.99). Unintentional weight loss or weight gain was not associated with overall obesity-related cancer risk., Conclusion: Intentional weight or WC loss in postmenopausal women was associated with lower risk of obesity-related cancer. These findings suggest that postmenopausal women who intentionally lose weight can reduce their obesity-related cancer risk., (© The Author(s) 2019. Published by Oxford University Press.)

Context: Patients with gastrointestinal (GI) cancers undergoing chemotherapy (CTX) experience multiple cooccurring symptoms., Objectives: The aim of this study was to describe the occurrence, severity, and distress of 38 symptoms and to identify symptom clusters based on three symptom dimensions (i.e., occurrence, severity, and distress) in patients with GI cancers receiving CTX (n = 399). We compared whether the numbers and types of symptom clusters differed based on the dimension of the symptom experience used to create the clusters., Methods: A modified version of the Memorial Symptom Assessment Scale was used to assess the occurrence, severity, and distress of 38 symptoms before the initiation of the patient's next dose of CTX. Exploratory factor analysis was used to determine the symptom clusters., Results: These patients experienced 13.0 (±7.1) symptoms before their second or third dose of CTX. For all three symptom dimensions, four symptom clusters were identified, namely psychological distress, CTX-related, GI, and weight change. The number and types of symptom clusters were relatively similar using all three symptom dimensions. However, some variability was found in the specific symptoms within each of the clusters., Conclusion: Our findings suggest that patients with GI cancers experience multiple cooccurring symptoms. Consistent with previous studies of patients with a variety of cancer diagnoses, psychological and GI clusters are common. Clinicians need to assess for and tailor interventions for these symptom clusters., (Copyright © 2019 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Although obesity is an established risk factor for postmenopausal breast cancer, the results of weight loss and breast cancer studies are inconsistent. Therefore, we evaluated associations between weight change and breast cancer risk in postmenopausal women in the Women's Health Initiative Observational Study., Methods: Postmenopausal women (n = 61,335) who had no prior breast cancer and a normal mammogram had body weight and height measured and body mass index (BMI) calculated at baseline and year 3. Weight change at year 3 was categorized as stable (<5%), loss (≥5%), or gain (≥5%) with further assessment of weight loss intentionality by self-report. Multivariable Cox proportional hazard regression models were used to evaluate relationships between weight change and subsequent breast cancer incidence., Results: During a mean follow-up of 11.4 years with 3061 incident breast cancers, women with weight loss (n = 8175) had a significantly lower risk of breast cancer compared with women whose weight remained stable (n = 41,139) (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.78-0.98; P = .02) with no interaction by BMI. Adjustment for mammography did not alter findings (HR, 0.88; 95% CI, 0.78-0.99) with no significant difference by weight loss intentionality. Weight gain (≥5%) (n = 12,021) was not associated with breast cancer risk (HR, 1.02; 95% CI, 0.93-1.11) but was associated with higher triple-negative breast cancer incidence (HR, 1.54; 95% CI, 1.16-2.05)., Conclusions: Postmenopausal women who lose weight have lower breast cancer risk than those with stable weight. These findings suggest that postmenopausal women who lose weight may reduce their breast cancer risk., (© 2018 American Cancer Society.)

A set of pair-rule (PR) segmentation genes (PRGs) promotes the formation of alternate body segments in Drosophila melanogaster Whereas Drosophila embryos are long-germ, with segments specified more or less simultaneously, most insects add segments sequentially as the germband elongates. The hide beetle Dermestes maculatus represents an intermediate between short- and long-germ development, ideal for comparative study of PRGs. We show that eight of nine Drosophila PRG orthologs are expressed in stripes in Dermestes Functional results parse these genes into three groups: Dmac - eve , - odd and - run play roles in both germband elongation and PR patterning; Dmac - slp and - prd function exclusively as complementary, classic PRGs, supporting functional decoupling of elongation and segment formation; and orthologs of ftz , ftz-f1 , h and opa show more variable function in Dermestes and other species. While extensive cell death generally prefigured Dermestes PRG RNAi-mediated cuticle defects, an organized region with high mitotic activity near the margin of the segment addition zone is likely to have contributed to truncation of eve RNAi embryos. Our results suggest general conservation of clock-like regulation of PR stripe addition in sequentially segmenting species while highlighting regulatory rewiring involving a subset of PRG orthologs., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

Hemiptera is a large clade of insects understudied in terms of developmental biology. Halyomorpha halys , the Brown Marmorated Stink Bug (BMSB, referred to throughout as H. halys ), is an invasive hemipteran pest of the mid-Atlantic region of the USA that has rapidly spread to other regions in recent years, devastating a wide range of crops using a piercing and sucking mechanism. Its phylogenetic position, polyphagous habits, and rapid spread in the USA suggested that H. halys would be an ideal system to broaden our knowledge of developmental mechanisms in insects. We and others previously generated transcriptome sequences from different life stages of this insect. Here, we describe tools to examine gene expression patterns in whole-mount H. halys embryos and to test the response of H. halys to RNA interference (RNAi). We show that spatial and temporal patterns of gene expression in H. halys can be effectively monitored by both immunostaining and in situ hybridization. We also show that delivery of dsRNA to adult females knocks down gene function in offspring, using the homeotic gene Sex combs reduced ( Scr ). Knockdown of Hh - Scr resulted in dramatic malformations of the mouthparts, demonstrating for the first time that RNAi is effective in this species. Our results suggest that, despite difficulties with long-term laboratory culture of H. halys , this species shows promise as a developmental system.

Advances in genomics have raised the possibility of probing biodiversity at an unprecedented scale. However, sequence alone will not be informative without tools to study gene function. The development and sharing of detailed protocols for the establishment of new model systems in laboratories, and for tools to carry out functional studies, is thus crucial for leveraging the power of genomics. Coleoptera (beetles) are the largest clade of insects and occupy virtually all types of habitats on the planet. In addition to providing ideal models for fundamental research, studies of beetles can have impacts on pest control as they are often pests of households, agriculture, and food industries. Detailed protocols for rearing and maintenance of D. maculatus laboratory colonies and for carrying out dsRNA-mediated interference in D. maculatus are presented. Both embryonic and parental RNAi procedures-including apparatus set up, preparation, injection, and post-injection recovery-are described. Methods are also presented for analyzing embryonic phenotypes, including viability, patterning defects in hatched larvae, and cuticle preparations for unhatched larvae. These assays, together with in situ hybridization and immunostaining for molecular markers, make D. maculatus an accessible model system for basic and applied research. They further provide useful information for establishing procedures in other emerging insect model systems.

Persistent exposure to environmental stressors causes dysregulation of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis and alters GABAA receptor (GABAAR) levels throughout the brain. Social subordination in socially housed female rhesus results in distinctive stress-related physiological and behavioral phenotypes that are dependent on the ovarian hormone estradiol (E2). In the present study, we utilized ovariectomized adult female rhesus monkeys undergoing hormone replacement with E2 to test the hypothesis that the chronic psychosocial stress of subordination alters GABAAR binding potential (GABAAR BPND) in limbic regions implicated in emotional processing including the prefrontal cortex, temporal lobe (amygdala and hippocampus), and hypothalamus. Furthermore, we tested the hypothesis that peripheral administration of a corticotropin-releasing hormone (CRH) receptor antagonist (astressin B) would reverse the alterations in GABAAR binding within these regions in subordinate females. After subjects received astressin B or saline for three consecutive days, GABAAR BPND was determined by positron emission tomography (PET) using (18)F-flumazenil as a radioligand. T1-weighted structural magnetic resonance imaging scans were also acquired for PET scan co-registration, in order to perform a region of interest analysis using the pons as a reference region. Compared to socially dominant females, subordinate females exhibited increased GABAAR BPND in the prefrontal cortex but not in the temporal lobe or the hypothalamus. Administration of astressin B eliminated the status difference in GABAAR BPND in the prefrontal cortex, suggesting that the chronic stressor of social subordination modulates GABAergic tone via effects on CRH and the LHPA axis, at least in prefrontal regions., (Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.)

Estrogen (E2) has activational effects on sexual motivation and mitigating effects on anxiety-like behaviors that can be attenuated with chronic exposure to psychosocial stress. Some studies suggest that this attenuation can be overcome by higher doses of E2, while others show that chronic psychosocial stress may alter the mechanisms of E2 function, thus reducing any positive benefit from higher doses of E2. To determine the interaction between psychosocial stress and E2 dose on behavior, we examined the scope of attenuation across a suite of socioemotional behaviors, including reproduction, affiliation, aggression, submission, and anxiety-like behaviors on 36 ovariectomized female rhesus monkeys. Females were exposed to graded psychosocial stress, established by an intrinsic female dominance hierarchy, where subordinate animals receive high amounts of harassment. Our data show that E2 dose-dependently increased sexual motivation and male-affiliation in dominant (e.g. low-stress) females, while subordinate females showed no positive effects of E2, even at higher doses. In addition, contact aggression was attenuated in dominant females, while non-contact aggression was attenuated in both dominant and middle-ranking females. These results suggest that the stress-induced attenuation of E2's activational effects on sexual behavior and affiliation with males may not be overcome with higher doses of E2. Furthermore, the observed behavioral consequences of psychosocial stress and E2 dose may be dependent on the behaviors of all the females in the social-group, and better resolution on these effects depends on isolating treatment to individuals within the group to minimize alterations in social-group interactions., (Copyright © 2012 Elsevier Inc. All rights reserved.)

We examined the relationship of pre-injury intelligence, demographic variables, lesion location, brain tissue volume loss and a number of genetic markers to long-term cognitive decline in a group of Vietnam veterans with predominantly penetrating head injury (PHI) suffered more than 30 years ago. Using linear and stepwise regression procedures, we found that those with PHI demonstrated a greater degree of cognitive decline overall during the years following recovery from injury compared with a control group of uninjured Vietnam veterans. This became increasingly significant later in life. We also found that pre-injury intelligence was the most consistent predictor of cognitive outcome across all phases of potential recovery and decline after such injuries. While laterality of lesion was not a factor, we did find some associations between atrophy and specific regions of tissue loss and long-term cognitive functioning. Finally, we found evidence for an association between level of cognitive decline following PHI and the possession of certain genetic markers that have been linked with brain injury and neurodegeneration. Thus exacerbated decline does occur in Vietnam veterans with PHI and it is apparently unrelated to dementia and is determined by multiple factors (most notably pre-injury intelligence).

Although home visits by psychiatrists have been shown to be an effective treatment strategy, the practice is not a common one in the United States. A survey of psychiatrists (n = 212) examined their attitudes toward home visits and their recent practice patterns. The researchers hypothesized that psychiatrists employed by community mental health centers were more likely to have a positive attitude toward home visits and were more likely to treat patients in their own homes than psychiatrists not working at such centers. This hypothesis was not confirmed. While a majority of the respondents agreed that home visits had diagnostic and treatment value, only 15 percent had made a home visit in the past year.