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Breast cancer is the most prevalent form of cancer in elderly women. Information on breast cancer explicitly relevant to elderly women was examined in 113 articles in the professional nursing literature and popular magazines. Content analysis on the nature or extent of information about breast cancer indicated that authors in the professional nursing literature and the popular media have inadequately addressed the degree of risk and the special needs of the elderly woman. Few authors in either the lay or professional literature have explicitly discussed the needs of elderly women, nursing research on breast cancer typically did not include elderly women, and popular articles and accompanying photographs tended to feature younger women. [ABSTRACT FROM AUTHOR]

The molecular underpinnings of high-grade endometrial carcinoma (HGEC) metastatic growth and survival are poorly understood. Here, we show that ascites-derived and primary tumor HGEC cell lines in 3D spheroid culture faithfully recapitulate key features of malignant peritoneal effusion and exhibit fundamentally distinct transcriptomic, proteomic, and metabolomic landscapes compared with conventional 2D monolayers. Using a genetic screening platform, we identify MAPK14 (which encodes the protein kinase p38α) as a specific requirement for HGEC in spheroid culture. MAPK14/p38α has broad roles in programming the phosphoproteome, transcriptome, and metabolome of HGEC spheroids, yet has negligible impact on monolayer cultures. MAPK14 promotes tumorigenicity in vivo and is specifically required to sustain a sub-population of spheroid cells that is enriched in cancer stemness markers. Therefore, spheroid growth of HGEC activates unique biological programs, including p38α signaling, that cannot be captured using 2D culture models and are highly relevant to malignant disease pathology., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Human metabolomics has made significant strides in understanding metabolic changes and their implications for human health, with promising applications in diagnostics and treatment, particularly regarding the gut microbiome. However, progress is hampered by issues with data comparability and reproducibility across studies, limiting the translation of these discoveries into practical applications., Objectives: This study aims to evaluate the fit-for-purpose of a suite of human stool samples as potential candidate reference materials (RMs) and assess the state of the field regarding harmonizing gut metabolomics measurements., Methods: An interlaboratory study was conducted with 18 participating institutions. The study allowed for the use of preferred analytical techniques, including liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR)., Results: Different laboratories used various methods and analytical platforms to identify the metabolites present in human stool RM samples. The study found a 40% to 70% recurrence in the reported top 20 most abundant metabolites across the four materials. In the full annotation list, the percentage of metabolites reported multiple times after nomenclature standardization was 36% (LC-MS), 58% (GC-MS) and 76% (NMR). Out of 9,300 unique metabolites, only 37 were reported across all three measurement techniques., Conclusion: This collaborative exercise emphasized the broad chemical survey possible with multi-technique approaches. Community engagement is essential for the evaluation and characterization of common materials designed to facilitate comparability and ensure data quality underscoring the value of determining current practices, challenges, and progress of a field through interlaboratory studies., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The molecular underpinnings of H igh G rade E ndometrial C arcinoma (HGEC) metastatic growth and survival are poorly understood. Here we show that ascites-derived and primary tumor HGEC cell lines in 3D spheroid culture faithfully recapitulate key features of malignant peritoneal effusion and exhibit fundamentally distinct transcriptomic, proteomic and metabolomic landscapes when compared with conventional 2D monolayers. Using genetic screening platform we identify MAPK14 (which encodes the protein kinase p38α) as a specific requirement for HGEC in spheroid culture. MAPK14 /p38α has broad roles in programing the phosphoproteome, transcriptome and metabolome of HGEC spheroids, yet has negligible impact on monolayer cultures. MAPK14 promotes tumorigenicity in vivo and is specifically required to sustain a sub-population of spheroid cells that is enriched in cancer stemness markers. Therefore, spheroid growth of HGEC activates unique biological programs, including p38α signaling, that cannot be captured using 2D culture models and are highly relevant to malignant disease pathology.

Frank Ramsey's philosophy of science is considered abstruse due to the incompleteness and difficulty of his paper "Theories". This has not prevented various authors from arguing that Ramsey is committed to meaning holism for scientific theories, and that his philosophy of science is anti-realist but anti-reductionist. However, it is unclear exactly how meaning holism works for Ramsey, and how he can be both anti-realist and anti-reductionist. I argue that clarity can be gained on both issues by examining Ramsey's philosophy of science through a reconstruction of his decision theory compatible with his later philosophical beliefs. I develop an account of how credences can be formed over singular, theoretical propositions despite those propositions being fictions. Credences are ultimately measured by preferences over conditionals whose antecedents are the verification conditions of theoretical propositions and outcomes are elements of a privileged partition on an agent's possibility space induced by the language of the theory. Those verification conditions are the observational elements formed from the unions of this induced partition. Meaning holism is explained as the sensitivity of theoretical propositions to their verification conditions. And anti-realism and anti-reductionism can be maintained due to theoretical propositions forming a finer partition of possibility space than observational propositions, which prevents the former from being truth-functions of the latter., Competing Interests: Declaration of Competing Interest The authors have no relevant financial or non-financial interests to disclose. The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Drug-induced acute interstitial nephritis (AIN) presents as acute kidney injury (AKI) with the use of certain offending drugs. Antibiotics, such as β-lactams, trimethoprim-sulfamethoxazole, fluoroquinolones, and rifampin, account for up to 50% of drug-induced AIN cases. The onset of drug-induced AIN following drug exposure usually ranges from few days to several weeks or months. We present a patient with lupus who had rapid decline in renal function with a single dose of vancomycin and piperacillin-tazobactam (VPT) administration, termed as the "workhorse" regimen at many institutions. In addition, she did not exhibit many clinical and laboratory signs of AIN, making diagnosis challenging. Prompt kidney biopsy and early steroid therapy had a critical role in recovery of the patient's renal function. The median duration for renal impairment in vancomycin-induced AIN is 26 days. Onset of AKI is usually rapid from VPT, within 3 - 5 days of drug exposure. However, the severity of AKI is often low, in contrast to this patient whose AKI reached a stage 3 (AKIN/KDIGO) within 2 days from drug exposure. This study highlights the nephrotoxic potential of piperacillin, especially when used along with vancomycin, concurrent with recent evidence. Within rising antibiotic usage rates, is important to consider AIN in the differential diagnosis of rapidly declining AKI, especially with the combined use of VPT., Competing Interests: On behalf of all authors, the corresponding author states that there is no conflict of interest. Figure 1.H & E photomicrograph showing mild edema and focal tubular injury, evidenced by cytoplasmic vacuolization, slightly dilated tubules with a thin epithelial lining, and diffuse loss of the brush border. The glomeruli are normal with wide-open loops and smooth, thin capillary membranes.Figure 2.H & E photomicrograph showing mild edema and focal inflammatory infiltrate. Several neutrophils are identifiable.Figure 3.Patient’s serum creatinine trend during hospitalization and during follow-up visits after discharge., (© Dustri-Verlag Dr. K. Feistle.)

Marginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. In the present study, we characterized the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot metabolome among 267 African American dyads in Atlanta, Georgia between 2016 and 2020. Pregnant people with higher serum perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations had increased odds of an early birth. After false discovery rate correction, the effect of prenatal PFAS exposure on reduced length of gestation was associated with 8 metabolomic pathways and 52 metabolites in newborn dried blood spots, which suggested perturbed tissue neogenesis, neuroendocrine function, and redox homeostasis. These mechanisms explain how prenatal PFAS exposure gives rise to the leading cause of infant death in the United States., (© 2023. The Author(s).)

Scope: This study presents a workflow to construct a Dietary Exposome Library (DEL) comprised of phytochemicals and their metabolites derived from host and gut microbiome metabolism for use in peak identification/annotation of untargeted metabolomics datasets., Methods and Results: An evidence mapping initiative established target analytes related to the consumption of phytochemical-rich foods. Analytes were confirmed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS(n)) analysis of human biospecimens from dietary intervention studies of (poly)phenol-rich diets. One hundred and sixty six verified compounds were subsequently analyzed on an untargeted metabolomics platform to acquire chromatographic and high-resolution mass spectral data for construction of a DEL. The DEL facilitated identification/annotation of 123 metabolites associate with exposure to (poly)phenol enriched diets, which included aromatic ketones, benzoic acids, ellagic acids, caffeoylquinic acids, catecholamines, coumarins, hippuric acid, hydroxytoluenes, phenylamines, stilbenes, urolithins, valerolactones, and xanthonoids, in untargeted metabolomics datasets acquire from human plasma and urine reference materials., Conclusions: The DEL focusing on (poly)phenols and their metabolites of dietary exposure facilitated identification/annotation of ingested food components and their associated pathways in untargeted metabolomics datasets acquired from human biospecimens. The DEL continues to expand with the aim to provide evidence-based data for dietary metabolites in exposome research and inform the development of dietary intervention strategies., (© 2022 Wiley-VCH GmbH.)

Objective: The objective of this exploratory study was to determine if perturbations in gut microbial composition and the gut metabolome could be linked to individuals with obesity and osteoarthritis (OA)., Methods: Fecal samples were collected from obese individuals diagnosed with radiographic hand plus knee OA (n = 59), defined as involvement of at least 3 joints across both hands, and a Kellgren-Lawrence (KL) grade 2-4 (or total knee replacement) in at least one knee. Controls (n = 33) were without hand OA and with KL grade 0-1 knees. Fecal metabolomes were analyzed by a UHPLC/Q Exactive HFx mass spectrometer. Microbiome composition was determined in fecal samples by 16 S ribosomal RNA amplicon sequencing (rRNA-seq). Stepwise logistic regression models were built to determine microbiome and/or metabolic characteristics of OA., Results: Untargeted metabolomics analysis indicated that OA cases had significantly higher levels of di- and tripeptides and significant perturbations in microbial metabolites including propionic acid, indoles, and other tryptophan metabolites. Pathway analysis revealed several significantly perturbed pathways associated with OA including leukotriene metabolism, amino acid metabolism and fatty acid utilization. Logistic regression models selected metabolites associated with the gut microbiota and leaky gut syndrome as significant predictors of OA status, particularly when combined with the rRNA-seq data., Conclusions: Adults with obesity and knee plus hand OA have distinct fecal metabolomes characterized by increased products of proteolysis, perturbations in leukotriene metabolism, and changes in microbial metabolites compared with controls. These metabolic perturbations indicate a possible role of dysregulated proteolysis in OA., (Copyright © 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background: After long-term androgen deprivation therapy, 25-30% prostate cancer (PCa) acquires an aggressive neuroendocrine (NE) phenotype. Dysregulation of YAP1, a key transcription coactivator of the Hippo pathway, has been related to cancer progression. However, its role in neuroendocrine prostate cancer (NEPC) has not been assessed., Methods: Immunohistochemistry and bioinformatics analysis were conducted to evaluate YAP1 expression levels during PCa initiation and progression., Results: YAP1 expression was present in the basal epithelial cells in benign prostatic tissues, lost in low-grade PCa, but elevated in high-grade prostate adenocarcinomas. Interestingly, the expression of YAP1 was reduced/lost in both human and mouse NEPC., Conclusions: The expression of YAP1 is elevated in high-grade prostate adenocarcinomas but lost in NEPC.

Background: Neonatal abstinence syndrome is an array of signs and symptoms experienced by a newborn due to abrupt discontinuation of intrauterine exposure to certain drugs, primarily opioids. In the United States, the incidence of neonatal abstinence syndrome has tripled over the past decade. The current standard of care for drug testing includes the analysis of infant urine and meconium. Sample collection is associated with several limitations, including diaper media interferences, limited sample amount, sample heterogeneity, and the need for professional staff for collection. Umbilical cord tissue has emerged as a convenient sample matrix for testing owing to its universal availability. The purpose of this study was to examine umbilical cords using an untargeted metabolomics approach to determine the detected drugs and validate an analytical method to confirm and quantify the identified drugs., Methods: A metabolomics analysis was performed with 21 umbilical cords to screen for drugs and drug metabolites by liquid chromatography-mass spectrometry. Drugs were identified using the National Institute of Standards and Technology database, and an analytical method was developed and validated using secondary liquid chromatography-mass spectrometry instrument for positive confirmation and quantitative analysis., Results: Twenty-one random umbilical cords from women were tested: 4 were positive for cocaine and the primary and secondary metabolites; one was positive for methadone, the primary metabolite; 3 were positive for cotinine, the metabolite of nicotine; and 5 were positive for acetyl norfentanyl., Conclusions: Our research is a prospective method development study using untargeted and targeted approaches to characterize steady-state drug metabolite levels in the umbilical cord matrix at the time of delivery. By characterizing drug type and concentration, this methodology can be used to develop a reliable complementary testing method for meconium toxicology screens.

Adult T-cell Leukemia (ATL) is a lymphoproliferative disease of CD4+ T-cells infected with Human T-cell Leukemia Virus type I (HTLV-1). With the exception of allogeneic hematopoietic stem cell transplantation, there are no effective treatments to cure ATL, and ATL cells often acquire resistance to conventional chemotherapeutic agents. Accumulating evidence shows that development and maintenance of ATL requires key contributions from the viral protein, HTLV-1 basic leucine zipper factor (HBZ). In this study we found that HBZ activates expression of Heme Oxygenase 1 (HMOX-1), a component of the oxidative stress response that functions to detoxify free heme. Transcription of HMOX1 and other antioxidant genes is regulated by the small Mafs. These cellular basic leucine zipper (bZIP) factors control transcription by forming homo- or heterodimers among themselves or with other cellular bZIP factors that then bind Maf responsive elements (MAREs) in promoters or enhancers of antioxidant genes. Our data support a model in which HBZ activates HMOX1 transcription by forming heterodimers with the small Mafs that bind MAREs located in an upstream enhancer region. Consistent with this model, we found that HMOX-1 is upregulated in HTLV-1-transformed T-cell lines and confers these cells with resistance to heme-induced cytotoxicity. In this context, HBZ-mediated activation of HMOX-1 expression may contribute to resistance of ATL cells to certain chemotherapeutic agents. We also provide evidence that HBZ counteracts oxidative stress caused by two other HTLV-1-encoded proteins, Tax and p13. Tax induces oxidative stress as a byproduct of driving mitotic expansion of infected cells, and p13 is believed to induce oxidative stress to eliminate infected cells that have become transformed. Therefore, in this context, HBZ-mediated activation of HMOX-1 expression may facilitate transformation. Overall, this study characterizes a novel function of HBZ that may support the development and maintenance of ATL., Competing Interests: The authors have declared that no competing interests exist.

Effective and reliable training aids for victim recovery canine teams is essential for law enforcement and investigative purposes. Without adequate training aids, the rate of recovery for sub surface or surface human remains deposition using canine teams may be adversely affected and result in confusing information. The composition of three commercially available canine training aids that purportedly generate volatile components responsible for the odor of human decomposition is relatively simple and not closely related to those compounds experimentally determined to be present at the site of surface or sub-surface human remains. In this study, these different commercial formulations were chemically characterized using six different sampling approaches, including two applications of direct liquid injection, solid-phase microextraction (SPME), purge and trap, ambient preconcentration/thermal desorption, and cryogenic preconcentration/thermal desorption. Direct liquid injections resulted in the fewest number of detected compounds, while a cryogen based thermal desorption method detected the greatest number of compounds in each formulation. Based solely upon the direct liquid injection analysis, Pseudo™ Scent I was composed of approximately 29±4% and 71±5% of 2-pyrrolidinone and 4-aminobutanoic acid, respectively. This same analysis showed that Pseudo™ Scent II was composed of approximately 11±1, 11±1, 24±5, and 54±7% of putrescine, cadaverine, 2-pyrrolidinone, and 4-aminobutanoic acid, respectively. Headspace analysis was conducted to more closely simulate the process whereby a canine's nose would capture a volatiles profile. More compounds were detected using the headspace sampling method; however, the vast majority was not consistent with current data on human decomposition. Additionally, the three formulations were tested in outdoor and indoor scenarios by a double-blinded canine team, using a certified and specifically trained victim recovery canine with multiple confirmed recoveries, to determine if the formulations would be recognized by that canine as being related to human decomposition. The canine used in this study did not provide a positive response to any of the formulations tested in either test scenario. The implications for locating residual human decomposition odor in the absence of recoverable material are discussed in light of these data., (Published by Elsevier Ireland Ltd.)

A phytochrome-like protein called Ppr was discovered in the purple photosynthetic bacterium Rhodospirillum centenum. Ppr has a photoactive yellow protein (PYP) amino-terminal domain, a central domain with similarity to phytochrome, and a carboxyl-terminal histidine kinase domain. Reconstitution experiments demonstrate that Ppr covalently attaches the blue light-absorbing chromophore p-hydroxycinnamic acid and that it has a photocycle that is spectrally similar to, but kinetically slower than, that of PYP. Ppr also regulates chalcone synthase gene expression in response to blue light with autophosphorylation inhibited in vitro by blue light. Phylogenetic analysis demonstrates that R. centenum Ppr may be ancestral to cyanobacterial and plant phytochromes.

The purple photosynthetic bacterium Rhodospirillum centenum is capable of forming swarm colonies that rapidly migrate toward or away from light, depending on the wavelength of excitation. To identify components specific for photoperception, we conducted mini-Tn5-mediated mutagenesis and screened approximately 23,000 transposition events for mutants that failed to respond to either continuous illumination or to a step down in light intensity. A majority of the ca. 250 mutants identified lost the ability to form motile swarm cells on an agar surface. These cells appeared to contain defects in the synthesis or assembly of surface-induced lateral flagella. Another large fraction of mutants that were unresponsive to light were shown to be defective in the formation of a functional photosynthetic apparatus. Several photosensory mutants also were obtained with defects in the perception and transmission of light signals. Twelve mutants in this class were shown to contain disruptions in a chemotaxis operon, and five mutants contained disruptions of components unique to photoperception. It was shown that screening for photosensory defective R. centenum swarm colonies is an effective method for genetic dissection of the mechanism of light sensing in eubacteria.

Women's health status is investigated in the context of stratification in the world-system. We investigate three alternative conceptualizations of the world-system for their effects on women's health status, using country-level data. The models investigate the effects of world-system position, military expenditures, and health resources on women's health status. Comparison of the alternative conceptualizations of world-system position indicate that a continuous model is only negligibly better than three- or five-block models at explaining women's health status. Regardless of how it is measured, world-system position has dramatic effects on women's health.

The health status of women is examined within the context of a global political economy. The authors present a beginning attempt to model some key macrolevel processes linked to the health of women. In particular, a structural modeling technique known as LVPLS (or "soft modeling") is used to empirically test one recent formulation of world-system theory. The findings give added emphasis to the importance of the larger economic forces that affect women's health.

This paper examines race differences in the effects of social roles on physical health. Using data from the older men cohort of the National Longitudinal Surveys of Labor Market Experience, we examine the impact of employment, marriage, and being a supporter on health limitations and mortality. Employment has the most consistent health-protective effect, and the benefits of employment are more pronounced for Blacks than for Whites. Marriage affects health in conjunction with employment. These findings lend further support to the growing literature on the effects of roles on health. The results further illustrate the importance of ascribed statuses as structural determinants of the relationship between roles and health, highlighting the very real differences in the meanings and expectations of social roles for Blacks and Whites.

The nodulation (nod) genes of the symbiont Rhizobium meliloti are transcriptionally controlled by protein activators in the nodD gene family. While NodD1 and NodD2 act in concert with small molecular weight inducers provided by the host legume plant, NodD3 is an inducer-independent activator of the nod promoters. We determined the sequence of the nodD3 gene, confirmed the expression of a 35 kDa protein in vitro, and determined the insertion points of five Tn5 insertions in the region of the nodD3 gene. We found the NodD3 amino acid sequence to be markedly diverged from the sequences of NodD1 and NodD2, which were more similar to the inducer-dependent NodD of another species, Rhizobium leguminosarum biovar viciae. The expression of nodD3 is not well understood, but involves at least SyrM, another positive activator related to the LysR-NodD family. One of the phenotypically mutant Tn5 insertions used in genetic studies of NodD3-dependent nod regulation lacks NodD3 protein as determined by Western blots, but another expresses about 50-60% of the wild type level. The location of these Tn5 insertions substantially upstream of the open reading frame for NodD3 suggests importance of relatively distant regulatory sequences for nodD3 expression. An insertion that did not cause a NodD3- phenotype is located in the extreme C-terminus of the protein coding region.