In situ measurement of damage evolution in shocked magnesium as a function of microstructure.

Accurate modeling and prediction of damage induced by dynamic loading in materials have long proved to be a difficult task. Examination of postmortem recovered samples cannot capture the time-dependent evolution of void nucleation and growth, and attempts at analytical models are hindered by the necessity to make simplifying assumptions, because of the lack of high-resolution, in situ, time-resolved experimental data. We use absorption contrast imaging to directly image the time evolution of spall damage in metals at ∼1.

Pre- and post-LEEP: analysis of the female urogenital tract microenvironment and its association with sexual dysfunction.

Background: The loop electrosurgical excision procedure (LEEP) to treat cervical dysplasia (CD) is known to alter the cervical microbiota, the community of bacteria that play a central role in female genital health. Perturbations to the microbiota of the female urogenital tract (FUT), including the urethra, vagina, and cervix, have been linked with symptoms of sexual dysfunction (SD), though correlations among LEEP, the microenvironment, and SD have not yet been described.

Aims: To characterize the FUT microbiota before and after LEEP and investigate possible associations with SD.

Single-cell transcriptomic analysis of renal allograft rejection reveals insights into intragraft TCR clonality.

Bulk analysis of renal allograft biopsies (rBx) identified RNA transcripts associated with acute cellular rejection (ACR); however, these lacked cellular context critical to mechanistic understanding of how rejection occurs despite immunosuppression (IS). We performed combined single-cell RNA transcriptomic and TCR-α/β sequencing on rBx from patients with ACR under differing IS drugs: tacrolimus, iscalimab, and belatacept. We found distinct CD8+ T cell phenotypes (e.

Inequities in COVID-19 Omicron infections and hospitalisations for Māori and Pacific people in Te Manawa Taki Midland region, New Zealand.

COVID-19 impacts population health equity. While mRNA vaccines protect against serious illness and death, little New Zealand (NZ) data exist about the impact of Omicron - and the effectiveness of vaccination - on different population groups. We aim to examine the impact of Omicron on Māori, Pacific, and Other ethnicities and how this interacts with age and vaccination status in the Te Manawa Taki Midland region of NZ.

Single cell transcriptomic analysis of renal allograft rejection reveals novel insights into intragraft TCR clonality.

Bulk analysis of renal allograft biopsies (rBx) identified RNA transcripts associated with acute cellular rejection (ACR); however, these lacked cellular context critical to mechanistic understanding. We performed combined single cell RNA transcriptomic and TCRα/β sequencing on rBx from patients with ACR under differing immunosuppression (IS): tacrolimus, iscalimab, and belatacept. TCR analysis revealed a highly restricted CD8 T cell clonal expansion (CD8 ), independent of HLA mismatch or IS type.

A class-mismatched TCR bypasses MHC restriction via an unorthodox but fully functional binding geometry.

MHC restriction, which describes the binding of TCRs from CD4 T cells to class II MHC proteins and TCRs from CD8 T cells to class I MHC proteins, is a hallmark of immunology. Seemingly rare TCRs that break this paradigm exist, but mechanistic insight into their behavior is lacking. TIL1383I is a prototypical class-mismatched TCR, cloned from a CD4 T cell but recognizing the tyrosinase tumor antigen presented by the class I MHC HLA-A2 in a fully functional manner.

Factors associated with naloxone availability and dispensing through Michigan's pharmacy standing order.

Pharmacy standing order policies allow pharmacists to dispense naloxone, thereby increasing access to naloxone. To describe pharmacy standing order participation and associations of pharmacy and community characteristics that predict naloxone availability and dispensing across eight counties in Michigan. We conducted a telephone survey of 662 standing order pharmacies with a response rate of 81% (n = 539).

Exposure to Outdoor Particulate Matter Air Pollution and Risk of Gastrointestinal Cancers in Adults: A Systematic Review and Meta-Analysis of Epidemiologic Evidence.

Background: Outdoor air pollution is a known lung carcinogen, but research investigating the association between particulate matter (PM) and gastrointestinal (GI) cancers is limited.

Objectives: We sought to review the epidemiologic literature on outdoor PM and GI cancers and to put the body of studies into context regarding potential for bias and overall strength of evidence.

Methods: We conducted a systematic review and meta-analysis of epidemiologic studies that evaluated the association of fine PM [PM with an aerodynamic diameter of ()] and (aerodynamic diameter ) with GI cancer incidence or mortality in adults.

Assessing how assay types predict toxicology data.

animal bioassays are increasingly being supplemented with assays to serve as the new standard for chemical toxicity tests. Despite this shift, investigators face challenges related to increased reliance on data. The aim of this study was to deploy a streamlined method to assess the ability of data to predict similar results as data by correlating chemical toxicity rankings obtained using Benchmark Doses and Benchmark Dose Lower Limits (BMD(L)s) derived from and assays.

The Pebble Remains in the Master's Hand: Two Careers Spent Learning (Still) from John Evans.

In this article, we discuss four vexing problems in risk-based decision making that John Evans has addressed over the last nearly 40 years and has perennially challenged the two of us and others to think about. We tackle the role in decision making of potential thresholds in dose-response functions, how the lack of health reference values for many chemicals may distort risk management, the challenge of model uncertainty for risk characterization, and the yet-untapped potential for value-of-information analysis to enhance public health decision making. Our theme is that work remains to be done on each of these, but that some of that work would merely involve listening to ideas that John has already offered.

Oxidative Cyclization-Induced Activation of a Phosphoinositide 3-Kinase Inhibitor for Enhanced Selectivity of Cancer Chemotherapeutics.

In this work, we designed a prodrug that reacts with cellular oxidative equivalents leading to ether cleavage and cyclization to release an active phosphatidylinositol 3-kinase (PI3K) inhibitor. We show that the compound reduces affinity for PI3KA relative to the PI3K inhibitor, is slow to intercellularly oxidize, and is resistant to liver microsomes. We observed modest activity in untreated acute myeloid leukemia cells and 14-fold selectivity relative to non-cancerous cells.

Pesticide interactions and risks of sperm chromosomal abnormalities.

Disentangling the separate and synergistic effects of chemicals poses methodological challenges for accurate exposure assessment and for investigating epidemiologically how chemicals affect reproduction. We investigated combined exposures to ubiquitous contemporary use pesticides, specifically organophosphates (OP) and pyrethroids (PYR), and their association with germ cell abnormalities among adult men. Fluorescence in situ hybridization was used to determine disomy in sperm nuclei and urine was analyzed for concentrations of PYR metabolites (3-phenoxybenzoic acid; 3PBA) and OP dialkyl phosphate (DAP) metabolites.

Stereochemical Dependences of P-C Spin-Spin Coupling Constants of Heterocyclic Phosphines.

Phosphorus-carbon spin-spin coupling constants in a series of salient heterocyclic phosphines were calculated at the SOPPA(MP2) level including evaluation of relativistic and solvent effects. A number of the locally dense basis set schemes were thoroughly investigated in terms of their accuracy versus computational demands. The most effective computational scheme was tested in a benchmark series to provide a very good correlation between calculated at the SOPPA(MP2) level and experiment.

A review of prospective registration of trials published in nursing science journals in 2017.

Aim: To determine the proportion of trials published in nursing science journals in 2017 that were prospectively registered.

Design: A review of randomized controlled trials published in a Journal Citation Report nursing science journal in 2017.

Data Source: Table of contents of included journals.

UV cell stress induces oxidative cyclization of a protective reagent for DNA damage reduction in skin explants.

UV irradiation is a major driver of DNA damage and ultimately skin cancer. UV exposure leads to persistent radicals that generate ROS over prolonged periods of time. Toward the goal of developing long-lasting antioxidants that can penetrate skin, we have designed a ROS-initiated protective (RIP) reagent that, upon reaction with ROS (antioxidant activity), self-cyclizes and then releases the natural product apocynin.

Challenges and Considerations When Balancing the Risks of Contaminants with the Benefits of Fruits and Vegetables for Infants and Toddlers.

Background: Fruits and vegetables are key to a healthy diet, particularly in children; however, parents may be concerned about contaminants found in fruits and vegetables. Making informed food choices for children requires understanding and balancing the risks of contaminant exposure with the importance of providing a healthy diet. The objective of this work is to identify fruits and vegetables commonly consumed by infants and toddlers; identify potential contaminants in fruits and vegetables; and outline considerations in assessing contaminant risks in food categories with a critical role in a healthy diet.

Genomic medicine must reduce, not compound, health inequities: the case for hauora-enhancing genomic resources for New Zealand.

Precision medicine seeks to draw on data from both individuals and populations across disparate domains to influence and support diagnosis, management and prevention in healthcare at the level of the individual patient and their family/whānau. Central to this initiative is incorporating the effects of the inherent variation that lies within genomes and can influence health outcomes. Identifying and interpreting such variation requires an accurate, valid and representative dataset to firstly define what variants are present and then assess the potential relevance for the health of a person, their family/whānau and the wider community to which they belong.

Which is most sensitive? Assessing responses of mice and rats in toxicity bioassays.

Rodent species are commonly used in traditional toxicology testing guidelines to predict human health toxicity outcomes. The use of a consistent species in test guidelines is important for maintaining consistency and comparability between tests and testing guidelines. This recommendation was operationalized for this study as the implicit assumption of uniform species and species-sex sensitivities.

Correlation of Noncancer Benchmark Doses in Short- and Long-Term Rodent Bioassays.

This study investigated whether, in the absence of chronic noncancer toxicity data, short-term noncancer toxicity data can be used to predict chronic toxicity effect levels by focusing on the dose-response relationship instead of a critical effect. Data from National Toxicology Program (NTP) technical reports have been extracted and modeled using the Environmental Protection Agency's Benchmark Dose Software. Best-fit, minimum benchmark dose (BMD), and benchmark dose lower limits (BMDLs) have been modeled for all NTP pathologist identified significant nonneoplastic lesions, final mean body weight, and mean organ weight of 41 chemicals tested by NTP between 2000 and 2012.