Effects of Environmentally Relevant Concentrations of Roundup on Oxidative-Nitrative Stress, Cellular Apoptosis, Prooxidant-Antioxidant Homeostasis, Renin and CYP1A Expressions in Goldfish: Molecular Mechanisms Underlying Kidney Damage During Roundup Exposure.

Roundup is one of the most widely used glyphosate-based harmful herbicides in the United States as well as globally, which poses a severe risk for terrestrial and aquatic organisms. In order to identify the detrimental effects of Roundup exposure in aquatic organisms, we investigated the environmentally relevant concentrations of Roundup exposure (low dose: 0.5 μg/L and high dose: 5.

Evaluation of the analytical and clinical accuracy of four blood glucose meters in pregnant women with hyperglycaemia.

Aims: Physiological changes during pregnancy can infuence the performance of blood glucose meters. This study aimed to evaluate the analytical and clinical accuracy of glucose meters in pregnant women with hyperglycaemia.

Materials And Methods: Glucose was measured by four commonly used meters among consecutive women with diabetes in pregnancy.

A Generalized Bayesian Stochastic Block Model for Microbiome Community Detection.

Advances in next-generation sequencing technology have enabled the high-throughput profiling of metagenomes and accelerated microbiome studies. Recently, there has been a rise in quantitative studies that aim to decipher the microbiome co-occurrence network and its underlying community structure based on metagenomic sequence data. Uncovering the complex microbiome community structure is essential to understanding the role of the microbiome in disease progression and susceptibility.

Nitrogen fixation may not alleviate stoichiometric imbalances that limit primary production in eutrophic lake ecosystems.

Ecosystem-scale primary production may be proximately limited by nitrogen (N) but ultimately limited by phosphorus (P) because N fixation contributes new N that accumulates relative to P at ecosystem scales. However, the duration needed to transition between proximate N limitation and ultimate P limitation remains unknown for most ecosystems, including lakes. Here we present the results of a fully replicated, multi-annual lake mesocosm experiment that permitted full air-water-sediment interactions that mimicked lake ecosystem ecology.

International Validation of a Novel PEACE Scale to Improve the Quality of Upper Gastrointestinal Mucosal Inspection During Endoscopy.

Introduction: The performance of a high quality esophagogastroduodenoscopy (EGD) is dependent on the mucosal cleanliness. Recently, the Polprep: Effective Assessment of Cleanliness in EGD (PEACE) scale was created to assess the degree of mucosal cleanliness during EGD. The aim of this study was to validate this scoring system in a cohort of international endoscopists.

A phase 2 basket study of talabostat, a small-molecule inhibitor of dipeptidyl peptidases, administered in combination with pembrolizumab in patients with advanced solid cancers.

Background: Talabostat, an oral small molecule inhibitor of dipeptidyl peptidases (DPP4 and DPP8/9), has shown synergistic activity with immune checkpoint inhibitors in preclinical studies. This open label, phase 2 basket trial assessed the antitumor activity of combining talabostat and pembrolizumab (anti-programmed death-1 antibody) in advanced solid tumor patients.

Methods: The primary objective was assessment of dose-limiting toxicity (DLT) rates in the first six patients (lead-in stage) and response rate (efficacy stage; included cohort A [checkpoint inhibitor (ICI) naive] and cohort B [ICI pretreated]) for the study treatment using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.

An Insect Effector Mimics Its Host Immune Regulator to Undermine Plant Immunity.

Plants activate defense machinery when infested by herbivorous insects but avoid such costs in the absence of herbivory. However, the key signaling pathway regulators underlying such flexibility and the mechanisms that insects exploit these components to disarm plant defense systems remain elusive. Here, it is reported that immune repressor 14-3-3e in rice Oryza sativa (OsGF14e) regulates immune homeostasis.

The MASCC COG-IMPACT: An unmet needs assessment for cancer-related cognitive impairment impact developed by the Multinational Association of Supportive Care in Cancer.

Purpose: Cancer-related cognitive impairment (CRCI) can have a profound impact on the lives of cancer survivors. A multitude of subjective and objective assessment tools exist to assess the presence and severity of CRCI. However, no purpose-built tool exists to assess the unmet needs of cancer survivors directly relating to CRCI.

The family medicine accelerated track at Texas Tech University Health Sciences Center: results from a 10-year program to bend the primary care curve.

Background: Texas is one of the states with the lowest access to usual sources of primary care; most critically, family medicine (FM) has been projected to have the greatest physician shortage increase between 2018 and 2032. Texas Tech University Health Sciences Center (TTUHSC) School of Medicine developed the Family Medicine Accelerated Track (FMAT), a 3-year curriculum that culminates in the MD degree and links medical students to FM residency programs at TTUHSC campuses in Lubbock, Amarillo or the Permian Basin. This article reflects on 10 years of experience with the program, and particularly its impact on the primary care physician workforce in Texas.

Nitric oxide transfer between nominal Fe and Co biomimetics of the nitrile hydratase active site.

Related to the inactive form of nitrile hydratase, NHase, that contains Fe(NO) within tripeptide NS binding environment, the NO transfer reactivity of (bis-mercaptoethane diazacycloheptane)Fe(NO) and (bis-mercaptoethane diazadimethylethane)Fe(NO) is compared to Co(NO) analogs. Acceptors of NO include cobalt octaethylporphyrin and the [(NS)M] dimeric precursors in the synthesis of the Fe(NO) and Co(NO) biomimetics. Qualitative rates are augmented by a definitive kinetic study finding that rates of NO transfer from (NS)M(NO) to [(NS)M'] are dependent on M and M' as well as the hydrocarbon N to N and N to S linkers.

Design, Synthesis, and Biological Evaluation of Thieno[3,2-]pyrimidine Derivatives as the First Bifunctional PI3Kδ Isoform Selective/Bromodomain and Extra-Terminal Inhibitors.

The concomitant inhibition of PI3Kδ and bromodomain and extra-terminal (BET) that exerts a synergistic effect on the B-cell receptor signaling pathway provides a new strategy for the treatment of aggressive diffuse large B-cell lymphoma (DLBCL). Herein, a merged pharmacophore strategy was utilized to discover a series of thieno[3,2-]pyrimidine derivatives as the first-in-class bifunctional PI3Kδ-BET inhibitors. Through optimization, a highly potent compound () was identified to possess excellent and balanced activities against PI3Kδ [inhibitory concentration (IC) = 112 ± 8 nM] and BRD4-BD1 (IC = 19 ± 1 nM) and exhibited strong antiproliferative activities in DLBCL cells.

Clinical use of measurable residual disease in adult ALL: recommendations from a panel of U.S. experts.

Measurable residual disease (MRD) is a powerful predictor of clinical outcomes in acute lymphoblastic leukemia (ALL). In addition to its clear prognostic importance, MRD information is increasingly used in clinical decision algorithms to guide therapeutic interventions. While it is well-established that achievement of MRD-negative remission is an important endpoint of ALL therapy, the prognostic and therapeutic implications of MRD in an individual patient are influenced by both disease-related factors (e.

Radical -Adenosylmethionine Sulfurtransferase MybB Catalyzed Formation of the 4-Thiazolidinone Core in Mycobacidin Represents an Intersection between Primary and Secondary Metabolism.

Mycobacidin is an antitubercular antibiotic structurally composed of a sulfur-containing 4-thiazolidinone ring, yet its biosynthesis including the mechanism of sulfur incorporation has remained an open question since its discovery in 1952. In this study, the mycobacidin biosynthetic gene cluster is identified from soil-dwelling , and the corresponding biosynthetic pathway starting with 7-oxoheptanoate is characterized. The radical SAM enzyme MybB catalyzes two sulfur insertion reactions, thereby bridging C and C to complete the 4-thiazolidinone heterocycle as the final step in mycobacidin maturation.

Cutaneous dysbiosis characterizes the post-allogeneic hematopoietic stem cell transplantation period.

Gut dysbiosis is linked to mortality and the development of graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT), but the impact of cutaneous dysbiosis remains unexplored. We performed a pilot observational study and obtained retroauricular and forearm skin swabs from 12 adult patients prior to conditioning chemotherapy/radiation, and at 1-week, 1-month and 3-months after allogeneic HSCT, and performed shotgun metagenomic sequencing. The cutaneous microbiome among HSCT patients was enriched for gram-negative bacteria such as E coli and Pseudomonas, fungi, and viruses.

TP53 Mutant Variant Allele Frequency and Cytogenetics Determine Prognostic Groups in MDS/AML for Transplantation.

Results following hematopoietic stem cell transplantation (HSCT) for TP53-mutated myeloid malignancies are disappointing. Several HSCT centers decline to perform HSCT for patients with TP53 mutation because of poor outcomes. In this study, we analyzed 240 patients with TP53-mutated myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) that underwent HSCT.

Accumulation of CD38 in Hybrid Epithelial/Mesenchymal Cells Promotes Immune Remodeling and Metastasis in Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer. The epithelial-to-mesenchymal transition is a nonbinary process in the metastatic cascade that generates tumor cells with both epithelial and mesenchymal traits known as hybrid EM cells. Recent studies have elucidated the enhanced metastatic potential of cancers featuring the hybrid EM phenotype, highlighting the need to uncover molecular drivers and targetable vulnerabilities of the hybrid EM state.

Prenatal Lipopolysaccharide Stimulation Modulates Gastrointestinal Immunity and Oxidative Status in Weaned Pigs.

Gastrointestinal immunity and antioxidant defenses may be bolstered in young animals through prenatal immune system stimulation (PIS), but this is largely uninvestigated in swine. This study tested the hypothesis that PIS could regulate offspring's gastrointestinal immune response and oxidative stress profile. To this end, a PIS model was utilized in sows, delivering low-dose LPS during the final third of gestation to target the developing immune system.

Effects of a New Enzymatic Debrider (SN514-066b) on Eschar Protein Digestion, Burn Wound Debridement, and Healthy Skin Irritation.

SN514 is a thermolysin-like enzyme under development as a debrider. Preclinical and non-clinical studies supported a first in human healthy volunteer study to predict the need for protection of periwound skin. Pharmacologic activity testing compared digestion of collagen, fibrin, and elastin with relevant enzymes.

Long-Term Family Needs After a Traumatic Brain Injury: A VA TBI Model Systems Study.

Objective: To describe the self-reported needs of family caregivers of service members and veterans (SMVs) with traumatic brain injury (TBI) at 10 to 15 years post-injury and to identify unique predictors of unmet family needs.

Setting: Five Department of Veterans Affairs Polytrauma Rehabilitation Centers.

Participants: A total of 209 family caregivers of SMVs with TBI from the VA TBI Model Systems national database who completed a 10- or 15-year follow-up assessment.

The role of Iowa gambling task performance in response to citalopram treatment for cocaine use disorder.

Cocaine use disorder (CUD) is associated with executive functioning impairments linked to serotonergic function. Previous studies reported efficacy with the selective serotonin reuptake inhibitor citalopram in reducing cocaine use. The current study explored moderation and mediation of citalopram effects on cocaine use by performance across executive function domains.

Non-invasive ventilation as a pre-oxygenation strategy during in-flight rapid sequence intubation: A case report.

Non-invasive ventilation has been used as a pre-oxygenation strategy for rapid sequence intubation in the emergency department and the intensive care unit, yet, limited research has examined its use in the transport setting. These case reports discuss the use of non-invasive ventilation via a Hamilton T1 ventilator (Hamilton Medical) during transport by an air medical crew for pre-oxygenation before intubation in two cases. In both cases, a non-invasive, bilevel-positive airway pressure mode with a backup rate was used to achieve adequate airway pressures while allowing for a two-handed seal by one EMS clinician as the other prepared the equipment and medications.

Development and Pilot Implementation of a Theory-Based Cognitive Rehabilitation Protocol for Adults With Chronic Cognitive Complaints After Mild Traumatic Brain Injury.

Purpose: The aim of this study was to describe the development of and pilot feasibility outcomes for a strategy-based, brief, intensive cognitive rehabilitation intervention delivered to U.S. service members and veterans with mild traumatic brain injury in a recently completed 3-year pragmatic clinical trial: Symptom-Targeted Approach to Rehabilitation for Concussion (STAR-C).