Docking and structure activity relationship studies of potent and selective thiazolidinethione GSK-3 inhibitors.

Glycogen synthase kinase-3 (GSK-3) plays a key role in several biochemical pathways and is an attractive target for pharmacological intervention. We prepared a series of analogs of a highly selective thiazolidinethione inhibitor of GSK-3. The structure-activity relationship indicated a precise structural requirement for potent inhibition.

Lumpfish, , distribution in the Gulf of Maine, USA: observations from fisheries independent and dependent catch data.

The Gulf of Maine (GoM) is one of the fastest-warming parts of the world's oceans. Some species' distributional shifts have already been documented, especially for commercially-important species. Less is known about species that are not currently exploited but may become so in the future.

Fine-scale environmentally associated spatial structure of lumpfish () across the Northwest Atlantic.

Lumpfish, , have historically been harvested throughout Atlantic Canada and are increasingly in demand as a solution to controlling sea lice in Atlantic salmon farms-a process which involves both the domestication and the transfer of lumpfish between geographic regions. At present, little is known regarding population structure and diversity of wild lumpfish in Atlantic Canada, limiting attempts to assess the potential impacts of escaped lumpfish individuals from salmon pens on currently at-risk wild populations. Here, we characterize the spatial population structure and genomic-environmental associations of wild populations of lumpfish throughout the Northwest Atlantic using both 70K SNP array data and whole-genome re-sequencing data (WGS).

Do Organizational Values and Leadership Impact Staff Engagement, Wellbeing, and Patient Satisfaction?

Purpose: Organizational culture has been shown to be an important characteristic that influences behaviors of groups and individuals within an organization. This study seeks to examine the relationships among various organizational values, staff engagement, staff wellbeing, and patient satisfaction in community hospitals.

Participants And Methods: Organizational values and engagement data were retrieved from all-staff survey results from 387 clinical units at Mayo Clinic Health Systems.

Perinatal outcomes of young adolescent pregnancies in an urban inner city.

Background: Although substantial efforts have been made to reduce the rates of adolescent pregnancy, the United States continues to have higher rates than other industrialized countries. Research and reporting usually focus on adolescents aged 15 to 19 years. Although less common, there are pregnant young adolescents that are ≤15 years of age, with developmental and social differences from older, high school-aged adolescents.

Prenatal Considerations and Outcomes for Girls Aged 14 and Under: Development of a Multidisciplinary Team in a Large Tertiary Care Facility.

Introduction: Adolescent girls account for 11% of all births that occur globally every year. Among developing countries, the United States continues to have one of the highest adolescent birth rates, despite a decreasing trend between 1990 and 2010. Pregnant adolescents are a vulnerable population who are at increased risk for maternal morbidity and mortality.

The lay of the land: What we know about non-operating agricultural and absentee forest landowners in the U.S. and Europe.

While non-operating agricultural and absentee forest landowners across the U.S. and Europe are an important group of landowners, our understanding of them remains relatively limited.

University Title IX Requirements have Chilling Effect on Gender Discrimination Research: A Call for a More Nuanced Approach.

The full extent of gender discrimination in university settings remains uncertain. More research is needed to understand the scope of gender discrimination experiences in universities and to develop effective prevention approaches. However, Title IX and Institutional Review Board policies may hinder researchers' abilities to study gender discrimination in university settings.

RNA sequence and ligand binding alter conformational profile of SARS-CoV-2 stem loop II motif.

Antiviral drug discovery continues to be an essential complement to vaccine development for overcoming the global pandemic caused by SARS-CoV-2. The genomic RNA of SARS-CoV-2 contains structural elements important for viral replication and/or pathogenesis making them potential therapeutic targets. Here we report on the stem-loop II motif, a highly conserved noncoding RNA element.

Relationships Among Organizational Values, Employee Engagement, and Patient Satisfaction in an Academic Medical Center.

Objective: To examine the relationships among various organizational values, employee engagement, and patient satisfaction in an academic medical center.

Participants And Methods: Organizational values and engagement data were retrieved from 2015 all-staff survey results from 1876 clinical units at Mayo Clinic. For patient satisfaction data, Press Ganey scores from visits from July 1, 2015, through January 1, 2016, were matched with data for 26 outpatient units from the all-staff survey.

Consumer-resource dynamics is an eco-evolutionary process in a natural plankton community.

When traits affecting species interactions evolve rapidly, ecological dynamics can be altered while they occur. These eco-evolutionary dynamics have been documented repeatedly in laboratory and mesocosm experiments. We show here that they are also important for understanding community functioning in a natural ecosystem.

Implementation of Robert's Coping with Labor Algorithm in a large tertiary care facility.

Objective: to implement use of Roberts' Coping with Labor Algorithm (CWLA) with laboring women in a large tertiary care facility.

Design: this was a quality improvement project to implement an alternate approach to pain assessment during labor. It included system assessment for change readiness, implementation of the algorithm across a 6-week period, evaluation of usefulness by nursing staff, and determination of sustained change at one month.

The Raf Kinase Inhibitor Sorafenib Inhibits JAK-STAT Signal Transduction in Human Immune Cells.

Sorafenib is an oral multikinase inhibitor that was originally developed as a Raf kinase inhibitor. We hypothesized that sorafenib would also have inhibitory effects on cytokine signaling pathways in immune cells. PBMCs from normal donors were treated with varying concentrations of sorafenib and stimulated with IFN-α or IL-2.

Cross-Site Scheduling of Endoscopic Procedures Improves Efficiency While Maintaining Patient Safety.

Background And Aim: Accuracy in scheduling complex procedures is improved through technology to aid nonmedically trained allied health professionals. We used a new computer technology to assess whether a single coordinator could schedule endoscopic procedures across sites of a multisite academic medical institution, thus improving efficiency within the clinic overall.

Methods: A multidisciplinary team designed a cross-site scheduling model.

MiR-21 enhances melanoma invasiveness via inhibition of tissue inhibitor of metalloproteinases 3 expression: in vivo effects of MiR-21 inhibitor.

Metastatic melanoma is the most aggressive form of this cancer. It is important to understand factors that increase or decrease metastatic activity in order to more effectively research and implement treatments for melanoma. Increased cell invasion through the extracellular matrix is required for metastasis and is enhanced by matrix metalloproteinases (MMPs).

miR-21 and miR-155 are associated with mitotic activity and lesion depth of borderline melanocytic lesions.

Background: Expression of microRNAs (miRs) has been shown to be altered in many solid tumours and is being explored in melanoma. The malignant potential of some melanocytic lesions is difficult to predict. We hypothesised that characterisation of miR expression in borderline melanocytic proliferations would lead to the identification of a molecular profile that could be used with known prognostic factors to differentiate lesions with high malignant potential.

Shiftwork and industrial injuries at a chemical plant in southeast Texas.

A historical retrospective study of 242 shiftworker (SW) and 224 non-SW (NSW) injuries at a chemical manufacturing plant in southeast Texas (U.S.A.

The influence of inhaled formaldehyde on rat lung cytochrome P450.

The effect of formaldehyde (HCHO) inhalation on total cytochrome P450 in the lungs of Sprague-Dawley rats was assessed after single and repeated exposures to 0, 0.5, 3, and 15 ppm HCHO. Whole-body exposures were conducted in dynamic, monitored exposure systems for 6 hr/day, 5 days/week, for periods of exposure of 1 day, 4 days, 12 weeks, or 24 weeks.

The mutagenicity of urine fractions from patients administered antineoplastic therapy.

A concern among hospital personnel is their exposure to mutagenic drugs and in the incidental exposures that could occur in caring for the patients. In a recent published study the mutagenicity of urine from patients administered antineoplastic drugs was determined and techniques were developed to chemically inactivate the mutagenicity. A question still remained as to what components of the excreted urine were mutagenic.

Distribution of DNA and RNA content in the bone marrow and alveolar macrophages of rats after subchronic inhalation of formaldehyde.

The technique of flow cytometry was used to monitor the cell-cycle distribution of DNA and RNA in selected tissues of rats that were subchronically exposed to formaldehyde (HCHO) inhalation. Male Sprague-Dawley rats inhaled HCHO vapor concentrations of 0, 0.5, 3, or 15 ppm for 6 hr/day, 5 days/week, for up to 24 weeks.

Induction of metallothionein synthesis in human peripheral blood leukocytes.

Metallothionein (MT), a low molecular weight, metal-binding protein, has recently been shown to protect murine mononuclear phagocytic cells from the cytotoxic effects of bacterial lipopolysaccharides (LPS), the endotoxic component of Enterobacteriaceae. MT appears to function intracellularly as an antioxidant since autolysis results from lipid peroxidation initiated by free radicals of O2. Since this activity is distinct from MT's capacity to specifically sequestrate heavy metals, we examined whether MT synthesis can be induced by direct membrane activation or through interaction with soluble leukocyte mediators.

Toxicologic interactions between ozone and bacterial endotoxin.

The effects of acute exposure of mice to bacterial lipopolysaccharide (LPS), the endotoxin of gram negative microorganisms, and ozone (O3) have been investigated. Intraperitoneal (ip) administration of 5 mg/kg LPS to CD-1 mice followed by exposure to 15 ppm O3 for 1.5 hr produced synergistic effects as measured by pulmonary edemagenesis and lethality assays.

Stability and inactivation of mutagenic drugs and their metabolites in the urine of patients administered antineoplastic therapy.

Urine samples from patients administered mutagenic antineoplastic drugs are mutagenic in the Ames assay, and hence may pose a genotoxic hazard to hospital personnel or family members caring for the patient. The urine samples in the present study were tested for mutagenicity in several strains of Salmonella typhimurium that were uvr negative (TA98, TA100) or positive (TA102, UTH8413, UTH8414), and were analyzed for the presence of drugs and their metabolites using high-pressure liquid chromatography (HPLC). Urine samples from cancer patients were kept at room temperature and their mutagenicity as well as the chemical stability of the drugs was tested for a period of 14 days.

Respiratory responses in the lower respiratory tract of Sprague-Dawley rats to formaldehyde inhalation.

This study was conducted to determine the characteristic response of Sprague-Dawley rats to formaldehyde (HCHO) challenges to the lower respiratory tract, and whether these response patterns are altered in rats that have received repeated exposures to HCHO. Male Sprague-Dawley rats were exposed to 0, 0.5, or 15 ppm HCHO for 6 hours/day, 5 days/week, for 8 or 16 weeks.