Navigating uncertainty: exploring parents' knowledge of concussion management and neuropsychological baseline testing.

Introduction: Parents play an important role in preventing and managing sport-related concussions among youth sport participants. Research indicates that parents understand the severity and consequences associated with the injury but gaps exist in their knowledge of its management. Neuropsychological baseline testing (NBT) is a modality that has gained interest in youth sport to purportedly better manage concussion injuries.

Targeting TGFβR2-mutant tumors exposes vulnerabilities to stromal TGFβ blockade in pancreatic cancer.

TGFβ is important during pancreatic ductal adenocarcinoma (PDA) progression. Canonical TGFβ signaling suppresses epithelial pancreatic cancer cell proliferation; as a result, inhibiting TGFβ has not been successful in PDA. In contrast, we demonstrate that inhibition of stromal TGFβR2 reduces IL-6 production from cancer-associated fibroblasts, resulting in a reduction of STAT3 activation in tumor cells and reversion of the immunosuppressive landscape.

Inhibition of Discoidin Domain Receptor 1 Reduces Collagen-mediated Tumorigenicity in Pancreatic Ductal Adenocarcinoma.

The extracellular matrix (ECM), a principal component of pancreatic ductal adenocarcinoma (PDA), is rich in fibrillar collagens that facilitate tumor cell survival and chemoresistance. Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that specifically binds fibrillar collagens and has been implicated in promoting cell proliferation, migration, adhesion, ECM remodeling, and response to growth factors. We found that collagen-induced activation of DDR1 stimulated protumorigenic signaling through protein tyrosine kinase 2 (PYK2) and pseudopodium-enriched atypical kinase 1 (PEAK1) in pancreatic cancer cells.

Hypoxia and Transforming Growth Factor β Cooperate to Induce Fibulin-5 Expression in Pancreatic Cancer.

The deposition of extracellular matrix (ECM) is a defining feature of pancreatic ductal adenocarcinoma (PDA), where ECM signaling can promote cancer cell survival and epithelial plasticity programs. However, ECM signaling can also limit PDA tumor growth by producing cytotoxic levels of reactive oxygen species. For example, excess fibronectin stimulation of α5β1 integrin on stromal cells in PDA results in reduced angiogenesis and increased tumor cell apoptosis because of oxidative stress.

Stromal TGFβR2 signaling: a gateway to progression for pancreatic cancer.

The function of transforming growth factor β (TGFβ) in the progression of pancreatic ductal adenocarcinoma (PDA) is complex and therapeutic targeting of this pathway is challenging. We showed that antibody-mediated inhibition of stromal Tgfβr2 prevented or reversed epithelial plasticity resulting in a potent reduction of metastasis in xenograft models of PDA.

Neutralizing murine TGFβR2 promotes a differentiated tumor cell phenotype and inhibits pancreatic cancer metastasis.

Elevated levels of TGFβ are a negative prognostic indicator for patients diagnosed with pancreatic cancer; as a result, the TGFβ pathway is an attractive target for therapy. However, clinical application of pharmacologic inhibition of TGFβ remains challenging because TGFβ has tumor suppressor functions in many epithelial malignancies, including pancreatic cancer. In fact, direct neutralization of TGFβ promotes tumor progression of genetic murine models of pancreatic cancer.

Detection of sulfur mustard-induced DNA modifications.

Sulfur mustard is acutely toxic to the skin, eyes, and respiratory tract, and is considered carcinogenic to humans by the IARC. Since all of these toxicities are thought to be initiated by DNA alkylation, the level of DNA damage should serve as a biomarker for exposure. To develop methods of detecting this damage, DNA was modified by [14C]-labeled sulfur mustard and DNA adducts were released by mild acid hydrolysis.

Thirteen-week toxicology studies of 1-amino-2,4-dibromoanthraquinone in Fischer 344/N rats and B6C3F1 mice.

1-Amino-2,4-dibromoanthraquinone (ADBAQ), an intermediate in the production of commercial dyes for wool, silk, and synthetic fibers, was selected for toxicology and carcinogenesis studies in two rodent species. In advance of the 2-year studies, 13-week studies were conducted in male and female F344/N rats and B6C3F1 mice which were fed a diet containing ADBAQ at concentrations of 0, 0.25, 0.

Analysis of chlorthalidone in biological fluids by high-performance liquid chromatography using a rapid column cleanup procedure.

A high-performance liquid chromatographic assay usable for clinical monitoring of chlorthalidone in biological fluids was developed. Extraction efficiency was greater than 80% for blood and urine using a rapid, disposable column cleanup procedure. Chlorthalidone could be reliably measured in the range of 100-4,000 ng/ml in biological fluids with excellent day-to-day reproducibility and within-day precision.

The microscopic distribution of tetracycline in human teeth.

The distribution of tetracycline fluorescence was studied in a random collection of 378 teeth extracted in 1976 in Farmington, Connecticut, using ultra-violet microscopy of longitudinal ground sections. The sample consisted of 4 deciduous molars and the following numbers of permanent teeth: 72 incisors, 41 canines, 63 premolars, 26 first molars, 24 second molars, and 148 third molars. Narrow fluorescent lines reflecting short regimens of drug administration and broad bands corresponding to long term administration were identified in the dentin and tabulated in relation to their anatomical position.

Uptake and secretion of carcinogenic chemicals by the dog and rat prostate.

Because the prostate of laboratory animals seems relatively resistant to the carcinogenic effects of systematically administered chemicals--an observation of some significance in attempts to establish the etiology of human prostatic adenocarcinoma and to produce animal models of prostatic cancer--we studied the penetration of eight carcinogenic chemicals into both the prostate gland and the prostatic secretion of the dog and the rat. The eight chemicals were 3-methylcholanthrene, 7,12-dimethylbenz[a]anthracene, N-hydroxyurethane, aflatoxin B1, 3-amino-1,2,4-triazole, 2-acetylaminofluorene, N-Methyl-N'-nitro-N-nitrosoguanidine, and cadmium. In both species all eight substances and/or their metabolites were found to rapidly enter the prostate, and all except cadmium were recovered from prostatic fluid.

Carcinogenesis bioassay of acetamide, hexanamide, adipamide, urea and P-tolylurea in mice and rats.

As a part of the National Cancer Institute's effort to screen environmental and occupational chemicals for chronic toxicity and carcinogenicity, the amides acetamide, hexanamide, adipamide, urea, and p-tolylurea were fed to male and female C57B1/6 mice and Fischer 344 rats from 12 months. Rats received the following concentrations of compounds in their diets: acetamide, 2.36%; hexanamide, 1.

Carcinogenicity of 4-chloro-o-phenylenediamine, 4-chloro-m-phenylenediamine, and 2-chloro-p-phenylenediamine in Fischer 344 rats and B6C3F1 mice.

In both male and female Fischer rats, feeding 4-chloro-o-phenylenediamine at 0.5 or 1% in the diet led to a significant increase in hyperplasia, papilloma and carcinoma of the urinary bladder. Neoplastic nodules of the liver and squamous cell papillomas of the stomach were also increased slight.

Hemangioendothelial sarcoma of penis.

Hemangioendothelial sarcoma of the penis in a 44-year-old man was treated by preoperative radiation, penectomy, and chemotherapy. The patient was free of evident disease 2 years later. Electronmicroscopy showed differentiated vascular structures at the periphery of the lesion and anaplastic cells throughout the remainder of the tumor.

The uptake and secretion of 3-methylcholanthrene by the prostate glands of the rat and dog.

In anesthetized rats in which prostatic fluid was collected over a 2-hour interval from 24 to 26 hours after a single ip dose of 5 mg [6-14C]3-methylcholanthrene ([14C]MCA)/kg, radioactivity was found in the fluid at levels only slightly less than those in plasma; at 26 hours after treatment, levels of radioactivity within the prostate were higher than those in prostatic fluid or plasma. When unanesthetized dogs with surgically prepared prostatic fistulas were given a single ip dose of 0.5 mg [14C]MCA/kg and when serial prostatic fluid and plasma samples were collected over the ensuing 50 hours (2 dogs) or 212 hours (1 dog), radioactivity appeared in the prostatic fluid at levels initially greater than those in plasma and then fell progressively with time to less than those of plasma.

Lipid droplet accumulation in cardiac muscle cells of the bat: potential auto-toxicity of the cardiac sympathetic innervation.

The previously described ability of reserpine and parachlorophenylalanine to induce the accumulation of lipid droplets in ventricular cardiac muscle cells of the bat was investigated. Lipid droplet accumulation was assessed qualitatively by light microscopy and quantitatively by morphometric analysis of electron micrographs. An hypothesis that the action of the drugs was an indirect one, mediated by the cardiac adrenergic innervation, was framed and tested.

An electron microscope autoradiographic study of the neuronal and extraneuronal localization of labeled amine in the heart of the bat after administration of tritiated norepinephrine.

The localization of labeled amine in the heart of the bat after administration of tritiated norepinephrine (NE) was studied by means of electron microscope autoradiography. Monoamine oxidase was inhibited so that the distribution of amine in both neuronal (Uptake(1)) and extraneuronal (Uptake(2)) sites could be analyzed. Labeling was nonrandom in both the atrial and ventricular myocardium.