Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection.

Genome-sequence-based newborn screening (gNBS) has substantial potential to improve outcomes in hundreds of severe childhood genetic disorders (SCGDs). However, a major impediment to gNBS is imprecision due to variants classified as pathogenic (P) or likely pathogenic (LP) that are not SCGD causal. gNBS with 53,855 P/LP variants, 342 genes, 412 SCGDs, and 1,603 therapies was positive in 74% of UK Biobank (UKB470K) adults, suggesting 97% false positives.

First Report of Downy Mildew caused by on in New York.

Hemp ( <0.3% tetrahydrocannabinol) is an emerging crop used for grain, fiber, and cannabinoid production (Fike et al. 2020).

A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases.

Newborn screening (NBS) dramatically improves outcomes in severe childhood disorders by treatment before symptom onset. In many genetic diseases, however, outcomes remain poor because NBS has lagged behind drug development. Rapid whole-genome sequencing (rWGS) is attractive for comprehensive NBS because it concomitantly examines almost all genetic diseases and is gaining acceptance for genetic disease diagnosis in ill newborns.

Bisphenol A: Update on newly developed data and how they address NTP's 2008 finding of "Some Concern".

Bisphenol A (BPA) is a component of polycarbonate plastics and epoxy resins used in many commercial products including coatings and liners of food containers. Low levels of BPA can be detected in over 90% of human urine samples in the US, indicating that exposure to BPA is widespread. In 2008, the US National Toxicology Program's Center for the Evaluation of Risks to Human Reproduction (NTP-CERHR) expressed concerns regarding BPA's potential health effects, and suggested improved study designs and methodologies that they believed would address those concerns.

Dermatological toxicity of hexavalent chromium.

Hexavalent chromium causes two types of dermatological toxicities: allergic contact dermatitis (ACD) and skin ulcers. This report reviews the etiology, prevalence, pathology, dose-response, and prognosis of both of these reactions. Reports in the literature indicate that repeated exposure to hexavalent chromium in concentrations of 4-25 ppm can both induce sensitization and elicit chromium ACD.

Pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein in men and women after consumption of a soy beverage.

Background: The soy isoflavones genistein and daidzein are found in blood and tissues as aglycones, glucuronides, and sulfates. Isoflavone conjugates may serve as sources of aglycones at specific target tissues and may have bioactivity. Yet, very little is known about the plasma pharmacokinetics of isoflavone conjugates after soy ingestion.

Urinary pharmacokinetics of the glucuronide and sulfate conjugates of genistein and daidzein.

Consumption of soybean-rich diets is thought to provide significant health benefits such as prevention of cancer, primarily because of the high contents of factors such as the isoflavones genistein and daidzein. Isoflavones circulate and are excreted into the urine mainly as glucuronide and sulfate conjugates. This study was conducted to determine the urinary pharmacokinetics of sulfate and glucuronide conjugates of genistein and daidzein.

Diets containing whey proteins or soy protein isolate protect against 7,12-dimethylbenz(a)anthracene-induced mammary tumors in female rats.

A study was conducted to determine the protective effects of two common dietary proteins, soy protein isolate (soy) and bovine whey, against chemically induced mammary tumors in female Sprague Dawley rats. Rats were fed AIN-93G diets having casein, soy, or whey as the sole protein source. Rats within the same dietary groups were mated to obtain the F1 and F2 generations.

An LC-MS method to determine concentrations of isoflavones and their sulfate and glucuronide conjugates in urine.

Most methods for detecting isoflavones in biological samples do not measure the concentration of sulfate conjugates. An LC-MS method is reported here to estimate urinary concentrations of genistein and daidzein, their sulfate and glucuronide conjugates and other major metabolites. Human and rat urine samples were extracted with diethyl ether, or pre-digested with sulfatase and/or beta-glucuronidase followed by extraction.

Sexual dimorphism in phencyclidine in vitro metabolism and pharmacokinetics in rats.

Studies were conducted to determine the differences in phencyclidine (PCP) in vitro metabolism and pharmacokinetics in female and male Sprague-Dawley (SD) rats. Formation rates of five major PCP metabolites in liver microsomes were significantly higher (p <.05) in males compared with females in three different rat strains (SD, Fischer 344, and Dark Agouti).

Diet and risk of ethanol-induced hepatotoxicity: carbohydrate-fat relationships in rats.

Nutritional status is a primary factor in the effects of xenobiotics and may be an important consideration in development of safety standards and assessment of risk. One important xenobiotic consumed daily by millions of people worldwide is alcohol. Some adverse effects of ethanol, such as alcohol liver disease, have been linked to diet.

Phencyclidine continuous dosing produces a treatment time-dependent regulation of rat CYP2C11 function, protein expression and mRNA levels.

These studies determined the effects of continuous phencyclidine (PCP) administration on cytochrome P450 2C11 (CYP2C11) function, protein expression and mRNA levels. Male Sprague-Dawley rats received s.c.

Phencyclidine metabolite irreversible binding in the rat: gonadal steroid regulation and CYP2C11.

These studies were conducted to determine the effect of hormones on sex-related differences in phencyclidine (PCP) metabolite irreversible binding and to determine the cytochrome P450 isoform(s) involved in this process. Sprague-Dawley male rats were castrated or administered estradiol and Sprague-Dawley female rats were ovarectomized or ovarectomized and given testosterone. Liver microsomal metabolism studies demonstrated that PCP metabolite binding to proteins was significantly altered by testosterone and estrogen administration.

Effects of cocaine and ethylcocaine on schedule-controlled responding in rats.

The effects of cocaine and benzoylecognine ethyl ester (ethylcocaine), its metabolite found only in simultaneous users of cocaine and ethanol, were studied in rats responding for food under a multiple fixed-ratio fixed-interval schedule of food presentation. Both cocaine and ethylcocaine increased rates of responding under the fixed-interval component and decreased the quarter life. Both drugs only decreased rates of responding under the fixed-ratio component.