A Flexible, Pooled CRISPR Library for Drug Development Screens.

Functional genomic screening with CRISPR has provided a powerful and precise new way to interrogate the phenotypic consequences of gene manipulation in high-throughput, unbiased analyses. However, some experimental paradigms prove especially challenging and require carefully and appropriately adapted screening approaches. In particular, negative selection (or sensitivity) screening, often the most experimentally desirable modality of screening, has remained a challenge in drug discovery.

Equine renal hemangiosarcoma: clinical presentation, pathologic features, and pSTAT3 expression.

Hemangiosarcoma is an uncommon tumor in horses. We characterized 3 cases of equine renal hemangiosarcoma, focusing on clinical and pathologic features, and describe occurrence of the epithelioid variant of hemangiosarcoma in one of these cases. Nuclear expression of phosphorylated STAT3 (pSTAT3) was assessed to analyze potential inappropriate STAT3 activation as a component of tumor pathogenesis.

Stat3 modulates chloride channel accessory protein expression in normal and neoplastic mammary tissue.

Mammary gland regression at the cessation of lactation (involution) is an exquisitely orchestrated process of cell death and tissue remodelling in which Stat3 signalling has an essential role. The involution microenvironment of the mammary gland is considered to be pro-tumourigenic and a proportion of cases of pregnancy-associated breast cancer are suggested to originate in tandem with involution. However, the apparent paradox that STAT3 is required for cell death in normal mammary gland, but is associated with breast cancer cell survival, has not been resolved.

Percutaneous penetration and absorption of parathion using human and pig skin models in vitro and human skin grafted onto nude mouse skin model in vivo.

This study determined and compared the percutaneous penetration and absorption of an organophosphorus (OP) pesticide, parathion (PA), using three experimental skin models: namely the human abdominal- and pig-ear skin in vitro models and the Human Skin grafted onto a nude mouse (HuSki) in vivo model. The percentage of topically applied dose absorbed and the doses present in the stratum corneum and skin were systematically determined at 24 h under similar experimental conditions. The three experimental skin models were first compared.

Evaluation of the plaque removal efficacy of two commercially available dental floss devices.

Objective: This single blind, crossover design, clinical trial provided a comparative assessment of the oral cleaning of two dental devices as demonstrated through the removal of dental plaque when used according to marketed product-use directions.

Methodology: Twenty-six subjects, both male and female between the ages of 19 and 64 years, completed this two-cell crossover study. Subjects were assessed for whole mouth plaque levels, both before and after use of each of the randomly assigned floss devices, by assessing disclosed plaque using the Modified Turesky Plaque Index.

[Functional amblyopia: a functional MRI evaluation of the visual cortex response after treatment].

Purpose: Functional MRI evaluation of the cortical response in treated amblyopic patients.

Material And Methods: Clinical and functional MRI exploration of ten patients, seven men and three women aged from 21 to 59 years, with strabismus management during childhood. Functional evaluations were performed on a 1.

Clinical evaluation of a novel whitening gel, containing 6% hydrogen peroxide and a standard fluoride toothpaste.

Objectives: The aim of this study was to determine the effect on tooth colour (after 1 and 2 weeks use) of a self-applied tooth-whitening gel containing 6% hydrogen peroxide using a novel applicator, compared to a standard fluoride toothpaste.

Methods: A 2-week, examiner-blind, stratified, parallel design clinical trial was conducted. Efficacy was measured by comparing the Vita shade scores recorded at baseline and after 1 and 2 weeks of product application.

[Difficulties in the surgical treatment of hyperthyroid myopathy].

Surgery can help patients affected with Graves' myositis. This surgery is very delicate because it is performed on muscles modified with retractile sclerosis transforming muscular fibers into fibrous and rigid strings. The surgical treatment must be decided with endocrinologists.

[Oculocerebral anomalies in Walker's lissencephaly].

Two new cases of Walker's lissencephaly are reported. In this disease first described by Walker in 1942 important cerebral malformations and various ocular anomalies are associated. The main cerebral malformations consist of hydrocephalus and agyria, and the ocular anomalies concern the anterior segment as well as the retina which is frequently dysplastic.

[Electroretinography in nephronophthisis. Role of the Senior-Loken syndrome].

The authors report 20 cases of a syndrome named nephronophtisis and probably the same as the syndrome of medullar cystic disease. In all cases systematic electroretinography is performed. Nine cases show important deterioration of the outline.

Absorption, distribution and excretion of terephthalic acid and dimethyl terephthalate.

Data from a radiotracer study in rabbits and rats to determine the absorption, distribution, and excretion of terephthalic acid (TA) and dimethyl terephthalate (DMT) following oral, intratracheal, dermal and ocular administration indicate the following: (1) a rapid absorption and excretion of 14C-TA and 14C-DMT with no evidence of tissue accumulation in rats following single or repeated oral and intratracheal administration; (2) no evidence of skin irritation in rats after a single or repeated dermal application of 80 mg of 14C-TA or 14C-DMT and no significant skin absorption of 14C-TA; (3) recovery of approximately 11% of a single dose and 13% of five repeated cutaneous doses of 14C-DMT from the urine and feces of rats within 10 days after initial dosing; (4) no significant absorption of 14C-TA when applied to the conjunctival sac of one eye of eight rabbits; (5) excretion of approximately 33% of a single ocular dose (50 mg) of 14C-DMT in the urine and feces of rabbits within 10 days after instillation with no evidence of tissue accumulation or ocular damage. These results suggest that TA and DMT are rapidly absorbed and excreted and that no significant quantities of these compounds accumulate in the tissues following single or repeated oral, intratracheal, dermal, or ocular administration to laboratory animals.