Integrating multiscale and machine learning approaches towards the SAMPL9 log challenge.

The partition coefficient (log ) is an important physicochemical property that provides information regarding a molecule's pharmacokinetics, toxicity, and bioavailability. Methods to accurately predict the partition coefficient have the potential to accelerate drug design. In an effort to test current methods and explore new computational techniques, the statistical assessment of the modeling of proteins and ligands (SAMPL) has established a blind prediction challenge.

Antimicrobial efficacy of aqueous ozone in combination with short chain fatty acid buffers.

Background: Mitigating surface contamination by microbes such as , , or , is an ongoing problem in hospital and food production environments.

Aim: To determine whether addition of buffering solution to source water used for manufacture of aqueous ozone increases ozone efficacy against ozone-resistant bacterial species.

Methods: Antimicrobial effects of aqueous ozone were studied in combination with acetate, propionate, or butyrate short chain fatty acids (SCFA) as well as citrate or oxalate buffer formulations against on glass coupons.

The Addition of Viriditec Aqueous Ozone to Peracetic Acid as an Antimicrobial Spray Increases Air Quality While Maintaining Typhimurium, Non-pathogenic , and Reduction on Whole Carcasses.

Currently, the most utilized antimicrobial in processing facilities is peracetic acid, PAA; however, this chemical is increasingly recognized as a hazard to human health. Preliminary evidence suggests that ozone, when introduced in a specific manner, can reduce the noxious nature of PAA. Therefore, the objective of the current study was to evaluate the efficacy of TetraClean Systems aqueous ozone, O, in combination with PAA as an antimicrobial spray on whole chicken carcasses.

Development of a new test cell to measure cumulative permeation of water-insoluble pesticides with low vapor pressure through protective clothing and glove materials.

A collaborative approach, involving resources and expertise from several countries, was used to develop a test cell to measure cumulative permeation by a solid-state collection technique. The new technique was developed to measure the permeation of pesticide active ingredients and other chemicals with low vapor pressure that would otherwise be difficult to test via standard techniques. The development process is described and the results from the final chosen test method are reported.

Mechanism of action of the novel aminomethylcycline antibiotic omadacycline.

Omadacycline is a novel first-in-class aminomethylcycline with potent activity against important skin and pneumonia pathogens, including community-acquired methicillin-resistant Staphylococcus aureus (MRSA), β-hemolytic streptococci, penicillin-resistant Streptococcus pneumoniae, Haemophilus influenzae, and Legionella. In this work, the mechanism of action for omadacycline was further elucidated using a variety of models. Functional assays demonstrated that omadacycline is active against strains expressing the two main forms of tetracycline resistance (efflux and ribosomal protection).

Diagnosing rupture of membranes using combination monoclonal/polyclonal immunologic protein detection.

Objective: To compare the accuracy of a new combination monoclonal/polyclonal immunoassay point-of-care test with that of current conventional clinical assessment for diagnosis of ruptured amniotic membranes.

Study Design: This was a multicenter prospective observational study performed in patients presenting with signs or symptoms of ruptured amniotic membranes. This clinical trial included 3 sites in the United States.

In vitro and in vivo antimalarial efficacies of optimized tetracyclines.

With increasing resistance to existing antimalarials, there is an urgent need to discover new drugs at affordable prices for countries in which malaria is endemic. One approach to the development of new antimalarial drugs is to improve upon existing antimalarial agents, such as the tetracyclines. Tetracyclines exhibit potent, albeit relatively slow, action against malaria parasites, and doxycycline is used for both treatment (with other agents) and prevention of malaria.

A randomized, evaluator-blind, phase 2 study comparing the safety and efficacy of omadacycline to those of linezolid for treatment of complicated skin and skin structure infections.

A randomized, investigator-blind, multicenter phase 2 trial involving patients with complicated skin and skin structure infections (cSSSI) compared the safety and efficacy of omadacycline, a broad-spectrum agent with activity against methicillin-resistant Staphylococcus aureus (MRSA), to those of linezolid (with or without aztreonam). Patients were randomized 1:1 to omadacycline (100 mg intravenously [i.v.

N-Hydroxybenzimidazole inhibitors of ExsA MAR transcription factor in Pseudomonas aeruginosa: In vitro anti-virulence activity and metabolic stability.

ExsA is a multiple adaptational response (MAR) transcription factor, regulating the expression of a virulence determinant, the type III secretion system (T3SS) in Pseudomonas aeruginosa. Non-cytotoxic, non-antibacterial N-hydroxybenzimidazoles were identified as effective inhibitors of ExsA-DNA binding, and their potential utility as anti-virulence agents for P. aeruginosa was demonstrated in a whole cell assay.

Tetracyclines that promote SMN2 exon 7 splicing as therapeutics for spinal muscular atrophy.

There is at present no cure or effective therapy for spinal muscular atrophy (SMA), a neurodegenerative disease that is the leading genetic cause of infant mortality. SMA usually results from loss of the SMN1 (survival of motor neuron 1) gene, which leads to selective motor neuron degeneration. SMN2 is nearly identical to SMN1 but has a nucleotide replacement that causes exon 7 skipping, resulting in a truncated, unstable version of the SMA protein.

Gng12 is a novel negative regulator of LPS-induced inflammation in the microglial cell line BV-2.

Background: Inflammation plays a central role in many neurodegenerative diseases, including Parkinson's, Alzheimer's, multiple sclerosis, amyotrophic lateral sclerosis, and AIDS dementia. Microglia are the resident macrophages of the central nervous system and are the cells primarily responsible for the inflammatory component of these diseases.

Methods: Using gene expression profiling, we compared the profile of the neurospecific microglial cell line BV-2 after LPS stimulation to that of a macrophage cell line (J774A.

Transmission and amplification of information and properties in nanostructured liquid crystals.

In recent years the design of chemical structures of liquid-crystalline materials has developed rapidly, and in many cases changed radically. Since Reinitzer's days, liquid crystals have either been classed as rodlike or disclike, with combinations of the two leading to phasmidic liquid crystals. The discovery that materials with bent molecular structures exhibited whole new families of mesophases inspired investigations into the liquid-crystal properties of materials with widely varying molecular topologies-from pyramids to crosses to dendritic molecules.

Selective estrogen receptor modulators: an update on recent clinical findings.

Recent clinical data on selective estrogen receptor modulators (SERMs) have provided the basis for reassessment of the SERM concept. The molecular basis of SERM activity involves binding of the ligand SERM to the estrogen receptor (ER), causing conformational changes which facilitate interactions with coactivator or corepressor proteins, and subsequently initiate or suppress transcription of target genes. SERM activity is intrinsic to each ER ligand, which accomplishes its unique profile by specific interactions in the target cell, leading to tissue selective actions.

Raloxifene: a selective estrogen-receptor modulator for postmenopausal osteoporosis - a clinical update on efficacy and safety.

Selective estrogen-receptor modulators are molecules with specific estrogen-receptor binding affinity. Each selective estrogen-receptor modulator induces a unique conformation in the ligand-receptor complex, which leads to transcriptional activation and/or inhibition. Raloxifene 60 mg/day, a benzothiophene selective estrogen-receptor modulator, is approved for the prevention and treatment of postmenopausal osteoporosis.

A new selective estrogen receptor modulator with potent uterine antagonist activity, agonist activity in bone, and minimal ovarian stimulation.

The use of selective estrogen receptor modulators for the treatment of estrogen-dependent diseases in premenopausal women has been hindered by undesirable ovarian stimulation and associated risks of ovarian cysts. We have identified a selective estrogen receptor modulator compound (LY2066948) that is a strong estrogen antagonist in the uterus yet has minimal effects on the ovaries of rats. LY2066948 binds with high affinity to both estrogen receptors and has potent estrogen antagonist activity in human uterine and breast cancer cells.

Raloxifene treatment is associated with increased serum estradiol and decreased bone remodeling in healthy middle-aged men with low sex hormone levels.

Unlabelled: In healthy middle-aged men, raloxifene treatment was associated with increased serum estradiol and decreased biochemical markers of bone turnover in subjects with estradiol levels below a threshold of 101.8 pM.

Introduction: We investigated the effects of the selective estrogen receptor modulator raloxifene on bone remodeling in healthy middle-aged men.

A comparison of the effects of raloxifene and conjugated equine estrogen on bone and lipids in healthy postmenopausal women.

Background: Although many studies have assessed the effects of estrogen and raloxifene hydrochloride on bone mineral density and serum lipid concentrations, there are few direct comparative data.

Methods: Randomized placebo-controlled trial for 3 years, intention-to-treat analysis. Six hundred nineteen postmenopausal women with prior hysterectomy (mean age, 53.

The role of selective estrogen receptor modulators (SERMs) in postmenopausal health.

Concerns about long-term therapy with HRT have recently highlighted interest in a class of compounds active in the estrogen receptor, but with selectivity in their actions, known as the selective estrogen receptor modulators (SERMs). Tamoxifen is recognized as the first widely marketed SERM, but its selectivity focuses interest on its approved indications: the treatment and prevention of breast cancer. Raloxifene has been approved in most countries of the world for the treatment and prevention of osteoporosis, and it displays a pattern of actions highly matched to the needs and concerns of many postmenopausal women.

Prevention of osteoporosis and uterine effects in postmenopausal women taking raloxifene for 5 years.

Objective: Raloxifene hydrochloride (60 mg/day) is a selective estrogen receptor modulator indicated for the prevention and treatment of postmenopausal osteoporosis. Raloxifene treatment for 3 years increases bone mineral density (BMD) and, unlike tamoxifen (a triphenylethylene selective estrogen receptor modulator), does not stimulate the endometrium in healthy postmenopausal women. The effect of longer duration of treatment with raloxifene is not known.

Complications associated with optical-access laparoscopic trocars.

Objective: To investigate the number and type of serious complications associated with optical-access trocars reported by sources other than the medical literature.

Methods: Optical-access trocars, first introduced in 1994, were designed to decrease the risk of injury to intra-abdominal structures by allowing the surgeon to visualize abdominal wall layers during placement. To date, very few complications with their use have been reported in the medical literature.

Rapid prenatal diagnosis of trisomies 13, 18, 21 and sex chromosome anomalies by fluorescence in situ hybridization: a year's experience.

The present paper summarizes our first 12 months' experiences of rapid prenatal diagnosis using commercially available diagnostic fluorescence in situ hybridization (FISH) probes for chromosomes X, Y, 13, 18 and 21. The data clearly demonstrate that the advantage of using FISH as an adjunct technique is the fast and reliable determination of the common fetal chromosomal aneuploidies; the results are available in less than 24 hours instead of the 7-14 days with standard techniques.