Emerging technologies for biotherapeutic bioanalysis from a high-throughput and multiplexing perspective: insights from an AAPS emerging technology action program committee.

This manuscript aims to provide insights and updates on emerging technologies from a throughput and multiplexing perspective and to update readers on changes in previously reported technologies. The technologies discussed range from nascent (ultrasensitive Cira, Intellicyt, Dynaxi and Captsure™) to the more established (Ella and SQIDlite™). For the nascent technologies, there was an emphasis on user interviews and reviews, where available, to help provide an unbiased view to our readers.

Next generation ligand binding assays-review of emerging technologies' capabilities to enhance throughput and multiplexing.

The purpose of this manuscript is to provide a summary of the evaluation done by the Throughput and Multiplexing subteam on five emerging technologies: Single molecule array (Simoa™), Optimiser™, CyTOF® (Mass cytometry), SQIDLite™, and iLite™. Most of the information is presented with a minimum amount of published data and much is based on discussions with users and the vendor, to help provide the reader with an unbiased assessment of where the subteam sees each technology fitting best in the bioanalysis of large molecules. The evaluation focuses on technologies with advantages in throughput and multiplexing, but is wide enough to capture their strengths in other areas.

Identification of facilitators and barriers to home dialysis selection by canadian adults with ESRD.

Home dialysis (home HD or home PD) remains underutilized in most jurisdictions. Physicians, advanced-practice nurses, and policy makers working with chronic kidney disease populations can provide insights into patient, healthcare professional, and system-level barriers to home dialysis selection by suitable patients. We used in-depth interviews, with a purposive sampling strategy until informational redundancy was achieved, to elicit barriers and facilitators to home dialysis selection from thirteen informants.

Assay formats: Recommendation for best practices and harmonization from the global bioanalysis consortium harmonization team.

As part of the GBC (Global Bioanalysis Consortium), the L3 assay format team has focused on reviewing common platforms used to support ligand binding assays in the detection of biotherapeutics. The following review is an overview of discussions and presentations from around the globe with a group of experts from different companies to allow an international harmonization of common practices and suggestions for different platforms. Some of the major platforms include Gyrolab, Erenna, RIA, AlphaLISA, Delfia, Immuno-PCR, Luminex, BIAcore, and ELISAs.

Large molecule specific assay operation: recommendation for best practices and harmonization from the global bioanalysis consortium harmonization team.

The L2 Global Harmonization Team on large molecule specific assay operation for protein bioanalysis in support of pharmacokinetics focused on the following topics: setting up a balanced validation design, specificity testing, selectivity testing, dilutional linearity, hook effect, parallelism, and testing of robustness and ruggedness. The team additionally considered the impact of lipemia, hemolysis, and the presence of endogenous analyte on selectivity assessments as well as the occurrence of hook effect in study samples when no hook effect had been observed during pre-study validation.

Lead optimization of ethyl 6-aminonicotinate acyl sulfonamides as antagonists of the P2Y12 receptor. separation of the antithrombotic effect and bleeding for candidate drug AZD1283.

Synthesis and structure-activity relationships of ethyl 6-aminonicotinate acyl sulfonamides, which are potent antagonists of the P2Y12 receptor, are presented. Shifting from 5-chlorothienyl to benzyl sulfonamides significantly increased the potency in the residual platelet count assay. Evaluation of PK parameters in vivo in dog for six compounds showed a 10-fold higher clearance for the azetidines than for the matched-pair piperidines.

Dihydrotestosterone alters cyclooxygenase-2 levels in human coronary artery smooth muscle cells.

Both protective and nonprotective effects of androgens on the cardiovascular system have been reported. Our previous studies show that the potent androgen receptor (AR) agonist dihydrotestosterone (DHT) increases levels of the vascular inflammatory mediator cyclooxygenase (COX)-2 in rodent cerebral arteries independent of an inflammatory stimulus. Little is known about the effects of androgens on inflammation in human vascular tissues.

Hitting home: a survey of housing conditions of homes used for long-term care in Ontario.

A telephone survey of a random sample of 811 long-term home care clients from three geographically distinct regions in Ontario was conducted to illuminate the living and working conditions in households receiving long-term care services. The median age of clients was 77 years and 75 percent were female. The majority had not completed high school.

A new series of pyridinyl-alkynes as antagonists of the metabotropic glutamate receptor 5 (mGluR5).

Synthesis and some structure-activity relationships for a new series of propargyl ethers as mGluR5 antagonists are reported.

Structure-activity relationships for the linker in a series of pyridinyl-alkynes that are antagonists of the metabotropic glutamate receptor 5 (mGluR5).

Studies of structure-activity relationships for the linker in a new series of metabotropic glutamate receptor 5 antagonists are presented together with in vitro and in vivo pharmacokinetic data.

Structure-activity relationship of thiopyrimidines as mGluR5 antagonists.

Structure-activity relationship investigations of the thiopyrimidine (1), an HTS hit with micromolar activity as a metabotropic glutamate receptor 5 (mGluR5) antagonist, led to compounds with sub-micromolar activity.

Phenyl ureas of creatinine as mGluR5 antagonists. A structure-activity relationship study of fenobam analogues.

Fenobam (1) was developed by McNeil Laboratories as an anxiolytic agent with an unknown molecular target in the late 1970s. In a recent publication, it was revealed that fenobam is a non-competitive mGluR5 antagonist. Herein, we present the structure-activity relationship of fenobam and its analogues and similarities between the SAR of mGluR5 antagonism and the SAR of CNS properties originally reported by McNeil are discussed.

[Premature rupture of fetal membranes, risk of infection and infant prognosis--a comparison of 2 regions].

The question to be answered was: Does premature rupture of membranes (PROM) and duration of PROM lead to increased mortality, neonatal and late morbidity and adverse cognitive developmental outcome? We present data of a bi-national cohort observation study in South Bavaria (SBy) and South Finland (SF). The sample included all children, who were admitted to a children's hospital (SBy N: 7505/70,600 live births; SF N: 1536/15,618), and some not transferred control infants (916 and 658, respectively). Obstetric details like PROM were obtained from perinatal records.

An epidemiologic longitudinal study of sleeping problems and feeding experience of preterm and term children in southern Finland: comparison with a southern German population sample.

Objective: To determine the influence of breast-feeding on the prevalence and persistence of sleeping problems in southern Finland (SF) and southern Germany (SG).

Design: Prospective binational population study of infants admitted to special care units (SCUs) in geographically defined areas in SF and SG.

Subjects: In SF, the number of SCU infants was 1057 (very preterm, 47; preterm, 258; term, 752); 485 term infants were control subjects.

Unexpected binding mode of a cyclic sulfamide HIV-1 protease inhibitor.

Two cyclic, C2-symmetric HIV-1 protease inhibitors, one sulfamide and one urea derivative, both comprising phenyl ether groups in the P1/P1' positions, were cocrystallized with HIV-1 protease, and the crystal structures were determined to 2.0 A resolution. The structure of the urea 2 showed a conformation similar to that reported for the related urea 3 by Lam et al.

High hydrostatic pressures in traumatic joints require elevated synovial capillary pressure probably associated with arteriolar vasodilatation.

Three out of the four Starling pressures were determined at arthroscopy of traumatic effusions of the knee. The range of the joint fluid hydrostatic pressure Pjoint was 5-83 cmH2O (0.5-8.

A new alpha-helical coiled coil protein encoded by the Salmonella typhimurium virulence plasmid.

A new protein of Salmonella typhimurium was identified and characterized. The gene (tlpA) encoding this protein (TlpA) was isolated from the large virulence-associated plasmid of S. typhimurium and sequenced in order to predict the primary structure of TlpA.

Structural and functional features of Pseudomonas cytochrome c peroxidase.

The secondary structure of Pseudomonas cytochrome c peroxidase (ferrocytochrome c: hydrogen-peroxide oxidoreductase, EC 1.11.1.

Solution structure of human plasma fibronectin as a function of NaCl concentration determined by small-angle X-ray scattering.

The structure of human plasma fibronectin in 50 mM Tris-HCl buffer, pH 7.4, containing varying concentrations of NaCl, has been investigated using the small-angle X-ray method. Below 0.