Complications Associated With Same-Day Bilateral Total Knee Arthroplasties.

Same-day bilateral total knee arthroplasties (SBTKAs) are associated with shorter rehabilitation and lower cost. However, controversy surrounding the safety of SBTKAs exists. Recent studies are lacking to determine whether patient selection has brought SBTKA in line with unilateral total knee arthroplasty (UTKA).

Educational programs implemented for pharmacists after state passage of a standing order for naloxone: A systematic review of current practices.

Objective: This review describes the current educational interventions that have been created for pharmacists after the implementation of a standing order for naloxone.

Methods: Search strategies were constructed for 3 databases (PubMed, SCOPUS, and CINAHL), which were queried between February 1, 2019, and March 5, 2019. Two reviewers independently screened 224 titles and abstracts from these databases.

Comparing Outcomes for Female Total Knee Arthroplasty Patients Under Global Budget Revenue.

Maryland implemented the all-payer, rater-setting Global Budget Revenue (GBR) payment model in 2014 to reduce cost and improve quality. This study assessed the effect of GBR on total knee arthroplasty (TKA) outcomes by sex. Specifically, the authors assessed (1) demographics and (2) outcomes of males and females undergoing TKA before and after GBR implementation.

Addition of Optimized Bovine Serum Albumin Level in a High-Throughput Caco-2 Assay Enabled Accurate Permeability Assessment for Lipophilic Compounds.

The Caco-2 permeability assay is a well-accepted in vitro model to evaluate compounds' potential for oral absorption at early discovery. However, for many lipophilic compounds, no meaningful Caco-2 data could be generated due to their low solubility in assay buffer and/or poor recovery from the assay. In our previous study, we reported an organic catch approach to improve compound recovery.

Poor Safety and Tolerability Hamper Reaching a Potentially Therapeutic Dose in the Use of Thalidomide for Alzheimer's Disease: Results from a Double-Blind, Placebo-Controlled Trial.

Introduction: To date there is no cure for Alzheimer's disease (AD). After amyloid beta immunotherapies have failed to meet primary endpoints of slowing cognitive decline in AD subjects, the inhibition of the beta-secretase BACE1 appears as a promising therapeutic approach. Pre-clinical data obtained in APP23 mice suggested that the anti-cancer drug thalidomide decreases brainBACE1 and Aβ levels.

Reduced protein turnover mediates functional deficits in transgenic mice expressing the 25 kDa C-terminal fragment of TDP-43.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-TDP) are two neurodegenerative disorders characterized by the accumulation of TDP-43. TDP-43 is proteolitically cleaved to generate two major C-terminal fragments of 35 and 25 kDa. The latter, known as TDP-25, is a consistent feature of FTLD-TDP and ALS; however, little is known about its role in disease pathogenesis.

A cellular model of amyloid precursor protein processing and amyloid-β peptide production.

Background: A hallmark pathologic feature of Alzheimer's disease (AD) is accumulation of neuritic senile plaques in the brain parenchyma. Neurotoxic plaque cores are composed predominantly of amyloid-β (Aβ) peptides of 40 and 42 amino acids in length, formed by sequential cleavage of amyloid precursor protein (APP) by β-, and γ-secretases. There is a great interest in approaches to modulate Aβ peptide production and develop therapeutic interventions to reduce Aβ levels to halt or slow the progression of neurodegeneration.

BACE1 levels by APOE genotype in non-demented and Alzheimer's post-mortem brains.

The APOE genotype is a known susceptibility factor for Alzheimer's disease (AD). It is apparent that the presence of the APOE ε40 allele increases the risk for developing AD, lowers the age of onset in AD, and may influence the pathological burden seen in AD. In this study, we asked whether BACE1 levels differ by APOE genotype in the AD and non-demented (ND) brain.

Can platelet BACE1 levels be used as a biomarker for Alzheimer's disease? Proof-of-concept study.

To date there is no validated peripheral biomarker to assist with the clinical diagnosis of Alzheimer's disease (AD). Platelet proteins have been studied as AD biomarkers with relative success. In this study, we investigated whether platelet BACE1 levels differ between AD and cognitively normal (CN) control patients.

Approach to improve compound recovery in a high-throughput Caco-2 permeability assay supported by liquid chromatography-tandem mass spectrometry.

The Caco-2 cell culture system is widely employed as an in vitro model for prediction of intestinal absorption of test compounds in early drug discovery. Poor recovery is a commonly encountered issue in Caco-2 assay, which can lead to difficulty in data interpretation and underestimation of the apparent permeability of affected compounds. In this study, we systematically investigated the potential sources of compound loss in our automated, high-throughput Caco-2 assay, sample storage, and analysis processes, and as a result found the nonspecific binding to various plastic surfaces to be the major cause of poor compound recovery.

Development of a specific ELISA to measure BACE1 levels in human tissues.

The aspartyl protease BACE1 is the rate limiting enzyme in the synthesis of amyloid beta, which accumulation in the human brain is a hallmark of Alzheimer's disease (AD). BACE1 has been proposed as a surrogate marker of AD; however, very few BACE1 immunoassays have been reported. In the present study we have screened ten BACE1 antibodies by Western blot and several antibody pairs to develop a new BACE1 sandwich ELISA procedure.

Genetic targeting aromatase in male amyloid precursor protein transgenic mice down-regulates beta-secretase (BACE1) and prevents Alzheimer-like pathology and cognitive impairment.

As brain testosterone plays both androgenic and estrogenic actions due to its conversion into estrogen via aromatase naturally, it is unclear that the age-related reduction of testosterone increased risk of Alzheimer's disease (AD) in men is mediated through androgen alone or both androgen and estrogen mechanisms. Our previous studies using a gene-based approach in mouse model to block the conversion of testosterone into estrogen (aromatase gene knock-out, ArKO), found a depletion of estrogen and increase in testosterone endogenously in males. Here, we use crossing the ArKO mice with APP23 transgenic mice, a mouse model of AD, to produce APP23/Ar(+/-) mice to study the estrogen-independent effect of testosterone on AD.

Effects of hyperoxia on ventilation and pulmonary hemodynamics during immersed prone exercise at 4.7 ATA: possible implications for immersion pulmonary edema.

Immersion pulmonary edema (IPE) can occur in otherwise healthy swimmers and divers, likely because of stress failure of pulmonary capillaries secondary to increased pulmonary vascular pressures. Prior studies have revealed progressive increase in ventilation [minute ventilation (Ve)] during prolonged immersed exercise. We hypothesized that this increase occurs because of development of metabolic acidosis with concomitant rise in mean pulmonary artery pressure (MPAP) and that hyperoxia attenuates this increase.

Dynamic leaching test of personal computer components.

A dynamic leaching test (DLT) was developed and used to evaluate the leaching of toxic substances for electronic waste in the environment. The major components in personal computers (PCs) including motherboards, hard disc drives, floppy disc drives, and compact disc drives were tested. The tests lasted for 2 years for motherboards and 1.

A low-cost optical pachymeter for the diagnosis of glaucoma and ocular hypertension.

Glaucoma and ocular hypertension are major causes of vision loss worldwide. Recent clinical studies have highlighted the importance of central corneal thickness in diagnosing these disorders. However, current instrumental methods of measuring corneal thickness are not ideal for widespread clinical deployment.

Three-component, stereoselective palladium-catalyzed synthesis of functionalized bicyclopentanoids.

1,5-Cyclooctadiene can be stereoselectively transformed into a substituted bicyclo[3.3.0]octane ring system under palladium catalysis with concomitant formation of three carbon-carbon bonds.