The Impact of Residual Disease After Preoperative Systemic Therapy on Clinical Outcomes in Patients with Inflammatory Breast Cancer.

Background: Inflammatory breast cancer (IBC) is a rare and aggressive disease treated with multimodality therapy: preoperative systemic therapy (PST) followed by modified radical mastectomy (MRM), chest wall and regional nodal radiotherapy, and adjuvant biologic therapy and/or endocrine therapy when appropriate. In non-IBC, the degree of pathologic response to PST has been shown to correlate with time to recurrence (TTR) and overall survival (OS). We sought to determine if pathologic response correlates with oncologic outcomes of IBC patients.

Prior Authorization for Medications in a Breast Oncology Practice: Navigation of a Complex Process.

Introduction: The cost and burden associated with prior authorization (PA) for specialty medications are concerns for oncologists, but the impact of the PA process on care delivery has not been well described. We examined PA processes and approval patterns within a high-volume breast oncology clinic at a major academic cancer center.

Methods: We met with institutional staff to create a PA workflow and process map.

Randomized phase 2 trial of a coordinated breast cancer follow-up care program.

Background: Previous research has demonstrated that cancer survivors often fail to receive recommended care and also undergo unnecessary care; this reduces care quality and increases costs.

Methods: This phase 2 trial randomized 100 stage 0 to IIIa breast cancer patients who had primary care providers within a large Massachusetts-based hospital network (with accessible online records) to either coordinated follow-up care (CC), which entailed a tailored survivorship care plan (SCP) and patient navigator calls every 3 months, or standard care (SC), which did not include an SCP or patient navigation, for 1 year after the completion of their last chemotherapy, surgery, or radiation treatment. The primary endpoint was the frequency of redundant examinations (>1 breast/chest wall examination per patient within any 30-day period in the absence of a new breast or chest wall complaint) over the year of follow-up.

Phytase, a new life for an "old" enzyme.

Phytases are phosphohydrolytic enzymes that initiate stepwise removal of phosphate from phytate. Simple-stomached species such as swine, poultry, and fish require extrinsic phytase to digest phytate, the major form of phosphorus in plant-based feeds. Consequently, this enzyme is supplemented in these species' diets to decrease their phosphorus excretion, and it has emerged as one of the most effective and lucrative feed additives.

Japanese macaque encephalomyelitis: a spontaneous multiple sclerosis-like disease in a nonhuman primate.

Objective: To describe Japanese macaque encephalomyelitis (JME), a spontaneous inflammatory demyelinating disease occurring in the Oregon National Primate Research Center's (ONPRC) colony of Japanese macaques (JMs, Macaca fuscata).

Methods: JMs with neurologic impairment were removed from the colony, evaluated, and treated with supportive care. Animals were humanely euthanized and their central nervous systems (CNSs) were examined.

Vanadate inhibition of fungal PhyA and bacterial AppA2 histidine acid phosphatases.

The fungal PhyA protein, which was first identified as an acid optimum phosphomonoesterase (EC 3.1.3.

Site-directed mutagenesis of disulfide bridges in Aspergillus niger NRRL 3135 phytase (PhyA), their expression in Pichia pastoris and catalytic characterization.

Earlier studies have established the importance of five disulfide bridges (DBs) in Aspergillus niger phytase. In this study, the relative importance of each of the individual disulfide bridge is determined by its removal by site-directed mutagenesis of specific cysteines in the cloned A. niger phyA gene.

Exploring family management of childhood brain tumor survivors.

Family management of childhood chronic conditions consists of 6 family factors: (1) the family's view of the child's daily life, (2) the impact of the condition on family life, (3) the difficulty of family life, (4) the family's effort managing the child's condition, (5) the family's ability managing the child's condition, and (6) parental mutuality. Recently, the Family Management Measure (FaMM), which measures family management of children with chronic conditions (excluding cancer), was validated. The purpose of this descriptive study was to examine the comparability of these 6 factors in families with childhood brain tumor survivors.

Proteomic and functional characterization of the outer membrane vesicles from the gastric pathogen Helicobacter pylori.

The gastric pathogen Helicobacter pylori causes a spectrum of gastro-duodenal diseases, which may be mediated in part by the outer membrane vesicles (OMVs) constitutively shed by the pathogen. We aimed to determine the proteome of H. pylori OMV to help evaluate the mechanisms whereby these structures confer their known immuno-modulatory and cytotoxic activities to host cells, as such disease-associated activities are also conferred by the bacterium from which the vesicles are derived.

Impact of assay conditions on activity estimate and kinetics comparison of Aspergillus niger PhyA and Escherichia coli AppA2 phytases.

Aspergillus niger PhyA and Escherichia coli AppA2 are increasingly used in animal feed for phosphorus nutrition and environmental protection. The objective of this study was to determine the impacts of assay conditions on activity estimates of these two phytases and to compare their biochemical characteristics at a pH similar to the stomach environment. The activities of the unpurified AppA2 were more variable than those of PhyA with three commonly used phytase activity assays.

Unfolding and refolding of Aspergillus niger PhyB phytase: role of disulfide bridges.

The role of disulfide bridges in the folding of Aspergillus niger phytase pH 2.5-optimum (PhyB) was investigated using dynamic light scattering (DLS). Guanidinium chloride (GuCl) at 1.

Kinetic characterization of O-phospho-L-tyrosine phosphohydrolase activity of two fungal phytases.

Fungal phytases belonging to "histidine acid phosphatase" or HAP class of phosphohydrolases that catalyze the hydrolysis of phytic acid could also hydrolyze O-phospho-L-tyrosine, which is also called phosphotyrosine. Two phytases from Aspergillus niger and Aspergillus awamori with pH optima 2.5 were tested for phosphotyrosine hydrolase activity; both enzymes cleaved the phosphomonoester bond of phosphotyrosine efficiently at acidic pH.

Salt effect on the pH profile and kinetic parameters of microbial phytases.

The pH profiles of two microbial phytases were determined using four different general purpose buffers at different pH values. The roles of calcium chloride, sodium chloride, and sodium fluoride on activity were compared in these buffers. For Aspergillus niger phytase, calcium extended the pH range to 8.

Altering the substrate specificity site of Aspergillus niger PhyB shifts the pH optimum to pH 3.2.

Phytases are of biotechnological importance as animal feed additives for their ability to catalyze the hydrolysis of phosphate from phytate for absorption by simple-stomached animals, and to reduce their fecal phosphorus excretion. Aspergillus niger PhyB has high catalytic activity at low pHs around 2.5, but has little activity at the commonly observed gastric pH of young animals (3.

Adopting selected hydrogen bonding and ionic interactions from Aspergillus fumigatus phytase structure improves the thermostability of Aspergillus niger PhyA phytase.

Although it has been widely used as a feed supplement to reduce manure phosphorus pollution of swine and poultry, Aspergillus niger PhyA phytase is unable to withstand heat inactivation during feed pelleting. Crystal structure comparisons with its close homolog, the thermostable Aspergillus fumigatus phytase (Afp), suggest associations of thermostability with several key residues (E35, S42, R168, and R248) that form a hydrogen bond network in the E35-to-S42 region and ionic interactions between R168 and D161 and between R248 and D244. In this study, loss-of-function mutations (E35A, R168A, and R248A) were introduced singularly or in combination into seven mutants of Afp.

Shifting the pH profile of Aspergillus niger PhyA phytase to match the stomach pH enhances its effectiveness as an animal feed additive.

Environmental pollution by phosphorus from animal waste is a major problem in agriculture because simple-stomached animals, such as swine, poultry, and fish, cannot digest phosphorus (as phytate) present in plant feeds. To alleviate this problem, a phytase from Aspergillus niger PhyA is widely used as a feed additive to hydrolyze phytate-phosphorus. However, it has the lowest relative activity at the pH of the stomach (3.

Conservation of cysteine residues in fungal histidine acid phytases.

Amino acid sequence analysis of fungal histidine acid phosphatases displaying phytase activity has revealed a conserved eight-cysteine motif. These conserved amino acids are not directly associated with catalytic function; rather they appear to be essential in the formation of disulfide bridges. Their role is seen as being similar to another eight-cysteine motif recently reported in the amino acid sequence of nearly 500 plant polypeptides.

Monitoring of unfolding and refolding in fungal phytase (phyA) by dynamic light scattering.

Role of disulfide bridges in phytase's unfolding-refolding was probed using dynamic light scattering. Phytase was unfolded by guanidinium chloride and then refolded by removing the denaturant by dialysis. Thiol reagents prevented refolding; thus, disulfide bridge formation is an integral step in phytase folding.

Advances in phytase research.

Since its discovery in 1907, a complex of technological developments has created a potential $500 million market for phytase as an animal feed additive. During the last 30 years, research has led to increased use of soybean meal and other plant material as protein sources in animal feed. One problem that had to be overcome was the presence of antinutritional factors, including phytate, in plant meal.

Fungal phyA gene expressed in potato leaves produces active and stable phytase.

Fungal phyA gene from Aspergillus ficuum (niger) was cloned and expressed in potato leaves. The recombinant enzyme was stable and catalytically active. The expressed protein in the leaves of the dicotyledonous plant retained most physical and catalytic properties of the benchmark A.

Site-directed mutagenesis of Aspergillus niger NRRL 3135 phytase at residue 300 to enhance catalysis at pH 4.0.

Increased phytase activity for Aspergillus niger NRRL 3135 phytaseA (phyA) at intermediate pH levels (3.0-5.0) was achieved by site-directed mutagenesis of its gene at amino acid residue 300.

Cloned and expressed fungal phyA gene in alfalfa produces a stable phytase.

The phyA gene from Aspergillus ficuum that codes for a 441-amino-acid full-length phosphomonoesterase (phytase) was cloned and expressed in Medicago sativa (alfalfa) leaves. The expressed enzyme from alfalfa leaves was purified to homogeneity and biochemically characterized, and its catalytic properties were elucidated. The expressed phytase in alfalfa leaves retained all the biochemical properties of the benchmark A.

A new sterigmatocystin-producing Emericella variant from agricultural desert soils.

An unusual, sterigmatocystin-producing taxon with characteristics of both Emericella nidulans (anamorph Aspergillus nidulans) and Emericella rugulosa (anamorph Aspergillus rugulovalvus, formerly A. rugulosus) was isolated repeatedly during a mycofloral survey of desert cotton field soils where aflatoxin is a chronic problem. Members of this taxon had ascospores with smooth convex walls like E.