Mitotically Active Nevus and Nevoid Melanoma: A Clinicopathological and Molecular Study.

The distinction between nevoid melanoma and a mitotically active nevus can be challenging at the microscopic level. In this study, we performed cytogenetic testing on a cohort of 25 mitotically active melanocytic proliferations resembling common melanocytic nevus from 25 patients. Based on cytogenetic findings, the lesions were classified as "nevoid melanoma" (n = 13) or "mitotically active nevus" (n = 12).

Detection of Low-level EGFR c.2369 C > T (p.Thr790Met) Resistance Mutation in Pre-treatment Non-small Cell Lung Carcinomas Harboring Activating EGFR Mutations and Correlation with Clinical Outcomes.

Increasing evidence points to the presence of low-level de novo T790M mutations in patients with non-small cell lung carcinoma (NSCLC) harboring activating EGFR mutations. We utilized digital PCR (dPCR), a highly sensitive gene mutation detection method, to detect pre-treatment T790M mutations in NSCLC tumor samples and correlated the T790M status with clinical features and patient outcomes. DNA extracted from pre-treatment NSCLC tumor tissue with known activating EGFR mutations, diagnosed between October 2010 and May 2017 at PathWest laboratory, was used to perform targeted dPCR for quantitative detection of T790M mutations.

Invasive lobular carcinoma of the breast: assessment of proliferative activity using automated Ki-67 immunostaining.

Invasive lobular carcinoma (ILC) is almost always classified as Nottingham histological grade 2. Despite this, prognosis is markedly varied, with some ILCs behaving more akin to grade 3 invasive ductal carcinoma (IDC). Methods to separate these aggressive ILCs are needed.

Laboratory validation studies in Ki-67 digital image analysis of breast carcinoma: a pathway to routine quality assurance.

Ki-67 proliferative index (PI) has prognostic and predictive value in invasive breast carcinoma (IBC), but clinical uptake has been hampered by suboptimal accuracy, reproducibility and standardisation. Published guidelines have addressed pre-analytical and analytical factors to improve Ki-67 PI utility; however, practicalities of ongoing monitoring of Ki-67 PI quality in IBC reporting have not been established. We aimed to evaluate the internal and external quality of our established digital Ki-67 PI IBC reporting practice at a tertiary institution.

Central Nervous System Processing of Emotions in Children with Fecal Incontinence and Constipation.

Objective: Fecal incontinence and constipation are common disorders in childhood. The enteric nervous system and the central nervous system are highly interactive along the brain-gut axis. The interaction is mainly afferent.

Detection of copy number variations in melanocytic lesions utilising array based comparative genomic hybridisation.

Distinction between melanocytic naevi and melanoma occasionally poses a diagnostic challenge in ambiguous cases showing overlapping histological features. Melanomas are characterised by the presence of multiple genomic copy number variants (CNVs), while this is not a feature of naevi. We assessed the feasibility and utility of array-based comparative genomic hybridisation (aCGH) to assess CNVs in melanocytic lesions.

Coordination of Diagnostic Efforts in the Great Plains: Wheat Virus Survey and Modeling of Disease Onset.

Following the discovery of two new wheat virus diseases in the United States, the Great Plains region (Colorado, Kansas, Montana, Nebraska, North Dakota, Oklahoma, South Dakota, Texas, and Wyoming) of the National Plant Diagnostic Network (NPDN) initiated a project to measure the prevalence of five wheat diseases using indirect ELISA. Wheat streak mosaic virus (WSMV), Wheat mosaic virus (WMoV), and Triticum mosaic virus (TriMV) were found in all nine states. WSMV was the most prevalent, averaging 23 to 47% of samples each year.

Expression of proliferation genes in formalin-fixed paraffin-embedded (FFPE) tissue from breast carcinomas. Feasibility and relevance for a routine histopathology laboratory.

Aim: Breast carcinoma proliferative activity, histological grade and commercial molecular tests are all important in prognostication and treatment. There is a particular need for improved, standardised techniques for subclassification of grade 2 breast cancers into low-risk and high-risk prognostic groups. In this study we investigated whether gene expression profiling of five proliferation genes was feasible using breast cancer tissue in a clinical setting and whether these profiles could enhance pathological assessment.

BRAF mutation detection in hairy cell leukaemia from archival haematolymphoid specimens.

Hairy cell leukaemia (HCL) is a rare, indolent chronic B-cell leukaemia accounting for approximately 2% of all adult leukaemias. The recent association of the BRAF p.Val600Glu (V600E) mutation in HCL makes it a valuable molecular diagnostic marker.

Reconsidering Leaf Wetness Duration Determination for Plant Disease Management.

Relationships between leaf wetness and plant diseases have been studied for centuries. The progress and risk of many bacterial, fungal, and oomycete diseases on a variety of crops have been linked to the presence of free water on foliage and fruit under temperatures favorable to infection. Whereas the rate parameters for infection or epidemic models have frequently been linked with temperature during the wet periods, leaf wetness periods of specific time duration are necessary for the propagule germination of most phytopathogenic fungi and for their penetration of plant tissues.

Practical issues concerning the implementation of Ki-67 proliferative index measurement in breast cancer reporting.

Commercial molecular tests which rely heavily on proliferation markers to stratify breast cancer are in increasing demand, but are expensive and not widely available. There is heightened interest in the use of Ki-67 immunohistochemistry as a marker of proliferation. This study sought to examine practical issues in the incorporation of Ki-67 measurement into breast cancer reporting.

Coil fraction-dependent phase behaviour of a model globular protein-polymer diblock copolymer.

The self-assembly of the model globular protein-polymer block copolymer mCherry-b-poly(N-isopropyl acrylamide) is explored across a range of polymer coil fractions from 0.21 to 0.82 to produce a phase diagram for these materials as a function of molecular composition.

The nature of protein interactions governing globular protein-polymer block copolymer self-assembly.

The effects of protein surface potential on the self-assembly of protein-polymer block copolymers are investigated in globular proteins with controlled shape through two approaches: comparison of self-assembly of mCherry-poly(N-isopropylacrylamide) (PNIPAM) bioconjugates with structurally homologous enhanced green fluorescent protein (EGFP)-PNIPAM bioconjugates, and mutants of mCherry with altered electrostatic patchiness. Despite large changes in amino acid sequence, the temperature-concentration phase diagrams of EGFP-PNIPAM and mCherry-PNIPAM conjugates have similar phase transition concentrations. Both materials form identical phases at two different coil fractions below the PNIPAM thermal transition temperature and in the bulk.

Effect of small molecule osmolytes on the self-assembly and functionality of globular protein-polymer diblock copolymers.

Blending the small molecule osmolytes glycerol and trehalose with the model globular protein-polymer block copolymer mCherry-b-poly(N-isopropyl acrylamide) (mCherry-b-PNIPAM) is demonstrated to improve protein functionality in self-assembled nanostructures. The incorporation of either additive into block copolymers results in functionality retention in the solid state of 80 and 100% for PNIPAM volume fractions of 40 and 55%, respectively. This represents a large improvement over the 50-60% functionality observed in the absence of any additive.

Retinal spectral domain optical coherence tomography in early atrophic age-related macular degeneration (AMD) and a new metric for objective evaluation of the efficacy of ocular nutrition.

Purpose: A challenge in ocular preventive medicine is identification of patients with early pathological retinal damage that might benefit from nutritional intervention. The purpose of this study is to evaluate retinal thinning (RT) in early atrophic age-related macular degeneration (AMD) against visual function data from the Zeaxanthin and Visual Function (ZVF) randomized double masked placebo controlled clinical trial (FDA IND #78973).

Methods: Retrospective, observational case series of medical center veterans with minimal visible AMD retinopathy (AREDS Report #18 simplified grading 1.

Kinetically controlled nanostructure formation in self-assembled globular protein-polymer diblock copolymers.

Aqueous processing of globular protein-polymer diblock copolymers into solid-state materials and subsequent solvent annealing enables kinetic and thermodynamic control of nanostructure formation to produce block copolymer morphologies that maintain a high degree of protein fold and function. When model diblock copolymers composed of mCherry-b-poly(N-isopropylacrylamide) are used, orthogonal control over solubility of the protein block through changes in pH and the polymer block through changes in temperature is demonstrated during casting and solvent annealing. Hexagonal cylinders, perforated lamellae, lamellae, or hexagonal and disordered micellar phases are observed, depending on the coil fraction of the block copolymer and the kinetic pathway used for self-assembly.

Assessing the continuum of event-based biosurveillance through an operational lens.

This research follows the Updated Guidelines for Evaluating Public Health Surveillance Systems, Recommendations from the Guidelines Working Group, published by the Centers for Disease Control and Prevention nearly a decade ago. Since then, models have been developed and complex systems have evolved with a breadth of disparate data to detect or forecast chemical, biological, and radiological events that have a significant impact on the One Health landscape. How the attributes identified in 2001 relate to the new range of event-based biosurveillance technologies is unclear.

Randomized, double-blind, placebo-controlled study of zeaxanthin and visual function in patients with atrophic age-related macular degeneration: the Zeaxanthin and Visual Function Study (ZVF) FDA IND #78, 973.

Background: The purpose of this study is to evaluate whether dietary supplementation with the carotenoid zeaxanthin (Zx) raises macula pigment optical density (MPOD) and has unique visual benefits for patients with early atrophic macular degeneration having visual symptoms but lower-risk National Institute of Health/National Eye Institute/Age-Related Eye Disease Study characteristics.

Methods: This was a 1-year, n = 60 (57 men, 3 women), 4-visit, intention-to-treat, prospective, randomized controlled clinical trial of patients (74.9 years, standard deviation [SD] 10) with mild-to-moderate age-related macular degeneration (AMD) randomly assigned to 1 of 2 dietary supplement carotenoid pigment intervention groups: 8 mg Zx (n = 25) and 8 mg Zx plus 9 mg lutein (L) (n = 25) or 9 mg L ("Faux Placebo," control group, n = 10).

Chondrocyte apoptosis determined by caspase-3 expression varies with fibronectin distribution in equine articular cartilage.

Aim: The purpose of this study was to investigate associations between the extent of chondrocyte apoptosis and expression of the articular cartilage (AC) extracellular matrix (ECM) molecules, cartilage oligomeric matrix protein (COMP) and fibronectin.

Method: Cartilage from four sites (when available) on equine left middle carpal joints (n = 12) were used. Expression of COMP and fibronectin was determined using specific polyclonal antibodies and a biotin-streptavidin/peroxidase method.

Solid-state nanostructured materials from self-assembly of a globular protein-polymer diblock copolymer.

Self-assembly of three-dimensional solid-state nanostructures containing approximately 33% by weight globular protein is demonstrated using a globular protein-polymer diblock copolymer, providing a route to direct nanopatterning of proteins for use in bioelectronic and biocatalytic materials. A mutant red fluorescent protein, mCherryS131C, was prepared by incorporation of a unique cysteine residue and site-specifically conjugated to end-functionalized poly(N-isopropylacrylamide) through thiol-maleimide coupling to form a well-defined model protein-polymer block copolymer. The block copolymer was self-assembled into bulk nanostructures by solvent evaporation from concentrated solutions.