The prevalence and pattern of chemotherapy-induced peripheral neuropathy among women with breast cancer receiving care in a large community oncology practice

Purpose To describe the prevalence, severity, and risk factors of chemotherapy-induced peripheral neuropathy (CIPN) and its impact on function and quality of life (QOL) among women treated for breast cancer in a large U.S. Community Oncology practice. Methods Women previously treated with taxane-based chemotherapy for early-stage breast cancer completed the EORTC QLQ–C30, QLQ–BR23, and QLQ–CIPN20. Subscales are scored 0–100; higher scores indicate greater symptom severity. Pre-specified hypotheses were tested. Results 126 women with mean age 56.7 years (SD 11.8) were stage I–II (79.4%) or stage III (20.6%) at the time of the survey; 65.1% were White and 27.8% were Black or African American. The mean time since last taxane chemotherapy cycle was 144.9 weeks (SD 112.9). 73.0% reported having CIPN. QLQ–CIPN20 mean scores for the sensory, motor, and autonomic subscales were 18.9 (SD 23.1), 18.6 (SD 18.7), and 17.1 (SD 21.8), respectively. CIPN symptom severity was negatively correlated with global health status/QOL and physical and role functioning (range of r = -0.46 to -0.72). It was not associated with age, body mass index, diabetes, or cumulative taxane dosage, but was greater for Black or African American women (e.g., sensory, p<0.002). CIPN sensory impairment was marginally greater for patients treated with paclitaxel compared to docetaxel (p<0.064). Conclusions CIPN was prevalent in this community oncology practice and significantly impacts function and QOL. These data highlight the importance of developing methods to mitigate CIPN, and for screening for CIPN particularly among Black or African American women

Telehealth implementation at MedZou Community Health Clinic in response to the COVID-19 pandemic

This study aims to describe the transition in care delivery which occurred at MedZou in response to the COVID-19 pandemic and how implementation of telehealth services was achieved

Comparative Analysis of Tandem Repeats from Hundreds of Species Reveals Unique Insights into Centromere Evolution

Centromeres are essential for chromosome segregation, yet their DNA sequences evolve rapidly. In most animals and plants that have been studied, centromeres contain megabase-scale arrays of tandem repeats. Despite their importance, very little is known about the degree to which centromere tandem repeats share common properties between different species across different phyla. We used bioinformatic methods to identify high-copy tandem repeats from 282 species using publicly available genomic sequence and our own data. The assumption that the most abundant tandem repeat is the centromere DNA was true for most species whose centromeres have been previously characterized, suggesting this is a general property of genomes. Our methods are compatible with all current sequencing technologies. Long Pacific Biosciences sequence reads allowed us to find tandem repeat monomers up to 1,419 bp. High-copy centromere tandem repeats were found in almost all animal and plant genomes, but repeat monomers were highly variable in sequence composition and in length. Furthermore, phylogenetic analysis of sequence homology showed little evidence of sequence conservation beyond ~50 million years of divergence. We find that despite an overall lack of sequence conservation, centromere tandem repeats from diverse species showed similar modes of evolution, including the appearance of higher order repeat structures in which several polymorphic monomers make up a larger repeating unit. While centromere position in most eukaryotes is epigenetically determined, our results indicate that tandem repeats are highly prevalent at centromeres of both animals and plants. This suggests a functional role for such repeats, perhaps in promoting concerted evolution of centromere DNA across chromosomes

Cognitive consequences of perceiving social exclusion

Although a great deal is now known about how people mentally represent individuals and groups, less attention has been paid to the question of how interpersonal relationships are represented in memory. Drawing on principles of categorization, this paper reports an investigation into how we mentally represent the relationships of others. In three experiments, evidence for assimilation effects following social exclusion (and subsequent categorization) is found. Experiment 1 uses a judgment paradigm to demonstrate that social exclusion influences the perception of interpersonal closeness. Experiments 2 and 3 employ a memory confusion paradigm to establish that representations of relationship partners are assimilated following the exclusion of a third party. © 2008 Elsevier Inc. All rights reserved

Paradoxical activation of the protein kinase-transcription factor ERK5 by ERK5 kinase inhibitors.

The dual protein kinase-transcription factor, ERK5, is an emerging drug target in cancer and inflammation, and small-molecule ERK5 kinase inhibitors have been developed. However, selective ERK5 kinase inhibitors fail to recapitulate ERK5 genetic ablation phenotypes, suggesting kinase-independent functions for ERK5. Here we show that ERK5 kinase inhibitors cause paradoxical activation of ERK5 transcriptional activity mediated through its unique C-terminal transcriptional activation domain (TAD). Using the ERK5 kinase inhibitor, Compound 26 (ERK5-IN-1), as a paradigm, we have developed kinase-active, drug-resistant mutants of ERK5. With these mutants, we show that induction of ERK5 transcriptional activity requires direct binding of the inhibitor to the kinase domain. This in turn promotes conformational changes in the kinase domain that result in nuclear translocation of ERK5 and stimulation of gene transcription. This shows that both the ERK5 kinase and TAD must be considered when assessing the role of ERK5 and the effectiveness of anti-ERK5 therapeutics

Lamotrigine ethanol monosolvate

Lamotrigine is an active pharmaceutical ingredient used as a treatment for epilepsy and psychiatric disorders. Single crystals of an ethanolate solvate, C9H7Cl2N5·C2H5OH, were produced by slow evaporation of a saturated solution from anhydrous ethanol. Within the crystal structure, the lamotrigine molecules form dimers through N—H...N hydrogen bonds involving the amine N atoms in the ortho position of the triazine group. These dimers are linked into a tape motif through hydrogen bonds involving the amine N atoms in the para position. The ethanol and lamotrigine are present in a 1:1 ratio in the lattice with the ethyl group of the ethanol molecule exhibiting disorder with an occupancy ratio of 0.516 (14):0.484 (14)

In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications

The human adenovirus phylogenetic tree is split across seven species (A–G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-existing immunity detected across screened populations. However, many aspects of the basic virology of species D—such as their cellular tropism, receptor usage, and in vivo biodistribution profile—remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)—a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications