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Biomedical subjects

Thomas M Pearce

Publications and source records attributed to Thomas M Pearce.

5 recordsLinked to original sources

Genomic hallmarks of depot medroxyprogesterone acetate-associated meningiomas.

BACKGROUND: Population-based studies have linked progestin exposure to increased meningioma risk. However, the molecular basis of meningiomas associated with depot medroxyprogesterone acetate (DMPA)-a common injectable contraceptive-remains undefined. METHODS: We performed an integrated clinicopathologic and genomic analysis of meningiomas from 10 women with long-term DMPA exposure. Tumors underwent histopathological analysis, targeted sequencing, and DNA methylation profiling. Data were integrated with reference cohorts (Baylor and Heidelberg) and analyzed through classifier assignment, consensus clustering, copy number analysis, differential methylation testing, and dimensionality reduction. RESULTS: Depot medroxyprogesterone acetate-associated meningiomas were all newly diagnosed, World Health Organization grade 1 tumors with a predilection for the anterior and central skull base (n = 6). Nine patients harbored multiple meningiomas. Four experienced regression of untreated meningiomas following DMPA cessation, while 5 demonstrated stabilization. Histopathology demonstrated relative overrepresentation of metaplastic morphology, an uncommon meningioma subtype. All DMPA-associated meningiomas mapped to benign molecular groups, and most exhibited low copy number alteration burden. Targeted sequencing revealed enrichment for TRAF7 mutations (n = 5), with no NF2 mutations detected. Eight tumors shared consensus cluster identity, with cohesive grouping on principal component analysis and t-distributed stochastic neighbor embedding. No differential methylation was identified at the progesterone receptor locus. CONCLUSIONS: Depot medroxyprogesterone acetate-associated meningiomas represent a recognizable phenotype within the broader NF2-wildtype/TRAF7-enriched spectrum of benign meningiomas, characterized by chromosomal stability, a shared methylation profile, tumor multiplicity, and regression or stabilization following DMPA cessation. While derived from a small single-institution cohort, these findings provide a molecular framework for understanding progestin-associated meningioma biology, reinterpreting epidemiologic literature, and informing population-level risk stratification.

Humans↗

Microtechnology: meet neurobiology.

The field of neuroscience has always been attractive to engineers. Neurons and their connections, like tiny circuit elements, process and transmit information in a dramatic way that is intimately curious to researchers in the computer science and engineering fields. Of particular interest has been the recent push in applying microtechnology to the field of neuroscience. This review is meant to provide an overview of some of the subtle nuances of the nervous system and outline recent advances in lab on a chip applications in neurobiology. It also aims to highlight some of the challenges the field faces in the hopes of encouraging new engineering researchers to collaborate with neurobiologists to help advance our basic understanding of the nervous system and create novel applications based on neuroengineering principles.

Animals↗

Dynamic control of extracellular environment in in vitro neural recording systems.

A technique is presented for rapid fabrication of microfluidic channels on top of multichannel in vitro neural recording electrode arrays. The channels allow dynamic control of both stable and transient flow patterns over localized areas of the array, over biologically relevant timescales. A cellular model consisting of thermally sensitive dorsal root ganglion neurons was integrated into the devices. The device was used to demonstrate precise control of the extracellular microenvironment of individual cells on the array. Since the methods presented here are not specific to a particular cell type or neural recording system, the technique is amenable to a wide range of applications within the neuroscience field.

Animals↗

Integrated microelectrode array and microfluidics for temperature clamp of sensory neurons in culture.

A device for cell culture is presented that combines MEMS technology and liquid-phase photolithography to create a microfluidic chip that influences and records electrical cellular activity. A photopolymer channel network is formed on top of a multichannel microelectrode array. Preliminary results indicated successful local thermal control within microfluidic channels and control of lamina position over the electrode array. To demonstrate the biological application of such a device, adult dissociated dorsal root ganglion neurons with a subpopulation of thermally-sensitive cells are attached onto the electrode array. Using laminar flow, dynamic control of local temperature of the neural cells was achieved while maintaining a constant chemical culture medium. Recording the expected altered cellular activity confirms the success of the integrated device.

Action Potentials↗

An externally driven magnetic microstirrer.

In this paper, an inexpensive, easy-to-fabricate active magnetic mixer is presented. This mixer functions on top of a common magnetic stir plate and is capable of mixing two streams, each at flow rates up to 5 ml min(-1). A liquid-phase photopolymerization technique is used to fabricate the device. An analysis of mixing efficiency is based on greyscale intensity measurements of two coloured streams passing through the mixer. A brief hypothesis of the mechanism of mixing is also presented.

Complex Mixtures↗