Publications by authors named "John Barrett"

Spiking activity along synaptic circuits linking primary somatosensory (S1) and motor (M1) areas is fundamental for sensorimotor integration in cortex. Circuits along the ascending somatosensory pathway through mouse hand/forelimb S1 and M1 were recently described in detail (Yamawaki et al., 2021).

View Article and Find Full Text PDF

The αβ integrin has been identified as a target for the treatment of fibrotic diseases, based on the role it has in activating TGF-β, a protein implicated in the pathogenesis of fibrosis. However, the development of orally bioavailable αβ inhibitors has proven challenging due to the zwitterionic pharmacophore required to bind to the RGD binding site. This work describes the design and development of a novel, orally bioavailable series of αβ inhibitors, developing on two previously published αβ inhibitors, GSK3008348 and GSK3335103.

View Article and Find Full Text PDF

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer type worldwide. In recent years, there has been an increase in the rate of HNSCC cases attributed to the infection of the oropharynx by the human papillomavirus (HPV). Given the significant treatment-related toxicities of the current standard of care for HPV-positive HNSCC, there is an urgent need for the development of precision patient stratification and treatment strategies to improve patients' quality of life while maintaining excellent survival rates.

View Article and Find Full Text PDF

A series of 3-aryl(()-3-fluoropyrrolidin-1-yl)butanoic acids were developed as potent orally bioavailable αβ integrin inhibitors. Starting from a zwitterionic peptidomimetic series optimized for inhaled administration, the balancing of potency and passive permeability to achieve suitable oral agents through modification and exploration of aryl substituents and p of the central cyclic amine is described. ()-4-(()-3-Fluoro-3-(2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl)pyrrolidin-1-yl)-3-(3-(2-methoxyethoxy)phenyl)butanoic acid was found to have highly desirable oral pharmacokinetic profiles in rat, dog, and minipig, with low to moderate clearance (26%, 7%, and 18% liver blood flow, respectively), moderate volumes of distribution (3.

View Article and Find Full Text PDF

Rodent jaws evolved structurally to support dual functionality, for either biting or chewing food. Rodent hands also function dually during food handling, for actively manipulating or statically holding food. How are these oral and manual functions coordinated? We combined electrophysiological recording of muscle activity and kilohertz kinematic tracking to analyze masseter and hand actions as mice of both sexes handled food.

View Article and Find Full Text PDF

Introduction: Military exposures may present a cumulative load and increased individual susceptibility to negative health outcomes. Currently, there are no comprehensive and validated environmental exposure assessment tools covering the full spectrum of occupational and environmental exposures for Veterans. The Veterans Affairs (VA) War Related Illness and Injury Study Center in Washington, DC, developed the Veteran Military Occupational and Environmental Exposure Assessment Tool (VMOAT) to establish a structured, comprehensive self-report tool that captures military and non-military occupational and environmental exposures.

View Article and Find Full Text PDF

Boxazomycins A-C are potent broad-spectrum antibiotics isolated from Actinomycetes strain G495-1 in 1987. We now report that boxazomycin A inhibits bacterial growth by selectively inhibiting protein synthesis, its effect is bacteriostatic, and it is equally active against drug resistant bacterial strains. No cross-resistance to protein synthesis inhibitors was observed suggesting that its inhibition is distinct from clinical protein synthesis inhibitors.

View Article and Find Full Text PDF
Article Synopsis
  • - Understanding military exposures is crucial for Veterans' health, as about 43% report concerns related to these exposures to VA providers, highlighting the need for better assessment methods.
  • - The complex nature of military exposures demands a standardized approach to developing clinically meaningful metrics, which can help clinicians and researchers assess and communicate exposure risks effectively.
  • - The Linked Exposures Across Databases (LEAD) framework offers a solution by integrating various military exposure data sources, facilitating a cohesive evaluation that could enhance how these exposures are managed in health care and research contexts.
View Article and Find Full Text PDF

Drylands are unique among terrestrial ecosystems in that they have a significant proportion of primary production facilitated by non-vascular plants such as colonial cyanobacteria, moss, and lichens, i.e., biocrusts, which occur on and in the surface soil.

View Article and Find Full Text PDF

Background: Magnetic hyperthermia (MHT) has emerged as a promising therapeutic approach in the field of radiation oncology due to its superior precision in controlling temperature and managing the heating area compared to conventional hyperthermia. Recent studies have proposed solutions to address clinical safety concerns associated with MHT, which arise from the use of highly concentrated magnetic nanoparticles and the strong magnetic field needed to induce hyperthermic effects. Despite these efforts, challenges remain in quantifying therapeutic outcomes and developing treatment plan systems for combining MHT with radiation therapy (RT).

View Article and Find Full Text PDF

Introduction: In the Medscape 2020 Compensation Report, family physicians ranked low for feeling fairly compensated, choosing their specialty again and choosing medicine again. However, the Medscape data may not represent military family physicians.

Methods: A large survey was emailed to 2,562 military family physicians via a military professional organization list-serve from February to April 2021.

View Article and Find Full Text PDF

Background: Transoral surgical resectability (TOS) is a prognostic factor for patients with HPV+ T1-2 oropharyngeal squamous cell carcinoma (OPSCC) disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative (HPV-) patients. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage HPV- OPSCC.

View Article and Find Full Text PDF

Estrogen receptor positive (ER) breast cancer is the most common breast cancer diagnosed annually in the US with endocrine-based therapy as standard-of-care for this breast cancer subtype. Endocrine therapy includes treatment with antiestrogens, such as selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs). Despite the appreciable remission achievable with these treatments, a substantial cohort of women will experience primary tumor recurrence, subsequent metastasis, and eventual death due to their disease.

View Article and Find Full Text PDF

Recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC) is associated with a poor prognosis and short survival duration. There is an urgent need to identify personalized predictors of drug response to guide the selection of the most effective therapy for each individual recurrence. We tested the feasibility of patient-derived xenografts (PDX) for guiding their RMHNSCC salvage treatment.

View Article and Find Full Text PDF
Article Synopsis
  • Anaplastic thyroid carcinoma is one of the deadliest cancers and frequently occurs alongside differentiated thyroid cancers, but its aggressive nature is not well understood.
  • Researchers analyzed tumor DNA from 329 regions of thyroid cancer, revealing that anaplastic thyroid carcinomas have more mutations and unique mutational patterns compared to other thyroid cancers.
  • The study shows that although anaplastic and differentiated thyroid carcinomas can occur in the same patient, they have different mutated genes and share a common genetic origin that allows them to develop from a similar malignant environment.
View Article and Find Full Text PDF

Introduction: Buprenorphine extended-release subcutaneous injection (BUP-XR) is a medication used to treat opioid use disorder. It is a long-acting formulation of buprenorphine, which is a partial opioid agonist. Buprenorphine extended-release subcutaneous injection is injected into the subcutaneous space forming a depot that can last up to a month.

View Article and Find Full Text PDF

Human papillomavirus (HPV) is the major causative agent for cervical and many head and neck cancers (HNCs). HPVs randomly acquire single nucleotide polymorphisms (SNPs) that may become established via positive selection. Within an HPV type, viral isolates differing by <2% in the L1 region are termed "variants" and classified based on combinations of SNPs.

View Article and Find Full Text PDF

Background: We aimed to analyze and compare the timing and patterns of treatment failure, and survival after progression between HPV-positive (HPV+) and HPV-negative (HPV-) patients undergoing chemoradiation for oropharyngeal squamous cell carcinomas (OPSCC).

Methods: A retrospective review was performed of all patients undergoing primary chemoradiation for OPSCC between 2008 and 2021. Demographic and clinical data were collected.

View Article and Find Full Text PDF
Article Synopsis
  • Researchers looked at cancer in the head and neck to see how certain features after surgery affect survival and treatment.
  • They found that different problems like nerve invasion and tumor spread were linked to worse survival rates.
  • Specific changes in molecules in the tumors were also found, which could help understand why these issues lead to poorer outcomes for patients.
View Article and Find Full Text PDF

Laryngeal cancer most frequently develops in males aged 60-70 years with a history of tobacco and/or alcohol use, while fewer cases occur in young patients in which tobacco and alcohol are often absent or less significant, highlighting the importance of other etiologies. We present cases of human papillomavirus (HPV)-associated laryngeal cancer in two previously healthy young women. A retrospective case review was carried out for both patients.

View Article and Find Full Text PDF

Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. The etiology of these Anomalous Health Incidents (AHI) and subsequent symptoms remains unknown. This report investigates putative exposure-symptom pathology by assembling a network model of published bio-behavioral pathways and assessing how dysregulation of such pathways might explain loss of function in these subjects using data available in the published literature.

View Article and Find Full Text PDF

Objectives: Although human papillomavirus positive (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients typically experience excellent survival, 15-20 % of patients recur after treatment with chemotherapy and radiation. Therefore, there is a need for biomarkers of treatment failure to guide treatment intensity.

Materials And Methods: Whole genome sequencing was carried out on HPV+OPSCC patients who were primarily treated with concurrent chemotherapy (cisplatin) and radiation.

View Article and Find Full Text PDF

Background: Despite widespread study of dendritic cell (DC)-based cancer immunotherapies, the in vivo postinjection fate of DC remains largely unknown. Due in part to a lack of quantifiable imaging modalities, this is troubling as the amount of DC migration to secondary lymphoid organs correlates with therapeutic efficacy. Magnetic particle imaging (MPI) has emerged as a suitable modality to quantify in vivo migration of superparamagnetic iron oxide (SPIO)-labeled DC.

View Article and Find Full Text PDF

Stereotactic radiotherapy (SRT) methods have become common for the treatment of small tumors in various parts of the body. Small field dosimetry has a unique set of challenges when it comes to the pre-treatment validation of a radiotherapy plan that involves film dosimetry or high-resolution detectors. Comparison of commercial quality assurance (QA) devices to the film dosimetry method for pre-treatment evaluation of stereotactic radiosurgery (SRS), fractionated SRT, and stereotactic body radiation therapy treatment plans have been evaluated in this study.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: