Brick by Brick: Building a Transdiagnostic Understanding of Inflammation in Psychiatry.

ABSTRACT: Inflammatory phenomena are found in many psychiatric disorders-notably, depression, schizophrenia, and posttraumatic stress disorder. Inflammation has been linked to severity and treatment resistance, and may both contribute to, and result from, the pathophysiology of some psychiatric illnesses. Emerging research suggests that inflammation may contribute to symptom domains of reward, motor processing, and threat reactivity across different psychiatric diagnoses. Reward-processing deficits contribute to motivational impairments in depression and schizophrenia, and motor-processing deficits contribute to psychomotor slowing in both depression and schizophrenia. A number of experimental models and clinical trials suggest that inflammation produces deficits in reward and motor processing through common pathways connecting the cortex and the striatum, which includes the nucleus accumbens, caudate nucleus, and putamen.The observed effects of inflammation on psychiatric disorders may cut across traditional conceptualizations of psychiatric diagnoses. Further study may lead to targeted immunomodulating treatments that address difficult-to-treat symptoms in a number of psychiatric disorders. In this review, we use a Research Domain Criteria framework to discuss proposed mechanisms for inflammation and its effects on the domains of reward processing, psychomotor slowing, and threat reactivity. We also discuss data that support contributing roles of metabolic dysregulation and sex differences on the behavioral outcomes of inflammation. Finally, we discuss ways that future studies can help disentangle this complex topic to yield fruitful results that will help advance the field of psychoneuroimmunology.

Ultra-High-Field Magnetic Resonance Imaging of the Human Inner Ear at 11.7 Tesla.

OBJECTIVE: To evaluate the ability of ultra-high-field magnetic resonance imaging (UHF-MRI) at 11.7 T to visualize membranous structures of the human inner ear. SPECIMENS: Three temporal bones were extracted from cadaveric human heads for use with small-bore UHF-MRI. INTERVENTION: Ex vivo cadaveric temporal bone specimens were imaged using an 11.7 T magnetic resonance imaging (MRI) scanner via T1- and T2-weighted-imaging with and without contrast. MAIN OUTCOME MEASURE: Qualitative visualization of membranous components of the inner ear compared with reports of UHF-MRI at lower field strengths. RESULTS: The membranous anatomy of the inner ear was superbly visualized at 11.7 T. In the cochlea, Reissner's membrane, the scala media, and the basilar membrane were clearly shown on the scan. In the vestibular labyrinth, the wedge-shaped crista ampullaris and the maculae of both the saccule and utricle were visible. Details of the endolymphatic sac and duct were also demonstrated. CONCLUSION: To our knowledge, this report presents the first images of the ex vivo human inner ear using 11.7 T UHF-MRI, offering near-histologic resolution. Increased field strength may be particularly useful when imaging the delicate membranous anatomy of the inner ear. Further research on the use of UHF-MRI in clinical and research settings could illuminate structural changes associated with inner ear disorders.

Overcoming radioresistance in head and neck squamous cell carcinoma.

Radiation therapy plays an essential role in the treatment of head and neck squamous cell carcinoma (HNSCC), yet therapeutic efficacy is hindered by treatment-associated toxicity and tumor recurrence. In comparison to other cancers, innovation has proved challenging, with the epidermal growth factor receptor (EGFR) antibody cetuximab being the only new radiosensitizing agent approved by the FDA in over half a century. This review examines the physiological mechanisms that contribute to radioresistance in HNSCC as well as preclinical and clinical data regarding novel radiosensitizing agents, with an emphasis on those with highest translational promise.

The effect of human papillomavirus on DNA repair in head and neck squamous cell carcinoma.

Much of the current literature regarding the molecular pathophysiology of human papillomavirus (HPV) in head and neck squamous cell carcinoma (HNSCC) has focused on the virus's effect on cell cycle modulation and cell proliferation. A second mechanism of pathogenicity employed by HPV, dysregulation of cellular DNA repair processes, has been more sparsely studied. The purpose of this review is to describe current understanding about the effect of HPV on DNA repair in HNSCC, taking cues from cervical cancer literature. HPV affects DNA-damage response pathways by interacting with many proteins, including ATM, ATR, MRN, γ-H2AX, Chk1, Chk2, p53, BRCA1, BRCA2, RAD51, Rb-related proteins 107 and 130, Tip60, and p16INK4A. Further elucidation of these pathways could lead to development of targeted therapies and improvement of current treatment protocols.

Device Life of Two Generations of Provox Voice Prostheses.

BACKGROUND: Tracheoesophageal voice prostheses are invaluable for speech rehabilitation in patients who have received total laryngectomy, but device failure impedes communication and creates psychosocial and financial burdens. This study compares the Provox 2 and Provox Vega voice prostheses on the parameter of device life. METHODS: This was a retrospective observational study of 21 patients with 181 device replacements at an academic tertiary care medical center. Disparity in device life and factors that may influence device life were analyzed. RESULTS: The mean device life for Provox 2, at 115.6 days (SE = 5.8), was longer than for Provox Vega, at 65.1 days (SE = 7.5) (P < .001). CONCLUSIONS: Device longevity was greater for Provox 2 over Provox Vega. These results will facilitate the design of prospective studies to assess reasons for variations in device life between patients and device types.