Effect of Head Position and Magnetic Resonance Sequence on Cochlear Implant-Related Artifact Size and Internal Auditory Canal Visibility.

HYPOTHESIS: To assess whether cochlear implant (CI)-related magnetic resonance imaging (MRI) artifact and visibility of the internal auditory canal (IAC) can be improved with head positioning and select MRI sequences. BACKGROUND: CI-related MRI artifact limits the use of CIs in otherwise good candidates because of the need for serial MRIs for monitoring of pathology. This most notably impacts patients with tumors of the cerebellopontine angle and IAC. METHODS: Two cadaver heads were implanted with either a Med-El CONCERT (fixed magnet) or SYNCHRONY (rotating magnet) device. Each head was imaged in a 1.5T scanner in 11 different positions. The SYNCHRONY-implanted head was also imaged in a 3.0T scanner in seven positions. Artifact size and IAC visibility (graded on a Likert scale) were measured for each head position by a neuroradiologist. RESULTS: The CONCERT CI produced significantly smaller artifact than the SYNCHRONY CI (effect size, 14.65 mm; p < 0.001). There was no significant difference between CI models in regard to IAC visibility. No head positions were statistically significantly better than neutral position for minimizing artifact size or IAC visibility, although some positions resulted in significantly larger artifact (effect sizes, 2.1-14.3 mm; p < 0.05) or significantly poorer IAC visibility (effect size, 1.4; p < 0.01). The T2 three-dimensional (CISS/FIESTA) sequence demonstrated significantly smaller artifact than T1 sequences, whereas T1 sequences demonstrated significantly better IAC visibility than T2 sequences. CONCLUSION: Head positioning and magnetic resonance sequence selection impact CI-related artifact size and IAC visibility.

The domestic cat antibody response to feline herpesvirus-1 increases with age.

Herpesviruses establish lifelong infections, normally characterized by prolonged periods of latency with intermittent episodes of viral reactivation. Feline herpesvirus-1 (FHV-1) infects domestic cats, and epidemiological studies indicate that many or most domestic cats are exposed to FHV-1, but the strength and longevity of the antibody response to FHV-1 is not fully characterized. Here we describe development of an ELISA, using lysates of cat cells infected with FHV-1, that measure feline antibodies against FHV-1. The assay is sensitive, quantitative and has a large dynamic range. We found that serum anti-FHV-1 antibodies primarily recognize FHV-1 proteins of the Late (L) class and are primarily of the IgG isotype. We then analyzed serum from a cross-sectional cohort of 100 client-owned cats that differed in age, sex and vaccination history. While there was no difference in FHV-1 antibody responses between females and males, antibody levels were significantly increased in older cats in comparison with younger animals (p=0.01). Surprisingly, as the length of time since the most recent vaccination increased, there was no corresponding drop in serum anti-FHV-1 antibody. These data suggest that FHV-1 immunity is very long-lived and support the current recommendation that many cats do not require revaccination against FHV-1 annually.

Correction: Natalizumab stabilizes physical, cognitive, MRI, and OCT markers of disease activity: A prospective, non-randomized pilot study.

[This corrects the article DOI: 10.1371/journal.pone.0173299.].

Natalizumab stabilizes physical, cognitive, MRI, and OCT markers of disease activity: A prospective, non-randomized pilot study.

Natalizumab is an effective therapy for multiple sclerosis (MS). Its effectiveness has been demonstrated in several clinical and imaging studies. The objective of this study was to further demonstrate the efficacy of natalizumab using a comprehensive battery of clinical and imaging markers in the same cohort of patients followed longitudinally, hence capturing the multi-faceted nature of the MS disease process. A prospective, open-label, pilot study of 20 MS patients treated with natalizumab was conducted. High resolution MRI, Symbol-Digit Modalities Test (SDMT), and Optical Coherence Tomography (OCT) scans were obtained at baseline, 48, and 96 weeks. 15 patients completed the study. Natalizumab treatment decreased Expanded Disability Status Scale score (EDSS) and no change in SDMT, Brain Parenchymal Fraction (BPF), or any of the OCT markers of retinal degeneration was observed. Thalamic and whole brain volume as assessed by Percentage Brain Volume Change (PBVC) showed continuous deterioration. Higher baseline T2 lesion load correlated with increased rate of PBVC at 96-weeks (r = 0.566, R2 = 0.320, p = 0.035) and thalamic volume loss (r = -0.586, R2 = 0.344, p = 0.027). Most patients, 93%, achieved no evidence of disease activity (NEDA) at 2 years, likely due to early disease duration and lower initial baseline lesion load. This study further demonstrates stabilization of clinical and imaging markers of disease activity during natalizumab treatment.

Anatomic basis of the middle temporal artery periosteal rotational flap in otologic surgery.

OBJECTIVES/HYPOTHESIS: To describe the elements critical to successful middle temporal artery periosteal rotational flap harvest and utilization based on the anatomic features of the middle temporal artery. STUDY DESIGN: Description of anatomy based on cadaver dissection. METHODS: Seventy temporal fossa dissections were performed on 35 adult human cadavers. RESULTS: Sixty-nine of 70 dissections had an identifiable middle temporal artery muscular branch pedicle in the periosteum deep to the temporalis muscle. Pedicle length was at least 7 cm in 32 of 38 (84%) male cadavers and in 20 of 31 (65%) female cadavers (P = 0.054), whereas the average length required to reach the digastric ridge from the pedicle base to the digastric ridge in a mastoidectomy cavity was 5.2 cm. The pedicle sharply transitions from a posterior to a posterior-superior course 0.93 cm superior (range: 0.5-1.9 cm) and 0.04 cm posterior (range: 1.4 cm posterior-0.7 cm anterior) to the spine of Henle. Branching occurred in 26 of 69 pedicles (38%), and 20 of 31 (65%) branches were oriented posteriorly. If temporalis muscle fibers are not incorporated into the flap, the thickness is roughly three times that of a standard temporalis fascia graft. CONCLUSION: The muscular branch of the middle temporal artery is reliably identified in the periosteum deep to the posterior aspect of the temporalis muscle, and this vessel is sufficiently robust to provide axial blood supply to a rotational periosteal flap that has sufficient thickness and length to allow a variety of applications in otologic surgery. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:1426-1432, 2016.

Structural and functional analysis of the human nuclear xenobiotic receptor PXR in complex with RXRα.

The human nuclear xenobiotic receptor PXR recognizes a range of potentially harmful drugs and endobiotic chemicals but must complex with the nuclear receptor RXRα to control the expression of numerous drug metabolism genes. To date, the structural basis and functional consequences of this interaction have remained unclear. Here we present 2.8-Å-resolution crystal structures of the heterodimeric complex formed between the ligand-binding domains of human PXR and RXRα. These structures establish that PXR and RXRα form a heterotetramer unprecedented in the nuclear receptor family of ligand-regulated transcription factors. We further show that both PXR and RXRα bind to the transcriptional coregulator SRC-1 with higher affinity when they are part of the PXR/RXRα heterotetramer complex than they do when each ligand-binding domain is examined alone. Furthermore, we purify the full-length forms of each receptor from recombinant bacterial expression systems and characterize their interactions with a range of direct and everted repeat DNA elements. Taken together, these data advance our understanding of PXR, the master regulator of drug metabolism gene expression in humans, in its functional partnership with RXRα.

HLA-A2-matched peripheral blood mononuclear cells from type 1 diabetic patients, but not nondiabetic donors, transfer insulitis to NOD-scid/γc(null)/HLA-A2 transgenic mice concurrent with the expansion of islet-specific CD8+ T cells.

OBJECTIVE: Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing ß-cells. NOD mice provide a useful tool for understanding disease pathogenesis and progression. Although much has been learned from studies with NOD mice, increased understanding of human type 1 diabetes can be gained by evaluating the pathogenic potential of human diabetogenic effector cells in vivo. Therefore, our objective in this study was to develop a small-animal model using human effector cells to study type 1 diabetes. RESEARCH DESIGN AND METHODS: We adoptively transferred HLA-A2-matched peripheral blood mononuclear cells (PBMCs) from type 1 diabetic patients and nondiabetic control subjects into transgenic NOD-scid/γc(null)/HLA-A*0201 (NOD-scid/γc(null)/A2) mice. At various times after adoptive transfer, we determined the ability of these mice to support the survival and proliferation of the human lymphoid cells. Human lymphocytes were isolated and assessed from the blood, spleen, pancreatic lymph node and islets of NOD-scid/γc(null)/A2 mice after transfer. RESULTS: Human T and B cells proliferate and survive for at least 6 weeks and were recovered from the blood, spleen, draining pancreatic lymph node, and most importantly, islets of NOD-scid/γc(null)/A2 mice. Lymphocytes from type 1 diabetic patients preferentially infiltrate the islets of NOD-scid/γc(null)/A2 mice. In contrast, PBMCs from nondiabetic HLA-A2-matched donors showed significantly less islet infiltration. Moreover, in mice that received PBMCs from type 1 diabetic patients, we identified epitope-specific CD8(+) T cells among the islet infiltrates. CONCLUSIONS: We show that insulitis is transferred to NOD-scid/γc(null)/A2 mice that received HLA-A2-matched PBMCs from type 1 diabetic patients. In addition, many of the infiltrating CD8(+) T cells are epitope-specific and produce interferon-γ after in vitro peptide stimulation. This indicates that NOD-scid/γc(null)/A2 mice transferred with HLA-A2-matched PBMCs from type 1 diabetic patients may serve as a useful tool for studying epitope-specific T-cell-mediated responses in patients with type 1 diabetes.