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Patients with established rheumatoid arthritis (RA) demonstrate altered immune responses to Epstein-Barr virus (EBV), but the presence and roles of EBV have not been fully explored during the pre-clinical disease period. This study was undertaken to determine if EBV infection, as evidenced by an altered anti-EBV antibody response, either plays an important role in driving the development of RA or is a result of expanded RA-related autoimmunity.A total of 83 subjects with RA according to the 1987 American College of Rheumatology (ACR) criteria and 83 age-, sex-, and race-matched control subjects without RA were included in our study. We collected sera from RA subjects and matched controls during the pre-RA and post-RA diagnosis periods and tested the sera for the presence of 5 anti-EBV antibodies (anti-EBV nuclear antigen 1 IgG isotype, anti-viral capsid antigen [anti-VCA] isotypes IgG and IgA, and anti-early antigen [EA] isotypes IgG and IgA), 7 RA-related autoantibodies (rheumatoid factor measured by nephelometry [RF-Neph] as well as isotype-specific IgA-RF, IgM-RF, and IgG-RF, and anti-cyclic citrullinated peptide [anti-CCP] antibodies, including anti-CCP2, anti-CCP3, and anti-CCP3.1), 22 cytokines/chemokines, 36 individual anti-citrullinated protein antibodies, and IgG-cytomegalovirus (CMV) antibodies. Random forest classification, mixed modeling, and joint mixed modeling were used to determine differences in anti-EBV antibody levels between RA subjects and controls.Random forest analysis identified the presence of preclinical EBV antibodies in the serum that differentiated RA subjects from controls without RA. Specifically, IgG-EA antibody levels were higher in RA subjects (mean ± SD 0.82 ± 0.72 international standardized ratio [ISR]) compared to controls (mean ± SD 0.49 ± 0.28 ISR). In subjects with RA, elevated serum IgG-EA levels in the preclinical period before seroconversion were significantly correlated with increased serum IgM-RF levels (P = 0.007), whereas this correlation was not seen in control subjects without RA (P = 0.15). IgG-CMV antibody levels did not differ between groups.Subjects whose serum IgG-EA antibody levels are elevated in the preclinical period will eventually develop RA, which suggests that EBV reactivation cycles are increased during the preclinical period of RA. A combination of RF and EBV reactivation may play an important role in the development of RA.

Introduction Paranasal sinus mucoceles result from obstruction of mucous glands resulting in a cystic fluid collection that expands and encroaches upon surrounding structures. Transnasal endoscopic marsupialization has largely replaced open resection. However, mucoceles located in the orbital region or the lateral frontal sinus continue to be difficult to approach via the transnasal approach alone and often require additional approaches, such as the frontal trephine. This study sought to investigate the feasibility of the transorbital technique as an adjunct to traditional transnasal approaches in the management of paranasal sinus mucoceles. Methods A retrospective case series of paranasal sinus mucoceles approached with a transorbital technique from a tertiary care center. Results From 2008 to 2016, 17 patients were treated with a transorbital approach for 20 mucoceles. Of note, 24% of the patients in our series had undergone previous surgical management of the mucocele (nontransorbital approach), representing revision cases. Most mucoceles involved the frontal sinus (82%). The total complication rate was 6%. We observed no new or worsened diplopia, ptosis, or permanent visual loss. Recurrence rate was 6%. Conclusions The endoscopic transorbital approach is a feasible complement to transnasal approaches for treatment of mucoceles located in technically challenging locations. We have demonstrated that transorbital approaches can be performed with no resultant orbital damage, visual change, ptosis, or permanent diplopia. While most patients can be treated with a standard transnasal approach, the transorbital approach can be used as part of a multiportal strategy for those with difficult to access mucoceles. Future prospective studies are needed to further characterize patient selection and outcomes.

Despite common goals of frontal sinus fracture treatment (restoring forehead contour and creating a safe sinus), there remains significant variability in evaluation and treatment.To describe our experience with a minimally disruptive treatment protocol for the treatment of frontal sinus fractures.Analysis of prospectively collected data from 2010 through 2015 at a level 1 trauma center. All patients with frontal sinus fractures treated with our protocol from January 2010 to December 2015. Patients with poor follow-up and/or incomplete medical records were excluded from analysis.Presence of an aerated frontal sinus and aesthetically acceptable forehead contour. Secondary outcome measures were complications related to frontal sinus fractures.A total of 39 patients were treated under our minimally disruptive protocol, and 25 patients were included in the study; 18 (72%) were male and 7 (28%) were female. Their ages ranged from 6 to 62 years. After review, 22 patients had both clinical and radiographic follow-up. No patients underwent immediate frontal sinus repair. Five of 22 patients underwent surgery for indications other than their frontal sinus fracture: 1 of 5 patients underwent immediate surgical repair due to bilateral LeFort fractures, and 4 of 5 underwent delayed surgery due to nasal polyps (1 patient), scar revision (1 patient), and concomitant LeFort fractures (2 patients). Two of 22 patients (9%) underwent frontal sinus repair after outpatient surveillance due to persistent cerebrospinal fluid leak (1 patient) and orbital roof fracture (1 patient). The remaining 20 patients were treated nonoperatively, and 19 of 20 (95%) had spontaneous improvement in opacification and/or contour deformity. Twelve of 20 patients (60%) had improvement or resolution in both. One patient had ongoing partial opacification and deformity at the 3-month follow-up but was asymptomatic and had bony contour that was aesthetically acceptable to the patient. There were no complications. The median of all follow-up was 3 months.Frontal sinus fractures treated nonoperatively had a high rate of spontaneous ventilation and bony autoreduction with aesthetically acceptable frontal bone remodeling. There were no complications in the nonoperative group. The initial results of this study support further study of the safety and efficacy of a minimally disruptive protocol for frontal sinus fractures.4.

Purpose Automated delineation of structures and organs is a key step in medical imaging. However, due to the large number and diversity of structures and the large variety of segmentation algorithms, a consensus is lacking as to which automated segmentation method works best for certain applications. Segmentation challenges are a good approach for unbiased evaluation and comparison of segmentation algorithms. Methods In this work, we describe and present the results of the Head and Neck Auto-Segmentation Challenge 2015, a satellite event at the Medical Image Computing and Computer Assisted Interventions (MICCAI) 2015 conference. Six teams participated in a challenge to segment nine structures in the head and neck region of CT images: brainstem, mandible, chiasm, bilateral optic nerves, bilateral parotid glands, and bilateral submandibular glands. Results This paper presents the quantitative results of this challenge using multiple established error metrics and a well-defined ranking system. The strengths and weaknesses of the different auto-segmentation approaches are analyzed and discussed. Conclusions The Head and Neck Auto-Segmentation Challenge 2015 was a good opportunity to assess the current state-of-the-art in segmentation of organs at risk for radiotherapy treatment. Participating teams had the possibility to compare their approaches to other methods under unbiased and standardized circumstances. The results demonstrate a clear tendency toward more general purpose and fewer structure-specific segmentation algorithms.

BACKGROUND Defensins are peptides shown to activate LGR6 stem cells to stimulate the production of new basal stem cells in the epidermis. Use of topical definsin-containing products has been shown to address signs of global skin aging including decrease of wrinkles and increase of epidermal thickness. AIMS To investigate the ability of a topical defensin-containing skincare product in improving the structure and function of aging periocular skin using objective and subjective outcome measures. PATIENTS/METHODS A prospective pilot trial of a defensin-containing eye cream was performed in patients with periocular rhytids over 6 weeks. Subjective changes in skin quality and aging characteristics were compared using a patient survey tool. Objective changes in periocular skin quality were analyzed using the QuantifiCare imaging system and the DermLab ultrasound scanner by blinded reviewers. RESULTS A total of eight patients completed treatment; two were male, and six were female. The average age was 51 years (range 37-63). Compliance with product application as reported on the participant application log was over 90%. Overall, there was an average 2.1 point improvement in subjective measures of skin quality on the consumer questionnaire (P = .002). QuantifiCare imaging of pores, wrinkles, and oiliness showed 370% improvement, 55% improvement, and 12% improvement, respectively. DermaLab noninvasive measurements of elasticity, skin thickness, and hydration showed improvement of 120%, 28%, and 6%, respectively. CONCLUSION The use of topical formulations of definsin-containing eye cream statically improves patient-reported outcomes of skin quality, especially redness, sensitivity to weather, age spots, and crow's feet.

The tumor suppressor p53 plays a critical part in determining cell fate both as a regulator of the transcription of several proapoptotic genes and through its binding interactions with Bcl-2 family proteins at mitochondria. We now demonstrate that p53 protein levels are increased in infected brains during reovirus encephalitis. This increase occurs in the cytoplasm of reovirus-infected neurons and is associated with the activation of caspase 3. Increased levels of p53 in reovirus-infected brains are not associated with increased expression levels of p53 mRNA, suggesting that p53 regulation occurs at the protein level. Increased levels of p53 are also not associated with the increased expression levels of p53-regulated, proapoptotic genes. In contrast, upregulated p53 accumulates in mitochondria. Previous reports demonstrated that the binding of p53 to Bak at mitochondria causes Bak activation and results in apoptosis. We now show that Bak is activated and that activated Bak is bound to p53 during reovirus encephalitis. In addition, survival is enhanced in reovirus-infected Bak −/− mice compared to controls, demonstrating a role for Bak in reovirus pathogenesis. Inhibition of the mitochondrial translocation of p53 with pifithrin μ prevents the formation of p53/Bak complexes following reovirus infection of ex vivo brain slice cultures and results in decreased apoptosis and tissue injury. These results suggest that the mitochondrial localization of p53 regulates reovirus-induced pathogenesis in the central nervous system (CNS) through its interactions with Bak. IMPORTANCE There are virtually no specific treatments of proven efficacy for virus-induced neuroinvasive diseases. A better understanding of the pathogenesis of virus-induced CNS injury is crucial for the rational development of novel therapies. Our studies demonstrate that p53 is activated in the brain following reovirus infection and may provide a therapeutic target for virus-induced CNS disease.

Array Comparative Genomic Hybridization (aCGH) is a widely used technique to assess chromosomal copy number alterations. Chromosomal content, however, is often not uniform throughout cell populations. Here we evaluated to what extent aCGH can detect DNA copy number alterations in heterogeneous cell populations. A systematic evaluation is currently lacking, despite its importance in diagnostics and research. The detection limits reported are a compound of analytical software and laboratory techniques and do not account for the number of probes in relation to sample homogeneity. Detection limits were explored with DNA isolated from a patient with intellectual disability (ID) and from tumor cell line BT474. Both were diluted with increasing amounts of normal DNA to simulate different levels of cellularity. Samples were hybridized on microarrays containing 180,880 oligonucleotides evenly distributed over the genome (spacing similar to 17 kb). Single copy number alterations, represented by down to 249 probes (4 Mb) and present in 10 % of a cell population, could be detected. Alterations encompassing as few as 14 probes (similar to 238 Kb) could also be detected, but for this a 35 % mosaic level was required. DNA copy number alterations can be detected in cell populations containing 10 % abnormal cells. Detection of sub-megabase alterations requires a higher percentage of abnormal cells or microarrays with a higher probe density

Hintergrund. Die Messung der Lebensqualitat (LQ) gehort bei Patienten mit Kopf-Hals-Tumoren nicht zum Routineprogramm jeder Nachsorgesprechstunde, obwohl die Lebensqualitat bei diesen Patienten eingeschrankt ist.