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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.

Mechanical ventilators are beneficial in treating and managing various respiratory diseases, including interstitial pneumonia associated with Coronavirus infection (COVID-19). The unprecedented COVID-19 pandemic has led to the emergence of a worldwide need for more accessible and affordable mechanical ventilatory devices. This project, known as the Third Coast Ventilator, aims to create a low-cost, open-source solution to the ventilator shortage created by the COVID-19 pandemic; this device can additionally be implemented in developing countries with limited medical resources, where ventilators are often inaccessible. Using readily available components found within hospitals and local stores, our team designed a prototype that can be assembled and functional within an hour. Our testing demonstrated accurate tidal volume delivery while modulating commonly used ranges of inspiratory to expiratory ratios, air flow rates, and respiratory rates. These promising results are an important step toward our goal of creating a low-cost, open-source, globally accessible ventilator in areas where shortages exist.

Purpose Service learning consists of service activities that respond to community-identified concerns, active learning about the population being served, and self-reflecting on the experience. The Service Learning Program (SLP) is a novel, student-led, longitudinal volunteering experience designed to address social determinants of health (SDOH) education in the undergraduate medical school curriculum. In this program, medical students complete requirements in three domains of service, education, and self-reflection over the span of one academic year. Methods and materials Participating students are sent surveys prior to and after a year of participation in SLP, which are aimed to measure changes in their perceived knowledge, attitudes, and skills in multiple domains related to service learning and social determinants of health. Results Over the course of the 2019-2020 year, 110 students who participated in SLP responded to both pre- and post-surveys. These students reported significant improvements in their confidence in various knowledge and skills related to SDOH, such as identifying vulnerable populations and assessing community needs. They also were more likely to report that learning about social determinants of health was 'very important' after participating the program. Conclusions Medical students participating in a longitudinal service learning program focused on SDOH can acquire knowledge and skills that will empower them to understand, advocate, and care for underserved populations as future physicians. This program provides a model for integrating service learning into undergraduate medical education.

Objective.We investigated the association of age and anticyclic citrullinated peptide antibodies (anti-CCP) in subjects without rheumatoid arthritis (RA).Methods.Serum was tested for anti-CCP3.1 (IgG/IgA) in 678 first-degree relatives (FDR) of patients with RA and 330 patients with osteoarthritis (OA). Individual isotypes (anti–CCP-IgA and anti–CCP-IgG) were also tested in all FDR.Results.In FDR, increasing age was significantly associated with positivity for anti-CCP3.1 (per year, OR 1.03) and anti–CCP-IgA (per year, OR 1.05) but not anti–CCP-IgG. In FDR and OA subjects, anti-CCP3.1 prevalence was significantly increased after age 50 years.Conclusion.Increasing age in individuals without RA should be considered in the interpretation of anti-CCP3.1 positivity.

Treatment of pediatric skull base disorders is complex and requires individual planning. Compared to adult patients, the pathologies are more congenital and benign. Advanced surgical planning has been shown to improve outcomes and involves a variety of different software platforms to enable sophisticated review of image data sets, including virtual endoscopy and the details of surgical approach options. There are greater than 50 open and endoscopic surgical approaches described. Endoscopic approaches in patients under age 4 are extremely challenging due to the underdeveloped sinuses and overall smaller size of the craniofacial skeleton and nasal cavity. A multidisciplinary surgical team should develop and review surgical plan options with the patient and family.

Purpose The risks and benefits of remote corticosteroid weaning in heart transplant recipients more than 2 years post-transplant are unknown. We compared outcomes in patients undergoing early and remote steroid weaning after heart transplantation. Methods We performed a retrospective study (range 09, 1991-04, 2017). Primary outcomes included short-term and long-term mortality, allograft dysfunction, and burden of rejection. Secondary outcomes included impact on hemoglobin A1c, lipid panel, bone scan T-score, and body mass index. Results 63 patients underwent corticosteroid weaning between 2012 and 2017. Outcomes of patients weaned early (n = 34; median time from transplant = 1.1 years) were compared with those weaned late (n = 29; median time from transplant = 4.4 years). 52 (82.5%) patients were successfully weaned off corticosteroids. No statistically significant difference in outcomes was found between the early and late weaning groups (p = .20). There were no differences in allograft function (p-value = .16), incidence of rejection (p = .46), or mortality (p = .15). Improvement in metabolic profile was seen in both groups but was not statistically significant. Conclusions In heart transplant recipients, remote vs early weaning of corticosteroids is not associated with significant differences in graft function or the incidence of rejection after 1-year follow-up. Moreover, there were no significant differences in survival up to 3 years between the two groups.

Einleitung Knapp ein Viertel der Bevölkerung Deutschlands sind Menschen mit Migrationshintergrund (MMH), wichtige Herkunftsländer sind die Türkei, Kasachstan und die Russische Föderation. Bisherige Studienergebnisse deuten an, dass MMH eine geringe Gesundheitskompetenz (GK) aufweisen; allerdings fehlen vertiefende Daten zu einzelnen Gruppen, ebenso wie zu Gründen und Konsequenzen geringer GK bei MMH. Das von der Robert Bosch-Stiftung geförderte Projekt HLS-MIG hat diese Datenlücke nun weiter geschlossen. Methoden Der bisher eingesetzte Fragebogen aus der HLS-GER-Studie wurde auf der Basis von Literaturrecherchen und Fokusgruppen-Interviews durch migrations- und kulturspezifische Aspekte ergänzt und ins Türkische und Russische übersetzt. GK wird mit dem HLS-EU-Q47 erhoben. Im Frühjahr 2020 werden ca. 1.000 MMH (jeweils ca. 500 Personen mit russisch- und türkischsprachigem Hintergrund) bundesweit durch bilinguale Interviewer*innen persönlich befragt. Die Daten werden stratifiziert für die beiden Gruppen multivariat analysiert. Ergebnisse Auf der DGSMP-Tagung 2020 werden erste Ergebnisse aus dem HLS-MIG präsentiert. Die Daten zur umfassenden GK der MMH werden dabei unter Berücksichtigung spezifischer Determinanten der Zielgruppe (u.a. soziodemographische Aspekte, Sprachkenntnisse, Aufenthaltsdauer, Religiosität, Diskriminierungserfahrungen, Informationspräferenzen, soziale Unterstützung) analysiert, eingeordnet und diskutiert. Fazit Der HLS-MIG liefert erstmals vertiefte Ergebnisse zur GK bei MMH und ihren zielgruppenspezifischen Determinanten. Diese dienen als Basis für die systematische und empirisch fundierte Entwicklung zielgruppenspezifischer Interventionen zur Förderung der Gesundheitskompetenz.

We report the case of a 23-year-old female patient with recurrent episodes of chest and back pain. A cardiac mass of uncertain etiology was discovered and she was referred to our multidisciplinary cardiac tumor team. Pathologic analysis from the surgical specimen confirmed this mass was a giant aneurysm of the left anterior descending artery.

The International Space Station (ISS) serves as a research lab for a wide variety of experiments including some that study the biological effects of microgravity and spaceflight using the Rodent Habitat and Microgravity Science Glovebox (MSG). Astronauts train for onboard dissections of rodents following basic training. An alternative approach for conducting these experiments is teleoperation of a robot located on the ISS from earth by a scientist who is proficient in rodent dissection. This pilot study addresses (1) the effects of extreme time delay on skill degradation during Fundamentals of Laparoscopic Surgery (FLS) tasks and rodent dissections using RAVEN II; (2) derivation and testing of rudimentary interaction force estimation; (3) elicitation of design requirements for an onboard dissection robot, RAVEN-S; and (4) simulation of the RAVEN-S prototype design with dissection data. The results indicate that the tasks’ completion times increased by a factor of up to 9 for a 3 s time delay while performing manipulation and cutting tasks (FLS model) and by a factor of up to 3 for a 0.75 s time delay during mouse dissection tasks (animal model). Average robot forces/torques of 14N/0.1Nm (peak 90N/0.75Nm) were measured along with average linear/angular velocities of 0.02m/s / 4rad/s (peak 0.1m/s / 40rad/s) during dissection. A triangular configuration of three arms with respect to the operation site showed the best configuration given the MSG geometry and the dissection tasks. In conclusion, the results confirm the feasibility of utilizing a surgically-inspired RAVEN-S robot for teleoperated rodent dissection for successful completion of the predefined tasks in the presence of communications time delay between the ISS and ground control.

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.

Reovirus encephalitis in mice was used as a model system to investigate astrocyte activation (astrogliosis) following viral infection of the brain. Reovirus infection resulted in astrogliosis, as evidenced by increased expression of glial fibrillary acidic protein (GFAP), and the upregulation of genes that have been previously associated with astrocyte activation. Astrocyte activation occurred in regions of the brain that are targeted by reovirus but extended beyond areas of active infection. Astrogliosis also occurred following reovirus infection of ex vivo brain slice cultures (BSCs), demonstrating that factors intrinsic to the brain are sufficient to activate astrocytes and that this process can occur in the absence of any contribution from the peripheral immune response. In agreement with previous reports, reovirus antigen did not colocalize with GFAP in infected brains, suggesting that reovirus does not infect astrocytes. Reovirus-infected neurons produce interferon beta (IFN-β). IFN-β treatment of primary astrocytes resulted in both the upregulation of GFAP and cytokines that are associated with astrocyte activation. In addition, the ability of media from reovirus-infected BSCs to activate primary astrocytes was blocked by anti-IFN-β antibodies. These results suggest that IFN-β, likely released from reovirus-infected neurons, results in the activation of astrocytes during reovirus encephalitis. In areas where infection and injury were pronounced, an absence of GFAP staining was consistent with activation-induced cell death as a mechanism of inflammation control. In support of this, activated Bak and cleaved caspase 3 were detected in astrocytes within reovirus-infected brains, indicating that activated astrocytes undergo apoptosis. IMPORTANCE Viral encephalitis is a significant cause of worldwide morbidity and mortality, and specific treatments are extremely limited. Virus infection of the brain triggers neuroinflammation; however, the role of neuroinflammation in the pathogenesis of viral encephalitis is unclear. Initial neuroinflammatory responses likely contribute to viral clearance, but prolonged exposure to proinflammatory cytokines released during neuroinflammation may be deleterious and contribute to neuronal death and tissue injury. Activation of astrocytes is a hallmark of neuroinflammation. Here, we show that reovirus infection of the brain results in the activation of astrocytes via an IFN-β-mediated process and that these astrocytes later die by Bak-mediated apoptosis. A better understanding of neuroinflammatory responses during viral encephalitis may facilitate the development of new treatment strategies for these diseases.

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.

Purpose: Antivascular endothelial growth factor agents are increasingly used in diabetic macular oedema (DME); however, there are few studies exploring their use in DME in real-world settings. Methods: POLARIS was a noninterventional, multicentre study to monitor 12-month outcomes in patients starting ranibizumab treatment in routine practices. The primary outcome was mean change in visual acuity (VA) from baseline to month 12 (last observation carried forward approach). Other outcomes included mean change in central retinal thickness (CRT) and resource utilization. Visual acuity (VA) outcomes were also stratified by country, baseline visual acuity score (VAS), sex, age and injection frequency. Results: Outcomes were analysed from all treated patients (n = 804) and from first-year completers (patients who had a visual acuity assessment at 12 months; n = 568). The mean (SD) baseline VAS was 59.4 (15.9) letters, and the mean change in visual acuity was 4.4 letters (95% confidence interval: 3.3–5.4) at month 12 (study eye; first-year completers). The mean number of injections (study eye) was 4.9, and the mean number of all visits (any eye) was 10 (58% were injection visits) over 12 months (first-year completers). The mean (SD) baseline CRT was 410.6 (128.8) μm, and the mean change in CRT was −115.2 μm at month 12 (study eye; first-year completers). Visual acuity (VA) outcomes were generally comparable across most countries and subgroups and were greatest in patients with the lowest baseline VAS (≤60 letters). Conclusion: POLARIS showed that real-world outcomes in DME patients starting treatment with ranibizumab were lower than those observed in clinical studies, in spite of extensive monitoring. © 2018 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.

We present a fully automatic method for segmenting orbital structures (globes, optic nerves, and extraocular muscles) in CT images. Prior anatomical knowledge, such as shape, intensity, and spatial relationships of organs and landmarks, were utilized to define a volume of interest (VOI) that contains the desired structures. Then, VOI was used for fast localization and successful segmentation of each structure using predefined rules. Testing our method with 30 publicly available datasets, the average Dice similarity coefficient for right and left sides of [0.81, 0.79] eye globes, [0.72, 0.79] optic nerves, and [0.73, 0.76] extraocular muscles were achieved. The proposed method is accurate, efficient, does not require training data, and its intuitive pipeline allows the user to modify or extend to other structures.

Objective Pregnancy is associated with an increase in total cholesterol, high density lipoproteins (HDL), and low-density lipoproteins (LDL). Postpartum, HDL and LDL decrease over the first 12 weeks postpartum. Oxidized LDL (ox-LDL) is a marker of oxidative stress-related inflammation, which is associated with obesity and also with development of cardiovascular disease. Cardiovascular protection and weight loss are benefits from metformin, especially in women with diabetes. The objective of this study was to compare changes in lipid profiles and biomarkers for obesity during the initial 6 weeks postpartum between women with gestational diabetes mellitus (GDM) treated with metformin versus placebo. Methods This was a planned ancillary study of a randomized controlled trial compares metformin versus placebo in women with GDM for postpartum weight loss. Two 3 mL blood samples were collected within 24 h of delivery and 6 weeks postpartum immediately processed after collection then stored at −20°C until completion of clinical trial prior to analysis. Change in the median plasma concentrations of total cholesterol, HDL, ox-LDL, glucose, insulin, leptin, and unacylated ghrelin were compared between study groups. Results Of the 77 postpartum women were included, 35 received metformin and 42 received placebo. There was less of a reduction in HDL in the metformin group compared to placebo (−2.3 versus −7.5 mg/dL, p = 0.019). In addition, there was a greater reduction in ox-LDL in those receiving metformin (−12.2 versus −3.8 mg/dL, p = 0.038). No other differences were observed in the selected biomarkers evaluated. Conclusion Biomarker levels of HDL and ox-LDL were positively affected during the initial 6 weeks postpartum in GDM women treated with metformin. Additional studies with a longer duration of metformin treatment in the postpartum period are warranted to evaluate long-term potential benefits.

Purpose of review To review the recent literature in regards to complications after reconstruction of Mohs defects, outline common pitfalls and to discuss the literature on avoiding complications as outlined per aesthetic subunit. Recent findings Complications in facial Mohs reconstruction commonly consist of infection, wound necrosis and dehiscence, hematoma and suboptimal scarring. However, site-specific complications such as hairline or eyebrow distortion, eyelid retraction or ectropion, nasal contour abnormality, alar retraction, nasal valve compromise, significant facial asymmetry or even oral incompetence must also be considered. Summary A successful reconstruction mimics the premorbid state and maintains function. The use of perioperative antibiotics, sterile technique, meticulous hemostasis, subcutaneous dissection and deep sutures to minimize wound tension should be considered for all Mohs reconstructions. Cartilage grafting can minimize nasal deformity and obstruction. Reconstruction near the lower eyelid should employ periosteal suspension sutures to minimize downward tension and lid retraction. Perioral complications, such as microstomia and oral incompetence, typically improve with time and therapy. Always consider secondary procedures such as dermabrasion, steroid injection, scar revision and laser resurfacing to help optimize aesthetic outcome.

Objective: To develop a method to measure intraoperative surgical instrument motion. This model will be applicable to the study of surgical instrument kinematics including surgical training, skill verification, and the development of surgical warning systems that detect aberrant instrument motion that may result in patient injury. Design: We developed an algorithm to automate derivation of surgical instrument kinematics in an endoscopic endonasal skull base surgery model. Surgical instrument motion was recorded during a cadaveric endoscopic transnasal approach to the pituitary using a navigation system modified to record intraoperative time-stamped Euclidian coordinates and Euler angles. Microdebrider tip coordinates and angles were referenced to the cadaver’s preoperative computed tomography scan allowing us to assess surgical instrument kinematics over time. A representative cadaveric endoscopic endonasal approach to the pituitary was performed to demonstrate feasibility of our algorithm for deriving surgical instrument kinematics. Conclusions: Technical feasibility of automatically measuring intraoperative surgical instrument motion and deriving kinematics measurements was demonstrated using standard navigation equipment.

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

Background Anterior and posterior ethmoid arteries supply the paranasal sinuses, septum, and lateral nasal wall. Precise identification of these arteries is important during anterior skull base procedures, endoscopic sinus surgery, and ligation of ethmoid arteries for epistaxis refractory to standard treatment. There is controversy in the literature regarding the prevalence of supernumerary ethmoid arteries. Objective This study examined the prevalence of supernumerary ethmoid arteries by using direct visualization after transorbital endoscopic dissection. Methods Nineteen cadaveric specimens were evaluated by using a superior lid crease (blepharoplasty) incision and an endoscopic approach to the medial orbital wall. Ethmoid arteries were identified as they pierced the lamina papyracea coplanar with the skull base and optic nerve. The distances from the anterior lacrimal crest to the ethmoid arteries and optic nerve were measured with a surgical ruler under endoscopic guidance. Results Thirty-eight cadaveric orbits were measured. Overall, there were three or more ethmoid arteries (including anterior and posterior arteries) in 58% of orbits, with 8% of the total sample that contained four or more ethmoid arteries. The average number of ethmoid arteries was 2.7. Bilateral supernumerary ethmoid arteries were noted in 42% of the specimens. The distance between the anterior lacrimal crest and the anterior ethmoid, posterior ethmoid, and optic nerve averaged 20, 35, and 41 mm, respectively. The average distance to the supernumerary or middle ethmoid artery was 29 mm. Conclusion This study found supernumerary ethmoid arteries in 58% of cadaveric specimens, a prevalence much higher than previously reported. Recognition of these additional vessels may improve safety during endoscopic sinus surgery and skull base surgery, and may permit more effective ligation for refractory epistaxis originating from the ethmoid system.

Objectives Describe instrument motion during live endoscopic skull base surgery (ESBS) and evaluate kinematics within anatomic regions. Design Case series. Setting Tertiary academic center. Participants A single skull base surgeon performed six anterior skull base approaches to the pituitary. Main Outcomes and Measures Time-stamped instrument coordinates were recorded using an optical tracking system. Kinematics (i.e., mean cumulative instrument travel, velocity, acceleration, and angular velocity) was calculated by anatomic region including nasal vestibule, anterior and posterior ethmoid, sphenoid, and lateral opticocarotid recess (lOCR) regions. Results We observed mean (standard deviation, SD) velocities of 6.14 cm/s (1.55) in the nasal vestibule versus 1.65 cm/s (0.34) near the lOCR. Mean (SD) acceleration was 7,480 cm/s2 (5790) in the vestibule versus 928 cm/s2 (662) near the lOCR. Mean (SD) angular velocity was 17.2 degrees/s (8.31) in the vestibule and 5.37 degrees/s (1.09) near the lOCR. We observed a decreasing trend in the geometric mean velocity, acceleration, and angular velocity when approaching the pituitary (p Conclusion Using a novel method for analyzing instrument motion during live ESBS, we observed a decreasing trend in kinematics with proximity to the pituitary. Additional characterization of surgical instrument motion is paramount for optimizing patient safety and training.

Encephalitis induced by reovirus serotype 3 (T3) strains results from the apoptotic death of infected neurons. Extrinsic apoptotic signaling is activated in reovirus-infected neurons in vitro and in vivo , but the role of intrinsic apoptosis signaling during encephalitis is largely unknown. Bax plays a key role in intrinsic apoptotic signaling in neurons by allowing the release of mitochondrial cytochrome c . We found Bax activation and cytochrome c release in neurons following infection of neonatal mice with T3 reoviruses. Bax −/− mice infected with T3 Abney (T3A) have reduced central nervous system (CNS) tissue injury and decreased apoptosis, despite viral replication that is similar to that in wild-type (WT) Bax +/+ mice. In contrast, in the heart, T3A-infected Bax −/− mice have viral growth, caspase activation, and injury comparable to those in WT mice, indicating that the role of Bax in pathogenesis is organ specific. Nonmyocarditic T3 Dearing (T3D)-infected Bax −/− mice had delayed disease and enhanced survival compared to WT mice. T3D-infected Bax −/− mice had significantly lower viral titers and levels of activated caspase 3 in the brain despite unaffected transneuronal spread of virus. Cytochrome c and Smac release occurred in some reovirus-infected neurons in the absence of Bax; however, this was clearly reduced compared to levels seen in Bax +/+ wild-type mice, indicating that Bax is necessary for efficient activation of proapoptotic mitochondrial signaling in infected neurons. Our studies suggest that Bax is important for reovirus growth and pathogenesis in neurons and that the intrinsic pathway of apoptosis, mediated by Bax, is important for full expression of disease, CNS tissue injury, apoptosis, and viral growth in the CNS of reovirus-infected mice.