Analysis of proteome-wide degradation dynamics in ALS SOD1 iPSC-derived patient neurons reveals disrupted VCP homeostasis.

Mutations in SOD1 cause amyotrophic lateral sclerosis (ALS) through gain-of-function effects, yet the mechanisms by which misfolded mutant SOD1 (mutSOD1) protein impairs human motor neurons (MNs) remain unclear. Here, we use induced-pluripotent-stem-cell-derived MNs coupled to metabolic stable isotope labeling and mass spectrometry to investigate proteome-wide degradation dynamics. We find several proteins, including the ALS-causal valosin-containing protein (VCP), which predominantly acts in proteasome degradation and autophagy, that degrade slower in mutSOD1 relative to isogenic control MNs. The interactome of VCP is altered in mutSOD1 MNs in vitro, while VCP selectively accumulates in the affected motor cortex of ALS-SOD1 patients. Overexpression of VCP rescues mutSOD1 toxicity in MNs in vitro and in a C. elegans model in vivo, in part due to its ability to modulate the degradation of insoluble mutSOD1. Our results demonstrate that VCP contributes to mutSOD1-dependent degeneration, link two distinct ALS-causal genes, and highlight selective protein degradation impairment in ALS pathophysiology.

Active Control of Plasmonic-Photonic Interactions in a Microbubble Cavity.

Active control of light-matter interactions using nanophotonic structures is critical for new modalities for solar energy production, cavity quantum electrodynamics (QED), and sensing, particularly at the single-particle level, where it underpins the creation of tunable nanophotonic networks. Coupled plasmonic-photonic systems show great promise toward these goals because of their subwavelength spatial confinement and ultrahigh-quality factors inherited from their respective components. Here, we present a microfluidic approach using microbubble whispering-gallery mode cavities to actively control plasmonic-photonic interactions at the single-particle level. By changing the solvent in the interior of the microbubble, control can be exerted on the interior dielectric constant and, thus, on the spatial overlap between the photonic and plasmonic modes. Qualitative agreement between experiment and simulation reveals the competing roles mode overlap and mode volume play in altering coupling strengths.

Elucidating Energy Pathways through Simultaneous Measurement of Absorption and Transmission in a Coupled Plasmonic-Photonic Cavity.

Control of light-matter interactions is central to numerous advances in quantum communication, information, and sensing. The relative ease with which interactions can be tailored in coupled plasmonic-photonic systems makes them ideal candidates for investigation. To exert control over the interaction between photons and plasmons, it is essential to identify the underlying energy pathways which influence the system's dynamics and determine the critical system parameters, such as the coupling strength and dissipation rates. However, in coupled systems which dissipate energy through multiple competing pathways, simultaneously resolving all parameters from a single experiment is challenging as typical observables such as absorption and scattering each probe only a particular path. In this work, we simultaneously measure both photothermal absorption and two-sided optical transmission in a coupled plasmonic-photonic resonator consisting of plasmonic gold nanorods deposited on a toroidal whispering-gallery-mode optical microresonator. We then present an analytical model which predicts and explains the distinct line shapes observed and quantifies the contribution of each system parameter. By combining this model with experiment, we extract all system parameters with a dynamic range spanning 9 orders of magnitude. Our combined approach provides a full description of plasmonic-photonic energy dynamics in a weakly coupled optical system, a necessary step for future applications that rely on tunability of dissipation and coupling.

Direct Observation of Infrared Plasmonic Fano Antiresonances by a Nanoscale Electron Probe.

In this Letter, we exploit recent breakthroughs in monochromated aberration-corrected scanning transmission electron microscopy (STEM) to resolve infrared plasmonic Fano antiresonances in individual nanofabricated disk-rod dimers. Using a combination of electron energy-loss spectroscopy and theoretical modeling, we investigate and characterize a subspace of the weak coupling regime between quasidiscrete and quasicontinuum localized surface plasmon resonances where infrared plasmonic Fano antiresonances appear. This work illustrates the capability of STEM instrumentation to experimentally observe nanoscale plasmonic responses that were previously the domain only of higher-resolution infrared spectroscopies.

Comparison of Online and Face-to-Face Parent Education for Children with Autism and Sleep Problems.

Many children with autism spectrum disorder (ASD) have sleep disorders. Face-to-face (F2F) sessions have empowered parents to help their child sleep. Our goal was whether online technologies could provide similar improvements in children's sleep while also improving parents' quality of life. Identical programs were taught in two sessions to F2F and online parents. Measurements were compared from baseline to 4 and 8 weeks post teaching sessions. Twenty-three participants completed the program. Parent quality of life improved for both groups. Parent fatigue scores were improved and sustained for the online group. The total sleep score improved for both groups, while the online group had sustained decreases in night wakings. Online methods can conveniently help improve sleep for children with ASD.

Sculpting Fano Resonances To Control Photonic-Plasmonic Hybridization.

Hybrid photonic-plasmonic systems have tremendous potential as versatile platforms for the study and control of nanoscale light-matter interactions since their respective components have either high-quality factors or low mode volumes. Individual metallic nanoparticles deposited on optical microresonators provide an excellent example where ultrahigh-quality optical whispering-gallery modes can be combined with nanoscopic plasmonic mode volumes to maximize the system's photonic performance. Such optimization, however, is difficult in practice because of the inability to easily measure and tune critical system parameters. In this Letter, we present a general and practical method to determine the coupling strength and tailor the degree of hybridization in composite optical microresonator-plasmonic nanoparticle systems based on experimentally measured absorption spectra. Specifically, we use thermal annealing to control the detuning between a metal nanoparticle's localized surface plasmon resonance and the whispering-gallery modes of an optical microresonator cavity. We demonstrate the ability to sculpt Fano resonance lineshapes in the absorption spectrum and infer system parameters critical to elucidating the underlying photonic-plasmonic hybridization. We show that including decoherence processes is necessary to capture the evolution of the lineshapes. As a result, thermal annealing allows us to directly tune the degree of hybridization and various hybrid mode quantities such as the quality factor and mode volume and ultimately maximize the Purcell factor to be 104.

Peer Victimization in Adolescents With Severe Obesity: The Roles of Self-Worth and Social Support in Associations With Psychosocial Adjustment.

Objective: To examine the associations of peer victimization with internalizing symptoms, externalizing symptoms, social competence, and academic performance in a clinical sample of adolescents with severe obesity, and whether self-worth and social support affect these associations. Methods: Multisite cross-sectional data from 139 adolescents before weight loss surgery ( M age = 16.9; 79.9% female, 66.2% White; M Body Mass Index [BMI] = 51.5 kg/m 2 ) and 83 nonsurgical comparisons ( M age = 16.1; 81.9% female, 54.2% White; M BMI = 46.9 kg/m 2 ) were collected using self-reports with standardized measures. Results: As a group, participants did not report high levels of victimization. Self-worth mediated the effects of victimization on a majority of measures of adjustment, and further analyses provided evidence of the buffering effect of social support for some mediational models. Conclusions: Self-worth and social support are important targets for prevention and intervention for both victimization and poor adjustment in adolescent severe obesity.

Treatment of purpura with lasers and light sources.

The potential for bruising is a frequent concern for patients undergoing minimally invasive procedures, particularly injection-based soft tissue fillers and botulinum toxin type A. Decreasing the risk of this side effect with good technique and careful patient selection is key, but interventions that quicken the resolution of bruising are also helpful. Many practitioners have employed the theory of selective photothermolysis, using laser and light devices, to target hemoglobin and its breakdown products to speed time to bruise resolution. 585-595 nm pulsed dye, pulsed 532 nm and 1064 nm long-pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers and intense pulsed light may be utilized with best results achieved when treatment is performed 1-2 days after the appearance of purpura. Specific therapy recommendations, side effects and contraindications will be addressed in this review.

Bariatric surgery in adolescents: what's the rationale? What's rational?

Rates of obesity in adolescents continue to rise, and available lifestyle and pharmacological interventions have had limited success in reducing excess weight and risk for comorbid health issues. However, ongoing health risks, psychosocial issues, and increased risk of mortality place these adolescents in jeopardy and warrant ongoing investigation for available treatments. Bariatric surgery for adults has had positive medical and psychological outcomes. However, bariatric surgery is a relatively new option for adolescents. Initial findings suggest positive results for excess weight loss and psychosocial improvements, but not without possible risks. Selection of appropriate candidates is essential in the process, specifically considering developmental maturity, family support, and resultant disease burden without surgery. Surgery is not a panacea for the obesity epidemic. Outcome studies are limited and long-term results are unknown, but for extremely obese adolescents, bariatric surgery is promising and should be considered a viable option for appropriate adolescent candidates.

Botulinum toxin type A: new information about an old medicine.

Now that several formulations of botulinum toxin type-A (BoNT-A) are on the market in North America and throughout the world, it is of great practical importance for those who administer these medications to be familiar with the differences between the formulations. These differences pertain to the stability of the medications, in particular during the period of time between reconstitution and administration, which may affect the degree of diffusion through various tissues after injection. A variety of relatively new uses of BoNT-A for dermatological conditions will be discussed.

Technical characteristics of fractional light devices.

This article deals with the technical characteristics of fractional light devices, fractional lasers, and light sources that cause their biologic effects by increasing the temperature of the target tissues to the point where the target is either killed, or in other cases where the temperature of the target tissue is increased to the point where repair and remodeling systems are turned on but tissue is not killed. Resurfacing devices act by causing ablation and/or coagulation.

YSGG 2790-nm superficial ablative and fractional ablative laser treatment.

The 2790-nm wavelength YSGG laser was introduced for aesthetic purposes under the trade name Pearl by Cutera in 2007. In clinical use, the Pearl superficial resurfacing laser has proved effective and well tolerated for the correction of superficial brown epidermal dyschromia and superficial fine lines and scars, and the Pearl Fractional laser produces excellent improvement in both dyschromia and improvement of deeper lines and moderately deep acne scarring. The two laser treatments can be combined in a single treatment session on different parts of the face or on the entire face, depending on patient needs and priorities.

Repair of acne scars with Dermicol-P35.

Acne vulgaris is a prevalent skin condition that can cause disfiguring residual scarring. While the complete removal of acne scars is unlikely, several treatments exist that can improve the appearance of acne scars. Dermal fillers offer a simple, nonsurgical corrective procedure that can provide improved skin texture. Dermicol-P35 (Evolence [Ortho Dermatologics, Skillman, NJ]) is a new, highly purified, ribose cross-linked, porcine collagen-based dermal filler that has demonstrated low immunogenicity and results that persist for at least 12 months. This article presents the aesthetic results of a male patient treated with Dermicol-P35 for severe facial acne scars.

New fillers for the new man.

Two new collagen-based lidocaine-containing dermal fillers, ArteSense/ArteFill (Artes Medical, San Diego, CA) and Evolence (Colbar LifeScience Ltd., Herzliya, Israel), have proved to be of particular interest to men, many of whom seek a long-lasting or permanent correction. ArteFill has been available in the United States since 2006, and it is expected that Evolence will reach the American market in 2008. The properties of the two products will be described, and experience based on the administration of many hundreds of syringes of both products by a Canadian dermatologist will be detailed here, with tips and precautions to optimize patient outcomes.

Practical use of Juvéderm: early experience.

BACKGROUND: This article is intended to provide practical information on the use of Juvéderm Ultra and Juvéderm Ultra Plus injectable gel fillers and to highlight differences between the injection techniques and uses of these fillers and those of gel-particle suspensions. The author's purpose was to provide early information to clinicians who perform aesthetic surgery. METHODS: The author discusses the properties of the Juvéderm family of products, compares these with particulate gel fillers, and makes recommendations for achieving optimal outcomes with Juvéderm as well as dermal fillers in general. RESULTS: When correcting relatively fine and superficial lines, or for first-time treatment of the lips, Juvéderm Ultra is preferred. Juvéderm Ultra Plus is useful for correction of deeper wrinkles and folds. Cohesive, homogenous gel fillers such as Juvéderm require gentle, gradual injection, which facilitates very accurate delivery to the site while minimizing the risk of disengagement of the needle from the Luer lock hub of the syringe. These fillers appear to remain in the desired location and do not flow away from the injection point into unintended areas, so that a somewhat smaller amount of filler is required for a given degree of correction. Both the Juvéderm preparations tend to blend in with the treated area in a shorter period of time compared with gel-particle suspensions. Finally, cohesive gels appear to be associated with a lesser degree of swelling in the 24-hour period after the procedure, particularly in the lips. CONCLUSIONS: Juvéderm Ultra and Juvéderm Ultra Plus are new-generation hyaluronic acid fillers used to treat superficial lines and deeper folds, respectively. They require administration by gentle, gradual, and precise injection.

A comprehensive approach to the recognition, diagnosis, and severity-based treatment of focal hyperhidrosis: recommendations of the Canadian Hyperhidrosis Advisory Committee.

BACKGROUND: Hyperhidrosis can have profound effects on a patient's quality of life. Current treatment guidelines ignore disease severity. OBJECTIVE: The objective was to establish clinical guidelines for the recognition, diagnosis, and treatment of primary focal hyperhidrosis. METHODS AND MATERIALS: A working group of eight nationally recognized experts was convened to develop the consensus statement using an evidence-based approach. RECOMMENDATIONS: An algorithm was designed to consider both disease severity and location. The Hyperhidrosis Disease Severity Scale (HDSS) provides a qualitative measure that allows tailoring of treatment. Mild axillary, palmar, and plantar hyperhidrosis (HDSS score of 2) should initially be treated with topical aluminum chloride (AC). If the patient fails to respond to AC therapy, botulinum toxin A (BTX-A; axillae, palms, soles) and iontophoresis (palms, soles) should be the second-line therapy. In severe cases of axillary, palmar, and plantar hyperhidrosis (HDSS score of 3 or 4), both BTX-A and topical AC are first-line therapy. Iontophoresis is also first-line therapy for palmar and plantar hyperhidrosis. Craniofacial hyperhidrosis should be treated with oral medications, BTX-A, or topical AC as first-line therapy. Local surgery (axillary) and endoscopic thoracic sympathectomy (palms and soles) should only be considered after failure of all other treatment options. CONCLUSIONS: These guidelines offer a rapid method to assess disease severity and to treat primary focal hyperhidrosis according to severity.

Benefits of a musculoskeletal screening examination for initial entry training soldiers.

Soldiers reporting for Individual Entry Training from basic training posts frequently arrive unable to initiate or complete training due to musculoskeletal injuries. Therefore, a screening examination was developed to identify musculoskeletal injuries and provide appropriate medical intervention as needed. During a consecutive 5-week period, 1013 soldiers reported for training to Fort Lee, Virginia. Of these, 105 (10.4%) reported for medical screening because they stated that they had an injury or could not pass a physical fitness test. After screening, 76 (72%) were found to have physical restrictions that would limit their ability to fully participate in training. The injured soldiers were referred for and received medical intervention. Of the total number of soldiers screened, 97 (92%) were able to complete their training, pass a physical fitness test, and graduate on time. This study documents the use and benefits of a brief musculoskeletal screening examination for individual entry training soldiers.

Ice minimizes discomfort associated with injection of botulinum toxin type A for the treatment of palmar and plantar hyperhidrosis.

BACKGROUND: The value of botulinum toxin type A (BTX-A) for treatment of palmar and plantar hyperhidrosis (HH) has been limited by injection pain, which in the past has generally required administration of a nerve block. We describe the successful use of ice applied to the intended injection point followed immediately by application of either ice or vibration to skin adjacent to the injection point to reduce discomfort associated with injection of BTX-A for the treatment of palmar and plantar HH. RESULTS: During needle insertion and injection of BTX-A, both the application of ice to the intended injection point followed by application of ice adjacent to the injection point (ice+ice) and the application of ice to the intended injection point followed by application of vibration adjacent to the injection point have been preferred by our patients to nerve block. These two techniques allow efficient treatment of both hands and/or both feet in a single session. CONCLUSION: By eliminating the need for nerve blocks, the techniques described here will enlarge the pool of physicians who can administer BTX-A for palmar and plantar HH, and will enlarge the pool of patients who are willing to have this treatment.